HCM-related Mortality Research Articles

Mortality from Hypertrophic Cardiomyopathy in Brazil—Historical Series

Hypertrophic cardiomyopathy (HCM) is a relatively prevalent disease, primarily of a genetic etiology, affecting both sexes and characterized by left ventricular hypertrophy. However, limitations within healthcare systems, socioracial factors, and the issue of underdiagnosis hinder accurate mortality assessments in our region. This study, therefore, aimed to assess the mortality trends associated with HCM in Brazil from 2010 to 2020, with a focus on socioracial factors and healthcare disparities. This ecological, time-series study employed a quantitative approach based on secondary data from the Mortality System (SIM) developed by the Brazilian Ministry of Health. Mortality incidence and trend analyses were conducted using the average annual percent change (AAPC) and the annual percent change (APC). The results indicated a predominance of HCM-related deaths among white males aged 40 years and older. Additionally, an increasing trend in HCM-related mortality was observed among white and brown males and females aged 40 years and above from 2010 to 2018. Throughout the entire period covered in the study, the incidence of deaths due to HCM increased by 18.3% and 69.8% in the northeastern and southeastern regions. The findings suggest that health system managers should consider addressing the factors influencing HCM mortality and encourage the development and implementation of clinical protocols across healthcare institutions nationwide. Such protocols are recommended to facilitate early diagnosis and establish effective treatment strategies, ultimately aiming to improve the survival rates and quality of life for individuals affected by HCM.

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.

Trends of hypertrophic cardiomyopathy-related mortality in United States young adults: a nationwide 20-year analysis.

Data regarding hypertrophic cardiomyopathy (HCM)-related mortality in United States young adults, defined as those aged between 25 and 44 years, are lacking. We sought to assess the trends in HCM-related mortality among US young adults between 1999 and 2019 and determine differences by sex, race, ethnicity, urbanization and census region. Mortality data were retrieved by the Centers for Disease Control and Prevention (CDC) Wide-Ranging Online Data for Epidemiologic Research (WONDER) dataset from January 1999 to December 2019. Age-adjusted mortality rates (AAMRs) were assessed using the Joinpoint regression modeling and expressed as estimated average annual percentage change (AAPC) with relative 95% confidence intervals (95% CIs). Over 20-year period, the AAMR from HCM in US young adults linearly decreased, with no differences between sexes [AAPC: -5.3% (95% CI -6.1 to -4.6), P < 0.001]. The AAMR decrease was more pronounced in Black patients [AAPC: -6.4% (95% CI -7.6 to -5.1), P < 0.001], Latinx/Hispanic patients [AAPC: -4.8% (95% CI -7.2 to -2.36), P < 0.001] and residents of urban areas [AAPC: -5.4% (95% CI -6.2 to -4.6), P < 0.001]. The higher percentages of HCM-related deaths occurred in the South of the country and at the patient's home. HCM-related mortality in US young adults has decreased over the last two decades in the United States. Subgroup analyses by race, ethnicity, urbanization and census region showed ethnoracial and regional disparities that will require further investigation.

Clinical characteristics and outcome of end stage hypertrophic cardiomyopathy: Role of age and heart failure phenotypes

BackgroundA minority of patients with hypertrophic cardiomyopathy (HCM) presents advanced heart failure (HF) during their clinical course, in the context of left ventricular (LV) remodeling with reduced LV ejection fraction (LVEF), or of severe diastolic dysfunction without impaired LVEF. Aim of this study was to describe a multicentric end stage (ES) HCM population and analyze clinical course and outcome among its different phenotypes. MethodsData of all HCM patients from 7 Italian referral centres were retrospectively evaluated. ES was diagnosed in presence of: LVEF <50% (ES-rEF) or NYHA functional class ≥II with severe diastolic dysfunction (ES-pEF). Outcomes were: HCM-related and all-cause mortality; combined arrhythmic events; advanced HF treatments. ResultsStudy population included 331 ES patients; 87% presented ES-rEF and 13% ES-pEF. At ES recognition, patients with ES-pEF were more commonly females, had more frequently NYHA III/IV, atrial fibrillation and greater maximal LV wall thickness. Over a median follow-up of 5.6 years, 83 (25%) patients died, 46 (15%) experienced arrhythmic events and (26%) 85 received advanced HF treatments. Incidence of HCM-related and all-cause mortality, and of combined arrhythmic events did not differ in ES-pEF and ES-rEF patients, but ES-pEF patients were less likely to receive advanced HF treatments. Older age at ES recognition was an independent predictor of increased HCM-related mortality (p = 0.01) and reduced access to advanced HF treatments (p < 0.0001). ConclusionsTwo different HCM-ES phenotypes can be recognized, with ES-pEF showing distinctive features at ES recognition and receiving less frequently advanced HF treatments. Older age at ES recognition has a major impact on outcomes.

Mortality in hypertrophic cardiomyopathy is unrelated to genotype

Abstract Background Hypertrophic cardiomyopathy (HCM) patients with a pathogenic variant are presumed to have worse prognosis than patients without a pathogenic mutation. However, the genetic basis of hypertrophic cardiomyopathy (HCM) is complex, and relationship between genotype status and outcomes have not been completely resolved. Objective We assessed a large international HCM cohort to define the natural history and clinical consequences of genotype status. Methods Consecutive patients (n=1468) with established clinical HCM diagnosis underwent genetic testing focused on HCM-related genes. Patients with pathogenic or likely pathogenic variants were considered genotype positive (G+), and those without definite disease-causing mutation or a variant of uncertain significance (VUS) were considered genotype negative (G-). Patients were followed for 9.6 ± 8.2 years for clinical outcomes. Results Of 1468 HCM patients, 1156 (79%) were G - and 312 (21%) were G+. Over the follow-up 116 (10%) G- patients died at 70 ± 14 years, including in 26 (2.2%) from HCM-related causes. HCM-related mortality was not significantly different in G- patients (0.3%/year) as compared to G+ patients (0.3%/year) when adjusted for age (HR 0.93, 95% CI 0.38-2.30, p=0.87). All-cause mortality was not different among these groups (0.7%/year G- vs. 0.6%/year G+) when adjusted for age (HR 0.62, 95% CI 0.3-1.2, p=0.14) or comorbidities (HR 0.78, 95% CI 0.46-1.31, p=0.35). Rate of progression to advanced heart failure NYHA class III/IV in nonobstructive patients was not different in G- (4%/ year) vs. G+ (3%/year, HR 1.20, 95% CI 0.63-2.26, p=0.58). Sudden death events (appropriate ICD shocks, aborted cardiac arrest and sudden death) were more frequent in G+ patients (1.7%/year) than in G- patients (0.5%/year), albeit of borderline statistical significance when adjusted for age and SD risk factors (HR 1.58, 95% CI 1.00-2.49, p=0.05). Conclusions In this large consecutive genotyped cohort, all-cause and HCM-related mortality was unrelated to genotype status. Substantial proportion of G- patients experienced progressive HF, at a similar rate when compared to G+ patients. Although G- patients had less frequently SD events, genotype negative status could not be considered benign.FiguresTable

Lifetime Clinical Course of Hypertrophic Cardiomyopathy: Outcome of the Historical Florence Cohort Over 5 Decades

BackgroundThe current understanding of the clinical course and long-term outcome of patients with hypertrophic cardiomyopathy (HCM) has been extrapolated from cohorts with relatively short follow-up, usually <10 years. Extended assessments more closely reflecting HCM lifetime burden are not available. ObjectivesThe purpose of this study was to report the lifetime clinical course of HCM. MethodsWe analyzed the clinical course of HCM patients diagnosed at our center from 1970 to 1992 and followed annually to the present. Cumulative incidence functions were used to estimate the incidence of HCM-related mortality (including heart failure [HF]/stroke related, sudden cardiac death [SCD]) and non-HCM related. ResultsA total of 202 patients (age 41 ± 17 years; 63% male) were followed 27 ± 6 [range: 3-50] years. Overall, 97 (48%) survived and 105 (52%) died during the particularly long follow-up; 69 deaths were related to HCM, including 53 HF related, 11 fatal embolic strokes, and 16 SCDs. Annual overall HCM-related mortality was 1.3%/y, increasing from 0.7% during the first decade to 1.8% in the second/third decade (P < 0.01), mainly driven by increase in HF-/stroke-related events (from 0.6% to 1.3%). The SCD mortality rate was similar in the 2 periods (0.1% vs 0.44%, P = 0.10). Of the 69 HCM deaths, 29 (42%) occurred before the widespread availability of effective contemporary treatment strategies and are considered potentially preventable. ConclusionsIn this unique HCM cohort followed for up to 50 years, often before contemporary therapies became widely implemented for HCM, HF frequently progressed over time, while arrhythmic SCD events were less common and remained constant over time. Despite spanning different management eras over 5 decades, HCM-related mortality remained relatively low (1.3%/y).

Clinical scenarios of hypertrophic cardiomyopathy-related mortality: Relevance of age and stage of disease at presentation

The evolving epidemiology of hypertrophic cardiomyopathy (HCM) has progressively changed our perception of HCM-related mortality. However, recent studies detailing individual causes of death based on age and clinical setting are lacking. Thus, the present study aimed to describe the modes of death in a consecutive cohort of HCM patients based on presenting clinical features and stage of disease. MethodsBy retrospective analysis of a large HCM cohort, we identified 161 patients with >1 year follow-up who died between 2000 and 2020 and thoroughly investigated their modes of death. HCM stage at presentation was defined as “classic”, “adverse remodeling” or “overt dysfunction”. ResultsOf the 161 patients, 103 (64%) died of HCM-related causes, whereas 58 (36%) died of non-HCM-related causes. Patients who died of HCM-related causes were younger than those who died of non-HCM related causes. The most common cause of death was heart failure (HF). Sudden cardiac death (SCD) ranked third, after non cardiovascular death, and mostly occurred in young individuals. The proportion of HF related death and SCD per stage of disease was 14% and 27% in “classic”, 38% and 21% in “adverse remodeling” and 74% and 10% in “overt dysfunction”. ConclusionsMost HCM patients die due to complications of their own disease, mainly in the context of HF. While SCD tends to be juvenile, HF related deaths often occur in age groups no longer amenable to cardiac transplant. Modes of death vary with the stage of disease, with SCD becoming less prevalent in more advanced phases, when competitive risk of HF becomes overwhelming.

Clinical scenarios of HCM-related mortality: relevance of age and stage of disease at presentation

Abstract In the early days, Hypertrophic cardiomyopathy (HCM) has long been considered a malignant disease. However, contemporary descriptions of HCM report low mortality rates, largely due to heart failure-related complications (HF), while sudden cardiac death (SCD) rates are consistently low. Ageing with HCM is not uncommon and competing risk of acquired cardiovascular (CV) and non-CV diseases becomes relevant over time. Purpose To describe the disease stage at presentation and the modes of death in a cohort of consecutive HCM patients followed at a national referral centre over the last two decades. Stages of disease were defined according to Circ. Heart Fail. 2012, as follows: 1) “Classic HCM phenotype” characterized by LV ejection fraction (EF) &amp;gt;65%. 2) “Adverse remodeling” characterized by LVEF in the range of 50% to 65%. 3) “Overt dysfunction” is the end-stage clinical evolution characterized by a LVEF &amp;lt;50%. Methods By searching our centralized database, we identified 1491 HCM patients with at least &amp;gt;1 year of follow-up between January 2000 and December 2020, 191 of whom died in the same period. In 30 the cause of death could not be ascertained. The remaining 161 constituted our study cohort. Results Of the 161 patients who died, 103 (64%) died due to HCM-related causes, whereas 58 (36%) died from non-HCM-related causes such as coronary artery disease (other CV) or other non CV causes. Modes of death varied based on the stage of disease at diagnosis: – Fifty-six (35%) patients had a “classic” HCM phenotype at diagnosis. Of these, about half died of HCM-related causes (n=30; 54%), versus 45% with non-HCM-related death. Differently from the other 2 stages, the single most common cause of death was “other non-CV related” mortality, in 44%. Among HCM-related causes, SCD prevailed (n=15; 27%) while HF-related events were only 8 (14%). – Of the 86 (53%) patients with “adverse remodeling” at diagnosis, more than half died of HCM-related causes (n=57, 66%), largely due to HF (n=33, 38%); SCD occurred in 18 (21%) individuals. This stage included the highest percentage of patients who died of stroke (n=6; 7%). – Of the 19 (12%) patients in “overt dysfunction” at diagnosis, HF represented the cause of demise in almost three quarters (n=14, 74%); SCD and non-HCM causes accounted for only 10% and 16% respectively. Conclusions Most HCM patients die due to complications of their own disease, mainly in the context of HF. Modes of death vary with the stage of disease, with SCD becoming less prevalent in more advanced phases of progression, when competitive risks of HF-related events become overwhelming. These data highlight an unmet medical need in the prevention of disease progression associated with HCM. Funding Acknowledgement Type of funding sources: None.

Demographic and Regional Trends of Hypertrophic Cardiomyopathy-Related Mortality in the United States, 1999 to 2019.

Hypertrophic cardiomyopathy (HCM)-related mortality has been decreasing within the United States; however, persistent disparities in demographic subsets may exist. In this study, we assessed nationwide trends in mortality related to HCM among people ≥15 years of age in the United States from 1999 to 2019. Trends in mortality related to HCM were assessed through a cross-sectional analysis of the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiological Research database. Age-adjusted mortality rates per 1 000 000 people and associated annual percent changes with 95% CIs were determined. Joinpoint regression was used to assess the trends in the overall, demographic (sex, race and ethnicity, age), and regional groups. Between 1999 and 2019, 39 200 HCM-related deaths occurred. In the overall population, age-adjusted mortality rate decreased from 11.2 in 1999 to 5.4 in 2019. Higher mortality rates were observed for males, Black patients, and patients ≥75 years of age. Large metropolitan counties experienced pronounced declines in age-adjusted mortality rate over the study period. In addition, California had the highest overall age-adjusted mortality rate. Over the past 2 decades, HCM-related mortality has decreased overall in the United States. However, demographic and geographic disparities in HCM-related mortality have persisted over time and require further investigation.

Very long-term prognosis in patients with hypertrophic cardiomyopathy: a longitudinal study with a period of 20years.

AimsWe aim to clarify the prognosis on patients with hypertrophic cardiomyopathy (HCM) for a follow‐up period of more than 10 years.Methods and resultsWe retrospectively analysed 102 consecutive patients with HCM diagnosed by 31 December 2000. Complete and detailed clinical records were obtained for 93 (91%) of the 102 patients. Sixty‐three (68%) of the 93 patients were men, and the mean age of the patients at the initial evaluation was 51.5 ± 13.0 years. During the mean follow‐up period of 19.6 ± 8.1 years (median 20.1 years), HCM‐related deaths occurred in 20 patients (21% [1.1%/year]). HCM‐related adverse events (including HCM‐related deaths and nonfatal HCM‐related events: hospitalization for heart failure, embolic stroke admission, and sustained ventricular tachycardia with haemodynamic instability or appropriate implantable cardioverter‐defibrillator discharge) occurred in 45 patients (48%). The first HCM‐related adverse events occurred in approximately 20% of the patients in every decade, the first decade to the third decade, from the initial evaluation. Forty‐seven patients (51%) had documentation of atrial fibrillation at the last follow‐up. There were seven patients in the end‐stage HCM group at the initial evaluation, and 22 patients (24%) had progression to end‐stage HCM during the follow‐up period.ConclusionsIn our cohort of patients, HCM‐related mortality was relatively favourable. However, approximately half of the patients suffered from HCM‐related adverse events during the follow‐up period of 20 years. It is important for HCM patients to be carefully followed up over the long‐term because HCM is a lifelong disease.

Therapeutic effects of alcohol septal ablation in mildly symptomatic patients with hypertrophic obstructive cardiomyopathy

Objective: To observe the therapeutic effects of alcohol septal ablation (ASA) in mildly symptomatic patients (NYHA class Ⅱ) with hypertrophic obstructive cardiomyopathy(HOCM). Methods: This retrospective study included 150 mildly symptomatic patients with HOCM hospitalized in Beijing Anzhen Hospital affiliated to Capital Medical University from March 2001 to December 2017, consisting of medical therapy group (n=102) and ASA group (n=48). Baseline clinical data were collected, patients were followed up to a mean of 6.0 (3.5, 8.1) years. Overall and HCM-related mortality events (including chronic heart failure, atrial fibrillation related stroke, sudden cardiac death) were observed in the two groups. Moreover, the improvement of NYHA function classification and left ventricular outflow tract gradient (LVOTG) were also evaluated. Survival analysis was performed by Kaplan-Meier method. Results: Age of this cohort was (52.9±14.5)years, 92 cases(61.3%) were male. In the follow-up, LVOTG was reduced from (85.8±35.4)mmHg (1 mmHg=0.133 kPa) to (27.7±19.8)mmHg (P<0.001) in the ASA group, and from (66.3±35.0)mmHg to (56.5±27.7)mmHg in medical therapy group(P<0.01). At the last clinical follow-up, there were 32 patients (66.7%) whose LVOTG were<30 mmHg, septal thickness decreased from (20.3±3.8)mm to (16.1±3.4)mm (P<0.001), NYHA classification was also remarkably improved (P<0.001). New-onset atrial fibrillation tended to be lower in the ASA group compared to medical therapy group (9.3%(4/43) vs. 20.8%(20/96),P=0.096). Eleven patients (10.8%) in the medical therapy group and 2 patients (4.2%) in the ASA group died during the follow-up. One patient received pacemaker during the peri-procedural period, 1 patient was implanted with two-chamber pacemaker due to Ⅲ° atrioventricular block at 10 years after operation in the ASA group. Survival free of all-cause mortality of ASA group at 5 and 10 years was 97.9% and 97.9%, respectively, which was comparable to the medical therapy group (P=0.231). Survival free of HCM-related mortality was similar between the two groups (P=0.397). Conclusions: Compared with medical therapy in mildly symptomatic patients with HOCM, long-term survival rate is similar after ASA. Meanwhile, ASA can remarkably reduce LVOTG and improve the clinical status of the patients. Therefore, ASA may be used as an alternative therapy for mildly symptomatic HOCM patients.

Comparison of mortality and cause of death between adults with and without hypertrophic cardiomyopathy

Insufficient evidence is available comparing mortality and cause of death between general hypertrophic cardiomyopathy (HCM) and general non-HCM populations. We aimed to investigate how causes of death and mortality differ in subjects with and without HCM. Using the National Health Insurance Service database from 2009 to 2016, individuals who underwent health check-up(s) with or without a history of HCM were identified. Participants in the HCM group were matched at a 1:1 ratio with those in the non-HCM group using propensity scores calculated from the baseline covariates. Mortality rates and risks were compared between the groups. In total, 14,858 participants (7,429 each in the HCM and non-HCM groups) were followed up over a mean 4.4 ± 2.2 years (mean age, 61.0 years; male proportion, 66.8%). Compared to the non-HCM group, the HCM group showed a higher risk of all-cause and HCM-related mortality and a similar risk for non-cardiovascular mortality (hazard ratio [95% confidence interval] 1.57 [1.38–1.78], 2.71 [1.92–3.83], and 1.04 [0.88–1.23], respectively). The sensitivity analyses consistently showed that the HCM group showed higher risks of all-cause and HCM-related mortality than the non-HCM group. The female participants with HCM were associated with an increasing trend of the risks of all-cause mortality but not HCM-related mortality compared to their male counterparts (p for interaction < 0.001 and 0.185, respectively). In conclusion, compared to the non-HCM population, the general HCM population showed higher risks of both all-cause and HCM-related mortality, but had a similar risk of non-cardiovascular mortality.

Midterm Outcome After Septal Myectomy and Medical Therapy in Mildly Symptomatic Patients With Hypertrophic Obstructive Cardiomyopathy.

ObjectiveThe purpose of this study was mainly to determine the midterm outcome of septal myectomy (SM) and medical therapy (MT) in mildly symptomatic patients (NYHA class II) with hypertrophic obstructive cardiomyopathy (HOCM).MethodsThe study cohort consisted of 184 mildly symptomatic patients with HOCM evaluated in Beijing Anzhen Hospital, Capital Medical University between March 2001 and December 2017, including 82 patients in the SM group and 102 patients in the MT group. Overall survival and HCM-related survival were mainly observed.ResultsThe average follow-up time was 5.0 years. Compared to patients accepting MT, patients treated with SM were associated with comparable overall survival (96.5% and 93.1% vs. 92.9% and 83.0% at 5 and 10 years, respectively; P = 0.197) and HCM-related survival (98.7% and 98.7% vs. 94.2% and 86.1% at 5 and 10 years, respectively; P = 0.063). However, compared to MT, SM was superior at improvement of NYHA class (1.3 ± 0.6 vs. 2.1 ± 0.5, P < 0.001) and mean reduction of resting left ventricular outflow (LVOT) gradient (78.5 ± 18.6% vs. 28.3 ± 18.4%, P < 0.001). Multivariate analysis suggested that resting LVOT gradient in the last clinical examination was an independent predictor of all-cause mortality (HR = 1.017, 95%CI: 1.000–1.034, P = 0.045) and HCM-related mortality (HR = 1.024, 95%CI: 1.005–1.043, P = 0.012) in the entire cohort.ConclusionCompared with MT, SM had comparable overall survival and HCM-related survival in mildly symptomatic HOCM patients, but SM had advantages on improving clinical symptoms and reducing resting LVOT gradient. Resting LVOT gradient in the last clinical examination was an independent predictor of all-cause mortality and HCM-related mortality.

Prediction of major adverse cardiovascular events in patients with hypertrophic cardiomyopathy using proteomics profiling

Abstract Background Hypertrophic cardiomyopathy (HCM) is one of the most common genetic cardiac diseases, affecting 1 in 200–500 people in the US. HCM often causes major adverse cardiovascular events (MACE) – e.g., arrhythmias (atrial fibrillation, ventricular tachycardia/fibrillation), cerebrovascular accident, heart failure (HF), and sudden cardiac death (SCD). Although these HCM-related morbidities and mortality substantially affect the patients' quality and quantity of life, no systems are available to predict MACE. Furthermore, it remains unclear which signaling pathways mediate MACE. Purpose To prospectively determine protein biomarkers that predict MACE in patients with HCM and to identify signaling pathways differentially regulated in patients with HCM who subsequently develop MACE. Methods In this multi-center prospective cohort study of patients with HCM, we carried out plasma proteomics profiling of 4,979 proteins upon enrollment. We defined MACE as a composite of new-onset arrhythmias, cerebrovascular accident, increase in New York Heart Association class, HF death, SCD, and emergency department visit or non-elective hospitalization for HCM-related morbidities. We performed a sparse partial least squares discriminant analysis to develop a proteomics-based model to predict MACE using data from one institution (i.e., the training set). We tested the predictive ability in independent samples from the other institution (i.e., the test set) and performed time-to-event analysis. Additionally, we executed pathway analysis of the predictive proteins. A pathway was declared positive (i.e., dysregulated) if the false discovery rate (FDR) of the pathway was &amp;lt;0.01 and there were ≥5 proteins that map to the pathway. Results The study included 257 patients with HCM (n=186 in the training set; n=71 in the test set). The median follow-up duration was 2.5 years (interquartile range, 1.4–3.1 years). Each year, 11.7% of patients had MACE. Using the proteomics-based prediction model derived from the training set, the area under the receiver-operating-characteristic curve was 0.84 (95% confidence interval [CI] 0.72–0.96) in the test set (Figure 1). The sensitivity was 0.82 (95% CI, 0.72–0.91) and the specificity was 0.84 (95% CI, 0.79–0.89) in the test set. In the test set, high-risk group determined by the proteomics-based predictive model had significantly higher rate of developing MACE (hazard ratio 20.2; 95% CI 2.4–168; p=0.005; Figure 2). The Ras-MAPK and related pathways were upregulated in patients who subsequently developed MACE (FDR&amp;lt;0.001). Pathways involved in inflammation and fibrosis – e.g., the TGF-β pathway – were also upregulated. Conclusions This multi-center prospective cohort study with validation serves as the first to demonstrate the ability of proteomics profiling to predict MACE in HCM, exhibiting both novel (e.g., Ras-MAPK) and known (e.g., TGF-β) pathways that are differentially regulated in patients who subsequently experience MACE. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Institute of Health, American Heart Association Figure 1Figure 2

GENDER-RELATED DIFFERENCES IN HYPERTROPHIC CARDIOMYOPATHY: A SYSTEMATIC REVIEW AND META-ANALYSIS

Background Gender-related differences in phenotypic expression and outcomes have been established in many cardiac conditions; however, the impact of gender in hypertrophic cardiomyopathy (HCM) remains unclear. We conducted a systematic review and meta-analysis to assess the differences in clinical outcomes between female and male HCM patients. Methods We searched MEDLINE and EMBASE from inception to October 2020. Included were cohort studies that compared outcomes of interest including all-cause mortality, HCM-related mortality, and worsening heart failure (HF) or HF hospitalization between male and female. Data from each study were combined using the random effects model to calculate pooled odds ratio (OR) with 95% confidence interval (CI). Results Eleven retrospective cohort studies with a total of 9,427 patients (3,719 females) were included. Female gender was significantly associated with an increased risk of all-cause mortality (pooled OR = 1.63, 95% CI: 1.26-2.10, p ≤ 0.001), HCM-related mortality (pooled OR = 1.47, 95% CI: 1.08-2.01, p = 0.015), and worsening HF or HF hospitalization (pooled OR = 2.05, 95% CI: 1.76-2.39, p ≤ 0.001). Conclusions Female gender was associated with a worse prognosis in HCM. These findings suggest the need for improved care in women including early identification of disease and more possible aggressive management. Moreover, gender-based strategy may benefit in HCM patients.

Gender-Related Differences in Hypertrophic Cardiomyopathy: A Systematic Review and Meta-Analysis

Background: Gender-related differences in phenotypic expression and outcomes have been established in many cardiac conditions; however, the impact of gender in hypertrophic cardiomyopathy (HCM) remains unclear. We conducted a systematic review and meta-analysis to assess the differences in clinical outcomes between female and male HCM patients. Methods: We searched MEDLINE and EMBASE from inception to October 2020. Included were cohort studies that compared outcomes of interest including all-cause mortality, HCM-related mortality, and worsening heart failure (HF) or HF hospitalization between male and female. Data from each study were combined using the random effects model to calculate pooled odds ratio (OR) with 95% confidence interval (CI). Results: Eleven retrospective cohort studies with a total of 9,427 patients (3,719 females) were included. Female gender was significantly associated with an increased risk of all-cause mortality (pooled OR = 1.63, 95% CI: 1.26–2.10, p ≤ 0.001), HCM-related mortality (pooled OR = 1.47, 95% CI: 1.08–2.01, p = 0.015), and worsening HF or HF hospitalization (pooled OR = 2.05, 95% CI: 1.76–2.39, p ≤ 0.001). Conclusions: Female gender was associated with a worse prognosis in HCM. These findings suggest the need for improved care in women including early identification of disease and more possible aggressive management. Moreover, gender-based strategy may benefit in HCM patients.

Low Risk of Hypertrophic Cardiomyopathy With Contemporary Management Strategies Implemented in Non-Referral Regional Community-Based Practices

Major advances in diagnosis and treatment have emerged for hypertrophic cardiomyopathy (HCM), largely in major tertiary referral centers dedicated to this disease. Whether these therapeutic benefits are confined to patients in such highly selected cohorts, or can be implemented effectively in independent regional or community-based populations is not generally appreciated. We assessed management and clinical outcomes in a non-referral HCM center (n = 214 patients) in Eastern Pennsylvania. Over a 6.0 ± 3.2-year follow-up, the HCM-related mortality rate was 0.1% per year attributed to a single disease-related death, in a 49-year-old man with end-stage heart failure, ineligible for heart transplant. Fifteen patients (7%) with prophylactically placed implantable cardioverter-defibrillators (ICDs) experienced appropriate therapy terminating life-threatening ventricular tachyarrhythmias. In 23 other patients (11%; 5%/year), heart failure due to left ventricular outflow obstruction was reversed by surgical septal myectomy (n = 20) or percutaneous alcohol septal ablation (n = 3). This regional HCM cohort was similar to a comparison tertiary center referral population in terms of HCM-mortality: 0.1%/year vs 0.3%/year (p = 0.3) and ICD therapy (31% vs 16% of primary prevention implants), although more frequently with uncomplicated benign clinical course (62% vs 46%; p <0.01). In conclusion, effective contemporary HCM management strategies and outcomes in referral-based HCM centers can be successfully replicated in regional and/or non-referral settings. Therefore, HCM is now a highly treatable disease compatible with normal longevity when assessed in a variety of clinical venues not limited to tertiary centers.

Myocardial contraction fraction predicts mortality for patients with hypertrophic cardiomyopathy

The myocardial contraction fraction (MCF: stroke volume to myocardial volume) is a novel volumetric measure of left ventricular myocardial shortening. The purpose of the present study was to assess whether MCF could predict adverse outcomes for HCM patients. A retrospective cohort study of 438 HCM patients was conducted. The primary and secondary endpoints were all-cause mortality and HCM-related mortality. The association between MCF and endpoints was analysed. During a follow-up period of 1738.2 person-year, 76 patients (17.2%) reached primary endpoint and 50 patients (65.8%) reached secondary endpoint. Both all-cause mortality rate and HCM-related mortality rate decreased across MCF tertiles (24.7% vs. 17.9% vs. 9.5%, P trend = 0.003 for all-cause mortality; 16.4% vs. 9.7% vs. 6.1%, P trend = 0.021 for HCM-related mortality). Patients in the third tertile had a significantly lower risk of developing adverse outcomes than patients in the first tertile: all-cause mortality (adjusted HR: 0.26, 95% CI: 0.12–0.56, P = 0.001), HCM-related mortality (adjusted HR: 0.17, 95% CI: 0.07–0.42, P < 0.001). At 1-, 3-, and 5-year of follow-up, areas under curve were 0.699, 0.643, 0.618 for all-cause mortality and 0.749, 0.661, 0.613 for HCM-related mortality (all P value < 0.001), respectively. In HCM patients, MCF could independently predict all-cause mortality and HCM-related mortality, which should be considered for overall risk assessment in clinical practice.

Hypertrophic Cardiomyopathy 2020.

To briefly review the pathophysiology and natural history of hypertrophic cardiomyopathy (HCM) and to describe the diagnosis, assessment, and contemporary management strategies. HCM-related mortality remains low; however, symptoms due in large part to LVOT obstruction remain a clinical dilemma. Several medical therapies have been shown to reduce symptoms and improve functional capacity, including several recent phase 2 clinical trials involving the novel myosin modulator mavacamten. In patients with refractory symptoms, septal reduction therapy or advanced therapies remain viable options in many cases. HCM is a complex and heterogeneous disease with diverse presentations and variable anatomy and clinical outcomes. The majority of patients will remain asymptomatic or with minimal symptoms and long-term survival remains high. For symptomatic patients, a variety of medical therapies, along with septal reduction therapies, have been shown to reduce symptoms and improve functional capacity.

U-shaped association between serum uric acid concentration and mortality in hypertrophic cardiomyopathy patients

Background. No study has examined the effect of low serum uric acid (SUA) concentrations on mortality in hypertrophic cardiomyopathy (HCM) patients. The aim of the present study was to assess the relations between both low and high SUA concentrations and the risk of mortality across the full range of SUA concentrations in a retrospective cohort of HCM patients.Methods. A total of 454 HCM patients were enrolled in the study, and SUA concentrations were measured at baseline. The primary and secondary endpoints were all-cause mortality and HCM-related mortality, respectively. The associations between SUA concentrations and endpoints were analysed.Results. During a median follow-up of 3.8 years, there were 80 (17.6%) all-cause mortality events, and 52 of them (11.5%) were ascribed to HCM-related mortality. Patients with SUA concentrations of 250–350 µmol/L had the lowest all-cause mortality rate (11.8%) and HCM-related mortality rate (5.0%). Both low and high SUA concentrations were associated with increased all-cause and HCM-related mortality. Adjusted HRs were 2.52 (95% CI 1.13–5.61, p = 0.024) and 4.86 (95% CI 1.74–13.58, p = 0.003) for all-cause mortality and HCM-related mortality in the lowest SUA group (<250 µmol/L) when compared with the reference group (250–350 µmol/L), respectively. The corresponding HRs in the highest SUA group (≥450 µmol/L) were 2.73 (95% CI 1.42–5.23, p = 0.003) and 4.14 (95% CI 1.70–10.13, p = 0.002), respectively.Conclusions. Both low and high SUA concentrations were significantly associated with increased risk of all-cause mortality and HCM-related mortality, which supported a U-shaped association between SUA concentrations and mortality in HCM patients.