Wiki Master Index

Page Description Tags Date
CONCEPTS
concepts/ECLS-in-PH VA-ECMO and PA-LA approach for refractory RV failure in PH; bridge to transplant the only established indication; awake ECMO preferred; RVAD contraindicated in PAH; ECMO watershed phenomenon; 94% bridged to Tx; 78% hospital discharge extracorporeal-membrane-oxygenation, right-ventricular-failure, pulmonary-hypertension, lung-transplantation, mechanical-circulatory-support 2026-05-31
concepts/Lung-Transplantation-PAH Referral (ESC/ERS intermediate/high or REVEAL >7); listing (high risk or REVEAL ≥10); bilateral Tx procedure of choice; no RV dysfunction precludes Tx; perioperative + prolonged postoperative ECMO prevents early LV graft dysfunction; 1-year survival >90%; RV recovers universally post-Tx lung-transplantation, pulmonary-hypertension, right-ventricular-failure, extracorporeal-membrane-oxygenation, intensive-care 2026-05-31
concepts/Paroxysmal-AV-Block PAVB: sudden complete AV block with asystole; TD-PAVB (atrial rate acceleration → repetitive concealed conduction in diseased His-Purkinje with postrepolarization refractoriness) vs PD-PAVB (pause → source-sink mismatch ± phase 4 depolarization); His bundle most common site (7/10 EPS cases); "phase 3/4 block" are misnomers; Mobitz II closely associated paroxysmal-AV-block, His-Purkinje-system, tachycardia-dependent-block, concealed-conduction, atrioventricular-block 2026-05-30
concepts/NOAC-AF-Management NOAC use in AF: EHRA VHD Type 1/2 classification; drug-specific renal clearance (dabigatran 80%→apixaban 27%); CKD dosing; Child-Pugh liver dosing; drug-drug interactions (P-gp/CYP3A4); dose-reduction criteria; bleeding management (idarucizumab/andexanet alfa); cardioversion anticoagulation; SAMe-TT2R2; no bridging perioperatively atrial-fibrillation, anticoagulation, noac, stroke-prevention, pharmacokinetics 2026-05-30
concepts/NOAC-Perioperative Perioperative NOAC management: no LMWH bridging; timing tables (dabigatran CrCl-dependent: 24–96h; FXa inhibitors 24–48h); dental surgery no-stop; device implantation last-dose-morning-before; neuraxial ≥3–5 days; AF ablation uninterrupted or 12h before (ACT 300–350s); urgent surgery tiers (immediate/urgent/expedite) with reversal agent decision tree anticoagulation, noac, perioperative, surgery, bridging 2026-05-30
concepts/AI-ECG-HCM-Scar XplainScar: explainable ML model for LV scar detection/localization in HCM from 12-lead ECG; F1=89% external validation; unsupervised clustering + SCARF + SHAP; basal scar → Q wave/intrinsicoid QRS in aVR; apical scar → T wave inversion V2–V6; cannot quantify scar; prospective validation pending hypertrophic-cardiomyopathy, artificial-intelligence, ECG, LV-scar, explainability 2026-05-30
concepts/Fascicular-Blocks LAH (LAFB) and LPH (LPFB): anatomy (posterior division dual blood supply — LAD + PDA, most protected); LAH ECG (AQRS −45° to −90°; S III > S II; CCW VCG loop = pathognomonic); LPH ECG (AQRS +100° to +180°; S1Q3; rS in I/aVL; CW VCG loop); 7 MI masking/simulation patterns; masquerading RBBB (LAH conceals RBBB S waves); RBBB+LPH = near-trifascicular: 80–87% acute MI mortality, 42% AV block; LAH epidemiology (2.77% healthy population; 62% in <40yr; CAD 41% in hospital patients); Lev vs Lenègre disease left-anterior-hemiblock, fascicular-block, intraventricular-conduction-delay, myocardial-infarction-masking, electrocardiography 2026-05-30
concepts/RBBB RBBB clinical overview: 2–3% prevalence, strongly age/sex-dependent (1% age 50 → 18% age 80 men); thin long RV bundle (LAD supply); initial 30–40 ms normal → MI co-diagnosis preserved; rSR' most common V1 pattern; Brugada = pseudo-RBBB (no wide S in I/V6; Chiale maneuver unmasks concealed Brugada in true RBBB); CRT generally no benefit except RBBB+LAFB or prolonged PR; isolated RBBB benign; RBBB+CVD = independent mortality predictor right-bundle-branch-block, ECG-criteria, ventricular-conduction-delay, Brugada-syndrome, bifascicular-block 2026-05-30
entities/Vectorcardiography Frank lead system (gold standard, 7 electrodes); Kors regression (~98%) and IDT (~97.2%) best ECG→VCG transforms; quasi-orthogonal NOT reliable; QRS-T spatial angle most analyzed parameter; QRS area outperforms QRS duration and LBBB morphology for CRT response; VCG superior for LQTS (86% vs 69%), MI (98% vs 73%), atrial enlargement; mid-end QRS loop delay pathognomonic of true LBBB; IDT contraindicated for AF f-wave analysis vectorcardiography, ECG-derived-VCG, Frank-lead-system, QRS-T-angle, cardiac-signal-processing 2026-05-30
concepts/LBBB-Criteria Conventional AHA criteria (QRS ≥120 ms) vs Strauss strict criteria (≥140/130 ms men/women + mid-QRS notching/slurring ≥2 leads); ~1/3 of conventional LBBB = pseudo-LBBB (LVH+LAFB); concordant LBBB (~28–32%, milder disease, LVEF ~51%, better prognosis) vs discordant LBBB (~68–70%, lower LVEF ~36%, worse prognosis, greater CRT benefit); VCG mid-end QRS loop conduction delay pathognomonic of true LBBB; gender differences (women exhibit LBBB at shorter QRSd); ~30% CRT non-responder rate linked to false LBBB diagnosis left-bundle-branch-block, ECG-criteria, cardiac-resynchronization-therapy, vectorcardiography, ventricular-conduction-delay 2026-05-30
concepts/Atrial-Septal-Defect Most common CHD diagnosed in adulthood (25–30% of new diagnoses); 4 subtypes (secundum 80%/primum 15%/sinus venosus 5%/coronary sinus); proactive closure normalises prognosis; PVR <5 WU safe / ≥5 WU contraindicated; cardiac erosion — atrial septal malalignment novel risk factor; PCWP monitoring in elderly (abandon if rise >10 mmHg or >20 mmHg absolute); ASD closure does NOT reliably reduce AF; ~1/3 >60yr and ~1/2 >70yr have AF; PVI before closure for symptomatic paroxysmal/persistent AF (age <75, LA <50 mm); ASD closure beneficial even in permanent AF; Eisenmenger contraindication; COstatus transpulmonary ultrasound dilution for Qp/Qs in critically ill paediatric patients; Qp:Qs is a relative ratio — absolute flow burden varies widely at identical Qp:Qs; exercise-induced shunt dynamics contradictory across 3 studies (no clear guideline on exercise restriction); late-onset post-closure PAH risk factors: delayed repair >40yr, BMPR2 variants, microvascular disease atrial-septal-defect, adult-congenital-heart-disease, congenital-heart-disease, pulmonary-arterial-hypertension, arrhythmia-management 2026-05-28
concepts/Intracardiac-Shunts Qp/Qs ratio classification (<1.0 R→L / 1.0–1.5 small / 1.5–2.0 moderate / ≥2.0 large L→R); Qp/Qs is a relative index — absolute flow differs widely at identical ratios (7.2 vs 10.8 L/min at Qp:Qs 1.8 with CO 4 vs 6 L/min); echocardiography detects but cannot quantify Qp/Qs; oximetric shunt equation (invasive gold standard); perivascular flow probes (coronary flow excluded → Qs underestimate); COstatus ultrasound dilution sensitivity 95.7%/specificity 97.6% for shunt detection but underestimates Qp/Qs magnitude in moderate/small shunts; PVFP vs OSE percentage error 58.8% — no true gold standard intracardiac-shunt, congenital-heart-disease, pediatric-hemodynamics, cardiac-output, hemodynamic-monitoring 2026-05-28
concepts/Cardiac-Output-Measurement 5 method classes: Fick (direct O₂ = gold standard, CO₂ rebreathing ±35–49%), indicator dilution (PAC TD gold standard — revival in cardiac ICUs; CCOM every 20s; 9 error sources; TCPTD/PiCCO + GEDV/EVLW; LiDCO; COstatus shunt detection), pulse contour (PiCCO ±32%, LiDCO ±24%, Vigileo ±41%, Modelflow ±17%), CCE/TTE ±25% (acceptable; proposed future reference), bioreactance (NICOM: poor in cardiogenic shock), esCCO/USCOM 42.7%/CO₂ rebreathing (all unacceptable in critically ill); Critchley-Critchley ±28% criterion; no method surpasses 3-synchronized-injection TD cardiac-output, hemodynamic-monitoring, thermodilution, pulmonary-artery-catheter, critical-care-echocardiography, critical-care, pulse-contour-analysis 2026-05-29
concepts/Invasive-Hemodynamic-Monitoring-CS PAC-guided monitoring in CS; CPO = (MAP × CO)/451 — strongest hemodynamic mortality predictor; CPO/lactate 12–24h decision rule (escalate vs wean); CI unreliable beyond 24h (MODS/SIRS take over); LV/RV/biventricular congestion profiles; PAWP/PAPi thresholds for device weaning; HF-CS vs AMI-CS distinction (HF-CS: severe hemodynamics but preserved end-organs + normal lactate); no RCT for PAC in CS (PACCS ongoing) cardiogenic-shock, hemodynamic-monitoring, pulmonary-artery-catheter, cardiac-power-output, right-ventricular-failure 2026-05-25
concepts/Pulmonary-Artery-Pulsatility-Index PAPi = PAPP/RAP; NOT a direct RV function measure — composite of SV, pulmonary arterial capacitance (PAC), and RAP; PAWP reduces PAC and raises PAPi independently of RV function; population-specific cutoffs non-interchangeable (≤0.9 RV MI / <1.85 LVAD / <3.65 advanced HF / ≥1.0 VA-ECMO wean); PAPi NOT associated with 30-day mortality in SHOCK trial; post-LVAD PAC normalisation reduces PAPi sensitivity cardiogenic-shock, hemodynamic-monitoring, right-ventricular-failure, mechanical-circulatory-support, pulmonary-arterial-capacitance 2026-05-25
concepts/Vasoactive-Agents-in-CS No mortality-reducing agent in CS (Cochrane); norepinephrine first-line; dopamine → more arrhythmias; epinephrine → lactic acidosis; dobutamine = milrinone (DOREMI); phenylephrine discouraged; levosimendan failed VA-ECMO weaning RCT; β-blockers/RAAS contraindicated in active CS cardiogenic-shock, vasopressors, inotropes, pharmacology, hemodynamic-monitoring 2026-05-26
entities/Levosimendan Quadruple-mechanism inodilator (TnC calcium sensitisation + vascular KATP vasodilation + mitochondrial KATP/mPTP/cytochrome-C cardioprotection + endothelial NO via p38 MAPK; PDE3 only supratherapeutic); OR-1896 t½ ≈70–80h → ≥1 week pharmacodynamic effect; ONLY inotrope with zero myocardial O₂ cost; AF risk (increased vs dobutamine/placebo); VT discordant (REVIVE vs SURVIVE) but real-world ICD/VT unchanged (LEVO-D); LIDO 180-day HR 0.57; enoximone CS/AMI survival 69% vs 37%; VA-ECMO weaning mixed; PPCM/takotsubo preferred; cardiac surgery LCOS reduction; septic shock positive meta-analyses; LEVO-D registry (n=403 destination therapy): HF hosp 77.9%→38.7%; 43.7% responders; LEVO-D score AUC 0.71; no strategy or dose superiority; ESC 2021 palliative/bridge to transplant/LVAD calcium-sensitizer, inotropes, advanced-heart-failure, destination-therapy, cardiogenic-shock 2026-05-26
concepts/IABP IABP device mechanics (8-9.5Fr, helium, tip distal to left subclavian); 4 timing error patterns; coronary flow limited by autoregulation/stenosis; Benchmark Registry major complications 2.6%; NRMI-2 benefit with thrombolysis but not PCI; contraindications (AR, dissection, aneurysm, PVD); JCS/ESC/ACC guideline discordance intra-aortic-balloon-pump, cardiogenic-shock, mechanical-circulatory-support, hemodynamic-monitoring, acute-myocardial-infarction 2026-05-25
concepts/ECPELLA Combined VA-ECMO + Impella for cardiogenic shock; counteracts VA-ECMO retrograde afterload; Schrage 2020 HR 0.79 (observational); higher complication burden (bleeding/hemolysis/limb ischemia/RRT); three-step weaning (PAPi ≥1.0 for VA-ECMO; PAWP <20+CPO ≥0.6W for Impella); optimal PVA during recovery unresolved cardiogenic-shock, mechanical-circulatory-support, VA-ECMO, Impella, ECPELLA 2026-05-25
concepts/OTVA-ECG-Localization 12-lead ECG localization of outflow tract VAs (RVOT 70–80%, LVOT 15–25%, LV summit 12%); ECG signatures for 11+ sites; 18 published algorithms — combined TZ+V2S/V3R best overall (Youden 0.77); V3R/V7 index best AUC (0.95); V3 transition and preferential conduction are key pitfalls; stepwise algorithm included outflow-tract-ventricular-arrhythmia, ECG-localization, catheter-ablation, PVC, ventricular-tachycardia 2026-05-29
concepts/Sudden-Cardiac-Death Updated with AHA 2017 US epidemiology: 230,000–350,000 SCD/year; 356,500 OHCA/year; 10% OHCA overall survival (6% at home; 24% in-hospital); ≥25% SCD is first cardiac event; ischemic HD predominates but declining; age-stratified risk; mechanisms: automaticity/triggered activity/reentry ventricular-arrhythmia, sudden-cardiac-death, epidemiology, ICD-risk-stratification, guideline 2026-05-23
entities/ICD Updated with AHA 2017 Class I primary prevention thresholds: ischemic HD LVEF ≤35%+NYHA II-III (≥40d post-MI, ≥90d post-revasc); LVEF ≤30%+NYHA I; NICM LVEF ≤35%+NYHA II-III+≥3m GDMT; secondary prevention SCA survivor/unstable VT; Lamin A/C ≥2 of 4 risk factors (IIa); value statements (primary prevention = high value <$50K/QALY; secondary = intermediate $64-100K/QALY) ICD, primary-prevention, secondary-prevention, sudden-cardiac-death, heart-failure 2026-05-23
concepts/Electrical-Storm AHA 2017 definition: ≥3 episodes sustained VT, VF, or appropriate ICD shocks within 24h; acute management: correct reversible triggers + IV beta-blockers + IV amiodarone + deep sedation; catheter ablation for drug-refractory cases ventricular-arrhythmia, ICD-risk-stratification, arrhythmia-management 2026-05-23
concepts/HCM-Risk-SCD Updated with AHA/ACC 2017 risk factor table: established factors (SCA, sustained VT, FHx SCD-HCM, LV wall ≥30mm, unexplained syncope <6mo, NSVT, abnormal BP exercise response); potential modifiers (age <30, LGE-CMR, LVOTO); high-risk subsets (LV aneurysm, LVEF <50%); contrasts with ESC quantitative HCM Risk-SCD calculator approach sudden-cardiac-death, HCM, risk-stratification, ICD-risk-stratification, guideline 2026-05-23
concepts/Sinus-Node-Dysfunction SND (sick sinus syndrome): age-dependent fibrosis → bradycardia/pause/tachy-brady syndrome; pacing requires symptom–bradycardia temporal correlation (no minimum HR/pause threshold); primary benefit QOL; atrial-based pacing over VVI; rate-responsive for chronotropic incompetence bradycardia, sinus-node-dysfunction, permanent-pacing, tachy-brady-syndrome, chronotropic-incompetence 2026-05-23
concepts/Atrioventricular-Block AV block classification (first-degree through third-degree), etiology (degenerative/Lyme/sarcoidosis/neuromuscular), site-based prognosis; Mobitz II/high-grade/third-degree → PPM regardless of symptoms; infranodal block does NOT respond to atropine; TAVR conduction disturbances; LVEF 36–50% + >40% ventricular pacing → CRT/His bundle pacing preferred atrioventricular-block, bradycardia, permanent-pacing, infranodal-block, cardiac-conduction-delay 2026-05-23
concepts/Permanent-Pacing-Indications Comprehensive 2018 ACC/AHA/HRS pacing indications: SND (symptom-required), AV block (Mobitz II/high-grade/complete → PPM regardless), neuromuscular disease (myotonic dystrophy/Kearns-Sayre), TAVR, acute MI, alternating BBB; LVEF 36–50% pacing mode selection; shared decision-making and pacemaker withdrawal rights permanent-pacing, bradycardia, sinus-node-dysfunction, atrioventricular-block, cardiac-conduction-delay 2026-05-23
concepts/Marfan-Syndrome FBN1 haploinsufficiency → aortic root aneurysm + ectopia lentis + dolichostenomelia; TGF-β dysregulation central mechanism; Ghent 2010 criteria (4 sporadic + 3 family-history routes; systemic score max 20 pts ≥7; Ao Z≥2 cardinal); prevalence 1.5–17.2/100,000 (far below 1:5,000 estimate); diagnostic delay median 2yr (EURORDIS); seven-signs screening tool; atenolol = losartan (Lacro 2014 NEJM); beta-blocker standard of care; aortic root replacement at 5 cm; Type B dissection surgery >5.5 cm; Loeys-Dietz key differential marfan-syndrome, connective-tissue-disorders, aortic-aneurysm, fibrillin-1, tgf-beta-signaling 2026-05-23
concepts/Cardiac-Glycosides-in-HFrEF Digoxin/digitoxin in HFrEF: HF hospitalization HR=0.79 (benefit); all-cause mortality HR=0.98 (no benefit); digitoxin vs digoxin indirect comparison NS; DIGIT-HF 2025 only contemporary-GDMT trial; hospitalization benefit DIG-sensitive; TDM-guided dosing key; AHA/ACC COR IIb for symptom reduction cardiac-glycosides, heart-failure, HFrEF, digoxin, digitoxin 2026-05-22
entities/Cardiac-Glycosides Na⁺/K⁺-ATPase inhibitor drug class (digoxin + digitoxin); positive inotropy + vagotonic rate control; HFrEF COR IIb; HF hospitalization HR=0.79 (no mortality benefit); DIGIT-HF 2025 HR 0.82 composite; digoxin renal-cleared / digitoxin hepatic; Class III Harm in pre-excited AF; Fab antidote for toxicity cardiac-glycosides, digoxin, digitoxin, heart-failure, drug-toxicity 2026-05-22
concepts/Cardiac-Rehabilitation-HF Class 1A ACC/AHA recommendation; 10–30% participation worldwide; FITT exercise prescription; HF-ACTION protocol (60–70% HRR; 36 sessions); MCT mainstay; HIIT not superior to MCT (SMARTEX-HF); inspiratory muscle training in respiratory weakness; LVEF not a reliable marker of benefit; no CMS coverage for HFpEF; 6-week wait removal proposed heart-failure, cardiac-rehabilitation, exercise-training, HFrEF, HFpEF 2026-05-22
concepts/SVT-Management AHA 2015 + ESC 2019 framework: vagal maneuvers (modified Valsalva 43% conversion) → adenosine → IV CCB/BB → cardioversion; catheter ablation first-line; Class III/Harm AV nodal blockers in pre-excited AF; PROCAMIO trial: procainamide superior to amiodarone in stable wide QRS; ESC vs AHA comparison table supraventricular-tachycardia, arrhythmia-management, catheter-ablation, antiarrhythmic-drugs, guidelines 2026-05-21
concepts/AVNRT Most common SVT (>60% female); dual AV nodal physiology; typical (slow-fast): pseudo-S inferior + pseudo-R' V1 (short RP); 50% minimally symptomatic improve spontaneously within 1–3 years; slow-pathway ablation 97% success, 2% recurrence, 0.3% complications (ESC 2019 Table 11); cryoablation lower AV block but higher recurrence supraventricular-tachycardia, AVNRT, catheter-ablation, arrhythmia-management 2026-05-21
concepts/AVRT-Accessory-Pathway Orthodromic AVRT (narrow; 90%) vs antidromic AVRT (wide; 5%); WPW SCD risk ~2.4/1000 person-years; pre-excited AF: amiodarone Class III/B (ESC) + Class III/Harm (AHA); EPS now Class I/B for athletes/high-risk occupations (ESC 2019); intermittent pre-excitation downgraded as imperfect low-risk marker supraventricular-tachycardia, accessory-pathway, AVRT, wolff-parkinson-white, pre-excitation 2026-05-21
concepts/Tachycardia-Induced-Cardiomyopathy TCM = reversible LV dysfunction from persistent tachycardia; any SVT can cause; focal AT commonest in <18 years; PJRT classic example; catheter ablation Class I/B; beta-blockers Class I/A if ablation fails; consider in any LVEF-reduced patient with HR >100 bpm; IST does NOT cause TCM tachycardiomyopathy, heart-failure, catheter-ablation, arrhythmia-management, cardiomyopathy 2026-05-21
concepts/AF-Stable-CAD-Antithrombotic Antithrombotic strategy in AF + stable CAD: OAC monotherapy vs dual therapy; AFIRE (rivaroxaban, non-standard dose, noninferior); EPIC-CAD (NEJM 2024; edoxaban; NACE HR 0.44; NNT 10.6; bleeding HR 0.34; ischemic events NS — underpowered); COR 2b/C-LD expected to be upgraded; East Asian population caveat atrial-fibrillation, coronary-artery-disease, edoxaban, antithrombotic-therapy, anticoagulation 2026-05-20
concepts/Venous-Thromboembolism-Anticoagulation COBRRA (NEJM 2026; n=2,760): apixaban vs rivaroxaban head-to-head — clinically relevant bleeding 3.3% vs 7.1% (RR 0.46; P<0.001); major bleeding 0.4% vs 2.4%; VTE recurrence equal (1.1% vs 1.0%); bleeding difference attributed to rivaroxaban's higher 21-day loading dose. HI-PRO (NEJM 2025; n=600): extended apixaban 2.5 mg BID vs placebo in provoked VTE + enduring risk factors — VTE recurrence 1.3% vs 10.0% (HR 0.13; P<0.001); major bleeding 0.3% vs 0%; CRNMB trend 4.8% vs 1.7% (NS); 10% placebo recurrence challenges the provoked/unprovoked binary venous-thromboembolism, noac, apixaban, rivaroxaban, extended-anticoagulation, provoked-VTE, bleeding-risk 2026-05-20
concepts/Aldosterone-Synthase-Inhibitors ASIs block CYP11B2 to reduce aldosterone production (vs MRAs which block the receptor); baxdrostat BaxHTN phase 3 (NEJM 2025; n=794): −8.7/−9.8 mmHg placebo-corrected office SBP at 12 weeks (P<0.001); lorundrostat ADVANCE-HTN phase 2b (NEJM 2025; n=285): −7.9/−6.5 mmHg placebo-adjusted 24h ambulatory SBP at 12 weeks (P<0.001); 50 mg optimal lorundrostat dose; MATE1 interaction → cystatin C preferred; no CV outcomes; no head-to-head vs spironolactone resistant-hypertension, aldosterone-synthase-inhibitor, baxdrostat, hypertension, renin-angiotensin-aldosterone-system 2026-05-20
concepts/Angiography-Based-Coronary-Physiology FAST III (NEJM 2026; n=2,235; NI P=0.004): vFFR (3D-QCA, no wire, no adenosine) noninferior to pressure-wire FFR for death/MI/revasc at 1yr (7.5% vs 7.5%); vFFR detects more functionally significant lesions (40.9% vs 31.3%) → higher revasc rate (45% vs 36%); procedure −5 min shorter; complication rate lower (3.7% vs 6.0%); FAVOR III Europe (QFR) showed higher MACE than FFR — not all angiography-based indices equivalent angiography-based-physiology, fractional-flow-reserve, coronary-physiology, intermediate-coronary-lesions, pci-guidance 2026-05-20
concepts/Blood-Pressure-Target-T2DM BPROAD (NEJM 2025; n=12,821; HR 0.79; P<0.001): intensive SBP <120 vs standard <140 mmHg in T2DM; 21% CV event reduction; stroke primary driver; albuminuria HR 0.87; resolves ACCORD null result; ESC 2024 Class I SBP 120–129 mmHg in T2DM (most aggressive guideline target, now BPROAD-corroborated); hyperkalemia/hypotension monitoring required type-2-diabetes, hypertension, blood-pressure-control, cardiovascular-outcomes-trial, randomized-controlled-trial 2026-05-20
concepts/Hypertension-HMOD ESC 2024 HMOD framework: structural/functional target organ damage (heart/kidney/arteries/eye/brain) from sustained elevated BP; HMOD positive at elevated BP (120–139 mmHg) triggers treatment without SCORE2; renal HMOD (eGFR <60 or ACR ≥30 mg/g); cardiac HMOD (ECG LVH: Sokolow-Lyon/Cornell/RaVL; echo LVH: sex-specific LV mass/height²·⁷ thresholds; hs-cTnT/NT-proBNP); vascular HMOD (PWV >10 m/s; plaque >1.5 mm; CAC >100); retinal HMOD Class I at BP >180/110 hypertension, hmod, left-ventricular-hypertrophy, chronic-kidney-disease, cardiovascular-risk 2026-05-20
concepts/HF-COPD-Comorbidity Bidirectional HF-COPD pathophysiology: 70% of COPD+HF is HFpEF; hyperinflation → preload failure; pulmonary congestion → dynamic airway obstruction; NP unreliable in HFpEF+COPD; spirometry under euvolemic conditions; CPET VE intercept ≥2.6 L/min identifies COPD in HF; bisoprolol preferred in HFrEF+COPD (β1/β2 14:1; anti-inflammatory; FEV1 +0.46 L per Feng 2023 MA); β-blockers avoided in HFpEF+COPD; LAMA+ICS over LABA; BLOCK COPD (NEJM 2019): metoprolol without cardiac indication increased COPD hospitalisation (HR 1.91); active contradiction: bisoprolol MA (Feng 2023) shows HF-independent benefit — drug-class difference plausible but unconfirmed by RCT heart-failure, COPD, cardiopulmonary-interaction, HFpEF, beta-blockers 2026-05-21
concepts/Cardiopulmonary-Exercise-Testing CPET in HF: VE/VCO2 slope prognostic but non-discriminatory for COPD; VE intercept (VEint ≥2.6–4.07 L/min) identifies COPD as HF comorbidity across EF spectrum; recommended for stable dyspnoeic HF patients to confirm/exclude COPD; peak VO2 bounded by Fick equation; transplant threshold <12–14 mL/kg/min CPET, heart-failure, COPD, exercise-physiology, cardiopulmonary-interaction 2026-05-28
concepts/VO2max VO2max = (LVEDV−LVESV) × HR × a-v O2 diff — true parametric ceiling (Hawkins 2007 n=156: supramaximal work never exceeded VO2max); elite advantage = large cardiac output from LV EDV/compliance (not contractility or a-v O2); altitude VO2max −0.6%/100m via O2 transport (not motor recruitment); peripheral fatigue: Ca2+/Na-K pump/ROS → reduced central motor drive; Central Governor Model rebutted; ACE gene not confirmed; HF transplant threshold <12–14 mL/kg/min VO2max, exercise-physiology, cardiac-output, endurance-athletes, oxygen-transport 2026-05-28
concepts/Athletes-Heart Cardiac remodeling in elite endurance athletes: large LV EDV (not reduced ESV or higher contractility) from enhanced myocardial + pericardial compliance; Levine 1991 direct P-V curves; active diastolic suction from elevated equilibrium volume; pericardial constraint limits normal hearts (pericardiectomy → increased CO + VO2max in dogs/pigs); 1 year training achieves LV mass but not EDV/compliance of elite athletes; largest CO 42.3 L/min; largest SV 212 mL endurance-athletes, cardiac-remodeling, LV-compliance, cardiac-output, exercise-physiology 2026-05-28
concepts/Iron-Deficiency-in-HF IV iron in HFrEF/HFmrEF: ESC Class I (symptoms) + Class IIa (hospitalizations); FAIR-HF/CONFIRM-HF/EFFECT-HF positive for QoL; AFFIRM-AHF near-significant (acute HF, RR 0.79); HEART-FID (n=3,065 ambulatory) primary missed (win ratio 1.10; P=0.02 vs threshold 0.01); TSAT <20% emerging as preferred diagnostic criterion; SGLT2i era gap heart-failure, iron-deficiency, ferric-carboxymaltose, HFrEF, intravenous-iron 2026-05-17
concepts/NSTEMI-Elderly-Invasive-Strategy SENIOR-RITA (NEJM 2024; n=1,518; mean age 82; 32% frail; 4.1yr): invasive vs conservative in elderly NSTEMI — primary composite neutral (HR 0.94; P=0.53); nonfatal MI HR 0.75 (P<0.05); CV death HR 1.11 NS; time-varying benefit erodes by 5yr; radial access 89.3%; <1% complications; subsequent revasc 3.9% vs 13.7%; After Eighty positive at 18 months (contradicts); Kotanidis meta-analysis neutral; frailty not a contraindication to angiography nstemi, elderly-patients, invasive-strategy, frailty, coronary-artery-disease 2026-05-18
concepts/Fractional-Flow-Reserve FFR physiology (Pd/Pa at hyperemia; ≤0.80 threshold); validated in stable CAD; FULL REVASC (NEJM 2024; n=1,542; 4.8yr): FFR-guided complete revascularization NEUTRAL vs culprit-only (HR 0.93; P=0.53) + stent thrombosis HR 2.80; 40% of patients deferred all nonculprit lesions; diverges from angiography-guided COMPLETE (26% CV death/MI reduction) — FFR cannot detect vulnerable plaque; iFR equivalent in stable CAD; guideline: Class IIa AHA 2025 for intermediate STEMI lesions; FAST III (NEJM 2026): wire-free vFFR noninferior to FFR for intermediate lesions (7.5% vs 7.5%; P=0.004 NI) fractional-flow-reserve, coronary-physiology, complete-revascularization, acute-coronary-syndrome, coronary-artery-disease 2026-05-20
concepts/Multivessel-PCI-STEMI-Timing Immediate vs staged complete revascularization in STEMI with multivessel CAD; MULTISTARS AMI (NEJM 2023): immediate superior (8.5% vs 16.3%; RR 0.52; P<0.001); iMODERN (NEJM 2026): immediate iFR-guided NOT superior to deferred MRI-guided (HR 0.95; P=0.81); FULL REVASC (NEJM 2024): FFR-guided complete revascularization NEUTRAL (HR 0.93; P=0.53) vs angiography-guided COMPLETE (benefit); Class IIb/B-R AHA 2025 stemi, multivessel-pci, complete-revascularization, fractional-flow-reserve, pci-timing 2026-05-20
concepts/Instantaneous-Wave-Free-Ratio iFR: resting pressure-wire index (≤0.89 ischemic); no adenosine required; 2× higher lesion detection than cardiac stress MRI in STEMI (iMODERN); false-positive rate ~11% in STEMI due to elevated resting flow; validated equivalent to FFR in stable CAD (DEFINE-FLAIR, iFR-SWEDEHEART) ifr-guided-pci, coronary-physiology, fractional-flow-reserve, stemi, coronary-artery-disease 2026-05-19
concepts/Cardiac-Resynchronization-Therapy CRT-D vs ICD: COMPANION (HR 0.64 mortality), CARE-HF (CRT-P HR 0.64 mortality), MADIT-CRT (QRS ≥150ms HR 0.48; women HR 0.37), RAFT Long-Term (AF 0.80 at 14yr; curves converge >12yr); non-LBBB/AF benefit attenuated; conduction system pacing emerging alternative; CRT benefit on modern GDMT uncertain cardiac-resynchronization-therapy, heart-failure-reduced-EF, biventricular-pacing, QRS-duration, device-therapy 2026-05-17
concepts/ClinGen-Gene-Disease-Validity ClinGen 7-tier evidence framework (Definitive→Refuting) for gene-disease pairs; cardiovascular GCEPs; key disputed/refuting findings across HCM/BrS/ARVC/CPVT/LQTS/PAH; clinical actionability of classification clingen, gene-disease-validity, hereditary-cardiovascular-disease, variant-interpretation, genetics 2026-05-09
concepts/Atrial-Cardiomyopathy ESC/HFA 2025 diagnostic framework: electrical dysfunction (P-wave score ≥1) + mechanical dysfunction/enlargement/fibrosis; P-wave score 0–4; LAVi >40 ml/m², LASr <23%; atrial failure as end-stage; NLRP3/BMP10/epicardial adipose targets atrial-cardiomyopathy, atrial-fibrillation, heart-failure, atrial-fibrosis, electrocardiography 2026-05-01
concepts/Inter-Atrial-Block IAB defined by P-wave ≥120 ms; partial (bimodal, positive inferior leads) vs advanced (biphasic inferior leads = Bayes syndrome); P-wave score 1–2 (partial/advanced); partial IAB 2× AF risk; advanced IAB 4× AF risk; AHA 2009 LAA criteria: PTF-V1 >40 mm·ms / P duration ≥120 ms / terminal axis −30 to −90°; "intraatrial conduction delay" preferred over interatrial inter-atrial-block, atrial-cardiomyopathy, electrocardiography, atrial-fibrillation, stroke 2026-05-16
concepts/Atrial-Failure End-stage AtCM: persistent AF or HF with dyspnoea/fatigue attributable to atrial disease; progressive structural/electrophysiological/functional changes; manage per AF + HF guidelines atrial-cardiomyopathy, atrial-fibrillation, heart-failure 2026-05-01
concepts/Cancer-Associated-VTE Most common CV complication of malignancy; 7–8× VTE risk; Ottawa recurrence score; LMWH preferred over VKA; emerging DOAC evidence; API-CAT (NEJM 2025): reduced-dose apixaban 2.5 mg BID noninferior for VTE (2.1% vs 2.8%; SHR 0.76) AND superior for bleeding (12.1% vs 15.6%; SHR 0.75; P=0.03) vs full-dose 5.0 mg BID in extended-phase cancer VTE; first RCT to establish dose-reduced extended anticoagulation in cancer cancer-associated-VTE, venous-thromboembolism, anticoagulation, cardio-oncology, thrombosis 2026-05-19
concepts/Clonal-Hematopoiesis CH/CHIP: somatic HSC clonal expansion (DNMT3A/TET2/ASXL1/JAK2); 1.7–2× ASCVD risk; 25% HF risk; TET2→IL-1β/NLRP3; canakinumab/colchicine in TET2-CH; therapy-related CH amplifies cardiotoxicity; no proven CVD therapy clonal-hematopoiesis, cardiovascular-risk, inflammation, atherosclerosis, cardio-oncology 2026-05-02
concepts/CAM-in-Heart-Failure Complementary and alternative medicine in HF: omega-3 PUFA Class 2b AHA rec; CoQ10 uncertain; hawthorn harm in LVEF ≤35%; licorice/Vit E/grapefruit juice harm; yoga/tai chi recommended; drug-interaction catalog heart-failure, complementary-alternative-medicine, drug-interactions, nutraceuticals, guidelines 2026-04-30
concepts/AAV-Gene-Delivery AAV9 cardiac gene delivery platform; 4.7 kb packaging constraint; Danon (RP-A501): LVM −23%, troponin −84%, grade 4 TMA risk; Pompe (GC301): no anti-GAA antibodies, BBB penetration; DMD clinical fatalities (innate immune/AAV vector): 27-yr-old death + AAV-Cas12 minimal long-term rescue; LNP vs AAV strategic rule (LNP for liver targets) gene-therapy, viral-vectors, danon-disease, pompe-disease, lysosomal-storage-disorder 2026-05-23
concepts/Danon-Disease X-linked LAMP2 LOF → severe HCM + autophagic vacuoles; males die/transplant age 19–21yr; RP-A501 (rAAV9-LAMP2B) Phase 1: LVM −23%, troponin −84%, 7/7 alive at 4.5yr; grade 4 complement-mediated TMA; grade 3 steroid-induced myopathy; anti-LAMP2B antibodies without sequelae lysosomal-storage-disorder, hypertrophic-cardiomyopathy, gene-therapy, LAMP2, X-linked 2026-05-18
concepts/Pompe-Disease Lysosomal GAA deficiency; infantile-onset rarely survives >1yr untreated; ERT limitations (no CNS penetration, anti-rhGAA IgG, short half-life); GC301 (rAAV9-coGAA) first human trial: no anti-GAA immunity, BBB crossing, cardiac/psychomotor improvement in 3/4 patients lysosomal-storage-disorder, gene-therapy, acid-alpha-glucosidase, cardiomyopathy, enzyme-replacement-therapy 2026-05-17
concepts/Lipid-Gene-Therapy GET for lipid disorders using LNP/GalNAc hepatic delivery: PCSK9 base editing (VERVE-102/Heart-2 NEJM 2026 n=35: 1.0 mg/kg → PCSK9 −88%, LDL-C −62%, −78 mg/dL absolute, stable ≥18 months, no DLTs); ANGPTL3 editing (CTX310: LDL-C −49%, TG −55%); LPA/apolipoprotein(a) editing (CTX320 −94% Lp(a) NHP; VERVE-301 in development); APOC3 base editing for FCS; AGT editing for refractory hypertension (CTX340); primary prevention paradigm gene-therapy, lipid-lowering-therapy, PCSK9, familial-hypercholesterolemia, cardiovascular-genetics 2026-05-27
concepts/AF-Biological-Therapy Preclinical biological strategies for AF: gene transfer, miRNA, cell therapy; anti-miR-21 most replicated (4 labs); OR 0.15 AF inducibility, −6.7% fibrosis, +6.4 sinus rhythm days (meta-analysis 25 studies); 5 strategy classes; delivery/pre-AF design/single-target translational barriers; AAV durable delivery = path forward atrial-fibrillation, gene-therapy, microRNA, atrial-fibrosis, biological-therapy 2026-05-15
concepts/AF-CARE ESC 2024 structured AF management: Comorbidity, Avoid stroke, Rate/rhythm, Evaluation atrial-fibrillation, guidelines 2026-04-12
concepts/AF-Staging AHA 2023 four-stage AF classification (At Risk → Pre-AF → AF → Permanent) atrial-fibrillation, risk-stratification 2026-04-12
concepts/Subclinical-AF SCAF: CIED-detected asymptomatic AF; 2.4× stroke risk; dose-dependent episode duration; ARTESIA (2024): apixaban vs aspirin HR 0.63 stroke (37% RRR), disabling stroke HR 0.51 (49%), major bleeding HR 1.80 — net benefit favours OAC at CHA₂DS₂-VASc ~3.9; NOAH-AFNET 6 (2023): edoxaban vs placebo in AHREs — primary composite neutral (HR 0.81), safety harm (HR 1.31), major bleeding HR 2.10, stroke ~1%/yr (unexpectedly low = low arrhythmia burden); ARTESIA-NOAH discordance: different comparators + NOAH underpowered + diluted endpoint; AHA IIa ≥24h; ESC IIb any duration subclinical-atrial-fibrillation, atrial-fibrillation, stroke-prevention, anticoagulation, randomized-controlled-trial 2026-05-25
concepts/Poststroke-AF-Monitoring ACC 2024 ECDP three-population framework: (1) cardioembolic stroke → monitoring limited; (2) small/large-vessel stroke → 2–4 weeks, ICM for HF+LA enlargement (23.4% AF detection); (3) ESUS/cryptogenic → 2–4 weeks mandatory if OAC candidate, ICM in select cases; OAC threshold: AF ≥5 min + CHA₂DS₂-VASc ≥3; CHASE-LESS/AS5F best risk scores; CRYSTAL-AF 30% AF at 36 months; LOOP trial: no stroke reduction on ITT (HR 0.80; NS); consumer devices supplementary only atrial-fibrillation, stroke-prevention, cardiac-monitoring, anticoagulation, guidelines 2026-05-25
concepts/ARVC-Task-Force-Criteria 2010 Modified Task Force five-domain scoring for ARVC diagnosis diagnostics, ARVC 2026-04-11
concepts/Arrhythmogenic-Cardiomyopathy ACM umbrella concept; HRS 2019 vs ESC 2023 nomenclature; 7-gene genotype-specific natural history; family screening yield 33%+33%; Padua criteria limitations; gene-specific risk calculators (ARVC/DSP/PLN); AAV-PKP2 Phase I/II; exercise gene-specific (not in PLN) arrhythmogenic-cardiomyopathy, sudden-cardiac-death, genotype-phenotype, gene-therapy 2026-05-05
concepts/Bidirectional-Ventricular-Tachycardia Beat-to-beat 180° QRS axis alternation; hallmark arrhythmia of CPVT arrhythmia, CPVT 2026-04-11
concepts/Biological-Pacemaker Gene therapy approaches to restore intrinsic cardiac automaticity (TBX18, HCN) gene-therapy, bradyarrhythmia 2026-04-11
concepts/CHA2DS2-VA ESC 2024 stroke risk score for AF; sex category removed vs CHA2DS2-VASc atrial-fibrillation, anticoagulation 2026-04-12
concepts/CRISPR-Cas9-in-Channelopathies CRISPR gene editing mechanisms (nuclease/base/prime/epigenome); LNP vs AAV delivery; first in-vivo RYR2 repair; nex-z in ATTR-CM (MAGNITUDE Phase 3 paused Oct 2025 hepatotoxicity); PCSK9/ANGPTL3 base editing clinical trials; DMD AAV clinical fatality gene-therapy, channelopathies, CRISPR-Cas9, attr-cardiomyopathy, lipid-lowering-therapy 2026-05-23
concepts/Calcium-Homeostasis-in-HCM SR Ca²⁺ overload and CaMKII-mediated triggered arrhythmia in HCM hypertrophic-cardiomyopathy, calcium-homeostasis 2026-04-11
concepts/Cardiac-Action-Potential Ion channel basis of phases 0–4; ischemia-induced partial depolarization shortens APD; hyperkalemia/hypokalemia effects; mutations cause specific channelopathies; regional/transmural APD heterogeneity underlies T-wave shape cardiac-electrophysiology, channelopathies, myocardial-ischemia 2026-05-01
concepts/Cardiac-Repolarization T-wave physiology; primary vs secondary ST-T classification; injury current mechanism in ischemia; regional IKs/IKr/INaL heterogeneity; EAD/R-from-T triggers; TdP focal-to-reentry; repolarization reserve; 176 QT-SNPs; AHA 2009 QT standards: linear regression preferred over Bazett; prolonged QT women ≥460 ms / men >450 ms; QT dispersion NOT recommended long-qt-syndrome, cardiac-repolarization, channelopathies, myocardial-ischemia 2026-05-16
concepts/ST-T-Changes Primary vs secondary ST-T changes; injury current mechanism; AHA 2009 sex/age J-point thresholds; coronary artery localization (LAD proximal/mid/distal; RCA vs LCx; left main 8-lead pattern; V3R/V4R RV infarction); Wellens syndrome; Sgarbossa criteria for LBBB (concordant high spec/low sens; discordant modified ratio); hyperkalemia sine-wave; T-wave quantitative descriptors; U wave norms; giant T-wave inversion entities (HCM/NSTEMI/ICH) electrocardiography, ST-T-changes, myocardial-ischemia, cardiac-electrophysiology, electrolyte-disturbances 2026-05-16
concepts/ECG-Ventricular-Hypertrophy LVH criteria (Sokolow-Lyon/Cornell/Romhilt-Estes/voltage-duration); sensitivity <50%, specificity 85–90%; no single superior criterion; confounders (age/sex/race/obesity diverge Sokolow-Lyon vs Cornell); "secondary ST-T abnormality" not "strain" (AHA 2009); LVH in LBBB cautious; RVH criteria (best in CHD; COPD pattern); biventricular hypertrophy low sensitivity; left/right atrial abnormality P-wave criteria (PTF-V1 >40 mm·ms; P II >2.5 mm) electrocardiography, left-ventricular-hypertrophy, cardiac-chamber-hypertrophy, ECG-standardization, atrial-abnormality 2026-05-16
concepts/Wellens-Syndrome Deeply inverted T waves (>0.5 mV) in V2–V4 + QT prolongation in pain-free state = critical proximal LAD stenosis warning; identical pattern from ICH; missed = high risk anterior STEMI; stress testing contraindicated myocardial-ischemia, ECG-diagnosis, LAD-occlusion, acute-coronary-syndrome, electrocardiography 2026-05-16
concepts/ECG-Lead-Standards AHA 2007 ECG recording standards: lead placement (V5 horizontal plane of V4; V1/V2 4th ICS; common misplacement consequences); Cabrera sequence (aVL→I→−aVR→II→aVF→III) highly recommended; global measurement preferred and systematically longer than single-lead; Mason-Likar NOT interchangeable for ST comparison; right-sided leads (V3R/V4R) in inferior STEMI; 40 Hz monitor invalidates amplitudes; "unipolar" terminology discouraged; computer ECG adjunct only electrocardiography, ECG-technology, ECG-standardization, digital-ECG, lead-placement 2026-05-16
concepts/ECG-Conduction-Disturbances AHA 2009 IVCD criteria: normal QRS duration (>110 ms abnormal adults); complete RBBB (rsr'/rsR'/rSR' in V1/V2; S > R in I/V6; QRS ≥120 ms); complete LBBB (8 criteria; negative concordance = abnormal — formal Sgarbossa basis); LAFB (axis −45° to −90°; qR aVL; R-peak ≥45 ms); LPFB; nonspecific IVCD; WPW; deprecated terms (bifascicular/trifascicular/Brugada pattern in auto algorithms) electrocardiography, bundle-branch-block, intraventricular-conduction, ECG-standardization, ventricular-preexcitation 2026-05-16
concepts/Sgarbossa-Criteria LBBB + AMI diagnosis: concordant STE/STD ≥1 mm (high specificity, low sensitivity); discordant STE ≥5 mm (very low spec/sens, superseded); modified criterion: STE:S ratio ≥0.25; applies to ventricular paced rhythms; AHA 2009 Part III LBBB criterion 7 is the multi-society formal basis for concordant criteria myocardial-ischemia, LBBB, ECG-diagnosis, acute-coronary-syndrome, electrocardiography 2026-05-16
concepts/OMI-NOMI-Paradigm Paradigm shift from STEMI/NSTEMI to Occlusion MI (OMI) vs Non-Occlusion MI (NOMI); STEMI criteria 41–62% sensitivity for total occlusion; OMI ECG features beyond STE (hyperacute T-waves, subtle STE, Q-waves, reciprocal STD); HATW score first objective OMI ECG tool; AI ECG achieves 100% sensitivity occlusion-MI, STEMI-criteria, ECG-diagnosis, acute-coronary-syndrome, artificial-intelligence-ECG 2026-05-03
concepts/Hyperacute-T-waves Tall, broad, symmetric T-waves in early OMI; HATW score first quantitative definition (T-wave magnitude + symmetry, ≥0.7 in 2 leads → 98.4% spec); T-wave amplitude alone insufficient; do not reliably evolve to STEMI criteria; requires automated software measurement occlusion-MI, ECG-diagnosis, LAD-occlusion, myocardial-ischemia, hyperacute-T-waves 2026-05-03
concepts/Polygenic-Risk-Score PRS for QT/LQTS/HCM/DCM/BrS arrhythmias + CAD: CAD top 5% PRS = 3-5× risk; intermediate-risk reclassification prevents 1 event/340 screened; young-adult PRS (30-40% vs 10% CAD by 70); high-PRS derives greater statin/PCSK9i benefit; lifestyle nearly counterbalances high PRS; genotype-negative LQTS has higher PRS; ancestry limitation polygenic-risk-score, coronary-artery-disease, long-qt-syndrome, cardiac-repolarization, genetics 2026-05-16
concepts/Cascade-Family-Screening Systematic cardiovascular and genetic evaluation of ACM and HCM families arrhythmogenic-cardiomyopathy, genetics 2026-04-11
concepts/Catheter-Ablation-AF PVI for AF; energy sources (RF/cryo/PFA); ablation strategies; QOL/cognition/AF progression evidence; CASTLE-HTx (2023): ablation in end-stage HFrEF HR 0.24 primary composite (death/LVAD/urgent HTx), HR 0.29 mortality — landmark benefit in most advanced HF; OPTION (2025): LAAO superior for bleeding (HR 0.44) and NI for stroke/death vs NOAC post-ablation atrial-fibrillation, catheter-ablation, heart-failure, end-stage-heart-failure 2026-05-17
concepts/Pulsed-Field-Ablation Non-thermal electroporation ablation; tissue-selective; no PV stenosis/oesophageal injury; ADVENT RCT (NEJM 2023): NI vs thermal for efficacy (73.3% vs 71.3%) and safety (2.1% vs 1.5%); superior PV preservation (−0.9% vs −12.0%); asymptomatic MRI cerebral lesions 3/33 PFA vs 0/37 thermal; SINGLE SHOT CHAMPION RCT (NEJM 2025): PFA NI AND superior to cryoablation (37.1% vs 50.7%; P=0.046); ICM-based continuous monitoring; lower blanking-period recurrence suggests less inflammation atrial-fibrillation, catheter-ablation, ablation-technology, pulsed-field-ablation 2026-05-18
concepts/Atrial-Myopathy-in-HCM Sarcomeric gene variants (MYBPC3/MYH7) drive primary LA fibrosis independent of LA pressure; progressive; predicts more ablation procedures hypertrophic-cardiomyopathy, atrial-fibrillation, atrial-myopathy, genetics 2026-04-12
concepts/Cardiogenetic-Centers Interdisciplinary arrhythmia/cardiomyopathy genetics centres; variant reclassification responsibility; panel strategy genetics, arrhythmia, channelopathy 2026-04-12
concepts/Variant-Reclassification >36% reclassification rate in cardiovascular genetics; channelopathies 38%; predominantly downgrading; notification gap genetics, channelopathy, cardiomyopathy 2026-04-12
concepts/Desmosome Cardiac intercalated disc adhesion complex; structural basis of ARVC pathogenesis arrhythmogenic-cardiomyopathy, ARVC 2026-04-11
concepts/Early-Onset-Atrial-Fibrillation AF before age 66; 10% carry P/LP variants, mainly cardiomyopathy genes atrial-fibrillation, genetics 2026-04-11
concepts/Electrical-Storm ≥3 VA episodes in 24h; step-by-step management algorithm by ESC 2022 ventricular-arrhythmia, arrhythmia-management 2026-04-11
concepts/Exercise-Restriction-in-ARVC Dose-dependent exercise-penetrance; gene-specific: harmful in PKP2/TMEM43/gene-elusive; NOT harmful in PLN-p.Arg14del (unique); DSP uncertain; gene-informed SDM per 2024 HRS ARVC, lifestyle, arrhythmogenic-cardiomyopathy, genotype-phenotype 2026-05-05
concepts/Exercise-in-HCM 2024 paradigm shift: no universal exercise restriction for most HCM patients (AHA) hypertrophic-cardiomyopathy, lifestyle 2026-04-11
concepts/Final-Common-Pathway Hypothesis that cardiomyopathy subtypes converge on intercalated disc dysfunction arrhythmogenic-cardiomyopathy, ARVC 2026-04-11
concepts/Gene-Silencing-Therapy ASO/siRNA/shRNA strategies for cardiac gain-of-function or dominant-negative mutations gene-therapy, channelopathies 2026-04-11
concepts/Genetic-Testing-in-AF Cardiomyopathy/arrhythmia panel testing in early-onset AF; 10% yield up to age 66 genetic-testing, atrial-fibrillation 2026-04-11
concepts/Cardio-Oncology New clinical discipline integrating cardiology + oncology; MDT approach; care pathways by risk; HFA-ICOS stratification cardio-oncology, cardiovascular-toxicity, cancer 2026-04-12
concepts/Cancer-Therapy-Related-CV-Toxicity CTRCD severity grading; BTK/ICI/VEGF inhibitor toxicity profiles; ibrutinib drug interactions (diltiazem/amiodarone 6–9× levels; dabigatran contraindicated); Salem abatacept+ruxolitinib 3.4% vs 60% ICI myocarditis mortality; CPK 20-day pre-clinical rise; VEGF HTN target <130/80; dual antihypertensive ≥160/100; permissive CV toxicity concept cardio-oncology, cardiovascular-toxicity, heart-failure, cancer 2026-05-24
concepts/Radiation-Vasculopathy Spectrum of RT-induced vascular injury: premature CAD (linear dose-response, no safe threshold), carotid disease, axillary/aortic stenosis, autonomic dysfunction (4× higher HRR abnormality, 4× all-cause mortality in Hodgkin survivors); inferior PCI/CABG outcomes post-RT; surveillance: stress test 5–10 yr post-mediastinal RT radiation-vasculopathy, cardio-oncology, premature-CAD, radiation-therapy, vascular-toxicity 2026-05-09
concepts/PAH-Risk-Stratification 3-strata at diagnosis; 4-strata at follow-up; low-risk haemodynamic targets; treat-to-target approach; vasoreactivity testing algorithm pulmonary-hypertension, pulmonary-arterial-hypertension, risk-stratification 2026-04-13
concepts/Pulmonary-Hypertension mPAP >20 mmHg (2022 ESC/ERS); 5-group classification; pre/post-capillary definitions; IpcPH vs CpcPH; exercise PH; Group 1–5 aetiologies; PAH drug therapy (ERA+PDE5i Class I/B); sotatercept ZENITH+HYPERION; PDE5i Class III in HFpEF PH; genetics (BMPR2/CAV1/ATP13A3/EIF2AK4); perioperative management; 11 sources pulmonary-hypertension, classification, PAH, CTEPH, right-heart-failure, pulmonary-arterial-hypertension 2026-05-22
concepts/HFA-ICOS-Risk-Stratification Pre-treatment CV toxicity risk tool: Low/Moderate/High/VH across 6 treatment categories; anthracycline dose thresholds cardio-oncology, risk-stratification, cardiovascular-toxicity 2026-04-12
concepts/Genetic-Testing-in-Cardiomyopathy Systematic framework for multigene panel testing in HCM/DCM/ARVC/RCM; yields by phenotype; gene-specific management; VUS management; paediatric and incidental findings genetics, cardiomyopathy, genetic-testing, guideline 2026-04-15
concepts/HCM-Risk-SCD HCM Risk-SCD and Risk-Kids calculators; ESC threshold-driven vs AHA decision-aid sudden-cardiac-death, HCM 2026-04-11
concepts/Ion-Channel-Mutations GOF/LOF mutations in cardiac ion channels; mechanistic basis of all channelopathies genetics, channelopathies 2026-04-11
concepts/Epigenetics-Cardiac-Arrhythmia Epigenetic regulation of arrhythmia-susceptibility genes: miR-19b multi-channel regulation (LQTS/SQTS), circulating miRNA biomarkers, U1 snRNA/KCNH2 splicing therapy, SCN5A H558R promoter methylation (BrS modifier), KCNQ1OT1 imprinting, KChIP2/H3K4me3 histone regulation, SCN10A 3D enhancer–SCN5A promoter loop epigenetics, ventricular-arrhythmia, non-coding-RNA, DNA-methylation, channelopathies 2026-05-09
concepts/Sex-Differences-in-Channelopathies Sex-specific arrhythmic risk windows: males 4× higher risk age 10–12; females 11% vs 2% risk age 18–40; postpartum = highest-risk period; estrogen inhibits IKr (prolongs QT); testosterone shortens QT; BrS 8–10× male predominance via Ito augmentation; SQTS male predominance channelopathies, sex-differences, long-qt-syndrome, arrhythmia, hormonal-effects 2026-05-09
concepts/Ion-Channel-Remodeling-in-HCM Pre-structural INaL/ILTCC changes in HCM; detectable before hypertrophy hypertrophic-cardiomyopathy, arrhythmia 2026-04-11
concepts/Electrical-Remodeling Disease-driven ion channel changes in AF (↑IKACh constitutive, ↓ICaL, triangulated AP), HF (↑INaLate/CaMKII, ↑If, ↑NCX, ↓IKr/IKs/Ito/IK1), HCM, and MI; repolarization reserve concept cardiac-electrophysiology, arrhythmia-mechanisms, ion-channels, electrical-remodeling, channelopathies 2026-04-30
concepts/LVOTO LV outflow obstruction in HCM; Doppler/hemodynamic assessment; stepwise pharmacology (BB → CCB → disopyramide → mavacamten/aficamten); EXPLORER-HCM: mavacamten −35.6 mmHg LVOT, 37% vs 17% primary endpoint; SEQUOIA-HCM: aficamten −50 mmHg Valsalva gradient; MAPLE-HCM: aficamten superior to metoprolol monotherapy; AHA Class I vs ESC Class IIa mavacamten positioning cardiomyopathy, HCM, mavacamten, cardiac-myosin-inhibitors, LVOT-obstruction 2026-05-22
concepts/Late-Gadolinium-Enhancement CMR fibrosis marker; LGE ≥15% LV mass elevates SCD risk 2.32× in HCM; HR 5.55 in DCM; transmural extent predicts viability recovery (>50% → <10% recovery); 23–44% post-STEMI ECGs non-diagnostic despite persistent LGE scar multimodality-imaging, cardiomyopathy, myocardial-viability, myocardial-infarction 2026-05-01
concepts/Left-Atrial-Strain LASr <23% threshold for mechanical atrial dysfunction (AtCM framework); more predictive of stroke/dementia risk than AF itself; better predictor of HFpEF outcomes than AF presence; LA booster strain <8%; LA emptying fraction <48%; CMR LGE ≥10–15% predicts ablation recurrence/stroke left-atrial-strain, atrial-cardiomyopathy, echocardiography, atrial-fibrillation, HFpEF 2026-05-09
concepts/Q-Wave-Remodeling Post-infarct Q-wave regression; pseudo-normalization confirmed by LGE-CMR; size (not transmurality) determines Q-wave presence; 6.2% LV mass cutoff; 44% non-diagnostic ECG at 5 years post-STEMI myocardial-infarction, electrocardiography, late-gadolinium-enhancement, stemi, cardiac-mri 2026-05-01
concepts/Myocardial-Viability Hibernation vs stunning; LGE-CMR transmural extent tiers (>50% → <10% recovery); STICH/PARR-2/REVIVED-BCIS2 show viability imaging does not discriminate revascularisation benefit; CABG vs PCI divergence; modality performance table myocardial-viability, ischemic-cardiomyopathy, cardiac-imaging, coronary-revascularization 2026-05-11
concepts/Left-Cardiac-Sympathetic-Denervation Thoracoscopic lower stellate ganglion removal for refractory LQTS and CPVT surgery, channelopathies 2026-04-11
concepts/Phenotypic-Approach-to-Cardiomyopathy ESC 2023 framework: identify morphological phenotype first, then aetiological diagnosis cardiomyopathy, diagnostics 2026-04-11
concepts/Schwartz-Score Point-based clinical probability score for LQTS and SQTS diagnostics, LQTS 2026-04-11
concepts/Septal-Reduction-Therapy Surgical myectomy and alcohol septal ablation for obstructive HCM cardiomyopathy, HCM 2026-04-11
concepts/Shanghai-Score-System Point-based probability score for Brugada syndrome and ERS diagnosis diagnostics, channelopathies 2026-04-11
concepts/Sports-Cardiology-SDM AHA/ACC 2025 SDM framework for competitive athletes with CVD; sports classification continuum; preparticipation evaluation; PKP2 vs non-PKP2 ACM distinction; LQTS/CPVT/BrS participation guidance sports-cardiology, shared-decision-making, sudden-cardiac-death, guidelines 2026-04-25
concepts/Sudden-Cardiac-Death Epidemiology and mechanisms of SCD across inherited cardiac diseases sudden-cardiac-death, channelopathies 2026-04-12
concepts/SupRep-Therapy Suppression-and-replacement gene therapy for LQTS; mutation-agnostic; validated in rabbits gene-therapy, channelopathies 2026-04-11
concepts/Torsades-de-Pointes Polymorphic VT in LQTS; EAD-mediated; sex hormone modulation of risk arrhythmia, channelopathies 2026-04-11
concepts/VA-Risk-Stratification-DCM Multi-parameter VA risk stratification in DCM; LGE + genotype + LVEF over LVEF alone; DANISH trial no all-cause mortality benefit (HR 0.87; SCD HR 0.50; age <68 HR 0.64); grade III diastolic dysfunction adds LVEF-independent arrhythmic risk (HR 3.52, pilot data) dilated-cardiomyopathy, ICD, diastolic-dysfunction, sudden-cardiac-death 2026-05-14
concepts/PVC-Induced-Cardiomyopathy Reversible LV dysfunction from frequent PVCs (burden >10–24%); ABC-VT risk score; wide QRS/epicardial origin/interpolated PVCs as risk factors; ablation normalises LVEF in 82%; Class I/IIa indications premature-ventricular-complexes, PVC-induced-cardiomyopathy, ventricular-arrhythmias, heart-failure, electrophysiology 2026-05-01
concepts/PVC-Mapping-Ablation Comprehensive mapping/ablation guide: ECG localisation rules by site; activation/pace mapping/ECGI; RF/cryo/ethanol/PFA/stereotactic energy sources; site-by-site strategies (RVOT, LV summit, Purkinje, papillary muscles, intramural); 84% acute success, 2.4% complications premature-ventricular-complexes, catheter-ablation, ventricular-arrhythmias, electrophysiology, mapping 2026-05-01
concepts/iPSC-Derived-Cardiomyocytes Patient-specific cardiomyocyte models for channelopathy and HCM research and drug testing precision-medicine, channelopathies 2026-04-11
concepts/OSA-Arrhythmogenic-Substrate Dual mechanism: acute apnea-associated electrophysiological changes + long-term structural remodeling creating dynamic AF substrate in OSA obstructive-sleep-apnea, atrial-fibrillation, atrial-remodeling 2026-04-18
concepts/Valvular-Heart-Disease Overview of acquired VHD: aetiology, Heart Team model, imaging, associated conditions; A–D staging (ACC/AHA 2020); CHA2DS2-VASc for AF anticoagulation valvular-heart-disease, guideline 2026-04-19
concepts/PCI-Before-TAVI FFR-guided or angiographic PCI in TAVI candidates with concomitant stable CAD; NOTION-3 (NEJM 2024; n=455; FFR ≤0.80 or ≥90% stenosis; median age 82): MACE HR 0.71 (P=0.04); MI HR 0.54; urgent revasc HR 0.20; all-cause death HR 0.85 NS; bleeding HR 1.51; AKI HR 0.45; supersedes neutral ACTIVATION trial; ESC 2025 Class IIa B for ≥90% stenosis; optimal timing pre- vs peri- vs post-TAVI unresolved TAVI, aortic-stenosis, coronary-artery-disease, fractional-flow-reserve, randomized-controlled-trial 2026-05-19
concepts/TAVI Transcatheter aortic valve implantation; PARTNER 3 5yr: composite NS (22.8% vs 27.2%; P=0.07), valve thrombosis 2.5% vs 0.2%, AF 13.7% vs 42.4%; DEDICATE-DZHK6 (NEJM 2024; industry-independent; n=1,414; pragmatic device-choice): death/stroke HR 0.53 (5.4% vs 10.0%), all-cause death HR 0.43, AF HR 0.36, pacemaker HR 1.81; EARLY TAVR (NEJM 2025): asymptomatic AS primary composite HR 0.50 (P<0.001), death HR 0.93 NS, stroke HR 0.62 NS, 87% surveillance crossover; NOTION-3 PCI: MACE HR 0.71 (P=0.04); CEP (BHF PROTECT-TAVI 2025): routine CEP null — stroke 2.1% vs 2.2% (P=0.94) valvular-heart-disease, TAVI, aortic-stenosis 2026-05-20
concepts/Cerebral-Embolic-Protection-TAVI Sentinel CEP device (Boston Scientific) during TAVI: BHF PROTECT-TAVI (NEJM 2025; n=7,635; 33 UK centres; largest RCT; stopped for futility): stroke 2.1% CEP vs 2.2% control (P=0.94); disabling stroke 1.2% vs 1.4% (NS); serious adverse events 0.6% vs 0.3% (doubled); confirmed by PROTECTED TAVR (n=3,000); routine CEP not supported; DWI-MRI subclinical lesion reduction does not translate to clinical stroke prevention TAVI, cerebral-embolic-protection, stroke-prevention, aortic-stenosis, randomized-controlled-trial 2026-05-20
concepts/Aortic-Stenosis AS grading (high/low-flow low-gradient); symptomatic and asymptomatic management; TAVI vs SAVR decision; RECOVERY 10-yr (NEJM 2026): early SAVR CV death 3% vs 24% (HR 0.10), NNT=6; EARLY TAVR (NEJM 2025): asymptomatic AS composite HR 0.50 (P<0.001), death NS, stroke NS, 87% crossover, KCCQ/LV-LA health benefit; CAVD molecular mechanisms valvular-heart-disease, aortic-stenosis, guideline 2026-05-19
concepts/Aortic-Regurgitation AR evaluation; surgical thresholds (LVESD, LVESDi, LVESVi, LVEF); VSARR preferred in young patients; new TAVI option for inoperable patients valvular-heart-disease, aortic-regurgitation 2026-04-18
concepts/Primary-Mitral-Regurgitation PMR evaluation; surgical indications including new asymptomatic criteria (3-of-4 rule); TEER for high-risk; minimally invasive surgery valvular-heart-disease, mitral-regurgitation 2026-04-18
concepts/Secondary-Mitral-Regurgitation Atrial vs ventricular SMR distinction; GDMT before intervention; TEER Class I A ESC 2025 for ventricular SMR; COAPT 5yr: HF hosp HR 0.53, mortality HR 0.72; RESHAPE-HF2: moderate-to-severe SMR all 3 primaries met (HF hosp RR 0.59; NNT 5.1); MATTERHORN (NEJM 2024): first TEER vs surgery RCT — noninferior efficacy (16.7% vs 22.5%; NI P<0.001); TEER dramatically safer (30-day safety 14.9% vs 54.8%); MR recurrence ≥3+ higher with TEER (8.9% vs 1.5%); evidence base spans EROA 0.20–0.40 cm² valvular-heart-disease, mitral-regurgitation, heart-failure 2026-05-19
concepts/Mitral-Stenosis Rheumatic MS (PMC criteria); degenerative MS with MAC (TMVI emerging); VKA not DOACs if MVA ≤2.0 cm² with AF valvular-heart-disease, mitral-stenosis 2026-04-18
concepts/Tricuspid-Regurgitation TR aetiology (atrial vs ventricular secondary TR); anatomy (40% annular dilatation threshold; RCA <3mm; AV node 3-5mm from commissure); severe TR 1yr mortality 36–42%; HR 2.74 vs normal; 5-grade severity scale; TRILUMINATE Pivotal (NEJM 2023) TEER WR 1.48 — QoL-driven (KCCQ ≥15pts 49.7% vs 26.4%; PPM no increase; HF hosp paradox); TRISCEND II (NEJM 2025) TTVR WR 2.02 — TR ≤mild 95.2%; bleeding 15.4%; PPM 17.4%; RV reverse remodeling; TriClip + EVOQUE FDA-approved; ESC 2025 Class IIa A valvular-heart-disease, tricuspid-regurgitation, transcatheter-interventions, right-heart-failure, echocardiography 2026-05-19
concepts/Heart-Valve-Centre Specialised centre requirements; volume-outcome evidence; regional Heart Valve Network model; Heart Team composition valvular-heart-disease, heart-team 2026-04-18
concepts/Structural-Valve-Deterioration Unified SVD definitions 2025: moderate SVD (PG increase ≥10 mmHg + absolute ≥20 mmHg); severe SVD (≥20 mmHg increase + absolute ≥40 mmHg) valvular-heart-disease, prosthetic-valves 2026-04-18
concepts/LQTS-Pregnancy-Management LQTS risk paradox: pregnancy protective, 9-month postpartum 2.7× risk; LQT2 highest risk; progesterone antiarrhythmic; beta-blockers Class I (nadolol preferred; propranolol/metoprolol if breastfeeding); three-tier delivery risk stratification; QTc >500ms postpartum → consider ICD/WCD; HRS 2023 primary current guideline long-qt-syndrome, pregnancy, arrhythmia-management, channelopathies 2026-05-22
concepts/Arrhythmia-in-Pregnancy HRS 2023 (163 recommendations; 8 societies): AF most common sustained arrhythmia; cardioversion safe/same energy; lead apron only 3% fetal radiation reduction; DOACs contraindicated; flecainide 1st-line fetal SVT; perimortem C-section target 5 min; IAS pregnancies 8× stillbirth risk pregnancy, arrhythmia, antiarrhythmic-drugs, fetal-arrhythmia, inherited-arrhythmia-syndrome 2026-05-22
concepts/Fetal-Arrhythmia Fetal arrhythmias in 1% of fetuses; flecainide 1st-line SVT (superior with hydrops); sotalol/digoxin for AFL; verapamil avoided (unexpected fetal death); IV magnesium 1st-line fetal VT; congenital heart block (anti-Ro/SSA); close-to-term delivery preferred over escalating pharmacotherapy fetal-arrhythmia, pregnancy, antiarrhythmic-drugs, cardio-obstetrics, fetal-SVT 2026-05-22
concepts/Precision-Medicine-LQTS Genotype-specific LQTS therapy from 1,304-patient Mayo Clinic cohort: 18 configurations in LQT3; propranolol over nadolol (INaLate); IPAP for LQT2; mexiletine off-label; intentional nontherapy in 18%; LCSD monotherapy in 5%; cardiac transplant in 4 LQT3 patients; 0.3% mortality over 20+ years long-qt-syndrome, precision-medicine, beta-blockers, antiarrhythmic-drugs, left-cardiac-sympathetic-denervation 2026-05-09
concepts/Drug-Induced-Arrhythmia AHA 2020 taxonomy of drug-induced arrhythmias: bradyarrhythmia, AF/AFL, AT, AVNRT, monomorphic VT, Brugada unmasking, TdP; CAST trial; repolarization reserve; IKr blockade; TdP risk factors and management drug-induced-arrhythmias, torsades-de-pointes, QT-prolongation, arrhythmia-management 2026-04-19
concepts/Antiarrhythmic-Drugs Vaughan Williams Classes I–IV overview; flecainide: PRR mechanism, CV efficacy 90%, CAST contraindication, RyR2 blockade in CPVT; dronedarone: ATHENA 24.2% RRR, ANDROMEDA mortality hazard in severe HF (HR 2.13), IK-Ach 100× more potent than amiodarone; genotype-specific pharmacology (mexiletine LQT3, amiodarone ineffective in SQTS1) antiarrhythmic-drugs, atrial-fibrillation, ventricular-arrhythmia, pharmacology, proarrhythmia 2026-05-09
concepts/Fabry-Cardiomyopathy AFD cardiac phenotype: HCM genocopy; HFpEF dominant (40%/91%); CMR 4-stage model; ERT paradox (augments LGE); zebra bodies; Lyso-Gb3/NT-proBNP/hs-cTn biomarkers; amiodarone contraindicated fabry-disease, cardiomyopathy, hypertrophic-cardiomyopathy, lysosomal-storage-disorders, fibrosis 2026-04-19
concepts/Titin-PTMs Three PTM types (acetylation/oxidation/phosphorylation) regulating titin spring stiffness; N2Bus vs PEVK opposing effects; cGMP-PKG therapeutic failures (RELAX, VITALITY, SOCRATES) titin, sarcomere, heart-failure, HFpEF, post-translational-modifications 2026-04-19
concepts/Titin-Isoform-Switch N2B vs N2BA isoform ratio and Frank-Starling regulation; RBM20 as master switch; isoform changes in HFrEF/HFpEF; RBM20 pathogenic variants → DCM; therapeutic targeting limitations titin, sarcomere, heart-failure, HFpEF, dilated-cardiomyopathy 2026-04-19
concepts/Sarcomere-Biology Cardiac sarcomere architecture: MYH7, MYBPC3, troponin complex, titin; crossbridge cycling; cMyBP-C as brake (C1-M-C2/myosin S2 binding); PKA phosphorylation switch; increased myofilament Ca²⁺ sensitivity = HCM final common pathway; HCM mutations (MYBPC3 40–50%, MYH7 25–40%); mavacamten mechanism; DCM vs HCM distinction sarcomere, hypertrophic-cardiomyopathy, MYBPC3, crossbridge-cycling, cardiomyopathy 2026-05-09
concepts/Haploinsufficiency Mechanism by which truncating mutations cause loss-of-function: NMD/UPS/autophagy degrade truncated protein → half-normal WT protein; canonical example MYBPC3 (>60% truncating); therapeutic implication: gene replacement/exon skipping restores WT, not gene silencing; contrast with dominant-negative missense mechanism; bi-allelic → neonatal CMP haploinsufficiency, genetics, MYBPC3, hypertrophic-cardiomyopathy, gene-therapy 2026-05-09
concepts/LV-Diastolic-Function 2025 ASE algorithm: 2-step diastolic dysfunction definition; LAP estimation (e', E/e', TR velocity); LARS ≤18% primary variable; Grade 1/2/3 classification; diastolic exercise echo; special populations; grade III independently predicts arrhythmic death HR 3.52 (LVEF-independent, pilot data) echocardiography, diastolic-function, HFpEF, heart-failure 2026-05-14
concepts/Conduction-Disorders-in-Young-Adults CCDs in adults <50 years: acquired (Lyme/sarcoidosis/Chagas/autoimmune) and familial (SCN5A/LMNA/Fabry/neuromuscular/CHD-related); PM <50 → 3–4× risk; conduction system pacing preferred; ICD over PM in LMNA; genetic testing underused conduction-disorders, atrioventricular-block, genetics, cardiomyopathy, young-adults 2026-05-02
concepts/Conduction-System-Pacing CSP taxonomy (HBP/LBBP/LFP/LVSP/LBBAP/DSP); hemodynamics vs RVP/BVP; HOT-CRT/LOT-CRT outcomes; 7 published RCTs; PROTECT-HF (n=2,600) and Left vs Left (n=2,136) ongoing conduction-system-pacing, cardiac-pacing, his-bundle-pacing, left-bundle-area-pacing, cardiac-resynchronization-therapy 2026-04-19
concepts/His-Bundle-Pacing HBP technique; hemodynamics (–56 ms QRS, +5 mmHg SBP vs RVP); HOPE-HF trial; fluoroless implantation; threshold rise 17%; back-up lead indications conduction-system-pacing, his-bundle-pacing, cardiac-pacing 2026-04-19
concepts/Left-Bundle-Branch-Area-Pacing LBBAP sub-types (MELOS); V6RWPT/V6–V1 capture criteria; lead-position-dependent QRS transition; anodal capture; LOT-CRT (81% success, QRS 182→144 ms); LBBP RESYNC/LEVEL-AT RCTs conduction-system-pacing, left-bundle-area-pacing, cardiac-pacing, cardiac-resynchronization-therapy 2026-04-19
concepts/Constrictive-vs-Restrictive Haemodynamic differentiation of constrictive pericarditis vs restrictive cardiomyopathy; ventricular discordance vs concordance during respiration; effusive-constrictive pericarditis pericardial-disease, restrictive-cardiomyopathy, hemodynamics, cardiac-catheterization, right-heart-failure 2026-04-20
concepts/ANGPTL3-Inhibition ANGPTL3 hepatokine inhibits LPL (raises TG) + endothelial lipase (raises HDL-C); LOF variants → familial combined hypolipidemia + OR 0.59–0.66 CAD protection; evinacumab FDA/EMA-approved HoFH (−47% LDL-C, −55% TG; LDLR-independent); vupanorsen discontinued (TRANSLATE-TIMI 70 hepatotoxicity); ARO-ANG3 siRNA Phase 2b ongoing; BE3-Angptl3 murine base editing proof-of-concept angptl3, dyslipidemia, lipid-lowering-therapy, familial-hypercholesterolemia, atherosclerotic-cardiovascular-disease 2026-05-23
concepts/APOC3-Inhibition APOC3 as TG regulator (LPL inhibition + impaired TRL remnant clearance); genetic LOF validation; olezarsen (GalNAc-ASO) phase 3 −58–61 pp TG, remnant cholesterol −70%, ApoB −15%, LDL-C unchanged; plozasiran (siRNA) comparable class efficacy; GalNAc conjugation mitigates thrombocytopenia vs volanesorsen; safety: mild transaminase elevation, injection-site reactions, small HbA1c rise in diabetics; no CV outcomes data hypertriglyceridemia, antisense-oligonucleotide, apolipoprotein-C-III, lipid-lowering-therapy, cardiovascular-risk 2026-05-21
concepts/Hypertriglyceridemia-Management TG classification (150–499 moderate/≥500 severe/FCS); existing agents limited to 10–30% TG reduction; ESSENCE-TIMI 73b (NEJM 2025): olezarsen −58–61 pp TG; ~85–89% TG normalization at 6 months; remnant cholesterol −70%; no CV outcomes; regulatory: olezarsen FDA-approved FCS (COR 1 ACC/AHA); volanesorsen EMA-approved FCS (COR IIa B ESC); REDUCE-IT IPE COR 2b moderate HTG; no fibrate benefit on statin for ASCVD hypertriglyceridemia, antisense-oligonucleotide, apolipoprotein-C-III, lipid-lowering-therapy, cardiovascular-risk 2026-05-21
concepts/CETP-Inhibitors CETP inhibitor drug class: mechanism (HDL-C↑, LDL-C↓, Lp(a)↓); class history (torcetrapib harm → dalcetrapib/evacetrapib futility → anacetrapib partial success → obicetrapib); BROADWAY (NEJM 2025; n=2,530): obicetrapib −32.6 pp LDL-C on top of max LLT; Lp(a) −33.5%; safety comparable to placebo; BROOKLYN outcomes trial ongoing dyslipidemia, CETP-inhibitor, LDL-cholesterol, lipid-lowering-therapy, ASCVD 2026-05-20
concepts/Dyslipidemia-Management 2026 ACC/AHA framework: PREVENT equations, LDL-C/non-HDL-C/ApoB goals by risk category, statin + nonstatin agents, hypertriglyceridemia, SAMS management, special populations; Ez-PAVE (NEJM 2026): first RCT <55 vs <70 mg/dL LDL target in ASCVD — HR 0.67 (P=0.002); obicetrapib (BROADWAY 2025): −32.6 pp LDL-C + Lp(a) −33.5%; olezarsen (ESSENCE-TIMI 73b 2025): −60 pp TG; inclisiran ORION-10+11 Phase 3 (NEJM 2020): −52.3%/−49.9% LDL-C Q6m SC; ORION-4 CVOT HR 0.84 (neutral by own threshold); VERVE-102 PCSK9 base editing Heart-2 (NEJM 2026): −88% PCSK9/−62% LDL-C/−78 mg/dL absolute from single infusion, durable ≥18 months dyslipidemia, ldl-c, statin, primary-prevention, ASCVD, guidelines 2026-05-27
concepts/Intracoronary-Imaging-Guided-PCI IVUS vs OCT vs angiography guidance for PCI; prior Asian RCTs positive (RENOVATE, ULTIMATE, IVUS-XPL); two large European RCTs neutral (IVUS-CHIP NEJM 2026: complex PCI N=2020 HR 1.25 NS; IVUS-OPTIMAL NEJM 2026: left main PCI N=806 HR 1.11 NS); challenges Class IA guideline recommendation; stent thrombosis lower with IVUS despite neutral primary outcomes ivus, oct, intracoronary-imaging, pci, complex-pci, left-main-pci 2026-05-16
concepts/ASCVD-Risk-Assessment PREVENT-ASCVD equations (replace PCE); CPR Framework (Calculate–Personalize–Reclassify); risk categories; CAC scoring tiers; risk enhancers including Lp(a) and reproductive markers; polygenic risk scores ASCVD, primary-prevention, risk-stratification, dyslipidemia, guidelines 2026-04-20
concepts/Lipoprotein-a Lp(a) biology; CardiogramPlus4D: LPA = most potent CAD genetic locus; universal measurement COR 1; risk table (1.4×–4×); residual risk HR 1.61 on statins (pooled 13,167 pts); ASTRONOMER CAVS progression data; statin effect contradiction (ESC: no effect vs Tsimikas: +11%); >50% reduction threshold hypothesis; management (risk factor optimisation → PCSK9 mAb → PCSK9i); emerging RNA therapies; thrombogenicity mechanisms (GPIIb/IIIa RGD; TF/TFPI; PAI-1; fibrin competition); endothelial dysfunction (Rho/ROCK; EPC impairment; FMD r=−0.33); decorin 2-part arterial wall binding dyslipidemia, ASCVD, lipoprotein-a, primary-prevention, risk-stratification 2026-05-23
concepts/Familial-Hypercholesterolemia HeFH (1:250–300); HoFH; genetic FH diagnosis confers 2-3× extra CAD risk at same LDL-C; LDL-C targets by ASCVD status (<100/<70/<55 mg/dL); other monogenic CAD forms (LDLRAP1/ABCG5-8/ABCC6/GUCY1A1/PDE5A/APOA5/SCARB1); genetic panel testing COR 2a; PREVENT equations contraindicated in FH; evinacumab for HoFH; cascade screening; inclisiran COR 2a add-on; VERVE-102 PCSK9 base editing Phase 1 dyslipidemia, ldl-c, genetics, primary-prevention, ASCVD, guidelines 2026-05-27
concepts/TTR-Stabilizer-Therapy TTR tetramer stabilizer drug class: tafamidis (entropic, ATTR-ACT HR 0.70 mortality, 70.5% 30-month survival) vs acoramidis (enthalpic T119M-mimicry, >90% stabilization, ATTRibute-CM win ratio 1.8, 80.7% 30-month survival); dose–response concept; no head-to-head; comparison with vutrisiran RNAi class attr-cardiomyopathy, TTR-stabilizer, acoramidis, heart-failure, amyloidosis 2026-05-17
concepts/Cardiac-Amyloidosis-Imaging Multimodality imaging in cardiac amyloidosis: scintigraphy grading (Grade 0–3), SPECT mandatory, PSIR LGE, ECV >0.40, cherry-on-top GLS, 5-5-5 TDI sign; addendum protocol updates cardiac-amyloidosis, multimodality-imaging, ATTR-amyloidosis, echocardiography, radionuclide-imaging 2026-04-22
concepts/DAPT-Strategies DAPT duration and de-escalation post-ACS and CCD; ticagrelor monotherapy COR 1/A; CCD-phase antiplatelet (PEGASUS, COMPASS, AFIRE); ARC-HBR criteria; triple therapy with OAC acute-coronary-syndrome, chronic-coronary-disease, antiplatelet-therapy, DAPT, bleeding-risk 2026-04-22
concepts/Balloon-Pulmonary-Angioplasty BPA for inoperable/residual CTEPH; ESC 2022 Class I; disease-level 1–4 classification; lesion subtypes (ring/web/subtotal/total/tortuous); Pd:Pa >0.80; safety trends 2013–2022; RACE and MR BPA trials balloon-pulmonary-angioplasty, CTEPH, pulmonary-hypertension, interventional-cardiology 2026-04-28
concepts/Acute-PE-Clinical-Categories AHA/ACC 2026 five-category PE classification (A–E); replaces massive/submassive/ESC 4-tier; integrates clinical scores, haemodynamics, biomarkers, RV imaging; respiratory modifier (R); management by category; CDL for Cat C3/D now RCT-supported (HI-PEITHO 2026, RR 0.39 vs anticoagulation alone) pulmonary-embolism, risk-stratification, guidelines 2026-05-16
concepts/ACHD-AP-Classification ACHD anatomic (I–III) × physiologic (A–D) classification; Stage D now includes endocarditis/HF hospitalisation; Fontan/systemic-RV/truncus cannot be Stage A congenital-heart-disease, risk-stratification, guideline 2026-04-21
concepts/Tetralogy-of-Fallot Repaired TOF adult management; PVR criteria shift to RVESVi >80 mL/m²; SCD risk scores (PREVENTION-ACHD, Brompton, PACES); adjunctive VT ablation COR 2a congenital-heart-disease, tetralogy-of-fallot, sudden-cardiac-death, pulmonary-valve 2026-04-21
concepts/Fontan-Circulation Fontan adult management; annual liver surveillance + AFP COR 1; aspirin/anticoagulation all Fontan COR 1; rhythm control, pacing strategy, exercise, transplantation congenital-heart-disease, Fontan-circulation, single-ventricle, liver-disease, heart-failure 2026-04-21
concepts/Eisenmenger-Syndrome Eisenmenger: PAH monotherapy (ERA or PDE5i) COR 1; dual ERA+PDE5i COR 1; shunt closure COR 3:Harm; pregnancy COR 3:Harm; endocardial leads COR 3:Harm congenital-heart-disease, Eisenmenger-syndrome, pulmonary-arterial-hypertension, right-heart-failure 2026-04-21
concepts/Right-Ventricular-Failure RV failure pathophysiology (adaptive→maladaptive via neurohormonal, ischaemia, fibrosis, metabolic shift); classification by mechanism (preload: TR/shunts/AV fistulas; afterload: PE/chronic PH; contractility: RV MI/post-surgical/ARVC/sarcoidosis/LHF); diagnosis: TAPSE/TAPSE-PASP/FWS/CMR/RHC; treatment: preload (volume not universally helpful), afterload (PDE5i harmful in Group 2), contractility (dobutamine/milrinone/MCS; isolated RVAD contraindicated in severe PAH) right-ventricular-failure, pulmonary-hypertension, hemodynamics, right-heart-catheterization, right-ventricular-remodeling 2026-05-17
concepts/RV-PA-Coupling RV–PA coupling defined by Ees/Ea ratio (optimal 1.5–2.0; uncoupling <0.6–0.8); TAPSE/sPAP and CMR SV/ESV ratio as noninvasive surrogates; in PH: Ees rises to offset Ea until contractile reserve exhausted; single-beat methods under validation; adaptive vs maladaptive remodeling transition; sotatercept/FK506 as therapeutic targets right-ventricular-failure, pulmonary-hypertension, RV-PA-coupling, hemodynamics 2026-05-17
concepts/Right-Heart-Catheterization RHC methodology; PAWP pitfalls; provocative protocols (vasodilator challenge, volume challenge, exercise); HFpEF invasive criteria (Table 4); LVAD ramp/reverse ramp; remote PA monitoring; cardiogenic shock haemodynamics; HF-CS vs AMI-CS phenotype distinction; portal HTN vs HF-congestion assessment (hepatic vein wedge pressure gradient >5 = portal HTN); high-output HF (CI >4.0); haemodynamic variable reference table right-heart-catheterization, pulmonary-hypertension, heart-failure, cardiogenic-shock, invasive-hemodynamics 2026-05-25
concepts/Perioperative-Cardiovascular-Assessment 2024 AHA stepwise perioperative framework; RCRI/NSQIP/DASI; frailty; biomarkers; stress testing; MINS (20% incidence, 10% mortality); pharmacotherapy table; anticoagulation management; POAF; special populations perioperative-medicine, noncardiac-surgery, cardiovascular-risk, guideline, anticoagulation 2026-04-22
concepts/Heart-Healthy-Dietary-Patterns AHA 2026 9-feature framework: energy balance, vegetables/fruits, whole grains, healthy protein (plant-first, fish; NOT fish oil supplements), unsaturated fat, minimally processed foods, ↓added sugars, ↓sodium/↑potassium, alcohol avoidance; DASH in HF: pilot data (hs-cTnI −20%, NT-proBNP −23%; HFpEF diastolic function improvement); MedDiet MetS risk RR 0.81; DASH MetS risk −48%; head-to-head RCT (Filippou 2023): MedDiet = DASH on 24h ambulatory BP (gold standard), MedDiet > DASH office SBP only (−3.2 mmHg); both outperform salt restriction alone; network MA DASH-superiority claim contradicted by direct RCT; ketogenic short-term MetS benefit vs uncertain LDL/long-term CV safety; U-shaped CH-mortality curve (optimal 50–55%); adherence decisive factor cardiovascular-prevention, dietary-control, nutrition-guidelines, ultraprocessed-foods, primary-prevention 2026-05-28
concepts/Metabolic-Syndrome MetS = ≥3 of: central obesity, dyslipidaemia, impaired glucose, elevated BP, low HDL-c; prevalence 20–25% adults; 2-fold T2DM risk, 5-fold CVD risk; MedDiet best overall (RR 0.81, 19% MetS risk reduction); DASH strong for BP (−3.2/−2.5 mmHg; 48% less MetS); head-to-head RCT: MedDiet = DASH on 24h ambulatory BP, MedDiet > DASH office SBP (−3.2 mmHg); plant-based: SBP −4.8 mmHg, weight −2.88 kg; ketogenic: short-term TG/weight benefit; low-fat: conflicting results; optimal CH mortality = 50–55% (U-curve); adherence = decisive factor metabolic-syndrome, dietary-patterns, mediterranean-diet, cardiovascular-prevention, insulin-resistance 2026-05-28
concepts/Cuffless-BP-Monitoring Cuffless BP technology mechanisms (PPG/tonometry/PAT/PTT), calibration dependency, validation gaps (ISO 81060-7 pending); 2025 AHA/ACC COR 3: No Benefit for clinical use; poor performance tracking exercise/nocturnal/treatment-induced BP changes hypertension, blood-pressure-monitoring, digital-health, wearable-technology, photoplethysmography 2026-04-24
concepts/DTC-Genetic-Testing Direct-to-consumer cardiovascular genetic testing: regulatory landscape (23andMe only FDA-authorized), SNP-chip vs. sequencing, monogenic/PRS/pharmacogenomic testing, ACCE framework, clinical approach to DTC results, cascade testing gaps genetic-testing, direct-to-consumer-genetics, polygenic-risk-scores, pharmacogenomics, precision-medicine 2026-04-25
concepts/Periprocedural-CIED-Management AHA 2024 framework for periprocedural CIED care: EMI management, device-specific magnet responses (Micra has NO response), leadless/S-ICD/EV-ICD specifics, three-phase multidisciplinary workflow; ICD re-enablement post-procedure is safety-critical cied-management, perioperative-care, leadless-pacemaker, electromagnetic-interference, icd 2026-04-25
concepts/Cardiac-Rehabilitation AHA/AACVPR 2024: 9 core components; hybrid delivery; ~24% enrollment nationally (target 70%); NNT=12 readmission, NNT=34 death at 1yr post-PCI; 1–2% mortality/session (dose-response, observational); Cochrane RCTs neutral for all-cause mortality; home-based CR: 43% vs 13% initiation, 36% lower mortality (VA); disparity by sex/race/age/SES; 4-phase structure (I: in-hospital, II: post-discharge 6–12 wks, III: long-term outpatient, IV: maintenance); illness perception (BIPQ) as Phase II adherence driver; RESILIENT RCT: mHealth-CR fails in older adults cardiac-rehabilitation, secondary-prevention, exercise-training, heart-failure, participation-disparities 2026-05-22
concepts/AI-in-Cardio-Oncology AI/ML applications in cardio-oncology: multi-omics biomarkers (TTNtv/RARG/hemopexin/TCA metabolites), AI risk models (90% discrimination), AI-ECG (ICI myocarditis arrhythmia, n=3364 LV dysfunction), NLP/LLM for EHR extraction; ethical challenges; national registry call cardio-oncology, artificial-intelligence, precision-medicine, cardiotoxicity, multi-omics 2026-04-25
concepts/Hormonal-Therapy-CV-Risk CV risks of breast cancer endocrine therapy (AI RR 1.19 vs tamoxifen; CDK4/6 inhibitor QT/HTN) and prostate cancer ADT (GnRH agonist metabolic syndrome; antagonist HR 0.44–0.46 for CV events; newer AR agents RR 1.36) cardio-oncology, breast-cancer, prostate-cancer, androgen-deprivation-therapy, cardiovascular-toxicity 2026-04-29
concepts/Sleep-Disordered-Breathing SDB umbrella (OSA/CSA/CSB); AHI vs ODI vs nocturnal hypoxic burden; endotypes; circadian KLF15 pathway; temporal pathophysiology (immediate/subacute/chronic); CPAP RCT failures; bradyarrhythmia/VTA/SCD associations; NABS/ODI screening sleep-disordered-breathing, obstructive-sleep-apnea, atrial-fibrillation, ventricular-arrhythmia, arrhythmia-management 2026-04-29
concepts/Pharmacogenomics-in-HF HF drug-response genetics: ADRB1 Arg389Gly (bucindolol 38% mortality reduction), GRK5 Leu41 (10× higher in Black patients; intrinsic beta-blockade), GNB3 (H-ISDN in African Americans), CYP2D6/CYP3A5 dosing implications; EHR preemptive genotyping strategy pharmacogenomics, heart-failure, precision-medicine, beta-blockers, CYP450 2026-04-29
concepts/Gut-Microbiome-in-HF Gut dysbiosis in HF: ischaemia → increased permeability → bacterial translocation → TNF-α/IL-6; TMAO independently predicts 5-year HF mortality; indoxyl sulfate predicts events in DCM; Mediterranean diet reduces HF risk 21%; Saccharomyces boulardii improves LVEF gut-microbiome, heart-failure, TMAO, dysbiosis, precision-medicine 2026-04-29
concepts/Cardiorenal-Syndrome Bidirectional HF-kidney interaction; 5-type CRS classification (Acute Dialysis Quality Initiative); CVP-driven renal venous hypertension as primary hemodynamic driver; reversibility assessment framework (TKPP >60 mmHg, H-K Profiles A/B/C); biomarkers (NGAL/ST2/galectin-3); UF trials (CARRESS-HF vs UNLOAD); GDMT paradox; LVAD/HTx kidney management; EMPA-KIDNEY legacy effect cardiorenal-syndrome, advanced-heart-failure, kidney-dysfunction, LVAD 2026-05-17
concepts/SGLT2-Inhibitors-in-CKD SGLT2i mechanism (tubuloglomerular feedback; haemodynamic eGFR dip is NOT nephrotoxic); DAPA-CKD (HR 0.61; NNT=19; first non-diabetes CKD benefit) + EMPA-KIDNEY (HR 0.72 active; HR 0.79 combined; legacy effect 12 months); benefit across diabetes/non-diabetes, all eGFR strata ≥20, all albuminuria categories; EMPACT-MI: NO benefit post-MI (HR 0.90) — benefit zone boundary sglt2-inhibitors, chronic-kidney-disease, dapagliflozin, cardiorenal-outcomes, randomized-controlled-trial 2026-05-22
concepts/Diuretic-Resistance Mechanisms of loop diuretic resistance in HF/CRS: braking phenomenon, distal tubular hypertrophy, CKD-reduced tubular secretion, hypochloremia; diuretic efficiency metric (ESCAPE HR 2.86); torsemide; thiazide augmentation; ADVOR: acetazolamide (proximal NHE3 blockade) RR 1.46 decongestion P<0.001 but no hard outcome benefit diuretic-resistance, heart-failure, kidney-dysfunction, cardiorenal-syndrome, acetazolamide 2026-05-14
concepts/Mitochondrial-Cardiomyopathy Cardiac manifestations of mitochondrial disease; HCM dominant phenotype; MELAS/MERRF/MIDD/KSS/LHON syndromes; ~30% of mitochondrial disease patients; CVD leading cause of death; cardiac screening every 3–5 years mitochondrial-genetics, cardiomyopathy, arrhythmia, cardiovascular-disease 2026-04-25
concepts/Heteroplasmy Coexistence of different mtDNA variants; dynamic VAF; biochemical and phenotypic thresholds; age-related accumulation; NuMT detection pitfalls; m.4977DEL predicts MACE; haplogroup CVD associations mitochondrial-genetics, cardiovascular-disease, genetics 2026-04-25
concepts/Incidental-Cardiovascular-Variants Bayesian framework (pretest probability + variant pathogenicity → posttest probability) for incidentally identified CVD gene variants from ES/GS/DTC; ACMG-78 CVD genes; LP/P-only cascade testing; 1–8%/year reclassification; 1–3-year follow-up incidental-variants, genetic-testing, heritable-cardiovascular-disease, variant-interpretation, precision-medicine 2026-04-28
concepts/Alcoholic-Cardiomyopathy ACM: dilated LV/HFrEF from excessive alcohol; 7–15 drinks/day over 5–15 years; TTN truncating variants increase vulnerability (gene-environment interaction); sex differences; alcohol reduction improves LV function cardiomyopathy, alcohol-consumption, heart-failure, genetics 2026-04-28
concepts/Prepregnancy-Cardiovascular-Health Prepregnancy period as critical CVH optimization window; Life's Essential 8 applied to reproductive-age women; graded APO risk with cumulative poor CVH metrics; intergenerational transmission; no large RCTs yet; multilevel interventions prepregnancy-cardiovascular-health, maternal-health, adverse-pregnancy-outcomes, lifes-essential-8, primary-prevention 2026-04-28
concepts/Adverse-Pregnancy-Outcomes HDP/preterm birth/SGA/GDM composite; CVD is #1 cause of pregnancy-related death (26.5%); 1-in-5 births affected; APOs associated with long-term maternal CVD and offspring CVD risk; placental malperfusion mechanism adverse-pregnancy-outcomes, maternal-health, prepregnancy-cardiovascular-health, hypertensive-disorders-of-pregnancy, gestational-diabetes 2026-04-28
concepts/Lifes-Essential-8 AHA 2022 CVH construct (updated from Life's Simple 7): diet, physical activity, sleep, nicotine, BMI, BP, non-HDL-C, fasting glucose; 0–100 score; mean US women 68.1/100; racial disparities across all metrics lifes-essential-8, cardiovascular-health, primary-prevention, ASCVD, guidelines 2026-04-28
concepts/Hypertensive-Disorders-of-Pregnancy HDP umbrella (4 types); 7.5% per pregnancy, 15.3% per woman; 2nd leading cause global maternal mortality; preeclampsia: HF HR 2.7, ESKD RR 6.6, dementia aHR 2.4; ACOG vs international BP threshold controversy; aspirin prevention hypertensive-disorders-of-pregnancy, maternal-health, preeclampsia, blood-pressure-in-pregnancy, adverse-pregnancy-outcomes 2026-04-28
concepts/Preeclampsia HT + proteinuria/organ damage after 20 wks; failed spiral artery remodeling → sFlt-1/VEGF imbalance → endotheliosis; placental (early/severe) vs maternal (late/preexisting vascular) phenotypes; aspirin reduces risk 10–20%; lifetime CVD risk aHR 4.9 preeclampsia, hypertensive-disorders-of-pregnancy, maternal-health, placenta, angiogenesis 2026-04-28
concepts/Cardio-Obstetrics Multidisciplinary pregnancy heart team; modified WHO classification only prospectively validated; prohibitive conditions (PAH/severe ventricular dysfunction); scope antepartum to 1-year postpartum; HRS 2023 three-tier IAS delivery risk framework; perimortem C-section at site of arrest within 5 min cardio-obstetrics, cardiovascular-disease-in-pregnancy, maternal-health, multidisciplinary-team, peripartum-cardiomyopathy 2026-05-22
concepts/MINOCA MINOCA working diagnosis in 5–6% of AMIs; 3-criterion definition; traffic-light algorithm; six causes (plaque disruption/vasospasm/MVD/embolism/SCAD/supply-demand); SWEDEHEART cardioprotective therapy evidence; 4.7% 12-month mortality MINOCA, myocardial-infarction, coronary-vasospasm, SCAD 2026-04-29
concepts/Coronary-Vasospasm Epicardial vasospasm (>90% constriction); Prinzmetal's vasospastic angina; 46% MINOCA prevalence by provocation testing; Asian predilection; intracoronary acetylcholine gold standard; CCBs cornerstone; β-blockers contraindicated coronary-vasospasm, MINOCA, vasospastic-angina 2026-04-30
concepts/Pharmacological-Provocation-Testing SCB testing for BrS (ajmaline preferred; false-positive rates; clinical scenarios; SCN5A guidance); epinephrine for CPVT; adenosine for SVT/WPW; acetylcholine/ergonovine for CAS; polygenic basis of positive SCB response brugada-syndrome, pharmacological-provocation, arrhythmia-diagnosis, channelopathies, sudden-cardiac-death 2026-04-30
concepts/Coronary-Microvascular-Dysfunction Impaired coronary microcirculation (<0.5 mm); CFR <2.0 / microvascular spasm / slow-flow; 30–50% of INOCA patients; cause vs consequence debate in MINOCA; limited pharmacological treatment options coronary-microvascular-dysfunction, MINOCA, ischemia 2026-04-29
concepts/Calmodulinopathy CALM1/2/3 mutations (identical CaM protein) → LQTS (CDI loss at Cav1.2, ICaL GOF) or CPVT (RyR2 destabilisation via CaM–RyR2 3D interface); 99% CaM pre-bound; 1:7 mutant:WT sufficient for CDI impairment; verapamil reverses QT in hiPSC-CMs; ClinGen Definitive LQTS / Moderate CPVT calmodulinopathy, calcium-handling, long-qt-syndrome, CPVT, channelopathies 2026-05-10
concepts/POTS Postural tachycardia syndrome: HR increase ≥30 bpm adults / ≥40 bpm teens, sustained ≥2 readings, ≥3 months, no orthostatic hypotension, minimum HR 90 bpm; CCS 2020 nomenclature ecosystem — POTS/POTS plus (+ comorbidities: hEDS 25%, CFS/ME 21%)/PSWT/PTOC; non-pharmacologic first (salt 10 g/day + 3 L fluid + semirecumbent exercise); midodrine + low-dose propranolol (strong first-line GRADE); ivabradine/pyridostigmine/fludrocortisone (weak); sinus node ablation, Chiari decompression, jugular venoplasty all contraindicated POTS, autonomic-dysfunction, orthostatic-intolerance, dysautonomia 2026-05-21
concepts/Inappropriate-Sinus-Tachycardia IST: resting HR >100 bpm + mean 24h HR >90 bpm, not from primary causes; prevalence 1.2%; ivabradine 5–7.5 mg BID slows HR 25–40 bpm, eliminated symptoms in 70% (small RCT); beta-blockers ineffective; sinus node ablation not routine (high recurrence + complications) inappropriate-sinus-tachycardia, autonomic-dysfunction, arrhythmia 2026-05-20
concepts/Vasovagal-Syncope VVS: transient LOC with hypotension/relative bradycardia after prolonged standing or emotional stress; cumulative incidence 42% women/32% men by age 60; two physiologic phenotypes by supine BP; AHA 2017: physical counterpressure Class IIa B-R; midodrine Class IIa B-R (43% RRR in 5 RCTs); pacing IIb in ≥40yr with documented spontaneous pauses (negative tilt selects responders) vasovagal-syncope, autonomic-dysfunction, orthostatic-intolerance, syncope 2026-05-23
concepts/Syncope Syncope: transient LOC from cerebral hypoperfusion; 2017 ACC/AHA/HRS guideline framework; trimodal distribution (20/60/80yr); reflex 21% > cardiac 9% = OH 9% > unexplained 37%; Class I: history + ECG mandatory; ICM 55% vs 19% conventional diagnosis; risk scores do NOT outperform clinical judgment; routine neuroimaging/EEG/carotid = III No Benefit syncope, risk-stratification, cardiac-syncope, transient-loss-of-consciousness, guidelines 2026-05-23
concepts/Orthostatic-Hypotension OH: SBP ≥20 mmHg or DBP ≥10 mmHg drop on standing; classic (≤3 min), delayed (>3 min — 54% progress to classic at 10yr), initial (<15s), neurogenic (MSA/PD/Lewy/peripheral neuropathy); AHA 2017: water ingestion Class I; midodrine + droxidopa Class IIa B-R; compression garments + physical countermeasures Class IIa C-LD orthostatic-hypotension, autonomic-dysfunction, syncope, neurogenic-OH, dysautonomia 2026-05-23
concepts/Carotid-Sinus-Syndrome CSS: reflex syncope with CSH (pause ≥3s or SBP drop ≥50 mmHg on carotid massage); cardioinhibitory/vasodepressor/mixed subtypes; AHA 2017: permanent pacing Class IIa B-R for cardioinhibitory/mixed (76% relative risk reduction); dual-chamber Class IIb B-R; pacing NOT supported for pure vasodepressor type carotid-sinus-syndrome, syncope, reflex-syncope, permanent-pacing, autonomic-dysfunction 2026-05-23
concepts/Remote-Patient-Monitoring Wearable DHTs and RPM for CV medicine: hub model; ECG sensitivity 78–88%/specificity 80–86% for AF; PPG AF screening PPV 84–98% (Apple/Fitbit); ambulatory ECG yield 32–34%; no validated cuffless BP; pulse oximetry racial bias; long-term outcome benefit unproven wearable-digital-health, remote-patient-monitoring, atrial-fibrillation, heart-failure, cardiovascular-monitoring 2026-05-17
concepts/Pericarditis ACC 2025 novel diagnostic criteria (pleuritic chest pain mandatory + ≥1 of 5 additional findings; 0=unlikely/1=possible/2+=definite); inflammatory (80–90%, elevated CRP) vs non-inflammatory (10–20%) phenotypes; anti-IL-1 agents (anakinra/rilonacept/goflikicept) paradigm shift as preferred second-line over corticosteroids for recurrent inflammatory pericarditis; CMR LGE central for risk stratification; exercise restriction ≥1 month; recurrence 15–30% after first episode pericarditis, consensus, guidelines, cardiac-imaging, anti-IL1 2026-05-27
concepts/Constrictive-Pericarditis Transient (inflammatory, potentially reversible with 3–6 months anti-inflammatory therapy) vs chronic (fibrotic/calcified, requires radical pericardiectomy); causes: idiopathic > post-cardiac surgery > mediastinal radiation (TB in endemic areas); TTE annulus reversus + hepatic vein expiratory reversal; CMR LGE/T2-STIR differentiates transient vs chronic; effusive constrictive pericarditis distinct entity; radical pericardiectomy preferred for chronic CP pericarditis, constrictive-pericarditis, cardiac-imaging, heart-failure, pericardiectomy 2026-05-27
concepts/Pericardial-Effusion ACC 2025: defined >50 mL; TTE sizing (trivial/small <1cm/moderate 1–1.9cm/large 2–2.5cm/very large >2.5cm); ~50% idiopathic; CCT Hounsfield units (transudate 0–20/exudate 20–50/hemorrhagic >50–60 HU); cardiac tamponade — hemodynamics related to rapidity not volume; diastolic RV collapse most specific sign; pericardiocentesis recommended for established tamponade; inflammatory effusion without tamponade → anti-inflammatory first pericarditis, pericardial-effusion, cardiac-tamponade, cardiac-imaging, pericardiocentesis 2026-05-27
entities/Tirzepatide Dual GIP/GLP-1 receptor agonist; SUMMIT (NEJM 2025): first hard composite endpoint benefit in obesity-HFpEF (HR 0.62 CV death/worsening HF; KCCQ +6.9 pts; weight −13.9%); greater weight loss than semaglutide; all-cause death numerically higher (HR 1.25 NS); SURMOUNT-MMO ongoing (n=15,374; CVD + no T2DM; estimated 2027); SURPASS-CVOT ongoing vs dulaglutide in T2DM+CVD heart-failure-preserved-ejection-fraction, GLP-1-receptor-agonist, GIP-receptor-agonist, obesity 2026-05-25
ENTITIES
entities/Evinacumab Anti-ANGPTL3 fully human mAb (VelocImmune); FDA/EMA-approved HoFH ≥12yr (15 mg/kg IV q4wk); Raal Phase 3 (n=65): −47% LDL-C, −55% TG; LDLR-independent via EL-dependent VLDL clearance; effective in null-null and non-null LDLR genotypes; ACC/AHA 2026 COR 2b vs ESC 2025 IIa B (paediatric ≥5yr) angptl3, familial-hypercholesterolemia, lipid-lowering-therapy, monoclonal-antibody 2026-05-23
entities/Olezarsen GalNAc-ASO targeting APOC3 mRNA; hepatocyte-selective delivery; FDA-approved FCS; ESSENCE-TIMI 73b (NEJM 2025) Phase 3: −58–61 pp TG; remnant cholesterol −70%; LDL-C unchanged; no CV outcomes; safety: injection-site reactions, mild transaminase elevations, thrombocytopenia NS antisense-oligonucleotide, hypertriglyceridemia, apolipoprotein-C-III, lipid-lowering-therapy 2026-05-21
entities/PMCardio-Queen-of-Hearts AI ECG model for OMI detection (Powerful Medical, Slovakia); 100% sensitivity for LAD TIMI-0 OMI on first ECG; double sensitivity vs STEMI criteria at fixed specificity; PMcardio software also used for automated HATW score measurement artificial-intelligence-ECG, occlusion-MI, ECG-diagnosis 2026-05-03
entities/Acute-Coronary-Syndrome ACS spectrum (UA/NSTEMI/STEMI); prehospital triage; PPCI; DAPT; complete revascularization; cardiogenic shock (DanGer-SHOCK Impella); colchicine; cardiac rehabilitation; EMPACT-MI SGLT2i neutral; CLEAR spironolactone arm neutral; SENIOR-RITA (NEJM 2024; elderly NSTEMI ≥75yr): invasive strategy neutral on primary composite (HR 0.94; P=0.53); early benefit at 1yr (12.8% vs 16.8%) erodes; nonfatal MI HR 0.75 acute-coronary-syndrome, STEMI, antiplatelet-therapy, revascularization, guidelines 2026-05-18
entities/Chronic-Coronary-Disease CCD: beta-blocker paradigm (COR 3 No Benefit if prior MI + EF >50% + >1 year); ISCHEMIA paradigm (no survival benefit from routine revascularisation); CABG for LVEF ≤35%; SGLT2i/GLP-1 RA; INOCA; SCAD; 2026 update: IVUS-CHIP + IVUS-OPTIMAL challenge Class IA IVUS recommendation for complex/left main PCI chronic-coronary-disease, secondary-prevention, revascularization, antiplatelet-therapy, guidelines 2026-05-16
entities/Left-Main-Coronary-Disease Unprotected LMCA disease (4–6% of angiographies); PCI acceptable for low-intermediate complexity (SYNTAX ≤33); OPTIMAL trial (NEJM 2026, N=806): IVUS guidance NOT superior to angiography for patient-oriented composite (HR 1.11; P=0.40) at 2.9 years; challenges Class IA IVUS recommendation; expertise and volume may substitute for routine imaging left-main-pci, coronary-artery-disease, revascularization, ivus, pci 2026-05-16
entities/Amiodarone Class III antiarrhythmic affecting all 4 AP phases; ACLS first-line for VF; multisystem toxicity (thyroid, lung, liver, eye, skin); t½ 50–60d; warfarin/statin/digoxin/sofosbuvir interactions amiodarone, antiarrhythmic-drugs, drug-toxicity, ventricular-arrhythmias, atrial-fibrillation 2026-04-19
entities/CORIN Transmembrane serine protease (left atrial cardiomyocytes); cleaves proANP→ANP; homozygous LOF → isolated LA cardiomyopathy (fibrosis + hypertrophic remodelling) + resistant hypertension + refractory AF; BNP partial compensation; first human monogenic LA-CMP (NEJM 2023); amiloride/soluble corin as therapeutic concepts natriuretic-peptides, atrial-cardiomyopathy, genetics, hypertension, atrial-fibrosis 2026-05-17
entities/ALVC LV-predominant arrhythmogenic cardiomyopathy; no validated diagnostic criteria; DSP/LMNA/PLN/FLNC arrhythmogenic-cardiomyopathy, sudden-cardiac-death 2026-04-11
entities/ARVC Best-characterized ACM subtype; risk calculator performs poorly in DSP, overpredicts in gene-elusive; gene-specific exercise effects (PKP2/TMEM43 harmful; PLN not); flecainide PKP2cKO efficacy; family screening 33%+33% yield; 3 AAV-PKP2 Phase I/II trials cardiomyopathy, inherited-arrhythmias, arrhythmogenic-cardiomyopathy, gene-therapy 2026-05-05
entities/ATTR-Amyloidosis TTR-related infiltrative cardiomyopathy; bone scintigraphy diagnostic; tafamidis (ATTR-ACT HR 0.70) + acoramidis (ATTRibute-CM win ratio 1.8) as TTR stabilizers; vutrisiran (HELIOS-B HR 0.65) + patisiran (APOLLO-B proof-of-concept; not ATTR-CM approved) as RNAi class; nex-z CRISPR-Cas9 Phase 1 (−90% TTR, Phase 3 MAGNITUDE ongoing); four disease-modifying approaches; no head-to-head comparisons cardiomyopathy, amyloidosis, TTR-stabilizer, attr-cardiomyopathy, RNA-interference 2026-05-17
entities/Nexiguran-Ziclumeran CRISPR-Cas9 LNP in vivo TTR gene knockout therapy (nex-z/NTLA-2001); Phase 1 ATTR-CM (n=36): −90% serum TTR at 12 months, durable 24 months; disease stable 66%; manageable safety; single IV infusion — one-time permanent knockdown vs lifelong RNAi/stabilizer dosing; Phase 3 MAGNITUDE trial ongoing gene-therapy, attr-cardiomyopathy, CRISPR-Cas9, TTR-knockdown, lipid-nanoparticle 2026-05-17
entities/Andersen-Tawil-Syndrome LQT7; KCNJ2 LOF; triad: arrhythmia + periodic paralysis + dysmorphic features channelopathies, inherited-arrhythmias 2026-04-11
entities/Anderson-Fabry-Disease X-linked GLA mutation → α-Gal A deficiency; HCM genocopy (0.5–1% HCM); HFpEF dominant; ERT/migalastat/gene therapy; amiodarone contraindicated; 14-year diagnostic delay fabry-disease, cardiomyopathy, hypertrophic-cardiomyopathy, lysosomal-storage-disorders, enzyme-replacement-therapy 2026-04-19
entities/Atrial-Fibrillation Most prevalent sustained arrhythmia; AF-CARE + AHA staging; ESC/AHA diverge on CHA2DS2 and ablation; OPTION (NEJM 2025): LAAO NI + bleeding superiority (HR 0.44) vs NOAC post-ablation; CLOSURE-AF (NEJM 2026): LAAO failed NI in highest-risk AF; CHAMPION-AF (NEJM 2026): LAAO NI + superior bleeding in NOAC-eligible AF; EPIC-CAD (NEJM 2024): edoxaban monotherapy superior to dual antithrombotic in stable CAD+AF (NACE HR 0.44; NNT 10.6); biological therapies preclinical only atrial-fibrillation, anticoagulation, left-atrial-appendage-closure, stroke-prevention 2026-05-20
entities/LAAO Left atrial appendage occlusion; Watchman FLX/Amulet devices; surgical closure (LAAOS III); OPTION (2025): NI + bleeding superiority (HR 0.44) in post-ablation AF (CHA₂DS₂-VASc 3.5); CHAMPION-AF (2026): NI + bleeding superiority in NOAC-eligible AF; CLOSURE-AF (2026): NI failed in highest-risk AF; divergence driven by risk profile and post-implant antithrombotic strategy atrial-fibrillation, stroke-prevention, devices, anticoagulation, interventional-cardiology 2026-05-16
entities/Atrial-Flutter CTI-dependent macro-reentry; >50% develop AF; OAC as per AF guidelines atrial-fibrillation, cardiac-arrhythmias 2026-04-12
entities/Brugada-Syndrome Type 1 ECG + VF risk; SCN5A in 15–30%; three competing pathophysiology hypotheses channelopathies, inherited-arrhythmias 2026-04-11
entities/CPVT Exercise-triggered bidirectional VT; RYR2 GOF; largest database 964 patients (Chang 2025); median onset 11y; variant-specific treatment response (BB/flecainide/ICD); CSol/pore domain variants earliest onset 8y; markslab-cpvtdb.org channelopathies, inherited-arrhythmias, CPVT, RYR2, sudden-cardiac-death 2026-05-05
entities/DCM LV dilatation + dysfunction; TTN most common gene; DANISH trial reduced ICD class to IIa; IV iron Class I (ESC 2023); second hit paradigm; 12 definitive genes; gene therapy pipeline; Pinto 2016 relative diagnostic criteria; genotype-specific LVRR (TTN↑; LMNA/FLNC↓); apparent healing phenomenon cardiomyopathy, genetics 2026-05-10
entities/Heart-Failure HF hub across all EF phenotypes; classification (HFrEF/HFmrEF/HFpEF/HFimpEF); ACC/AHA staging A–D; SGLT2i Class I for HFmrEF/HFpEF; acute HF (EMPULSE, STRONG-HF); MCS in cardiogenic shock (DanGer-SHOCK Impella NNT=8); iron deficiency; Group 2 PH-LHD; TTS as acute HF syndrome; special populations (CH, CTRCD, perioperative, obesity) heart-failure, HFrEF, HFpEF, SGLT2-inhibitors, guideline, acute-heart-failure 2026-05-12
entities/HFrEF HFrEF-specific hub (LVEF ≤40%): 4-pillar GDMT (73% mortality reduction); PARADIGM-HF ARNi HR 0.80 NNT 21; RALES MRA RR 0.70 30% RRR; DAPA-HF SGLT2i HR 0.74 NNT 21; EMPEROR-Reduced HR 0.75 NNT 19; ICD/CRT AUC 2025 + SCD-HeFT (ICD HR 0.77); DEFINITE (NICM ICD HR 0.65 NS; SCD HR 0.20 P=0.006); COMPANION CRT-D HR 0.64 (P=0.003) mortality (NYHA III/IV; QRS ≥120ms); CARE-HF CRT-P HR 0.64 NNT≈9 (NYHA III/IV); MADIT-CRT CRT-D HR 0.66 HF events only (NYHA I/II; QRS ≥150ms HR 0.48 vs 130–149ms HR 1.06); ischaemic CMP (CABG COR 1; PCI HR 0.99); DIGIT-HF HR 0.82; GALACTIC-HF omecamtiv mecarbil HR 0.92 (LVEF ≤28% HR 0.84; not approved) heart-failure, HFrEF, GDMT, ischemic-cardiomyopathy, heart-failure-management 2026-05-16
entities/Omecamtiv-Mecarbil Selective cardiac myosin activator (myotrope); first-in-class; GALACTIC-HF (NEJM 2021; n=8,232; LVEF ≤35%; median 21.8 months): primary composite HR 0.92 (P=0.03); CV death HR 1.01 NS; all-cause death HR 1.00 NS; LVEF ≤28% HR 0.84 vs LVEF >28% HR 1.04 (prespecified interaction); calcium-independent mechanism (no ischemia/arrhythmia excess); not approved or guideline-listed cardiac-myosin-activator, heart-failure-reduced-EF, omecamtiv-mecarbil, systolic-function, myotrope 2026-05-15
entities/HFpEF HFpEF definition; SGLT2i Class I: EMPEROR-Preserved (HR 0.79, NNT=31) + DELIVER (HR 0.82); nonsteroidal MRA (finerenone FINEARTS-HF 2024: RR 0.84 P=0.007 — first MRA with positive primary endpoint); TOPCAT (spironolactone) HR 0.89 NS; PARAGON-HF ARNI borderline P=0.06; semaglutide STEP-HFpEF 2023: KCCQ +7.8 pts + weight −10.7 pp — largest symptom improvement of any HFpEF pharmacotherapy; no mortality benefit from any agent; obesity-HFpEF phenotype heart-failure, HFpEF, SGLT2-inhibitors, mineralocorticoid-receptor-antagonist, finerenone 2026-05-17
entities/Semaglutide GLP-1 receptor agonist; SELECT (n=17,604; CVD + no T2DM + BMI >27): MACE HR 0.80 — first MACE benefit without diabetes; STEP-HFpEF 2023 (HFpEF + obesity, no T2DM): KCCQ-CSS +7.8 pts + weight −10.7 pp; SOUL 2025 (oral; T2DM; n=9,650): MACE HR 0.86 (P=0.006) — first oral GLP-1 RA CV superiority; kidney composite HR 0.91 NS; FLOW (injectable; CKD): HR 0.76; ESSENCE (MASH, NEJM 2025): superior on both histologic endpoints heart-failure-preserved-ejection-fraction, semaglutide, GLP-1-receptor-agonist, type-2-diabetes, oral-semaglutide 2026-05-25
concepts/GLP-1-Receptor-Agonists GLP-1 receptor agonist drug class: mechanism (insulin secretion, appetite suppression, anti-inflammatory, antiatherosclerotic); class CVOT superiority (liraglutide LEADER HR 0.87; semaglutide SC SUSTAIN-6 HR 0.74; dulaglutide REWIND HR 0.88; oral semaglutide SOUL 2025 HR 0.86 — first oral GLP-1 RA with CV superiority); SELECT (semaglutide + CVD + no T2DM HR 0.80); oral vs injectable bioavailability (0.4–1% vs 89%); kidney dissociation (SOUL oral HR 0.91 NS vs FLOW injectable HR 0.76); HFpEF (STEP-HFpEF, SUMMIT); MASH (ESSENCE, SYNERGY-NASH); ACC 2025 NuSH framework GLP-1-receptor-agonist, type-2-diabetes, cardiovascular-outcomes, obesity, weight-management 2026-05-25
concepts/NuSH-Therapies ACC 2025 CCG framework for liraglutide/semaglutide/tirzepatide as "nutrient-stimulated hormone" obesity pharmacotherapy; no "try and fail" lifestyle before pharmacotherapy; weight thresholds (10–15% CVD, >15% HFpEF); SELECT MACE HR 0.80 (no T2DM); SUMMIT HR 0.62 HFpEF; eligibility BMI ≥30 or ≥27 + comorbidity; compounded agents discouraged; comorbidity de-escalation framework NuSH-therapy, GLP-1-receptor-agonist, obesity-management, cardiovascular-prevention, weight-management 2026-05-25
entities/Finerenone Nonsteroidal MRA (Kerendia/Bayer); FINEARTS-HF 2024 (n=6,001): first MRA with positive primary endpoint in HFpEF/HFmrEF (total HF events + CV death RR 0.84; P=0.007); HF events RR 0.82; CV death HR 0.93 NS; kidney composite HR 1.33 NS (opposite to CKD trials); hyperkalemia 3.0% vs 1.4%; benefit with and without SGLT2i heart-failure, HFpEF, finerenone, mineralocorticoid-receptor-antagonist, randomized-controlled-trial 2026-05-16
entities/Vericiguat Oral sGC stimulator; first new HF drug class with outcomes evidence since SGLT2i; VICTORIA (n=5050) primary HR 0.90 P=0.02; NNT ~24; no mortality benefit; no SGLT2i co-treatment data; contraindicated with nitrates/PDE5i heart-failure, HFrEF, vericiguat, nitric-oxide-cGMP, clinical-trial 2026-05-10
entities/Sacubitril-Valsartan ARNI (neprilysin inhibitor + AT1R blocker); Class I HFrEF: PARADIGM-HF HR 0.80 P<0.001 NNT 21, all-cause death HR 0.84, stopped early; PARAGON-HF HFpEF: primary RR 0.87 P=0.06 (negative); subgroup LVEF 45–57% and women; COR 2b AHA 2022 HFpEF; renal protection HR 0.50; NYHA improvement OR 1.45 heart-failure, HFrEF, HFpEF, sacubitril-valsartan, angiotensin-neprilysin-inhibition 2026-05-11
entities/ICD Implantable cardioverter-defibrillator; secondary prevention A(9) in VT/VF survivors; MADIT-II (ICM LVEF ≤30%): HR 0.69 P=0.016; SCD-HeFT (LVEF ≤35%; 52% ICM/48% NICM): ICD HR 0.77 P=0.007; establishes ≤35% guideline threshold; NYHA II HR 0.54 vs NYHA III HR 1.16 NS; DEFINITE (NICM LVEF <36%; n=458): all-cause mortality HR 0.65 NS, SCD HR 0.20 P=0.006; DANISH (NICM): HR 0.87 NS, SCD HR 0.50; NICM A(7–9); HCM A(8); Programming (HRS 2015): prolonged detection 30/40 intervals; VF cutoff ≥200 bpm; ATP first-line (188–250 bpm); DT omission safe for standard transvenous implants (SIMPLE n=2,500); POTCAST (NEJM 2025): potassium targeting reduces composite arrhythmia/death HR 0.76 (P=0.01; NNT=12.3) in ICD patients implantable-cardioverter-defibrillator, sudden-cardiac-death, heart-failure, arrhythmia, primary-prevention 2026-05-16
entities/CRT Cardiac resynchronization therapy; LVEF ≤35% + LBBB + QRS ≥150ms + NYHA II–IV = A(9); LBBB QRS 120–149ms = A(7); non-LBBB QRS ≥150ms NYHA III–IV = A(7); narrow QRS R(1); AF reduces by 1 tier unless AVJ ablation; RV pacing-induced CMP upgrade A(7); LVAD+CRT-D R(2–3); CSP-CRT M(5–6) pending PROTECT-HF/Left vs Left; COMPANION (NEJM 2004): CRT-D mortality HR 0.64 (P=0.003); CRT-P HR 0.76 (P=0.059 NS); both ↓ primary composite ~20%; non-ischaemic CRT-D HR 0.50; CARE-HF (NEJM 2005): CRT-P mortality HR 0.64 (NNT≈9; NYHA III/IV); MADIT-CRT (NEJM 2009): NYHA I/II CRT-D HR 0.66 (HF events 41% ↓; no mortality benefit); QRS ≥150ms HR 0.48 vs 130–149ms HR 1.06 cardiac-resynchronization-therapy, heart-failure, HFrEF, left-bundle-branch-block, biventricular-pacing 2026-05-16
entities/S-ICD Subcutaneous ICD; no intracardiac leads; no ATP capability; primary prevention LVEF ≤35% A(7) (PRAETORIAN noninferior; UNTOUCHED 95.9% shock-free); HCM A(7); CHD venous obstruction A(8); dialysis A(7); sustained MMVT M(4–5) — ATP needed; ARVC M(5); SENSE algorithm + dual-zone mandatory implantable-cardioverter-defibrillator, subcutaneous-ICD, sudden-cardiac-death, arrhythmia 2026-05-11
entities/CCM Cardiac contractility modulation; nonexcitatory refractory-period pulses; LVEF 25–45% + QRS <130ms + NYHA II–III not eligible for CRT; FDA-approved 2019; all scenarios M(4–5) in AUC 2025; FIX-HF-5C: pVO₂ +1.1 mL/kg/min, KCCQ +9.7 points; no mortality benefit; fills narrow-QRS HF gap cardiac-contractility-modulation, heart-failure, HFrEF, narrow-QRS, device-therapy 2026-05-11
entities/CTEPH Group 4 PH; PEA treatment of choice; BPA Class I (upgraded 2022) for inoperable; RACE/MR BPA trials; lesion classification; complication trends halved 2013–2022; expert centre criteria; riociguat Class I pulmonary-hypertension, CTEPH, right-heart-failure 2026-04-28
entities/DES Desmin; wide cardiomyopathy spectrum (DCM/RCM/ACM); 80% cardiac penetrance; high conduction disease burden often requiring CIED; skeletal myopathy; no gene-specific risk calculator genetics, arrhythmogenic-cardiomyopathy, dilated-cardiomyopathy, conduction-disease 2026-05-05
entities/DSP Desmoplakin; ALVC archetype; left-dominant/biventricular; female sex risk factor (unique); "hot phases" myocarditis-like episodes; ring-like LGE; DSP risk calculator; 2010 TFC poor performance; exercise effect uncertain genetics, arrhythmogenic-cardiomyopathy, DSP-cardiomyopathy 2026-05-05
entities/DSG2 Desmoglein-2; classical ARVC phenotype; may have earlier onset than PKP2; more biventricular involvement; autosomal dominant; limited penetrance data genetics, arrhythmogenic-cardiomyopathy, ARVC, desmosome 2026-05-05
entities/DSC2 Desmocollin-2; classical ARVC phenotype similar to PKP2; often autosomal recessive; limited penetrance data; small case series genetics, arrhythmogenic-cardiomyopathy, ARVC, desmosome 2026-05-05
entities/Early-Repolarization-Syndrome J-point elevation in VF survivors; J-wave syndrome partner of Brugada; quinidine/isoproterenol channelopathies, inherited-arrhythmias 2026-04-11
entities/FLNC Filamin-C; truncating variants cause ALVC with 82% SCD/VA; myofibrillar myopathy overlap genetics, arrhythmogenic-cardiomyopathy 2026-04-12
entities/HCM Most common inherited cardiomyopathy; MYBPC3/MYH7 primary genes; ESC/AHA diverge on 4 key issues cardiomyopathy, sudden-cardiac-death 2026-04-11
entities/Idiopathic-Ventricular-Fibrillation Diagnosis of exclusion after VF; short-coupled R-on-T PVCs; ICD Class I channelopathies, inherited-arrhythmias 2026-04-11
entities/JUP Plakoglobin; Naxos disease (AR); woolly hair + palmoplantar keratoses + ARVC triad; 97% penetrance by adolescence; more severe than PKP2-ARVC; biventricular common genetics, arrhythmogenic-cardiomyopathy, ARVC, desmosome, Naxos-disease 2026-05-05
entities/KCNH2 hERG/Kv11.1; LOF → LQT2; GOF → SQTS1; SupRep validated in rabbit models; dominant-negative for AF genetics, channelopathies 2026-04-11
entities/KCNJ2 Kir2.1; LOF → ATS/LQT7; GOF → SQTS3; IK1 suppression used in biological pacemaker research genetics, channelopathies 2026-04-12
entities/KCNQ1 Kv7.1/IKs; LOF → LQT1 (30–35% LQTS); recessive → Jervell-Lange-Nielsen; SupRep validated genetics, channelopathies 2026-04-11
entities/LMNA Lamin A/C; AF/conduction disease precede DCM by decades; highest malignant VA risk in cardiomyopathy genetics, arrhythmogenic-cardiomyopathy 2026-04-12
entities/Long-QT-Syndrome Most prevalent channelopathy; KCNQ1 ~50%/KCNH2 ~40%/SCN5A ~10% = 90% of cases; gene-specific ECG patterns, triggers, and therapy; triple therapy (BB + mexiletine + LCSD) sufficient for ~95%; ICD for ~5%; risk score application timing controversy; acquired LQTS predictors; SupRep validated channelopathies, inherited-arrhythmias, long-qt-syndrome, sudden-cardiac-death 2026-05-16
entities/MYBPC3 Most common HCM gene (~50%); higher arrhythmia/syncope vs other sarcomere genes; RyR2 interaction genetics, hypertrophic-cardiomyopathy 2026-04-11
entities/MYH6 Alpha-myosin heavy chain; atrial-predominant; sick sinus syndrome and EOAF association genetics, atrial-fibrillation 2026-04-11
entities/MYH7 Beta-myosin heavy chain; 2nd most common HCM gene; high-risk SCD mutations R403Q/R453C genetics, hypertrophic-cardiomyopathy 2026-04-11
entities/Aficamten Next-in-class cardiac myosin inhibitor (Cytokinetics); SEQUOIA-HCM 2024: phase 3 RCT vs placebo — peak VO2 +1.7 ml/kg/min (P<0.001), all 10 secondary endpoints significant, SRT eligibility −78 days, NT-proBNP −80%, benefit consistent regardless of beta-blocker use; MAPLE-HCM 2025: superior to metoprolol monotherapy (peak VO2 +2.3 ml/kg/min); LVEF <50% 1–3.5% (transient); shallow dose-response; no drug-drug interactions hypertrophic-cardiomyopathy, cardiac-myosin-inhibitor, obstructive-HCM, pharmacology, LVOTO 2026-05-17
entities/Vutrisiran GalNAc-siRNA (25 mg SC Q12W) silencing hepatic TTR mRNA; HELIOS-B 2025 (n=655): first RNAi therapy to reduce mortality in ATTR-CM — HR 0.65 all-cause death through 42 months; 81% TTR knockdown; benefits on and off tafamidis background; approved for ATTRv-PN and ATTR-CM attr-cardiomyopathy, RNA-interference, vutrisiran, amyloidosis, gene-silencing 2026-05-16
entities/Patisiran LNP-siRNA (IV Q3W) targeting TTR 3'UTR; 86.8% TTR knockdown; APOLLO-B 2023 (n=360; 12 months): 6MWT +14.69 m (P=0.02) + KCCQ +3.7 pts (P=0.04) met; hard composites NS (underpowered/too short); deaths 4 vs 10 HR 0.36 NS; not approved for ATTR-CM; approved for ATTRv-PN; proof-of-concept for cardiac RNAi; succeeded by vutrisiran attr-cardiomyopathy, patisiran, RNA-interference, TTR-knockdown, heart-failure 2026-05-17
entities/Mavacamten First cardiac myosin inhibitor; Class I AHA 2024 (obstructive HCM) vs Class IIa ESC 2023; ODYSSEY-HCM 2025: ineffective in nonobstructive HCM (both primary endpoints missed P=0.07/0.06; CHF 6.6% vs 1.7%); biomarker-clinical dissociation (NT-proBNP −59% without clinical benefit); contraindicated in pregnancy cardiomyopathy, pharmacology, hypertrophic-cardiomyopathy, nonobstructive-HCM, cardiac-myosin-inhibitor 2026-05-16
entities/NDLVC New ESC 2023 phenotype: non-dilated LV with non-ischaemic scar; replaces ALVC/arrhythmogenic DCM cardiomyopathy, sudden-cardiac-death 2026-04-11
entities/PKP2 Most common ARVC gene (~2/3 cases); desmosomal + Nav1.5 + Cx43; flecainide eliminates VA in PKP2cKO mice (RCT pending); 3 AAV-PKP2 Phase I/II trials (Rocket/LEXEO/Tenaya); MyoAAV4A variant; exercise major penetrance risk genetics, arrhythmogenic-cardiomyopathy, ARVC, gene-therapy 2026-05-05
entities/PLN Phospholamban/SERCA2a regulator; R14del founder; exercise NOT risk factor (unique among ACM); sex NOT risk factor; mixed HF+VA phenotype; gene-specific calculator usable pre-diagnosis; micro voltages; high end-stage HF risk genetics, arrhythmogenic-cardiomyopathy, PLN-cardiomyopathy 2026-05-05
entities/RCM Restrictive physiology + normal wall thickness; often transplant-required; biatrial enlargement cardiomyopathy, genetics 2026-04-11
entities/RYR2 SR Ca²⁺ release channel; GOF → CPVT1; 263 variants in 964 CPVT patients (Chang 2025); domain-specific onset: CSol/pore 8y, NTD 12y; variant-specific BB/flecainide/ICD response; R420Q vs R420W different phenotypes; markslab-cpvtdb.org; too large for AAV; CRISPR-SaCas9 repair in mice genetics, calcium-handling, CPVT, RYR2, ryanodine-receptor, variant-interpretation 2026-05-05
entities/CASQ2 Calsequestrin-2; Ca²⁺ buffer + RYR2 inhibitor via triadin/junctin; CPVT2 (AR, 2–5%); 100% penetrance; earlier onset/greater severity/more BB-resistant than CPVT1; AD evidence Moderate only; HCM disputed; most advanced CPVT gene therapy target — single AAV9 injection >85% arrhythmia reduction ≥1 year genetics, calcium-handling, channelopathies, CPVT, gene-therapy 2026-05-10
entities/SCN5A Nav1.5; GOF → LQT3 (INaL/window current); LOF → BrS + CCD + DCM; overlap syndromes (1795insD: simultaneous GOF+LOF); MEPPC (R222Q GOF); too large for AAV; MOG1 workaround genetics, ion-channels, channelopathies, SCN5A, dilated-cardiomyopathy 2026-05-05
entities/Short-QT-Syndrome QTc ≤360 ms (ESC 2022); 8 subtypes; quinidine first-line; amiodarone/sotalol ineffective in SQTS1 channelopathies, inherited-arrhythmias 2026-04-11
entities/TTN Titin; most common DCM gene and most common EOAF gene (27% of variants); second-hit theory genetics, dilated-cardiomyopathy 2026-04-11
entities/TMEM43 Transmembrane protein 43; p.Ser358Leu founder (Newfoundland); near-fully penetrant males; highly malignant; early ICD indicated; exercise harm; poor R-wave progression; first non-desmosomal ARVC gene genetics, arrhythmogenic-cardiomyopathy, ARVC, sudden-cardiac-death 2026-05-05
entities/Obstructive-Sleep-Apnea OSA: repetitive upper airway collapse during sleep; 21–74% prevalence in AF; acute + chronic AF substrate; CPAP treatment; AHI vs. hypoxemic burden obstructive-sleep-apnea, atrial-fibrillation, CPAP 2026-04-18
entities/Hypertension ESC 2024 + AHA 2025 dual-guideline coverage: ESC 3-category (Non-elevated/Elevated/Hypertension) vs AHA 4-tier classification; ESC SBP target 120–129 mmHg Class I vs AHA <130 mmHg Class I; SCORE2/SCORE2-OP risk stratification for elevated BP; primary aldosteronism screening all confirmed HT (ESC IIa) vs resistant only (AHA); RDN ESC IIb,A for uncontrolled on <3 drugs; BPROAD (NEJM 2025): SBP <120 mmHg superior in T2DM HR 0.79; BaxHTN (NEJM 2025): baxdrostat −8.7/−9.8 mmHg SBP hypertension, blood-pressure-management, cardiovascular-risk, guidelines, aldosterone-synthase-inhibitor 2026-05-20
entities/Type-2-Diabetes T2DM cardiovascular risk: HTN most common comorbidity; BPROAD (NEJM 2025; n=12,821) — intensive SBP <120 mmHg vs <140 mmHg: HR 0.79 (P<0.001); stroke primary driver; albuminuria HR 0.87; ACEi/ARB if eGFR <60 or albuminuria ≥30 mg/g type-2-diabetes, hypertension, cardiovascular-risk, blood-pressure-control 2026-05-20
entities/Pulmonary-Embolism Acute PE: AHA/ACC 2026 Cat A–E classification; CTPA diagnosis; D-dimer age-adjusted/YEARS; LMWH>UFH; DOACs>VKAs; PERT; advanced therapies by category; CTEPD surveillance; extended anticoagulation with half-dose DOAC; HI-PEITHO 2026 RCT: CDL superior to anticoagulation alone for intermediate-risk PE (RR 0.39, P=0.005, no ICH) pulmonary-embolism, venous-thromboembolism, anticoagulation 2026-05-16
entities/Ischemic-Stroke 2026 AHA/ASA 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; PES for dysphagia COR 2a acute-ischemic-stroke, endovascular-thrombectomy, thrombolysis, stroke-management 2026-04-24
entities/Peripheral-Artery-Disease Lower extremity PAD; 10–12M US; 4 clinical subsets (asymptomatic/claudication/CLTI/ALI); rivaroxaban+aspirin; high-intensity statin; SET as initial claudication therapy; BEST-CLI/BASIL-2 CLTI revascularisation peripheral-artery-disease, guidelines, revascularization, CLTI, claudication 2026-04-24
concepts/CLTI Chronic limb-threatening ischemia: rest pain/nonhealing wounds/gangrene >2 wk; WIfI/GLASS staging; multispecialty team mandatory; BEST-CLI (bypass superior with GSV) vs BASIL-2 (endovascular superior for infrapopliteal) CLTI, peripheral-artery-disease, revascularization 2026-04-24
concepts/PAD-Exercise-Therapy SET COR 1A: ≥30–45 min active walking, ≥3×/week, ≥12 weeks; CLEVER trial (SET = endovascular for aortoiliac); SET after revascularisation COR 1A; structured community/home exercise equally effective; unstructured ("go for a walk") is COR 2b; ~2% real-world referral rate despite Medicare coverage peripheral-artery-disease, exercise-therapy, claudication, supervised-exercise, rehabilitation 2026-05-09
concepts/PAD-Medical-Therapy Rivaroxaban 2.5 mg BID + aspirin COR 1A (COMPASS/VOYAGER PAD); high-intensity statin COR 1A (MALE −30%, amputation −35%); PCSK9i COR 2a; ACEi/ARB first-line HTN; GLP-1/SGLT-2i COR 1A in T2DM; cilostazol COR 1A for claudication (contraindicated in HF); pentoxifylline COR 3:No Benefit; smoking cessation COR 1A peripheral-artery-disease, antithrombotic-therapy, guideline, statin, GDMT 2026-05-09
concepts/Acute-Limb-Ischemia ALI: acute limb hypoperfusion ≤2 wk; Rutherford I–III classification; 4–6 h ischaemia tolerance; surgical thromboembolectomy vs catheter thrombolysis; compartment syndrome monitoring peripheral-artery-disease, vascular-emergency, revascularization 2026-04-24
concepts/Ankle-Brachial-Index ABI: ratio ankle systolic / higher brachial systolic; abnormal ≤0.90; TBI ≤0.70 for non-compressible vessels; cornerstone PAD diagnostic test peripheral-artery-disease, diagnostics 2026-04-24
concepts/Infective-Endocarditis IE framework: 2023 Duke-ISCVID criteria (surgical evidence + mNGS major criteria); echocardiography; advanced imaging; microbiology; NBTE differential infective-endocarditis, diagnostics, echocardiography, cardiac-surgery, guideline 2026-04-25
concepts/Blood-Culture-Negative-Endocarditis BCNE: prior antibiotics #1 cause (up to 30% IE); diagnostic algorithm (72h expand to mNGS/serology); fastidious pathogens (Coxiella/Bartonella/Whipple/Chimaera/Fungi); empiric regimens; NBTE infective-endocarditis, blood-culture-negative-endocarditis, molecular-diagnostics, fastidious-organisms 2026-04-25
concepts/Renal-Denervation Catheter-based renal sympathetic ablation for uncontrolled/resistant hypertension; FDA-approved (Spyral/Paradise 2023); 4–10 mmHg SBP reduction; 60–70% response rate; patient selection framework; no kidney function impairment hypertension, resistant-hypertension, renal-denervation, catheter-based-therapy, sympathetic-nervous-system 2026-04-25
concepts/CAVD-Mechanisms Molecular mechanisms of calcific aortic valve disease: VEC disruption, Lp(a)/LDL-C osteogenic cascade, EVs/TNAP, CHIP, interferonopathies; initiation vs progression distinction; statin paradox; ongoing trials (pelacarsen, colchicine) calcific-aortic-valve-disease, valvular-heart-disease, molecular-mechanisms, aortic-stenosis, lipoprotein-a 2026-04-25
entities/Mitral-Valve-Prolapse MVP: Barlow vs fibroelastic deficiency; TGF-β pathway central; FLNA/DCHS1/DZIP1/TNS1/LMCD1/SLC6A4 genes; serotonin transporter link; calcineurin/NFAT therapeutic target; equal sex prevalence but worse female outcomes valvular-heart-disease, mitral-valve-prolapse, molecular-mechanisms, genetics, TGF-beta 2026-04-25
entities/Bicuspid-Aortic-Valve BAV: 1.5% prevalence; 89% heritability; NOTCH1/GATA4-6/SMAD6 monogenic variants; 3–4× male predominance; accelerated calcification vs trileaflet valves due to abnormal shear stress valvular-heart-disease, bicuspid-aortic-valve, congenital-heart-disease, genetics, aortic-stenosis 2026-04-25
entities/Rheumatic-Heart-Disease RHD: >40M prevalent cases; 80% women; group A streptococcal molecular mimicry (M protein/laminin/myosin); VCAM-1/IFN-γ/IL-17/TGF-β; ficolin/MBL complement pathway; ProTα and female sex predilection; no effective medical therapy rheumatic-heart-disease, valvular-heart-disease, molecular-mechanisms, immunology, global-health 2026-04-25
entities/Maternal-Health-Disparities Non-Hispanic Black women bear disproportionate APO/maternal mortality burden; structural racism as root cause; weathering/allostatic load; "superwoman schema"; insurance churn; community/policy multilevel interventions maternal-health, health-disparities, adverse-pregnancy-outcomes, structural-racism, social-determinants 2026-04-28
entities/Peripartum-Cardiomyopathy PPCM: LVEF <45% last month pregnancy/5 months postpartum; vasculohormonal model (prolactin 16-kDa/sFlt-1/activin-A); ~15% carry DCM genes (2/3 TTN); IPAC: recovery almost exclusively first 6 months; major events EF <30%; BOARD framework; WCD preferred over ICD; bromocriptine (REBIRTH trial 2026 pending); 4× higher incidence Black women; CHC contraindicated; mWHO IV if any residual LV dysfunction peripartum-cardiomyopathy, cardiomyopathy, heart-failure, pregnancy, genetics, maternal-health 2026-05-17
entities/Obesity Chronic multifactorial disease; US 40.3% obesity / 9.4% severe; HF/SCD/AF/CAD/VTE risk; BMI limitations; NuSH therapies (ACC 2025): semaglutide SELECT MACE HR 0.80 (no T2DM), tirzepatide SUMMIT HFpEF HR 0.62; weight thresholds 10–15% CVD, >15% HFpEF; obesity paradox; class 3 = relative contraindication to HTx obesity, cardiovascular-disease, metabolic-syndrome, cardiometabolic-risk 2026-05-25
concepts/Obesity-Paradox Overweight/class 1 obesity confers better short-term CVD outcomes than normal weight; documented post-PCI, post-CABG, HFrEF, HFpEF, AHF; proposed mechanisms: lead time bias, fitness confounding, lean paradox obesity, cardiovascular-disease, heart-failure, coronary-artery-disease, prognosis 2026-04-29
concepts/Visceral-Adiposity VAT and ectopic fat (pericardial/epicardial/hepatic) as independent CVD risk markers; EAT drives AF and SCD substrate; metabolically healthy obesity is transient; exercise reduces VAT without weight loss obesity, cardiovascular-disease, visceral-adiposity, epicardial-fat, atrial-fibrillation 2026-04-29
concepts/Epicardial-Adipose-Tissue-Arrhythmogenesis Three EAT arrhythmogenic pathways: (1) structural infiltration → zigzag conduction/re-entry; (2) Cx43 electrotonic coupling → RMP depolarisation; (3) paracrine secretome (TNF-α/IL-1β/IL-6/TGF-β1/leptin) → APD prolongation, connexin downregulation, fibrosis; ECG correlates: P-wave/PR/QRS/TpTe epicardial-adipose-tissue, arrhythmias, atrial-fibrillation, electrophysiology, obesity 2026-05-01
concepts/Circadian-Rhythm-Cardiac-Electrophysiology Extrinsic (SCN/ANS) and intrinsic (BMAL1/CLOCK) circadian regulation of cardiac electrophysiology; Kcnh2/Gja1/Scn5a/Hcn4/Pkp2 as top REGs; KLF15→KChIP2 indirect pathway; Kv11.1 protein half-life and LQT2 time-of-day APD amplification; loss of morning SCA peak in modern populations; aging reduces circadian amplitude circadian-rhythm, sudden-cardiac-death, cardiac-electrophysiology, ion-channels, arrhythmia-mechanisms 2026-05-01
concepts/Noncoding-RNA-in-CVD Umbrella overview of all ncRNA classes (miRNA, snoRNA, Y-RNA, tsRNA, lncRNA, circRNA, exRNA) and their roles in CVD; computational tools; RNA therapeutics pipeline noncoding-RNA, microRNA, lncRNA, RNA-therapeutics, extracellular-RNA 2026-04-29
concepts/Cancer-Associated-Arrhythmia Drug-by-drug arrhythmia profiles in cancer (AF/QT/VA/bradycardia); ibrutinib RR 4.69 AF; ibrutinib-diltiazem/amiodarone MAJOR interaction (6–9× levels); pirtobrutinib 3.2% AF; ibrutinib-AF management (hemodynamic stability approach; Factor Xa preferred; dabigatran contraindicated); QTcF preferred; MADIT-CHIC CRT arrhythmia, cardio-oncology, atrial-fibrillation, QT-prolongation, BTK-inhibitors 2026-05-24
concepts/Autonomic-Dysfunction-in-Cancer Autonomic dysfunction in cancer patients/survivors: decreased HRV, orthostatic hypotension, IST/POTS; anthracycline/taxane/HSCT aetiology; exercise reversal; ivabradine for IST arrhythmia, cardio-oncology, autonomic-dysfunction, cancer-survivorship 2026-04-29
concepts/Long-Noncoding-RNA lncRNA classification (lincRNA/intronic/eRNA/AS-lncRNA; guide/scaffold/decoy/ceRNA); CVD loci (ANRIL/MIAT/H19/MALAT1/Mhrt/Chast/Chaer); lipid metabolism; cardiac hypertrophy; stroke; investigational tools lncRNA, noncoding-RNA, cardiac-hypertrophy, atherosclerosis, RNA-therapeutics 2026-04-29
concepts/MEPPC Multifocal ectopic premature Purkinje-related complexes; SCN5A R222Q gain-of-function; increased window current → premature Purkinje action potentials; narrow complex polymorphic PVCs; reversible DCM; flecainide/hydroquinidine/amiodarone responsive SCN5A, channelopathies, premature-ventricular-complexes, ventricular-arrhythmias 2026-05-05
concepts/Modifier-Genes Genetic factors that modify penetrance/expressivity of monogenic arrhythmia disorders; NOS1AP, KCNH2-K897T, KCNE1-D85N, AKAP9, iPSC-CM discovery approach modifier-genes, long-qt-syndrome, sudden-cardiac-death, NOS1AP 2026-05-05
entities/NOS1AP Nitric oxide synthase adaptor protein; most validated LQTS modifier gene (GWAS-derived); also implicated in drug-induced LQTS and AMI-VF modifier-genes, long-qt-syndrome, sudden-cardiac-death 2026-05-05
entities/Dronedarone Non-iodinated amiodarone derivative; multichannel blocker (IK-Ach 100x, INa 10x potency); ATHENA 24.2% RRR; contraindicated in NYHA III/IV HF (ANDROMEDA) dronedarone, atrial-fibrillation, antiarrhythmic-drugs, heart-failure 2026-05-07
entities/Flecainide Class 1C AAD; post-repolarization refractoriness mechanism; AF cardioversion up to 95% IV; pill-in-the-pocket; CAST context; RyR2 blockade in CPVT; contraindicated in CAD/structural disease flecainide, atrial-fibrillation, antiarrhythmic-drugs, proarrhythmia, CPVT 2026-05-07
concepts/Amiodarone-Induced-Thyroid-Disorders Type 1 AIT (iodine-driven autonomous overproduction; methimazole) vs Type 2 AIT (destructive thyroiditis; prednisone) vs mixed (both); AIH (Wolff-Chaikoff; levothyroxine); 23% ICU mortality in thyroid storm; ETA thyroidectomy criteria; 3-way warfarin/DOAC-thyrotoxicosis-amiodarone anticoagulant interaction amiodarone, thyroid-dysfunction, thyrotoxicosis, drug-toxicity, antiarrhythmic-drugs 2026-05-07
concepts/Wide-Complex-Tachycardia WCT (50–80% VT, context-dependent); clinical history PPVs (MI 98%, CHF/angina 100%); AV dissociation visible on ECG in ~1/5 VTs; algorithm taxonomy: multistep (Brugada/Vereckei/LLA), Bayesian (Lau 2000), VT-as-default (Griffith), single-criterion (Pava), point-based (Jastrzebski/Pachón); SWCT electrically constrained (near-identical to baseline) vs VT electrically free; Pachón 4 baseline criteria (100%/99% Sp); automated methods (WCT Formula AUC 0.97, VT Prediction 0.90, WCT Formula II 0.96 — require paired baseline ECG); Brugada Sp 59.5%; Chen LLA Sp 90.8%; Basel SN 93.3%; real-world performance unknown; limitations: fascicular VT, class Ic/III drugs, BBR-VT; default = VT; procainamide drug of choice wide-complex-tachycardia, ventricular-tachycardia, supraventricular-tachycardia, electrocardiography, ECG-algorithm 2026-05-22
concepts/Fascicular-Ventricular-Tachycardia LPF-VT (~80% of fascicular VTs); RBBB+left axis; verapamil-sensitive; Purkinje reentry → fast initial activation → all standard WCT algorithms misclassify as SVT; 4-criterion model vs RBBB+LAHB: atypical V1 + positive aVR + V6 R/S ≤1 + QRS ≤140 ms; ≥3 criteria Sn 82.1%/Sp 78.3% fascicular-ventricular-tachycardia, ventricular-arrhythmias, electrocardiography, idiopathic-VT, verapamil-sensitive 2026-05-21
concepts/Amiodarone-Pulmonary-Toxicity "Amiodarone effect" (ubiquitous asymptomatic lipoid pneumonia) vs "amiodarone toxicity" (9 distinct patterns: CEP/COP/AFOP/amiodaronoma/NSIP-like/IPF-like/DIP/ARDS/DAH); 3-mechanism pathophysiology (cytotoxic/immune/angiotensin); cumulative incidence 4.2%/7.8%/10.6% at 1/3/5 years; 3-fold APT risk per decade >60; DLCO key monitoring marker (≥15% sensitive, isolated decrease alone does NOT warrant stopping); KL-6 NPV 92%; CT density >70 HU absent in 27–55%; surgical biopsy avoid; prednisolone taper ≤5 mg/day; 21–33% hospitalisation mortality amiodarone, drug-induced-lung-disease, pulmonary-toxicity, antiarrhythmic-drugs, drug-toxicity 2026-05-07
concepts/GWAS-Cardiac-Genetics GWAS in inherited cardiac disease + CAD: 346 CAD loci; genetics-to-therapeutics pipeline (PCSK9i/statins/ezetimibe/bempedoic acid/LPA agents/colchicine/ANGPTL3); Mendelian randomization validates LDL-C/Lp(a)/TG and deprioritises HDL-C/CRP/vitamin D; inverse HCM-DCM loci; 21 BrS loci; NOS1AP LQTS modifier; European-ancestry limitation GWAS, polygenic-risk-score, coronary-artery-disease, cardiomyopathy, mendelian-randomization 2026-05-16
concepts/Gene-Editing-Risk-Benefit-Framework Structured criteria for gene editing candidacy in ICCs: WPW (ablation >90% — gene editing disproportionate) vs PRKAG2 syndrome (multisystem monogenic, ablation insufficient — gene editing appropriate); criteria: disease severity, existing therapy effectiveness, monogenic architecture, delivery feasibility gene-editing, CRISPR-Cas9, inherited-cardiac-conditions, gene-therapy, precision-medicine 2026-05-07
entities/PRKAG2-Cardiac-Syndrome Autosomal dominant γ2-AMPK subunit mutation; cardiac hypertrophy + pre-excitation (WPW) + glycogen storage + progressive conduction disease; ablation insufficient; paradigm case where gene editing is appropriate over standard ablation gene-editing, inherited-cardiac-conditions, CRISPR-Cas9, arrhythmia 2026-05-07
concepts/mWHO-Classification Modified WHO 5-tier maternal cardiac risk: Class I (2.5–5%) → IV (40–100%, pregnancy contraindicated); Class IV includes PAH, LVEF <30%/NYHA III–IV, prior PPCM with any residual LV dysfunction, severe MS/AS, systemic RV dysfunction, severe aortopathy >45/50 mm, vascular EDS, complicated Fontan; NT-proBNP >128 pg/mL at 20 wks predicts events; only prospectively validated tool pregnancy, cardiovascular-risk, maternal-health, risk-stratification, guidelines 2026-05-10
entities/Takotsubo International Registry (n=1750; 26 centres): 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 ↑ 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
concepts/Brain-Heart-Axis Bidirectional CNS–cardiac axis; neuropsychiatric comorbidity 55.8% in TTS vs 25.7% ACS; catecholamine-excess hypothesis for TTS; neurogenic stunned myocardium; beta-blocker survival benefit NOT confirmed despite mechanism rationale brain-heart-axis, takotsubo-cardiomyopathy, autonomic-nervous-system, catecholamines, neuro-cardiac 2026-05-10
concepts/Beta-Blocker-Post-MI Beta-blocker therapy after MI: cornerstone in HFrEF/LVEF<40%; LVEF≥50% no-indication: REDUCE-AMI (NEJM 2024) + IPD-MA (NEJM 2026, n=17,801, HR 0.97) — no benefit confirmed; ABYSS (NEJM 2024, n=3,698): NI not met (HR 1.16) but driven by soft CV hosp — hard outcomes identical; SMART-DECISION 2026: discontinuation NI met (HR 0.80); ACC/AHA Class I contradicted by IPD-MA evidence; BLOCK COPD (NEJM 2019): BB without cardiac indication in COPD increases hospitalisation (HR 1.91) — COPD-specific caveat added beta-blockers, myocardial-infarction, secondary-prevention, coronary-artery-disease, preserved-ejection-fraction 2026-05-21
concepts/Potassium-and-Ventricular-Arrhythmias POTCAST (NEJM 2025, n=1200, ICD patients): targeting high-normal K 4.5–5.0 mmol/L reduces composite VT/ICD therapy/arrhythmia hosp/all-cause death HR 0.76 (P=0.01; NNT=12.3); mechanism = avoidance of low-normal K, not achievement of high-normal; benefit present even without reaching target; MRA subgroup HR 0.75 ≈ non-MRA HR 0.77 — potassium rise may explain part of MRA landmark trial benefit ventricular-arrhythmias, potassium, ICD, mineralocorticoid-receptor-antagonist, arrhythmia-prevention 2026-05-16
entities/Frailty-in-Cardiovascular-Disease Frailty/prefrailty in post-MI elderly; SPPB 4–9 as rehabilitation target; Fried criteria; PIpELINe trial (NEJM 2025): multidomain rehab HR 0.57 for CV death/CV hosp, HF hosp HR 0.20; PAD subgroup no benefit frailty, elderly, cardiac-rehabilitation, myocardial-infarction, secondary-prevention 2026-05-16
entities/Sotatercept First-in-class ACTRIIA-Fc activin-signaling inhibitor for PAH; PULSAR→SPECTRA→STELLAR (FC II/III, 84% ↓ clinical worsening)→ZENITH (FC III/IV, REVEAL Lite 2 ≥9, HR 0.24 for death/transplant/hospitalization, stopped early); epistaxis/telangiectasia/↑Hb safety signal pulmonary-arterial-hypertension, sotatercept, activin-signaling, TGF-beta-superfamily, biologic-therapy 2026-05-16
concepts/VT-Ablation-Ischemic-Cardiomyopathy First-line catheter ablation vs antiarrhythmic drugs (sotalol/amiodarone) for VT in post-MI ischemic cardiomyopathy; VANISH2 (NEJM 2025): HR 0.75 composite primary endpoint (P=0.03); mortality NS; biggest effect on treated sub-threshold VT (HR 0.26); drug arm 21.6% nonfatal adverse events; challenges "drugs first" paradigm ventricular-tachycardia, catheter-ablation, ischemic-cardiomyopathy, antiarrhythmic-drugs, ICD 2026-05-16
concepts/ACMG-Secondary-Findings 73-gene ACMG SF v3.0 framework for reporting LP/P variants in clinical ES/GS; 4% population carry ≥1 actionable genotype (Iceland WGS n=57,933); cancer group −3 yr lifespan; LDLR −6.47 yr and MYBPC3 −2.18 yr are only CV genes with individual lifespan signal; KCNQ1/TGFBR2 cause-of-death associated; 10 candidate expansion genes (MYL4/F5-Leiden-hom/PKD1/PKD2) actionable-genotypes, ACMG-secondary-findings, genetics, population-genomics, genetic-testing 2026-05-17
concepts/Colchicine-in-Cardiovascular-Disease Anti-inflammatory secondary prevention: COLCOT (post-MI; 23% RRR) and LoDoCo2 (stable ASCVD; 31% RRR) vs CLEAR (NEJM 2025; n=7,062; HR 0.99; P=0.93 — no benefit), CHANCE-3 (neutral), CONVINCE (neutral); biological-clinical dissociation confirmed in CLEAR (CRP reduced but no MACE benefit); ESC Class IIa and FDA approval pre-date CLEAR; net benefit now uncertain colchicine, anti-inflammatory-therapy, secondary-prevention, acute-myocardial-infarction, coronary-artery-disease 2026-05-18
entities/COPD COPD as comorbidity in HFpEF: present in 14–34% of HFpEF populations; independent prognostic risk factor — hospitalization RR 1.66, all-cause mortality RR 1.62, post-discharge mortality RR 2.57 (meta-analysis, n=18,602); shared microvascular inflammation pathway; SGLT2i and ARNI (sacubitril/valsartan) as dual-benefit candidates; BLOCK COPD (NEJM 2019): metoprolol without cardiac indication increases COPD hospitalisation (HR 1.91); bisoprolol MA (Feng 2023; 35 RCTs): FEV1 +0.46 L, ↓IL-6/IL-8/CRP — effect independent of HF but low-quality evidence; active contradiction between bisoprolol MA and BLOCK COPD awaiting RCT resolution COPD, HFpEF, heart-failure, comorbidities, prognosis 2026-05-21
entities/AL-Amyloidosis Plasma cell dyscrasia producing misfolded immunoglobulin light chains (75–80% lambda); cardiac (70–80%, leading cause of death) and renal (60–70%) most common; daratumumab-CyBorD preferred first-line (ANDROMEDA: 78% VGPR+); SCT 10–20% eligible (CR 40%, median OS 7.6 yr); 5-year survival 15%→48% (1980s→2010s); antifibril antibodies (birtamimab, anselamimab) in phase 3; mass spectrometry gold standard for AL vs ATTR fibril typing al-amyloidosis, plasma-cell-dyscrasia, cardiac-amyloidosis, amyloidosis, hematology 2026-05-18
concepts/AL-Amyloidosis-Staging Mayo 2004 (NT-proBNP + troponin; best early death), Mayo 2012 (adds dFLC >180 mg/L; best late survival), European modification (NT-proBNP >8500 = stage IIIb), Boston University (BNP + troponin I), renal staging (24h protein + eGFR); dFLC <50 mg/L = excellent prognosis regardless of cardiac stage; organ response: cardiac 24 months, renal 29 months, hepatic 35 months; dFLC utility diminishing in modern daratumumab era al-amyloidosis, amyloid-staging, plasma-cell-dyscrasia, cardiac-amyloidosis, biomarkers 2026-05-18
entities/MASLD MASLD (formerly NAFLD): 38% adult prevalence; CVD is leading cause of death; increases CV events ×1.5 (×2.5 with advanced fibrosis), AF ×1.2–1.5, HF ×1.2–1.5, T2DM ×2.2; FIB-4 for staging; resmetirom first FDA-approved drug (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%); FGF21 analogues (efruxifermin SYMMETRY: cirrhosis reversal 29% vs 11%); SGLT2i (dapagliflozin: fibrosis reduction 45% vs 20%); no head-to-head comparisons; combination therapy next frontier MASLD, metabolic-syndrome, cardiovascular-risk, GLP-1-agonists, resmetirom 2026-05-18
concepts/Mineralocorticoid-Receptor-Antagonists-Post-MI MRA evidence in AMI: eplerenone Class I/A in MI+LVEF<40%+HF/DM (EPHESUS: 15% RRR); spironolactone Class I/A in HFrEF (RALES: 30% RRR); CLEAR (NEJM 2025; n=7,062; largest AMI RCT): routine spironolactone 25 mg neutral (HR 0.91/0.96; ITT); on-treatment HR 0.79/0.83 approaching significance; LVEF data not collected; gynecomastia 2.3%, hyperkalemia 1.1%, eGFR −1.8 ml/min/1.73m²; MRA benefit is EF/HF-dependent not a class effect across all AMI patients spironolactone, acute-myocardial-infarction, mineralocorticoid-receptor-antagonist, randomized-controlled-trial, STEMI 2026-05-18
entities/FBN1 Fibrillin-1 gene (15q21.1); 65 exons; haploinsufficiency threshold mechanism; TGF-β sequestration role; EGF-like domain mutations; >500 private mutations; also causes MASS phenotype, familial ectopia lentis, Weill-Marchesani, Shprintzen-Goldberg marfan-syndrome, fibrillin-1, connective-tissue-disorders, genetics 2026-05-23
entities/Loeys-Dietz-Syndrome TGFBR1/TGFBR2 LOF → paradoxically enhanced aortic TGF-β signalling; MFS overlap + hypertelorism, bifid uvula, arterial tortuosity; diffuse aneurysms dissecting at smaller diameters; critical Marfan differential; vascular disease more aggressive marfan-syndrome, connective-tissue-disorders, aortic-aneurysm, tgf-beta-signaling, genetics 2026-05-23
entities/Aneurysm-Osteoarthritis-Syndrome SMAD3 inactivating mutations; aortic aneurysms + arterial tortuosity + early-onset osteoarthritis + LDS-like craniofacial features; paradoxical TGFβ upregulation despite LOF; grouped with MFS-related aortopathies connective-tissue-disorders, aortic-aneurysm, tgf-beta-signaling, genetics, related-marfan-diseases 2026-05-23
concepts/PCSK9-Inhibitors PCSK9 biology (LDL receptor recycling; GoF/LoF variants); evolocumab 60% LDL-C reduction; alirocumab; FOURIER (HR 0.85 primary/HR 0.80 secondary; PAD −42% limb events); ODYSSEY Outcomes (HR 0.85; nominal 15% all-cause mortality); LDL-C benefit to <10 mg/dL; very-low LDL-C safe; optimal patient selection; inclisiran siRNA Q6 months PCSK9-inhibitors, cardiovascular-outcomes, LDL-cholesterol, dyslipidemia, lipid-lowering-therapy 2026-05-23
entities/Evolocumab Fully human PCSK9 mAb (Repatha/Amgen); 140 mg Q2W or 420 mg monthly; ~60% LDL-C reduction; HoFH genotype table (null-null: no response; defective: 47%); FOURIER CVOT HR 0.85/HR 0.80; PAD subgroup 42% major adverse limb event reduction; no neutralizing antibodies; EBBINGHAUS neurocognitive substudy PCSK9-inhibitors, LDL-cholesterol, cardiovascular-outcomes, lipid-lowering-therapy, monoclonal-antibody 2026-05-23
entities/Alirocumab Fully human PCSK9 mAb (Praluent/Regeneron-Sanofi); titrated 75→150 mg Q2W or fixed 300 mg Q4W; ~60% LDL-C at max dose; HoFH highly genotype-dependent; ODYSSEY Outcomes CVOT (n=18,924; post-ACS; HR 0.85; nominal 15% all-cause mortality; not statistically significant in hierarchy) PCSK9-inhibitors, LDL-cholesterol, cardiovascular-outcomes, lipid-lowering-therapy, monoclonal-antibody 2026-05-23
entities/Inclisiran GalNAc-siRNA PCSK9 inhibitor; RISC-catalytic durable hepatic mechanism; plasma t½ <48h; ORION-10+11 Phase 3 (NEJM 2020; n=3,178): SC 284 mg Q6m → LDL-C −52.3%/−49.9% (P<0.001), PCSK9 −83%/−79%; safety comparable to placebo except mild ISAEs; ORION-4 CVOT (Lancet 2024): HR 0.84 (P=0.01; did not meet pre-specified P<0.005 threshold — statistically neutral by own criteria) PCSK9-inhibitors, LDL-cholesterol, siRNA, lipid-lowering-therapy, RNA-therapeutics 2026-05-27
concepts/Atherosclerosis-Pathophysiology Plaque initiation (endothelial damage → Ox-LDL deposition); foam cell cycle (macrophage scavenger receptor → cytokines → monocyte recruitment); minimally vs extensively oxidized LDL; myeloperoxidase/lipoxygenase; HDL oxidation impairs reverse cholesterol transport; TLR4/NF-κB as chronic inflammatory driver; PCSK9's role in macrophage activation + VSMC transformation; PCSK9-resistin CRD structural homology hypothesis atherosclerosis, inflammation, oxidative-stress, foam-cells, cardiovascular-disease 2026-05-24
concepts/Cardiogenic-Shock CS = cardiac disorder causing end-organ hypoperfusion; 30–40% short-term / ~50% 1-year mortality; AMI-CS vs HF-CS phenotypes; SUSPECT CS mnemonic (7-component); SCAI A–E staging; Recognize/Rescue→Optimize→Stabilize→De-Escalate/Exit framework; Level 1/2/3 CS center tiers; norepinephrine first-line vasopressor; DanGer Shock 12.7% absolute mortality reduction with microaxial flow pump in STEMI-CS (first positive tMCS RCT); IABP-SHOCK II and ECLS-SHOCK negative; Stage B highest escalation risk within 24h cardiogenic-shock, mechanical-circulatory-support, heart-failure, acute-myocardial-infarction, hemodynamic-monitoring 2026-05-25
concepts/SCAI-Shock-Classification Five-stage (A–E) CS severity system: Stage A (at risk) → E (extremis/cardiac arrest); stepwise mortality A ~3% → E ~67%; Stage B = highest risk of shock escalation within 24h; most patients change stage within 24h; used for triage, transfer decisions, tMCS escalation thresholds cardiogenic-shock, risk-stratification, hemodynamic-monitoring, guidelines 2026-05-25
concepts/Temporary-Mechanical-Circulatory-Support tMCS in CS — goals: ventricular unloading + systemic perfusion; DanGer Shock (microaxial flow pump, STEMI-CS): +12.7% 180-day survival = first positive tMCS RCT; IABP-SHOCK II (IABP, AMI-CS): neutral at 30 days and 6 years; ECLS-SHOCK (VA-ECMO, AMI-CS): neutral; routine tMCS strongly discouraged; weaning protocol: stepwise 0.5–1 L/min decrease every 2–4h; major complications: bleeding (60%) and limb ischemia (4×) cardiogenic-shock, mechanical-circulatory-support, acute-myocardial-infarction, heart-failure, hemodynamic-monitoring 2026-05-25
concepts/Adult-Immunization-CVD ACC 2025 CCG vaccination framework for CVD patients: influenza (annual; MACE RR 0.64; IAMI HR 0.72 post-MI; 6× acute MI risk with infection); pneumococcal (PCV20/PCV21; HTN alone not qualifying); COVID-19 (annual; 3× severe disease risk in CVD; mRNA myocarditis 1–19/million, benign); RSV (one-time ≥60–75y; ~80% efficacy year 1); zoster (2-dose Shingrix ≥50y; MI/stroke/HF/arrhythmia reduction lasting 8yr); cardiovascular-focused messaging most effective for uptake vaccination, cardiovascular-prevention, influenza, immunization, preventive-cardiology 2026-05-25