Enhanced American College of Cardiology/American Heart Association Strategy for Prevention of Sudden Cardiac Death in High-Risk Patients With Hypertrophic Cardiomyopathy

Abstract

IMPORTANCE Strategies for reliable selection of high-risk patients with hypertrophic cardiomyopathy (HCM) for prevention of sudden cardiac death (SCD) with implantable cardioverter/defibrillators (ICDs) are incompletely resolved. OBJECTIVE To assess the reliability of SCD prediction methods leading to prophylactic ICD recommendations to reduce the number of SCDs occurring in patients with HCM. DESIGN, SETTING, AND PARTICIPANTS In this observational longitudinal study, 2094 predominantly adult patients with HCM consecutively evaluated over 17 years in a large HCM clinical center were studied. All patients underwent prospective ICD decision making relying on individual major risk markers derived from the HCM literature and an enhanced American College of Cardiology/American Heart Association (ACC/AHA) guidelines-based risk factor algorithm with complete clinical outcome follow-up. Data were collected from June 2017 to February 2018, and data were analyzed from February to July 2018. MAIN OUTCOMES AND MEASURES Arrhythmic SCD or appropriate ICD intervention for ventricular tachycardia or ventricular fibrillation. RESULTS Of the 2094 study patients, 1313 (62.7%) were male, and the mean (SD) age was 51 (17) years. Of 527 patients with primary prevention ICDs implanted based on 1 or more major risk markers, 82 (15.6%) experienced device therapy-terminated ventricular tachycardia or ventricular fibrillation episodes, which exceeded the 5 HCM-related SCDs occurring among 1567 patients without ICDs (0.3%), including 2 who declined device therapy, by 49-fold (95% CI, 20-119; P = .001). Cumulative 5-year probability of an appropriate ICD intervention was 10.5% (95% CI, 8.0-13.5). The enhanced ACC/AHA clinical risk factor strategy was highly sensitive for predicting SCD events (range, 87%-95%) but less specific for identifying patients without SCD events (78%). The C statistic calculated for enhanced ACC/AHA guidelines was 0.81 (95% CI, 0.77-0.85), demonstrating good discrimination between patients who did or did not experience an SCD event. Compared with enhanced ACC/AHA risk factors, the European Society of Cardiology risk score retrospectively applied to the study patients was much less sensitive than the ACC/AHA criteria (34% [95% CI, 22-44] vs 95% [95% CI, 89-99]), consistent with recognizing fewer high-risk patients. CONCLUSIONS AND RELEVANCE A systematic enhanced ACC/AHA guideline and practice-based risk factor strategy prospectively predicted SCD events in nearly all at-risk patients with HCM, resulting in prophylactically implanted ICDs that prevented many catastrophic arrhythmic events in this at-risk population.

The ESC Risk Score Is Less Reliable than ACC/AHA Risk Factors in Hypertrophic Cardiomyopathy: When Sensitivity Trumps Specificity

“…1A) the 5 HCM-related SCDs occurring in patients not implanted with ICDs, including 2 patients who declined device therapy despite our intention to treat. 5 Sensitivity of the ACC/AHA risk factor strategy was very high (95%), resulting in identification of nearly all at-risk patients with HCM ( Fig. 1B) On the other hand, consistent with the observations in the Wang et al meta-analysis, 17 sensitivity of the ESC risk score, when applied retrospectively to the same patients at Tufts, was particularly low (34%).…”

“…Notably, these observations are also consistent with the recent large (n ¼ 2094 patients) Tufts HCM Institute study, with prospective ICD decision making, which demonstrates that the most efficacious strategy for identifying high-risk patients with HCM deserving primary prevention ICD therapy is an individual risk marker strategy enhanced from the 2011 ACC/AHA guidelines and incorporating more contemporary risk markers. 5 In the Tufts study, 82 patients likely experienced lifesaving device therapy terminating ventricular fibrillation (VT/VF) episodes, which exceeded by approximately 50-fold (Fig. 1A) the 5 HCM-related SCDs occurring in patients not implanted with ICDs, including 2 patients who declined device therapy despite our intention to treat.…”

“…[1][2][3] The proven efficacy of the implantable cardioverter defibrillator (ICD) in aborting lethal ventricular tachyarrhythmias, changing clinical course, and saving young lives in patients with HCM has placed increasing weight on the importance of accurate selection of patients for device therapy. [3][4][5][6][7][8][9] Beginning in 2003, and most recently in 2017, North American expert consensus guidelines have recommended a strategy in which decisions for primary prevention ICDs are based on the presence of 1 or more risk markers regarded as major within the clinical profile of a patient with HCM. 1,2 Over this period of time, the American College of Cardiology/American Heart Association (ACC/AHA) riskfactor strategy has continued to evolve, incorporating novel markers for SCD including, most recently, extensive late gadolinium enhancement (LGE) and the left ventricular (LV) apical aneurysm.…”

“…Among the 82 patients with appropriate ICD interventions terminating VT/ VF, almost 50% had low ESC risk scores inconsistent with an ICD recommendation and therefore with this strategy would not likely have been protected from SCD. 5 The higher sensitivity associated with the enhanced ACC/ AHA risk marker strategy is due, in part, to its inherent flexibility, which allows the opportunity to incorporate novel high-risk markers such as extensive LGE, systolic dysfunction with ejection fraction <50% and LV apical aneurysms, which account for a significant proportion (w25%) of appropriate Figure 1. Superior sensitivity of enhanced American College of Cardiology/American Heart Association (ACC/AHA) risk-factor strategy compared with European Society of Cardiology (ESC) risk score in identifying high-risk patients with hypertrophic cardiomyopathy (HCM) for prevention of sudden cardiac death (SCD).…”

Mechanisms of Arrhythmogenicity in Hypertrophic Cardiomyopathy: Insight From Non-invasive Electrocardiographic Imaging

“…Patients with hypertrophic cardiomyopathy (HCM) are at high risk of life-threatening ventricular arrhythmias and sudden cardiac death (SCD) (Maron et al, 2019). Mechanisms of arrhythmogenicity in HCM are complex and incompletely understood.…”