Faculty Bibliography

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.

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.

BACKGROUND:Metabolic dysfunction-associated steatotic liver disease (MASLD) increases risk of cardiovascular disease (CVD). Despite the high prevalence of MASLD among Hispanic populations, there is a scarcity of research on the associations between non-invasive markers of liver disease and incident CVD and all-cause mortality. In this study we investigated the association of liver related biomarkers with CVD events and all-cause mortality in a population based Hispanic/Latino cohort. METHODS:We included 15,216 participants from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) aged 18-74 years with no pre-existing CVD. The composite outcome combined incident CVD and all-cause mortality. Having "elevated ALT/AST" was defined as ALT > 40 IU/mL or AST > 37 IU/mL for males, and ALT or AST > 31 IU/mL for females. We estimated adjusted hazard ratios (HR) and 95% confidence intervals (CI) relating our composite outcome to elevated ALT/AST, FIB-4 and MASLD. Using interaction terms, we assessed whether the relationship between elevated ALT/AST and the composite outcome differed by MASLD status. RESULTS:The study population was 40 years old on average, 52.7% female and had 740 CVD or all-cause mortality events. Elevated FIB-4 had the strongest association with incident CVD or all-cause mortality (comparing FIB-4 > 2.67 versus ≤ 2.67, HR:3.47; CI:2.34-5.14). Elevated AST was found to be associated with incident CVD or all-cause mortality (HR:1.53; CI:1.14-2.05). MASLD was not associated with incident CVD or all-cause mortality (HR:1.14; CI: 0.94-1.40), but it was associated with incident CVD alone (HR:1.69; CI:1.19-2.39). The relationship between elevated ALT/AST and incident or all-cause mortality was modified by MASLD, such that the strongest association between elevated ALT/AST and incident CVD or all-cause mortality was in the absence of MASLD (HR:1.95; CI:1.20-3.18). CONCLUSIONS:Among Hispanic adults FIB-4 was strongly associated with CVD or all-cause mortality and among persons without MASLD, elevated ALT/AST were associated with CVD or all-cause mortality.

BACKGROUND:The clinical benefits of mavacamten in patients with obstructive hypertrophic cardiomyopathy previously treated with advanced therapies are not established. METHODS:Clinical and echocardiographic outcomes of patients treated with mavacamten for left ventricular outflow obstruction for at least 8 weeks were assessed based on prior treatment with one or more advanced therapies: disopyramide, septal myectomy, alcohol septal ablation, dual-chamber ventricular pacing with short atrioventricular delay; we also evaluated patients with left ventricular outflow obstruction that emerged as major driver of symptoms after aortic valve replacement. RESULTS:=0.31). CONCLUSIONS:Mavacamten is a safe and effective treatment for symptomatic left ventricular outflow obstruction in patients with obstructive hypertrophic cardiomyopathy resistant to previous advanced pharmacologic therapy, surgery, or alcohol septal ablation or who develop manifest left ventricular outflow obstruction after aortic valve replacement.

BACKGROUND:Disopyramide, used in obstructive hypertrophic cardiomyopathy (oHCM) for its negative inotropic properties mediated by its reduction in cytosolic calcium, has been recommended for decades as an option to relieve resistant obstruction. Aficamten is a selective cardiac myosin inhibitor that reduces hypercontractility directly by reducing myosin-actin interaction. OBJECTIVES/OBJECTIVE:This study aims to investigate the safety and efficacy of concomitant use and withdrawal of disopyramide in patients with symptomatic oHCM receiving aficamten. METHODS:Patients with oHCM enrolled in REDWOOD-HCM Cohort 3 (open-label), SEQUOIA-HCM (placebo-controlled), and FOREST-HCM (open-label) were analyzed. The authors identified 4 groups, each with patients symptomatic despite background therapy with disopyramide who received: 1) disopyramide plus aficamten and subsequent aficamten withdrawal per protocol (Diso-Afi Withdrawal); 2) disopyramide plus placebo (Diso-Pbo); 3) aficamten plus disopyramide with subsequent disopyramide withdrawal (Afi-Diso Withdrawal); and 4) continued both disopyramide and aficamten (Diso+Afi Continuous). Assessments were performed at baseline, after aficamten or placebo add-on therapy, and after washout (except at week 24 for Diso+Afi Continuous group). RESULTS:Overall, 50 unique patients from 3 trials enrolled, resulting in 93 subjects (segments) across 4 groups: Diso-Afi Withdrawal (n = 29), Diso-Pbo (n = 20), Afi-Diso Withdrawal (n = 17), and Diso+Afi Continuous (n = 27); mean disopyramide dose was 331 ± 146 mg/d. The addition of aficamten to disopyramide alleviated left ventricular outflow tract (LVOT) obstruction (resting: change [Δ] in least squares mean -27.0 ± 3.6, Valsalva: Δ least squares mean -39.2 ± 5.0, both P < 0.0001), symptoms (≥1 NYHA functional class improvement: 77.8% [95% CI: 61.0-94.5]; P < 0.0001; Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score: 12.3 ± 3.3 [P < 0.001]), and reduced N-terminal pro-B-type natriuretic peptide ratio: 0.35 [95% CI: 0.26-0.48]; P < 0.0001, and there was no significant change with placebo. Withdrawal of aficamten while on disopyramide resulted in return of LVOT obstruction, worsening of symptoms, and increase in NT-proBNP to baseline values. Conversely, withdrawal of disopyramide while on aficamten did not impact efficacy. There were no safety events associated with aficamten or disopyramide withdrawal, and no episodes of atrial fibrillation after disopyramide withdrawal. CONCLUSIONS:In this cohort of patients with symptomatic oHCM with persistent LVOT obstruction, combination therapy with aficamten and disopyramide was safe and well tolerated but did not enhance clinical efficacy vs aficamten alone. For such oHCM patients, aficamten treatment may be considered with an option to discontinue disopyramide. (Dose-finding Study to Evaluate the Safety, Tolerability, PK, and PD of CK-3773274 in Adults With HCM [REDWOOD-HCM]; NCT04219826) (Aficamten vs Placebo in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy [SEQUOIA-HCM]; NCT05186818) (Open-label Extension Study to Evaluate the Long-term Safety and Tolerability of Aficamten in Adults With HCM [FOREST-HCM]; NCT04848506).

BACKGROUND:Calcific aortic valve disease (CAVD), and ensuing severe aortic stenosis (AS), is the foremost valvular disorder of aging, yet preventive therapies are lacking. A better understanding of the molecular underpinnings of aortic valve calcification (AVC) is necessary to develop pharmacologic interventions. METHODS AND RESULTS/RESULTS:=0.009). CONCLUSIONS:This study of older adults newly identified and largely replicated associations of 3 circulating proteins with calcific aortic valve disease, of which the relationship of plasma KLKB1 may have a causal basis. Additional investigation is necessary to determine if KLKB1 could be harnessed for calcific aortic valve disease therapeutics.

Hypertrophic cardiomyopathy is a common but underrecognized cardiac disorder characterized by a heterogenous phenotype that includes increased left ventricular thickness, outflow obstruction, diastolic dysfunction, and arrhythmia. Hypertrophic cardiomyopathy is often heritable and associated with pathogenic variants in sarcomeric genes. While not curable, an integrated approach involving medical, interventional, and surgical care can have a considerable impact on disease burden, quality of life, and mortality. This review provides a practical overview of important topics in hypertrophic cardiomyopathy, including evaluation of differential diagnosis, imaging, provocation of left ventricular outflow obstruction, treatment of obstructive and nonobstructive hypertrophic cardiomyopathy with negative inotropic therapy and myosin inhibition, as well as surgical and interventional approaches to septal reduction and mitral valve intervention.