| Page | Description | Tags | Date |
|---|---|---|---|
| sources/PHT-RVsupport-WSPH-2019 | Hoeper et al. 2019 ERJ WSPH 6th consensus: ICU management of PH/RV failure (avoid intubation/fluid loading; IV prostacyclin; inotropes; vasopressors); ECLS — VA-ECMO or PA-LA as bridge to transplant (only established indication); awake ECMO preferred; RVAD contraindicated in PAH; bilateral lung Tx with perioperative + prolonged postoperative ECMO; 1-year survival >90%; REVEAL >7 → referral; REVEAL ≥10 → listing | #pulmonary-hypertension, #right-ventricular-failure, #extracorporeal-membrane-oxygenation, #lung-transplantation, #intensive-care | 2026-05-31 |
| sources/PAVB-HR-2009 | El-Sherif/Jalife 2009 Heart Rhythm review: paroxysmal AV block — TD-PAVB (atrial rate acceleration triggers repetitive concealed conduction in diseased His-Purkinje with postrepolarization refractoriness → prolonged asystole) vs PD-PAVB (pause-dependent; source-sink mismatch is sufficient; phase 4 depolarization distal to block zone may facilitate, not impair, conduction); His bundle most common block site (7/10 EPS cases); "phase 3/4 block" are misnomers | #paroxysmal-AV-block, #His-Purkinje-system, #tachycardia-dependent-block, #concealed-conduction, #atrioventricular-block | 2026-05-30 |
| sources/noac-ehra-2018 | Steffel/Verhamme et al. 2018 EHRA Practical Guide (EHJ 2018;39:1330–1393): 20-topic consensus on NOAC use in AF — EHRA VHD Type 1/2 classification (Type 1=VKA-mandatory; Type 2=NOAC-eligible); drug-specific renal clearance fractions (dabigatran 80%/edoxaban 50%/rivaroxaban 35%/apixaban 27%); perioperative management without bridging; AF+CAD dual therapy over triple (PIONEER AF-PCI, RE-DUAL PCI); cardioversion anticoagulation (3 weeks or TOE-guided); reversal agents (idarucizumab for dabigatran; andexanet alfa for FXa inhibitors); CKD dosing tables; Child-Pugh liver dosing | #atrial-fibrillation, #anticoagulation, #noac, #guidelines, #stroke-prevention | 2026-05-30 |
| sources/lvh-scar-aiecg-naturesr-2025 | Nezamabadi et al. 2025 Sci Rep: XplainScar — first explainable ML model detecting and localizing LV scar in HCM from 12-lead ECG; trained JH n=500, external validation UCSF n=248; global LV scar F1=89%, Se=91%, Sp=78% on held-out set; unsupervised ECG clustering + SCARF self-supervised learning + SHAP explainability; basal scar → deep Q/intrinsicoid QRS delay in aVR/V1; apical scar → T wave inversion V2–V6; outperforms 5 deep learning comparators | #hypertrophic-cardiomyopathy, #artificial-intelligence, #ECG, #LV-scar, #explainability | 2026-05-30 |
| sources/hemiblock-circ-2007 | Elizari/Acunzo/Ferreiro 2007 Circulation review from original Rosenbaum group: LAH and LPH anatomy (posterior division = most protected, dual LAD+PDA blood supply), ECG/VCG criteria (CCW frontal loop = pathognomonic of LAH; CW excludes LAH), 7 MI masking/simulation patterns (negative T in II/III/aVF = inferior ischemia despite LAH; VCG loop rotation differentiates LA from inferolateral infarction), masquerading RBBB (LAH eliminates RBBB S waves from I and V5-V6), RBBB+LPH = near-trifascicular (80–87% MI mortality; 42% complete AV block; Adams-Stokes 58.6%), LAH epidemiology (2.77% healthy population; 62% cases <40yr; spontaneous VSD closure underrecognized cause), Lev vs Lenègre disease | #left-anterior-hemiblock, #fascicular-block, #intraventricular-conduction-delay, #myocardial-infarction-masking, #electrocardiography | 2026-05-30 |
| sources/lbbb-europace-2017 | Surkova et al. 2017 Europace review: LBBB from cardiac mechanics to clinical challenges — TAVR-induced LBBB (CoreValve 45.2% vs Sapien 14.0%; Dutch registry mortality 37.8% vs 24.0% vs PARTNER no difference); pathophysiology (SF driven by RV free wall, not IVS; SF ≠ septal systolic rebound stretch; apical rocking; lateral hypertrophy; pro-arrhythmic state); echocardiographic CRT predictors (systolic stretch index >9.7% at QRS 120–149ms; LV pressure-strain loops; 1/3 of LBBB lack typical speckle-tracking pattern); stress testing meta-analysis (66 studies: stress echo highest specificity 88.7%/accuracy 84.4%; vasodilator preferred); Sgarbossa meta-analysis (score ≥3: sensitivity 20%, specificity 98%); connexin 40/43 genetics | #left-bundle-branch-block, #cardiac-mechanics, #echocardiography, #TAVR-complications, #LV-dyssynchrony | 2026-05-30 |
| sources/rbbb-ccr-2021 | Ikeda 2021 Curr Cardiol Rev review: RBBB anatomy (thin Purkinje structure, LAD supply), epidemiology (2–3% prevalence; 1% age 50 → 18% age 80 in men), ECG criteria (rSR' most common; initial 30–40 ms normal → MI diagnosis preserved), differential (Brugada pseudo-RBBB: no wide S in I/V6; Chiale maneuver unmasks concealed Brugada in RBBB), CRT generally no benefit in RBBB except RBBB+LAFB or prolonged PR; prognosis: isolated RBBB benign but RBBB+CVD = independent mortality predictor | #right-bundle-branch-block, #ECG-criteria, #ventricular-conduction-delay, #Brugada-syndrome, #bifascicular-block | 2026-05-30 |
| sources/vcg-fronphysiol-2022 | Vondrak/Penhaker 2022 Front. Physiol. review: VCG processing and transformation methods — Kors regression (~98%) and IDT (~97.2%) best ECG→VCG transforms; quasi-orthogonal NOT reliable; QRS area from VCG outperforms QRS duration and LBBB morphology for CRT response prediction; VCG superior to ECG for LQTS (86% vs 69%), MI detection (98% vs 73%), atrial enlargement; QRS-T spatial angle most commonly analyzed parameter; IDT contraindicated for AF f-wave analysis | #vectorcardiography, #ECG-derived-VCG, #Frank-lead-system, #QRS-T-angle, #cardiac-signal-processing | 2026-05-30 |
| sources/lbbb-evg-ane-2019 | Pérez-Riera et al. 2019 Ann Noninvasive Electrocardiol review: re-evaluating ECG/VCG criteria for CLBBB — Strauss strict criteria (QRS ≥140/130 ms men/women + mid-QRS notching/slurring in ≥2 leads) vs conventional AHA ≥120 ms; ~1/3 of conventional LBBB may be pseudo-LBBB (LVH+LAFB); concordant LBBB (~28–32%) vs discordant LBBB (~68–70%) with distinct clinical profiles and CRT prognosis; VCG mid-end conduction delay pathognomonic of true LBBB; gender differences in LBBB expression; ~30% CRT non-responder problem linked to false LBBB diagnosis | #left-bundle-branch-block, #cardiac-resynchronization-therapy, #ECG-criteria, #vectorcardiography, #ventricular-conduction-delay | 2026-05-30 |
| sources/co-cocc-2022 | Arya/Al-Moustadi/Dutta 2022 Curr Opin Crit Care review: CO monitoring in ICU — PAC thermodilution gold standard rebounding in cardiac ICUs (CCOM algorithm CO/SvO₂/SVR/RVEF every 20s; RV port for RV decompensation detection); TPT unreliable in ECMO/hypothermia/low CO; CCE/TTE ±25% error vs PAC (acceptable); noninvasive methods (bioimpedance/bioreactance/finger cuff/esCCO/USCOM 42.7% error/CO₂ rebreathing 40-49%) all unacceptable in critically ill; NICOM study: bioreactance poor in cardiogenic shock | #cardiac-output, #hemodynamic-monitoring, #pulmonary-artery-catheter, #critical-care-echocardiography, #critical-care | 2026-05-29 |
| sources/co-bjcp-2010 | Geerts/Aarts/Jansen 2010 BJCP review: all CO measurement methods for pharmacological studies — Fick (direct O₂ gold standard; CO₂ rebreathing limited by shunts), indicator dilution (PAC TD, continuous PAC, PiCCO, LiDCO), pulse contour (PiCCO/PRAM/LiDCO/Vigileo/Modelflow), echo-Doppler, bioimpedance; comparative Table 1 vs PAC TD; Critchley-Critchley ±28% criterion; calibrated Modelflow best pulse contour; no method surpasses 3-synchronized-injection thermodilution | #cardiac-output, #hemodynamic-monitoring, #thermodilution, #pulse-contour-analysis, #fick-principle | 2026-05-29 |
| sources/RVOT-LVOT-circ-ep-2019 | Anderson 2019 Circ Arrhythm Electrophysiol review: ECG signatures and 18 prediction algorithms for RVOT vs LVOT outflow tract VAs; combined TZ+V2S/V3R formula best overall (Youden 0.77); V3R/V7 index best AUC (0.95); preferential conduction in 25% of aortic sinus OTVAs is key pitfall | #outflow-tract-ventricular-arrhythmia, #ECG-localization, #catheter-ablation, #PVC, #ventricular-tachycardia | 2026-05-29 |
| sources/vo2max-jphysiol-2008 | Levine 2008 J Physiol topical review: VO2max bounded by Fick equation — (LVEDV−LVESV) × HR × a-v O2 diff; Hawkins 2007 (n=156) proves VO2max is a true parametric ceiling (subjects at >30% supramaximal work never exceeded it); elite athlete advantage = large LV EDV from enhanced chamber + pericardial compliance (not contractility; not a-v O2 extraction); Levine 1991 direct P-V curves; largest CO 42.3 L/min; largest SV 212 mL; highest VO2max 7.48 L/min; altitude VO2max reduction 0.6%/100m = O2 transport not motor recruitment (Wehrlin & Hallen 2006); peripheral fatigue mechanisms (Ca2+/Na-K pump/ROS/cross-bridge); Central Governor Model rebutted; ACE gene not confirmed as endurance gene | #VO2max, #exercise-physiology, #cardiac-output, #endurance-athletes, #oxygen-transport | 2026-05-28 |
| sources/asd-japc-2025 | Shah 2026 Ann Pediatr Cardiol brief communication: three ASD knowledge gaps — (1) Qp:Qs is a relative ratio masking absolute flow burden (7.2 vs 10.8 L/min at identical Qp:Qs 1.8 with CO 4 vs 6 L/min); (2) exercise-induced shunt dynamics contradictory across 3 small studies (Bay: increased; Nielsen: decreased; Stephensen: unchanged); (3) post-closure PAH predictors unvalidated — delayed closure >40yr, elevated pre-closure PVR, BMPR2 variants, pulmonary microvascular disease; no current exercise restriction guideline for unrepaired ASD | #atrial-septal-defect, #exercise-physiology, #pulmonary-arterial-hypertension, #hemodynamics, #congenital-heart-disease | 2026-05-28 |
| sources/shunt-nature-sr-2020 | Sigurdsson/Lindberg 2020 Sci Rep prospective method-comparison (n=44, mean age 12 months, ASD/VSD surgical cohort): COstatus transpulmonary ultrasound dilution vs perivascular flow probes + oximetric shunt equation for Qp/Qs estimation — sensitivity 95.7%/specificity 97.6%/AUC 0.97 for L→R shunt detection; significant Qp/Qs underestimation in moderate/small shunts (p<0.05); algorithm optimisation needed for young children; less invasive than catheterisation (existing arterial + central venous lines only) | #pediatric-hemodynamics, #intracardiac-shunt, #indicator-dilution, #congenital-heart-disease, #cardiac-output | 2026-05-28 |
| sources/dash-meddiet-cn-2023 | Filippou et al. 2023 Clinical Nutrition 4-arm RCT (n=240, 3 months, Greek adults, high-normal BP/grade 1 HT, never-treated): FIRST head-to-head DASH vs MedDiet on salt restriction background — MedDiet superior office SBP (MDG vs DDG −3.2 mmHg, P<0.001); EQUAL on 24h ambulatory SBP/DBP (gold standard); both outperform salt restriction alone; DASH NOT superior to salt restriction for 24h ambulatory DBP; contradicts network meta-analysis DASH superiority claim | #hypertension, #mediterranean-diet, #DASH-diet, #blood-pressure, #dietary-patterns | 2026-05-28 |
| sources/diet-mets-nutrients-2020 | Castro-Barquero et al. 2020 Nutrients comprehensive review: 7 dietary patterns benchmarked against all MetS criteria — MedDiet best overall (RR 0.81 MetS risk, 19% lower); DASH best for BP (−3.2/−2.5 mmHg, 30 RCTs, most effective vs 13 patterns); low-CH improves short-term TG/weight/HbA1c but U-shaped mortality curve (optimal 50–55% CH per PURE+Seidelmann); ketogenic benefits may be energy-restriction-mediated; DIETFITS: equal weight loss low-fat vs low-CH; high-protein: only TG reduction consistently; adherence is the decisive factor | #metabolic-syndrome, #dietary-patterns, #mediterranean-diet, #cardiovascular-prevention, #insulin-resistance | 2026-05-27 |
| sources/asd-closure-jc-2015 | Akagi 2015 JC review: transcatheter ASD closure in adults and elderly — atrial septal malalignment as novel cardiac erosion risk factor beyond aortic rim deficiency; updated ASO IFU (IVC rim <5 mm added as contraindication); LUPV/RUPV and balloon-assist techniques for large/complex ASD; PCWP monitoring protocol (abandon if PCWP rises >10 mmHg from baseline or >20 mmHg absolute during test balloon occlusion); ~1/3 of patients >60yr and ~1/2 of patients >70yr have AF; PVI before ASD closure for symptomatic paroxysmal/persistent AF (age <75, LA <50 mm, 3-month SR confirmation); ASD closure beneficial even in permanent AF | #atrial-septal-defect, #transcatheter-closure, #adult-congenital-heart-disease, #pulmonary-arterial-hypertension, #atrial-arrhythmia | 2026-05-27 |
| sources/dash-nutrients-2021 | Wickman/Steinberg et al. UC Davis 2021 Nutrients review: DASH diet in outpatient HF management — DASH + sodium restriction reduces hs-cTnI −20% and NT-proBNP −23% vs control; 3-week DASH in HFpEF improves ventricular diastolic function; short-chain acyl carnitine metabolomics correlate with LV function; precision nutrition framework; no large HF-specific RCT yet | #heart-failure, #DASH-diet, #nutrition-therapy, #precision-nutrition, #metabolomics | 2026-05-27 |
| sources/inclisiran-orion-nejm-2020 | Ray/Wright/Kallend et al. NEJM 2020: ORION-10 (US ASCVD; n=1,561) + ORION-11 (Europe/SA ASCVD/risk-equiv; n=1,617) Phase 3 RCTs; SC inclisiran 284 mg day 1/90/Q6m vs placebo; LDL-C −52.3%/−49.9% at day 510 (P<0.001); PCSK9 −83.3%/−79.3%; absolute −54.1/−51.9 mg/dL; consistent across all subgroups; safety comparable to placebo except mild ISAEs (2.6%/4.7% excess); no liver/platelet toxicity; ORION-4 CVOT (HR 0.84; P=0.01; did not meet pre-specified threshold P<0.005) | #inclisiran, #siRNA, #PCSK9, #LDL-cholesterol, #lipid-lowering-therapy | 2026-05-27 |
| sources/verve102-pcsk9-nejm-2026 | Vafai/Kathiresan et al. NEJM 2026: Heart-2 Phase 1 (n=35; HeFH/premature CAD); single IV infusion VERVE-102 (GalNAc-LNP ABE8.8 mRNA + gRNA → PCSK9 splice site A→G edit); at 1.0 mg/kg: PCSK9 −88%, LDL-C −62% (absolute −78 mg/dL; 128→51 mg/dL), stable ≥18 months; no DLTs/deaths; transient ALT ≤2.4×ULN; no thrombocytopenia; LNP t½ <20h; 15-year follow-up required | #base-editing, #PCSK9, #familial-hypercholesterolemia, #gene-therapy, #LDL-cholesterol | 2026-05-27 |
| sources/pericarditis-acc-2025 | Wang/Klein/Imazio et al. 2025 ACC Expert Consensus Statement (JACC 2025;86:2691-2719): novel diagnostic criteria (pleuritic chest pain mandatory + ≥1 of 5 additional findings; 0=unlikely/1=possible/2+=definite); paradigm shift — anti-IL-1 agents (anakinra/rilonacept/goflikicept) preferred over corticosteroids for recurrent inflammatory pericarditis; CMR LGE grading for risk stratification/monitoring; constrictive pericarditis transient vs chronic distinction; effusion sizing; tamponade diagnosis; pericarditis in oncology; Pericardial Diseases Center model | #pericarditis, #consensus, #guidelines, #cardiac-imaging, #anti-IL1 | 2026-05-27 |
| sources/asd-lancet-2014 | Geva/Martins/Wald 2014 Lancet Seminar: ASD foundational review — incidence 56–100/100,000 livebirths; 3rd most common CHD; spontaneous closure rates by size (56% at 4-5mm → 0% >10mm); life expectancy without closure (mortality 0.6%/yr decade 1-2; 7.5%/yr decade 6); surgical survival by age at repair (Murphy 27-32yr: <25yr near-normal; >41yr 40% vs 59%); device meta-analysis (28,142 pts): major complications 1.6%, cardiac erosion 0.1%; PVR >8 WU precluding closure per 2008/2010 guidelines (differs from ESC 2020 ≥5 WU); arrhythmia benefit short-term (OR 0.66) but lost at ≥5yr; maternal mortality 28% with ASD+PAH | #atrial-septal-defect, #congenital-heart-disease, #adult-congenital-heart-disease, #device-closure, #natural-history | 2026-05-26 |
| sources/asd-ehj-2022 | Brida/Gatzoulis et al. 2022 EHJ state-of-the-art review: ASD most common adult CHD (25–30%); 4 subtypes (secundum 80%/primum 15%/sinus venosus 5%/coronary sinus); proactive closure normalises prognosis; PVR thresholds for closure (safe <5 WU; contraindicated ≥5 WU despite PAH Rx); ASD closure NOT associated with AF reduction (meta-analysis 25 studies); pre-closure ablation before percutaneous closure (79% vs 37% AF-free); RV remodelling inversely related to age at closure; Eisenmenger closure contraindicated | #atrial-septal-defect, #adult-congenital-heart-disease, #congenital-heart-disease, #pulmonary-arterial-hypertension, #arrhythmia-management | 2026-05-26 |
| sources/levosimendan-eschf-2023 | Dobarro et al. 2023 ESC Heart Failure LEVO-D registry (n=403; 23 Spanish hospitals; retrospective; destination therapy — not HT/LVAD candidates): HF hosp 77.9%→38.7% (P<0.0001); unplanned visits 43.7%→22.7% (P<0.0001); 1-year mortality 26.8%; median survival 24.7 months; 43.7% responders; ICD/VT unchanged; 3.7% withdrawal due to adverse events; LEVO-D score (TEER+2, BB+1.5, Hgb>12+1.5, amiodarone−1.5, unplanned HF visit−1.5, HR>70−2; AUC 0.71 vs MAGGIC 0.60); no dosing strategy or dose per administration independently associated with response | #advanced-heart-failure, #levosimendan, #intermittent-inotropes, #heart-failure, #destination-therapy | 2026-05-26 |
| sources/levosimendan-ecr-2024 | Susilo et al. 2024 ECR comprehensive CS-focused review: triple mechanism confirmed (TnC, vascular KATP, mito-KATP/mPTP/cytochrome C); PDE3 only at supratherapeutic doses; endothelial NO via p38 MAPK; enoximone vs levosimendan survival 69% vs 37% (refractory CS/AMI); LIDO 180-day HR 0.57 (95% CI 0.34–0.95); VA-ECMO weaning mixed evidence (positive studies vs n=200 cohort negative + failed RCT); tVAD adjuvant improved weaning + 6-month mortality; PPCM preferred over dobutamine (teratogenicity); takotsubo LV recovery only levosimendan group; cardiac surgery LCOS reduction vs placebo/dobutamine/milrinone; septic shock meta-analyses positive; REVIVE VT contradiction vs SURVIVE; hypothermia safety (no triangulation at 26°C vs milrinone/isoprenaline); SBP >90 monotherapy threshold; levo+dobutamine combination MACE prevention | #cardiogenic-shock, #levosimendan, #inotropes, #advanced-heart-failure, #mechanical-circulatory-support | 2026-05-26 |
| sources/rhc-hf-jacchf-2024 | Rajagopalan/Borlaug et al. 2024 JACC HF state-of-the-art review (12:1141-1156): practical RHC guidance across HF spectrum — CS staging (SCAI 5 stages; RAP 8-12/PCWP ≤15/CI ≥2.2 targets; CPO <0.6W → escalate); HF-CS vs AMI-CS (HF-CS severe hemodynamics but preserved end-organs + normal lactate); HFpEF exercise RHC gold standard (1/3 normal resting PCWP; 2.4× risk with exercise PCWP elevation; normal PCWP <25 mmHg on exercise); LVAD risk predictors (RAP >15/RAP:PCWP >0.63/PAPI <1.85); LVAD goals post-implant (RAP <12/PCWP <18; ISHLT 2023 Class IIa ramp optimization); transplant assessment (PVR >5 WU/TPG >16 → vasodilator challenge; PVR <3 + SBP >85 → favorable); portal HTN assessment (hepatic vein wedge pressure gradient >5 mmHg = portal HTN; elevated hepatic vein pressure + normal gradient = HF congestion); high-output HF (CI >4.0; AV fistula compression test) | #right-heart-catheterization, #heart-failure, #hemodynamic-monitoring, #cardiogenic-shock, #HFpEF | 2026-05-25 |
| sources/papi-ejhf-2020 | Lim/Gustafsson 2020 EJHF review (22:32-38): physiological basis of PAPi — PAPP = SV/PAC equation; PAC-PVR hyperbolic relationship and RC time constant; PAWP disproportionately reduces PAC; same PAPi value reflects different hemodynamic states (PAC 5/SV 50/RAP 5 vs PAC 1.5/SV 40/RAP 14 both = PAPi 2.0); context-specific thresholds (≤0.9 RV infarction; <1.85 LVAD; <3.65 advanced HF; <3.7 PAH); PAPi NOT associated with 30-day mortality in SHOCK trial/registry; post-LVAD PAC improvement makes PAPi less sensitive; no single threshold applies across populations | #pulmonary-artery-pulsatility-index, #right-ventricular-failure, #hemodynamic-monitoring, #pulmonary-arterial-capacitance, #cardiogenic-shock | 2026-05-25 |
| sources/iabp-ajc-2006 | Trost/Hillis 2006 AJC review (97:1391-1398): IABP — history (Kantrowitz 1952/1968; Bregman 1980 percutaneous); device (8-9.5Fr, helium, 25-50mL, tip 2-3cm distal to left subclavian); 4 timing error patterns and hemodynamic consequences; coronary flow augmentation limited to impaired autoregulation, NOT past fixed severe stenoses; Benchmark Registry (n=16,909) major complications 2.6% (limb-threatening ischemia 0.9%, bleeding 0.8%); NRMI-2 IABP+thrombolysis benefited (49% vs 67%) but IABP+primary PCI did not (45% vs 47% NS); contraindications: AR/dissection/aneurysm/PVD/bleeding diathesis | #intra-aortic-balloon-pump, #cardiogenic-shock, #mechanical-circulatory-support, #hemodynamic-monitoring, #acute-myocardial-infarction | 2026-05-25 |
| sources/mcs-jic-2023 | Nakata/Yamamoto/Saku et al. 2023 J Intensive Care review (11:64): tMCS in cardiogenic shock — PV loop framework for IABP/VA-ECMO/Impella/ECPELLA; device complication rates (IABP: bleeding 12.9%/limb 1.5%; Impella: 27.7%/4.2%; VA-ECMO: 28.2%/14.3%); ECPELLA Schrage 2020 HR 0.79; J-PVAD Impella LVEF 35%→44.7%; three-step Impella/ECPELLA weaning protocol (PAPi ≥1.0 for VA-ECMO; PAWP <20+CPO ≥0.6W for Impella); SCAI-based selection protocol; IABP Shock II/SAVE/ENCOURAGE risk scores; shock team mortality reduction 40%→28% | #cardiogenic-shock, #mechanical-circulatory-support, #Impella, #VA-ECMO, #ECPELLA | 2026-05-25 |
| sources/lpa-molecules-2023 | Lampsas/Xenou/Oikonomou et al. 2023 Molecules narrative review (28:969): Lp(a) pathophysiology to treatment; distinct contribution — molecular thrombogenicity mechanisms: platelet GPIIb/IIIa via RGD epitope (cAMP-dependent); TF upregulation via Mac-1/NF-κB; TFPI inhibition (lysine-dependent); PAI-1 upregulation; fibrin clot tightening (Lp(a) ≥30 mg/dL → lower clot permeability); endothelial dysfunction (Rho/ROCK pathway → barrier disruption; EPC impairment; FMD r=−0.33; small apo(a) ≤22 KIV → lower FMD independent of Lp(a) level); arterial wall attachment via decorin 2-part interaction (apoB-GAG electrostatic + apo(a)-protein core hydrophobic); smaller isoform effects on OxPL/fibrin binding/thrombogenicity; dose-dependent OxPL bidirectionality (low Lp(a) anti-inflammatory; high pro-inflammatory); treatment: niacin only approved agent (25–38%); PCSK9i 26.7% (n=64,107, 41 studies); ASO up to 90% | #lipoprotein-a, #atherosclerotic-cardiovascular-disease, #oxidized-phospholipids, #thrombogenicity, #vascular-inflammation | 2026-05-23 |
| sources/lpa-jacc-2017 | Tsimikas S. 2017 JACC review (JACC 69:692-711): Lp(a) structure (apo[a] KIV-2 repeats 1→>40; disulfide bond at KIV-9/apoB; evolved from plasminogen), metabolism (>90% LPA-gene determined; LDLR modest role; longer plasma residence), CVD mechanisms (OxPL-apoB primary carrier; monocyte trafficking via radiolabeled study; antifibrinolytic potential limited in vivo), CAVS (LPA rs10455872 only monogenic CAVS risk factor; ASTRONOMER: Lp[a] >58.5 mg/dL + OxPL-apoB >5.5 nM → 0.26 vs 0.17 m/s/yr progression; rosuvastatin raised Lp[a] +20% OxPL-apoB +46%), residual risk (AIM-HIGH HR +89%; JUPITER HR +71%; LIPID HR +23%; pooled HR 1.61 across 13,167 statin-treated pts), 9 controversies, statin analysis (3,896 pts: mean +11% Lp[a]; +24% OxPL-apoB), >50% reduction threshold hypothesis, IONIS-APO(a)-LRx 66-92% reduction; CardiogramPlus4D: LPA locus most potent CAD genetic variant | #lipoprotein-a, #atherosclerotic-cardiovascular-disease, #calcific-aortic-valve-stenosis, #antisense-oligonucleotide, #oxidized-phospholipids | 2026-05-23 |
| sources/angptl3-inhibition-tcm-2024 | Luo/Das/Khetarpal/Rosenson/Qamar et al. 2024 Trends Cardiovasc Med review: ANGPTL3 biology (460aa hepatokine; LXR-regulated; chromosome 1p31; furin cleavage; inhibits LPL→raises TG + EL→raises HDL-C; ANGPTL8 complex; LDLR-independent LDL-C lowering via EL-dependent VLDL clearance); genetic epidemiology (DiscovEHR n=58,335 OR 0.59; MI Genetics Consortium n=180,180 OR 0.66; familial combined hypolipidemia Musunuru 2010 WES); evinacumab Phase 3 HoFH (Raal; n=65; −47% LDL-C −55% TG; null-null −43.4% vs non-null −49.1%); vupanorsen discontinued TRANSLATE-TIMI 70 (liver fat + ALT/AST); ARO-ANG3 siRNA ARCHES-2 Phase 2b ongoing; BE3-Angptl3 murine base editing 35% editing rate; VLP vaccine mouse models; FDA/EMA approved evinacumab HoFH ≥12yr | #angptl3, #dyslipidemia, #lipid-lowering-therapy, #familial-hypercholesterolemia, #atherosclerotic-cardiovascular-disease | 2026-05-23 |
| sources/syncope-aha-acc-hrs-2017 | Shen/Sheldon et al. 2017 ACC/AHA/HRS Syncope Guideline (JACC 2017;70:e39-110): syncope definition (cerebral hypoperfusion, trimodal 20/60/80yr), evaluation framework (history+ECG Class I; ICM 55% vs 19% diagnostic yield; routine neuro-imaging Class III No Benefit), risk stratification (short/long-term factors; risk scores not superior to clinical judgment), VVS management (counterpressure IIa; midodrine IIa; pacing IIb ≥40yr + documented pauses), cause-specific management across reflex/cardiac/channelopathic/structural etiologies, OH management (water ingestion Class I; midodrine/droxidopa IIa), carotid sinus syndrome pacing IIa | #syncope, #guidelines, #vasovagal-syncope, #risk-stratification, #orthostatic-hypotension | 2026-05-23 |
| sources/va-scd-aha-2017 | Al-Khatib/Stevenson et al. 2017 AHA/ACC/HRS Guideline (JACC 2018;72:e91-220): VA management and SCD prevention — comprehensive primary/secondary prevention ICD indications (LVEF ≤35% thresholds, 40-day post-MI/90-day post-revasc waiting periods), HCM risk factor table, ARVC ICD criteria, channelopathy management, Lamin A/C ≥2 risk factors criterion, value statements (primary prevention = high value <$50K/QALY), procainamide superiority for stable VT | #ventricular-arrhythmia, #sudden-cardiac-death, #ICD-indications, #catheter-ablation, #guideline | 2026-05-23 |
| sources/gene-editing-acc-2026 | Ambardekar et al. 2026 ACC Scientific Statement (JACC 2026): comprehensive GET overview — 4 editing mechanisms (CRISPR-Cas9/base/prime/epigenome editing); LNP vs AAV delivery platforms; ATTR-CM (nex-z −90% TTR; MAGNITUDE Phase 3 paused Oct 2025 for hepatotoxicity/death); lipid GET (PCSK9 base editing −53% LDL-C; ANGPTL3 −49% LDL-C −55% TG; LPA targets); DMD AAV clinical fatality; ~1% genetic testing rate; 15-year FDA follow-up requirement; no clinical recommendations issued | gene-therapy, CRISPR-Cas9, attr-cardiomyopathy, lipid-lowering-therapy, cardiovascular-genetics | 2026-05-23 |
| sources/bradycardia-acc-aha-hrs-2018 | Kusumoto et al. 2018/2019 ACC/AHA/HRS multi-society guideline (JACC 2019;74:e51-156): definitive bradycardia/conduction delay guideline superseding 2008 device-based therapy document; SND pacing requires symptom–bradycardia correlation (no minimum HR/pause threshold); Mobitz II/high-grade/third-degree AV block → PPM regardless of symptoms; LVEF 36–50% + ventricular pacing >40% → CRT/His bundle pacing preferred over RV; TAVR conduction disturbances; atrial-based pacing over VVI for SND; shared decision-making and pacemaker withdrawal rights | bradycardia, sinus-node-dysfunction, atrioventricular-block, permanent-pacing, cardiac-conduction-delay | 2026-05-23 |
| sources/marfan-ghent-aclingene-2015 | von Kodolitsch/De Backer et al. 2015 Appl Clin Genet review: comparative analysis Berlin 1988→Ghent-1 1996→Ghent-2 2010 nosologies; prevalence 1.5–17.2/100,000 (6 studies; far below 1:5,000 estimate); diagnostic delay median 2yr (EURORDIS 682 families; 72% harmed); seven-signs adult screening tool (ectopia lentis 4pts; FHx 2pts; 5 single-point features); Ghent-1 vs Ghent-2 near-identical yields (FBN1+ 90% vs 92%; FBN1- 15% vs 13%); no external reference standard; >1,500 FBN1 mutations; VUS burden; Z-score BSA issue (Roman 1989 underestimates in tall patients); Lacro 2014 NEJM: atenolol = losartan (definitive) | marfan-syndrome, ghent-nosology, diagnostic-criteria, connective-tissue-disorders, FBN1 | 2026-05-23 |
| sources/marfan-ghent-jmg-2010 | Loeys/Dietz et al. 2010 J Med Genet original article: revised Ghent nosology for MFS — 4 sporadic + 3 family-history diagnostic routes; cardinal features Ao Z≥2 + ectopia lentis; systemic score (max 20 pts; ≥7 = systemic); bona fide FBN1 mutation criteria (Box 3); children provisions (potential MFS; non-specific CTD); related conditions (ELS/MASS/MVPS) formally defined; surgery at 5.0 cm; ~90% concordance with 1996 criteria | marfan-syndrome, ghent-nosology, connective-tissue-disorders, aortic-aneurysm, diagnostic-criteria | 2026-05-23 |
| sources/marfan-cv-clingene-2015 | Cook/Ramirez 2015 Clin Genet review: Ghent 2010 criteria; MVP ~75%; aortic stiffness as independent dissection risk factor; elastic fiber fragmentation before dilation; DCM as primary cardiomyopathy (Cook 2014 JCI — exception to anti-TGFβ therapy); canonical/non-canonical TGFβ pathways; AT1R/AT2R balance; losartan Groenink 2013 RCT; doxycycline + pravastatin preclinical; AOS (SMAD3), SGS (SKI), sTAA (TGFB2); two-pathway TAA model | marfan-syndrome, tgf-beta-signaling, mouse-models, aortopathy, related-connective-tissue-disorders | 2026-05-23 |
| sources/marfan-naturerc-2010 | Cañadas/Vilacosta/Fuster 2010 Nat Rev Cardiol Part 1 (pathophysiology + diagnosis): >1,000 FBN1 mutations; exon 24–32 severe/neonatal cluster; Habashi 2006 losartan mouse data; cystic medial necrosis; echo measurement standards (leading-edge, z-score >2); sinus:annulus ratio ≥1.45 pediatric screen; dural ectasia quantitative (L3 >0.47 / S1 >0.57 — 95% Sn/98% Sp); LDS Type I vs II; ACTA2/MYH11 familial TAAS | marfan-syndrome, connective-tissue-disorders, echocardiography, fibrillin-1, tgf-beta-signaling | 2026-05-23 |
| sources/marfan-lancet-2005 | Judge/Dietz 2005 Lancet Seminar: Marfan syndrome — FBN1 haploinsufficiency, Ghent 1996 criteria, multisystem manifestations (aortic root, ectopia lentis, skeletal, dural ectasia), TGF-β dysregulation mechanism, beta-blockers standard of care, Bentall vs valve-sparing surgery, Loeys-Dietz syndrome differential | marfan-syndrome, connective-tissue-disorders, aortic-aneurysm, fibrillin-1, tgf-beta-signaling | 2026-05-23 |
| sources/cardiac-glycosides-hfrEF-fcvm-2026 | Wang/Pan/Peng et al. 2026 Front. Cardiovasc. Med. systematic review + meta-analysis (6 RCTs; n=8,488; HFrEF): cardiac glycosides vs placebo — all-cause mortality HR=0.98 (NS); HF hospitalization HR=0.79 (P<0.05); indirect digitoxin vs digoxin comparison NS for both outcomes; hospitalization result sensitive to DIG trial exclusion; DIGIT-HF (2025) only contemporary GDMT trial included | cardiac-glycosides, heart-failure, HFrEF, digoxin, meta-analysis | 2026-05-22 |
| sources/crp-hf-jacc-2021 | Bozkurt et al. 2021 JACC Expert Panel: CR in HF — Class 1A ACC/AHA; HF-ACTION backbone evidence; 10–30% participation worldwide; FITT framework; HF-ACTION protocol (60–70% HRR; 36 sessions); MCT mainstay; HIIT not superior (SMARTEX-HF); inspiratory muscle training in respiratory weakness; LVEF not reliable CR benefit marker; no CMS HFpEF coverage; 6-week wait removal + telemedicine expansion proposed | #heart-failure, #cardiac-rehabilitation, #exercise-training, #HFrEF, #HFpEF | 2026-05-22 |
| sources/mavacamten-explorer-hcm-lancet-2020 | Olivotto et al. 2020 Lancet EXPLORER-HCM phase 3 RCT (N=251; 30 weeks; obstructive HCM NYHA II–III): mavacamten vs placebo — primary composite (pVO2 + NYHA) 37% vs 17% (p=0.0005); post-exercise LVOT gradient −35.6 mmHg (p<0.0001); NYHA ≥1 class 65% vs 31%; complete response (LVOT <30+NYHA I) 27% vs 1%; NT-proBNP 80% greater reduction; hs-cTnI 41% greater reduction; LVEF <50% transient in 7 patients, all recovered; pivotal trial establishing mavacamten as first disease-specific HCM therapy | #hypertrophic-cardiomyopathy, #mavacamten, #LVOT-obstruction, #cardiac-myosin-inhibitor, #randomized-controlled-trial | 2026-05-22 |
| sources/wct-baseline-jecg-2021 | Evenson/Kashou/May et al. 2021 J Electrocardiol correspondence: conceptual basis — SWCT electrically constrained by His-Purkinje (near-identical QRS to baseline); VT has electrical freedom (markedly different from baseline); exceptions: fascicular VT + BBR-VT resemble baseline; literature timeline: Sandler 1965 (44% SVT vs 4% PVC shared initial vector), Dongas 1985 (unchanged V1/II/III morphology → SWCT), Griffith 1991 (≥40° axis shift 83% VT vs 36% SWCT), Pachón 2019 (4 baseline criteria: QRS normalisation AF 100% Sp; QRS narrower 99% Sp; discordant BBB 99% Sp; identical morphology 99% Sp SWCT); WCT Formula II 2020 (PTVAC; AUC 0.96); all 3 automated AUCs: WCT Formula 0.97, VT Prediction 0.90, WCT Formula II 0.96 | #wide-complex-tachycardia, #ventricular-tachycardia, #ECG-algorithm, #automated-ECG-interpretation, #baseline-ECG-comparison | 2026-05-22 |
| sources/wct-kashou-jaha-2020 | Kashou/May et al. 2020 JAHA mini review: comprehensive WCT algorithm taxonomy — multistep (Brugada/Vereckei/LLA), VT-as-default (Griffith), Bayesian (Lau 2000; pretest LR×serial multiplication), single-criterion (Pava), point-based (Jastrzebski PPV 100%≥4; Pachón PPV 100%≥2/PPV 98%−1); AV dissociation visible on 12-lead ECG in ~1/5 VTs; all algorithms EP-lab validated only — real-world performance unknown; automated methods: WCT Formula (frontal/horizontal amplitude change→VT probability 0–100%) and VT prediction model (QRS/T axis/duration change); both require paired baseline ECG; ML future direction; authors have CoI in automated methods | #wide-complex-tachycardia, #ventricular-tachycardia, #ECG-algorithm, #automated-ECG-interpretation, #electrocardiography | 2026-05-22 |
| sources/vt-chen-hrs-2019 | Chen/Natale et al. 2019 Heart Rhythm prospective original article (n=528 EP-confirmed WCTs; 397 VT, 131 SVT; Texas Cardiac Arrhythmia Institute + Henan Provincial Hospital China): introduces Limb Lead Algorithm (LLA) — (1) monophasic R aVR; (2) neg I+II+III; (3) OQL: concordant monophasic inferior leads + opposite polarity remaining limb leads; any one criterion = VT; Sn 87.2%, Sp 90.8% (highest), PPV 96.7% (highest), κ 0.98 (best), AUC 0.89; no measurements required; Brugada specificity 59.5% overall/48.1% RBBB (most granular independent validation); LLA fails for fascicular/para-Hisian/papillary muscle VT | #ventricular-tachycardia, #wide-QRS-complex, #electrocardiography, #ECG-algorithm, #differential-diagnosis | 2026-05-22 |
| sources/lpfvt-svt-circep-2017 | Michowitz/Tovia-Brodie/Belhassen et al. 2017 Circ EP original article (n=183 LPF-VT ECGs vs 61 RBBB+LAHB controls; Tel Aviv/Sheba ablation centres + Medline): first systematic ECG characterisation of LPF-VT; 4-criterion multivariate model — atypical V1 (OR 5.1), positive aVR (OR 19.2), V6 R/S ≤1 (OR 6.7), QRS ≤140 ms (OR 7.7); ≥3 criteria = high probability LPF-VT; Sn 82.1%/Sp 78.3%; confirms RS interval 62 ms (not discriminating from RBBB+LAHB P=0.4); Vi/Vt >1; Wellens >140 ms criterion inverted; all standard WCT algorithms fail for LPF-VT | #fascicular-ventricular-tachycardia, #wide-QRS-complex, #electrocardiography, #ECG-algorithm, #differential-diagnosis | 2026-05-21 |
| sources/vt-vereckei-ehj-2007 | Vereckei/Duray/Miller et al. 2007 EHJ prospective original article (n=453 EP-confirmed WCTs; 331 VT, 105 SVT, 17 PXT; Indiana University EP lab): introduces Vereckei 2007 12-lead algorithm — (1) AV dissociation; (2) initial R wave in aVR → VT (never positive in 17 PXTs); (3) morphology inconsistent with BBB/fascicular block → VT; (4) Vi/Vt ≤1 → VT (Vi/Vt = voltage initial 40 ms / terminal 40 ms); overall accuracy 90.3% vs Brugada 84.8% (P=0.006); Sn 95.7% vs 88.2%; Step 4 Vi/Vt TA 82.2% vs Brugada morphological 68% (P=0.004); superior in pre-existing BBB, AAD treatment, idiopathic VT subgroups; Vi/Vt not applicable in 3.5% (all VTs); first true head-to-head comparison vs Brugada; led to 2008 aVR-only simplification | #ventricular-tachycardia, #wide-QRS-complex, #electrocardiography, #ECG-algorithm, #differential-diagnosis | 2026-05-21 |
| sources/vt-brugada-circ-1991 | Brugada P et al. 1991 Circulation prospective original article (n=554 EP-confirmed WCTs; 384 VT, 170 SVT-A; OLV Hospital Aalst): landmark paper introducing the Brugada 4-step algorithm — (1) absence of RS in all precordials Sp 100%; (2) RS interval >100 ms in any precordial Sp 98%; (3) AV dissociation Sp 98%; (4) morphological criteria V1/V2 + V6 (RBBB: monophasic R/qR/RS R>S; V6 QS/QR/R≤S; LBBB: R>30 ms/RS>60 ms/notched S; V6 any Q) — overall Sn 98.7% Sp 96.5%; defines RS interval measurement; highlights fascicular VT and pre-excited SVT as algorithm limitations | #ventricular-tachycardia, #wide-QRS-complex, #electrocardiography, #ECG-algorithm, #differential-diagnosis | 2026-05-21 |
| SOURCES | |||
| sources/svt-esc-2019 | Brugada/Katritsis et al. 2019 ESC Guidelines for SVT (EHJ 2019;40:4768–4817): replaces 2003 ESC guidelines; 22 recommendation tables covering all SVT subtypes; key new evidence: PROCAMIO trial (procainamide superior to amiodarone in stable WCT); modified Valsalva (43% vs 17% conversion); asymptomatic pre-excitation EPS Class I for high-risk/athletes; TCM Class I for catheter ablation; intermittent pre-excitation downgraded as low-risk marker; amiodarone Class III/B in pre-excited AF (mechanism confirmed); anticoagulation IIa/C for flutter without AF; IST catheter ablation explicitly not recommended | #supraventricular-tachycardia, #catheter-ablation, #arrhythmia-management, #accessory-pathway, #guidelines | 2026-05-21 |
| sources/svt-aha-2015 | Page/Joglar/Caldwell et al. 2015/2016 ACC/AHA/HRS multi-society guideline (Circulation 2016;133:e506-e574): comprehensive SVT management (excluding AF) in adults — AVNRT, AVRT/WPW, focal/multifocal AT, atrial flutter, IST, junctional tachycardia; hierarchical acute management (vagal maneuvers → adenosine → IV CCB/BB → cardioversion); catheter ablation Class I first-line for symptomatic AVNRT/AVRT; Class III/Harm AV nodal blockers in pre-excited AF; atrial flutter anticoagulation mirrors AF; CTI ablation >97% success; full drug tables (acute/ongoing) and special populations (pregnancy, ACHD, pediatrics, elderly) | #supraventricular-tachycardia, #arrhythmia-management, #catheter-ablation, #antiarrhythmic-drugs, #guidelines | 2026-05-21 |
| sources/svt-vt-europace-2011 | Alzand/Crijns 2011 Europace review (Maastricht UMC): 45-year historical evolution of BCT diagnostic criteria — clinical history PPVs (MI 98%, CHF/angina 100%); AV dissociation in up to 50% of VTs (VA conduction); canon A waves vs frog sign; Lewis lead technique; classical criteria (Sandler-Marriott 1965 concordance/rabbit ears; Wellens 1978; Swanick 1972; Griffith 1991 multivariate; Alberca 1997 specificity); Brugada 4-step (Sn 0.987/Sp 0.965); Vereckei aVR 2007 vs 2008 simplified; limitations: class Ic/III drug-induced BCT, bundle branch reentry (rapid intrinsicoid deflection), fascicular VT (RS <80 ms — below Brugada threshold), pre-excited SVT; default VT diagnosis + procainamide when uncertain | #broad-complex-tachycardia, #ventricular-tachycardia, #ECG-algorithm, #supraventricular-tachycardia, #electrocardiography | 2026-05-21 |
| sources/svt-vt-basel-jaccep-2022 | Moccetti/Yadava/Reichlin et al. 2022 JACC CEP original research (n=206 derivation + 203 validation WCT episodes; EP-confirmed diagnoses; Basel University Hospital + OHSU): Basel Algorithm — 3-criterion WCT differentiation tool (clinical high-risk + lead II TFP >40 ms + lead aVR TFP >40 ms; VT if ≥2 of 3 met); SN 93.3%, SP 90.4% (validation); comparable to Brugada/Vereckei accuracy; time to diagnosis 38 sec vs 106 sec (Brugada; P=0.002) and 48 sec (Vereckei; P=0.02); superior diagnostic accuracy vs Vereckei (81% vs 72%; P=0.002) in clinical applicability test; underperforms in fascicular VT, antidromic AVRT, Mahaim | #wide-complex-tachycardia, #ventricular-tachycardia, #supraventricular-tachycardia, #electrocardiography, #ECG-algorithm | 2026-05-21 |
| sources/bisoprolol-copd-jcopd-2023 | Feng/Zhang/Liu et al. 2023 IJCOPD PRISMA meta-analysis of 35 RCTs (n=3,269; bisoprolol vs control in COPD; 32/35 Chinese studies; 2/35 placebo-controlled; 2/35 blinded): bisoprolol improved FEV1 +0.46 L (P<0.001), FVC +0.20 L (P=0.008), FEV1% +0.64pp (P<0.001), 6MWD (P<0.001); reduced IL-6 −1.16, IL-8 −0.94, CRP −1.74 (all P<0.001); adverse events NS vs control (RR 0.83; P=0.38); subgroup analyses showed effects independent of HF status; high heterogeneity (I²=66–95%); BLOCK COPD (metoprolol, placebo-controlled) not addressed; two ongoing bisoprolol RCTs (ISRCTN10497306; NCT03917914) | #bisoprolol, #COPD, #beta-blockers, #meta-analysis, #systematic-review | 2026-05-21 |
| sources/metoprolol-block-copd-nejm-2019 | Dransfield/Bhatt et al. 2019 NEJM BLOCK COPD double-blind RCT (n=532; 26 US centres; moderate-severe COPD, mean FEV1 41% predicted; no established BB indication; extended-release metoprolol vs placebo; ~1yr): primary endpoint (time to first COPD exacerbation) neutral (202 vs 222 days; HR 1.05; P=0.66) — trial stopped early for futility and safety; metoprolol increased hospitalisation for exacerbation (HR 1.91; 95% CI 1.29–2.83); very severe exacerbation rate ratio 3.71; 11 vs 5 deaths (7 vs 1 COPD-attributed); worsened dyspnea (SOBQ +4.80 pts, exceeds MCID) and COPD symptoms (CAT +1.47 pts); no FEV1 change; directly refutes observational data suggesting BB benefit in COPD without cardiac indication | #beta-blockers, #COPD, #exacerbations, #metoprolol, #randomized-controlled-trial | 2026-05-21 |
| sources/olezarsen-essence-timi73b-nejm-2025 | Bergmark/Marston/Sabatine et al. 2025 NEJM ESSENCE–TIMI 73b Phase 3 double-blind RCT (n=1,349; moderate HTG TG 150–499 mg/dL + elevated CV risk; 160 sites; monthly SC olezarsen 50 mg or 80 mg vs placebo; 12 months): primary 6-month placebo-adjusted TG reduction −58.4 pp (50 mg; P<0.001) and −60.6 pp (80 mg; P<0.001); TG <150 mg/dL achieved 85–89% vs 12.5% placebo; APOC3 −62–70%; remnant cholesterol up to −70%; non-HDL-C −22%; ApoB −15%; LDL-C unchanged; safety comparable to placebo except more injection-site reactions and mild transaminase elevations (no clinically significant hepatotoxicity); no platelet safety signal; first phase 3 RCT of APOC3 inhibition in broad moderate HTG population | #hypertriglyceridemia, #antisense-oligonucleotide, #apolipoprotein-C-III, #lipid-lowering-therapy, #cardiovascular-risk | 2026-05-21 |
| sources/pots-ccs-2020 | Raj/Guzman/Sheldon et al. 2020 CCS Position Statement on POTS and Related Disorders (Can J Cardiol 2020;36:357–372): novel nomenclature ecosystem for chronic orthostatic intolerance — POTS (core criteria with CCS clarifications: minimum HR 90 bpm adults/100 bpm teens; sustained ≥2 readings ≥1 min apart; ≥3 months), POTS plus (POTS + debilitating non-CV symptoms ± comorbidities: hEDS 25%, CFS/ME 21%, fibromyalgia 20%, MCAS 9%), PSWT (symptoms without tachycardia — NOT POTS), PTOC (secondary identifiable cause — NOT POTS), asymptomatic orthostatic tachycardia; GRADE-graded treatment: salt 10 g/day + 3 L fluid + semirecumbent exercise (strong first-line); midodrine (strong, moderate QOE) + low-dose propranolol (strong, moderate QOE) as first-line pharmacotherapy; pyridostigmine/fludrocortisone/ivabradine/clonidine/methyldopa weak suggestions; strong recommendations AGAINST chronic IV saline, RF sinus node ablation, Chiari decompression, jugular venoplasty | #postural-orthostatic-tachycardia-syndrome, #orthostatic-intolerance, #autonomic-dysfunction, #dysautonomia, #guidelines | 2026-05-21 |
| sources/POTS-IST-VVS-HRS-2015 | Sheldon et al. 2015 HRS/AAS/ACC/AHA/APHRS/EHRA/PACES/SOLAECE multi-society consensus on POTS, IST, and VVS: POTS defined by HR ≥30 bpm increase on standing (≥40 bpm aged 12–19), 4 subtypes (neuropathic/hypovolemic/hyperadrenergic/deconditioning), prevalence 0.2%; IST defined by resting HR >100 bpm + mean 24h HR >90 bpm, ivabradine 70% symptom elimination in small RCT; VVS cumulative incidence 42% women/32% men by age 60, physical counterpressure maneuvers 39% RRR, ISSUE-3 pacing 57% RRR in asystole + negative tilt test; pacing and sinus node ablation not recommended for POTS/IST | #POTS, #vasovagal-syncope, #inappropriate-sinus-tachycardia, #autonomic-dysfunction, #orthostatic-intolerance | 2026-05-20 |
| sources/ht-esc-2024 | McEvoy/McCarthy/Bruno et al. 2024 ESC Guidelines for Elevated Blood Pressure and Hypertension (European Heart Journal 2024;45:3912–4018): new 3-category BP classification (Non-elevated <120/70; Elevated 120–139/70–89; Hypertension ≥140/90); unified SBP target 120–129 mmHg (Class I, A); SCORE2/SCORE2-OP risk-stratified treatment of elevated BP; primary aldosteronism ARR screening ALL confirmed HT patients (Class IIa, B); renal denervation upgraded Class III → IIb; HMOD triggers treatment at elevated BP without SCORE2; pregnancy threshold lowered to ≥140/90 mmHg; single guideline replacing 2018 ESC/ESH | hypertension, blood-pressure, cardiovascular-risk, pharmacotherapy, guidelines | 2026-05-20 |
| sources/obicetrapib-broadway-nejm-2025 | Nicholls/Nelson/BROADWAY Investigators 2025 NEJM phase 3 double-blind RCT (n=2,530; 188 sites; China/Europe/Japan/US; HeFH 17% or ASCVD 89% on max LLT; 2:1 obicetrapib 10 mg OD vs placebo; 365 days): primary LDL-C change Day 84: −32.6 pp between-group difference (P<0.001); achieved LDL 62.8 vs 92.3 mg/dL; <55 mg/dL attainment 51% vs 8%; Lp(a) −33.5%; ApoB −18.9%; HDL-C +136.3%; adverse events comparable to placebo; new-onset DM/glycaemia numerically lower (35.1% vs 40.0%); exploratory CV events HR 0.79 (NS; underpowered); BROOKLYN outcomes trial ongoing | dyslipidemia, CETP-inhibitor, LDL-cholesterol, familial-hypercholesterolemia, lipid-lowering-therapy | 2026-05-20 |
| sources/lorundrostat-advancehtn-nejm-2025 | Laffin/Nissen/Advance-HTN Investigators 2025 NEJM phase 2b double-blind RCT (n=285; 103 US sites; uncontrolled HT on 2–5 drugs; standardized regimen + 24h ABPM; 12 weeks): lorundrostat 50 mg vs 50→100 mg dose-adjustment vs placebo; primary 24h ambulatory SBP placebo-adjusted −7.9 mmHg (50 mg; P=0.001) and −6.5 mmHg (dose-adjusted; P=0.006); week 4 combined −5.3 mmHg (P<0.001); 53% Black; hyperkalemia K>6.0: 5–7% vs 0%; eGFR −13–15% (reversible); MATE1 inhibition → spurious creatinine rise (cystatin C preferred); no adrenal insufficiency | resistant-hypertension, aldosterone-synthase-inhibitor, lorundrostat, ambulatory-blood-pressure, randomized-controlled-trial | 2026-05-20 |
| sources/edoxaban-af-cad-nejm-2024 | Cho/Kang/Ahn et al. 2024 NEJM EPIC-CAD open-label RCT (n=1,040; 18 South Korean sites; AF + stable CAD; 12 months): edoxaban monotherapy vs edoxaban + antiplatelet (aspirin/clopidogrel) — NACE 6.8% vs 16.2% (HR 0.44; 95% CI 0.30–0.65; P<0.001; NNT 10.6); major ischemic events 1.6% vs 1.8% (HR 1.23; NS; underpowered); major + CRNM bleeding 4.7% vs 14.2% (HR 0.34); benefit driven by bleeding reduction; first RCT with standard-dose edoxaban including medically managed stable CAD; East Asian population only | atrial-fibrillation, coronary-artery-disease, edoxaban, antithrombotic-therapy, anticoagulation | 2026-05-20 |
| sources/NOAC-VTE-COBRRA-NEJM-2026 | Castellucci/Le Gal/Rodger et al. 2026 NEJM COBRRA PROBE RCT (n=2,760; 32 centres; Canada/Australia/Ireland; 3-month treatment; acute PE or proximal DVT): apixaban vs rivaroxaban — clinically relevant bleeding 3.3% vs 7.1% (RR 0.46; 95% CI 0.33–0.65; P<0.001); major bleeding 0.4% vs 2.4% (RR 0.16); CRNMB 2.9% vs 4.9% (RR 0.59); recurrent VTE 1.1% vs 1.0% (NS); first head-to-head RCT establishing apixaban as safer NOAC for acute VTE; bleeding difference concentrated in rivaroxaban loading-dose period (days 1–21) | venous-thromboembolism, noac, apixaban, rivaroxaban, bleeding-risk | 2026-05-20 |
| sources/Apixaban-VTE-HIPRO-NEJM-2025 | Piazza/Bikdeli/Goldhaber et al. 2025 NEJM HI-PRO double-blind RCT (n=600; single-centre Brigham and Women's Hospital; provoked VTE + ≥1 enduring risk factor; ≥3 months prior anticoagulation completed; 12-month extension): apixaban 2.5 mg BID vs placebo — recurrent VTE 1.3% vs 10.0% (HR 0.13; 95% CI 0.04–0.36; P<0.001; 87% reduction); major bleeding 0.3% vs 0% (NS); CRNMB 4.8% vs 1.7% (HR 2.68; P=0.06 trend); 10% placebo recurrence rate in "provoked" VTE challenges provoked/unprovoked binary; enduring risk factors (obesity, autoimmune, lung disease, ASCVD) identify high-recurrence subpopulation | venous-thromboembolism, apixaban, extended-anticoagulation, provoked-VTE, randomized-controlled-trial | 2026-05-20 |
| sources/baxdrostat-baxhtn-nejm-2025 | Flack/Williams/BaxHTN Investigators 2025 NEJM phase 3 double-blind RCT (n=794; 214 sites; uncontrolled HT ≥2 drugs or resistant HT ≥3 drugs including diuretic; SBP 135–170 mmHg; 12-week Part 1 + 8-week randomised-withdrawal Part 3): baxdrostat 1 mg and 2 mg once daily vs placebo added to background therapy — primary endpoint met: placebo-corrected SBP −8.7 mmHg (1 mg; 95% CI −11.5 to −5.8; P<0.001) and −9.8 mmHg (2 mg; 95% CI −12.6 to −7.0; P<0.001); BP <130 mmHg at 12 weeks ~40% vs 18.7%; resistant HT subgroup consistent (−9.1 and −9.8 mmHg); randomised-withdrawal confirmed slow BP offset (−5.1 mmHg difference; P=0.002); hyperkalemia K>5.5: 6.1% (1 mg) and 11.1% (2 mg) vs 0.4%; hyponatremia ~20%; eGFR −7 ml/min (reversible); no adrenal insufficiency; funded by AstraZeneca | resistant-hypertension, aldosterone-synthase-inhibitor, baxdrostat, randomized-controlled-trial, hypertension | 2026-05-20 |
| sources/vffr-fastiii-nejm-2026 | Daemen/FAST III Investigators 2026 NEJM investigator-initiated noninferiority RCT (n=2,235; 37 centers; 7 European countries; intermediate coronary lesions 30–80% stenosis; chronic or ACS; 1yr follow-up): vFFR (3D-QCA, no wire, no adenosine) vs pressure-wire FFR for revascularization guidance — primary MACE (death/MI/revasc) NONINFERIOR: 7.5% vs 7.5% (risk diff −0.02 pp; 95% CI −2.25 to 2.21; P=0.004 NI); vFFR detected more functionally significant lesions (40.9% vs 31.3%); higher revascularization rate (45% vs 36%); procedure time −5.1 min; intraprocedural complications 3.7% vs 6.0%; first RCT establishing angiography-based vFFR as equivalent to wire-based FFR for clinical outcomes | angiography-based-physiology, fractional-flow-reserve, coronary-physiology, intermediate-coronary-lesions, randomized-controlled-trial | 2026-05-20 |
| sources/bp-dm-bproad-nejm-2025 | Bi et al. 2025 NEJM BPROAD RCT (n=12,821; T2DM ≥50 years; SBP <120 vs <140 mmHg; 145 Chinese sites; median 4.2yr): primary composite (nonfatal stroke/MI, HF hosp, CV death) HR 0.79 (95% CI 0.69–0.90; P<0.001); stroke HR 0.79; albuminuria HR 0.87; SAE equivalent; hypotension 0.1% vs <0.1%; hyperkalemia 2.8% vs 2.0%; first adequately-powered RCT to confirm SBP <120 mmHg superior to <140 mmHg in T2DM | type-2-diabetes, hypertension, blood-pressure-control, cardiovascular-outcomes-trial, randomized-controlled-trial | 2026-05-20 |
| sources/ffrpci-mi-fullrevasc-nejm-2024 | Böhm/James et al. 2024 NEJM FULL REVASC RCT (n=1,542; STEMI + very-high-risk NSTEMI + multivessel CAD; FFR-guided complete revascularization vs culprit-only PCI; 32 centres, 7 countries; median 4.8yr): primary composite (death/MI/unplanned revasc) neutral (19.0% vs 20.4%; HR 0.93; P=0.53); death/MI HR 1.12 NS; unplanned revasc HR 0.76 NS; any revascularization HR 0.59 (lower with complete); stent thrombosis HR 2.80 (2.5% vs 0.9%; significant harm); 40% of FFR arm deferred all nonculprit lesions (FFR >0.80); diverges from angiography-guided COMPLETE trial (26% CV death/MI reduction); FFR cannot detect vulnerable plaque | stemi, multivessel-pci, fractional-flow-reserve, complete-revascularization, randomized-controlled-trial | 2026-05-20 |
| sources/cep-tavi-bhfprotecttavi-nejm-2025 | Kharbanda/BHF PROTECT-TAVI Investigators 2025 NEJM RCT (n=7,635; 33 UK centres; aortic stenosis; 1:1 Sentinel CEP vs no CEP during TAVI; stopped for futility Oct 2024): routine CEP did NOT reduce stroke (2.1% CEP vs 2.2% control; diff −0.02 pp; 95% CI −0.68 to 0.63; P=0.94); disabling stroke 1.2% vs 1.4% (NS); death within 72h 0.8% vs 0.7% (NS); serious adverse events 0.6% vs 0.3% (doubled with CEP); lower 99% CI excluded ≥40% RRR; device (both filters) deployed in 81.2%; CACE analysis concordant; confirms/supersedes PROTECTED TAVR (n=3,000) null result; definitively settles routine CEP in TAVI | TAVI, cerebral-embolic-protection, stroke-prevention, randomized-controlled-trial, aortic-stenosis | 2026-05-20 |
| sources/mvteer-matterhorn-nejm-2024 | Baldus/Doenst/Pfister et al. 2024 NEJM MATTERHORN investigator-initiated noninferiority RCT (n=210; Germany; HF + secondary MR; LVEF ≥20%; TEER MitraClip vs MV surgery; 1yr follow-up): first head-to-head TEER vs surgery in SMR — primary efficacy composite (death/HF hosp/reintervention/LVAD/stroke) TEER 16.7% vs surgery 22.5% (diff −6 pp; 95% CI −17 to 6; NI P<0.001); RRR 0.74 (0.41–1.34); primary 30-day safety: 14.9% vs 54.8% (diff −40 pp; P<0.001); major bleeding 3.1% vs 24.4%; new-onset AF 3.1% vs 27.8%; stroke 0% vs 4.4%; MR ≥3+ recurrence at 1yr: 8.9% vs 1.5% (NI met but directionally worse); NYHA/6MWD similar between groups; MR ≤2+ at 1yr 96.1% vs 98.6%; lower-risk population than COAPT (mean LVEF 43%; STS-PROM 2.0%); industry-independent academic oversight | secondary-mitral-regurgitation, transcatheter-edge-to-edge-repair, mitral-valve-surgery, heart-failure, randomized-controlled-trial | 2026-05-19 |
| sources/mvteer-reshapehf2-nejm-2024 | Anker/Friede/von Bardeleben et al. 2024 NEJM RESHAPE-HF2 investigator-initiated RCT (n=505; 30 sites; 9 countries; symptomatic HFrEF LVEF 20–50% + moderate-to-severe SMR 3+/4+ despite GDMT; median EROA 0.23 cm²; MitraClip TEER + GDMT vs GDMT alone; 24-month follow-up): all 3 co-primary endpoints met — HF hosp/CV death 37.0 vs 58.9/100 pt-yr (RR 0.64; P=0.002); HF hosp alone 26.9 vs 46.6/100 pt-yr (RR 0.59; P=0.002); KCCQ-OS +10.9 pts (P<0.001); NNT 5.1 for HF hosp; all-cause mortality NS (HR 0.90; consistent with less advanced disease than COAPT); NYHA I/II 74.5% vs 58.5% at 12m; MR ≤2+ 90.4% vs 36.1%; device safety 1.6%; extends TEER evidence below EROA 0.40 cm² threshold; first trial in moderate-to-severe SMR | secondary-mitral-regurgitation, transcatheter-edge-to-edge-repair, MitraClip, heart-failure, randomized-controlled-trial | 2026-05-19 |
| sources/mvteer-coapt-nejm-2023 | Stone/Mack et al. 2023 NEJM COAPT 5-year RCT follow-up (n=614; 78 US/Canadian sites; symptomatic HFrEF LVEF 20–50% + moderate-to-severe/severe SMR despite maximal GDMT; MitraClip TEER + GDMT vs GDMT alone): annualized HF hosp 33.1% vs 57.2%/yr (HR 0.53); all-cause mortality 57.3% vs 67.2% (HR 0.72; 95% CI 0.58–0.89); death/HF hosp 73.6% vs 91.5% (HR 0.53); device-specific safety events 1.4% (all ≤30 days); landmark analysis: benefit concentrated first 2–3 years; 44.9% of eligible control crossover after 2yr attenuates late divergence; days alive out of hospital 1124 vs 895; MR ≤1+ at discharge 82.3%; severe MS 7.6% device (no surgery); first-generation MitraClip; SGLT2i used in only 3 patients | secondary-mitral-regurgitation, transcatheter-edge-to-edge-repair, MitraClip, heart-failure, randomized-controlled-trial | 2026-05-19 |
| sources/tavr-dedicate-nejm-2024 | Blankenberg/Seiffert et al. 2024 NEJM DEDICATE-DZHK6 RCT (n=1,414; 38 German sites; severe symptomatic AS; low/intermediate surgical risk; median STS-PROM 1.8%; mean age 74; operator-choice CE-marked devices; industry-independent; 1yr follow-up): primary composite (death or stroke) TAVI 5.4% vs SAVR 10.0%; HR 0.53 (95% CI 0.35–0.79; P<0.001 noninferiority); all-cause death 2.6% vs 6.2% (HR 0.43); disabling stroke 1.3% vs 3.1% (HR 0.42); new-onset AF 12.4% vs 30.8% (HR 0.36); pacemaker 11.8% vs 6.7% (HR 1.81); major bleeding 4.3% vs 17.2% (HR 0.24); vascular complications 7.9% vs 0.7%; valve hemodynamics equivalent at 1yr; SAVR event rates higher than PARTNER 3 (COVID-19 + higher female proportion); largest industry-independent pragmatic TAVI–SAVR RCT | aortic-stenosis, TAVI, SAVR, randomized-controlled-trial, valvular-heart-disease | 2026-05-19 |
| sources/tvteer-triluminate-nejm-2023 | Sorajja/Adams et al. 2023 NEJM TRILUMINATE Pivotal RCT (n=350; 1:1; 65 centers US/Canada/Europe; severe symptomatic TR; intermediate/high surgical risk; 93.9% functional TR; 70.7% massive/torrential; mean age 78; 1yr follow-up): win ratio 1.48 (95% CI 1.06–2.13; P=0.02) favouring TriClip TEER; QoL-driven — KCCQ ≥15pts 49.7% vs 26.4%; mean KCCQ +12.3 vs +0.6 (P<0.001); TR ≤moderate 87.0% at 30 days, 88.1% at 1yr; NYHA I/II 83.9% vs 59.5%; 6MWD NS (−8.1 vs −25.2m); death/TV surgery 9.4% vs 10.6% NS; HF hosp 0.21 vs 0.17/pt-yr NS (control lower); safety: 98.3% MAE-free 30 days; PPM 2.9% both groups (no increase); BARC ≥3a 5.2%; no device embolization/thrombosis; single-leaflet attachment 7.0%; QoL-TR correlation: ≥2 grade reduction +18pts KCCQ vs no-change +2pts; echo core lab unblinded to group assignment | tricuspid-regurgitation, transcatheter-edge-to-edge-repair, TriClip, structural-heart-disease, randomized-controlled-trial | 2026-05-19 |
| sources/ttvr-triscendii-nejm-2025 | Hahn/Kodali et al. 2025 NEJM TRISCEND II RCT (n=400; 45 centers US+Germany; severe symptomatic TR; 2:1 EVOQUE TTVR + med therapy vs med therapy alone; 1yr follow-up): win ratio 2.02 (95% CI 1.56–2.62; P<0.001) favoring TTVR; QoL-driven — KCCQ-OS ≥10pts 66.4% vs 36.5%; NYHA ≥1 class 78.9% vs 24.0%; 6MWD ≥30m 47.6% vs 31.8%; TR ≤mild 95.2% vs 2.3%; RV EDD −5.8 mm (reverse remodeling); all-cause death 12.6% vs 15.2% (NS; not powered); HF hosp 20.9% vs 26.1% (NS); severe bleeding 15.4% vs 5.3% (P=0.003); new PPM 17.4% vs 2.3% (P<0.001); PPM 27.8% in naive patients; periprocedural anticoagulation protocol drives excess 30-day bleeding; no RVAD/transplant in either group; pivotal trial under FDA Breakthrough Device Program | tricuspid-regurgitation, transcatheter-valve-replacement, EVOQUE, structural-heart-disease, randomized-controlled-trial | 2026-05-19 |
| sources/tavi-earlytavr-nejm-2025 | Généreux/Leon et al. 2025 NEJM EARLY TAVR RCT (n=901; 75 US/Canadian sites; asymptomatic severe AS; LVEF ≥50%; STS-PROM ≤10%; mean age 75.8; 83.6% low surgical risk; SAPIEN 3/3 Ultra; median 3.8yr): early TAVR vs clinical surveillance — primary composite (death+stroke+unplanned CV hosp) HR 0.50 (95% CI 0.40–0.63; P<0.001); death HR 0.93 NS; stroke HR 0.62 NS; unplanned CV hosp HR 0.43; favorable outcome at 2yr 86.6% vs 68.0% (P<0.001); LV/LA health 48.1% vs 35.9% (P=0.001); 87% surveillance crossover at median 11.1 months; 39.2% with advanced symptoms before conversion; HF hosp HR 0.32 (exploratory); supports ESC 2025 Class IIa early intervention in asymptomatic severe AS | aortic-stenosis, asymptomatic-AS, TAVR, randomized-controlled-trial, valvular-heart-disease | 2026-05-19 |
| sources/iFR-PPCI-iMODERN-NEJM-2026 | Nijveldt/Maeng/van Royen et al. 2026 NEJM iMODERN RCT (n=1,146; 41 sites; STEMI + multivessel CAD; 3-year follow-up): immediate iFR-guided nonculprit PCI (iFR ≤0.89) vs deferred cardiac stress MRI-guided PCI within 6 weeks — primary composite (death/recurrent MI/HF hosp) NOT superior: 9.3% vs 9.8% (HR 0.95; 95% CI 0.65–1.40; P=0.81); iFR treated more lesions (42.6% vs 18.7%); HF hosp HR 0.24 (0.07–0.84) lower in iFR; stroke/TIA HR 0.36 (0.15–0.86) lower in iFR; stent thrombosis 1.7% vs 0.6% (higher iFR); first trial comparing physiologic (iFR) vs noninvasive imaging (MRI) guidance for nonculprit revascularization | stemi, multivessel-pci, ifr-guided-pci, complete-revascularization, randomized-controlled-trial | 2026-05-19 |
| sources/reduced-apixaban-apicat-nejm-2025 | Mahé/Carrier et al. 2025 NEJM API-CAT double-blind RCT (N=1,766; active cancer; ≥6 months prior anticoagulation for proximal DVT or PE; 121 centers; 11 countries; 12 months): apixaban 2.5 mg BID vs 5.0 mg BID — recurrent VTE noninferior (2.1% vs 2.8%; SHR 0.76; 95% CI 0.41–1.41; P=0.001); clinically relevant bleeding superior (12.1% vs 15.6%; SHR 0.75; P=0.03); major bleeding 2.9% vs 4.3% (NS); mortality 17.7% vs 19.6% (HR 0.96; NS); first RCT establishing reduced-dose apixaban as preferred extended-duration strategy in cancer-associated VTE | cancer-associated-VTE, apixaban, venous-thromboembolism, extended-anticoagulation, randomized-controlled-trial | 2026-05-19 |
| sources/PCI-TAVI-NOTION3-NEJM-2024 | Lønborg/Jabbari/Engstrøm et al. 2024 NEJM NOTION-3 RCT (n=455; 12 Nordic-Baltic sites; severe AS + FFR ≤0.80 or ≥90% stenosis; median age 82; STS-PROM 3%; SYNTAX 9; median 2yr follow-up): PCI + TAVI vs conservative + TAVI — primary MACE (death/MI/urgent revasc) HR 0.71 (95% CI 0.51–0.99; P=0.04); MI HR 0.54; urgent revasc HR 0.20 (both significant); all-cause death HR 0.85 (NS); bleeding HR 1.51 (higher with PCI); AKI HR 0.45 (lower with PCI); 89% complete revascularisation; supersedes neutral ACTIVATION trial; informs ESC 2025 Class IIa B recommendation for PCI ≥90% stenosis before TAVI | TAVI, aortic-stenosis, coronary-artery-disease, fractional-flow-reserve, randomized-controlled-trial | 2026-05-19 |
| sources/PCI-Elderly-SENIORRITA-NEJM-2024 | Kunadian/Fox et al. 2024 NEJM BHF SENIOR-RITA RCT (n=1,518; ≥75 years; mean age 82; 45% women; 32% frail; 62.5% cognitively impaired; 48 UK sites; median 4.1 years): invasive strategy (angiography ± revascularisation + best medical therapy) vs conservative (best medical therapy alone) — primary composite CV death or nonfatal MI neutral (HR 0.94; P=0.53); nonfatal MI HR 0.75 (P<0.05); CV death HR 1.11 NS; time-varying benefit: early advantage at 1 year (12.8% vs 16.8%) erodes by 5 years; subsequent revascularisation 3.9% vs 13.7%; radial access 89.3%; procedural complications <1%; largest and longest RCT in elderly NSTEMI | nstemi, elderly-patients, invasive-strategy, frailty, randomized-controlled-trial | 2026-05-18 |
| sources/oral-semaglutide-soul-nejm-2025 | McGuire/Marx/Mulvagh et al. 2025 NEJM SOUL superiority RCT (n=9,650; T2DM HbA1c 6.5–10%; age ≥50; ASCVD, CKD, or both; 444 sites, 33 countries; median 49.5 months; Novo Nordisk): oral semaglutide 14mg once daily vs placebo — primary 3-point MACE HR 0.86 (95% CI 0.77–0.96; P=0.006); nonfatal MI HR 0.74 (dominant); CV death HR 0.93 NS; nonfatal stroke HR 0.88 NS; kidney composite (confirmatory secondary) HR 0.91 (P=0.19) — not significant; major adverse limb events HR 0.71 (directional); HbA1c −0.56 pp; weight −2.95 kg; hsCRP 1.56 vs 2.01 mg/L; serious AEs 47.9% vs 50.3% (P=0.02 lower); GI discontinuations 6.4% vs 2.0%; first oral GLP-1 RA with CV superiority | type-2-diabetes, GLP-1-receptor-agonist, cardiovascular-outcomes-trial, oral-semaglutide, MACE | 2026-05-18 |
| sources/spironolactone-ami-clear-nejm-2025 | Jolly/d'Entremont/Pitt et al. 2025 NEJM CLEAR RCT spironolactone arm (n=7,062; 104 centres; 14 countries; 2×2 factorial; 95.1% STEMI post-PCI; spironolactone 25 mg vs placebo; median 3yr follow-up): both primary endpoints neutral — CV death/new HF HR 0.91 (P=0.51); MACE composite HR 0.96 (P=0.60); on-treatment HR 0.79/0.83 (approaching significance; driven by 28% dropout); gynecomastia 2.3% vs 0.5%; hyperkalemia 1.1% vs 0.6%; eGFR −1.8 ml/min/1.73m²; no LVEF data; largest RCT of routine MRA in unselected AMI — definitively negative ITT | spironolactone, acute-myocardial-infarction, mineralocorticoid-receptor-antagonist, randomized-controlled-trial, STEMI | 2026-05-18 |
| sources/as-recovery-nejm-2026 | Kang/Park et al. 2026 NEJM RECOVERY trial 10-year extended follow-up (N=145; asymptomatic very severe AS; AVA ≤0.75 cm² + Vmax ≥4.5 m/s; early SAVR vs conservative care; median 144 months): primary composite (CV death + operative mortality) 3% vs 24% (HR 0.10; P=0.002); all-cause mortality 15% vs 32% (HR 0.42); NNT=6 CV death, NNT=7 all-cause; 0% vs 19% HF hospitalisation; Kaplan-Meier curves diverged continuously at 10 years | aortic-stenosis, surgical-avr, asymptomatic-AS, randomized-controlled-trial, valvular-heart-disease | 2026-05-18 |
| sources/hf-copd-hfreview-2025 | Magrì/Fiori/Agostoni et al. 2025 narrative review (Heart Failure Reviews; Italian Society of Cardiology HF Working Group): bidirectional HF-COPD pathophysiology; 70% of COPD+HF is HFpEF; COPD 13% of HF patients (highest in HFpEF 16%); CPET VE intercept (≥2.6 L/min) identifies COPD in HF across EF spectrum; bisoprolol preferred in HFrEF+COPD; β-blockers contraindicated in HFpEF+COPD; LAMA+ICS preferred over LABA in new COPD diagnosis in HF | heart-failure, COPD, cardiopulmonary-interaction, HFpEF, beta-blockers | 2026-05-18 |
| sources/aav9-danon-nejm-2025 | Greenberg/Taylor/Rossano et al. 2025 NEJM Phase 1 open-label trial (n=7 males; Danon disease; rAAV9-LAMP2B single IV infusion 6.7×10¹³ or 1.1×10¹⁴ gc/kg + prednisone/calcineurin inhibitor/rituximab; 24–54 months follow-up): all 7 alive; 6 evaluable — LVM index median −23%; troponin I −84%; natriuretic peptides −57%; LAMP2 protein confirmed biopsy 6/6 at 12 months; adult patients now 21–24 yr (beyond typical transplant/death age 19–21 yr); grade 4 TMA in 1 high-dose patient (LVEF 32% baseline) requiring RRT → transplant; grade 3 steroid-induced myopathy (3 patients); anti-LAMP2B antibodies in several patients (no clinical sequelae); longest published AAV cardiac follow-up | gene-therapy, danon-disease, AAV9, hypertrophic-cardiomyopathy, LAMP2 | 2026-05-18 |
| sources/aav9-pompe-nejm-2025 | Ma/Zhuang/Feng et al. 2025 NEJM pilot trial (n=4 infants; infantile-onset Pompe disease; single IV rAAV9-coGAA 1.2×10¹⁴ vg/kg + prednisolone; 52-week observation): 3/4 survived with improved LVM index, LVEF, and HINE scores; 2 patients reached normal neurological milestones by 12 months; walked without assistance by 22–25 months — no anti-GAA antibodies detected in any patient (vs universal anti-rhGAA IgG with ERT); AAV9 crosses BBB (potential CNS benefit); respiratory infections (all 4 patients) worsened cardiac function and reduced GAA activity; 1 death (parental withdrawal); first human systemic AAV9-GAA data | gene-therapy, pompe-disease, AAV9, lysosomal-storage-disorder, acid-alpha-glucosidase | 2026-05-17 |
| sources/empagliflozin-empactmi-nejm-2024 | Butler/Jones/Udell et al. 2024 NEJM EMPACT-MI double-blind RCT (n=6,522; 451 sites; 22 countries; median 17.9 months): empagliflozin 10 mg within 14 days of MI (LVEF <45% or in-hospital congestion + ≥1 HF enrichment factor; 74.8% STEMI; 89.3% revascularised) — primary composite HF hosp or all-cause death NEUTRAL (8.2% vs 9.1%; HR 0.90; 95% CI 0.76–1.06; P=0.21); HF hosp alone HR 0.77 (0.60–0.98); all-cause death HR 0.96 (NS); CV death HR 1.03 (NS); total HF hosp rate ratio 0.67 (exploratory; 0.51–0.89); all secondary endpoints NS; safety comparable to placebo | empagliflozin, acute-myocardial-infarction, sglt2-inhibitors, heart-failure-prevention, randomized-controlled-trial | 2026-05-17 |
| sources/dapagliflozin-dapackd-nejm-2020 | Heerspink/Wheeler et al. 2020 NEJM DAPA-CKD double-blind RCT (n=4,304; 386 sites; 21 countries; eGFR 25–75; UACR 200–5000; 67.5% T2DM; 32.5% non-DM; dapagliflozin 10 mg vs placebo; median 2.4 years; stopped early for efficacy): primary composite (≥50% eGFR decline/ESKD/renal or CV death) HR 0.61 (9.2% vs 14.5%; P<0.001; NNT=19); renal-specific HR 0.56; CV composite HR 0.71; all-cause mortality HR 0.69; non-T2DM subgroup HR 0.50; eGFR chronic slope +1.92 mL/min/yr benefit; no DKA; first SGLT2i trial establishing benefit in non-diabetic CKD | sglt2-inhibitors, chronic-kidney-disease, dapagliflozin, cardiorenal-outcomes, randomized-controlled-trial | 2026-05-22 |
| sources/empagliflozin-empakidney-nejm-2025 | Herrington/Staplin et al. 2025 NEJM EMPA-KIDNEY post-trial follow-up (n=6,609 randomised; 4,891 in post-trial; ~4 years total; 185 sites; 7 countries): empagliflozin 10 mg vs placebo in CKD (eGFR 20–44 any UACR; or eGFR 45–89 + UACR ≥200) — combined primary composite (KD progression or CV death) HR 0.79 (95% CI 0.72–0.87; 26.2% vs 30.3%); ESKD HR 0.74; CV death HR 0.75; post-trial-only HR 0.87 (CI 0.76–0.99); legacy effect up to 12 months after stopping (6-month HR 0.60, year 2 HR 0.90 NS); benefits consistent across diabetes/non-diabetes, all eGFR/albuminuria strata; no non-CV death effect | sglt2-inhibitors, chronic-kidney-disease, empagliflozin, cardiorenal-outcomes, post-trial-follow-up | 2026-05-17 |
| sources/bb-mi-abyss-nejm-2024 | Silvain/Montalescot et al. 2024 NEJM ABYSS RCT (n=3,698; LVEF ≥40%; median 2.9yr post-MI; 49 French sites; PROBE design; median 3yr follow-up): BB interruption vs continuation — primary composite (death/MI/stroke/CV hosp) 23.8% vs 21.1%; HR 1.16 (95% CI 1.01–1.33); upper CI 5.5pp exceeds 3pp NI margin; noninferiority NOT met; hard outcomes identical (death 4.1 vs 4.0%; MI 2.5 vs 2.4%; stroke 1.0 vs 1.0%); CV hospitalisation drove composite (18.9 vs 16.6%); QoL no improvement (EQ-5D diff 0.002); concordant with REDUCE-AMI on hard outcomes | beta-blockers, myocardial-infarction, secondary-prevention, noninferiority-trial, coronary-artery-disease | 2026-05-17 |
| sources/tirzepatide-hfpef-summit-nejm-2025 | Packer/Zile/Borlaug et al. 2025 NEJM SUMMIT Phase 3 double-blind RCT (n=731; LVEF ≥50%; BMI ≥30; NYHA II–IV; 129 centres; 9 countries; median 104 weeks; Eli Lilly): tirzepatide up to 15 mg SC weekly vs placebo — both primary endpoints met: composite CV death/worsening HF HR 0.62 (95% CI 0.41–0.95; P=0.026); KCCQ-CSS +6.9 pts (P<0.001); weight −13.9% vs −2.2%; 6MWT +18.3m; CRP −38.8% (all P<0.001); all-cause death HR 1.25 NS (19 vs 15); first hard composite outcome benefit in obesity-HFpEF | heart-failure-preserved-ejection-fraction, tirzepatide, GLP-1-receptor-agonist, GIP-receptor-agonist, obesity | 2026-05-17 |
| sources/nexz-crispr-attrcm-nejm-2024 | Fontana/Gillmore et al. 2024 NEJM Phase 1 open-label trial (n=36; ATTR-CM; 50% NYHA III; 31% ATTRv; single site UK; median 18 months follow-up): nexiguran ziclumeran (nex-z/NTLA-2001), CRISPR-Cas9 LNP gene editing therapy, single IV infusion; mean serum TTR −89% at 28 days, −90% at 12 months (95% CI −93 to −87), sustained through 24 months; disease stable in 66% on all prognostic markers; NYHA improved 47%; KCCQ +8 pts; safety manageable (5 infusion reactions, 2 transient AST elevations, 1 unrelated death); first clinical CRISPR-Cas9 in ATTR-CM; Phase 3 MAGNITUDE trial ongoing | gene-therapy, attr-cardiomyopathy, CRISPR-Cas9, TTR-knockdown, lipid-nanoparticle | 2026-05-17 |
| sources/fe-hf-heartfid-nejm-2023 | Mentz et al. 2023 NEJM HEART-FID RCT (n=3,065; ambulatory HFrEF LVEF ≤40%; iron deficiency; median 1.9 yr): IV ferric carboxymaltose vs placebo; hierarchical primary composite (death/HF hosp/6MWT) win ratio 1.10 (99% CI 0.99–1.23; P=0.02) — did NOT meet pre-specified p<0.01; CV death/HF hosp HR 0.93 NS; all-cause death HR 0.90 NS; safe; largest IV iron RCT; contrasts with AFFIRM-AHF (acute HF) near-significant result | heart-failure, iron-deficiency, ferric-carboxymaltose, HFrEF, randomized-controlled-trial | 2026-05-17 |
| sources/tavr-partner3-5yr-nejm-2023 | Mack/Leon et al. 2023 NEJM PARTNER 3 5-year RCT (n=1,000; 71 sites; low-risk AS; STS-PROM 1.9%; SAPIEN 3 vs SAVR): composite death/stroke/rehospitalization TAVR 22.8% vs SAVR 27.2% (P=0.07; HR 0.79) — NS; win ratio 1.17 (NS); early TAVR superiority attenuated by year 5; mortality 10.0% vs 8.2% (NS; landmark years 1–5 HR 1.17 favoring surgery); AF 13.7% vs 42.4%; valve thrombosis 2.5% vs 0.2%; bioprosthetic-valve failure 3.3% vs 3.8%; KCCQ-OS 86.2 vs 85.9 | aortic-stenosis, TAVR, low-surgical-risk, bioprosthetic-valve-durability, randomized-controlled-trial | 2026-05-17 |
| sources/complete-pci-multistars-ami-nejm-2023 | Stähli et al. 2023 NEJM MULTISTARS AMI RCT (n=840; 37 European sites; hemodynamically stable STEMI + multivessel CAD): immediate multivessel PCI vs staged (19–45 days); primary composite (death/MI/stroke/unplanned revasc/HF hosp) 8.5% vs 16.3%; RR 0.52 (95% CI 0.38–0.72); P<0.001 noninferiority AND superiority; benefit in first 45 days from lower MI (2.0% vs 5.3%) and unplanned revasc (4.1% vs 9.3%); death/stroke/HF NS; major bleeding NS | stemi, multivessel-pci, complete-revascularization, coronary-artery-disease, pci-timing | 2026-05-17 |
| sources/pfa-advent-nejm-2023 | Reddy et al. 2023 NEJM ADVENT RCT (n=607; 30 US centers; Bayesian NI): PFA vs thermal ablation (RF/cryo) in drug-refractory PAF — efficacy NI (73.3% vs 71.3%; posterior NI >0.999); safety NI (2.1% vs 1.5%; posterior NI >0.999); PV area superior (−0.9% vs −12.0%; posterior superiority >0.999); 1 death (catheter manipulation); 3 asymptomatic MRI cerebral lesions PFA vs 0 thermal; first RCT of PFA vs thermal ablation | paroxysmal-atrial-fibrillation, pulsed-field-ablation, catheter-ablation, randomized-controlled-trial, noninferiority-trial | 2026-05-17 |
| sources/pfa-cryo-singleshotchampion-nejm-2025 | Reichlin/Kueffer/Sticherling 2025 NEJM SINGLE SHOT CHAMPION RCT (n=210; 2 Swiss centers; Farapulse pentaspline PFA vs Arctic Front cryo; all patients ICM continuous monitoring): PFA NI (P<0.001) AND superior (P=0.046) to cryoablation (37.1% vs 50.7% recurrence days 91–365; −13.6 pp; 95% CI −26.9 to −0.3); lower recurrence during blanking period too (−20.0 pp); PFA 18 min shorter; safety comparable (1 stroke PFA vs 2 tamponades cryo); first RCT with superiority signal for PFA over cryo | atrial-fibrillation, pulsed-field-ablation, cryoballoon-ablation, randomized-controlled-trial, continuous-rhythm-monitoring | 2026-05-18 |
| sources/crt-longterm-raft-nejm-2024 | Sapp/Tang 2024 NEJM RAFT Long-Term (n=1,050; 8 sites from original 1,798-patient RAFT; median 7.7yr all/13.9yr survivors; ITT; exponential AFT model): CRT-D vs ICD; primary all-cause death acceleration factor 0.80 (95% CI 0.69–0.92; P=0.002); secondary composite (death/HTx/LVAD) AF 0.85 (0.74–0.98); curves converge after 12yr; ~80% mortality at 15yr in CRT-D; benefit sustained despite AF and non-LBBB inclusion; longest CRT survival data available | cardiac-resynchronization-therapy, heart-failure-reduced-EF, long-term-outcomes, implantable-cardioverter-defibrillator, randomized-controlled-trial | 2026-05-17 |
| sources/tr-nejm-2023 | Hahn 2023 NEJM comprehensive TR review: anatomy (40% annular dilation threshold; RCA <3mm inferiorly; AV node 3–5mm from anteroseptal commissure), epidemiology (severe TR 1yr mortality 36–42%; HR 2.74 vs aortic HR 1.62 vs mitral HR 1.25), atrial/ventricular/CIED classification, 5-grade echo scheme, surgical (10–12% isolated TV mortality), TEER (80–85% ≤moderate; 30–50% ≤mild), TRILUMINATE Pivotal (WR 1.48 QoL-driven) | #tricuspid-regurgitation, #valvular-heart-disease, #transcatheter-interventions, #right-heart-failure, #echocardiography | 2026-05-17 |
| sources/semaglutide-stephfpef-nejm-2023 | Kosiborod/Borlaug 2023 NEJM STEP-HFpEF RCT (n=529; HFpEF LVEF ≥45% + BMI ≥30; no diabetes; 96 sites; 13 countries; 52 weeks): semaglutide 2.4mg SC weekly vs placebo — both dual primary endpoints met P<0.001: KCCQ-CSS +7.8 pts (vs 0.5–2.3 pts in prior HFpEF pharmacotherapy) and body weight −10.7 pp; all confirmatory secondary endpoints met: 6MWT +20.3m; hierarchical composite win ratio 1.72; CRP −43.5% vs −7.3%; HF hospitalizations 1 vs 12 (exploratory); serious adverse events 13.3% vs 26.7% (P<0.001; cardiac events 2.7% vs 11.3%); first obesity-targeting pharmacotherapy in HFpEF | heart-failure-preserved-ejection-fraction, semaglutide, GLP-1-receptor-agonist, obesity, randomized-controlled-trial | 2026-05-17 |
| sources/patisiran-attrcm-apollob-nejm-2023 | Maurer/Gillmore/APOLLO-B Investigators 2023 NEJM Phase 3 double-blind RCT (n=360; ~80% ATTRwt; 25% on tafamidis; 12 months): patisiran 0.3 mg/kg IV Q3W (LNP-siRNA) vs placebo in ATTR-CM — primary 6MWT +14.69 m (P=0.02) ✓ below MCID; KCCQ-OS +3.7 pts (P=0.04) ✓; composite death/CV events win ratio 1.27 NS ✗; composite death/hosp HR 0.88 NS ✗; deaths 4 vs 10 (HR 0.36 NS; underpowered); 86.8% TTR knockdown; exploratory: LV mass −9.45 g, NT-proBNP ratio 0.80, troponin I ratio 0.87; infusion reactions/arthralgia/muscle spasms more common; patisiran not approved for ATTR-CM; proof-of-concept for cardiac RNAi; succeeded by vutrisiran (HELIOS-B 2025 mortality benefit) | attr-cardiomyopathy, patisiran, RNA-interference, TTR-knockdown, heart-failure | 2026-05-17 |
| sources/CA-HF-CASTLEHTx-NEJM-2023 | Sohns/Marrouche/CASTLE-HTx Investigators 2023 NEJM single-center open-label RCT (n=194; end-stage HFrEF LVEF ≤35% + symptomatic AF + transplant/LVAD evaluation; ablation + GDMT vs GDMT alone; stopped early at 18-month median follow-up): primary composite (death/LVAD/urgent HTx) 8% vs 30% HR 0.24 (P<0.001); all-cause mortality 6% vs 20% HR 0.29; LVEF +7.8 vs +1.4 pp at 12mo; AF burden −31.4 vs −8.6 pp; first RCT demonstrating ablation benefit in end-stage HFrEF; single-center limitation | atrial-fibrillation, catheter-ablation, heart-failure, end-stage-heart-failure, randomized-controlled-trial | 2026-05-17 |
| sources/edoxaban-ahre-noahafnet6-nejm-2023 | Kirchhof/NOAH-AFNET 6 Investigators 2023 NEJM double-blind RCT (N=2,536; age ≥65; CIED-detected AHREs ≥6 min; no ECG-confirmed AF; median CHA₂DS₂-VASc 4; median AHRE duration 2.8h; 206 sites; 18 European countries; stopped early at 21 months): edoxaban vs placebo; primary composite (CV death + stroke + SE) HR 0.81 (NS); safety composite (death + major bleeding) HR 1.31 (P=0.03); major bleeding HR 2.10; stroke ~1%/yr in both groups (far below ECG-confirmed AF comparators); 18.2% developed ECG-confirmed AF during follow-up; low arrhythmia burden = unexpectedly low embolic risk; companion/contrasting trial to ARTESIA | subclinical-atrial-fibrillation, anticoagulation, edoxaban, atrial-high-rate-episodes, stroke-prevention | 2026-05-17 |
| sources/apixaban-scaf-artesia-nejm-2024 | Healey/Connolly ARTESIA Investigators 2024 NEJM Phase 3 double-blind RCT (N=4,012; mean CHA₂DS₂-VASc 3.9; mean age 76.8; CIED-detected SCAF 6 min–24 h; 247 sites; 16 countries; mean 3.5yr): apixaban vs aspirin; stroke/SE HR 0.63 (P=0.007; 37% RRR); disabling/fatal stroke HR 0.51 (49% RRR); major bleeding HR 1.80 (P=0.001); fatal bleeding and ICH NS; 90% bleeds managed without invasive procedures; net clinical benefit favours OAC at CHA₂DS₂-VASc ~3.9; contradicts neutral NOAH-AFNET 6 (edoxaban vs placebo, underpowered) | subclinical-atrial-fibrillation, anticoagulation, stroke-prevention, apixaban, randomized-controlled-trial | 2026-05-17 |
| sources/crp-nejm-2024 | Thomas RJ 2024 NEJM review: cardiac rehabilitation — 36-session multidisciplinary secondary prevention program; only 24% of eligible US patients participate; 1–2% mortality reduction per session attended (dose-response, observational); NNT=12 readmission, NNT=34 death at 1yr post-PCI; women/Black/Hispanic patients <19%; home-based CR: 43% vs 13% initiation, 36% lower mortality (VA); Cochrane RCTs neutral for all-cause mortality; future: wearables, prehabilitation, expanded eligibility (AF, HFpEF, cancer+CVD) | cardiac-rehabilitation, secondary-prevention, coronary-artery-disease, exercise-training, participation-disparities | 2026-05-17 |
| sources/crp-jcm-2025 | Aleksova et al. 2025 J Clin Med review (Part 1 of 2): four-phase CR programme after acute MI — Phase I (in-hospital, 3–7 days post-PCI; 25% mortality reduction in 1988 meta-analysis); Phase II (post-discharge 6–12 wks; illness perception/BIPQ as adherence driver); Phase III/IV sparse evidence; RESILIENT RCT: mHealth-CR failed in older adults; historical evolution from bedrest to early mobilisation | cardiac-rehabilitation, myocardial-infarction, exercise-training, secondary-prevention, illness-perception | 2026-05-22 |
| sources/corin-acmp-nejm-2023 | Baris Feldman et al. 2023 NEJM Brief Report: two Filipino siblings with homozygous CORIN LOF (c.684dupG; p.Met229Aspfs*16) — first human case of complete corin deficiency; phenotype: isolated LA cardiomyopathy (fibrosis + hypertrophic remodelling) + resistant hypertension + refractory AF; plasma corin undetectable, NT-proANP negligible, BNP compensatory; β-ENaC upregulated; PICP elevated; TIMP-1 normal; soluble corin replacement as therapeutic concept | #atrial-cardiomyopathy, #natriuretic-peptides, #genetics, #hypertension, #atrial-fibrosis | 2026-05-17 |
| sources/bb-mi-reduceami-nejm-2024 | Yndigegn/Jernberg/REDUCE-AMI Investigators 2024 NEJM RCT (n=5,020; 45 centres; LVEF ≥50%; metoprolol/bisoprolol vs no BB; median 3.5 yr): primary composite death/new MI HR 0.96 (95% CI 0.79–1.16; P=0.64) — neutral; all secondary endpoints (CV death, all-cause death, MI, AF hosp, HF hosp) and safety endpoints similar; annual event rate 2.4% vs 2.5%; first contemporary well-powered RCT showing no benefit of BBs in preserved-EF post-MI | beta-blockers, myocardial-infarction, preserved-ejection-fraction, secondary-prevention, randomized-controlled-trial | 2026-05-17 |
| sources/wearable-cv-nejm-2024 | Spatz/Ginsburg/Turakhia 2024 NEJM review: wearable DHTs for CV monitoring — RPM for HF/HTN/AF; single-lead ECG sensitivity 78–88%/specificity 80–86% for AF; Apple (PPV 84%) and Fitbit (PPV 98%) Heart Studies; ambulatory ECG diagnostic yield 32–34%; no validated cuffless BP device (www.validatebp.org); hub model for RPM; pulse oximetry racial bias; long-term outcome benefit unproven | wearable-digital-health, remote-patient-monitoring, atrial-fibrillation, heart-failure, cardiovascular-monitoring | 2026-05-17 |
| sources/finerenone-hfpef-fineartshf-nejm-2024 | Solomon, McMurray et al. 2024 NEJM Phase 3 double-blind RCT (n=6,001; 654 sites; 37 countries; median 32 months): finerenone (nonsteroidal MRA) vs placebo in HF with LVEF ≥40% — primary composite (total worsening HF events + CV death) rate ratio 0.84 (P=0.007); HF events RR 0.82 (P=0.006); CV death HR 0.93 (NS); all-cause death HR 0.93 (NS); KCCQ +1.6 pts (below MCID); kidney composite HR 1.33 (NS, numerically worse); hyperkalemia 3.0% vs 1.4%; benefit consistent in SGLT2i users; first MRA with positive primary endpoint in HFpEF/HFmrEF | #heart-failure, #HFpEF, #finerenone, #mineralocorticoid-receptor-antagonist, #randomized-controlled-trial | 2026-05-16 |
| sources/vutrisiran-attrcm-heliosb-nejm-2025 | Fontana et al. 2025 NEJM Phase 3 double-blind RCT (n=655; 87 sites; 26 countries; up to 36 months): vutrisiran (GalNAc-siRNA, 25 mg SC Q12W; 81% TTR knockdown) vs placebo in ATTR-CM — primary composite endpoint met (death + recurrent CV events HR 0.72; P=0.01); all-cause mortality HR 0.65 through 42 months (P=0.01); 6MWT +26.5 m; KCCQ-OS +5.8 pts; benefits on and off background tafamidis; first RNAi therapy to reduce mortality in ATTR-CM | #attr-cardiomyopathy, #RNA-interference, #vutrisiran, #heart-failure, #randomized-controlled-trial | 2026-05-16 |
| sources/aficamten-sequoiahcm-nejm-2024 | Maron et al. 2024 NEJM Phase 3 double-blind RCT (N=282; 101 sites; 14 countries; 24 weeks): aficamten (5–20 mg) vs placebo on background therapy in symptomatic obstructive HCM — primary endpoint met (peak VO2 +1.7 ml/kg/min; P<0.001); all 10 secondary endpoints significant (NYHA 58.5% vs 24.3%; KCCQ-CSS +7 pts; Valsalva LVOTO −50 mmHg; post-Valsalva <30 mmHg 49.3% vs 3.6%; SRT eligibility −78 days); NT-proBNP 80% reduction; LVEF <50% in 3.5% (transient, no HF exacerbations); benefit consistent regardless of background beta-blocker use | #hypertrophic-cardiomyopathy, #aficamten, #cardiac-myosin-inhibitor, #obstructive-HCM, #randomized-controlled-trial | 2026-05-17 |
| sources/aficamten-maplehcm-nejm-2025 | Garcia-Pavia et al. 2025 NEJM Phase 3 head-to-head RCT (N=175; 71 sites; 24 weeks): aficamten monotherapy vs metoprolol monotherapy in obstructive HCM — primary endpoint met (peak VO2 difference +2.3 ml/kg/min; P<0.001); aficamten superior on NYHA (51% vs 26% improved), KCCQ-CSS (+6.9 points), Valsalva gradient (−40.7 vs −3.8 mmHg), NT-proBNP (81% relative difference), LAVi; metoprolol failed to improve any objective hemodynamic endpoint despite HR −23.4 bpm; LVEF <50% only 1% with aficamten; first RCT of cardiac myosin inhibitor superiority over beta-blockers as monotherapy | hypertrophic-cardiomyopathy, aficamten, obstructive-HCM, cardiac-myosin-inhibitor, beta-blockers | 2026-05-16 |
| sources/mavacamten-odysseyhcm-nejm-2025 | Desai et al. 2025 NEJM Phase 3 RCT (N=580; 201 centers; 22 countries; 48 weeks): mavacamten in symptomatic nonobstructive HCM — both primary endpoints missed (peak VO2 P=0.07; KCCQ-CSS P=0.06); NT-proBNP reduced 59% (biomarker-clinical dissociation); LVEF <50% in 21.5% vs 1.7% placebo; serious CHF 6.6% vs 1.7%; confirms LVOTO relief is primary mechanism of benefit in obstructive HCM; no approved therapy exists for nonobstructive HCM | hypertrophic-cardiomyopathy, mavacamten, nonobstructive-HCM, cardiac-myosin-inhibitor, clinical-trial | 2026-05-16 |
| sources/ecg-technology-aha-2007 | Kligfield et al. 2007 AHA/ACCF/HRS scientific statement (Part I of 6-part ECG standardization series): digital ECG technology and recording standards; high-frequency cutoff ≥150 Hz adults (≥250 Hz children); 40 Hz monitor cutoff invalidates amplitudes; global measurement preferred over single-lead (systematically longer — all QRS/QT criteria require recalibration); V5 on horizontal plane of V4; V1/V2 superior misplacement → false anterior infarction; Cabrera sequence (aVL→I→−aVR→II→aVF→III) "highly recommended"; Mason-Likar NOT interchangeable with standard ECG; right-sided leads recommended in inferior STEMI; computerized ECG is adjunct only — physician overreading required (cardiologist 96% vs computer 91%) | electrocardiography, ECG-technology, ECG-standardization, digital-ECG, lead-placement | 2026-05-16 |
| sources/ecg-bbb-aha-2009 | Surawicz/Childers/Deal/Gettes 2009 AHA/ACCF/HRS scientific statement (Part III of 6-part ECG standardization series): intraventricular conduction disturbances; normal QRS duration (>110 ms abnormal in adults); frontal plane axis table by age; complete RBBB (QRS ≥120 ms; rsr'/rsR'/rSR' in V1/V2; S duration > R in I/V6; R-peak >50 ms in V1); complete LBBB (8 criteria; criterion 7: negative concordance = ABNORMAL — formal AHA basis for Sgarbossa concordant criteria); LAFB (axis −45° to −90°; qR in aVL; R-peak ≥45 ms in aVL; QRS <120 ms); LPFB; WPW criteria; nonspecific IVCD; deprecated terms ("bifascicular block," "trifascicular block," "Brugada pattern" in automated algorithms) | electrocardiography, bundle-branch-block, intraventricular-conduction, ECG-standardization, ventricular-preexcitation | 2026-05-16 |
| sources/ecg-chambers-aha-2009 | Hancock/Deal/Mirvis/Okin/Kligfield/Gettes 2009 AHA/ACCF/HRS scientific statement (Part V of 6-part ECG standardization series): cardiac chamber hypertrophy; LVH voltage criteria (Sokolow-Lyon SV1+RV5 ≥35 mm; Cornell SV3+RaVL ≥28 mm men / ≥20 mm women; Romhilt-Estes point score); sensitivity <50% all criteria; specificity 85–90%; confounders (age/sex/race/obesity diverge Sokolow-Lyon vs Cornell); "strain" → "secondary ST-T abnormality" (AHA recommended); LVH in LBBB with caution; RVH (best in CHD; COPD pattern); atrial abnormality terminology ("intraatrial" not "interatrial"); PTF-V1 >40 mm·ms; RAA criteria P II >2.5 mm | electrocardiography, left-ventricular-hypertrophy, cardiac-chamber-hypertrophy, ECG-standardization, atrial-abnormality | 2026-05-16 |
| sources/ecg-ischemia-aha-2009 | Wagner/Macfarlane/Wellens 2009 AHA/ACCF/HRS scientific statement (Part VI of 6-part ECG standardization series): acute ischemia/infarction ECG criteria; sex/age J-point elevation thresholds; Cabrera contiguous lead format; coronary artery localization from ST-segment spatial vector; V3R/V4R for RV infarction; Wellens T-wave pattern (proximal LAD stenosis warning); Sgarbossa criteria for LBBB (concordant STE/STD high specificity; discordant ≥5 mm very low specificity per HERO-2); left main/multivessel 8-lead STD pattern; Selvester QRS score | electrocardiography, myocardial-ischemia, ST-segment, acute-coronary-syndrome, ECG-standardization | 2026-05-16 |
| sources/ecg-sttu-aha-2009 | Rautaharju/Surawicz/Gettes 2009 AHA/ACCF/HRS scientific statement (Part IV of 6-part ECG standardization series): ST/T/U wave and QT interval standards; primary vs secondary repolarization distinction; ST elevation thresholds by age/sex/race (V2: 0.30 mV men <40; 0.15 mV women); T-wave quantitative descriptors (inverted/deep negative/giant negative); U wave norms; linear regression preferred over Bazett for QT correction; QT thresholds (women ≥460 ms; men >450 ms prolonged; ≤390 ms short); QT dispersion NOT recommended for routine reports | electrocardiography, QT-interval, ST-segment, repolarization, ECG-standardization | 2026-05-16 |
| sources/cdf-pe-hipeitho-nejm-2026 | Rosenfield/Klok/Piazza/HI-PEITHO Investigators 2026 NEJM RCT (N=544; intermediate-risk PE; 59 US/European sites; adaptive design; ITT): ultrasound-facilitated CDL (EkoSonic + alteplase) + anticoagulation vs anticoagulation alone; primary composite (PE-related death + cardiorespiratory decompensation/collapse + PE recurrence at 7 days) 4.0% vs 10.3% (RR 0.39; 95% CI 0.20–0.77; P=0.005); major bleeding 4.1% vs 3.0% (P=0.64); no intracranial hemorrhage in either group; first RCT to demonstrate CDL superiority over anticoagulation alone in intermediate-risk PE | pulmonary-embolism, catheter-directed-fibrinolysis, intermediate-risk, RCT, thrombolysis | 2026-05-16 |
| sources/ivus-chip-nejm-2026 | Diletti/Daemen/IVUS-CHIP Investigators 2026 NEJM RCT (N=2020; complex high-risk PCI; 37 European centres; median 19 months): IVUS-guided vs angiography-guided PCI; TVF 13.9% vs 11.1%; HR 1.25 (95% CI 0.97–1.60; P=0.08) — NOT superior; stent thrombosis lower with IVUS (0.2% vs 1.0%; HR 0.20); stent optimisation met in only 48% of IVUS lesions; neutral result despite Class IA guideline recommendation | ivus, complex-pci, intracoronary-imaging, pci-outcomes, coronary-artery-disease | 2026-05-16 |
| sources/ivus-optimal-nejm-2026 | Testa/Spitzer/Banning/OPTIMAL Investigators 2026 NEJM RCT (N=806; unprotected left main PCI; 28 European centres; median 2.9 years): IVUS-guided vs angiography-guided PCI; patient-oriented composite (stroke/MI/revascularisation/death) 33.7% vs 30.9%; HR 1.11 (95% CI 0.87–1.42; P=0.40) — NOT superior; stroke 3.0% vs 1.0% (HR 3.11; unexpected/unexplained); challenges Class IA IVUS recommendation for left main PCI | ivus, left-main-pci, intracoronary-imaging, pci-outcomes, coronary-artery-disease | 2026-05-16 |
| sources/intensive-ldl-ezpave-nejm-2026 | Lee YJ/Byeong-Keuk Kim/Ez-PAVE Investigators 2026 NEJM RCT (n=3,048; ASCVD; 17 South Korean sites; open-label; median 3.0 years; investigator-initiated): LDL-C target <55 mg/dL vs <70 mg/dL; first RCT directly comparing the two current guideline targets; primary composite (CV death/nonfatal MI/stroke/revascularisation/UA hosp) HR 0.67 (P=0.002); revascularisation HR 0.63; nonfatal MI HR 0.46; CV death NS; achieved LDL 56 vs 66 mg/dL; only 60.8% reached <55 mg/dL target; creatinine elevation lower in intensive group (1.2% vs 2.7%; P=0.004) | dyslipidemia, ldl-c, secondary-prevention, ASCVD, randomized-controlled-trial | 2026-05-16 |
| sources/crt-companion-nejm-2004 | Bristow/COMPANION Investigators 2004 NEJM RCT (n=1,520; NYHA III/IV; LVEF ≤35%; QRS ≥120ms + PR >150ms; ischaemic/non-ischaemic CM; 1:2:2 OPT/CRT-P/CRT-D; 128 US centres; Guidant-funded; stopped early): primary composite (death or any-cause hosp) HR 0.81 CRT-P (P=0.014) and HR 0.80 CRT-D (P=0.010); CRT-P mortality HR 0.76 (P=0.059 NS); CRT-D mortality HR 0.64 (P=0.003); HF death/hosp CRT-P 34% ↓, CRT-D 40% ↓; non-ischaemic CRT-D mortality HR 0.50 (P=0.015); 26% OPT withdrawal requiring reconsent; foundational CRT-D mortality RCT in NYHA III/IV | cardiac-resynchronization-therapy, heart-failure-reduced-EF, implantable-cardioverter-defibrillator, randomized-controlled-trial, intraventricular-conduction-delay | 2026-05-16 |
| sources/biological-tx-af-hrs-2019 | McRae/Davis 2019 Heart Rhythm systematic review + meta-analysis (25 preclinical animal studies; PubMed+Embase July 2018; CIHR-funded; SYRCLE/CAMARADES quality): biological therapies (gene transfer, miRNA, cell therapy) reduced AF inducibility OR 0.15 (P<0.01), fibrosis −6.7% (P<0.01), sinus rhythm +6.4 days (P<0.01); anti-miR-21 most replicated (4 labs); zero clinical trial translation; delivery/pre-AF design/single-target barriers identified | atrial-fibrillation, gene-therapy, microRNA, atrial-fibrosis, biological-therapy | 2026-05-15 |
| sources/icd-nicm-definite-nejm-2004 | Kadish/DEFINITE Investigators 2004 NEJM RCT (n=458; NICM; LVEF <36%; NSVT or ≥10 PVCs/hour; ACEi + BB background; 37 US centres; mean 29 months; St. Jude Medical-funded): single-chamber ICD vs standard therapy; primary all-cause mortality HR 0.65 (P=0.08 — NS); sudden arrhythmic death HR 0.20 (P=0.006); subgroups: men HR 0.49 (P=0.018), NYHA III HR 0.37 (P=0.02); underpowered (~1/3 arrhythmic deaths vs >50% assumed); first large NICM-specific primary prevention ICD trial; pattern replicated in DANISH | implantable-cardioverter-defibrillator, non-ischaemic-cardiomyopathy, primary-prevention, sudden-cardiac-death, randomized-controlled-trial | 2026-05-15 |
| sources/crt-maditcrt-nejm-2009 | Moss/MADIT-CRT Investigators 2009 NEJM RCT (n=1,820; LVEF ≤30%; QRS ≥130ms; NYHA I/II ischaemic or NYHA II non-ischaemic; CRT-D vs ICD; 3:2; 110 centres; mean 2.4 years; stopped early; Boston Scientific): primary composite (death/nonfatal HF event) HR 0.66 (P=0.001); HF events 41% ↓; no mortality difference; QRS ≥150ms HR 0.48 vs 130–149ms HR 1.06 (P=0.001 interaction); women HR 0.37 vs men HR 0.76; LV reverse remodeling at 1 year; foundational NYHA I/II CRT trial | cardiac-resynchronization-therapy, heart-failure-reduced-EF, randomized-controlled-trial, QRS-duration, left-ventricular-remodeling | 2026-05-15 |
| sources/icd-programming-hrs-2015 | Wilkoff/HRS 2015 international consensus (32 recommendations; 96% consensus; HRS/EHRA/APHRS/SOLAECE): ICD programming guidance across 4 domains — bradycardia mode (minimise RV pacing; MVP; biventricular ≥98%); tachycardia detection (prolonged 30/40 intervals; VF ≥200 bpm; SVT-VT discriminators); tachycardia therapy (ATP first-line 188–250 bpm; 71% shock reduction PainFREE Rx II; shocks = 5× mortality in SCD-HeFT); DT omission safe for standard left-sided transvenous implants (SIMPLE n=2,500 RCT; NORDIC-ICD noninferior); DT still required for S-ICD | implantable-cardioverter-defibrillator, ICD-programming, tachycardia-detection, antitachycardia-pacing, defibrillation-threshold-testing | 2026-05-15 |
| sources/crt-carehf-nejm-2005 | Cleland/CARE-HF Investigators 2005 NEJM multicenter RCT (n=813; NYHA III/IV; LVEF ≤35%; QRS ≥120ms + echo dyssynchrony criteria; CRT-P vs medical therapy; 82 European centres; mean 29.4 months): primary composite (death/unplanned CV hosp) HR 0.63 (P<0.001); all-cause mortality HR 0.64 (P<0.002; NNT≈9); HF hosp 18% vs 33%; LV reverse remodeling confirmed by core-lab echo; 7% residual SCD despite CRT-P; definitive CRT mortality trial | cardiac-resynchronization-therapy, heart-failure-reduced-EF, dyssynchrony, randomized-controlled-trial, all-cause-mortality | 2026-05-15 |
| sources/omecamtiv-galactichf-nejm-2021 | Teerlink/GALACTIC-HF Investigators 2021 NEJM phase 3 RCT (n=8,232; LVEF ≤35%; NYHA II–IV; inpatients + outpatients; >19% ARNi; 2.6% SGLT2i; 945 sites, 35 countries; median 21.8 months; Amgen/Cytokinetics/Servier): omecamtiv mecarbil vs placebo; primary composite (HF event or CV death) HR 0.92 (P=0.03); CV death HR 1.01 NS; all-cause death HR 1.00 NS; HF hosp HR 0.95 NS; KCCQ NS; LVEF ≤28% HR 0.84 vs LVEF >28% HR 1.04 (prespecified interaction); not approved/guideline-listed | cardiac-myosin-activator, heart-failure-reduced-EF, omecamtiv-mecarbil, randomized-controlled-trial, systolic-function | 2026-05-15 |
| sources/digitoxin-hfref-digithf-nejm-2025 | Bavendiek/Bauersachs 2025 NEJM DIGIT-HF RCT: digitoxin vs placebo in HFrEF (LVEF ≤40%; n=1,212; ARNi 39.5%, SGLT2i 19.3%; 65 sites Austria/Germany/Serbia; median 36 months); primary composite (death or first HF hosp) HR 0.82 (P=0.03; NNT=22); all-cause death noninferiority confirmed; individual components NS; underpowered (1,212 vs planned 2,190); digitoxin ≠ digoxin; first cardiac glycoside RCT on contemporary GDMT | cardiac-glycosides, heart-failure-reduced-EF, digitoxin, randomized-controlled-trial, cardiovascular-outcomes | 2026-05-14 |
| sources/mra-hfref-rales-nejm-1999 | Pitt/RALES Investigators 1999 NEJM double-blind RCT (n=1,663; LVEF ≤35%; NYHA III/IV; ACEi + loop diuretic; no BB required; pre-BB era; 195 centres; mean 24 months; stopped early; Searle-funded): spironolactone 25 mg OD; all-cause mortality RR 0.70 (P<0.001; 30% RRR); progressive HF death RR 0.64; SCD RR 0.71; HF hospitalisation RR 0.65; hyperkalemia 2% vs 1% NS; foundational MRA Class I NYHA III/IV trial | mineralocorticoid-receptor-antagonist, heart-failure-reduced-EF, spironolactone, randomized-controlled-trial, aldosterone-antagonist | 2026-05-14 |
| sources/icd-hfref-scdheft-nejm-2005 | Bardy/SCD-HeFT Investigators 2005 NEJM three-arm RCT (n=2,521; LVEF ≤35%; NYHA II/III; ischaemic 52%/NICM 48%; pre-SGLT2i/ARNi; median 45.5 months): ICD HR 0.77 (P=0.007; 23% RRR; absolute −7.2% at 5 years); amiodarone HR 1.06 (NS); no aetiology interaction (P=0.68); NYHA II ICD HR 0.54 vs NYHA III HR 1.16 NS; amiodarone NYHA III HR 1.44 harm (P=0.004 interaction); establishes LVEF ≤35% primary prevention ICD threshold | ICD, heart-failure-reduced-EF, sudden-cardiac-death, primary-prevention, randomized-controlled-trial | 2026-05-14 |
| sources/spironolactone-hfpef-topcat-nejm-2014 | Pitt/Pfeffer 2014 NEJM TOPCAT RCT: spironolactone vs placebo in HFpEF (LVEF ≥45%; n=3,445; 6 countries; mean 3.3y); primary composite HR 0.89 (NS); HF hosp HR 0.83 (P=0.04); BNP-stratum HR 0.65 (P=0.003); Russia/Georgia data integrity concern (canrenone in only 38% of "active" patients); Americas-only HR 0.82; basis for COR 2b/IIb MRA in HFpEF | mineralocorticoid-receptor-antagonist, heart-failure-preserved-EF, spironolactone, randomized-controlled-trial, cardiovascular-outcomes | 2026-05-14 |
| sources/icd-icm-maditii-nejm-2002 | Moss 2002 NEJM MADIT-II RCT: primary prevention ICD in ICM (prior MI + LVEF ≤30%; n=1,232; no EPS required; mean 20 months); all-cause mortality HR 0.69 (95% CI 0.51–0.93; P=0.016); 14.2% vs 19.8%; consistent across all subgroups; benefit at ~9 months; HF hospitalisation trend higher ICD arm (19.9% vs 14.9%); stopped early; foundational basis for Class I/AUC A(8–9) in ischaemic CMP | ICD, ischaemic-cardiomyopathy, primary-prevention, sudden-cardiac-death, randomized-controlled-trial | 2026-05-14 |
| sources/icd-nicm-danish-nejm-2016 | Køber 2016 NEJM DANISH RCT: primary prevention ICD in NICM (LVEF ≤35%; n=1,116; 58% CRT; median 67.6 months); all-cause mortality HR 0.87 (NS); SCD HR 0.50 (P=0.005); CV death HR 0.77 (NS); 31% non-CV deaths; age <68 HR 0.64 (significant); pre-SGLT2i/ARNi era; supports ESC Class IIa (not I) for NICM primary prevention | ICD, non-ischaemic-cardiomyopathy, sudden-cardiac-death, primary-prevention, randomized-controlled-trial | 2026-05-14 |
| sources/empagliflozin-hfpef-nejm-2021 | Anker/Packer 2021 NEJM EMPEROR-Preserved RCT: empagliflozin vs placebo in HFpEF/HFmrEF (LVEF >40%, n=5988, ~50% T2DM, median 26.2 months); primary composite CV death or HF hospitalisation HR 0.79 (NNT=31; P<0.001); HF hospitalisation HR 0.71; CV death HR 0.91 (NS); all-cause death HR 1.00; eGFR decline slower; first large positive pharmacotherapy trial in HFpEF | SGLT2-inhibitors, heart-failure-preserved-EF, empagliflozin, randomized-controlled-trial, cardiovascular-outcomes | 2026-05-14 |
| sources/empagliflozin-hfref-nejm-2020 | Packer 2020 NEJM EMPEROR-Reduced RCT: empagliflozin vs placebo in HFrEF (LVEF ≤40%, n=3730, 73% LVEF ≤30%, median 16 months); primary composite CV death or HF hospitalisation HR 0.75 (NNT=19); eGFR decline 4× slower (−0.55 vs −2.28 mL/min/yr; P<0.001); composite renal outcome HR 0.50; renal benefit persists post-discontinuation (disease-modifying); CV death and all-cause death NS | SGLT2-inhibitors, heart-failure-reduced-EF, empagliflozin, randomized-controlled-trial, cardiovascular-outcomes | 2026-05-14 |
| sources/dapagliflozin-hfref-nejm-2019 | McMurray 2019 NEJM DAPA-HF RCT: dapagliflozin vs placebo in HFrEF (LVEF ≤40%, n=4744, 55% no T2DM, median 18.2 months); primary composite worsening HF or CV death HR 0.74 (P<0.001; NNT=21); all-cause death HR 0.83; serious renal AEs lower (1.6% vs 2.7%); benefit identical in T2DM and non-T2DM; landmark trial establishing SGLT2i as fourth-pillar Class I GDMT for HFrEF | SGLT2-inhibitors, heart-failure-reduced-EF, dapagliflozin, randomized-controlled-trial, cardiovascular-outcomes | 2026-05-14 |
| sources/acetazolamide-acutehf-nejm-2022 | Mullens 2022 NEJM ADVOR RCT: IV acetazolamide 500mg OD + loop diuretics vs placebo in ADHF + volume overload (n=519, Belgium); successful decongestion within 3 days 42.2% vs 30.5% (RR 1.46; P<0.001); higher natriuresis (468 vs 369 mmol); shorter hospital stay; death/HF rehospitalization at 3 months HR 1.07 (NS); no metabolic acidosis; SGLT2i excluded | acute-heart-failure, decongestion, diuretics, acetazolamide, volume-overload | 2026-05-14 |
| sources/arrhythmia-diastolic-circep-2020 | Pezawas 2020 Circ EP prospective pilot (n=210; ICM/DCM; 7-year follow-up): grade III diastolic dysfunction independently predicts arrhythmic death/RCA (HR 3.52; P<0.001), LVEF-independent (persists in LVEF ≤35% and >35%); 58% 8-year AD/RCA risk in grade III vs 5% in normal; no patient with normal diastolic function died of arrhythmic death | diastolic-dysfunction, sudden-cardiac-death, risk-stratification, ventricular-arrhythmia, ICD | 2026-05-14 |
| sources/dapagliflozin-deliver-nejm-2022 | Solomon 2022 NEJM DELIVER RCT: dapagliflozin vs placebo in HFmrEF/HFpEF (LVEF >40%, n=6263, 2.3 years); primary composite worsening HF or CV death HR 0.82 (P<0.001); worsening HF HR 0.79; CV death HR 0.88 (NS); KCCQ +2.4 pts; consistent benefit across full LVEF spectrum including ≥60% and diabetes-independent; established ESC 2023 Class I, Level A | SGLT2-inhibitors, heart-failure-preserved-EF, dapagliflozin, randomized-controlled-trial, cardiovascular-outcomes | 2026-05-12 |
| sources/clingen-summary-2026-05-09 | ClinGen 2026-05-09 Curation Activity Summary: 419 cardiovascular gene-disease curations across 258 genes; 7-tier validity framework; highlights disputed/refuting BrS/HCM/ARVC genes; SCN5A broad designation; PAH definitive genes | clingen, gene-disease-validity, hereditary-cardiovascular-disease, dosage-sensitivity, clinical-actionability | 2026-05-09 |
| sources/levosimendan-jcm-2022 | Masarone/Kittleson/Pollesello et al. 2022 JCM narrative review (11:6408; COI: Pollesello = Orion Pharma employee): levosimendan in advHFrEF — triple mechanism (calcium sensitisation + vascular KATP + mitochondrial KATP); OR-1896 active metabolite t½ ≈80h, peak 48–72h post-infusion, pharmacodynamic effect 10–14 days; severe CKD (CrCl <30): OR-1896 AUC 2× → dose reduction required; AF risk signal vs dobutamine and placebo (unlike VT/VF which remains low); contraindications (SBP <70, severe MS/AS, CrCl <30, MELD >30); pulsed infusion RCTs: LevoRep (n=120, primary FAILED), LION-HEART (n=69, HF hosp HR 0.25 p=0.001, NT-proBNP p<0.001), LAICA (n=97, primary NS but 12m survival p=0.044); meta-analysis (n=984): CV death lower p=0.02, all-cause mortality NS; pre-LVAD RCT (n=84): RV failure NS; HELP trial (HFpEF, n=37): exercise PCWP −3.9 mmHg + 6MWT +29.3m; ESC 2021 Class IIb palliative/bridge-to-transplant/LVAD; practical dosing protocol | advanced-heart-failure, levosimendan, inotropes, heart-failure, mechanical-circulatory-support | 2026-05-26 |
| sources/levosimendan-drugs-2001 | Figgitt/Gillies/Goa 2001 Drugs new drug profile review (61:613-627): levosimendan pharmacodynamics (calcium sensitisation via troponin C binding — calcium-dependent, avoids diastolic impairment; KATP channel vasodilation; neutral myocardial energetics vs dobutamine; RV efficiency +24%; PVR reduced 22–27% post-CPB; non-arrhythmogenic — 0% VF vs 50% milrinone in dog model; no QTc prolongation); pharmacokinetics (t½β ≈1h; OR-1896 active metabolite extends haemodynamic effects; 97–98% protein binding; linear PK); LIDO trial (decompensated CHF, n=203: primary endpoint 28% vs 15% dobutamine p=0.022; 30-day worsening HF/death 6.8% vs 17% p=0.039); RUSSLAN trial (post-AMI, n=504: 14-day mortality 11.4% vs 19.6% placebo p=0.029); drug interactions clean (captopril/felodipine/β-blockers/digoxin/warfarin/isosorbide/carvedilol/alcohol/itraconazole all NS); approved Sweden 2000; US in late-phase development at time of publication | calcium-sensitizer, inotropes, decompensated-heart-failure, pharmacology, heart-failure | 2026-05-26 |
| sources/hatw-jacc-advances-2025 | Meyers 2025 JACC:Advances: first quantitative HATW definition — T-wave magnitude (AUC/QRS amplitude) + symmetry; HATW score ≥0.7 in 2 contiguous leads → 98.4% spec, 20.7% sens in non-STEMI; T-wave amplitude alone insufficient | hyperacute-T-waves, occlusion-MI, ECG-diagnosis, acute-coronary-syndrome, STEMI-criteria | 2026-05-03 |
| sources/conduction-disorders-jaha-2025 | Balla 2025 JAHA Contemporary Review: CCDs in young adults — acquired (Lyme 80–90% AVB, sarcoidosis 30% unexplained AVB, Chagas RBBB+LAFB, autoimmune RA/SLE) and familial (SCN5A 76% familial CCD, LMNA 33% DCM+CCD, Fabry 6% devices, Kearns-Sayre PM, Holt-Oram/NKX2-5 CHD-related); conduction system pacing preferred; PM <50 → 3–4× risk; ESC rec ICD over PM in LMNA | conduction-disorders, atrioventricular-block, genetics, cardiomyopathy, young-adults | 2026-05-02 |
| sources/ch-aha-2026 | AHA 2026 Scientific Statement: CH cardiovascular implications — gene-specific mechanisms (TET2/IL-1β/NLRP3; DNMT3A/efferocytosis/HB-EGF; JAK2/thrombosis); 25% HF risk (n=56,597); TET2 2.4× HFpEF; therapy-related CH (TP53/PPM1D); CANTOS canakinumab benefit in TET2-CH; colchicine/vitamin C/metformin strategies; no proven CH-specific CVD therapy | clonal-hematopoiesis, cardiovascular-risk, inflammation, atherosclerosis, cardio-oncology | 2026-05-02 |
| sources/membrane-potential-physrev-2021 | Varró 2021 Physiol Rev: comprehensive review of all cardiac ion channels (INa/IKr/IKs/Ito/ICaL/IK1/If/NCX), AP phases, regional differences, EAD/DAD/reentry mechanisms, electrical remodeling in AF/HF/HCM/MI, all channelopathy genes | cardiac-electrophysiology, ion-channels, arrhythmia-mechanisms, channelopathies, electrical-remodeling | 2026-04-30 |
| sources/cardio-oncology-vascular-metabolic-aha-2019 | AHA 2019 Scientific Statement: vascular and metabolic perspectives in cardio-oncology — vascular toxicity mechanisms table (5-FU/platinum/taxane/bleomycin/RT), VEGF HTN mechanisms, Ottawa VTE score, LMWH vs DOAC, CHIP as shared cancer-CVD risk, ADT metabolic risk | cardio-oncology, vascular-toxicity, cancer-associated-VTE, metabolic-complications, clonal-hematopoiesis | 2026-04-30 |
| sources/alt-medicine-hf-aha-2023 | AHA 2023 Scientific Statement: CAM in HF — omega-3 PUFA Class 2b rec; CoQ10 uncertain; hawthorn harm in LVEF ≤35%; licorice/Vit E/grapefruit juice harm; yoga/tai chi beneficial; drug-interaction catalog | heart-failure, complementary-alternative-medicine, drug-interactions, nutraceuticals, guidelines | 2026-04-30 |
| sources/subclinical-af-aha-2019 | AHA 2019 Scientific Statement: SCAF prevalence (10–55% CIED; 24% ESUS); 2.4× stroke risk; dose-dependent duration threshold; progression to clinical AF; pre-ARTESiA/NOAH OAC uncertainty | subclinical-atrial-fibrillation, atrial-fibrillation, stroke-prevention, cardiac-monitoring, anticoagulation | 2026-04-29 |
| sources/genetic-test-aha-2020 | AHA 2020 Scientific Statement: genetic testing framework across cardiomyopathies, arrhythmic disorders (SCN5A-only for BrS; KCNQ1/KCNH2/SCN5A definitive for LQTS), HTAD (11 definitive genes), and FH (Table 4 criteria); ACMG 59/30 CVD genes; cascade testing principles; GINA limitations | genetic-testing, cardiomyopathy, channelopathies, guideline, cascade-family-screening | 2026-04-29 |
| sources/imaging-viability-aha-2020 | AHA 2020 Scientific Statement: state-of-art viability imaging — hibernation/stunning pathophysiology; LGE-CMR transmural extent tiers; STICH/PARR-2 viability substudy; modality comparison table | myocardial-viability, cardiac-imaging, ischemic-cardiomyopathy, late-gadolinium-enhancement, coronary-revascularization | 2026-04-29 |
| sources/sdb-arrhythmia-aha-2022 | AHA 2022 Scientific Statement: SDB (OSA/CSA/CSB) and cardiac arrhythmias (AF/VTA/SCD/bradyarrhythmia); VARIOSA-AF directionality; CPAP RCTs all negative; NABS/ODI screening; circadian KLF15 mechanism; stepped clinical care model | sleep-disordered-breathing, atrial-fibrillation, ventricular-arrhythmia, obstructive-sleep-apnea, arrhythmia-management | 2026-04-29 |
| sources/BPA-AHA-2024 | AHA 2024 Scientific Statement: BPA for CTEPD with/without PH; Class I ESC 2022; RACE/MR BPA trials; disease-level classification; lesion subtypes; complication trends; expert centre requirements | balloon-pulmonary-angioplasty, CTEPH, pulmonary-hypertension, interventional-cardiology, pulmonary-embolism | 2026-04-28 |
| sources/incident-gene-aha-2023 | AHA 2023 Scientific Statement: Bayesian framework for interpreting incidentally identified variants in CVD genes; ACMG-78 (42 CVD genes); pretest probability + variant pathogenicity → posttest probability; LP/P-only cascade testing; 1–8%/year reclassification; diverse populations | incidental-variants, genetic-testing, heritable-cardiovascular-disease, variant-interpretation, precision-medicine | 2026-04-28 |
| sources/imaging-cardio-oncology-aha-2024 | AHA 2023 Scientific Statement: multimodality cardiovascular imaging in cardio-oncology; Tables 1 & 2 by therapy type and clinical presentation | cardio-oncology, cardiovascular-imaging, echocardiography, CMR, cancer-therapy-related-cardiac-dysfunction | 2026-04-28 |
| sources/ACS-AHA-2025 | 2025 ACC/AHA/ACEP/NAEMSP/SCAI full-revision ACS guideline; ticagrelor monotherapy Class I; Impella IIa (DanGer-SHOCK); complete revascularization; IABP/VA-ECMO no benefit | acute-coronary-syndrome, STEMI, antiplatelet-therapy, revascularization, guidelines | 2026-04-21 |
| sources/CCS-AHA-2023 | 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA guideline for Chronic Coronary Disease; beta-blocker COR 3 No Benefit without LV dysfunction; ISCHEMIA paradigm; SGLT2i/GLP-1 RA COR 1; COMPASS low-dose rivaroxaban | chronic-coronary-disease, secondary-prevention, revascularization, antiplatelet-therapy, guidelines | 2026-04-22 |
| sources/ACHD-AHA-2025 | 2025 ACC/AHA/HRS/ISACHD/SCAI full-revision guideline for adults with congenital heart disease; Eisenmenger PAH COR 1; new Fontan liver/TOF PVR criteria | congenital-heart-disease, guideline, tetralogy-of-fallot, Fontan-circulation, Eisenmenger-syndrome | 2026-04-21 |
| sources/STT-mechanism-ACA-2026 | Narrative review: electrophysiological basis of primary (ischemia/electrolytes) and secondary (LBBB/LVH/pacemaker) ST-T changes; injury current mechanism; hyperkalemia ECG progression | electrocardiography, ST-T-changes, myocardial-ischemia, cardiac-electrophysiology, electrolyte-disturbances | 2026-05-01 |
| sources/failure-stemi-criteria-lad-omi-ehjacc-2025 | Meyers 2025 EHJAcuteCVCare: STEMI criteria miss 38% of total LAD occlusions (TIMI-0 flow) on all serial ECGs; expert and AI (PMCardio Queen of Hearts) both 100% sensitive on first ECG; DBT 97 vs 40 min without vs with STEMI criteria; equivalent infarct size | occlusion-MI, STEMI-criteria, LAD-occlusion, ECG-diagnosis, artificial-intelligence-ECG | 2026-05-02 |
| sources/acm-hrs-2019 | 2019 HRS Expert Consensus on evaluation, risk stratification, and management of ACM | consensus, arrhythmogenic-cardiomyopathy | 2026-04-11 |
| sources/channelopathies-jaha-2025 | Clinical diagnosis and therapeutics for cardiac channelopathies | channelopathies, inherited-arrhythmias | 2026-04-11 |
| sources/repolarisation-jaccep-2023 | JACC:EP 2023 state-of-the-art review: cardiac repolarization genetics (ClinGen LQTS/SQTS), T-wave morphology by genotype, EAD/TdP mechanism, 176 QT-SNPs, PRS for LQTS, AI-ECG for concealed LQTS | long-qt-syndrome, cardiac-repolarization, channelopathies, polygenic-risk-score, short-qt-syndrome | 2026-04-30 |
| sources/eoaf-jama-2021 | Genetic yield of WGS in early-onset AF; 10.1% carry P/LP variants, mostly cardiomyopathy genes | atrial-fibrillation, genetics | 2026-04-11 |
| sources/gene-therapy-arrhythmia-2025 | Gene therapy modalities for cardiac arrhythmias (ARVC, CPVT, LQTS, biological pacemaker) | gene-therapy, channelopathies | 2026-04-11 |
| sources/HCM-AHA-2024 | 2024 AHA/ACC guideline for HCM management | hypertrophic-cardiomyopathy, guideline | 2026-04-11 |
| sources/HCM-VA-FCVMed-2022 | Bench-to-bedside review of ventricular arrhythmia and SCD in HCM | hypertrophic-cardiomyopathy, sudden-cardiac-death | 2026-04-11 |
| sources/VA-DCM-Sammani-2020 | Meta-analysis of VA predictors in DCM (n=11,451); LGE HR 5.55 strongest predictor | dilated-cardiomyopathy, ventricular-arrhythmias | 2026-04-12 |
| sources/VA-SCD-ESC-2022 | 2022 ESC guidelines for ventricular arrhythmias and SCD prevention | ventricular-arrhythmia, sudden-cardiac-death, guideline | 2026-04-11 |
| sources/esc-cmp-2023 | 2023 ESC guidelines for cardiomyopathy management | cardiomyopathy, guideline | 2026-04-11 |
| sources/AF-AHA-2023 | 2023 AHA/ACC/ACCP/HRS guideline for AF diagnosis and management | atrial-fibrillation, guideline | 2026-04-12 |
| sources/AF-ESC-2024 | 2024 ESC guidelines for AF management; AF-CARE framework; CHA2DS2-VA | atrial-fibrillation, guideline | 2026-04-12 |
| sources/EAST-AFNET4-NEJM-2020 | EAST-AFNET 4 RCT: early rhythm control reduces CV death/stroke in AF (HR 0.79) | atrial-fibrillation, rhythm-control, RCT | 2026-04-12 |
| sources/laao-closureaf-nejm-2026 | Landmesser/Skurk/Kirchhof 2026 NEJM CLOSURE-AF RCT (n=888; 42 German sites; mean CHA₂DS₂-VASc 5.2; HAS-BLED 3.0; LAAO vs physician-directed best medical care — 85% DOAC; median 3 yr follow-up): LAAO failed noninferiority for composite stroke/SE/major bleeding/CV death (16.8 vs 13.3/100 pt-yr; RMST −0.36 yr; P=0.44 for NI); stroke equal (2.6 vs 2.7/100 pt-yr); major bleeding higher with LAAO (7.4 vs 6.2); CV death higher (9.5 vs 7.7); periprocedural + DAPT-driven early bleeding negates stroke benefit in highest-risk elderly AF population | atrial-fibrillation, left-atrial-appendage-closure, stroke-prevention, anticoagulation, noninferiority-trial | 2026-05-16 |
| sources/laao-championaf-nejm-2026 | Doshi/Kar/Ellenbogen 2026 NEJM CHAMPION-AF RCT (n=3000; 141 sites; 16 countries; Boston Scientific–sponsored; Watchman FLX vs NOAC in NOAC-eligible AF; mean CHA₂DS₂-VASc 3.5; HAS-BLED 1.3; 85% NOAC post-implant): NI demonstrated for efficacy (CV death/stroke/SE 5.7% vs 4.8%; difference 0.9%; P<0.001 for NI); superiority demonstrated for non-procedure-related bleeding (10.9% vs 19.0%; HR 0.55; P<0.001); net clinical benefit favours device (15.1% vs 21.8%; HR 0.66); ischaemic stroke numerically higher with device (3.2% vs 2.2%); first large RCT showing LAAO reduces clinically relevant bleeding vs NOAC in NOAC-eligible patients | atrial-fibrillation, left-atrial-appendage-closure, stroke-prevention, anticoagulation, noninferiority-trial | 2026-05-16 |
| sources/laao-option-nejm-2025 | Wazni/Saliba/Nair/OPTION Investigators 2025 NEJM RCT (n=1,600; 106 sites; 10 countries; Boston Scientific–sponsored; Watchman FLX vs OAC — 95% NOAC — in post-ablation AF; CHA₂DS₂-VASc 3.5; HAS-BLED 1.2; post-implant OAC+ASA 90d → ASA alone): superiority demonstrated for non-procedure-related bleeding (8.5% vs 18.1%; HR 0.44; P<0.001); NI demonstrated for death/stroke/SE (5.3% vs 5.8%; P<0.001 for NI); ischemic stroke equally low (1.2% vs 1.3%); device success 98.8%; first large RCT of LAAO specifically in post-ablation AF patients | atrial-fibrillation, left-atrial-appendage-closure, catheter-ablation, stroke-prevention, bleeding-prevention | 2026-05-16 |
| sources/ca-af-ehj-2024 | State-of-art review: AF catheter ablation indications, PFA technology, QOL, cognition, AF progression | atrial-fibrillation, catheter-ablation, pulsed-field-ablation | 2026-04-12 |
| sources/MYBPC3-MYH7-JACCEP-2024 | AF substrate and catheter ablation outcomes in MYBPC3/MYH7-mediated HCM; primary atrial myopathy independent of LA pressure | hypertrophic-cardiomyopathy, atrial-fibrillation, catheter-ablation, genetics, atrial-myopathy | 2026-04-12 |
| sources/arrhythmia-genetics-mgenetik-2025 | Current-state review of inherited arrhythmia genetics; ClinGen gene curation, CRDS, variant reclassification, cardiogenetic centres | channelopathy, genetics, LQTS, sudden-cardiac-death, arrhythmia | 2026-04-12 |
| sources/eoaf-riskfactor-ehj-2026 | Prospective AF <40 without SHD (n=122): 89% lifestyle risk factors, 11.6% P/LP variants (TTN/LMNA/PKP2), 4.1% stroke with CHA₂DS₂-VA=0 | atrial-fibrillation, early-onset-atrial-fibrillation, genetics, lifestyle-risk-factors, catheter-ablation | 2026-04-12 |
| sources/HF-AHA-2022 | 2022 AHA/ACC/HFSA HF Guideline: 4-pillar HFrEF GDMT (SGLT2i COR 1); SGLT2i COR 2a HFpEF/HFmrEF; HFimpEF; cardiac amyloidosis pathway; genetic testing COR 2a | heart-failure, guideline, HFpEF, SGLT2-inhibitors, cardiac-amyloidosis | 2026-04-12 |
| sources/HF-ESC-2021 | 2021 ESC HF Guidelines: 4-pillar HFrEF therapy (SGLT2i added); HFmrEF category; AF management (CASTLE-AF, rate/rhythm); DCM minimum gene panel; gene-specific outcomes (LMNA, TTN) | heart-failure, guidelines, atrial-fibrillation, cardiomyopathy, genetic-testing | 2026-04-12 |
| sources/HF-update-ESC-2023 | 2023 ESC Focused HF Update: SGLT2i Class I for HFmrEF/HFpEF; STRONG-HF post-discharge strategy; finerenone + SGLT2i for CKD+T2DM; IV iron upgraded to Class I | heart-failure, HFpEF, SGLT2-inhibitors, guideline, acute-heart-failure | 2026-04-12 |
| sources/Cardio-Oncology-ESC-2022 | First ESC cardio-oncology guideline (272 recommendations): HFA-ICOS risk stratification; CTRCD grading; monitoring protocols for anthracyclines/HER2/ICI/RT; AF in cancer (TBIP algorithm); long-term survivorship | cardio-oncology, cardiovascular-toxicity, heart-failure, atrial-fibrillation, guideline | 2026-04-12 |
| sources/Biobank-AF-JAMA-2024 | UK Biobank WES (n=403,990): 6 pLOF genes (TTN/PKP2/CTNNA3/KDM5B/RPL3L) associated with AF; combined PRS+pLOF OR 7.08; TTNtv drives 3× cardiomyopathy risk before and after AF | atrial-fibrillation, genetics, polygenic-risk-score, cardiomyopathy, early-onset-atrial-fibrillation | 2026-04-13 |
| sources/PHT-ESC-2022 | 2022 ESC/ERS PH Guidelines: new mPAP >20 mmHg threshold; 5-group classification; 4-strata follow-up risk model; ERA+PDE5i Class I for PAH; BPA Class I for CTEPH; exercise training Class I | pulmonary-hypertension, pulmonary-arterial-hypertension, CTEPH, right-heart-failure, guideline | 2026-04-13 |
| sources/genetic-cmp-jcf-2018 | 2018 HFSA+ACMG joint guideline for genetic evaluation of cardiomyopathy; 9 guidelines; cascade screening intervals; gene-specific yields and ICD thresholds (LMNA Guideline 9) | genetics, cardiomyopathy, guideline, genetic-testing, cascade-family-screening | 2026-04-15 |
| sources/genetic-eoaf-ehj-2024 | State-of-art review: genetic testing in EOAF; 4–11% P/LP yield; TTN/LMNA/PKP2/MYBPC3 dominant genes; AF precedes cardiomyopathy in ~50% TTNtv carriers; Class IIb ACC/AHA rec ≤45 years; ~60% VUS rate | atrial-fibrillation, early-onset-atrial-fibrillation, genetic-testing, cardiomyopathy, cascade-family-screening | 2026-04-15 |
| sources/genetic-af-dxmx-jce-2022 | Invited review: genetic basis of AF (linkage/GWAS/single-gene); 5-criterion testing framework; 4q25 SNPs modulate ablation outcomes; GENETIC-AF trial (bucindolol vs metoprolol in ADRB1 Arg389Arg HFrEF) | atrial-fibrillation, genetic-testing, catheter-ablation, polygenic-risk-score, dilated-cardiomyopathy | 2026-04-15 |
| sources/genetic-af-cjc-2024 | CJC White Paper: 3-tier genetic testing framework for AF; ClinGen appraisal (only SCN5A/KCNA5/TTN definitive); ablatogenomics — largest SNP-ablation study (n=3259) negative; 3 case vignettes (PKP2/MYBPC3/LMNA) | atrial-fibrillation, genetic-testing, early-onset-atrial-fibrillation, cardiomyopathy, polygenic-risk-score | 2026-04-15 |
| sources/genetic-yield-jama-card-2022 | Combined cardiomyopathy + arrhythmia panel (n=4,782): 19.9% overall yield; 66% of positives have management implications; combined testing gains 10.9% diagnoses vs. disease-specific panels; 42% cascade yield | genetic-testing, cardiomyopathy, arrhythmia, diagnostic-yield, cascade-testing | 2026-04-16 |
| sources/cardiorenal-aha-2019 | AHA 2019 Scientific Statement: CRS 5-type classification (Acute Dialysis Quality Initiative); hemodynamic (CVP-driven, not just low CO) and non-hemodynamic (FGF-23/neurohormonal/inflammatory) pathophysiology; biomarkers (NGAL, TIMP-2×IGFBP7, ST2, galectin-3); UF trials (CARRESS-HF vs UNLOAD); RAAS/beta-blocker/MRA/ARNI evidence tables by GFR; SGLT-2i in diabetic CRS (EMPA-REG, CANVAS); ICD/CRT in CKD; HF in KT recipients; palliative care | cardiorenal-syndrome, heart-failure, kidney-dysfunction, diuretics, chronic-kidney-disease | 2026-04-30 |
| sources/lpa-aha-2021 | AHA 2021 Scientific Statement: Lp(a) as genetically determined causal ASCVD risk factor; KIV2 CNV mechanism; HR 1.11 per 50 nmol/L (UK Biobank n=460K); PCE risk adjustment formula; assay standardisation (nmol/L vs mg/dL); OxPL pathophysiology; CAVD; pelacarsen/ARO-LPA/SLN360 trials | lipoprotein-a, ASCVD, genetics, cardiovascular-risk, lipid-lowering | 2026-04-30 |
| sources/osa-af-jama-2018 | Review: OSA in AF (21–74% prevalence); dual acute/chronic arrhythmogenic mechanism; CPAP reduces AF recurrence (observational); AHI limitations; no RCT evidence | atrial-fibrillation, obstructive-sleep-apnea, CPAP, atrial-remodeling, catheter-ablation | 2026-04-18 |
| sources/vhd-esc-2025 | 2025 ESC/EACTS VHD guidelines: TAVI expanded (asymptomatic AS, BAV, AR); atrial vs ventricular SMR distinct; TEER Class I A for ventricular SMR; transcatheter TR upgraded Class IIa A; unified SVD definitions | valvular-heart-disease, guideline, TAVI, aortic-stenosis, mitral-regurgitation | 2026-04-18 |
| sources/arrhythmia-pregnancy-hrs-2023 | Joglar et al. 2023 HRS Expert Consensus (8 societies; 163 recommendations; 98.4% consensus): AF most common sustained arrhythmia in pregnancy; cardioversion safe/same energy; lead apron only 3% fetal dose reduction; flecainide 1st-line fetal SVT (especially with hydrops); verapamil avoided fetal SVT; DOACs contraindicated; perimortem C-section within 5 min; IAS pregnancies 8× stillbirth risk; LQTS2 highest postpartum risk; BrS/CPVT no increased pregnancy risk | pregnancy, arrhythmia, antiarrhythmic-drugs, fetal-arrhythmia, inherited-arrhythmia-syndrome | 2026-05-22 |
| sources/lqts-pregnancy-medicina-2022 | Review: LQTS in pregnancy; postpartum 2.7× cardiac event risk; LQT2 highest risk; beta-blockers Class I; propranolol/nadolol > metoprolol; amiodarone contraindicated | long-qt-syndrome, pregnancy, channelopathies, beta-blockers, arrhythmia-management | 2026-04-18 |
| sources/brs-jaccep-2022 | State-of-the-art review: BrS pathophysiology, quantified risk stratification (annual SAE rates by clinical subgroup), Brugada burden concept, QUIDAM trial, ICD vs. complications data, epicardial ablation outcomes | brugada-syndrome, risk-stratification, channelopathies, sudden-cardiac-death, inherited-arrhythmias | 2026-04-19 |
| sources/drug-arrhythmia-aha-2020 | AHA 2020 Scientific Statement: comprehensive catalog of drug-induced arrhythmias (7 types); TdP risk factors; repolarization reserve theory; CAST trial; 0.08%/year SCD for drug-induced BrS; IV Mg for TdP | drug-induced-arrhythmias, torsades-de-pointes, QT-prolongation, Brugada-syndrome, arrhythmia-management | 2026-04-19 |
| sources/amiodarone-cvdrug-2020 | Comprehensive clinical review: amiodarone mechanism (all 4 AP phases), indications (VF/VT/AF), pharmacokinetics (t½ 50–60d), multisystem toxicity monitoring, drug interactions (warfarin, sofosbuvir) | amiodarone, antiarrhythmic-drugs, drug-toxicity, ventricular-arrhythmias, atrial-fibrillation | 2026-04-19 |
| sources/HT-AHA-2025 | 2025 AHA/ACC multi-society hypertension guideline: PREVENT replaces PCEs; SPC for Stage 2; RDN COR 2b; primary aldosteronism screening in resistant HT; dementia prevention COR 1 | hypertension, guidelines, blood-pressure-management, cardiovascular-risk, PREVENT-score | 2026-04-20 |
| sources/TTN-CVResearch-2022 | Invited review: titin molecular biology — isoform switch (N2B/N2BA/RBM20), PTMs (acetylation/oxidation/phosphorylation), PQC, TTNtv-DCM triple pathomechanism; failed clinical trials (RELAX/VITALITY/SOCRATES) | titin, dilated-cardiomyopathy, heart-failure, sarcomere, post-translational-modifications | 2026-04-19 |
| sources/atrial-cmp-esc-2025 | ESC/HFA 2025 consensus: AtCM diagnostic framework (P-wave score 0–4 + LAVi >40 ml/m²/LASr <23%); atrial failure as end-stage; BMP10/mid-regional proANP biomarkers; NLRP3 inflammasome and epicardial adipose tissue targets | atrial-cardiomyopathy, atrial-fibrillation, heart-failure, atrial-fibrosis, electrocardiography | 2026-05-01 |
| sources/csp-ehra-2023 | 2023 EHRA consensus on CSP implantation: HBP and LBBAP technique, capture confirmation criteria, complications, device configuration; endorsed by APHRS/CHRS/LAHRS | conduction-system-pacing, his-bundle-pacing, left-bundle-area-pacing, cardiac-pacing, cardiac-resynchronization-therapy | 2026-04-19 |
| sources/csp-jaccep-2023 | JACC:EP 2023 state-of-the-art review: CSP hemodynamics (vs RVP/BVP), ventricular synchrony (UHF-ECG), LBB capture criteria, HOT/LOT-CRT, 7 published RCTs, ongoing PROTECT-HF/Left vs Left | conduction-system-pacing, his-bundle-pacing, left-bundle-area-pacing, cardiac-resynchronization-therapy, heart-failure | 2026-04-19 |
| sources/fabry-ehj-2024 | EHJ 2024 state-of-the-art review: cardiologist's role in AFD; cardiac HCM genocopy; HFpEF (40%); ERT/migalastat/gene therapy; amiodarone contraindicated; CMR 4-stage model; AI diagnostics | fabry-disease, hypertrophic-cardiomyopathy, lysosomal-storage-disorders, cardiomyopathy, enzyme-replacement-therapy | 2026-04-19 |
| sources/fabry-pcvd-2025 | PCVD 2025 systematic review: Fabry cardiomyopathy mechanisms (TLR4/NF-κB, TGF-β, impaired autophagy); ERT paradox (LGE augmented by ERT, meta-analysis n=11); animal model failure; female AFD (mean death 55.4y); miR-17/fatigue | fabry-disease, cardiomyopathy, enzyme-replacement-therapy, lysosomal-storage-disorders, fibrosis | 2026-04-19 |
| sources/rhc-hf-ehj-2025 | EHJ 2025 state-of-the-art review: RHC across HF spectrum; PAWP zone of uncertainty (12–18 mmHg); normal PAWP upper limit 13 mmHg; haemodynamic thresholds for acute/chronic HF, cardiogenic shock (SCAI), LVAD, HTX | right-heart-catheterization, pulmonary-hypertension, heart-failure, cardiogenic-shock, advanced-heart-failure | 2026-04-19 |
| sources/echo-hfpef-ase-2025 | ASE 2025 guideline update: LV diastolic function assessment; LARS as primary LAP parameter; new 2-step diastolic dysfunction definition; revised LAP algorithm (LAVi demoted); stepwise HFpEF diagnosis algorithm; diastolic exercise echo; special populations | echocardiography, diastolic-function, HFpEF, heart-failure, left-atrial-strain | 2026-04-19 |
| sources/VHD-AHA-2020 | 2020 ACC/AHA VHD guideline: A–D staging system; age-based TAVI vs SAVR selection; COAPT criteria for secondary MR TEER; prosthetic valve antithrombotic (INR 2.5/3.0; DOACs Class III:Harm); SVD surveillance schedule | valvular-heart-disease, guideline, aortic-stenosis, prosthetic-valves, TAVI | 2026-04-19 |
| sources/hemodynamics-circ-2012 | Circulation 2012 review: invasive hemodynamic catheterization principles; Gorlin/Hakki equations; AS/MS gradient measurement pitfalls; constrictive vs restrictive differential; HCM provocative maneuvers | hemodynamics, cardiac-catheterization, valvular-heart-disease, aortic-stenosis, pulmonary-hypertension | 2026-04-20 |
| sources/lipid-aha-2026 | 2026 ACC/AHA Dyslipidemia Guideline: PREVENT equations replace PCE; LDL-C/non-HDL-C goals reinstated; universal Lp(a) measurement COR 1; CAC-guided treatment tiers; bempedoic acid/inclisiran/olezarsen incorporated | dyslipidemia, guidelines, primary-prevention, ldl-c, ASCVD | 2026-04-20 |
| sources/lipid-esc-2025 | 2025 ESC/EAS Focused Update: SCORE2/SCORE2-OP replace SCORE; bempedoic acid COR I B for statin-intolerant; evinacumab COR IIa B for HoFH ≥5 y; ACS combination initiation; Lp(a) >105 nmol/L risk-enhancing COR IIa B; volanesorsen for FCS (EMA); statins for HIV/cancer | dyslipidemia, guidelines, ldl-c, ASCVD, ESC | 2026-04-20 |
| sources/acute-pe-aha-2026 | 2026 AHA/ACC multi-society PE guideline; introduces 5-category AHA/ACC Acute PE Clinical Categories (A–E); PERT COR 1; DOACs over VKAs; LMWH over UFH; advanced therapy by category; CTEPD surveillance | pulmonary-embolism, venous-thromboembolism, anticoagulation, guidelines, risk-stratification | 2026-04-21 |
| sources/periop-aha-2024 | 2024 AHA/ACC multi-society guideline for Perioperative Cardiovascular Management for NCS; stepwise algorithm; RCRI/NSQIP/DASI; MINS surveillance; BP targets (MAP ≥60–65); pharmacotherapy (SGLT2i COR 1 stop, BB COR 3 no start day-of); POAF; special populations (AS, PH, HCM, AF) | perioperative-medicine, noncardiac-surgery, cardiovascular-risk, guideline, anticoagulation | 2026-04-22 |
| sources/imaging-amyloidosis-aha-2021 | 2021 AHA 8-society consensus on multimodality imaging in cardiac amyloidosis (Part 1): evidence base + standardized protocols; scintigraphy Grade 0–3 system; SPECT mandatory addendum; PSIR LGE; ECV >0.40 | cardiac-amyloidosis, multimodality-imaging, ATTR-amyloidosis, echocardiography, radionuclide-imaging | 2026-04-22 |
| sources/imaging-amyloidosis-2nd-aha-2021 | 2021 AHA 8-society consensus on multimodality imaging in cardiac amyloidosis (Part 2): formal diagnostic criteria (ECV >0.40, apical GLS ratio >1, PET thresholds); AUC ratings for 32 clinical scenarios; scintigraphy Rarely Appropriate in AL | cardiac-amyloidosis, multimodality-imaging, ATTR-amyloidosis, appropriate-use-criteria, diagnostic-criteria | 2026-04-22 |
| sources/PVD-AHA-2024 | 2024 ACC/AHA multi-society guideline for lower extremity PAD; rivaroxaban+aspirin COR 1A; SET COR 1A for claudication; BEST-CLI vs BASIL-2; CLTI multispecialty care; ALI 4–6h ischaemia window; health disparities | peripheral-artery-disease, guidelines, revascularization, CLTI, claudication | 2026-04-24 |
| sources/rvfailure-nejm-2023 | Houston/Brittain/Tedford 2023 NEJM Review: RV failure pathophysiology (adaptive homeometric → maladaptive heterometric via β₁-adrenergic depletion, ischaemia, fibrosis, FAO→glycolysis shift); classification by mechanism (preload: TR/shunts/AV fistulas; afterload: acute PE/chronic PH; contractility: RV MI/post-surgical/LHF/ARVC/sarcoidosis); TAPSE/PASP ratio as noninvasive RV–PA coupling surrogate; PDE5i harmful in LHD-associated PH (SIOVAC); volume loading NOT universally beneficial; dobutamine/milrinone; isolated RVAD contraindicated in severe PAH | right-ventricular-failure, pulmonary-hypertension, hemodynamics, right-heart-catheterization, right-ventricular-remodeling | 2026-05-17 |
| sources/rv-failure-aha-2026 | 2026 AHA Scientific Statement: RV failure in PH — RV–PA coupling (Ees/Ea thresholds), adaptive vs maladaptive remodeling, multiomics biomarkers (H19/SPARCL1/CILP1/FSTL3), imaging (CMR/PET/4D flow), sotatercept RV effects | right-ventricular-failure, pulmonary-hypertension, RV-PA-coupling, ventricular-remodeling, multiomics-biomarkers | 2026-04-22 |
| sources/hemodynamic-hf-pht-aha-2026 | 2026 AHA Scientific Statement: standardized provocative RHC protocols — SNP/milrinone vasodilator challenge (Table 1), PAH AVT (adenosine dropped, Table 2), volume challenge (PAWP ≥19 threshold), invasive exercise HFpEF criteria (Table 4), LVAD ramp/reverse ramp, remote PA monitoring | right-heart-catheterization, heart-failure, pulmonary-hypertension, invasive-hemodynamics, HFpEF | 2026-04-22 |
| sources/diet-aha-2026 | 2026 AHA Scientific Statement: 9-feature heart-healthy dietary pattern; alcohol initiation not recommended (MR negates protection); fish oil supplement increases AF risk; ultraprocessed foods linked to CVD/T2DM/obesity; saturated→unsaturated fat lowers LDL-C; sodium↓+potassium↑ for BP | cardiovascular-prevention, dietary-control, nutrition-guidelines, ultraprocessed-foods, primary-prevention | 2026-04-24 |
| sources/cuffless-bp-aha-2026 | 2026 AHA Scientific Statement: cuffless BP devices (PPG/tonometry/PAT/PTT) — mechanism overview, theoretical applications, validation gaps; 2025 AHA/ACC recommends against clinical use (COR 3: No Benefit); ISO 81060-7 pending | hypertension, blood-pressure-monitoring, digital-health, wearable-technology, photoplethysmography | 2026-04-24 |
| sources/ais-aha-2026 | 2026 AHA/ASA full AIS guideline: tenecteplase COR 1A replaces alteplase; EVT expanded (ASPECTS 3–5 COR 1A; BAO 24h COR 1A); post-EVT SBP <140 mmHg COR 3:Harm; elastic stockings COR 3:Harm; DAPT 21d for minor AIS/TIA COR 1A | acute-ischemic-stroke, endovascular-thrombectomy, thrombolysis, stroke-management, guideline | 2026-04-24 |
| sources/DCM-Lancet-2023 | 2023 Lancet Seminar: DCM causes, mechanisms, and treatment; second hit paradigm; 12 definitive genes with genotype-phenotype table; REALM-DCM failure (LMNA p38-MAPK); TRED-HF 44% relapse; gene therapy (LAMP2/CRISPR/PLN-ASO) | dilated-cardiomyopathy, genetics, myocarditis, gene-therapy, heart-failure | 2026-04-25 |
| sources/periop-cied-aha-2024 | 2024 AHA Scientific Statement on periprocedural management of CIEDs; device-specific magnet responses (Micra no response; AVEIR response); leadless/S-ICD/EV-ICD distinctions; three-phase multidisciplinary workflow; ICD re-enablement safety imperative | cied-management, perioperative-care, leadless-pacemaker, electromagnetic-interference, icd | 2026-04-25 |
| sources/consumer-genetictest-aha-2025 | 2025 AHA Scientific Statement on DTC genetic testing for CVD; regulatory gaps, ACCE framework, monogenic/PRS/pharmacogenomic testing, clinical algorithm for actionable DTC results, cascade testing challenges | genetic-testing, direct-to-consumer-genetics, polygenic-risk-scores, pharmacogenomics, precision-medicine | 2026-04-25 |
| sources/cardiac-rehab-aha-2024 | AHA/AACVPR 2024 Scientific Statement: 9 CR core components; strength training and program quality newly standalone; hybrid/virtual delivery; LVEF ≤35% HF qualifying indication; LDL-C <70/<55, BP <130/80, HbA1c <7% targets; 70% enrollment goal | cardiac-rehabilitation, secondary-prevention, exercise-training, heart-failure, cardiovascular-disease | 2026-04-25 |
| sources/competitive-sports-aha-2025 | 2025 AHA/ACC Scientific Statement on competitive sports in athletes with CVD; SDM paradigm shift; HCM/DCM/ACM no universal restriction; PKP2 ACM restricted; LQTS/CPVT sports reasonable under supervision; BrS no restriction; myocarditis 4–6 wk return; masters athlete guidance | sports-cardiology, sudden-cardiac-death, shared-decision-making, cardiomyopathy, guidelines | 2026-04-25 |
| sources/ai-cardiooncology-aha-2025 | 2025 AHA Scientific Statement: AI for precision medicine in cardio-oncology; multi-omics biomarkers (genomics/transcriptomics/proteomics/metabolomics); AI risk models (90% discrimination); AI-ECG (ICI myocarditis, anthracycline LV dysfunction); NLP/LLM; national registry call; ethical challenges | cardio-oncology, artificial-intelligence, precision-medicine, cardiotoxicity, multi-omics | 2026-04-25 |
| sources/AKI-HF-AHA-2024 | 2024 AHA Scientific Statement: kidney dysfunction in advanced HF; Heart-Kidney Profiles A/B/C; reversibility framework (TKPP >60 mmHg); LVAD/HTx perioperative kidney management; peritoneal dialysis preferred in LVAD; sHKTx when eGFR <45/<30; palliative care integration | cardiorenal-syndrome, advanced-heart-failure, kidney-dysfunction, LVAD, heart-transplantation | 2026-04-25 |
| sources/BCNE-AHA-2025 | 2025 AHA Scientific Statement on BCNE: prior antibiotic exposure #1 cause; 2023 Duke-ISCVID criteria; metagenomic sequencing; 18F-FDG PET/CT; fastidious pathogen table (Coxiella/Bartonella/Whipple/M.chimaera/Fungi); empiric regimens; NBTE differential | infective-endocarditis, blood-culture-negative-endocarditis, molecular-diagnostics, fastidious-organisms, scientific-statement | 2026-04-25 |
| sources/mitochondrial-cv-aha-2025 | 2026 AHA Scientific Statement: mtDNA variation in CVD; heteroplasmy dynamics; ~30% cardiac involvement in mitochondrial disease; HCM dominant phenotype; MELAS/MERRF/MIDD/KSS syndromes; NGS best practices; TALE/zinc-finger gene editing; cGAS-STING inflammatory pathway | mitochondrial-genetics, cardiomyopathy, arrhythmia, genetic-testing, cardiovascular-disease | 2026-04-25 |
| sources/rnd-aha-2024 | 2024 AHA Scientific Statement: Renal denervation for hypertension; FDA approval (Spyral/Paradise Nov 2023); 22+ sham-controlled RCTs; 4–10 mmHg SBP reduction; patient selection, safety (no kidney impairment), shared decision-making | hypertension, resistant-hypertension, renal-denervation, catheter-based-therapy, sympathetic-nervous-system | 2026-04-25 |
| sources/vhd-mechanism-aha-2024 | 2024 AHA Scientific Statement: molecular mechanisms of VHD (CAVD, BAV, MVP, RHD); no effective medical therapy; Lp(a)/LDL-C osteogenic cascade; statin paradox; CHIP in CAVD; TGF-β in MVP; molecular mimicry in RHD; ongoing trials (pelacarsen, colchicine) | valvular-heart-disease, calcific-aortic-valve-disease, mitral-valve-prolapse, rheumatic-heart-disease, molecular-mechanisms | 2026-04-25 |
| sources/TV-Mx-AHA-2024 | 2024 AHA Scientific Statement: TV anatomy (Type I–IV leaflet nomenclature); 5-grade TR severity (massive/torrential); TRILUMINATE Pivotal RCT (win ratio 1.48, QoL benefit, no mortality gain); TriClip + EVOQUE FDA-approved; Cardioband annuloplasty; heterotopic replacement; lifetime management framework | tricuspid-regurgitation, valvular-heart-disease, transcatheter-interventions, right-heart-failure, multimodality-imaging | 2026-04-25 |
| sources/alcohol-cv-aha-2025 | 2025 AHA Scientific Statement: alcohol-CVD relationships across all conditions; heavy/binge drinking consistently harmful; MR does not confirm cardioprotective effect; AF causal dose-response (abstinence RCT); ACM dose-duration-TTNtv interaction; hypertension dose-response | alcohol-consumption, atrial-fibrillation, cardiomyopathy, hypertension, cardiovascular-risk | 2026-04-28 |
| sources/prepregnancy-aha-2023 | AHA 2023 Scientific Statement: prepregnancy CVH (Life's Essential 8) as critical window to reduce APOs and intergenerational CVD; graded CVH–APO dose-response; no large RCTs; multilevel interventions; racial/ethnic disparities | prepregnancy-cardiovascular-health, adverse-pregnancy-outcomes, maternal-health, health-disparities, lifes-essential-8 | 2026-04-28 |
| sources/ht-pregnancy-aha-2022 | AHA 2022 Scientific Statement: HDP diagnosis, BP goals, pharmacotherapy; ACOG ≥160/110 vs international ≥140/90 threshold controversy; preeclampsia sFlt-1/VEGF pathophysiology; HF HR 2.7, ESKD RR 6.6 long-term risk; Black maternal mortality 41/100k | hypertensive-disorders-of-pregnancy, preeclampsia, maternal-health, antihypertensive-therapy, blood-pressure-in-pregnancy | 2026-04-28 |
| sources/cv-pregnancy-aha-2020 | AHA 2020 Scientific Statement: cardio-obstetrics team framework; modified WHO classification (only prospectively validated); PPCM/IPAC (recovery first 6 months; major events EF <30%); SCAD/MINOCA in pregnancy; cerebrovascular (RCVS/PRES/ICH/CVT); anticoagulation table; contraception eligibility | cardio-obstetrics, cardiovascular-disease-in-pregnancy, peripartum-cardiomyopathy, maternal-health, anticoagulation-in-pregnancy | 2026-04-28 |
| sources/obesity-cv-aha-2021 | AHA 2021 Scientific Statement: obesity and CVD — visceral/epicardial fat as CVD risk markers; CAD diagnosis in obesity (PET preferred over SPECT); obesity paradox (post-PCI/CABG/HF); HFpEF more strongly associated than HFrEF; every 5-BMI-unit → 16% SCD risk +29% AF risk; ≥10% weight loss → 6-fold freedom from AF | obesity, cardiovascular-disease, heart-failure, atrial-fibrillation, coronary-artery-disease | 2026-04-29 |
| sources/noncoding-rna-aha-2020 | AHA 2020 Scientific Statement: all ncRNA classes (miRNA/snoRNA/Y-RNA/tsRNA/lncRNA/circRNA/exRNA) in CVD; computational tools; inclisiran/patisiran/anti-miR clinical pipeline; exRNA as CVD biomarkers | noncoding-RNA, microRNA, lncRNA, RNA-therapeutics, extracellular-RNA | 2026-04-29 |
| sources/HF-Precision-Medicine-AHA-2019 | AHA 2019 Scientific Statement: six-omics precision medicine in HF (genomics, pharmacogenomics, epigenomics, proteomics, metabolomics, microbiomics); ADRB1/GRK5/GNB3 beta-blocker pharmacogenomics; GUIDE-IT futility; TMAO as 5-year mortality predictor | precision-medicine, heart-failure, genomics, pharmacogenomics, omics | 2026-04-29 |
| sources/arrhythmia-cardio-oncology-aha-2021 | AHA 2021 Scientific Statement: arrhythmias in cancer (AF most common; ibrutinib RR 4.69; ICI-myocarditis-driven AF; QT prolongation up to 22%; MADIT-CHIC CRT trial); anticoagulation in cancer-AF; autonomic dysfunction in cancer survivors | arrhythmia, cardio-oncology, atrial-fibrillation, QT-prolongation, autonomic-dysfunction | 2026-04-29 |
| sources/cardio-oncology-drug-aha-2022 | AHA 2022 Scientific Statement: drug-drug interactions in cardio-oncology — pharmacodynamic (hypertension/CTRCD/ICI myocarditis/VTE/bleeding/QT) and pharmacokinetic (CYP1A2/2C8/2C9/2C19/2D6/3A4/P-gp/UGT enzyme tables); DOAC/warfarin/tamoxifen/TKI management | cardio-oncology, drug-drug-interactions, pharmacokinetics, cancer-therapy-toxicity, anticoagulation | 2026-04-29 |
| sources/Hormonal-Rx-AHA-2021 | AHA 2021 Scientific Statement: CV risks of breast cancer endocrine therapy (AI pooled RR 1.19 vs tamoxifen; ribociclib+tamoxifen avoid; CDK4/6 RR 1.39) and prostate cancer ADT (GnRH antagonist HR 0.44–0.46; AR-directed RR 1.36); ABCDE algorithm; racial disparities | cardio-oncology, breast-cancer, prostate-cancer, androgen-deprivation-therapy, cardiovascular-toxicity | 2026-04-29 |
| sources/minoca-aha-2019 | AHA 2019 Scientific Statement: MINOCA definition (4th Universal MI Definition); traffic-light diagnostic algorithm; six causes (plaque disruption/vasospasm/MVD/embolism/SCAD/supply-demand mismatch); SWEDEHEART statins HR 0.77, ACEi/ARBs HR 0.82, DAPT no benefit; 4.7% 12-month mortality | MINOCA, myocardial-infarction, coronary-vasospasm, SCAD, coronary-microvascular-dysfunction | 2026-04-29 |
| sources/pharmacological-provocation-europace-2025 | EHRA 2025 multi-society consensus: SCB testing (ajmaline preferred; false-positive rates by disease; indications/contraindications; clinical scenarios); epinephrine for CPVT when EST not feasible; adenosine for SVT/WPW; acetylcholine/ergonovine for CAS (COVADIS criteria); SCN5A carriers generally not tested | brugada-syndrome, pharmacological-provocation, sudden-cardiac-death, channelopathies, arrhythmia-diagnosis | 2026-04-30 |
| sources/PVC-ablation-jaccep-2024 | JACC:EP 2024 state-of-the-art review: PVC catheter ablation indications (symptomatic PVCs, PVC-induced CMP, PVC-triggered VF); ECG localization rules; activation/pace mapping/ECGI; RF/cryo/ethanol/PFA/stereotactic radioablation; site-by-site strategies (RVOT, LV summit, papillary muscles, Purkinje, intramural); 84% acute success, 2.4% major complications | premature-ventricular-complexes, catheter-ablation, ventricular-arrhythmias, electrophysiology, PVC-induced-cardiomyopathy | 2026-05-01 |
| sources/qwave-mri-jacc-imaging-2012 | JACC:Imaging 2012 prospective validation study (n=46, 5-year serial LGE-CMR): Q-wave presence determined by infarct size not transmurality; 23% non-diagnostic ECG at 1 week → 44% at 5 years post-STEMI; 6.2% LV mass cutoff; pseudo-normalization confirmed | myocardial-infarction, electrocardiography, late-gadolinium-enhancement, stemi, cardiac-mri | 2026-05-01 |
| sources/epi-adipose-arrhythmia-jacc-2021 | JACC 2021 state-of-the-art review: EAT arrhythmogenesis via structural infiltration (zigzag conduction, re-entry), electrotonic coupling (Cx43, RMP depolarisation), and paracrine secretome (TNF-α/IL-1β/IL-6 → APD prolongation, connexin downregulation, fibrosis); ECG correlates: P-wave/PR/QRS/TpTe | epicardial-adipose-tissue, arrhythmias, atrial-fibrillation, obesity, electrophysiology | 2026-05-01 |
| sources/circadian-scd-jmcc-2025 | JMCC 2025 narrative review: extrinsic (SCN/ANS) and intrinsic (BMAL1/CLOCK) circadian regulation of cardiac ion channel expression; Kcnh2/Gja1/Scn5a/Hcn4/Pkp2/Dsc2/Dsg2 as top REGs; KLF15→KChIP2 indirect pathway; LQT2 mutations shortening Kv11.1 t½ amplify time-of-day APD swings; loss of morning SCA peak in modern populations | circadian-rhythm, sudden-cardiac-death, cardiac-electrophysiology, ion-channels, arrhythmia-mechanisms | 2026-05-01 |
| sources/RYR2-CPVT-CircEP-2025 | Chang 2025 Circ:ArrhythmElectrophysiol: largest CPVT RYR2 database — 964 patients, 263 variants; domain-specific age of onset (CSol 8y, pore 8y, NTD 12y); variant-specific treatment response (R420Q vs R420W); structural mapping onto cryo-EM (PDB 7UA5); markslab-cpvtdb.org web app; proposes exons 37/42 added to hotspot II | CPVT, RYR2, ryanodine-receptor, variant-interpretation, sudden-cardiac-death | 2026-05-05 |
| sources/ACM-Genotype-Mx-JCE-2024 | Muller 2025 JCE: genotype-specific ACM diagnosis and management — 7-gene natural history (PKP2/DSP/DSG2/DSC2/JUP/TMEM43/PLN/DES); 2010 TFC inadequate non-PKP2; gene-specific risk calculators (ARVC/DSP/PLN); PKP2-flecainide RCT pending; AAV-PKP2 Phase I/II (Rocket/LEXEO/Tenaya); exercise is gene-specific (not harmful in PLN); Padua criteria limitations; family screening 33%+33% yield | arrhythmogenic-cardiomyopathy, genotype-phenotype, risk-stratification, gene-therapy, sudden-cardiac-death | 2026-05-05 |
| sources/scn5a-jaccep-2018 | Wilde & Amin 2018 JACC:CEP state-of-the-art: full clinical spectrum of SCN5A — LQT3 (INaL GOF), BrS (LOF, partial cardiomyopathy), SCN5A-DCM (3 pathomechanisms; conduction defects precede DCM 15-20 y), MEPPC (R222Q), overlap syndromes (1795insD); mutation-direction-specific management | SCN5A, channelopathies, long-qt-syndrome, brugada-syndrome, dilated-cardiomyopathy | 2026-05-05 |
| sources/modifier-genes-scd-ehj-2018 | Schwartz 2018 review of modifier genes explaining incomplete penetrance in LQTS and AMI-VF; NOS1AP, KCNH2-K897T, iPSC-CM approach | #modifier-genes, #long-qt-syndrome, #sudden-cardiac-death, #NOS1AP, #polygenic-risk-score | 2026-05-05 |
| sources/mybpc3-gene-2015 | Carrier 2015 review of MYBPC3 biology: mutation landscape, founder mutations, cMyBP-C structure/phosphorylation/PTMs, and early gene therapy (exon skipping, RNA trans-splicing, AAV replacement) | #MYBPC3, #hypertrophic-cardiomyopathy, #gene-therapy, #haploinsufficiency, #sarcomere | 2026-05-07 |
| sources/dronedarone-circ-2009 | Patel/Yan/Kowey 2009 review: dronedarone pharmacology (IK-Ach 100x, INa 10x vs amiodarone), DAFNE/EURIDIS-ADONIS/ERATO/ANDROMEDA(terminated)/ATHENA(24.2% RRR)/DIONYSOS trials; HF contraindication | #dronedarone, #atrial-fibrillation, #antiarrhythmic-drugs, #amiodarone, #heart-failure | 2026-05-07 |
| sources/flecainide-af-europace-2011 | Aliot 2011 review: flecainide class 1C pharmacology (PRR mechanism, RyR2 blockade), CAST reappraisal, cardioversion efficacy (up to 95% IV; 90% > propafenone > amiodarone), pill-in-the-pocket, Danish registry safety data; industry-funded (Meda) | #flecainide, #atrial-fibrillation, #antiarrhythmic-drugs, #proarrhythmia, #sodium-channel-blockade | 2026-05-07 |
| sources/amiodarone-thyroid-jcem-2021 | Ylli 2021 JCEM Approach-to-Patient: Type 1 AIT (iodine-driven/methimazole) vs Type 2 AIT (destructive/prednisone) vs mixed (both); AIH management; incidence 2–24% (not dose-dependent); 23% ICU mortality in thyroid storm; ETA thyroidectomy criteria; anticoagulant interactions (warfarin/rivaroxaban/apixaban) | #amiodarone, #thyroid-dysfunction, #thyrotoxicosis, #drug-toxicity, #antiarrhythmic-drugs | 2026-05-07 |
| sources/amiodarone-pulmonary-clin-chest-2004 | Camus 2004 Clin Chest Med authoritative review: 6 APT patterns (infiltrative/OP/fibrosis/nodules/ARDS/subclinical); 100–500× lung tissue accumulation; DLCO key monitoring marker; high-FiO₂ surgery ARDS trigger; prednisolone 0.75–1 mg/kg ≥6–12 months; 21–33% hospitalisation mortality; recurrence ~2/3 on rechallenge | #amiodarone, #drug-induced-lung-disease, #pulmonary-toxicity, #antiarrhythmic-drugs, #drug-toxicity | 2026-05-07 |
| sources/amiodarone-pulmonary-drugsafety-2010 | Papiris 2010 Drug Safety review: amiodarone effect vs toxicity distinction; 3-mechanism pathophysiology (cytotoxic/immune/angiotensin); full 9-pattern taxonomy (CEP/COP/AFOP/amiodaronoma/NSIP-like/IPF-like/DIP/ARDS/DAH); cumulative incidence 4.2%/7.8%/10.6% at 1/3/5 years; 3-fold APT risk per decade >60; KL-6 NPV 92% (sensitivity 25%); CT density >70 HU absent in 27–55%; BAL cellular breakdown; surgical biopsy avoid; corticosteroid taper ≤5 mg/day; ACE-I/ARB potentially protective | #amiodarone, #drug-induced-lung-disease, #pulmonary-toxicity, #antiarrhythmic-drugs, #drug-toxicity | 2026-05-07 |
| sources/gwas-arrhythmias-cmp-genes-2025 | Dababneh 2025 Genes review: GWAS and PRS utility in HCM/DCM/BrS/LQTS; inverse HCM-DCM risk loci (MYBPC3/ALPK3/FHOD3); BrS oligogenic with 21 loci (HEY2/MAPRE2); NOS1AP as LQTS modifier; PRS predicts disease risk independent of rare variant status; European-ancestry predominance limits generalisability | #polygenic-risk-score, #inherited-arrhythmias, #cardiomyopathy, #GWAS, #genetics | 2026-05-07 |
| sources/inherited-basis-cad-nejm-2026 | Schunkert/Natarajan/Samani 2026 NEJM CME review: inherited basis of CAD — FH (LDLR/APOB/PCSK9; 2-3× excess CAD risk at same LDL-C with genetic variant); 346 CAD GWAS loci; CAD PRS top 5% = 3-5× risk; intermediate-risk reclassification (1 event/340 screened); young-adult PRS (30-40% vs 10% CAD by age 70); Mendelian randomization validates LDL-C/Lp(a)/TG/BP and deprioritises HDL-C/CRP/vitamin D/uric acid; genetics-to-therapeutics: statins/PCSK9i/ezetimibe/bempedoic acid/LPA agents | coronary-artery-disease, polygenic-risk-score, familial-hypercholesterolemia, genetics, mendelian-randomization | 2026-05-16 |
| sources/gene-editing-cv-tcm-2025 | Abdul-Rahman 2025 TCM narrative review: CRISPR-Cas9/base editing/prime editing in ICCs; AAV mosaicism threshold >70%; risk-benefit framework (WPW — ablation superior; PRKAG2 syndrome — gene editing appropriate); disease table (HCM/Marfan/PAH/DMD/calmodulinopathy-LQTS/FH/PRKAG2); AI for target optimisation and safety | #gene-editing, #CRISPR-Cas9, #inherited-cardiac-conditions, #gene-therapy, #precision-medicine | 2026-05-07 |
| sources/precision-lqts-tcm-2024 | Neves/Ackerman 2024 TCM: 1,304-patient Mayo Clinic 20-year LQTS precision therapy cohort; 10–18 configurations per subtype; intentional nontherapy 18%; LCSD monotherapy 5%; IPAP/mexiletine for LQT2; propranolol>nadolol in LQT3; 0.3% mortality; >50% ICD extraction rate | #long-qt-syndrome, #precision-medicine, #beta-blockers, #left-cardiac-sympathetic-denervation, #antiarrhythmic-drugs | 2026-05-09 |
| sources/aav-gene-therapy-arrhythmia-hr-2024 | Mundisugih 2024 Heart Rhythm PRISMA meta-analysis: 26 preclinical studies; 22 novel targets; AAV9 92%; AF inducibility −81% (OR 0.19); VA inducibility −94% (OR 0.06); only PKP2 in clinical trial; 20% SCN5A base-editing threshold sufficient for LQT3; significant publication bias | #gene-therapy, #AAV-vectors, #atrial-fibrillation, #ventricular-arrhythmia, #channelopathies | 2026-05-09 |
| sources/genetics-va-fcvm-2022 | Wang/Tu 2022 Front Cardiovasc Med narrative review: 30+ gene reference table for non-structural VA; epigenetics — miR-19b multi-channel regulation, U1 snRNA/KCNH2 splicing, SCN5A H558R promoter methylation, KCNQ1OT1 imprinting, KChIP2/H3K4me3, SCN10A 3D enhancer-SCN5A promoter loop; TECRL mixed CPVT/LQTS phenotype; somatic RVOT-VT mutations (GNAI2/ADORA1/GNAS) | #ventricular-arrhythmia, #inherited-arrhythmias, #epigenetics, #channelopathies, #genetics | 2026-05-09 |
| sources/CALM-FCVM-2018 | Badone/Crotti/Zaza 2018 Front Cardiovasc Med: calmodulinopathy mechanism review — CaM pre-bound pool (99% bound in cardiomyocytes); LQTS via CDI loss at Cav1.2 (C-lobe affinity mutations: CALM1-p.D130G/F142L, CALM2-p.D96V); CPVT via RyR2 destabilisation (CALM1-p.N98S/N54I, CALM3-p.A103V); high penetrance via pre-bound pool dominance (1:7 mutant:WT sufficient); verapamil reverses QT in hiPSC-CMs; no clinical trial data (2018) | #calmodulinopathy, #calcium-handling, #long-qt-syndrome, #CPVT, #channelopathies | 2026-05-10 |
| sources/cv-pregnancy-esc-2018 | Regitz-Zagrosek 2018 ESC Guideline: comprehensive CVD-in-pregnancy reference — mWHO classification (I–IV, 40–100% event rate for class IV); PPCM BOARD framework + bromocriptine dosing (2.5 mg OD/BID); non-selective beta-blockers Class I for LQTS/CPVT throughout pregnancy + 40 weeks postpartum; catheter ablation IIaC; LMWH drug of choice for VTE (IB); FDA drug categories abandoned (IIIC); PAH/prior PPCM with residual LV dysfunction/severe valve disease = mWHO IV | #pregnancy, #guidelines, #arrhythmias, #PPCM, #anticoagulation | 2026-05-10 |
| sources/cpvt-jcm-2024 | Aggarwal/Zarich 2024 Yale J Clin Med review: comprehensive CPVT clinical reference — Giudicessi diagnostic scorecard (reduces RyR2 VUS rate 48%→7%; ≥3.5 pts = ≥90% CPVT probability); nadolol HR 2.04 vs selective BB (symptomatic children) and HR 5.8 (216 RYR2-variant cohort); 15% non-adherence (60% evening events from missed doses); LCSD 63-patient multicenter series (86%→21% events; 92% reduction); triple therapy (nadolol+flecainide+LCSD) for sentinel SCA; ICD paradigm shift — 47% vs 15.8% adverse outcomes (ICD vs no-ICD); 99% VT shock failure; catheter ablation — LV basal anterior wall as dominant source (not RVOT); ivabradine/verapamil ineffective; dantrolene preclinical only | #catecholaminergic-polymorphic-ventricular-tachycardia, #sudden-cardiac-death, #ventricular-arrhythmias, #left-cardiac-sympathetic-denervation, #gene-therapy | 2026-05-10 |
| sources/lqts-jaccep-2022 | Krahn 2022 JACC:CEP state-of-the-art: practical LQTS diagnosis/risk/management — exercise 4-min QTc ≥445 ms (90%/90%); QTc ≥500 ms 0.5–1.3% SAE/yr; JLN 35% SCD by 40; ~25% apparent acquired LQTS carry pathogenic variant; nadolol 1 mg/kg/day; 15-20% HR blunting endpoint; ICD 2.8%/yr inappropriate shocks | #long-qt-syndrome, #channelopathies, #risk-stratification, #arrhythmia-management, #cardiac-electrophysiology | 2026-05-10 |
| sources/vericiguat-victoria-nejm-2020 | Armstrong 2020 NEJM VICTORIA: phase 3 RCT vericiguat vs placebo in worsening HFrEF (n=5050; median NT-proBNP 2816; 41% NYHA III/IV); primary composite CV death/HF hosp HR 0.90 (0.82–0.98) P=0.02; NNT ~24; no all-cause mortality benefit; total HF hosp HR 0.91 P=0.02; anemia 7.6% vs 5.7%; no SGLT2i co-treatment data | #heart-failure, #vericiguat, #HFrEF, #clinical-trial, #nitric-oxide-cGMP | 2026-05-10 |
| sources/dcm-precision-hfreview-2022 | Orphanou 2022 Heart Failure Reviews: DCM precision medicine — Pinto 2016 relative diagnostic criteria (Major/Minor, definite/probable/possible); exercise echo LVEF >11% increase: 80% sens/90% spec for DCM vs athletic heart; genotype-specific LVRR (TTN higher; LMNA/FLNC/DES/DMD lower); "apparent healing phenomenon" 15% normalize → 5% deteriorate at 15 years; LMNA/FLNC high-intensity sports prohibited even phenotype-negative; SCN5A pR222Q GOF → Na-channel blocker response; gene reference table 20+ genes | #dilated-cardiomyopathy, #genetics, #precision-medicine, #risk-stratification, #arrhythmia-management | 2026-05-10 |
| sources/arni-paragon-hf-nejm-2019 | Solomon 2019 NEJM PARAGON-HF RCT: sacubitril–valsartan vs valsartan in HFpEF (LVEF ≥45%, n=4796, 35 months); primary composite RR 0.87 (P=0.06) — negative; NYHA improvement OR 1.45; renal protection HR 0.50; subgroup signal: lower LVEF (45–57%) and women | heart-failure, HFpEF, sacubitril-valsartan, clinical-trial, angiotensin-neprilysin-inhibition | 2026-05-11 |
| sources/arni-paradigm-hf-nejm-2014 | McMurray 2014 NEJM PARADIGM-HF RCT: sacubitril–valsartan (LCZ696) vs enalapril in HFrEF (LVEF ≤40%, n=8,399, 27 months, stopped early); primary composite HR 0.80 (P<0.001), NNT 21; CV death HR 0.80 NNT 32; all-cause death HR 0.84; HF hosp HR 0.79; KCCQ +1.64 pts; less renal impairment/hyperkalemia/cough vs enalapril; established ARNI as Class I HFrEF pillar | heart-failure, HFrEF, sacubitril-valsartan, clinical-trial, angiotensin-neprilysin-inhibition | 2026-05-11 |
| sources/pci-hf-revived-bcis2-nejm-2022 | Perera 2022 NEJM REVIVED-BCIS2 RCT: PCI + OMT vs OMT alone in ischaemic LV dysfunction (LVEF ≤35%, n=700, viability ≥4 segments, 40 UK centres, median 41 months); primary HR 0.99 (P=0.96) — no benefit; LVEF no difference at 6m or 12m; KCCQ +6.5 pts at 6m (above MCID) eroded to NS at 24m; challenges myocardial hibernation paradigm; 2023 AHA/ACC CCD guideline: PCI does not confer survival benefit in ischaemic cardiomyopathy | ischemic-cardiomyopathy, percutaneous-coronary-intervention, heart-failure, myocardial-viability, revascularization | 2026-05-11 |
| sources/icd-crt-auc-2025 | Russo 2025 JACC ACC/AHA/HRS 8-society AUC: 335 scenarios across 12 device domains (ICD secondary/primary prevention, S-ICD, CRT, LVAD+ICD, post-transplant ICD, CCM, leadless pacing, CSP); modified Delphi 17-member panel; key ratings: NICM primary prevention ICD A(7–9) after ≥3mo GDMT; age ≥85 M(5–6); LVEF ≤35% LBBB QRS ≥150ms CRT A(9); S-ICD primary prevention A(7) (PRAETORIAN/UNTOUCHED); CCM all M(4–5); DANISH caveat re: pre-SGLT2i/ARNI GDMT | implantable-cardioverter-defibrillator, cardiac-resynchronization-therapy, appropriate-use-criteria, heart-failure, arrhythmia | 2026-05-11 |
| sources/takotsubo-nejm-2015 | Templin/Ghadri 2015 NEJM International Takotsubo Registry (n=1750; 26 centres; 9 countries): 89.8% women; physical triggers 36% > emotional 27.7%; 28.5% no trigger; neuropsychiatric comorbidity 55.8%; in-hospital complications 21.8% = ACS; LVEF 40.7%; death 5.6%/yr; MACCE 9.9%/yr; ACEi/ARB improve survival; beta-blockers NO benefit; men: death 12.9% vs women 5.0%/yr | #takotsubo-cardiomyopathy, #heart-failure, #cardiomyopathy, #prognosis, #brain-heart-axis | 2026-05-10 |
| sources/BB-SMARTDECISION-NEJM-2026 | Choi/Kang/Kim 2026 NEJM SMART-DECISION RCT (n=2540; 25 Korean centres; LVEF ≥40%; no HF; ≥1 year BB; median 4.7 yr post-MI; BB discontinuation vs continuation; HR 0.80, 95% CI 0.57–1.13; upper CI 1.13 < NI margin 1.4; P=0.001 for NI): beta-blocker discontinuation noninferior to continuation for composite death/recurrent MI/HF hospitalisation in stable post-MI patients with preserved EF | beta-blockers, myocardial-infarction, secondary-prevention, noninferiority-trial, coronary-artery-disease | 2026-05-16 |
| sources/bb-mi-nejm-2026 | Kristensen/Rossello/Ibanez; Beta-Blocker Trialists' Collaboration 2026 NEJM IPD meta-analysis (n=17,801; 5 RCTs: REBOOT, REDUCE-AMI, BETAMI, DANBLOCK, CAPITAL-RCT; LVEF ≥50%; median 3.6 yr follow-up): beta-blockers vs no beta-blockers; composite death/MI/HF HR 0.97 (95% CI 0.87–1.07; P=0.54); all secondary endpoints null; consistent across all subgroups; I²=20%; definitively no benefit in preserved-EF post-MI without other BB indications | beta-blockers, myocardial-infarction, preserved-ejection-fraction, meta-analysis, coronary-artery-disease | 2026-05-16 |
| sources/lqts-nejm-2025 | Schwartz/Crotti 2025 NEJM narrative review: LQTS genetic basis (KCNQ1 ~50%/KCNH2 ~40%/SCN5A ~10% = 90% of cases), gene-specific triggers and ECG patterns, Schwartz score, exercise stress test as only useful provocation test, epinephrine challenge NOT recommended; therapy cornerstones: propranolol/nadolol (metoprolol NOT recommended), LCSD (90% ICD shock reduction in electrical storms), mexiletine (70% LQT2 responders, acute oral drug test), ICD in ~5% vs ~50% in some US centres; triple therapy with yearly reassessment; acquired LQTS predictors (age <40/QTc >440/arrhythmic events); KCNE1-D85N and SCN5A-S1103Y rare variants; SupRep validated in calmodulinopathy | long-qt-syndrome, channelopathies, sudden-cardiac-death, genotype-specific-therapy, ion-channels | 2026-05-16 |
| sources/potcast-nejm-2025 | Jøns/Bundgaard/POTCAST Study Group 2025 NEJM RCT (n=1,200; ICD patients; baseline K ≤4.3 mmol/L; 3 Danish centres; median 39.6 months; open-label; event-driven superiority): targeting K 4.5–5.0 mmol/L via KCl + MRA + diet + diuretic reduction; primary composite (sustained VT, appropriate ICD therapy, arrhythmia/HF hosp, all-cause death) 22.7% vs 29.2%; HR 0.76 (95% CI 0.61–0.95; P=0.01; NNT=12.3); appropriate ICD therapy/VT HR 0.75; arrhythmia hosp HR 0.63; all-cause death HR 0.85 NS; benefit regardless of whether target K range achieved — mechanism = avoidance of low-normal K; first large RCT of potassium targeting for arrhythmia prevention | ventricular-arrhythmias, potassium, ICD, mineralocorticoid-receptor-antagonist, arrhythmia-prevention | 2026-05-16 |
| sources/pipeline-mi-nejm-2025 | Tonet/Raisi/Campo 2025 NEJM PIpELINe RCT (n=512; median age 80; SPPB 4–9; 7 Italian sites; 12-month multidomain rehab vs usual care post-MI; primary composite CV death/unplanned CV hosp HR 0.57 P=0.01; HF hosp HR 0.20; CV death NS; no serious AEs; compliance 71%) | #myocardial-infarction, #cardiac-rehabilitation, #frailty, #elderly, #secondary-prevention | 2026-05-16 |
| sources/sotatercept-zenith-nejm-2025 | Humbert/McLaughlin/Hoeper 2025 NEJM ZENITH phase 3 DBRCT (n=172; WHO FC III/IV; REVEAL Lite 2 ≥9; max double/triple PAH therapy; sotatercept 0.3→0.7 mg/kg SC Q21d vs placebo); stopped early for efficacy; primary composite HR 0.24 (P<0.001); PAH hosp 9.3% vs 50%; all-cause death HR 0.42 (NS); epistaxis 44%; telangiectasia 26% | #pulmonary-arterial-hypertension, #sotatercept, #activin-signaling, #high-risk-PAH, #clinical-trial | 2026-05-16 |
| sources/sotatercept-hyperion-nejm-2025 | McLaughlin/Hoeper/Humbert 2025 NEJM HYPERION phase 3 DBRCT (n=320; WHO FC II/III; diagnosis <1 year; REVEAL Lite 2 ≥6 or COMPERA 2.0 ≥2; double/triple background therapy ≥90d; stopped early — equipoise loss); primary composite clinical worsening HR 0.24 (P<0.001); NNT=5 at 12mo; exercise testing deterioration dominant (5% vs 29%); death balanced (4.4% vs 3.8%); epistaxis 32%; telangiectasia 26%; serious bleeding 3.8% vs 1.9% | #pulmonary-arterial-hypertension, #sotatercept, #early-diagnosis, #clinical-worsening, #clinical-trial | 2026-05-16 |
| sources/vt-ablation-vanish2-nejm-2025 | Sapp/Tang/Parkash/VANISH2 Study Team 2025 NEJM RCT (n=416; ischemic cardiomyopathy; prior MI; clinically significant VT; all ICD recipients; no prior AAD for VT; 22 centres Canada/USA/France; median 4.3 years): first-line catheter ablation vs antiarrhythmic drug therapy (sotalol or amiodarone); primary composite (death/ICD shock/VT storm/treated VT) HR 0.75 (95% CI 0.58–0.97; P=0.03); mortality HR 0.84 NS; VT storm HR 0.95 NS; treated sub-threshold VT HR 0.26 (P<0.001); drug-arm nonfatal adverse events 21.6% vs ablation 3.4%; ablation 30-day death 1.0%; first large RCT supporting first-line ablation over AADs in ischemic VT | ventricular-tachycardia, catheter-ablation, ischemic-cardiomyopathy, antiarrhythmic-drugs, randomized-controlled-trial | 2026-05-16 |
| sources/genotype-lifespan-nejm-2023 | Jensson/Stefansson/Sulem 2023 NEJM population WGS cohort (n=57,933 Icelanders; deCODE Genetics): 4.0% (1 in 25) carry ≥1 actionable genotype in ACMG SF v3.0 genes; carriers median survival −1 yr; cancer group −3 yr (BRCA2/BRCA1/PALB2 dominant); cardiovascular group neutral overall — but LDLR −6.47 yr and MYBPC3 −2.18 yr individually; KCNQ1/TGFBR2 cause-of-death associated; MYBPC3 cardiomyopathy death OR 14.04 (composite diluted to NS); 10 new ACMG candidate genes (MYL4/PKD1/PKD2/F5-Leiden-hom/F2-hom); BRCA1 VUS reclassified pathogenic via RNA splicing evidence | actionable-genotypes, ACMG-secondary-findings, population-genomics, lifespan, genetics | 2026-05-17 |
| sources/peripartum-cmp-nejm-2024 | Arany Z 2024 NEJM review: PPCM definition (LVEF <45%, last month pregnancy/5 months post-delivery); vasculohormonal model (prolactin 16-kDa fragment + placental sFlt-1 trigger cardiac vascular damage); ~15% carry DCM-predisposing variants (2/3 TTN) — PPCM on shared genetic spectrum with DCM; bromocriptine under investigation in REBIRTH trial (NCT05180773, n=200, expected 2026); 4× higher incidence in Black women, 2× worse outcomes; mortality up to 20%; LVAD/transplant in up to 10%; wearable defibrillator preferred over ICD given frequent recovery | peripartum-cardiomyopathy, cardiomyopathy, heart-failure, pregnancy, genetics | 2026-05-17 |
| sources/acoramidis-attrcm-attributecm-nejm-2024 | Gillmore/Fox/ATTRibute-CM Investigators 2024 NEJM Phase 3 double-blind RCT (n=632; 90.3% ATTRwt; acoramidis 800 mg BID vs placebo; 30 months): 4-step hierarchical (death/CV hosp/NT-proBNP/6MWT) win ratio 1.8 (95% CI 1.4–2.2; P<0.001); CV hosp RR 0.496 (P<0.001); 6MWT +39.6 m; KCCQ-OS +9.94 pts; serum TTR +7.01 mg/dL; 30-month survival 80.7% vs 74.3% (curves diverged at ~19 months; log-rank NS); SAEs 54.6% vs 64.9%; acoramidis mimics T119M protective variant via enthalpic H-bonding; >90% TTR stabilization; second approved TTR stabilizer (Attruby, BridgeBio) | attr-cardiomyopathy, TTR-stabilizer, acoramidis, randomized-controlled-trial, heart-failure | 2026-05-17 |
| sources/colchicine-ami-clear-nejm-2025 | Jolly/d'Entremont/Yusuf 2025 NEJM CLEAR trial (n=7,062; 104 centres; 14 countries; 95.1% STEMI; 2×2 factorial; median 3 years; 649 events): colchicine 0.5 mg/day vs placebo — primary composite (CV death/recurrent MI/stroke/ischemia-driven revasc) HR 0.99 (95% CI 0.85–1.16; P=0.93) — no benefit; CRP confirmed reduced −1.28 mg/L (biological effect proven); diarrhea 10.2% vs 6.6%; no excess serious infections; noncardiovascular death numerically lower with colchicine; null result contradicts COLCOT and LoDoCo2; ESC Class IIa and FDA approval pre-dated these data | colchicine, acute-myocardial-infarction, anti-inflammatory-therapy, secondary-prevention, randomized-controlled-trial | 2026-05-18 |
| sources/copd-hfpef-eschf-2025 | Xu/Gu/Zhu/Feng et al. 2025 ESC Heart Failure systematic review and meta-analysis (11 studies, 3 post-hoc RCTs + 8 observational, n=18,602; PRISMA 2020; literature to April 2023): COPD as independent prognostic risk factor in HFpEF — all-cause hospitalization RR 1.66 (95% CI 1.47–1.87; I²=0%); all-cause mortality RR 1.62 (95% CI 1.34–1.95; I²=75%); post-discharge mortality RR 2.57 (95% CI 1.34–4.93); CV mortality RR 1.59 (I²=0%); SGLT2i dual benefit (HFpEF + COPD exacerbation reduction); ARNI dual mechanism (bronchodilation + cardiac remodelling); heterogeneity source Berry et al. (LVEF>40% definition) | HFpEF, COPD, heart-failure, comorbidities, prognosis | 2026-05-18 |
| sources/lc-amyloidosis-nejm-2024 | Sanchorawala V. 2024 NEJM review: AL amyloidosis — pathogenesis (lambda 75–80%; t(11;14) 50%; IGLV germline tropism); epidemiology (10–12 cases/million/year; 5-yr survival 15%→48%); diagnosis (fat-pad + marrow 85%; mass spectrometry gold standard for AL vs ATTR typing: Sn 88%/Sp 96%); Mayo 2004/2012/European staging; daratumumab-CyBorD first-line (ANDROMEDA: 78% VGPR+); SCT 10–20% eligible (CR 40%, median OS 7.6 yr); venetoclax for t(11;14) relapse; birtamimab and anselamimab antifibril phase 3 trials ongoing | al-amyloidosis, plasma-cell-dyscrasia, cardiac-amyloidosis, daratumumab, amyloid-staging | 2026-05-18 |
| sources/masld-nejm-2025 | Targher/Valenti/Byrne 2025 NEJM review: MASLD (formerly NAFLD) — 38% adult prevalence; 65% in T2DM; DALYs ×2.2 (1990→2021); CVD leading cause of death (×1.5 CV events, ×1.2–1.5 AF and HF risk, ×2.2 T2DM risk); FIB-4 staging (<1.30 low / 1.30–2.67 indeterminate / >2.67 high risk); resmetirom first FDA-approved (March 2024; MAESTRO-NASH: MASH resolution 62.9% vs 34.3%); semaglutide ESSENCE phase 3 superior on both histologic endpoints; tirzepatide SYNERGY-NASH (MASH resolution 56–62%; fibrosis 51–55%); retatrutide triple agonist (−80% liver fat); FGF21 analogues (SYMMETRY: cirrhosis reversal 29% vs 11%); SGLT2i dapagliflozin (fibrosis reduction 45% vs 20%); no head-to-head comparisons; TM6SF2 variant dissociates liver from CV risk | MASLD, metabolic-syndrome, cardiovascular-risk, GLP-1-agonists, resmetirom | 2026-05-18 |
| sources/cancer-rx-cv-acc-2025 | Ganatra/Barac 2025 ACC CCG (JACC 2026;87:654–682): CV toxicity management for BTK inhibitors (ibrutinib AF 3–16%, HTN 71.6% new; diltiazem/amiodarone 6–9× ibrutinib levels; dabigatran contraindicated; Factor Xa preferred), ICI (myocarditis incidence 0.04–1.14%; Salem abatacept+ruxolitinib 3.4% vs 60% mortality; CPK 99% sensitivity rising 20 days pre-clinical; cTnT >32× ULN = 9× MACE risk), and VEGF inhibitors (dual antihypertensives if ≥160/100; BP target <130/80; ACE-I+amlodipine preferred; LMWH for GI/GU VTE; Khorana/COMPASS-CAT for prophylaxis); introduces "permissive cardiovascular toxicity" concept | cardio-oncology, BTK-inhibitors, immune-checkpoint-inhibitors, VEGF-inhibitors, cardiovascular-toxicity | 2026-05-24 |
| sources/weight-mx-acc-2025 | Gilbert/Gulati/Gluckman et al. 2025 ACC CCG (JACC 2025;86(7):536–555): NuSH therapy framework (liraglutide/semaglutide/tirzepatide) for cardiologists; patients should NOT "try and fail" lifestyle before pharmacotherapy; weight thresholds: 10–15% for CVD reduction, >15% for CV mortality/HFpEF; SELECT (semaglutide 2.4mg + CVD + no T2DM, n=17,604): MACE HR 0.80; SUMMIT (tirzepatide HFpEF): HR 0.62 composite; multidisciplinary comorbidity de-escalation table (antihypertensives/diuretics/T2DM meds/CPAP); compounded NuSH discouraged; US annual cost semaglutide $14,080 / tirzepatide $8,126; SURMOUNT-MMO ongoing (2027) | obesity-management, NuSH-therapy, GLP-1-receptor-agonist, cardiovascular-prevention, weight-management | 2026-05-25 |
| sources/pcsk9-inhibitors-nrc-2018 | Sabatine MS. 2018/2019 Nature Reviews Cardiology review: PCSK9 genetics (gain/loss-of-function variants); evolocumab/alirocumab mAb pharmacology; HoFH genotype-specific response; FOURIER (evolocumab n=27,564 HR 0.85 primary/HR 0.80 secondary) and ODYSSEY Outcomes (alirocumab n=18,924 HR 0.85) CVOTs; very-low LDL-C safety down to <10 mg/dL; inclisiran siRNA Phase II (ORION-1 ~50% LDL-C reduction Q6 months); PCSK9 vaccine and CRISPR future directions | #PCSK9-inhibitors, #cardiovascular-outcomes, #LDL-cholesterol, #dyslipidemia, #lipid-lowering-therapy | 2026-05-23 |
| sources/pcsk9-jaha-2022 | Punch/Klein/Diaba-Nuhoho/Morawietz/Garelnabi 2022 JAHA contemporary review: PCSK9 roles beyond LDL-C — atherosclerosis pathophysiology (Ox-LDL, foam cells, myeloperoxidase, HDL oxidation); PCSK9 and TLR4/NF-κB inflammatory signalling (preclinical cell culture + murine ApoE-/- data); PCSK9-resistin CRD structural homology (unique 3-jelly-roll CRD; resistin binds TLR4 + CAP1 via same domain); PCSK9-CAP1 binding confirmed (HEK293); LDL-R-independent hypothesis unconfirmed clinically (evolocumab: no CRP effect in FOURIER; no plaque composition change in one imaging study); AT04A vaccine + alirocumab murine plaque data | #PCSK9-inhibitors, #atherosclerosis, #inflammation, #oxidative-stress, #TLR4-NF-κB | 2026-05-24 |
| sources/immunization-acc-2025 | Heidenreich/Bhatt/Nazir et al. 2025 ACC CCG (JACC 2025;86(21):2085–2098): adult immunizations in CVD — influenza (annual; MACE RR 0.64 in 6 RCTs; IAMI HR 0.72 post-MI; 6× acute MI risk with infection; Class I/A CCD guideline); pneumococcal (PCV20/PCV21 preferred; HTN alone not qualifying; all adults ≥50y or 19–49y with CHD/HF/DM/smoking); COVID-19 (annual 2024-2025 formulation; 3× severe disease risk in CVD; mRNA myocarditis 1–19 cases/million, benign course); RSV (one-time ≥60–75y; ~80% efficacy year 1; protein subunit GBS 7–9/million); zoster (Shingrix 2-dose ≥50y; MI/stroke/HF/arrhythmia benefit lasting 8yr by South Korean study n>1 million); NUDGE-FLU trial: cardiovascular-focused messaging most effective strategy for vaccination uptake | #vaccination, #cardiovascular-prevention, #influenza, #immunization, #preventive-cardiology | 2026-05-25 |
| sources/cardiogenic-shock-acc-2025 | Sinha/Morrow/Kapur et al. 2025 ACC CCG (JACC 2025;85:1618–1641): evaluation and management of CS — SUSPECT CS mnemonic; SCAI A–E staging; Level 1/2/3 CS center tiers; PAC hemodynamic profiling (congestion profiles + PAPi); norepinephrine first-line; DOREMI (dobutamine vs milrinone, neutral); DanGer Shock (microaxial flow pump STEMI-CS, first positive tMCS RCT, 12.7% absolute 180-day mortality reduction); IABP-SHOCK II and ECLS-SHOCK (negative); Recognize/Rescue→Optimize→Stabilize→De-Escalate/Exit framework; tMCS weaning protocol | #cardiogenic-shock, #mechanical-circulatory-support, #heart-failure, #acute-myocardial-infarction, #hemodynamic-monitoring | 2026-05-25 |
| sources/cardiogenic-shock-nejm-2026 | Thiele/Hassager 2026 NEJM review (N Engl J Med 2026;394:62-77; trial PIs): non-AMI CS now outnumbers AMI-CS; mortality by phenotype (mixed 48%>AMI 41%>new HF 31%>secondary 31%>acute-on-chronic HF-CS 25%); 71% AMI-CS patients are frail; only 5% all CS + 32% STEMI-CS meet DanGer Shock eligibility; DanGer Shock HR 0.74 at 180d + sustained 10 years; 4-trial VA-ECMO IPD meta-analysis negative + more complications; Altshock-2 (IABP HF-CS, n=101) negative; CULPRIT-SHOCK (culprit-only PCI preferred; 45.9% vs 55.4%); transseptal LV unloading RCT neutral; MAP 55 vs 65 mmHg trial ongoing; dopamine>arrhythmias vs norepinephrine; levosimendan fails VA-ECMO weaning | #cardiogenic-shock, #mechanical-circulatory-support, #acute-myocardial-infarction, #heart-failure, #revascularization | 2026-05-25 |
| sources/cardiogenic-shock-aha-2017 | van Diepen/Katz et al. 2017 AHA scientific statement (Circulation 2017;136:e232–e268): foundational CS framework — hemodynamic phenotype classification (cold/wet ~2/3; cold/dry 28%; normotensive 5.2%; RV CS 5.3%); CS spiral pathophysiology; hub-and-spoke regionalized care model (≥107 cases/year threshold); phenotype-specific vasoactive guide; SHOCK trial historical context; CRRT (KDIGO Stage 2 threshold; continuous preferred); INTERMACS profile 1-2 38% 30-day MCS mortality; bridge-to-bridge strategy; Impella RP/CentriMag RV support; palliative care framework; predates SCAI staging, DanGer Shock, ECLS-SHOCK | #cardiogenic-shock, #mechanical-circulatory-support, #heart-failure, #systems-of-care, #hemodynamic-monitoring | 2026-05-25 |
| sources/mcs-ehj-2014 | Werdan/Gielen/Hochman 2014 EHJ review (Eur Heart J 2014;35:156–167): post-IABP-SHOCK II reassessment of MCS in CSMI — central thesis: hemodynamic improvement ≠ survival benefit unless MCS initiated before MODS; MODS (APACHE II/SAPS II) + SIRS biomarkers (IL-6, RAGE) > CI for mortality prediction; cardiac power output/index = strongest hemodynamic mortality correlate; 4-category device framework; IABP mechanism/Cochrane HR 1.04/Sjauw PCI-treated 6% increased mortality; EUROSHOCK registry (Impella 2.5; n=120; 64.2% mortality); ISAR-SHOCK (Impella 2.5 vs IABP: better hemodynamics, neutral mortality); 3-trial LVAD meta-analysis (better hemodynamics, RR 1.06 mortality, RR 2.35 bleeding); VA-ECMO: no RCTs, 60% vs 35% single-center; predates DanGer Shock, ECLS-SHOCK | #cardiogenic-shock, #mechanical-circulatory-support, #intra-aortic-balloon-pump, #acute-myocardial-infarction, #hemodynamic-monitoring | 2026-05-25 |
| sources/arrhythmia-monitoring-stroke-acc-2024 | Spooner/Messé/Chaturvedi et al. 2024/2025 ACC ECDP (JACC 2025;85:657–681): three-population post-stroke AF monitoring framework — (1) cardioembolic/already-anticoagulated → monitoring limited; (2) small/large-vessel stroke → 2–4 weeks monitoring, ICM in HF+LA enlargement subgroup (23.4% vs 5.0% AF detection); (3) ESUS/cryptogenic → 2–4 weeks mandatory if OAC candidate, ICM in select cases; OAC threshold: AF ≥5 min + CHA₂DS₂-VASc ≥3 (Class 2b/B); ICM detection 12–16% at 1yr, 30% at 36 months (CRYSTAL-AF); LOOP trial no ITT stroke reduction (HR 0.80; NS); CHASE-LESS and AS5F best post-stroke AF risk scores; consumer devices supplementary only; ESUS anticoagulation trials (NAVIGATE-ESUS/RE-SPECT ESUS/ARCADIA) all negative — AF identification required | atrial-fibrillation, stroke-prevention, cardiac-monitoring, anticoagulation, guidelines | 2026-05-25 |
| sources/co-indicator-anesthanalg-2010 | Reuter/Huang/Edrich/Shernan/Eltzschig 2010 Anesth Analg review (110:799–811): indicator-dilution CO monitoring — Stewart-Hamilton equation; IB-PATD (PAC; 40-year standard; measures RV CO; 22% change threshold for significance; 9 error sources including TR, respiratory cycling, injectate warming, catheter conductive loss); CPATD (Vigilance II/Q2plus; 9–12 min response lag); TCPTD/PiCCO (PAC-free; femoral arterial thermistor; GEDV and EVLW additional variables; GEDV superior to filling pressures as preload estimate; EVLW-guided protocols shorten extubation/ICU stay); LiDCO (lithium dilution; peripheral venous feasible; contraindicated in lithium therapy/pregnancy/weight <40 kg) | #hemodynamic-monitoring, #cardiac-output, #thermodilution, #pulmonary-artery-catheter, #critical-care | 2026-05-27 |