Heart Failure in Hypertrophic Cardiomyopathy

Background: Heart failure (HF) in hypertrophic cardiomyopathy (HCM) is poorly characterized, especially in patients with preserved left ventricular ejection fraction (LVEF). Clarifying HF characteristics in HCM is essential to guide patient selection for emerging therapies. Research Questions: What is the prevalence of HF in HCM patients? What are the risk markers of HF? Methods: The study is a cross-sectional analysis of HiRO-HCM, an ongoing multicenter registry. This study included HCM patients aged ≥ 16 years with available data to allow for central ascertainment of HF, defined as i) history of hospitalization for HF requiring diuretics, heart transplantation or mechanical circulatory support; and/or ii) New York Heart Association (NYHA) class ≥ II with increased filling pressure (E/e′ ratio ≥ 14 and/or a NT-proBNP ≥ 400 ng/L [≥800 ng/L in atrial fibrillation]). The association of risk markers with HF was assessed with logistic regression. Analyses were performed in the overall cohort, and in 3 subgroups: obstructive HCM (oHCM), non-obstructive HCM (nHCM) with LVEF≥50%, and nHCM with LVEF<50%. The presence of obstruction and LVEF were assessed from echocardiography performed within 4 years (median 0.6 year) of HF ascertainment, using corelab interpretation when images are available (59% of the study cohort). NT-proBNP was systematically measured in patients with available plasma (81% of the cohort). Results: We included 1,632 patients (33% females; age 58±14 years). The maximal left ventricular wall thickness was 18±4 mm, and 613 (45%) patients carried a causal genetic variant. The median NT-proBNP was 490 [189-1140] ng/L and mean E/e’ was 11±4. In the overall cohort, 510 (31%) patients met the definition of HF, including 93 hospitalized for HF and 26 transplanted. The prevalence of HF was 41% in the oHCM subgroup, 26% in nHCM with LVEF≥50%, and 65% in nHCM with LVEF<50% (P<0.001). Several variables were associated with increased odds for HF (Figure). In multivariable analysis, female sex emerged as a strong risk factor for HF in all 3 subgroups, with a 3-fold increased risk for HF (P<0.001). Conclusion: HF affects one-third of patients with HCM. Female sex is a robust and consistent predictor of HF across all phenotypes. The findings underscore the importance of sex-specific evaluation and earlier recognition of HF symptoms in HCM management. These findings may inform risk stratification and selection for novel therapies targeting HCM-related HF.

case presentation: A 48-year-old woman presents with exertional dyspnea and recurrent syncope. One year earlier, a permanent pacemaker was placed after she complained of fatigue and was found to have high-grade atrioventricular block. Now, she has echocardiographic evidence of moderate to severe left ventricular (LV) systolic dysfunction with regional wall-motion abnormalities. Nuclear imaging is notable for heterogeneous myocardial uptake of technetium Tc99m sestamibi, and coronary angiography reveals widely patent epicardial vessels. Multiple episodes of nonsustained ventricular tachycardia (VT) are documented on continuous ECG monitoring. What are the diagnostic considerations for this patient, and what further evaluations are indicated? This patient presents with dilated cardiomyopathy (DCM) with electric instability (DCM+E), which we define as conduction disease and arrhythmia out of proportion to the severity of LV systolic dysfunction. Diverse causes can result in DCM+E and fall into general categories of inflammatory, infectious, hereditary, and infiltrative processes. Cardiac presentation associated with these conditions is distinct from more common causes of DCM such as ischemic heart disease, viral myocarditis, valvular dysfunction, pregnancy, or substance abuse. Clinical features that are suggestive of DCM+E include supraventricular arrhythmias or conduction disease that precedes cardiomyopathy, multiple VT morphologies, and features suggestive of ischemic heart disease (Q waves, regional wall-motion abnormalities, perfusion defects, ventricular aneurysm) in the absence of epicardial stenoses. In this Clinician Update, we focus on the diagnostic approach to patients with DCM+E. Emphasis is placed on diagnoses that are relatively common or for which the clinical management would be impacted significantly by recognition of the underlying cause. Ischemic heart disease may present with conduction disease and a high burden of arrhythmia, especially in the setting of acute myocardial ischemia/infarction. The exclusion of obstructive coronary artery disease is strongly recommended in patients with DCM+E because atherosclerosis is so prevalent, evidence-based treatment is readily available, and the …

Background: Hypertrophic cardiomyopathy (HCM) is a common genetic disease with diverse morphology, symptoms, and prognosis. Hypertrophied myocardium metabolism has not been explored in detail. We assessed the association between myocardium lipid metabolism and clinical severity of heart failure (HF) in HCM using imaging mass spectrometry (IMS). Methods and Results: We studied 16 endomyocardial biopsy (EMB) specimens from patients with HCM. Analysis was conducted using desorption electrospray ionization IMS. The Samples were assigned into two cohorts according to the period of heart biopsy (cohort 1, n=9 and cohort 2, n=7). In each cohort, samples were divided into two groups according to the clinical severity of HF in HCM: clinically severe and clinically mild groups. Signals showing a significant difference between the two groups were analyzed by volcano plot. In cohort 1, the volcano plot identified four signals; the intensity in the clinically severe group was more than twice that of the mild group. Out of the four signals, docosahexaenoic acid (DHA) showed significant differences in intensity between the two groups in cohort 2 (10575.8±2750.3 vs. 19839.3±4803.2, p=0.025). Conclusion: The intensity of DHA was significantly higher in EMB samples from the clinically severe HCM group than in those from the mild group. Funding Information: This study received funding from the Ministry of Education, Science, Sports and Culture of Japan, Grants-in-Aid for Scientific Research (Grant Number 18K08065 [YM]). Declaration of Interests: The authors have no conflicts of interest to disclose. Ethics Approval Statement: All the patients provided informed consent. The institutional review board of Hamamatsu University School of Medicine approved all aspects of this study (application number 17-261). The study was conducted in accordance with the regulations of Declaration of Helsinki.

Mitral regurgitation (MR) is a frequent comorbidity in patients with hypertrophic cardiomyopathy (HCM), which includes distinct subtypes with various characteristics. However, data on the long-term prognostic impact of MR and its progression or regression over time remain limited, particularly across individual HCM subtypes. Patients with HCM were retrospectively included from a Japanese multicenter registry and compared by MR severity (moderate or greater versus mild or less) within each subtype: hypertrophic obstructive cardiomyopathy (HOCM), end-stage HCM (ES-HCM), and other HCM (including nonobstructive, midventricular obstruction, and apical HCM). Among 3602 patients (HOCM: n=837; ES-HCM: n=275; other HCM: n=2490), the prevalence of moderate or greater MR was highest in HOCM (36.3%), followed by ES-HCM (21.5%) and other HCM (8.5%). During a median follow-up of 5.3 (interquartile range, 2.1-9.3) years, the cumulative 5-year incidence of all-cause death or heart failure hospitalization was not significantly different between the moderate or greater MR and mild or less MR groups in HOCM (14.6% versus 12.4%; P=0.35) or ES-HCM (60.7% versus 54.7%; P=0.84). After adjustment for clinical covariates, no significant association was observed in either subtype (HOCM: hazard ratio, 1.13 [95% CI, 0.79-1.60], P=0.51; ES-HCM: hazard ratio, 0.84 [95% CI, 0.55-1.28], P=0.42). In contrast, in other HCM, moderate or greater MR was significantly associated with the higher 5-year cumulative incidence of all-cause death or heart failure hospitalization (34.2% versus 13.9%, P<0.001), which remained significant after adjustment, with a significant interaction (hazard ratio, 1.45 [95% CI, 1.09-1.91], P=0.01; Pinteraction=0.02). MR severity improved over time in HOCM, showed no clear change in ES-HCM, and worsened in other HCM (P<0.001, 0.46, and <0.001, respectively; Pinteraction <0.001). In patients with HCM, moderate or greater MR was not associated with worse outcomes in HOCM or ES-HCM, but had significant prognostic implications in other HCM subtypes, suggesting the need for HCM subtype-specific MR management.

The clinical course of patients with hypertrophic cardiomyopathy and advanced heart failure (HF) subtended by progressive left ventricular dysfunction has received limited attention. Our aim was to assess the outcome of HF and impact of treatment options including the implantable cardioverter-defibrillator and heart transplantation (HT) in patients with hypertrophic cardiomyopathy evaluated at 2 Italian referral centers >3 decades. All-cause mortality and a combined end point including death, HT, or appropriate implantable cardioverter-defibrillator shock were assessed in 71 consecutive patients with HF not related to outflow obstruction (7% of the entire hypertrophic cardiomyopathy cohort) followed up for 6.1±6.9 years after development of New York Heart Association class III to IV symptoms. At enrollment, left ventricular ejection fraction was <50% in 55 patients and >50% in 16; all had restrictive left ventricular filling. During follow-up, 35 patients died (49%%; 5-year rate, 49%) and 53 met the combined end point (75%; 5-year rate, 62%). Most events occurred in the 3 years after HF onset (17% per year compared with only 3% per year subsequently). Appropriate implantable cardioverter-defibrillator shocks occurred in 11 of 34 implanted patients. Of 37 patients evaluated for HT, 14 were transplanted, 10 listed, and 13 excluded; 2 early post-HT deaths occurred in patients with elevated pulmonary vascular resistance. Eleven of the 14 HT patients were alive at 10±8 years. In hypertrophic cardiomyopathy, advanced HF not associated with outflow obstruction portends a severely unfavorable prognosis, particularly in the first 3 years after onset of symptoms, despite frequently preserved systolic function in about one quarter of the patients. Outcome of HT is favorable but requires early consideration, as the window of opportunity may be short.

<i>Circulation: Cardiovascular Interventions</i> Editors’ Picks

A industria brasileira, apos intenso processo de crescimento e consolidacao durante seu periodo de industrializacao substitutiva de importacoes (1956-1979), passou a sofrer, dentro de um contexto de mudanca de paradigma produtivo, um constante processo de defasagem quanto a incorporacao de tecnologias a partir dos anos 80. Esse atraso se manifestou tanto na obsolescencia das maquinas e equipamentos, quanto nos modelos administrativos e nas relacoes capital-trabalho, devido principalmente ao Estado, principal fomentador do desenvolvimento da economia e da industria ter perdido a capacidade de realizar politicas industriais (PI) e tecnologicas (PT) que promovessem uma rearticulacao interna das forcas produtivas. Nesse sentido, na presente pesquisa se concentrou a discussao na apresentacao dos determinantes fundamentais do atraso tecnologico da industria brasileira decisivamente a partir dos anos 80, analisando-se, para isso, as condicionantes politicas, economicas e ideologicas, tendo-se como foco as politicas industriais e tecnologicas promovidas pelo Estado brasileiro que, mesmo fomentando um crescimento industrial acelerado da economia com base no paradigma da producao em massa, basicamente prezou pelo desenvolvimento de uma industria voltada para a capacidade produtiva. Nesse sentido, quando se tornou premente uma transicao para o novo paradigma de producao flexivel, esta embasada na geracao de capacidade tecnologica, emergiram inumeras barreiras a essa mudanca. Mesmo a economia tendo buscado desenvolver um nucleo de pesquisa e desenvolvimento e ciencia e tecnologia proprios, esses nao foram suficientemente dinâmicos o bastante a ponto de colocar o pais em movimentos de catching up tecnologico constante como ocorria nos paises mais desenvolvidos, buscando-se direcionar o desenvolvimento da economia para o novo paradigma produtivo. De outro lado, quanto as PI e PT adotadas no desenvolvimento da Coreia do Sul, o fomento do processo de catching up produtivo e tecnologico possibilitou a esse pais absorver de forma dinâmica a “janela de oportunidade” que se abriu com o surgimento do novo paradigma, possibilitando ao pais, que teve um processo de industrializacao tardia como o Brasil, desenvolvesse uma das principais industrias do mundo no que tange a geracao de produtos intensivos em alta tecnologia, votados ao mercado internacional, levando a economia coreana a se situar proximo ou sobre a fronteira tecnologica em expansao do novo paradigma. Assim, o estudo parte do referencial teorico da abordagem schumpeteriana a fim apontar alguns dos elementos que levaram a estrutura industrial brasileira a se conformar com um dinamismo relativamente lento no seu processo de desenvolvimento tecnologico formando uma estrutura com pouca competitividade nos setores mais dinâmicos da industria, os de alta tecnologia e que representam, atualmente o segmento chave da competicao empresarial internacional. Este cenario contrasta com o caso oposto da Coreia do Sul onde esse setor da economia, atualmente, se mostra bastante dinâmico em termos de geracao e disseminacao das inovacoes tecnologicas.

Echocardiographic Predictors of Heart Failure in Hypertrophic Cardiomyopathy Secondary to Hypertension

A High-Fidelity Three-Dimensional Computational Model of a Patient with Hypertrophic Cardiomyopathy

Characterization of atrial histology in a patient with hypertrophic cardiomyopathy: Possible evidence of a primary atrial myopathy

Section 11: Evaluation and Management of Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction

Heart transplantation (HT) is the sole therapeutic option for selected patients with hypertrophic cardiomyopathy (HC) and refractory heart failure. However, the results of HT have not been systematically investigated in HC. We assessed the pathophysiologic profile of HT candidates and the outcome after transplantation in 307 patients with HC consecutively evaluated at our tertiary referral center from 1987 to 2005; follow-up was 9.9+8.2 years. Outcome of recipients with HC was compared with that of 141 patients who underwent transplantation for idiopathic dilated cardiomyopathy at our center over the same period. Of 21 patients with HC who entered the transplantation list, 20 had end-stage evolution with systolic dysfunction and 1 had an extremely small left ventricular cavity with impaired filling and recurrent cardiogenic shock during paroxysmal atrial fibrillation. Of 33 study patients with HC who showed end-stage evolution during follow-up, the 23 who were included on the waiting list or died from refractory heart failure (2 patients) were significantly younger than the 10 patients who remained clinically stable (37+/-14 vs 57+/-17 years, p=0.004). Of the 21 HT candidates, 18 underwent transplantation during follow-up. In heart transplant recipients, 7-year survival rate was 94% and not different from that of the 141 patients who received transplants for idiopathic dilated cardiomyopathy (p=0.66). In conclusion, long-term outcome after HT in patients with HC is favorable and similar to that of patients with idiopathic dilated cardiomyopathy. In patients with end-stage HC, young age is associated with more rapid progression to refractory heart failure.

Clinicopathological profiles of progressive heart failure in hypertrophic cardiomyopathy

Percutaneous Ventricular Assist Device in Hypertrophic Obstructive Cardiomyopathy With Cardiogenic Shock: Bridge to Myectomy

AimsTo describe the phenotype, genetics, and events associated with the development of hypertrophic cardiomyopathy (HCM) with reduced ventricular function (HCMr). Heart failure in HCM is usually associated with preserved ejection fraction, yet some HCM patients develop impaired systolic function that is associated with worse outcomes.Methods and resultsOur registry included 1328 HCM patients from two centres in Spain and Israel. Patients with normal baseline ventricular function were matched, and a competing‐risk analysis was performed to find factors associated with HCMr development. Patient records were reviewed to recognize clinically significant events that occurred closely before the development of HCMr. Genetic data were collected in patients with HCMr. A composite of all‐cause mortality or ventricular assist device (VAD)/heart transplantation was assessed according to ventricular function. Median age was 56, and 34% were female patients. HCMr at evaluation was seen in 37 (2.8%) patients, and 46 (3.5%) developed HCMr during median follow up of 9 years. HCMr was associated with younger age of diagnosis, poor functional class, and ventricular arrhythmia. Atrial fibrillation, pacemaker implantation, and baseline left ventricular ejection fraction (LVEF) of ≤55% were significant predictors of future HCMr development, while LV obstruction predicted a lower risk. Genetic testing performed in 53 HCMr patients, identifying one or more pathogenic variant in 38 (72%): most commonly in myosin binding protein C (n = 20). Six of these patients had an additional pathogenic variant in one of the sarcomere genes. Patients with baseline HCMr had a higher risk (hazard ratio 6.4, 4.1–10.1) for the composite outcome and for the individual components. Patients who developed HCMr in the course of the study had similar mortality but a higher rate of VAD/heart transplantation compared with HCM with normal LVEF.ConclusionsHypertrophic cardiomyopathy with reduced ejection fraction is associated with heart failure and poor outcome. Arrhythmia, cardiac surgery, and device implantation were commonly documented prior to HCMr development, suggesting they may be either a trigger or the result of adverse remodelling. Future studies should focus on prediction and prevention of HCMr.