Subcutaneous Implantable Cardioverter-defibrillator (S-ICD) Eligibility Over Time in Arrhythmogenic Cardiomyopathy

Background: Arrhythmogenic cardiomyopathy (ACM) is a genetic, progressive heart muscle disease characterized by fibrofatty replacement of the myocardium, which predisposes patients to ventricular arrhythmias, heart failure and sudden cardiac death. The disease was initially described as a predominantly right ventricular condition (arrhythmogenic right ventricular cardiomyopathy, ARVC), diagnosed by the 2010 Task Force criteria, but left ventricular and biventricular involvement are now recognized, were proposed to incorporate left ventricular manifestations (arrhythmogenic left ventricular cardiomyopathy, ALVC). In high-risk patients, an implantable cardioverter-defibrillator (ICD) is recommended for the prevention of sudden cardiac death.

The subcutaneous ICD (S-ICD) is an entirely extravascular alternative that avoids transvenous leads and their long-term complications. However, S-ICD candidates must undergo pre-implant surface electrocardiogram (ECG) screening to ensure appropriate sensing and to reduce the risk of inappropriate shocks due to T-wave oversensing. Because ACM is progressive, its characteristic depolarization and repolarization abnormalities (such as T-wave inversion, epsilon waves, low QRS voltage and conduction delay) may change over time and affect S-ICD eligibility after an initially favorable screening. Data on the performance and long-term eligibility of the S-ICD in this population remain scarce.

Study design: This is a prospective, longitudinal, single-center pilot cohort study conducted at the Arrhythmia Clinical Unit of the Heart Institute (InCor), Hospital das Clínicas, University of São Paulo Medical School, Brazil. The study includes three groups of 30 participants each: patients with ACM (study group); patients with Brugada syndrome, a condition in which the S-ICD is commonly indicated (reference group); and individuals without structural heart disease on transthoracic echocardiography (control group).

Study procedures: After informed consent, S-ICD eligibility is assessed using the LATITUDE programmer (Boston Scientific) and the manufacturer's screening algorithm, with surface ECG electrodes placed in the standard screening positions on the chest. Skin preparation may include shaving of chest hair and cleaning with alcohol. The screening is the only study procedure and is repeated at 6, 12 and 18 months after the baseline assessment, regardless of whether a device has been implanted. The study does not involve device implantation, device supply or any change in clinical management; implantation decisions remain at the discretion of each patient's care team.

Statistical analysis: Continuous variables will be described as means and standard deviations or medians and interquartile ranges, and categorical variables as absolute and relative frequencies. The proportion of patients eligible for the S-ICD at baseline and at each follow-up visit will be estimated with 95% confidence intervals and compared using logistic regression. Differences in the number of eligible sensing vectors between time points will be assessed by paired t-test or Wilcoxon signed-rank test, as appropriate, and eligibility across electrode positions will be compared using logistic regression for repeated measures. Factors associated with eligibility and loss of eligibility will be explored using Student's t-test or Mann-Whitney test for continuous variables and Pearson's chi-square or Fisher's exact test for categorical variables. Exploratory multivariable logistic regression models may be fitted, considering the limited sample size, with results reported as odds ratios and 95% confidence intervals. A two-sided significance level of 5% will be adopted.