Worldwide differences in primary prevention implantable cardioverter defibrillator utilization and outcomes in hypertrophic cardiomyopathy

Abstract

Aims: Risk stratification algorithms for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) and regional differences in clinical practice have evolved over time. We sought to compare primary prevention implantable cardioverter defibrillator (ICD) implantation rates and associated clinical outcomes in US vs. non-US tertiary HCM centres within the international Sarcomeric Human Cardiomyopathy Registry.

Methods and results: We included patients with HCM enrolled from eight US sites (n = 2650) and five non-US (n = 2660) sites and used multivariable Cox-proportional hazards models to compare outcomes between sites. Primary prevention ICD implantation rates in US sites were two-fold higher than non-US sites (hazard ratio (HR) 2.27 [1.89-2.74]), including in individuals deemed at high 5-year SCD risk (≥6%) based on the HCM risk-SCD score (HR 3.27 [1.76-6.05]). US ICD recipients also had fewer traditional SCD risk factors. Among ICD recipients, rates of appropriate ICD therapy were significantly lower in US vs. non-US sites (HR 0.52 [0.28-0.97]). No significant difference was identified in the incidence of SCD/resuscitated cardiac arrest among non-recipients of ICDs in US vs. non-US sites (HR 1.21 [0.74-1.97]).

Conclusion: Primary prevention ICDs are implanted more frequently in patients with HCM in US vs. non-US sites across the spectrum of SCD risk. There was a lower rate of appropriate ICD therapy in US sites, consistent with a lower-risk population, and no significant difference in SCD in US vs. non-US patients who did not receive an ICD. Further studies are needed to understand what drives malignant arrhythmias, optimize ICD allocation, and examine the impact of different ICD utilization strategies on long-term outcomes in HCM.

Keywords: Hypertrophic cardiomyopathy; Implantable cardioverter defibrillator; Outcomes; Primary prevention; Risk stratification; Sudden cardiac death.

Graphical abstract

Figure 1

Cumulative incidence of primary prevention implantable cardioverter defibrillator implantation in US vs. non-US sites.

Figure 2

Forest plot of multivariable association of US vs. non-US sites with primary prevention implantable cardioverter defibrillator implantation adjusting for clinical covariates. SCD, sudden cardiac death.

Figure 3

Hazard ratios of primary prevention implantable cardioverter defibrillator implantation for US vs. non-US sites across hypertrophic cardiomyopathy risk-sudden cardiac death score categories. HCM, hypertrophic cardiomyopathy; SCD, sudden cardiac death.

Figure 4

Forest plot of multivariable association of sudden cardiac death risk factors with primary prevention implantable cardioverter defibrillator implantation stratified by US vs. non-US sites. P-values correspond to tests of interaction between sites (US vs. non-US) and corresponding sudden cardiac death risk factor. Tests of interaction for clinical sudden cardiac death risk factors were performed in the full cohort adjusting for age at first Sarcomeric Human Cardiomyopathy Registry site visit, year of first visit, sex, race, atrial fibrillation, coronary artery disease, septal reduction therapy, unexplained syncope, family history of sudden cardiac death, and non-sustained ventricular tachycardia. Tests of interaction between sites and echocardiographic parameters were performed among study participants with available echocardiographic data further adjusting for maximum left ventricular wall thickness, maximum left ventricular outflow tract gradient, left atrial diameter and ejection fraction. CI, confidence interval; SD, standard deviation.

Figure 5

Distribution of number of traditional sudden cardiac death risk factors in US vs. non-US sites stratified by implantable cardioverter defibrillator vs. no implantable cardioverter defibrillator cohort. Risk factors included ejection fraction <50%, syncope, family history of sudden cardiac death, non-sustained ventricular tachycardia, and left ventricular wall thickness >30 mm. Data on late gadolinium enhancement and left ventricular aneurysm were not available in the Sarcomeric Human Cardiomyopathy Registry. Only individuals with non-missing data for all risk factors are included (n = 830/946 in implantable cardioverter defibrillator cohort and n = 4294/5089 in no implantable cardioverter defibrillator cohort). P-values are derived from Chi-square tests comparing the proportion of study participants in risk factor categories between US and non-US sites.

Figure 6

Kaplan–Meier estimates of overall survival (A) and survival free of appropriate implantable cardioverter defibrillator therapy (B) in the primary prevention implantable cardioverter defibrillator cohort stratified by US vs. non-US sites. Out of 69 appropriate therapy events, 64 were implantable cardioverter defibrillator shocks and 5 were anti-tachycardia pacing. Time-zero reflects time of implantable cardioverter defibrillator implant during follow-up or first Sarcomeric Human Cardiomyopathy Registry site visit among participants who had a primary prevention implantable cardioverter defibrillator device implanted prior to first Sarcomeric Human Cardiomyopathy Registry site visit.

Figure 7

Kaplan–Meier estimates of survival free of sudden cardiac death or resuscitated cardiac arrest composite endpoint in the no implantable cardioverter defibrillator cohort stratified by US vs. non-US sites. Out of 97 composite sudden cardiac death events 34 were sudden cardiac death and 63 were resuscitated cardiac arrest.