Methods

Among the participants of the Défibrillateur Automatique Implantable Prévention Primaire (DAI-PP) cohort ( NCT01992458 ), 847 presented with narrow QRS and were implanted with single- or dual-chamber ICDs: 155 patients in NYHA class I, 504 in NYHA class II, and 188 in NYHA class III were eligible for the purpose of this analysis. Briefly, DAI-PP included patients who were ≥18 years at the time of ICD implantation. Overall, from 2002 to 2012, all patients with ischemic or nonischemic cardiomyopathy, stable on maximally tolerated medical therapy, implanted with an ICD (biventricular, single or dual chamber) in the setting of primary prevention in 12 French reference centers were considered and enrolled in the DAI-PP follow-up program.

Exclusion criteria included secondary prevention ICD recipients and those without structural heart disease (including channelopathies) or other types of structural heart disease (e.g., hypertrophic cardiomyopathy, noncompaction, and arrhythmogenic right ventricular cardiomyopathy). We selected only patients with a QRS width <120 ms implanted with single- or dual-chamber ICDs for this particular analysis as evidence of benefit for patients with QRS width >120 ms and heart failure symptoms already exists and mandates cardiac resynchronization therapy with defibrillator (CRT)-D implantation. Only patients with NYHA class I to III symptoms on optimal medical therapy are eligible for primary prevention non-CRT ICDs, according to guidelines, and therefore, patients with NYHA class IV symptoms were excluded.

The study was funded by public sources, including the French Institute of Health and Medical Research (INSERM) and the French Society of Cardiology , and was coordinated by Clinique Pasteur, Toulouse, and the Paris Cardiovascular Research Center, European Georges Pompidou Hospital, Paris, in France. The study complied with the Declaration of Helsinki, and the data file of the DAI-PP study was declared to and authorized by the French data protection committee ( Commission Nationale Informatique et Liberté ).

All variables at the time of the procedure were defined and categorized according to the literature or common practice. In addition to NYHA functional class, assessed by the local DAI-PP investigator at the time of device implantation, we collected the etiology of the underlying heart disease (ischemic or dilated cardiomyopathy). Estimated glomerular filtration rate (eGFR) was estimated using the Cockroft-Gault formula and categorized into 2 categories (≥60 and <60 ml/min). Atrial fibrillation (AF) was defined as a history of AF (paroxysmal or persistent), documented on standard ECG or 24-hour Holter monitoring. Co-morbidities were systematically collected: cancer, chronic obstructive pulmonary disease, chronic renal failure, chronic liver disease, history of transient ischemic neurologic attack, and others (including diabetes mellitus). Device programming was left to the implanting/managing physician’s discretion.

Follow-up information was obtained from appointments every 4 to 6 months for device evaluation, according to French guidelines. The different end points included occurrence of appropriate therapies, early complications, inappropriate shocks, and overall and specific mortalities.

Device interrogation data were checked by local investigators for appropriate and inappropriate ICD therapies. Appropriate ICD therapy was defined as an episode of ventricular tachycardia/ventricular fibrillation resulting in a single or multiple shocks and/or antitachycardia pacing for arrhythmia termination. The date of the first appropriate ICD therapy and their cumulative number were recorded. The cause of inappropriate shock(s) was collected. Adjudication of therapy type (appropriate or inappropriate) was undertaken by the local investigator.

Early complications (defined as those appearing in the first 30 days after device implantation) included lead dysfunction, bleeding or hematoma, sepsis, cardiac tamponade, pneumothorax, and death.

Mortality data were obtained from the hospital or the general practitioner and were systematically controlled through the National Institute of Statistics Economical Studies (INSEE). Causes of death were obtained from the investigators and/or by the French Center on Medical Causes of Death (CépiDc-INSERM). The CépiDc-INSERM is a public, academic institution focused on the analysis of circumstances and causes of death based on death certificate and medical records. Causes of deaths were classified according to the International Classification of Diseases (10th Revision). This information was reviewed by 2 investigators and causes of death adjudicated after consideration of all available information and according to the following prespecified groups: cardiovascular (including progressive heart failure death, stroke), noncardiovascular, ICD-unresponsive sudden cardiac death (arrhythmic or non-arrhythmic whenever assessment possible), ICD-related death, and unknown when the quality of the information could not allow investigators to appropriately identify cause of death. Overall, cause of death assessment was possible in 91 of 104 deceased patients (87.5%).

Preparation of this report was in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology statement for reporting of observational studies.

Comparisons were performed across the different NYHA functional class strata. The chi-square test was used for comparison of nominal variables and Student’s t test for continuous variables; the Levene’s test was used to check the homogeneity of variance; when appropriate, nonparametric equivalent, Mann-Whitney test, was used. When baseline differences were present, adjustment was performed. Results with p <0.05 were regarded as significant.

We compared the adjusted outcomes of appropriate shock and death across different NYHA class strata using Cox proportional hazards regression analysis. Hazard curves were traced for comparison of the occurrence of events among the different NYHA functional classes after adjustment for baseline differences. Univariate Cox regression and subsequent multivariate Cox regression (forward likelihood ratio, probability for stepwise = 0.05) was performed for assessment of predictors of mortality and appropriate ICD interventions.

Data were filled into a predefined data introduction electronic sheet made available to all participant centers. After completion of follow-up, data from all centers was merged and analyzed at the Paris Cardiovascular Research Center (Inserm U970, Cardiovascular Epidemiology Unit) using SAS Program, v9.3 (SAS Institute Inc, Cary, North Carolina).