Nonobstructive Hypertrophic Cardiomyopathy Research Articles

Submucosal hemorrhage of the esophagus: a case report.

Submucosal hemorrhage of the esophagus is relatively rare and the course of this disease remains unclear. We report a case of this disease. The patient was a 68-year-old man who visited a clinic complaining of sudden-onset epigastric and back pain. He had been taking warfarin and a statin due to non-obstructive hypertrophic cardiomyopathy, right subclavian artery stenosis, and chronic atrial fibrillation. Contrast-enhanced computed tomography showed esophageal submucosal hemorrhage. Detailed endoscopic examination was difficult because of the massive hemorrhage and progressive esophageal mucosal edema. He was transferred to our hospital due to progression of anemia. Fortunately, hemorrhagic anemia showed no progression with conservative fasting therapy after admission to our hospital. Esophageal mucosa over the submucosal hemorrhage detached and regenerative tissue was observed on endoscopic examination 1week later. Esophageal submucosal hemorrhage should be included among the differential diagnoses for patients presenting with chest and back pain.

Abstract 4140118: Identification of Obstructive and Non-Obstructive Hypertrophic Cardiomyopathy Patients Using Natural Language Processing in a Large Integrated Healthcare System

Introduction: Accurately identifying and characterizing patients with hypertrophic cardiomyopathy (HCM) is critical for population management and care optimization. Research Question: To develop natural language processing (NLP) algorithms to identify and characterize obstructive (oHCM) and non-obstructive (nHCM) HCM patients directly from echocardiograms, and to compare with the presence or absence of HCM-related diagnosis codes. Methods: We developed and validated NLP algorithms to identify HCM from all adult (age≥18yrs) echocardiograms performed from 2010-2019 in Kaiser Permanente Northern CA (KPNC), capturing measures of any HCM, HCM subtype, hypertrophy subtype, septal and posterior LV wall thickness, resting and stress/Valsalva LVOT gradients, and systolic anterior motion. We developed a rules-based algorithm (following AHA/ACC criteria) to classify patients as having HCM, including oHCM or nHCM subtypes, and possible HCM (defined as wall thickness ≥2cm without other criteria meeting an HCM definition). We evaluated the presence of HCM-related ICD-9/10 diagnosis codes among patients classified as HCM/non-HCM from echocardiograms using NLP, and linked baseline demographics and clinical parameters from our integrated electronic medical record. Results: Among 472,405 adults with echocardiograms, we identified 2,892 patients with HCM based upon NLP-derived measures (all NLP measures achieved >95% positive predictive value and >95% negative predictive value), including 1,585 (55%) with oHCM, 1,145 (40%) with nHCM, and 162 (6%) which could not be classified (Figure). Among those 2,892 patients, 1,283 did not have any associated HCM ICD-9/10 diagnosis codes (Table). Among 469,513 patients with no identified HCM from NLP-based algorithms, HCM ICD-9/10 diagnosis codes existed in 1,567 patients (Table). We also identified 4,593 patients with possible HCM by NLP, only 4.5% of whom had an associated HCM code. Among confirmed HCM patients by NLP, oHCM patients were slightly older (66 vs 61 yrs), more likely female (53% vs 43%), had similar mean septal wall thickness (1.7cm vs 1.7cm), but were more likely to have a septal hypertrophy subtype (46% vs 28%) compared to nHCM patients. Conclusions: Echocardiogram-based NLP methods can improve the identification of and care for HCM patients. Many patients with possible HCM may be underdiagnosed, representing an opportunity for quality improvement.

Abstract 4134685: Cardiopulmonary Exercise Testing for Characterization and Prognostication in Hypertrophic Cardiomyopathy: A Meta-Analysis

Background: Hypertrophic cardiomyopathy (HCM) carries substantial risk of adverse cardiac events. Consequently, detailed physiologic assessment and accurate risk stratification in HCM are of high clinical importance. Aim: To synthesize current evidence on the utility of cardiopulmonary exercise testing (CPET) for characterization and prognostication of HCM. Methods: PubMed, Embase, Scopus, and Web of Science were systematically searched for eligible studies from database inception to November 2023. Studies that had at least one CPET performed in HCM patients, with corresponding test data reported, were included. Abstracts with no full-text and studies focused on pediatric populations were excluded. The primary outcome was a composite endpoint of cardiovascular adverse events. Hazard ratios (HR) and 95% confidence interval (CI) from Cox proportional hazard model were meta-analyzed. This study was performed following the PRISMA guidelines and registered under PROSPERO (CRD42023487759). Results: Sixty full-length manuscripts focused on CPETs performed in HCM patients were included, comprising 12,914 patients. Despite male predominance (66%) and average age of 48 years, peak VO 2 was only 6.2 [95% CI, 6.0-6.4] metabolic equivalents (21.8 [20.9-22.6] mL/kg/min), consistent with significant functional limitation. In subanalyses, peak VO 2 was 18.9 [18.0-19.9] mL/kg/min in obstructive HCM and 22.5 [20.8-24.2] mL/kg/min in non-obstructive HCM. Compared to commonly used metrics such as NYHA Class, CPET markedly enhances sensitivity to detect impaired cardiac performance ( Figure ). This meta-analysis highlights several easily-derived CPET variables that consistently predict HCM prognosis. An increase of 1 mL/kg/min in peak VO 2 was associated with a lower HR of 0.83 [0.76-0.90] for adverse cardiac events, while a 1 unit increase in the VE/VCO 2 slope was associated with a higher HR of 1.12 [1.03-1.23]. Abnormal blood pressure response to exercise conferred a 2.5-fold [2.0-3.1] increase in adverse events. Conclusion: CPET is a valuable objective method for multi-dimensional physiologic assessment and prognostication in HCM. With further standardization, CPET is well suited for more widespread clinical utilization in HCM patients.

Loss of quality of life and increased societal costs in patients with hypertrophic cardiomyopathy: the AFFECT-HCM study.

Hypertrophic cardiomyopathy (HCM) is the most prevalent inherited cardiac disease. The impact of HCM on quality of life (QoL) and societal costs remains poorly understood. This prospective multi-centre burden of disease study estimated QoL and societal costs of genotyped HCM patients and genotype-positive phenotype-negative (G+/P-) subjects. Participants were categorized into three groups based on genotype and phenotype: 1) G+/P- (left ventricular (LV) wall thickness <13 mm), 2) non-obstructive HCM (nHCM, LV outflow tract (LVOT) gradient <30 mmHg), and 3) obstructive HCM (oHCM, LVOT gradient ≥30 mmHg). We assessed QoL with EQ-5D-5L and Kansas City Cardiomyopathy Questionnaires (KCCQ). Societal costs were measured using medical consumption (iMCQ) and productivity cost (iPCQ) questionnaires. We performed subanalyses within three age groups: <40, 40-59, and ≥60 years. From three Dutch hospitals, 506 subjects were enrolled (84 G+/P-, 313 nHCM, 109 oHCM; median age 59 years, 39% female). HCM (both nHCM and oHCM) patients reported reduced QoL vs G+/P- subjects (KCCQ: 88 vs 98, EQ-5D-5L: 0.88 vs 0.96; both p<0.001). oHCM patients reported lower KCCQ scores than nHCM patients (83 vs 89, p=0.036). Societal costs were significantly higher in HCM patients (€19,035/year vs €7,385/year) compared to G+/P- controls, mainly explained by higher healthcare costs and productivity losses. Being symptomatic and of younger age (<60 years) particularly led to decreased QoL and increased costs. HCM is associated with decreased QoL and increased societal costs, especially in younger and symptomatic patients. oHCM patients were more frequently symptomatic than nHCM patients. This study highlights the substantial disease burden of HCM and can aid in assessing new therapy cost-effectiveness for HCM in the future.

Epidemiology and prognosis of obstructive and non-obstructive hypertrophic cardiomyopathy in Finland: a nationwide cohort study

Abstract Background Hypertrophic cardiomyopathy (HCM) is an often hereditary myocardial disease. The Finnish population has a specific genetic background, which may influence and even predispose people to various hereditary diseases. Whilst advances in genetic testing and imaging techniques may have influenced the detection of HCM and associated subtypes, contemporary data on incidence and prevalence remain limited. Purpose This study aimed to evaluate the current trends in the incidence, prevalence, and prognosis of obstructive and non-obstructive HCM in a nationwide cohort in Finland. Methods A population-based registry study was conducted using data from Finnish nationwide healthcare registries (HILMO/avoHILMO) including individuals aged at least 12 years with recorded HCM diagnosis between 2000 and 2021. The incidence was calculated by dividing the number of newly diagnosed HCM patients by the Finnish background population. Furthermore, the mean incidence per age-group was calculated by dividing the sum of age-group specific incidences by the number of age groups. The date and cause of death were obtained from national registries (Statistics Finland). Mortality was computed by dividing the number of deaths by follow-up length. Patients were followed from 2014 to 2021, and incident cases were defined as new diagnoses after 2014. HCM cases were stratified into obstructive HCM and non-obstructive HCM based on ICD-10 codes I42.1 and I42.2, respectively. Results Among 5,834 documented patients with HCM, the overall mean incidence by age-group was 2.64/100,000, with incidence increasing with age, peaking in those aged ≥85 years (6.22/100,000 patient-years [PY]). Annual incidence of obstructive HCM decreased from 2.2 to 1.4/100,000 PY, while non-obstructive HCM increased from 4.6 to 5.4/100,000 PY between 2014 and 2021 (Fig 1). Prevalence of non-obstructive HCM rose from 40 to 56/100,000 PY, while obstructive HCM prevalence remained stable (23-24/100,000 PY). All-cause mortality was 5.5/100 PY, with obstructive and non-obstructive HCM mortality at 5.7 and 4.6/100 PY, respectively. HCM-specific deaths accounted for 16% and 12% of all deaths in patients with non-obstructive and obstructive HCM, respectively. Conclusions This nationwide study in Finland revealed an increasing incidence and prevalence of non-obstructive HCM over time, contrasting with stable rates among patients with obstructive HCM. Incidence and prevalence were strongly age dependent. Non-HCM-related deaths were predominant in both HCM subtypes.

Relationship between six-minute walk distance and cardiopulmonary exercise testing in non-obstructive hypertrophic cardiomyopathy

Abstract Background Recent studies have shown the promise of new approaches to the management of hypertrophic cardiomyopathy (HCM) symptoms. However, as HCM is a chronic disorder that evolves slowly over decades with low annual event rates, therapeutic trials in the disease rely on surrogate measures of disease severity and progression rather than hard endpoints such as mortality. Exercise capacity is one potential surrogate endpoint. Purpose To examine the relationship between peak oxygen uptake (VO2) and six-minute walk test distance (6MWD) in patients with non-obstructive hypertrophic cardiomyopathy (nHCM) and describe the association with clinical parameters and quality of life. Methods We examined baseline data from patients with nHCM enrolled in a randomised placebo-controlled trial of trimetazidine therapy. The study was conducted in a single European centre. Cardiopulmonary exercise testing (CPET) was performed to assess peak oxygen consumption (pVO2), ventilatory anaerobic threshold (VAT) and ventilatory equivalent for carbon dioxide (minute ventilation to carbon dioxide production (VEVCO2). Health related quality of life was assessed with the Minnesota Living with Heart Failure Questionnaire (MLHFQ). ECG and echocardiography were performed on the same day and biomarkers (NT-proBNP and cardiac Troponin T, cTnT) were measured prior to exercise testing. Results In 51 patients (age 50 ± 13 years; 71% male) with nHCM, pVO2 ranged from 10 to 24.3 ml/kg/min and 6MWD from 188 to 650 metres. 6MWD correlated with peak VO2 (Pearson r=0.41, 95% CI 0.15 to 0.67, p=0.003) and anaerobic threshold (r=0.32, 95%CI 0.04 to 0.55, p=0.024). After adjusting for age and sex, NT-proBNP concentration correlated with peak VO2 (radi=-0.35, 95% CI -0.69 to -0.01, p=0.042) but not 6MWD (radj=-0.05, 95% CI -0.42 to 0.32, p=0.779). Health related quality of life assessed by the Minnesota Living with Heart Failure Questionnaire (MLHFQ) correlated moderately with 6MWD (radi=-0.54, 95% CI -0.79 to -0.29, p&amp;lt;0.001) but weakly with peak VO2 (radi 0.28, 95% CI -0.55 to -0.01, p=0.042). I Conclusions There is a modest correlation between peak VO2 and 6MWD in nHCM. The pVO2 correlates more strongly with NT-proBNP whereas 6MWD better reflects quality of life. These data suggest pVO2 and 6MWD provide complementary information about health status in nHCM.Relationship between 6MWD and CPETCharacteristics of study cohort

Characterizing disease burden and health care resource utilization in patients with hypertrophic cardiomyopathy: a nationwide real-world study in Finland

Abstract Background Hypertrophic cardiomyopathy (HCM) is an often hereditary myocardial disease with an estimated prevalence of 1:500 in the general population. Purpose This study aimed to investigate healthcare resource utilization (HCRU) and associated costs in patients diagnosed with HCM (and the associated subtypes: obstructive or non-obstructive) in a nationwide cohort in Finland. Methods This retrospective, registry-based cohort study included all Finnish patients diagnosed with HCM between 2000 and 2021, who were 12+ years old at the time of diagnosis, as identified from the national care registers for healthcare. HCRU data were collected between 2014 and 2021 from the Finnish national care registers for health care and the social insurance institution. Data pertaining to New York Heart Association (NYHA) classification were collected from three Finnish university hospitals. Results The study cohort comprised 5,834 patients with an HCM diagnosis; obstructive HCM accounted for 34% of cases. Mean per patient-year costs were €6638, 95% confidence interval (CI) €6472-€7415, and €6112, 95% CI €5957-€6560 for those with obstructive and non-obstructive HCM respectively. All-cause hospitalizations at specialized care were the most prominent cost associated with patients with obstructive and non-obstructive HCM equating to 46.3% and 46.1% of the total cost respectively (Fig 1.). Comorbidity burden, as measured by Charlson comorbidity index (CCI) score, was greater in patients with the obstructive than non-obstructive phenotype of the disease (CCI ≥4: 2.2 and 1.8, p&amp;lt;0.01, respectively). The highest utilization of invasive procedures was found for patients with NYHA class III-IV. Conclusion This population-based study, utilizing real-world data, provides novel insights into HCRU and related costs among Finnish patients with HCM (and associated subtypes). HCRU appears to be primarily driven by hospitalizations at specialized care. Furthermore, the data indicate that patients with obstructive HCM are likely to have a more severe disease, with higher comorbidity burden and requiring more invasive procedures than patients with the non-obstructive form of the disease. However, there were no statistically significant differences in health care costs between those with obstructive and non-obstructive HCM.

Clinical characteristics and burden of non-obstructive hypertrophic cardiomyopathy: a real-world survey in Italy and Spain

Abstract Background Research describing non-obstructive hypertrophic cardiomyopathy (nHCM) and the associated burden of illness is sparse. Purpose This research aimed to describe the clinical characteristics of patients with nHCM and the associated clinical and societal burden of illness in Italy (IT) and Spain (ES). Methods Data were from the Adelphi HCM Disease Specific Programme (DSP), a cross-sectional survey with retrospective data collection in IT and ES (July 2022–January 2023). Ethics approval was obtained from the Pearl Institutional Review Board. Cardiologists provided data on patient demographics, employment, clinical characteristics, symptoms, support needs and treatment for up to ten consecutively consulting adult HCM patients. Patients voluntarily completed a survey containing the Kansas City Cardiomyopathy Questionnaire-23 (KCCQ). Analyses were descriptive and the mean [SD] was summarized for continuous variables. Results Overall, 112 cardiologists provided data for 483 patients with nHCM from IT (243) and ES (240). The mean age [SD] was 54.3 [14.1] and 58.0 [16.0], with 66.3% and 61.7% of patients being male, in IT and ES respectively. Eighty-four percent and 92.1% of patients were classified as New York Heart Association (NYHA) II, 14.8% and 7.1% were NYHA III, and 1.2% and 0.8% were NYHA IV, in IT and ES respectively. Among patients who completed the KCCQ, the mean [SD] KCCQ-clinical summary score was 84.9 [12.9] in IT and 81.8 [20.7] in ES. Regarding work-related impact, 30.8% (IT) and 16.7% (ES) of patients had taken time off work due to nHCM in the last three months, and 41.6% (IT) and 48.4% (ES) were not working full-time, of which 5.6% (IT) and 11.0% (ES) were not working full time due to nHCM. Additionally, 17.6% and 18.2% of patients experienced a delayed diagnosis in IT and ES respectively, with 24.0% (IT) and 25.0% (ES) having multiple delays to diagnosis. The most common symptoms reported by physicians were dyspnoea when active (83.7%), palpitations (29.3%) and fatigue (25.7%). The most prevalent concomitant conditions were hypertension (20.5%), anxiety (18.6%), and atrial fibrillation (18.4%). In IT and ES, respectively, 77.8% and 74.2% of patients were currently prescribed treatment for nHCM. The most frequently prescribed treatments were beta-blockers (83.3%), diuretics (32.1%) and angiotensin converting enzyme inhibitors (20.5%), alone or in combination. In IT and ES respectively, 14.4% and 18.8% of patients required caregiver support, at a mean [SD] of 46.3 [52.4] and 44.2 [47.5] hours per week. Conclusions While the majority of patients with nHCM were classified as NYHA II, a considerable clinical and societal burden is evident. Burden was demonstrated by the high prevalence of symptoms, comorbidities, disruptions to employment and the requirement for caregiver support among these patients, highlighting the need for new treatment and management approaches to enhance health outcomes and reduce societal impact.

AFFECT-HCM: quality of life and costs in hypertrophic cardiomyopathy

Abstract Background Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease, characterised by increased wall thickness. Pathogenic DNA variants in sarcomeric genes are identified in about half of HCM patients, enabling pre-symptomatic testing in family members. Since the first description of HCM tremendous progress has been made in the evaluation and management of HCM patients. However, little is known on the impact of HCM on quality of life (QoL) and costs. Purpose The AFFECT-HCM study evaluates the QoL, healthcare and societal costs in HCM patients and genotype-positive phenotype-negative (G+/P-) subjects. Methods The AFFECT-HCM is a multi-centre prospective study including genotyped HCM patients aged 18-80 years and G+/P- subjects. The study cohort is divided into three groups based on phenotype: G+/P- (wall thickness &amp;lt;13 mm), non-obstructive HCM (nHCM, maximal left ventricular outflow tract (LVOT) gradient &amp;lt;30 mmHg) and obstructive HCM (oHCM, LVOT gradient ≥30 mmHg). For QoL, the generic five-domain five-level EQ-5D-5L with the attached visual analogue scale and disease-specific Kansas City Cardiomyopathy Questionnaire are used. Healthcare and societal costs are measured via a bottom-up approach using the cost questionnaires iMCQ and iPCQ and expressed with means (the standard in healthcare cost reporting despite non-normality) in 2023 Euro per patient per year (€ PPPY). QoL and costs are compared between phenotypes. Results Results are summarised in the table. Between November 2022 - December 2023, 506 subjects (mean age 55 years, 39% female) were included in three Dutch hospitals. The study included 84 G+/P-, 307 nHCM and 115 oHCM subjects. Questionnaire response rate was 92%. Compared to G+/P- subjects; HCM patients were older (57 vs 46 yrs), more often male (67% vs 32%) and had more cardiovascular risk factors. Compared to nHCM patients, oHCM patients were more often symptomatic (58% vs 34%), more often in NYHA class III (19% vs 2%) and used more HCM-related medications (79% vs 64%). HCM patients, and particularly oHCM patients, reported decreased QoL with lower QoL-related questionnaire scores (Figure). The utilities (EQ-5D-5L) of HCM patients were lower than G+/P- subjects and the Dutch overall average (0.87±0.17), and for oHCM comparable with another study (0.82±0.18). Costs were higher for HCM patients than G+/P- subjects (€14374 vs €5888 PPPY) and higher in oHCM patients compared to nHCM patients (€19672 vs €12419 PPPY). The leading between-group difference is higher productivity losses in oHCM patients. Conclusion HCM is associated with reduced QoL and increased costs, especially in oHCM patients. The primary cost driver are healthcare costs, but the difference between oHCM and nHCM patients is mainly caused by indirect costs due to productivity losses. These data provide novel insights in the BoD of HCM and can aid in assessing cost-effectiveness analyses of new therapies for HCM in the future.Baseline characteristics and resultsQuality of life-related questionnaires

Exploring the effects of mavacamten through hemodynamic force analysis in patients with obstructive hypertrophic cardiomyopathy

Abstract Introduction Mavacamten is a first-in-class allosteric myosin inhibitor effective in relieving left ventricular (LV) outflow tract obstruction in patients with obstructive hypertrophic cardiomyopathy (oHCM). To date, however, its effect on cardiac mechanics is still unclear. Hemodynamic force (HDF) analysis represents the fluid dynamics correlate of deformation imaging, showing a greater sensitivity in detecting early mechanical abnormalities or response to treatment [1]. Purpose To explore the in vivo effect of mavacamten on cardiac mechanics in patients with HCM after a 3 year-treatment, using HDF analysis. Methods LV HDF analysis was performed in 6 patients with oHCM (representing a cohort of the MAVA-LTE study) at baseline and after 3 years of treatment. Apical 4-, 2-, and 3-chamber echocardiographic views were analysed using a dedicated and sofisticated software. Base-apex forces (where positive deflections represent a force directed from the apex to the base of LV, whilst negative ones are directed toward the LV apex) were assessed in terms of timing indexed to cardiac cycle duration. HDF curves from the 6 patients treated with macavamten were compared to those obtained from oHCM patients (n=20), non-obstructive HCM (noHCM) patients (n=20), and healthy controls (n=22). Results Figure 1 shows a different pattern of transition between diastole and systole in HCM patients compared to controls. Specifically, HCM patients exhibited an earlier onset of the systolic phase, expressed as a fusion of late diastolic deceleration and systolic thrust. This was numerically represented as a decrease in diastolic-systolic transition time, which is 0.22 [0.20-0.24] for oHCM, 0.23 [0.21-0.25] for noHCM and 0.26 [0.26-0.30] for controls (p ≤0.001 for control vs oHCM, p ≤0.01 for control vs noHCM). Additionally, HCM patients showed an increased rate of force generation. The time to systolic peak (i.e., time interval from the onset of systole to the maximum force) was reduced in HCM patients compared to controls, and was shorter in oHCM than in noHCM patients (0.13 [0.11-0.15] vs 0.16 [0.14-0.17], p ≤0.01), thus reflecting an increased clinotropism in HCM. After 3 years of mavacamten treatment, the diastolic-systolic transition time and the time to systolic peak returned to a level similar to that of healthy controls (0.30 [0.27-0.30] in mavacamten group vs 0.26 [0.26-0.30], p &amp;gt;0.05, and 0.21 [0.20-0.22] vs 0.19[0.17-0.20], p=0.04, respectively) (Figure 2). Conclusion HDF analysis reveals that mavacamten affects the duration of transition from diastole to systole and prolongs time from the onset to the peak in systole. These findings may explain the removal of the mechanical coupling substrate responsible for the systolic anterior movement of mitralic leaflets and the subsequent resolution of LV outflow tract obstruction by mavacamten.Distribution of time parameters

Mavacamten in a real-world hypertrophic cardiomyopathy population: how many may be eligible?

Abstract Introduction Mavacamten is a newly approved drug for obstructive hypertrophic cardiomyopathy (oHCM) and is currently being studied in non-obstructive HCM (nHCM). Our goal was to evaluate how often patients with oHCM and nHCM in a real-world cohort would be eligible for the main mavacamten trials: EXPLORER-HCM, VALOR-HCM and MAVERICK-HCM. Methods Single-centre retrospective study enrolling consecutive patients with confirmed HCM, as per the 2023 ESC Guidelines, with at least yearly follow-up in our center, from 2017-2023. Key inclusion criteria from the three trials were considered: NYHA class II-III for all; obstructive forms (defined as peak left ventricle outflow tract [LVOT] gradient ≥50 mmHg at rest, after Valsalva manoeuvre or exercise) for EXPLORER-HCM and VALOR-HCM; left ventricular ejection fraction (LVEF) ≥55% for EXPLORER-HCM and MAVERICK-HCM; LVEF ≥60% and formal criteria for septal reduction therapy for VALOR-HCM, and NT-proBNP ≥300pg/mL for MAVERICK-HCM. Key exclusion criteria (estimated glomerular filtration rate [eGFR] &amp;lt;30mL/kg/1.73m2, QTc using the Fridericia’s formula &amp;gt;500ms, paroxysmal or intermittent atrial fibrillation present on screening electrocardiograph) were also considered. Results Overall, 410 patients were diagnosed with HCM, of whom 361 (88%) were alive at follow-up and included in the analysis: mean age of 63 ± 16 years, 196 (54%) were male, 272 (75%) with septal HCM and 60 (17%) with oHCM. According to the criteria of EXPLORER-HCM, VALOR-HCM and MAVERICK-HCM, 35 (10%), 6 (2%) and 27 (7%) patients would be eligible for enrolment, respectively. In patients with oHCM, 35 (58%) would be eligible for the EXPLORER-HCM trial. In the overall cohort, 65 (18%) would have criteria for at least one of the trials. The main reasons for exclusion were as follows: 191 (53%) NYHA I, 43 (12%) with NYHA IV, 12 (3%) had a LVEF &amp;lt;55%, 8 (2%) had both HCM and infiltrative myocardial disease and/or moderate-to-severe aortic stenosis and 8 (2%) had an eGFR &amp;lt;30mL/kg/1.73m2. In patients with nHCM, 16 (5%) would have been excluded due to NT-proBNP &amp;lt;300pg/mL and 8 (3%) due to paroxysmal atrial fibrillation. Conclusion In a real-word HCM cohort, we found that approximately 1 in every 5 patients would have criteria for either of the mavacamten trials, with more than half of oHCM being potential candidates for the EXPLORER-HCM. The main reasons for non-eligibility were NYHA I and LVEF &amp;lt;55%.

Impaired myocardial energetics in both sarcomere positive and negative HCM are linked to arrhythmic risk

Abstract Background Impaired myocardial energetics play a pivotal role in the complex pathophysiology of hypertrophic cardiomyopathy (HCM), and are thought to be mediated by energy-costly sarcomeric mutations and mitochondrial dysfunction (1). Two thirds of HCM patients, however, do not possess pathogenic sarcomeric mutations (2) and instead develop the condition due to a combination of increased polygenic susceptibility and comorbidities. Whether energetic impairment, a target of novel HCM treatments (e.g., myosin modulators such as Mavacamten), similarly affects sarcomere mutation positive (Sarc+) and negative (Sarc-) HCM remains unclear, as does the association between impaired energetics and markers of arrhythmic risk such as hypertrophy severity, cardiac function and non-sustained ventricular tachycardia (NSVT). This study aimed to investigate differences in resting myocardial energetics between Sarc+ and Sarc- HCM by measuring the phosphocreatine-to-adenosine triphosphate (PCr/ATP) ratio using phosphorus magnetic resonance spectroscopy (31P-MRS) and explore the association between impaired energetics and markers of arrhythmic risk in HCM. Methods We recruited one hundred (100) participants (80 non-obstructive HCM patients and 20 age- and sex-matched controls). Myocardial energetics were assessed using 31P-MRS to measure the PCr/ATP ratio. Cardiac magnetic resonance (CMR) imaging including cine, T1 (ShMOLLI), quantitative pixel-wise perfusion mapping (3) and late gadolinium enhancement (LGE) imaging was also performed. In addition, HCM patients underwent 7-day ECG monitoring to document NSVT episodes (3 beats ≥120 bpm). Results HCM patients had impaired myocardial energetics (PCr/ATP ratio) relative to controls (HCM 1.64±0.36 vs controls 1.97±0.32 p&amp;lt;0.001). PCr/ATP ratios did not differ between Sarc+ and Sarc- HCM even after adjustment for confounders including age, hypertrophy and fibrosis burden (Sarc+ 1.64 [1.50-1.78] vs Sarc- 1.64 [1.52-1.77], p=0.993). PCr/ATP ratio showed no correlation with maximum wall thickness (p=0.257), left ventricular ejection fraction (p=0.727) or myocardial perfusion reserve (p=0.851), but did inversely correlate with global longitudinal strain (r=-0.3, p=0.025). Reduced PCr/ATP was associated with presence of fibrosis (LGE+ 1.58±0.35 vs LGE- 1.79±0.37 p=0.025) and with NSVT, independent of age or fibrosis burden (NSVT+ 1.54 [1.40-1.67] vs NSVT- 1.73 [1.62-1.86], p=0.046). Conclusion Myocardial energetics are similarly impaired in Sarc+ and Sarc- HCM, and are independently associated with impaired contractility, greater fibrosis severity and heightened arrhythmic risk. Our findings provide novel mechanistic insights into the potentially favourable response of HCM patients to energy-sparing myosin modulator therapies irrespective of genotype and highlight the potential for cardiac energetics to serve as a marker of arrhythmic risk.

Skeletal and respiratory muscle weakness contributes to decreased exercise capacity in hypertrophic cardiomyopathy

Abstract Background and Aims Although decreased exercise capacity (due to dyspnea or angina-like symptoms) constitutes the fundamental characteristics of hypertrophic cardiomyopathy (HCM), the pathophysiology of these symptoms remains only partly understood. We investigated clinical and functional determinants of decreased exercise capacity in a broad range of HCM patients irrespective of primary disease aetiology (either genetic disorder or e.g. infiltrative phenocopies in the course of cardiac amyloidosis), overt heart failure (HF) and the presence of haemodynamically significant left ventricular outflow tract obstruction (LVOTO). Further, we deterimined the contribution of skeletal and respiratory muscle weakness to decresed exercise capacity. Methods We analyzed clinical data and functional assessments (skeletal and respiratory muscle strength, physical fitness) in relation to symptomatology and sub-maximal exercise capacity in 82 clinically stable patients with HCM (females: 32 %; age: 62±16 years; left ventricular ejection fraction [LVEF] 59±7%; intraventricular septum wall thickness [IVS] 19±4 mm; median plasma N-terminal pro-B-type natriuretic peptide [NT-proBNP]: 818 pg/mL [lower and upper quartile: 208-1917]; New York Heart Association [NYHA] class 0/I/II/III: 38/18/33/11 % [0 indicates no HF]; significant LVOTO: 29%). Results HCM patients with more severe symptomatology (NYHA class II-III vs 0-I) were older, had more frequently significant LVOTO and greater comorbidity burden, and had higher NT-proBNP and worse estimated renal function (all p≤0.03). Gender distribution, percentage of beta-blocker therapy and implanted device, body mass index, major echocardiography parameters (including LVEF, left ventricular end-diastolic diameter and IVS), high-sensitive (hs) cardiac troponin type I and hs-C-reactive protein were comparable in these 2 groups of subjects (all p&amp;gt;0.05). In multivariable linear regression models more advanced age, higher circulating natriuretic peptides (NT-proBNP) and previous coronary revascularization were independent predictors of more advanced NYHA class (standardized β-coefficient=0.30, p&amp;lt;0.01; β=0.27, p&amp;lt;0.01; and β=0.22, p&amp;lt;0.05; respectively). Similarly, more advanced age, female sex and higher NT-proBNP were independent correlates of shorter distance in 6-minute walking test (6MWT) (β=-0.46, p&amp;lt;0.001; β=-0.26, p&amp;lt;0.001; and β=-0.36, p&amp;lt;0.001; respectively). All analyzed muscle parameters (including respiratory muscle strength parameters) and objective measures of physical fitness (Functional Fitness Test for older adults) remained independently associated with 6MWT distance (all p&amp;lt;0.001) when adjusted for aforementioned clinical and laboratory correlates of 6MWT. Conclusions Muscle weakness and low physical fitness are related to decreased exercise capacity in HCM and may be potential therapeutic targets to alleviate disease symptoms also in non-obstructive HCM phenotype.

Global and national insights into the decline of hypertrophic cardiomyopathy as a cause of sudden death in the young

Abstract Background &amp; Objective Hypertrophic cardiomyopathy (HCM) has been reported as a leading cause of sudden cardiac death (SCD) in the young but appears less common in contemporary cohorts of young SCD. This research aimed to determine if HCM is a common cause of SCD in the young and whether this has changed over time. Methods We analysed three national databases, the National Echo Database Australia (NEDA), Centre for Disease Control Wide-ranging Online Data for Epidemiologic Research (CDC-WONDER) and the National Coronial Information System of Australia (NCIS) to determine incidence of SCD due to HCM in ≤ 35 years old from 1999-2017. Sub-analyses assessed for differences in sex and obstructive and non-obstructive HCM phenotypes. Results NEDA: Of 40,738 individual echocardiograms 2005-2017, 868 (2.13%) exhibited the HCM phenotype. 982 patients died ≤ 35 years, of which 4 deaths were attributable to HCM (0.4%). CDC-WONDER: 41% reduction in HCM related mortality/million people across 1999-2016 (p&amp;lt;.0001). Similar reduction was seen when stratified for age, sex and non-obstructive/obstructive HCM phenotype. NCIS: 36% reduction in HCM-related SCD was observed between 2001-2010 and 2011-2016 periods (p=.049). Conclusions HCM rarely causes SCD and accounts for &amp;lt;5% of SCD in the young. Rates of HCM-related SCD have been decreasing over the last two decades. Improved survival likely relates to improved case detection and medical management.Abstract Figure

The ventilatory efficiency parameters outperform peak oxygen consumption in monitoring the therapy effects on the right ventricular load in patients with hypertrophic cardiomyopathy

Abstract Aim We sought the cardiopulmonary exercise testing (CPET) parameter that is the most reflective of right ventricular (RV) load and its coupling with pulmonary artery (PA) in patients diagnosed with hypertrophic cardiomyopathy (HCM) undergoing medical therapy. Methods CPET on recumbent bike was performed in adult patients with symptomatic non-obstructive HCM with NYHA class I–III, during phase II, randomised, open-label multicentre study, before and after diverse medical treatment for 16 weeks. Endpoints were the changes in: 1) peak oxygen consumption (peak VO2); 2) minute ventilation (VE)/carbon-dioxide (CO2) production slope during the whole CPET; 3) VE/VCO2 slope before anaerobic threshold (AT); 4) VE/VCO2 slope after AT; 5) VE/VCO2 nadir; 6) VE/VCO2 at AT; and 7) VE/VCO2 intercept. Standard ehocardiography at rest was performed concomitantly with CPET to assess tricuspid annular plane systolic excursion (TAPSE), pulmonary artery systolic pressure (PASP), severity of mitral regurgitation (MR) and TAPSE/PASP ratio as a measure of RV-PA coupling. Results Of 115 screened patients, 61 (mean age 52 years [SD 14], 43% women) met the study inclusion criteria and underwent CPET. On regression analysis, among all CPET end-point variables, the best independent predictor of the change in PASP, TAPSE and MR severity after 16 weeks of medical treatment was VE/VCO2 below AT (B=-0.28, -0.01,-0.11; SE=0.10, 0.05, 0.01; CI=-0.48 to -0.08, -0.22 to -0.01; -0.02 to 0.01; p=0.007, 0.035, 0.004, respectively), whereas the best predictor of TAPSE/PASP ratio was intercept of the VE/VCO2 curve (B=0.014, CI=0.01to 0.03, p=0.005). Conclusion The changes in VE/VCO2 slope below anaerobic threshold, and intercept of the VE/VCO2 curve outperform peak VO2 in the monitoring of therapy effects on the right heart load and RV-PV coupling in patients with hypertrophic cardiomyopathy.

Discrimination of Left Atrial Strain Patterns in Hypertensive Heart Disease and Hypertrophic Cardiomyopathy: a Cardiac Magnetic Resonance Feature.

To assess left atrial (LA) strain parameters using cardiovascular magnetic resonance imaging feature tracking (cardiac MRI-FT) for differentiating hypertensive heart disease (HHD) from hypertrophic cardiomyopathy (HCM), which are two left ventricular hypertrophic diseases that could present with similar morphologies in early stage but differ in clinical symptoms and treatment strategies. 45 patients with HHD, 85 patients with HCM (non-obstructive hypertrophiccardiomyopathy [HNCM, n = 45] and obstructive hypertrophic cardiomyopathy [HOCM, n = 40]) and 30 healthy controls (HC) were retrospectively included. LA volumes, strain, and strain rate were determined by manually contouring on the two- and four-chamber views of the CMR-FT module using CVI 42 software. LA volume parameters including LA maximum, precontraction, and minimum volume index, and total, passive, and active emptying fractions were obtained using the biplane methods. The LA strain parameters, including total strain (εs), passive strain (εe), active strain (εa), peak positive strain rate (SRs), early peak negative strain rate (SRe), and late peak negative strain rate (SRa), were obtained from the LA strain curve. The LA strain and LA strain rate were impaired in both HHD group and HCM group, and they were the most severely impaired in the HOCM group. εs (AUC = 0.691, P = 0.006; the best cutoff value, 25.1%), εa (AUC = 0.654, P = 0.027; the best cutoff value, 10.5%), SRs (AUC = 0.710, P = 0.003; the best cutoff value, 0.81 1/s) and SRa (AUC = 0.667, P = 0.016; the best cutoff value, -1.30 1/s) showed significant differences in the identification between HHD and HNCM. All LA strain parameters were different in the identification between HHD and HOCM (all P < 0.05).LA strain parameters can be helpful for differentiating HHD from HCM, providing valuable insights for diagnosis.

Detection of Left Atrial Remodeling by Three-Dimensional Echocardiography in Symptomatic Patients Known to Had Non-Obstructive Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is one of the most prevalent inherited disorders and a common cause of sudden heart death. Left atrial (LA) dilatation frequently occurs in patients with HCM as a result of impaired left ventricular (LV) relaxation or associated involvement of LA myocardium in HCM. We enrolled 170 patients known to had HCM (non-obstructive type) and 30 healthy subjects (control group). All of them underwent two-dimensional (2D) echocardiography to measure LV dimensions, function, LA dimension, LA deformations, pulmonary artery pressure (PAP) and LV global longitudinal strain (LVGLS). LA volumes and mechanics were also measured by three-dimensional (3D) echocardiography. By 2D echocardiography, patient group revealed significantly lower all LA functions vs. control group including reservoir (26 ± 4 vs. 43 ± 3, P < 0.001), conduit (-14 ± 2 vs. -25 ± 2, P < 0.001), and booster pump functions (-12 ± 2 vs. -18 ± 1, P < 0.001). PAP was significantly higher in patient group (42 ± 7 vs. 27 ± 4 in control group). LVGLS was significantly lower in patient group (-15±1.4% vs. -23±2% in control group). Using 3D speckle tracking echocardiography (STE), there were a significantly higher indexed maximum LA volume (Vmax indexed) (43.5 ± 5.6 vs. 28.7 ± 3.7, P < 0.001), but significantly lower left atrial strain at reservoir function (LASr) (24 ± 4 vs. 41 ± 3, P < 0.001), left atrial strain at conduit function (LAScd) (-13 ± 2 vs. -24 ± 2, P < 0.001), and left atrial strain at contractile function (LASct) (-11 ± 2 vs. -18 ± 1, P < 0.001). Three-dimensional transthoracic echocardiography (TTE) is a feasible method for the assessment of LA remodeling, but there is adverse LA remodeling in patients with long-standing non-obstructive HCM including impaired all LA mechanics and with increased septal thickness, there are more diastolic dysfunction and more reduction of LA mechanics.

Hybrid versus catheter ablation for Hypertrophic CardioMyopathy with Atrial Fibrillation (HCM-AF): study protocol for a randomised controlled trial

IntroductionAtrial fibrillation (AF) is an independent predictor of adverse outcomes in patients with hypertrophic cardiomyopathy (HCM). Although catheter ablation is highly recommended for general AF populations, it is less effective...

Validity of a Hypertrophic Cardiomyopathy Diagnosis in Adult Patients in the Danish National Patient Register.

To assess the positive predictive value (PPV) of the diagnostic codes for hypertrophic cardiomyopathy (HCM) in the Danish National Patient Register (DNPR) and identify factors affecting the PPV. We randomly sampled 200 patients registered in DNPR with the diagnostic codes DI421 (obstructive) or DI422 (non-obstructive) HCM, from Eastern Denmark, between December 1st, 2017, and September 16th, 2021. We assessed patients' medical records and classified whether the diagnosis of HCM was correct, incorrect, or uncertain according to the European Society of Cardiology (ESC) guidelines. Overall PPVs were estimated for all hospitals irrespective of specialty and for dedicated centers for inherited cardiac diseases. Of the 200 patients, seven were excluded; six were younger than 18 years when initially diagnosed and one adult patient had requested that their medical records be unavailable for research purposes. Of the 193 patients (median age 61 years, Interquartile range (IQR) 50-70, 40% female) with medical records available for assessment, 148 (77%) patients were registered correctly, 41 (21%) were incorrectly registered and for four (2%) patients there was insufficient data to determine if the diagnosis was correct. The overall PPV was 0.77 (95% confidence interval (CI) 0.70-0.82). The PPV for patients diagnosed in dedicated centers for inherited cardiac diseases was 0.91 (95% CI 0.84-0.95). For patients diagnosed in a dedicated center for inherited cardiac diseases with more than one clinical visit, the PPV increased to 0.99 (95% CI 0.93-1), however with the risk of a reduced sensitivity as these patients constituted only 52% of the correctly registered patients. The overall PPV of the HCM diagnostic codes in the DNPR was 0.77 (95% CI 0.70-0.82). The validity of the diagnosis was higher at dedicated centers for inherited cardiac diseases. These findings may prove useful for future register-based research.

The ventilatory efficiency parameters outperform peak oxygen consumption in monitoring the therapy effects in patients with hypertrophic cardiomyopathy

AimWe sought the cardiopulmonary exercise testing (CPET) parameter that most accurately reflected therapeutic efficacy in patients with hypertrophic cardiomyopathy (HCM). MethodsWell-being questionnaire, N-terminal brain natriuretic peptide measurements, echocardiography, and CPET were performed in patients with symptomatic non-obstructive HCM during phase II, randomized, open-label multicentre study, before and after 16 weeks of traditional or sacubitril/valsartan treatment. Patients were followed 36 months after the initial CPET. Primary endpoints were changes in: 1) peak oxygen consumption (VO2); 2) VO2 at anaerobic threshold (AT); 3) oxygen pulse; 4) minute ventilation (VE)/carbon-dioxide (CO2) production slope; 5) VE/VCO2 at AT (VE/VCO2_AT); 6) VE/VCO2 nadir; 7) VE/VCO2 intercept; and 8) partial end-tidal pressure of carbon-dioxide (PETCO2) change during CPET. ResultsOf 115 screened patients, 61 (52 ± 14 years, 43 % women) were included. Within subject therapy effects were detected only by the VE/VCO2 intercept and PETCO2 change, whereas the differences between medical regimens were detected by differences in VE/VCO2 nadir and VE/VCO2_AT changes after the treatment. The best predictors of the change in well-being were left ventricular outflow tract maximal gradient and VE/VCO2 intercept (B = 0.41,0.36; SE = 0.16,0.30; CI = 0.14–0.79, 0.15–1.14; p = 0.006,0.016, respectively). Adverse cardiac events were best predicted by the initial VE/VCO2 nadir. ConclusionVentilatory efficiency parameters outperform peak VO2 in gauging therapy effects in patients with HCM.