Left Ventricular Hypertrophy and Hypertrophic Cardiomyopathy in Adult Solid Organ Transplant Recipients.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) in pediatric solid organ transplant recipients has been reported in association with use of calcineurin inhibitors. However, data on the incidence and prevalence of HCM in adult posttransplant patients are limited. We sought to describe the clinical characteristics of solid organ transplant recipients who were diagnosed with HCM from 2011 to 2021 at a single center. METHODS: Patients who had undergone solid organ transplant and exhibited left ventricular hypertrophy with left ventricular wall thickness ≥13 mm on transthoracic echocardiography were included. Clinical history, pedigree analysis, clinical genetic testing, transthoracic echocardiography, cardiac magnetic resonance imaging, treatment, and follow-up testing results were collected. Categorical variables were described as n (%). Continuous variables were described with medians and interquartile ranges and compared using the Wilcoxon rank-sum and Kruskal-Wallis tests. A 2-sided P < 0.05 was considered statistically significant. RESULTS: Three lung, 5 kidney, and 4 liver transplant recipients from 12 different families were included. Seven patients (58%) did not carry a preexisting diagnosis of hypertension, and none had a history of aortic or subaortic stenosis. A majority of patients exhibited asymmetric septal hypertrophy (67%; medial septal thickness versus left ventricular posterior wall thickness 17 versus 13 mm; P < 0.001) and dynamic left ventricular outflow tract (LVOT) obstruction (58%). All patients were managed long term with calcineurin inhibitors. Clinical genetic testing in 6 patients identified 2 with disease-causing variants in 2 sarcomere genes, myosin binding protein-C and myosin heavy chain 7. Four patients (33%) underwent successful septal reduction therapy for treatment of symptomatic LVOT obstruction. CONCLUSIONS: Symptomatic HCM with dynamic LVOT obstruction can develop in solid organ transplant recipients, and genetic testing can identify individuals with sarcomeric HCM. Medical management and septal reduction therapies are treatment options for severe symptomatic disease.

Baseline Characteristics of the VANISH Cohort.

BACKGROUND: The VANISH trial (Valsartan for Attenuating Disease Evolution in Early Sarcomeric Hypertrophic Cardiomyopathy) targeted young sarcomeric gene mutation carriers with early-stage hypertrophic cardiomyopathy (HCM) to test whether valsartan can modify disease progression. We describe the baseline characteristics of the VANISH cohort and compare to previous trials evaluating angiotensin receptor blockers. METHODS: Applying a randomized, double-blinded, placebo-controlled design, 178 participants with nonobstructive HCM (age, 23.3±10.1 years; 61% men) were randomized in the primary cohort and 34 (age, 16.5±4.9 years; 50% men) in the exploratory cohort of sarcomeric mutation carriers without left ventricular hypertrophy. RESULTS: In the primary cohort, maximal left ventricular wall thickness was 17±4 mm for adults and Z score 7.0±4.5 for children. Nineteen percent had late gadolinium enhancement on cardiac magnetic resonance. Mean peak oxygen consumption was 33 mL/kg per minute, and 92% of participants were New York Heart Association functional class I. New York Heart Association class II was associated with older age, MYH7 variants, and more prominent imaging abnormalities. Six previous trials of angiotensin receptor blockers in HCM enrolled a median of 24 patients (range, 19-133) with mean age of 51.2 years; 42% of patients were in New York Heart Association class ≥II, and sarcomeric mutations were not required. CONCLUSIONS: The VANISH cohort is much larger, younger, less heterogeneous, and has less advanced disease than prior angiotensin receptor blocker trials in HCM. Participants had relatively normal functional capacity and mild HCM features. New York Heart Association functional class II symptoms were associated with older age, more prominent imaging abnormalities, and MYH7 variants, suggesting both phenotype and genotype contribute to disease manifestations. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01912534.

Ventilatory inefficiency reflects right ventricular dysfunction in systolic heart failure.

BACKGROUND: An increased minute ventilation (VE)/carbon dioxide production (VCO2) relationship, an expression of ventilatory inefficiency (VI), is associated with increased morbidity and mortality in patients with left ventricular systolic dysfunction (LVSD). A direct link between VI and a specific cardiac abnormality has not been established. METHODS: We analyzed cardiopulmonary exercise test (CPET) data from patients (N=83) with severe LVSD (ischemic and nonischemic; left ventricular ejection fraction [LVEF] 19%±7%) and at least moderate exercise intolerance. Subjects were stratified into two groups based on the (VE/VCO2 ratio at anaerobic threshold (VE/VCO2@AT) (group 1 VE/VCO2@AT≤34; group 2 VE/VCO2@AT>34). Clinical, CPET, echocardiographic, and hemodynamic data were compared between groups. RESULTS: Group 2 subjects had lower exercise capacity (peak (VO2, 45.7%±11.8% vs 50.4±8.9% predicted; P<.05), with a significantly lower oxygen pulse (71.6%±24.5% vs 85.4±18.5% predicted) and maximum systolic BP (122±19 mm Hg vs 138±22 mm Hg; P<.001 for both), suggesting a more blunted stroke volume to exercise vs group 1. There were no differences in left ventricular (LV) size, LVEF, or mitral regurgitation between the two groups. In sharp contrast, group 2 had larger right ventricular (RV) dimensions (4.5±1.1 cm vs 3.9±0.8 cm) and more severe RV systolic dysfunction (RV fractional area change 26%±11% vs 33%±12%; tricuspid annular plane systolic excursion [TAPSE] 1.6±0.5 cm vs 2.0±0.5 cm; all P<.001) vs group 1. Multivariable analysis revealed that only TAPSE and Doppler-estimated pulmonary artery systolic pressure were independently associated with VE/VCO2@AT and the (VE/VCO2slope. The VE/VCO2@AT, VE/VCO2 slope, and TAPSE had nearly identical predictive value for death or transplant. CONCLUSIONS: The present study suggests that VI is a functional, noninvasive marker of more advanced right-sided heart dysfunction in patients with severe LVSD.