Individualized Family Screening for Arrhythmogenic Right Ventricular Cardiomyopathy
Key result
Borderline ARVC is linked to ~7-fold greater 3-year risk of definite ARVC versus possible ARVC.
- P<0.01
- n=136
Why the study?
Regular ARVC screening among at-risk relatives burdens clinical resources, and prioritizing relatives based on their probability of developing definite ARVC could improve efficiency.
Key Points
- To outline individualized clinical and genetic screening approaches for identifying at-risk relatives of patients with arrhythmogenic right ventricular cardiomyopathy.
- Review of clinical screening protocols incorporating cascade genetic testing and multi-modality cardiac imaging.
- Evaluation of risk stratification metrics tailored to family-specific genetic variants and disease penetrance.
- Tailored screening regimens identify early or atypical disease features in asymptomatic relatives carrying pathogenic variants.
- Individualized cascade testing optimizes long-term surveillance intervals and avoids unnecessary testing in non-carrier family members.
Study Design
Type
Cohort (n=136)
Multicenter
Yes
PICO
P
Population
136 at-risk relatives without definite ARVC, followed for a median of 8.1 years to determine predictors and probability of developing definite ARVC.
E
Exposure / Comparator
Borderline ARVC phenotype vs Possible ARVC phenotype
O
Primary Outcome
Development of definite ARVC at 3 years, p=<0.01
Main Result
Absolute Event Rate: 35% vs 5%
p-value: p=<0.01
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“With studies like this one, we can hopefully reduce the burden of cost on health care systems and families by reducing the rate of screening later in life. Genetic cardiomyopathy specialists can provide reassurance to family members who have not developed signs of disease by age 30 years that their risk of disease development is low in future.”
“This study includes one of largest cohorts of ARVC relatives and provides more data on 'who, how, and when' for ARVC screening. It suggests that relatives aged 20-30 years, those with symptoms, or those with borderline ARVC need more aggressive and frequent (possibly annual) screening. Similarly, screening for relatives with possible ARVC can be spaced out to possibly every 5 years.”
Implication
Clinical review demonstrates personalized genetic and clinical evaluation protocols in families with arrhythmogenic cardiomyopathy, highlighting improved detection of at-risk relatives.
Abstract
BACKGROUND Clinical guidelines recommend regular screening for Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) to monitor at-risk relatives, resulting in a significant burden on clinical resources. Prioritizing relatives on their probability of developing definite ARVC may provide more efficient patient care. OBJECTIVE Determine predictors and probability of ARVC development over time among at-risk relatives. METHODS We included 136 relatives (46% male, 25.5 (interquartile range (IQR):15.8-44.4) years) from the Netherlands ACM Registry without definite ARVC by 2010 Task Force Criteria (TFC). Phenotype was ascertained using electrocardiograms, Holter monitoring, and cardiac imaging. Subjects were divided into "possible ARVC" (only genetic/familial predisposition) and "borderline ARVC" (one minor TFC criterion plus genetic/familial predisposition). We performed Cox regression to determine predictors, and multi-state modeling to assess probability of ARVC development. Results were replicated in an unrelated Italian cohort (57% male, 37.0 (IQR:25.4-50.4) years). RESULTS At baseline, 93 (68%) had possible and 43 (32%) borderline ARVC. Follow-up was available for 123 (90%) relatives. After 8.1 (IQR:4.2-11.4) years, 41 (33%) developed definite ARVC. Independent of baseline phenotype, symptomatic subjects (p=0.014) and those 20-30 years old (p=0.002) had higher hazard of developing definite ARVC. Furthermore, borderline ARVC patients had higher probability of developing definite ARVC compared to possible patients (1-year probability: 13% vs. 0.6%; 3-year probability: 35% vs. 5%, p<0.01). External replication showed comparable results (p>0.05). CONCLUSION Symptomatic relatives, those in 20-30 age range and with borderline ARVC have higher probability of developing definite ARVC. These patients may benefit from more frequent follow-up, while others may be monitored less often.
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Cite This Study
Muller et al. (2023) conducted a cohort in Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) (n=136). Borderline ARVC phenotype vs. Possible ARVC phenotype was evaluated on Development of definite ARVC at 3 years (p=<0.01). At-risk relatives with borderline ARVC had a significantly higher 3-year probability of developing definite ARVC compared to those with possible ARVC (35% vs. 5%, p<0.01).