Sudden Cardiac Death Prediction in Arrhythmogenic Right Ventricular Cardiomyopathy

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Definite arrhythmogenic right ventricular cardiomyopathy (ARVC) (n=864). Intervention: 4-variable clinical prediction model (younger age, male sex, 24-hour PVC count, number of leads with T-wave inversion). Primary outcome: Time to first life-threatening ventricular arrhythmia (LTVA), a composite of sudden cardiac death (SCD), aborted SCD, ventricular fibrillation, and rapid ventricular tachycardia (>250 beats per minute) that was either sustained (≥30 seconds) or terminated by ICD (C-index 0.74, 95% CI 0.69-0.80).

Q: What does this research mean for the field?

A 4-predictor clinical model incorporating age, sex, 24-hour premature ventricular complex count, and number of leads with T-wave inversion predicts life-threatening ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy with an optimism-corrected C-index of 0.74. Novelty: ClaimNovelty.METHODOLOGICAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Julia Cadrin‐Tourigny; Laurens P. Bosman; Weijia Wang; Rafik Tadros; Aditya Bhonsale; Mimount Bourfiss; Øyvind Lie; Ardan M. Saguner; Anneli Svensson; Antoine Andorin; Crystal Tichnell; Brittney Murray; Katja Zeppenfeld; Maarten P. van den Berg; Folkert W. Asselbergs; Arthur A.M. Wilde; Andrew D. Krahn; Mario Talajic; Léna Rivard; Stephen P. Chelko; Stefan L. Zimmerman; Ihab R. Kamel; Jane E. Crosson; Daniel P. Judge; Sing‐Chien Yap; Jeroen F. van der Heijden; Harikrishna Tandri; Jan D.H. Jongbloed; J. Peter van Tintelen; Pyotr G. Platonov; Fırat Duru; Kristina H. Haugaa; Paul Khairy; Richard N.W. Hauer; Hugh Calkins; Anneline S.J.M. te Riele; Cynthia A. James

doi:10.1161/circep.120.008509

Figures

Why the study?

Existing models predicting sustained ventricular arrhythmias in ARVC may overestimate sudden cardiac death risk, warranting a model specifically predicting life-threatening ventricular arrhythmias.

Can clinical predictors at diagnosis accurately predict subsequent life-threatening ventricular arrhythmias as a closer surrogate for sudden cardiac death in patients with definite ARVC?

Key Points

To develop and validate a clinical prediction model specifically for life-threatening ventricular arrhythmias as a surrogate for sudden cardiac death in arrhythmogenic right ventricular cardiomyopathy.
Retrospective cohort of 864 patients with definite arrhythmogenic right ventricular cardiomyopathy (mean age 40±16 years; 53% male) from 15 centers across North America and Europe.
Evaluated 8 prespecified clinical predictors of life-threatening ventricular arrhythmia (sudden cardiac death, aborted sudden cardiac death, or ventricular tachycardia >250 beats per minute) over a median follow-up of 5.75 years (interquartile range, 2.77–10.58).
Model developed using Cox regression with backward selection and validated internally via bootstrapping.
Life-threatening ventricular arrhythmias occurred in 93 patients (10.8%; event rate 1.56%/year, 95% CI, 1.26–1.91), including 15 patients (1.7%) with sudden cardiac death or aborted sudden cardiac death.
The 4-variable model achieved an optimism-corrected C-index of 0.74 (95% CI, 0.69–0.80) and a calibration slope of 0.95 (95% CI, 0.94–0.98).

Study Design

Type

Cohort (n=864)

Blinding

Core laboratory ECG review blinded to outcome data

Multicenter

Yes

Structured PICO

Can clinical predictors at diagnosis accurately predict subsequent life-threatening ventricular arrhythmias as a closer surrogate for sudden cardiac death in patients with definite ARVC?

P

Population

864 patients with definite ARVC by 2010 Task Force Criteria (mean age 39.5 years, 53.4% male) from 15 centers in 6 countries across North America and Europe, followed for a median of 5.75 years.

E

Exposure

8 prespecified clinical predictors evaluated at diagnosis (sex, age at diagnosis, recent <6 months cardiac syncope, 24-hour Holter PVC count, prior sustained VA events, number of anterior and inferior leads with T-wave inversion, LVEF, and RVEF) to develop a 4-variable multivariable Cox regression risk prediction model (male sex, younger age at diagnosis, 24-hour PVC count, and total leads with TWI).

O

Outcome

Time to first life-threatening ventricular arrhythmia (LTVA) during follow-up, defined as a composite of sudden cardiac death (SCD), aborted SCD, ventricular fibrillation, and rapid ventricular tachycardia (>250 beats per minute) that was either sustained (lasting ≥30 seconds) or terminated by ICD, over a median follow-up of 5.75 years (IQR 2.77-10.58).composite

Main Result

Effect estimate: C-index 0.74 (95% CI 0.69-0.80)

Limitations

Cohort predominantly of white descent from North-European and North American academic centers with a high rate of pathogenic PKP2 variants
Lack of external validation
Excluded patients with possible or borderline ARVC or concealed phase of disease
RVEF may lack sensitivity in detecting subtle early structural disease
LTVA cutoff of 250 bpm is an imperfect surrogate that may still overestimate SCD risk or miss slower events that degenerate
Cohort is drawn from North-European and North American academic centers with a population predominantly of white descent with a high rate of pathogenic PKP2 variants, limiting generalizability
Lack of external validation, particularly in cohorts with underrepresented genotypes (e.g., Naxos disease, TMEM43 founder variant)
Only included patients with definite ARVC, excluding concealed phase, borderline/possible ARVC, or non-ARVC arrhythmogenic cardiomyopathy
RVEF might lack sensitivity in detecting subtle changes in early structural disease
LTVA with a cutoff of 250 beats per minute remains an imperfect surrogate outcome for SCD

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Implication

Life-threatening ventricular arrhythmias in definite ARVC can be predicted using a simple 4-variable clinical model (younger age, male sex, PVC count, and T-wave inversions), whereas prior sustained VA and ventricular ejection fraction do not independently predict these potentially fatal events.

Abstract

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with ventricular arrhythmias (VA) and sudden cardiac death (SCD). A model was recently developed to predict incident sustained VA in patients with ARVC. However, since this outcome may overestimate the risk for SCD, we aimed to specifically predict life-threatening VA (LTVA) as a closer surrogate for SCD. Methods: We assembled a retrospective cohort of definite ARVC cases from 15 centers in North America and Europe. Association of 8 prespecified clinical predictors with LTVA (SCD, aborted SCD, sustained, or implantable cardioverter-defibrillator treated ventricular tachycardia >250 beats per minute) in follow-up was assessed by Cox regression with backward selection. Candidate variables included age, sex, prior sustained VA (≥30s, hemodynamically unstable, or implantable cardioverter-defibrillator treated ventricular tachycardia; or aborted SCD), syncope, 24-hour premature ventricular complexes count, the number of anterior and inferior leads with T-wave inversion, left and right ventricular ejection fraction. The resulting model was internally validated using bootstrapping. Results: A total of 864 patients with definite ARVC (40±16 years; 53% male) were included. Over 5.75 years (interquartile range, 2.77–10.58) of follow-up, 93 (10.8%) patients experienced LTVA including 15 with SCD/aborted SCD (1.7%). Of the 8 prespecified clinical predictors, only 4 (younger age, male sex, premature ventricular complex count, and number of leads with T-wave inversion) were associated with LTVA. Notably, prior sustained VA did not predict subsequent LTVA ( P =0.850). A model including only these 4 predictors had an optimism-corrected C-index of 0.74 (95% CI, 0.69–0.80) and calibration slope of 0.95 (95% CI, 0.94–0.98) indicating minimal over-optimism. Conclusions: LTVA events in patients with ARVC can be predicted by a novel simple prediction model using only 4 clinical predictors. Prior sustained VA and the extent of functional heart disease are not associated with subsequent LTVA events.

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Cite This Study

Cadrin‐Tourigny et al. (2020) conducted a cohort in Definite arrhythmogenic right ventricular cardiomyopathy (ARVC) (n=864). 4-variable clinical prediction model (younger age, male sex, 24-hour PVC count, number of leads with T-wave inversion) was evaluated on Time to first life-threatening ventricular arrhythmia (LTVA), a composite of sudden cardiac death (SCD), aborted SCD, ventricular fibrillation, and rapid ventricular tachycardia (>250 beats per minute) that was either sustained (≥30 seconds) or terminated by ICD (C-index 0.74, 95% CI 0.69-0.80).

synapsesocial.com/papers/6a7348edd98d9ee37dc8fb9d https://doi.org/10.1161/circep.120.008509

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Sudden Cardiac Death Prediction in Arrhythmogenic Right Ventricular Cardiomyopathy

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Sudden Cardiac Death Prediction in Arrhythmogenic Right Ventricular Cardiomyopathy

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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