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.

Until now, peripheral vascular endothelial function testing has been performed in research laboratories under highly controlled conditions, thus limiting its clinical applicability. In this study, we evaluated endothelial function in two peripheral vascular beds before and during reactive hyperemia in an outpatient clinic setting. The brachial artery was imaged with a portable ultrasound device and changes in vessel diameter were expressed as percent flow-mediated dilation (%FMD). Pulse wave amplitude of the finger was detected by peripheral arterial tonometry (PAT) and PAT hyperemia was defined as the maximal plethysmographic recording compared to baseline. Sixty individuals (43 men) were enrolled with an average age 53 Ϯ 2 years (mean Ϯ SE). The 31 individuals with more than two cardiac risk factors (CRF) had lower FMD (7.0 Ϯ 1.1%) and PAT hyperemia (2.1 Ϯ 0.9) compared to the 29 individuals with 0-2 CRF (FMD 11.3 Ϯ 0.8%, PAT hyperemia 2.4 Ϯ 0.1; p Ͻ 0.05 for both). The 32 individuals with coronary artery disease (CAD) had lower FMD (6.8 Ϯ 1.1%) and PAT hyperemia (2.0 Ϯ 0.1) compared to the 28 individuals without CAD (FMD 11.5 Ϯ 0.8%, PAT hyperemia 2.4 Ϯ 0.1; p Ͻ 0.05 for both). Thus, peripheral vascular endothelial function testing in the ambulatory setting correlates with the extent of CAD risk and the presence or absence of CAD. In conclusion, these data suggest that peripheral vascular endothelial function testing is feasible in ambulatory patients, and this is an important next step in bringing this technology to clinical applicability.

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The ratio of pulse wave amplitude (PWA) during reactive hyperemia compared to baseline as measured by peripheral arterial tonometry (PAT) is a non-invasive measure of microvascular endothelial function referred to as the pulse wave amplitude reactive hyperemia index (PWA-RHI). Whether upstream conduit vessel structure may affect downstream resistance vessel PWA has not been clearly examined. We tested the hypothesis that digital PWA is influenced by brachial artery diameter (BAD) and that this association would influence comparison of PWA-RHI between genders. Measures of vascular structure and microvascular function were carried out in 115 patients varying in cardiovascular risk profiles (average age 57 years, male n = 79, CAD n = 43). PWA was assessed using plethysmography at baseline and following 5 minutes of brachial artery occlusion. BAD was assessed using high-resolution ultrasonography. Results: There was a negative association between BAD and PWA-RHI (r = -0.34, p < 0.05). Women had greater PWA-RHI and smaller BAD compared with men (p < 0.05). When co-varying for BAD, there were no longer gender differences in PWA-RHI. Moreover, when a sub-group of men and women without CAD (n = 40), matched for BAD, were examined, there were no gender differences in PWA-RHI. In conclusion, PWA-RHI obtained from PAT is associated with BAD. Studies examining gender differences in microvascular endothelial function with PAT may need to correct for BAD as a potential confounder.

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