Faculty Bibliography

IMPORTANCE/UNASSIGNED:Current risk prediction guidelines for hypertrophic cardiomyopathy predict only sudden cardiac death and are imperfect, leading to avoidable deaths and unnecessary implantable cardioverter defibrillators. OBJECTIVE/UNASSIGNED:To combine prospectively collected clinical history, imaging, genetic, and biomarker data to improve risk prediction of adverse events in hypertrophic cardiomyopathy. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:A total of 2750 patients with hypertrophic cardiomyopathy were prospectively enrolled in the registry-based study from 44 sites in North America and Europe with expertise in hypertrophic cardiomyopathy and cardiac magnetic resonance (CMR) imaging. Participants were enrolled from April 1, 2014, to April 7, 2017. EXPOSURES/UNASSIGNED:Patients underwent a health history questionnaire, blood sampling for biomarkers and genotyping, and contrast-enhanced CMR. Patients were followed up yearly by telephone and through records review regarding event documentation. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The predefined composite adjudicated primary end point was time to first event for hypertrophic cardiomyopathy-related deaths; nonfatal sustained ventricular arrhythmias (VAs) requiring cardioversion or defibrillation; and left ventricular (LV) assist device implant or heart transplant. A secondary end point was a composite of sudden cardiac death and nonfatal VA events. The elastic-net method identified the most important predictors. Cox proportional hazards regression assessed associations with time to the first end point. RESULTS/UNASSIGNED:Of the 2750 prospectively enrolled patients, 2698 (98%) had analyzable data after 9 were excluded because they had hypertrophic cardiomyopathy phenocopies and 43 withdrew. Of these remaining patients, 1919 (71%) were male, mean age was 50 years (SD, 11 years), and 423 (16%) were from underrepresented racial and minority groups. The mean follow-up was 6.9 years (SD, 2.1 years). The primary event model in 104 patients included LV scar as a percentage of LV mass by late gadolinium enhancement (LGE%; hazard ratio [HR], 1.86; 95% CI, 1.58-2.20; P < .001), LV mass index (HR, 1.09; 95% CI, 1.01-1.17; P = .03), LV end-systolic volume index (HR, 1.28; 95% CI, 1.12-1.46; P < .001 ), all per 10-unit increase, history of heart failure at study entry (HR, 2.89; 95% CI, 1.75-4.77; P < .001), and log N-terminal pro-B-type natriuretic peptide (NT-proBNP; HR, 1.41; 95% CI, 1.17-1.70; P < .001) level per log unit, (C index for all, 0.77). An LGE percentage of the LV mass of 9% or higher substantially increased the primary composite event rate (P = .001). The secondary sudden cardiac death and VA risk factor model (in 69 patients) included LGE%, LV mass index, LV ejection fraction, and log(NT-proBNP) (C index, 0.76). CONCLUSIONS AND RELEVANCE/UNASSIGNED:These results provide prospective evidence for incorporating cardiac magnetic resonance and NT-proBNP in the evaluation of patients with hypertrophic cardiomyopathy. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT01915615.

MR imaging is increasingly used in evaluation of patients with known or suspected hypertrophic cardiomyopathy (HCM), as it provides useful information on cardiac structure, function, and tissue characterization that is complementary to echocardiography. While the adverse effect of left ventricle (LV) outflow tract obstruction on blood flow patterns is well characterized by the midsystolic drop in LV ejection velocities and flow, flow patterns in HCM with mid-LV obstruction, with or without apical aneurysm, are less well characterized. MR imaging can provide additional information on alterations of blood flow patterns in these HCM phenotypes and "paradoxic" flows associated with apical aneurysms.

Once considered rare and essentially untreatable with a grim prognosis and reduced life expectancy, hypertrophic cardiomyopathy (HCM) has evolved substantially over 6 decades. Ultimately, HCM has become a contemporary global disease with pharmacologic and interventional options offering effective personalized treatment for all adverse disease pathways. Striking reduction in HCM-related mortality to ≤0.5%/year in optimally treated cohorts is now comparable to that expected in the US general population, lower than most other disease risks to living, and 10-fold less than the earliest estimates. The few deaths directly related to HCM are now largely attributable to advanced (end-stage) heart failure in patients with nonobstructive HCM. Determinants of this transformation to a lower risk disease are evident in hallmark clinical inflection points and breakthroughs, including dedicated HCM programs assembling large clinical databases in which focused (and unfunded) physician-investigators have derived data directly from patients in clinical practice. Evidence-based observational studies report emergence of contemporary treatment strategies enhancing survival: implantable defibrillators prevent arrhythmic sudden death globally with 95% sensitive patient selection using an American Heart Association/American College Cardiology risk stratification algorithm; low-risk, high-benefit surgical myectomy reverses outflow obstruction and heart failure in >90% with a long-term survival benefit; and aggressive anticoagulation has reduced embolic strokes. Recent novel pharmacologic alternatives (cardiac myosin inhibitors) are proving effective in relieving obstruction/symptom burden and changing disease management. These principles and time-tested patient-centered research strategies uniquely tailored to the heterogeneous HCM clinical spectrum are pivotal in providing practice insights, offering a vulnerable population more optimistic prognosis including opportunity to achieve normal longevity not available to prior generations of patients.

UNLABELLED:Hypertrophic cardiomyopathy (HCM) is the most common monogenic cardiac disease, affecting approximately 0.2% of the general population. Despite its prevalence, it remains significantly underdiagnosed clinically. Surgical management of obstructive HCM has advanced extensively, particularly in understanding the mitral valve's contribution to left ventricular outflow tract obstruction (LVOTO). Historically, LVOTO was attributed mainly to septal hypertrophy and treated through isolated septal myectomy. However, contemporary insights highlight the importance of mitral leaflet elongation and abnormal papillary muscle dynamics in this pathology. Mitral leaflet shortening, either through horizontal plication or direct excision (ReLex), alongside the release of abnormal papillary muscle attachments, has emerged as a complementary strategy to standard septal myectomy. These combined approaches have demonstrated improved surgical outcomes, including reduced mitral regurgitation, alleviation of LVOTO, and excellent mid-term survival. This review synthesizes current evidence and clinical experiences, providing insights into mitral leaflet shortening's role and the comprehensive surgical strategies for managing obstructive HCM. SUPPLEMENTARY INFORMATION/UNASSIGNED:The online version contains supplementary material available at 10.1007/s12055-025-02051-1.

OBJECTIVE/UNASSIGNED:During septal myectomy, once the heart is arrested and drained of blood on cardiopulmonary bypass, transesophageal echocardiography can no longer assess septal thickness. In the present study, we evaluated the effectiveness of on-pump intracardiac echocardiography (OPIE) for real-time intraoperative septal thickness assessment in patients with preoperative thickness ≤2.0 cm. Our hypothesis was that OPIE measurements would be conconcordant with the pre- and postcardiopulmonary bypass transesophageal echocardiography measurements that are at present the primary operative guides. METHODS/UNASSIGNED:We retrospectively reviewed patients with hypertrophic cardiomyopathy and septal thickness ≤2.0 cm on transthoracic echocardiography who underwent septal myectomy from July 2017 to July 2024. The OPIE probe was introduced into the left-ventricular chamber during cardioplegic arrest, with repeated measurements to assess the depth and adequacy of resection. Septal thickness was evaluated pre-myectomy using transthoracic echocardiography, cardiac magnetic resonance imaging, transesophageal echocardiography, and OPIE. Lin's concordance correlation coefficients and Bland-Altman analyses were used to evaluate agreement between modalities. RESULTS/UNASSIGNED:A total of 220 patients were included with preoperative thickness ≤2.0, 56 of whom underwent myectomy with OPIE guidance. Preresection transesophageal echocardiography and OPIE demonstrated the strongest agreement of all the imaging modalities (Lin's concordance correlation coefficient, 0.81; 95% CI, 0.72-0.88), with minimal bias (-0.73) and the narrowest limits of agreement (-3.76, +2.31]. OPIE-derived resection thickness estimates were tightly clustered. In the OPIE cohort, there was 1 ventricular septal defect (1.8%) and no 30-day mortality. CONCLUSIONS/UNASSIGNED:OPIE is a reliable tool for intraoperative assessment of septal thickness, particularly in patients with mild hypertrophy.