Atrial Standstill: From Molecular Genetics to Clinical Management — A Narrative Review

Authors, Journal, Affiliations, Type, DOI

• Authors: Min Lin and Xiaoqi Deng (equal contribution), Yu Xia, Yong Yang, Hairui Li, Xiangbin Meng, Ligang Ding, Haiying Li — Division of Cardiac Arrhythmia, Cardiac and Vascular Center, The University of Hong Kong–Shenzhen Hospital, Shenzhen; Cardiac Arrhythmia Center, Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing; Pengcheng Laboratory, Shenzhen
• Journal: Heart Rhythm. 2026 (Heart Rhythm Society); 15 pages
• Type: Narrative review with dual-author screening; no formal quality appraisal, no meta-analysis
• DOI: https://doi.org/10.1016/j.hrthm.2026.09.030
• AI disclosure: the authors state that Claude Code with the DeepSeek V4 Pro model was used to improve language and readability and to assist reference verification.

Overview

Atrial standstill is the complete absence of atrial electrical and mechanical activity caused by diffuse atrial myocardial disease — not sinus node failure. The atrium is present, dilated, often fibrotic, and electrically inexcitable: intracardiac recordings show no atrial electrograms and pacing at maximal output (≥10 mA, 2 ms) fails to capture. It is routinely mistaken for atrial fibrillation with a slow ventricular response, and it carries a thromboembolic burden of 30–54% that conventional AF risk scores systematically underestimate.

The review's contribution is to organise a literature that consists almost entirely of case reports into three convergent molecular pathways — ion channel/gap junction (SCN5A ± GJA5), natriuretic peptide (NPPA), and nuclear envelope (EMD/LMNA) — each mapping onto a different EHRAS histological class, while all ending in the same electrical silence. It then shows that this shared endpoint does not produce shared management: pacing mode, ICD eligibility and anticoagulation are decided by genotype, and the EMD-versus-LMNA divergence is the single most actionable discrimination in the whole field.

Keywords

Atrial standstill · atrial cardiomyopathy · atrial inexcitability · SCN5A · NPPA · Emery-Dreifuss muscular dystrophy · electroanatomic mapping · thromboembolism · atrial quiescence

Key Takeaways

Methods and case definition

• PubMed and Embase searched March 2026 with 12 synonym phrases, no date or language restriction: 264 + 330 records → 393 unique after deduplication → 401 screened after 8 hand-added references and backward citation tracking.
• The diagnostic criterion for inclusion was electrophysiologically confirmed AS: absent atrial electrical activity on intracardiac recordings and failure of atrial capture at maximal pacing output (≥10 mA, 2 ms).
• Studies reporting only surface ECG findings were kept for historical context; transient drug-induced AS was excluded from the primary analysis.
• No meta-analysis was possible — the evidence base is entirely case reports, case series and retrospective cohorts. All treatment recommendations are level C.

Terminology

Historical perspective

• Cushny induced AS experimentally with digitalis in dogs in 1897; Rosenbaum and Levine's 1939 review of 8 confirmed cases established it clinically.
• Bloomfield and Sinclair-Smith (1965) reported the first electrogram-confirmed persistent AS and proposed the temporary / terminal / persistent categories still in use.
• Allensworth et al. (1969) made the decisive distinction — atrial myocardial disease, not sinus node disease — and their index kindred had atrial amyloidosis on biopsy.
• Waldo et al. (1972) separated reversible atrial quiescence from irreversible persistent AS in the post-cardiac-surgery setting.
• Disertori et al. (1983) described 8 cases across 3 families in a community of 900 — endemic familial clustering with a ~30% cerebral embolism rate.
• 2003 onward: Groenewegen identified the first SCN5A mutation, Makita confirmed the digenic SCN5A + GJA5 model, Disertori discovered the homozygous NPPA pathway.

Clinical features

• Demographics track etiology. NPPA-related atrial dilated cardiomyopathy presents in adulthood, autosomal recessive, with age-dependent penetrance. X-linked EMD affects predominantly males (~80%); autosomal dominant LMNA shows female predominance in some series (73%). SCN5A-related congenital AS affects males from infancy to adolescence. Idiopathic fibrotic atrial cardiomyopathy presents at a mean age of 46 ± 13 years.
• Palpitations are the most common presenting symptom (~54% in the NPPA series). Dyspnoea presented in 4 of 13 NPPA patients (31%), usually NYHA I–II.
• Syncope and presyncope come from severe bradycardia or prolonged pauses; Holter monitoring has recorded maximum RR intervals of 5.42–6.65 s and episodes of 10–15 s of ventricular asystole.
• Stroke or TIA is the presenting manifestation in 8% of NPPA patients and 22% of EDMD patients, and has occurred in a girl aged 7 years.
• Bradycardia with absent "a" waves on the jugular venous pulse is near-universal.

ECG and intracardiac electrogram characteristics

• Core ECG feature: complete absence of P waves in all 12 leads, with a regular slow junctional escape (30–55 bpm) or a ventricular escape (30–40 bpm, QRS ≥0.12 s).
• Incomplete AS may instead show an irregular junctional rhythm with residual low-amplitude atrial activity confined to the septal region.
• QRS is typically normal in isolated atrial disease, but His-Purkinje involvement — common with SCN5A — produces bundle branch block and a prolonged HV interval.
• Evolutionary sequence: low-amplitude P waves and PR prolongation → AF/flutter with diminishing fibrillation-wave amplitude → partial AS with irregular junctional rhythm → complete AS with regular junctional or ventricular bradycardia and no atrial activity on intracardiac recordings.
• Figure 1 shows the accompanying echocardiographic signature: preserved E wave on mitral inflow with absent A wave, and absent a′ on septal tissue Doppler.

Natural history

• NPPA-ADCM: subclinical disease (<20 years) → early adult biatrial dilatation and atrial tachyarrhythmias (brady-tachy syndrome) → progressive atrial voltage reduction → complete AS → end-stage giant atria with preserved LVEF (54–74%). Thromboembolism 54% (7/13); death 38% (5/13).
• EDMD: sinus rhythm → low P-wave amplitude and PR prolongation → AF/AFL (61%) → AS (28% overall, 45% of those who had AF/AFL) → complete AV block → pacemaker dependency (100%).
• The EMD–LMNA divergence (Marchel et al.): AS in 14 of 30 EMD (46.7%) versus 0 of 15 LMNA (0%), P=.001; non-sustained VT/VT in 9 of 15 LMNA (60%) versus 2 of 30 EMD (6.7%), P<.001; ICD implantation 60% in LMNA versus 3.3% in EMD.

Genetic architecture

Three independent pathogenic pathways, each with a different tissue-level pathology and EHRAS class:

SCN5A (3p21, Nav1.5). Loss of function — reduced peak I_Na, hyperpolarising shift of inactivation, slowed recovery, haploinsufficiency. The proposed mechanism is "exit block": because sinus node pacemaking is driven primarily by Ca²⁺ channels, loss of SCN5A does not directly affect automaticity; the lesion is failure of impulse conduction from the sinus node into surrounding atrial myocardium. This hypothesis remains experimentally unconfirmed. gnomAD LOEUF for SCN5A is 0.42 — above the <0.35 haploinsufficiency threshold — so heterozygous loss of function is tolerated in the general population, and clinical disease likely requires coinherited modifiers or a second variant. Biallelic variants confer severe early-onset disease.

Digenic inheritance. GJA5 encodes connexin 40, the principal atrial gap junction protein. Two promoter polymorphisms (c.-44G>A and c.171A>G, in complete linkage disequilibrium) cut Cx40 promoter activity below 50%. In the Dutch and Japanese families, full phenotypic expression occurred only in individuals carrying both an SCN5A mutation and the Cx40 polymorphisms. The model rests on 2 families and has not been independently replicated in 20 years; the homozygous Cx40 polymorphism frequency is ~5.1% in the Japanese general population, so thousands likely carry the at-risk digenic combination without developing AS.

Key SCN5A variants: p.Leu212Pro, p.Asp1275Asn (the canonical digenic example), p.Val1340Leu (~50% I_Na reduction, homozygous/consanguineous), p.Arg222Gly (autosomal dominant, progressive biatrial dilatation).

Biallelic SCN5A (systematic review of 61 patients): sick sinus syndrome in 65%, AS in 59%, device implantation in 76%, major cardiac events in 50%, mortality 15% at a mean age of 9 years. Non-missense variants carry earlier onset and higher event risk.

SCN5A pleiotropy. The same variant can produce Brugada syndrome, LQT3, conduction disease, cardiomyopathy or AS in different family members. Cascade screening must therefore evaluate the full phenotype (BrS ECG, QTc, PR/QRS). Class Ic antiarrhythmics are contraindicated.

EMD (Xq28, emerin). An inner nuclear membrane protein that also localises to cardiac desmosomes and fasciae adherentes. X-linked recessive. Buckley et al. called AS "virtually characteristic" of EDMD, and 33% of all reported AS cases are attributable to EDMD. In Boriani's series 61% developed AF/AFL, of whom 45% progressed to AS. Emerinopathy with LV noncompaction can produce ventricular fibrillation.

LMNA (1q21.2–q21.3, lamins A/C). Autosomal dominant. By contrast with EMD, AS is rare in LMNA (0% in the Marchel cohort, though reported elsewhere); ventricular arrhythmias dominate (nsVT/VT 60%) and ICD requirement is high (60%), guided by the LMNA risk calculator (≥2 of male sex, non-missense, LVEF <45%, nsVT). Sudden cardiac death is the most common mode of death in LMNA carriers (46% of deaths in the van Berlo meta-analysis).

Molecular pathogenesis (nuclear envelope). Mutant lamin A/C activates TGFβ–ERK1/2–CTGF/CCN2 fibrotic signalling and Akt/mTOR pathways; rapamycin delays cardiomyopathy in Lmna H222P mice. LINC complex disruption and aberrant connexin 43 redistribution contribute to gap junction remodelling. Importantly, van Rijsingen found a prothrombotic state in LMNA carriers — increased thrombin generation and abnormal platelet function — independent of atrial tachyarrhythmias and LVEF (HR 4.8, 95% CI 2.2–10.6).

NPPA (1p36.22, prepro-ANP). Disertori identified the homozygous missense p.Arg150Gln in a 37-year follow-up cohort from Northeast Italy: LOD 3.38 (P=.002); all affected individuals homozygous; heterozygotes asymptomatic with normal ANP; median MR-pro-ANP 14.5 pmol/L in homozygotes (normal 18–120); SCN5A, GJA5, LMNA and EMD all sequenced and excluded; variant allele frequency in NHLBI ESP 0.015%.

• Phenotype: adult-onset biatrial dilatation to giant dimensions (RA volume up to 744 mL), early supraventricular arrhythmias evolving to complete AS, preserved LV function long-term (LVEF 54–74%), NYHA I–II. Thromboembolism 54% (7/13); mortality 38% (5/13 — 1 stroke, 4 sudden deaths; without autopsy, arrhythmic and thromboembolic causes could not be separated).
• Mechanism: loss of ANP function causes progressive atrial interstitial fibrosis and myocyte loss (consistent with Nppa⁻/⁻ mice) — the opposite of the SCN5A "primary electrical disease" model. Heterozygous NPPA frameshift mutations instead raise ANP, shorten atrial action potential duration and cause familial AF without severe dilatation or AS.
• A dual-mechanism model — loss of ANP signalling plus proteotoxic endoplasmic reticulum stress from mutant pro-ANP misfolding — remains experimentally unresolved.
• All genetically confirmed cases descend from a single founder population in Northeast Italy (6 families). Global prevalence beyond it is unknown.

Genes with limited evidence. CAV3 p.Leu84Pro in a single 12-year-old with progressive AS — a VUS, unreplicated, plausibly impairing Nav1.5 trafficking. RYR2 with AS and CPVT in 2 families, though the phenotype overlaps CPVT substantially. HCN4 in a single patient with AS and ischaemic stroke.

Population genetics. The ACMG/AMP framework was not designed for digenic inheritance — an SCN5A VUS may warrant reclassification in the presence of the Cx40 modifier genotype. gnomAD LOEUF (v2.1): LMNA 0.18 and EMD 0.31 are strongly constrained (<0.35); SCN5A at 0.42 is moderately constrained.

Cardiac imaging

LGE-MRI. Disertori compared LGE-MRI with electroanatomic mapping in NPPA carriers. Partial AS showed RA fibrosis of 36–70% and LA fibrosis of 63–82% (Utah stage IV). Advanced disease showed RA >35% and LA >50%, predominantly septal and extending to the RA free wall. Ventricular LGE was negative in all 21 patients imaged — a key criterion for excluding ventricular cardiomyopathy. CMR atrial dimensions were far larger than controls (RA area 25.0 ± 9.8 vs 14.2 ± 3.6 cm², P=.002). These percentages come from a single-centre 2014 protocol, and atrial LGE quantification remains technically difficult with limited interobserver reproducibility; Ju et al. found poor inter- and intraobserver reproducibility in idiopathic fibrotic ACM.

Echocardiography is the first-line screening modality. The characteristic triad:

1. Absent A wave on pulsed-wave Doppler of mitral/tricuspid inflow
2. Absent atrial wall motion on M-mode/2D
3. Biatrial dilatation (extreme in advanced cases)

An absent A wave is nonspecific — it also occurs in AF, junctional rhythm and post-cardioversion atrial stunning — so the triad raises suspicion but does not establish the diagnosis, which requires invasive confirmation. Bellmann et al. showed that newly emergent A waves after EAM-guided atrial lead implantation verified atrial capture in 3 of 4 patients, with 81–100% atrial pacing at 3.5 years.

Computed tomography is the anatomical gold standard for atrial volume. In NPPA patients: complete AS — LA 253 mL/m², RA 443 mL/m²; partial AS — LA 72–105, RA 98–195 mL/m². CT volumes systematically exceed echocardiographic volumes.

Electrophysiological studies and electroanatomic mapping

• Three voltage tiers: normal/preserved >0.5 mV bipolar; low-voltage zone 0.1–0.5 mV; scar/electrical silence <0.05–0.1 mV.
• Diagnostic hallmarks: absent atrial electrograms on intracardiac recordings plus failure of atrial capture at 10 mA, 2 ms. In advanced AS nearly the entire RA endocardial surface is electrically silent.
• Disease staging by EAM (Disertori): early-stage RA low voltage occupied 68.5 ± 6.0% of the RA surface with scar at 22.2 ± 10.2%; advanced-stage low voltage rose to 99.5 ± 0.7% with scar at 57.5 ± 33.2%.
• Canonical scar progression (Nakazato, 11 patients, >9 RA sites): high lateral RA → mid-lateral RA → low lateral RA → interatrial septum → peritricuspid annular region → coronary sinus ostium. Repeat studies in 2 patients confirmed this proximal-to-distal spread. Ju's mapping localised RA silence predominantly to the posterolateral wall and LA silence to the anterior wall — not fully concordant with Nakazato, so individual variation should be anticipated.
• Residual atrial activity matters. Massumi described "small discrete areas of independent atrial electrical activity interspersed within large scar zones." Baskar identified viable atrial tissue in the low RA septum only under isoproterenol challenge in an 11-year-old SCN5A compound heterozygote. The coronary sinus musculature can act as an isolated "fifth chamber," sustaining independent flutter or fibrillation that cannot be connected to the inert RA.
• His-Purkinje involvement is common. In Nakazato's series 2 patients had complete HV block and 1 had HV prolongation; Lehmann reported RBBB with HV intervals of 90–100 ms in an SCN5A p.Arg222Gly family.
• Progressive atrial lead failure with complete loss of sensing and capture within 3–8 years is common across etiologies.

Complications

Thromboembolism — the most preventable complication. Rates are consistent across etiologies: EDMD/LMNA 22%; NPPA-ADCM 54%; familial endemic AS ~30%. In a paediatric multicentre series, 35% (7 of 20) had TEs over a median 6.9 years — none of the 7 had functional atrial pacing, 6 were not anticoagulated, and 1 received aspirin alone.

Stroke risk in AS is driven by etiology-specific prothrombotic mechanisms rather than traditional AF risk factors. EDMD patients suffered disabling strokes before age 45. Beyond LMNA's HR of 4.8, population data show isolated sinus node dysfunction independently raises ischaemic stroke risk (subdistribution HR 2.28, UK Biobank) and sick sinus syndrome elevates stroke risk in AF with low CHA₂DS₂-VASc scores (HR 2.13). Atrial electrical disease therefore confers thromboembolic risk independently of AF, with AS at the extreme end of that continuum.

The conventional scores fail quantitatively. Untreated AS accrues a 33–54% cumulative burden — comparable to the highest-risk AF patients (CHA₂DS₂-VASc 8–9 carries 11–12% annual stroke risk, so a score-9 patient accrues that burden in ~3–5 years). Yet most AS patients are young, and CHA₂DS₂-VASc 0–1 predicts only 0.2–0.6% per year; their observed risk (~5% per year in the paediatric series) is an order of magnitude higher. ARCADIA, the closest randomised evidence, does not test anticoagulation in AS.

Heart failure is etiology dependent. In LMNA carriers, LVEF ≤50% rose from 44% at first contact to 57% during follow-up, and end-stage HF (inotropes, mechanical support or transplant) developed in 19%. NPPA-ADCM retains preserved LV function over 37 years — a genuine primary atrial cardiomyopathy. VVI pacing-associated AV dyssynchrony is one of the mechanisms of haemodynamic decompensation, alongside loss of the atrial booster pump (normally 20–30% of ventricular end-diastolic volume) and giant atrial dilatation causing annular dilatation with severe TR/MR.

Sudden cardiac death is genotype specific. In LMNA, SCD is the most common mode of death (46%). In EMD the risk is substantially lower (nsVT/VT 6.7%, ICD 3.3%), though from only 30 patients. In NPPA-ADCM, 4 out-of-hospital sudden deaths occurred without documented ventricular arrhythmias and without autopsy. With biallelic SCN5A, major cardiac events occurred in 50% and 15% died at a mean age of 9 — and haemodynamic collapse can occur in the absence of arrhythmia or device failure, extending the phenotype beyond rhythm disturbance.

Supraventricular arrhythmias are common in early-phase disease: 80% of children in the Howard series had atrial or supraventricular arrhythmias, and AF/AFL precedes AS in 61% of EDMD patients. In partial AS, surviving islands can sustain organised atrial tachycardia, and isolated coronary sinus flutter has been described.

Differential diagnosis and acquired etiologies

The distinction from sinus node dysfunction is fundamental: in SND the atrial myocardium remains excitable and captures with pacing; in AS, capture fails at maximal output, confirming the atrial myocardial substrate as the primary pathology.

• Cardiac amyloidosis (AL and ATTR) warrants consideration because identifying it may alter systemic therapy — though tafamidis has not been studied for reversal or prevention of AS in ATTR.
• Myocarditis (viral, eosinophilic, giant cell) may produce transient or permanent AS and can reverse with immunosuppression. Serial ECG and Holter at 1, 3 and 6 months are suggested, though no evidence-based protocol exists.
• Hyperkalaemia is the most common reversible mimic.
• Chagas cardiomyopathy remains important in endemic Latin America; cardiac sarcoidosis is rare but treatable.
• Drug-induced AS (digitalis) is largely of historical interest but establishes the principle of reversibility on withdrawal.
• Post-cardiac-surgery atrial quiescence reverses with isoproterenol; untreated patients in the original series reverted spontaneously within 24 hours. Failure to recover suggests underlying structural atrial disease.
• Extensive AF ablation can cause iatrogenic LA standstill with preserved RA, with TE risk driven by LA scar extent.
• AS has also been reported with LV noncompaction, so comprehensive imaging is needed to exclude concomitant ventricular disease.

Workup for confirmed AS: 3-generation family history; skeletal muscle examination for subclinical EDMD; serum potassium; echocardiography with Doppler; LGE-MRI. Suspected amyloidosis → serum free light chains plus ⁹⁹ᵐTc-PYP/DPD/HMDP scintigraphy; suspected sarcoidosis → FDG-PET with tissue biopsy; suspected haemochromatosis → ferritin. Genetic panel covering SCN5A, LMNA, EMD, NPPA, GJA5, CAV3, HCN4, plus a concurrent neuromuscular panel (EMD, LMNA, FHL1) when skeletal muscle involvement is present.

Treatment strategies

No randomised controlled trial exists for any intervention. Strength categories in the paper reflect author consensus, not formal guideline grading.

Pacing.

• Symptomatic bradycardia mandates permanent pacing — uniformly endorsed, though a no-pacing comparator is ethically impossible.
• In complete AS, VVI/VVIR is the default mode (9 of 10 implants in Boriani's series).
• In partial AS, EAM-guided localization of viable atrial myocardium can achieve DDD pacing and cut the right ventricular pacing burden from 100% to 4–19%. Dual-chamber pacing through the proximal coronary sinus has also been reported (93.7% atrial pacing, stable beyond 2 years).
• Whether maintaining atrial pacing reduces thromboembolic risk is unresolved: none of the 7 paediatric patients with TEs had functional atrial pacing, but only 4 of 15 in whom atrial leads were attempted achieved capture.
• LBBAP has been reported in 1 case only — insufficient evidence, and a theoretical concern about septal pacing in pre-existing His-Purkinje disease (SCN5A/LMNA). Leadless pacemakers are VVI-only and may suit 15–20%, though giant RA anatomy complicates implantation.

ICD is gene specific. EMD favours pacemaker (76.7% implantation) with ICD rarely required (3.3%). LMNA favours ICD for primary prevention (60%) and CRT-D for LV dysfunction with wide QRS. In biallelic SCN5A-AS the high rate of ventricular arrhythmia and major cardiac events (50%) argues for more aggressive ICD consideration.

Anticoagulation. The authors state that confirmed complete AS warrants anticoagulation across all etiologies, not withholding it on the basis of etiology alone, and reserving monitoring off anticoagulation for a contraindication or prohibitive bleeding risk. Their tiers stratify the strength of direct evidence, not whether to anticoagulate:

• Antiplatelet therapy is inadequate — in Boriani's series strokes occurred in patients on aspirin and in patients on no antithrombotic therapy.
• NOAC use is off-label, extrapolated from AF data; no AS-specific data exist.
• Paediatric considerations: warfarin in growing children, cumulative bleeding risk and age-specific dosing are all difficult. Dabigatran and rivaroxaban were both FDA-approved in 2021 for paediatric venous thromboembolism, offering alternatives to warfarin, but paediatric AS data remain absent. Decisions require multidisciplinary input.
• Periprocedural: uninterrupted or minimally interrupted anticoagulation is preferred for device procedures (consistent with BRUISE CONTROL). If TEE shows spontaneous echo contrast or LA/LA appendage thrombus, anticoagulation should be started regardless of etiology.

Genetic counseling and family management

• Reproductive options (prenatal diagnosis, preimplantation genetic diagnosis) should be discussed for autosomal recessive NPPA.
• Predictive testing in minors raises ethical complexity where penetrance is adult onset (NPPA penetrance begins after age 20).
• In EDMD, cardiac involvement can be life threatening even when skeletal muscle disease is mild, mandating independent cardiac surveillance per the 2017 AHA scientific statement.

Discussion

• Entity or spectrum? Within the EHRAS classification, AS represents the most extreme manifestation of fibrotic atrial cardiomyopathy (classes II–III). Diagnostic criteria are uniform regardless of etiology, yet management is gene specific: AS as a syndrome is the operative framework when diagnosing and anticoagulating; the etiology within the EHRAS spectrum is decisive when selecting device type and planning family screening.
• The EMD–LMNA divergence is the single most clinically actionable finding in the field, because it directly determines ICD eligibility.
• The generalizability problem: the clinician evaluating a sporadic AS case — the most common scenario — must extrapolate from founder populations and multiplex families.
• EAM and LGE-MRI enable precision management — EAM establishes the partial-to-complete spectrum, quantifies scar burden and identifies viable pacing sites; LGE-MRI gives non-invasive fibrosis estimation and excludes ventricular involvement.
• Registry proposal: a dedicated international registry with tiered enrolment — tier 1 EP-confirmed AS with full phenotyping, tier 2 clinically suspected AS without invasive confirmation, tier 3 asymptomatic mutation carriers identified by cascade screening — to escape the ascertainment bias of EP-only confirmation.

Limitations of the document

• Narrative review with no formal quality appraisal and no meta-analysis. The authors state plainly that all treatment recommendations are level C, and their strength categories reflect author consensus rather than guideline grading.
• The whole evidence base is case reports, case series and retrospective cohorts, selected for electrophysiologically confirmed disease — which inflates the observed severity distribution. Complication rates (30–54% thromboembolism; 46% SCD in LMNA) may overestimate true population risk; the prevalence of partial AS is probably higher and its natural history possibly more benign.
• Founder populations dominate the genotype-specific estimates. NPPA p.Arg150Gln is known from 6 families in one Italian community, and its 54% thromboembolic rate rests on 7 events in 13 patients.
• The digenic SCN5A + GJA5 model rests on 2 families and has never been independently replicated.
• LBBAP evidence is a single case report with short-term follow-up.
• Atrial LGE quantification is not standardised and reproducibility is poor.
• No cost, access or device-availability analysis, despite recommending EAM and LGE-MRI as best-practice standards — both are unavailable in much of the world.
• The authors disclose AI-assisted language editing and reference verification; a handful of reference numbers are duplicated in the converted text.

Key Concepts Mentioned

concepts/Atrial-Standstill · concepts/Atrial-Cardiomyopathy · concepts/Atrial-Failure · concepts/Sinus-Node-Dysfunction · concepts/Atrioventricular-Block · concepts/Permanent-Pacing-Indications · concepts/Cascade-Family-Screening · concepts/Late-Gadolinium-Enhancement · concepts/Sudden-Cardiac-Death

Key Entities Mentioned

entities/SCN5A · entities/LMNA · entities/EMD · entities/NPPA · entities/Brugada-Syndrome · entities/ATTR-Amyloidosis · entities/AL-Amyloidosis · entities/NDLVC · entities/DCM · entities/Atrial-Fibrillation

Named but unlinked: GJA5 (connexin 40) · CAV3 · RYR2 · HCN4 · FHL1 · EHRAS classification · ARCADIA trial · BRUISE CONTROL · Marchel cohort · van Rijsingen cohort

Wiki Pages Updated

• concepts/Atrial-Standstill — created
• entities/EMD — created
• entities/NPPA — created
• entities/SCN5A — expanded with exit-block mechanism, digenic model, biallelic disease burden
• entities/LMNA — corrected: AS is rare in LMNA and characteristic of EMD
• concepts/Atrial-Cardiomyopathy — linked AS as the extreme end of the fibrotic spectrum
• concepts/Atrial-Failure — linked
• concepts/Sinus-Node-Dysfunction — added the excitability-based distinction
• concepts/Permanent-Pacing-Indications — added AS pacing strategy
• concepts/Cascade-Family-Screening — added AS inheritance patterns
• index — hub entry added
• wiki/wikiindex — rows added
• wiki/sourceindex — row added