Outcome In Hypertrophic Cardiomyopathy Research Articles

Is Type 2 Diabetes Mellitus an Independent Risk Factor for Mortality in Hypertrophic Cardiomyopathy?

The mortality rate of hypertrophic cardiomyopathy (HCM) has decreased between 1999 and 2020. The risk factors for sudden cardiac death (SCD) in HCM were updated in the American Heart Association (AHA)/American College of Cardiology Foundation (ACCF) 2020 guidelines by adding new risk factors, like the late gadolinium enhancement on cardiac magnetic resonance imaging (MRI). Type 2 diabetes mellitus (T2DM) is a major risk factor for most cardiac diseases; however, it is not included in these guidelines due to a lack of strong evidence of a correlation between T2DM and mortality in HCM. Therefore, we sought to investigate if T2DM increases the 5-year risk rate for adverse outcomes, such as heart failure and all-cause mortality in patients with HCM. We collected patient data from January 1, 2018, to March 1, 2023, using the TriNetX database. The sample included 80,502 individuals with HCM, then divided into two cohorts based on the absence (58,573; cohort 1) or presence (15,296; cohort 2) of T2DM. The two matched groups then underwent survival and risk analyses for all-cause mortality or the first incidence of heart failure diagnosis within 5 years from the point in time when the selection criteria were first met. We found a statistically significant increase in all-cause mortality and new-onset heart failure in HCM patients with diabetes compared to those without diabetes after adjusting for major risk factors. This is one of the largest retrospective cohort studies that examined the correlation between T2DM and adverse outcomes in patients with HCM. This underlines the need for future prospective studies investigating the effects of T2DM on HCM outcomes.

Relationship Between Genotype Status and Clinical Outcome in Hypertrophic Cardiomyopathy.

The genetic basis of hypertrophic cardiomyopathy (HCM) is complex, and the relationship between genotype status and clinical outcome is incompletely resolved. We assessed a large international HCM cohort to define in contemporary terms natural history and clinical consequences of genotype. Consecutive patients (n=1468) with established HCM diagnosis underwent genetic testing. Patients with pathogenic (or likely pathogenic) variants were considered genotype positive (G+; n=312; 21%); those without definite disease-causing mutations (n=651; 44%) or variants of uncertain significance (n=505; 35%) were considered genotype negative (G-). Patients were followed up for a median of 7.8 years (interquartile range, 3.5-13.4 years); HCM end points were examined by cumulative event incidence. Over follow-up, 135 (9%) patients died, 33 from a variety of HCM-related causes. After adjusting for age, all-cause and HCM-related mortality did not differ between G- versus G+ patients (hazard ratio [HR], 0.78 [95% CI, 0.46-1.31]; P=0.37; HR, 0.93 [95% CI, 0.38-2.30]; P=0.87, respectively). Adverse event rates, including heart failure progression to class III/IV, heart transplant, or heart failure death, did not differ (G- versus G+) when adjusted for age (HR, 1.20 [95% CI, 0.63-2.26]; P=0.58), nor was genotype independently associated with sudden death event risk (HR, 1.39 [95% CI, 0.88-2.21]; P=0.16). In multivariable analysis, age was the only independent predictor of all-cause and HCM-related mortality, heart failure progression, and sudden death events. In this large consecutive cohort of patients with HCM, genotype (G+ or G-) was not a predictor of clinical course, including all-cause and HCM-related mortality and risk for heart failure progression or sudden death. G+ status should not be used to dictate clinical management or predict outcome in HCM.

Clinical and pathophysiologic determinants of catheter ablation outcome in hypertrophic cardiomyopathy with atrial fibrillation

AbstractBackgroundHypertrophic cardiomyopathy (HCM) is frequently associated with atrial fibrillation (AF). We compared clinical, echocardiographic, and electrophysiological parameters between HCM subtypes and those without HCM at AF catheter ablation (AFCA) and analyzed post‐AFCA reverse remodeling and AF recurrence based on HCM presence and subtype.MethodsAmong 5161 consecutive patients who underwent de novo AFCA, we included HCM patients and control patients who were age‐, gender‐, and AF type‐matched. Between AF‐HCM patients and controls, we compared baseline values for left atrium (LA) wall thickness (LAWT), reverse remodeling at 1‐year follow‐up, and procedural outcomes over the course of follow‐up between two groups.ResultsA total of 122 AF‐HCM patients and 318 control patients were included. AF‐HCM patients had more frequent heart failure and higher LA diameter, E/Em, and LA pressure (all, p < .001). However, LAWT did not differ from control group. A year after AFCA, degree of LA reverse remodeling was significantly lower in AF‐HCM than in control group (ΔLA dimension, p = .025). Nonapical HCM (HR 1.71; 95% CI 1.05–2.80), persistent AF (HR 1.46; 95% CI 1.05–2.04), and LA dimension (HR 1.04; 95% CI 1.01–1.06) were independent risk factors for AF recurrence. During 78.0 months of follow‐up, nonapical HCM patients showed higher AF recurrence rate than both apical HCM (log‐rank p = .005) and control patients (log‐rank p = .002).ConclusionsThe presence of HCM, particularly nonapical HCM, displayed increased LA hemodynamic loading with diastolic dysfunction and had poorer rhythm outcomes after AFCA compared to both apical HCM and control group.

Role of Biomarkers of Myocardial Injury to Predict Adverse Outcomes in Hypertrophic Cardiomyopathy.

Serum troponins and CK-MB (creatine kinase-MB) are readily detectable and reliable cardiac-specific biomarkers of subclinical myocardial injury. This study explores the roles of cTnI (cardiac troponin I) and CK-MB in hypertrophic cardiomyopathy (HCM). This study included 1045 patients with HCM who had baseline cTnI and CK-MB measurements at Fuwai Hospital between 1999 and 2019. Patients were excluded if they had undergone percutaneous coronary intervention or coronary artery bypass grafting, or had renal failure. Five end points were studied: all-cause death, cardiovascular death, noncardiovascular death, sudden cardiac death, and other cardiovascular death. Cox regression was used to assess the associations of cTnI and CK-MB levels with outcomes. Nine hundred seventy patients with available follow-up data were finally analyzed (mean age, 49.3 years; 36.4% female). During the median 4.3-year follow-up period, 87 patients reached the end points. Higher cTnI (per 0.05 ng/mL increase) and CK-MB (per 1 IU/L increase) levels were associated with increased risks of all-cause death (cTnI: adjusted hazard ratio [HR], 1.038, P<0.001; CK-MB: adjusted HR, 1.021, P=0.004), cardiovascular death (cTnI: adjusted HR, 1.040, P<0.001; CK-MB: adjusted HR, 1.025, P=0.006), and sudden cardiac death (cTnI: adjusted HR, 1.045, P<0.001; CK-MB: adjusted HR, 1.032, P=0.001). Patients with elevated levels of both cTnI and CK-MB had worse prognoses than patients with an elevated level of either biomarker alone and patients who did not have an elevated level of either biomarker. Addition of the binary indicator elevation of both cTnI and CK-MB significantly improved the discrimination and reclassification abilities of the standard HCM Risk- sudden cardiac death model (C statistics: P=0.002; net reclassification improvement, 0.652; integrated discrimination improvement, 0.064). Comprehensive evaluations of biomarkers of myocardial injury, cTnI and CK-MB, have considerable value for predicting adverse outcomes among patients with HCM. Routine cTnI and CK-MB assessments may help to guide implantable cardioverter defibrillator implantation for primary prevention in HCM.

Coronary flow velocity reserve during exercise stress echocardiography in hypertrophic cardiomyopathy

Abstract Background Coronary flow velocity reserve (CFVR) can be assessed with transthoracic echocardiography (TTE) as the stress/rest ratio of coronary flow velocity (CFV). Reduced CFVR during vasodilator stress (adenosine or dipyridamole) is a powerful predictor of adverse outcomes in hypertrophic cardiomyopathy (HCM). However, the feasibility and correlates of CFVR during the more physiological - and recommended - exercise stress echocardiography (ESE) is unresolved. Aim To assess the feasibility and functional correlates of CFVR during exercise in HCM. Methods We studied 56 HCM patients (age=49±13 years, 33 [59%] males) and 44 age- and sex-matched healthy subjects with symptom-limited semi-supine ESE. ESE assessment included CFVR (stress/rest diastolic CFV) in the mid-distal left anterior descending coronary artery, systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate reserve (HRR, peak/rest heart rate). Results CFVR was feasible in 46/56 HCM patients and in 41/44 controls (82% vs 93%, p=0.138). Median CFVR was significantly lower in patients with HCM compared to controls (1.72 [1.48; 2.10] vs 2.57 [2.25; 3.30], p&amp;lt;0.001), see Figure 1. In HCM patients, among resting parameters, CFVR was inversely correlated with left ventricular maximal septal thickness (r= -0.308, p=0.038), end-systolic diameter (r= -0.393, p=0.007), resting DBP (r= -0.398, p=0.006) and resting SBP (r= -0.321, p=0.030), while in controls CFVR correlated only with resting DBP (r= -0.322, p=0.040). During exercise, HCM patients with lower CFVR (&amp;lt;1.72, i.e. 1.72) showed lower peak CFV (78±20 vs 96±24 cm/s, p=0.003) and lower HRR (1.55±0.29 vs 1.76±0.25, p=0.020), see Figure 2. Exercise duration, peak stress workload or metabolic equivalents were not related to CFVR. In multivariable analysis, resting CFV (b=-0.034, 95% CI -0.037 and -0.030, p&amp;lt;0.001), resting DBP (b=-0.003, 95% CI -0.005 and -0.001, p=0.020), peak stress CFV (b=0.019, 95% CI 0.017 and 0.021, p&amp;lt;0.001) and HRR (b=0.126, 95% CI 0.005 and 0.247, p=0.041) were independently associated with CFVR. Conclusion CFVR assessment by TTE in the left anterior descending coronary artery is feasible during semi-supine exercise in most HCM patients. CFVR is markedly reduced in HCM patients on effort, particularly in the presence of high resting CFV and low HRR.Figure 1Figure 2

Abstract 18273: Mitral Annular Calcification is Associated With Higher Operative Risks and Worse Survival in Hypertrophic Cardiomyopathy

Background: Mitral annular calcification (MAC) is common in hypertrophic cardiomyopathy (HCM), usually accompanied by mitral leaflet calcification, subvalvular apparatus calcification, and mitral valve dysfunction. However, the impact of MAC on surgical strategy and clinical outcomes in HCM is not fully understood. Methods: This cohort enrolled 1035 consecutively recruited patients diagnosed with HCM between January 2016 and December 2021. All patients received a computed tomographic scan prior to surgery. Results: Of the 1035 patients, 112 (10.8%) had MAC, including 39 patients with moderate or severe MAC (calcification area greater than one-third of the annulus). Patients with MAC were significantly older (59.6±8.2 years vs. 47.5±12.3 years, p&lt;0.001) and more likely to be female (61.8% vs. 35.4%, p&lt;0.001). Echocardiography showed a higher proportion of mitral leaflet thickening (17.9% vs. 6.0%, p&lt;0.001) in patients with MAC. Moreover, patients with MAC had a higher rate of annular reconstruction (1.79% vs 0.11%, p=0.002), plastic ring implantation (5.36% vs 1.84%, p=0.017), chordae release (12.50% vs 5.09%, p=0.002), artificial neochordoplasty (2.68% vs 0.54%, p=0.015), and fibrous membrane removal (8.93% vs 4.12%, p=0.022), as well as longer ventilation time [19 hours, interquartile range (IQR) 17.0-26.0 vs. 18 hours, IQR 14.0-20.5, p&lt;0.001], intensive care unit stay [61 hours, IQR 36.5-96.0 hours vs. 48 hours IQR 24.0-72.0 hours, p&lt;0.001] and postoperative hospital stay [8days, IQR 7-11 days vs. 7 days, IQR 6-8 days, p&lt;0.001]. During a median follow-up time of 26.2 months (IQR, 17.0 to 39.5 months), 5 death and 158 major adverse cardiovascular events (MACE) were observed. Kaplan-Meier survival curves showed that patients with MAC had a higher cumulative rate of all-cause mortality (p=0.026) and MACE (p=0.003) compared to their counterparts. On multivariable Cox regression analysis, moderate or severe MAC was an independent risk factor for MACE (Hazard ratio =2.38, 95% confidence interval: 1.31-4.32). Conclusions: The prevalence of MAC was 10.8% in this study. The presence of MAC was associated with a higher rate of concomitant operations, longer hospital stays, and worse survival.

Echocardiographic predictors of outcomes in hypertrophic cardiomyopathy

The use of echocardiography, a straightforward and widely available technique, allows for a comprehensive assessment of the patient with hypertrophic cardiomyopathy (HCM) under both resting and stress conditions. The true prevalence of HCM has been redefined over time by this imaging approach, which has also made it feasible to pinpoint parameters that clinicians may use to stratify patients at risk for adverse cardiovascular events. The current and emerging prognostic predictors in HCM, assessed with transthoracic echocardiography at rest and during provocation, are discussed in this review.

Effects of sex on clinical outcomes of hypertrophic cardiomyopathy in Singapore.

Despite the growing recognition that sex can affect the presentation and outcomes in hypertrophic cardiomyopathy (HCM), this relationship is understudied in Asians. Therefore, we aimed to explore sex differences in Asian patients with HCM. A total of 295 consecutive patients diagnosed with HCM were recruited from a tertiary cardiology centre from 2010 to 2017 over a mean of 3.9±2.7 years. We evaluated the effects of sex on the outcomes of HCM in Asian patients. HCM patients were more commonly men (72%). Women were older and had more comorbidities, including hypertension and atrial fibrillation. On transthoracic echocardiography, the indexed left ventricular end-systolic and end-diastolic volumes were similar, but more women had more-than-moderate mitral regurgitation and had a smaller left ventricular outflow tract (LVOT). Women more commonly had findings of obstructive physiology with significant LVOT obstruction, defined as >30 mmHg at rest. The use of implantable cardioverter defibrillators was similar across sexes. On multivariable analysis, women were found to be more likely to develop progressive heart failure requiring admission (hazard ratio [HR] 2.10, 95% confidence interval [CI] 1.05-4.71, P=0.021) but had a lower rate of all-cause mortality (HR 0.36, 95% CI 0.19-0.70, P=0.003). Women diagnosed with HCM were older, had more comorbidities and were more likely to develop heart failure while men had a higher risk of all-cause mortality.

Inequities in Treatments and Outcomes Among Patients Hospitalized With Hypertrophic Cardiomyopathy in the United States.

Background Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiac disease. In small studies, sociodemographic factors have been associated with disparities in septal reduction therapy, but little is known about the association of sociodemographic factors with HCM treatments and outcomes more broadly. Methods and Results Using the National Inpatient Survey from 2012 to 2018, HCM diagnoses and procedures were identified by International Classification of Diseases, Ninth/Tenth Revision, Clinical Modification (ICD-9-CM and ICD-10-CM) codes. Logistic regression was used to determine the association of sociodemographic risk factors with HCM procedures and in-hospital death, adjusting for clinical comorbidities and hospital characteristics. Of 53 117 patients hospitalized with HCM, 57.7% were women, 20.5% were Black individuals, 27.7% lived in the lowest zip income quartile, and 14.7% lived in rural areas. Among those with obstruction (45.2%), compared with White patients, Black patients were less likely to undergo septal myectomy (adjusted odds ratio [aOR], 0.52 [95% CI, 0.40-0.68]), or alcohol septal ablation (aOR, 0.60 [95% CI, 0.42-0.86]). Patients with Medicaid were less likely to undergo each procedure (aOR, 0.78 [95% CI, 0.61-0.99] for myectomy; aOR, 0.54 [95% CI, 0.36-0.83] for ablation). Women (aOR, 0.66 [95% CI, 0.58-0.74]), patients with Medicaid (aOR, 0.78 [95% CI, 0.65-0.93]), and patients from low-income areas (aOR, 0.77 [95% CI, 0.65-0.93]) were less likely to receive implantable cardioverter-defibrillators. Women (aOR, 1.23 [95% CI, 1.10-1.37]) and patients from towns (aOR, 1.16 [95% CI, 1.03-1.31]) or rural areas (aOR, 1.57 [95% CI, 1.30-1.89]) had higher odds of in-hospital death. Conclusions Among 53 117 patients hospitalized with HCM, race, sex, social, and geographic risk factors were associated with disparities in HCM outcomes and treatment. Further research is required to identify and address the sources of these inequities.

Subendocardial Involvement as an Underrecognized LGE Subtype Related to Adverse Outcomes in Hypertrophic Cardiomyopathy

BackgroundLate gadolinium enhancement (LGE) has been established as an independent predictor for adverse outcomes in hypertrophic cardiomyopathy (HCM). However, the prevalence and clinical significance of some LGE subtypes have not been well demonstrated. ObjectivesIn this study, the authors sought to investigate the prognostic value of subendocardium-involved LGE pattern and location of right ventricle insertion points (RVIPs) with LGE in HCM patients. MethodsIn this single-center retrospective study, 497 consecutive HCM patients with LGE confirmed by cardiac magnetic resonance (CMR) were included. Subendocardium-involved LGE was defined as LGE involving subendocardium not corresponding to a coronary vascular distribution. Subjects with ischemic heart disease that would contribute to subendocardial LGE were excluded. Endpoints included a composite of heart failure–related events, arrhythmic events, and stroke. ResultsOf the 497 patients, subendocardium-involved LGE and RVIP LGE were observed in 184 (37.0%) and 414 (83.3%), respectively. Extensive LGE (≥15% of left ventricular mass) was detected in 135 patients. During a median follow-up of 57.9 months, 66 patients (13.3%) experienced composite endpoints. Patients with extensive LGE had a significantly higher annual incidence of adverse events (5.1% vs 1.9% per year; P < 0.001). However, spline analysis showed that the association between LGE extent and HRs for adverse outcomes tended to be nonlinear. The risk of composite endpoint increased with percentage increase in LGE extent in patients with extensive LGE, whereas a similar trend was not observed in patients with nonextensive LGE (<15%). In patients with extensive LGE, LGE extent significantly correlated with composite endpoints (HR: 1.05; P = 0.03) after adjusting for left ventricular ejection fraction <50%, atrial fibrillation, and nonsustained ventricular tachycardia, whereas in patients with nonextensive LGE, subendocardium-involved LGE rather than LGE extent was independently associated with adverse outcomes (HR: 2.12; P = 0.03). RVIP LGE was not significantly associated with poor outcomes. ConclusionsIn HCM patients with nonextensive LGE, the presence of subendocardium-involved LGE rather than LGE extent is associated with unfavorable outcomes. Given that the prognostic value of extensive LGE has been broadly recognized, subendocardial involvement as an underrecognized LGE pattern shows the potential to improve risk stratification in HCM patients with nonextensive LGE.

Contribution of artificial intelligence and left atrial strain in the prediction of sudden cardiac death in hypertrophic cardiomyopathy. Results of a multicentric cohort

Sudden cardiac death (SCD) remains a serious outcome in hypertrophic cardiomyopathy (HCM), with an estimated incidence of 1%/year. Its risk prediction stays challenging for clinicians. Implantation of cardioverter-defibrillator is recommended with a strong level of evidence when the HCM risk score is over 6%. However, the ESC HCM risk score is criticized for its moderate diagnostic performance (C-index 0,70), and its low sensibility. Recent studies suggest that low PALS (peak atrial longitudinal strain) is associated with poor prognosis in HCM. Artificial intelligence, wich is experiencing an unprecedented boom, may be an interesting tool in association to left atrial strain in Prognostication. This preliminar study aimed to evaluate the value of the left atrial strain coupled with artificial inteligence algorythm in the prediction of suddent cardiac death in hypertrophic cardiomyopathy. This restrospective multi-center cohort (Marseille la Timone, Bordeaux and Rennes) included 431 patients with sarcomeric HCM from 2007 to 2018. The average follow-up time was 57 months. The primary endpoint was all cause death, ventricular arythmias, recovered SCD and internal electric shock. Analyses were entrusted to the LIS laboratory specialized in Computer Science at Aix-Marseille University. Sixty-six percent of men composed the cohort with a mean age of 52 ± 16 yo. Sarcomeric mutations were found in 52% of them, the mean left ventricular ejection fraction was 63 ± 16, 23% had significant ventricular obstruction. The mean PALS was 25 ± 12%. In the multivariate analysis, PALS 4 chamber, left ventricular global longitudinal strain and syncope were associated with the primary endpoint, (respectivly HR 2,48 IC95% [1,09–5,63]; P 0,030; HR 1,13 IC95% [1,03–1,25]; P 0,012; HR 0,95 IC95% [0,92–0,99]; P: 0.023). The random Forrest algorithm was able to successfully classify the patient (occurrence of primary endpoint or not) in 92,2% of the cases. Left atrial strain coupled with the Random Forrest algorithm could offer an interesting implementative value for the prediction of sudden cardiac death in hypertrophic cardiomyopathy. Further analysis are required to define its sensibility and specificity.

Different clinical characteristics and outcomes of hypertrophic cardiomyopathy with and without hypertension: seeking the truth.

To determine the different clinical characteristics and outcomes of hypertrophic cardiomyopathy (HCM) patients with and without hypertension (HT). A total of 696 HCM patients were included in this study and all HCM diagnoses were confirmed by the genetic test. Patients were analyzed separately in the septal reduction therapy (SRT) cohort and the non-SRT cohort. The primary endpoint was cardiovascular death and the secondary endpoint was all-cause death. Outcome analyses were conducted to evaluate the associations between HT and outcomes in HCM. Medications before enrollment and at discharge were collected in the post-hoc analyses. HCM patients without HT were younger, had a lower body mass index, were more likely to have a family history of HCM, and had a smaller left ventricular (LV) end-diastolic diameter than those with HT in both cohorts. A thicker LV wall, a higher level of N-terminal pro-B-type natriuretic peptide, and a higher extent of LV late gadolinium enhancement were additionally observed in patients without HT in the non-SRT cohort. The presence of HT did not alter the distribution pattern of late gadolinium enhancement, as well as the constituent ratio of eight disease-causing sarcomeric gene variants in both cohorts. Outcome analyses showed that in the non-SRT cohort, patients without HT had higher risks of cardiovascular death (HR = 2.537, P = 0.032) and all-cause death (HR = 3.309, P = 0.032). While such prognostic divergence was not observed in the SRT cohort. Further post-hoc analyses in the non-SRT cohort found that patients without HT received fewer non-dihydropyridine calcium channel blockers and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers before enrollment and at discharge. HCM patients without HT had worse clinical conditions and higher mortality than patients with HT overall, which may result from active medical therapy in HT patients. Active SRT may have a substantial de-risking effect on patients meeting the indications.

Prognosis of patients with hypertrophic cardiomyopathy and low-normal left ventricular ejection fraction

ObjectiveTo investigate whether low-normal left ventricular ejection fraction (LVEF) is associated with adverse outcomes in hypertrophic cardiomyopathy (HCM) and evaluate the incremental value of predictive power of LVEF in the...

3-Dimensional Strain Analysis of Hypertrophic Cardiomyopathy: Insights From the NHLBI International HCM Registry

BackgroundAbnormal global longitudinal strain (GLS) has been independently associated with adverse cardiac outcomes in both obstructive and nonobstructive hypertrophic cardiomyopathy. ObjectivesThe goal of this study was to understand predictors of abnormal GLS from baseline data from the National Heart, Lung, and Blood Institute (NHLBI) Hypertrophic Cardiomyopathy Registry (HCMR). MethodsThe study evaluated comprehensive 3-dimensional left ventricular myocardial strain from cine cardiac magnetic resonance in 2,311 patients from HCMR using in-house validated feature-tracking software. These data were correlated with other imaging markers, serum biomarkers, and demographic variables. ResultsAbnormal median GLS (> –11.0%) was associated with higher left ventricular (LV) mass index (93.8 ± 29.2 g/m2 vs 75.1 ± 19.7 g/m2; P < 0.0001) and maximal wall thickness (21.7 ± 5.2 mm vs 19.3 ± 4.1 mm; P < 0.0001), lower left (62% ± 9% vs 66% ± 7%; P < 0.0001) and right (68% ± 11% vs 69% ± 10%; P < 0.01) ventricular ejection fractions, lower left atrial emptying functions (P < 0.0001 for all), and higher presence and myocardial extent of late gadolinium enhancement (6 SD and visual quantification; P < 0.0001 for both). Elastic net regression showed that adjusted predictors of GLS included female sex, Black race, history of syncope, presence of systolic anterior motion of the mitral valve, reverse curvature and apical morphologies, LV ejection fraction, LV mass index, and both presence/extent of late gadolinium enhancement and baseline N-terminal pro–B-type natriuretic peptide and troponin levels. ConclusionsAbnormal strain in hypertrophic cardiomyopathy is associated with other imaging and serum biomarkers of increased risk. Further follow-up of the HCMR cohort is needed to understand the independent relationship between LV strain and adverse cardiac outcomes in hypertrophic cardiomyopathy.

Sex disaggregated analysis of risk factors for adverse outcomes in hypertrophic cardiomyopathy

Abstract Background Patient sex has been associated with differences in disease penetrance and clinical expression in HCM. We sought to investigate sex-disaggregated differences in risk factors for adverse outcomes in a large international HCM registry. Methods This is a retrospective study of HCM patients from the Sarcomeric Human Cardiomyopathy Registry. Cox proportional hazards models were fit with a sex interaction term to determine significant differences between sexes. Results 6647 (38% women) probands with HCM were included. After a mean follow-up of 6.4 years from first encounter, women had a higher risk of heart failure (HF) composite (HR 1.77; 95% CI 1.56–1.99, p&amp;lt;0.0001), and death (1.22; 1.03–1.45, p=0.02) compared to men. No sex difference existed for ventricular arrhythmia composite (p=0.2) or atrial fibrillation (p=0.6). Sarcomere positive status (Sarc+) and causative variants in MYBPC3 reduced the risk of the HF composite for women, while for men there was no change in risk (P-heterogeneity=0.016 and &amp;lt;0.0001, respectively). Baseline LVEF &amp;lt;35% and larger LA size increased the risk of the HF composite for both sexes but to a greater magnitude in men (P-heterogeneity=0.0003 and 0.04 respectively) (Figure 1). Sarc+ increased the risk of death in men but not women (P-heterogeneity=0.041). Having the HF composite increased the risk of death by 45% in and 240% in men (P-heterogeneity=0.003) (Figure 2). Conclusion There are important sex differences in the risk of heart failure and death in those with HCM, with significant heterogeneity of outcomes based on subgroups defined by genetic and imaging factors. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): The Sarcomeric Human Cardiomyopathy Registry (SHaRe) is supported by an unrestricted research grant from Bristol Myer Squibb, including funds to individual sites for database support.

Coexistent diabetes is associated with the presence of adverse phenotypic features in patients with hypertrophic cardiomyopathy

Abstract Background Type 2 diabetes mellitus (DM) is associated with worsened clinical outcomes in hypertrophic cardiomyopathy (HCM) patients. The reasons for this adverse prognostic association are incompletely understood. Although distinct entities both HCM and DM share common features of impaired myocardial energetics and coronary microvascular function. Purpose We sought to test the hypothesis that co-existent diabetes is associated with greater reductions in myocardial energetics and perfusion, and higher scar burden in HCM. Research design and methods Seventy-five age- and sex-matched participants with concomitant HCM and DM (HCM-DM, n=20), isolated HCM (n=20), isolated DM (n=20) and healthy volunteers (HV, n=15) underwent 31phosphorus magnetic resonance spectroscopy and cardiovascular magnetic resonance imaging. The HCM groups were matched for HCM phenotype. The DM groups were matched for diabetes treatment, duration, HbA1c, body mass index and hypertension comorbidity. Results ESC sudden cardiac death risk scores were comparable between the HCM groups (HCM: 2.2±1.5%, HCM-DM: 1.9±1.2%; p=NS) and sarcomeric mutations were equally common. HCM-DM had the highest NT-proBNP levels (HV: 42 ng/L [IQR: 35–66], DM: 118 ng/L [IQR: 53–187], HCM: 298 ng/L [IQR: 157–837], HCM-DM: 726 ng/L [IQR: 213–8695]; p&amp;lt;0.0001). Left-ventricular ejection fraction, mass and wall thickness were similar between the HCM groups. HCM-DM displayed a greater degree of fibrosis burden with higher scar percentage, and lower global longitudinal strain compared to the isolated HCM. PCr/ATP was similarly decreased in the HCM-DM and DM (HV: 2.17±0.49, DM: 1.61±0.23, HCM: 1.93±0.38, HCM-DM: 1.54±0.27; p=0.0003). HCM-DM had the lowest stress myocardial blood flow (HV: 2.06±0.42 ml/min/g, DM: 1.78±0.45 ml/min/g, HCM: 1.74±0.44 ml/min/g, HCM-DM: 1.39±0.42 ml/min/g; p=0.004). Conclusions We show for the first time that HCM patients with DM comorbidity display greater reductions in myocardial energetics, perfusion, contractile function and higher myocardial scar burden and serum NT-proBNP levels compared to patients with isolated HCM despite similar LV mass and wall thickness and presence of sarcomeric mutations. These adverse phenotypic features may be important components of the adverse clinical manifestation attributable to a combined presence of HCM and DM. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Diabetes UK

Left atrial remodelling after septal myectomy is associated with a reduced 5-year risk of atrial fibrillation in hypertrophic cardiomyopathy

Abstract Background Left atrial diameter (LAD) is an established predictor of atrial fibrillation (AF) and adverse outcomes in hypertrophic cardiomyopathy (HCM). However, the impact of LAD remodelling after surgical myectomy on the development of late onset AF is still poorly understood. Purpose To investigate the association between LAD remodelling and new occurrence of AF in the first five years after surgical myectomy in a large patient population with HCM. Methods 1177 HCM patients without a history of AF, subjected to surgical myectomy at two referral centres between 2001 and 2020 were retrospectively reviewed. Paired echocardiographic studies before and shortly after surgical myectomy were available in 894 (76%) patients and 889 (75%) patients had complete LAD measurements, defined as the anteroposterior diameter at end-systole from parasternal long axis view. LAD was considered normal when ≤40mm. Late onset AF was determined as AF documented between one month and 5 years follow up after myectomy. Patients were grouped as having normal LAD pre- and post-myectomy (group 1), enlarged pre-myectomy LAD but normal post-myectomy LAD (group 2), and those with enlarged LAD post-myectomy (group 3). Cox proportional hazards models were applied to evaluate the impact of LAD on late onset AF. Results Late onset AF was detected in 63 (7%) patients, 56% male, with an incidence of 1%/year. Patients with AF were older (56±13 vs. 52±14 years, p=0.03), had a larger post-surgery LAD (44±7 vs. 41±6 mm, p&amp;lt;0.001) and a lower left ventricular ejection fraction (58±6 vs. 61±6%, p=0.002) compared to patients without AF. Postoperative left ventricular maximal wall thickness (14±4 mm vs. 15±4mm, p=0.53), left ventricular outflow tract obstruction (6% vs. 8%, p=0.49) or moderate/severe mitral regurgitation (13% vs. 9%, p=0.29) were similar between patients with and without late onset AF. Among the 227 patients in group 1, late onset AF occurred in only 5 (3%), in comparison to 8 (5%) of 182 patients in group 2, and in 36 (10%) of the 480 patients in group 3 (p=0.006). Using group 1 as reference, the hazard ratio for developing AF was 2.1 (95% CI 0.7–6.5, p=0.15) for patients in group 2 and 3.5 (95% CI 1.4–9.4, p=0.005) for patients in group 3. Conclusion In our study we were able to show that the overall post-myectomy 5-year risk for developing AF was 1%/year. Normal LAD and reverse LAD remodelling correlated with a lower risk for developing late onset AF, whereas a higher risk was associated with enlarged post-myectomy LAD. These results highlight the possible clinical benefit of LAD remodelling after myectomy in reducing late onset AF. Funding Acknowledgement Type of funding sources: None.

Coexistent Diabetes Is Associated With the Presence of Adverse Phenotypic Features in Patients With Hypertrophic Cardiomyopathy.

OBJECTIVEType 2 diabetes mellitus (T2DM) is associated with worsened clinical outcomes in hypertrophic cardiomyopathy (HCM) patients. We sought to investigate whether HCM patients with T2DM comorbidity exhibit adverse cardiac alterations in myocardial energetics, function, perfusion, or tissue characteristics.RESEARCH DESIGN AND METHODSA total of 55 participants with concomitant HCM and T2DM (HCM-DM) (n = 20) or isolated HCM (n = 20) and healthy volunteers (HV) (n = 15) underwent 31P-MRS and cardiovascular MRI. The HCM groups were matched for HCM phenotype.RESULTSMean ± SD European Society of Cardiology sudden cardiac death risk scores were comparable between the HCM groups (HCM 2.2 ± 1.5%, HCM-DM 1.9 ± 1.2%; P = not significant), and sarcomeric mutations were equally common. HCM-DM patients had the highest median NT-proBNP levels (HV 42 ng/L [interquartile range 35–66], HCM 298 ng/L [157–837], HCM-DM 726 ng/L [213–8,695]; P < 0.0001). Left ventricular (LV) ejection fraction, mass, and wall thickness were similar between the HCM groups. HCM-DM patients displayed a greater degree of fibrosis burden with higher scar percentage and lower global longitudinal strain compared with HCM patients. PCr/ATP (the relative concentrations of phosphocreatine and ATP) was significantly lower in the HCM-DM group than in both HCM and HV (HV 2.17 ± 0.49, HCM 1.93 ± 0.38, HCM-DM 1.54 ± 0.27; P = 0.002). In a similar pattern, stress myocardial blood flow was significantly lower in the HCM-DM group than in both HCM and HV (HV 2.06 ± 0.42 mL/min/g, HCM 1.74 ± 0.44 mL/min/g, HCM-DM 1.39 ± 0.42 mL/min/g; P = 0.002).CONCLUSIONSWe show for the first time that HCM-DM patients display greater reductions in myocardial energetics, perfusion, and contractile function and higher myocardial scar burden and serum NT-proBNP levels compared with patients with isolated HCM despite similar LV mass and wall thickness and presence of sarcomeric mutations. These adverse phenotypic features may be important components of the adverse clinical manifestation attributable to a combined presence of HCM and T2DM.

The impact of cardiopulmonary exercise-derived scoring on prediction of cardio-cerebral outcome in hypertrophic cardiomyopathy.

Sudden cardiac death (SCD) and stroke-related events accompanied by atrial fibrillation (AF) can affect morbidity and mortality in hypertrophic cardiomyopathy (HCM). This study sought to evaluate a scoring system predicting cardio-cerebral events in HCM patients using cardiopulmonary exercise testing (CPET). We investigated the role of a previous prediction model based on CPET, the HYPertrophic Exercise-derived Risk score for Heart Failure-related events (HyperHF), which is derived from peak circulatory power ventilatory efficiency and left atrial diameter (LAD), for predicting a composite of SCD-related (SCD, serious ventricular arrhythmia, death from cardiac cause, heart failure admission) and stroke-related (new-onset AF, acute stroke) events. The Novel HyperHF risk model using left atrial volume index (LAVI) instead of LAD was proposed and compared with the previous HCM Risk-SCD model. A total of 295 consecutive HCM patients (age 59.9±13.2, 71.2% male) who underwent CPET was included in the present study. During a median follow-up of 742 days (interquartile range 384-1047 days), 29 patients (9.8%) experienced an event (SCD-related event: 14 patients (4.7%); stroke-related event: 17 patients (5.8%)). The previous model for SCD risk score showed fair prediction ability (AUC of HCM Risk-SCD 0.670, p = 0.002; AUC of HyperHF 0.691, p = 0.001). However, the prediction power of Novel HyperHF showed the highest value among the models (AUC of Novel HyperHF 0.717, p<0.001). Both conventional HCM Risk-SCD score and CPET-derived HyperHF score were useful for prediction of overall risk of SCD-related and stroke-related events in HCM. Novel HyperHF score using LAVI could be utilized for a better prediction power.

Sex Disaggregated Analysis of Risk Factors for Adverse Outcomes in Hypertrophic Cardiomyopathy

Patient sex has been associated with differences in disease penetrance and clinical expression in hypertrophic cardiomyopathy (HCM). We sought to investigate sex-disaggregated differences in risk factors for adverse outcomes in a large international HCM registry.