Sex-specific cardiac phenotype and clinical outcomes in patients with hypertrophic cardiomyopathy

Lu, Dai Yin; Ventoulis, Ioannis; Liu, Hongyun; Kudchadkar, Shibani M.; Greenland, Gabriela V.; Yalçın, Hülya; Kontari, Effrosyni; Goyal, Sagar; Corona‐Villalobos, Celia P.; Vakrou, Styliani; Zimmerman, Stefan L.; Abraham, Theodore P.; Abraham, M. Roselle

doi:10.1016/j.ahj.2019.10.004

Cited by 26 publications

(32 citation statements)

References 59 publications

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“…Twenty-one studies were excluded due to reasons given in the PRISMA flow diagram in Figure 1. Therefore, 11 studies were included in this meta-analysis [11,12,[22][23][24][25][26][27][28][29][30].…”

Section: Literature Searchmentioning

confidence: 99%

“…Outcomes regarding all-cause mortality were available in 7 studies [11,12,24,25,27,28,30]. Female gender was associated with a higher risk of all-cause mortality (pooled OR = 1.63, 95% CI: 1.26-2.10, p ≤ 0.001, I 2 = 35%).…”

Section: All-cause Mortalitymentioning

confidence: 99%

“…Worsening HF or HF Hospitalization Outcomes regarding worsening HF or HF hospitalization were available in 7 studies [11,12,22,25,[28][29][30]. Female gender was associated with worsening HF or HF hospitalization than male gender (pooled OR = 2.05, 95% CI: 1.76-2.39, p ≤ 0.001, I 2 = 0%).…”

Section: Hcm-related Mortalitymentioning

confidence: 99%

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

Trongtorsak

Polpichai

Thangjui

et al. 2021

Pulse

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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.

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Section: Literature Searchmentioning

confidence: 99%

Section: All-cause Mortalitymentioning

confidence: 99%

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

Trongtorsak

Polpichai

Thangjui

et al. 2021

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“…Hypertrophic cardiomyopathy (HCM) caused by mutations in genes encoding sarcomeric proteins 1 , is the most common cause of sudden cardiac death in young individuals 2 – 4 . These mutations lead to myocyte hypertrophy, disarray, interstitial/replacement fibrosis and arteriolar remodeling 5 , which underlie atrial/ventricular arrhythmias, heart failure and angina 6 – 8 .…”

Section: Introductionmentioning

confidence: 99%

Differences in molecular phenotype in mouse and human hypertrophic cardiomyopathy

Vakrou

Liu

Zhu³

et al. 2021

Sci Rep

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Hypertrophic cardiomyopathy (HCM) is characterized by phenotypic heterogeneity. We investigated the molecular basis of the cardiac phenotype in two mouse models at established disease stage (mouse-HCM), and human myectomy tissue (human-HCM). We analyzed the transcriptome in 2 mouse models with non-obstructive HCM (R403Q-MyHC, R92W-TnT)/littermate-control hearts at 24 weeks of age, and in myectomy tissue of patients with obstructive HCM/control hearts (GSE36961, GSE36946). Additionally, we examined myocyte redox, cardiac mitochondrial DNA copy number (mtDNA-CN), mt-respiration, mt-ROS generation/scavenging and mt-Ca2+ handling in mice. We identified distinct allele-specific gene expression in mouse-HCM, and marked differences between mouse-HCM and human-HCM. Only two genes (CASQ1, GPT1) were similarly dysregulated in both mutant mice and human-HCM. No signaling pathway or transcription factor was predicted to be similarly dysregulated (by Ingenuity Pathway Analysis) in both mutant mice and human-HCM. Losartan was a predicted therapy only in TnT-mutant mice. KEGG pathway analysis revealed enrichment for several metabolic pathways, but only pyruvate metabolism was enriched in both mutant mice and human-HCM. Both mutant mouse myocytes demonstrated evidence of an oxidized redox environment. Mitochondrial complex I RCR was lower in both mutant mice compared to controls. MyHC-mutant mice had similar mtDNA-CN and mt-Ca2+ handling, but TnT-mutant mice exhibited lower mtDNA-CN and impaired mt-Ca2+ handling, compared to littermate-controls. Molecular profiling reveals differences in gene expression, transcriptional regulation, intracellular signaling and mt-number/function in 2 mouse models at established disease stage. Further studies are needed to confirm differences in gene expression between mouse and human-HCM, and to examine whether cardiac phenotype, genotype and/or species differences underlie the divergence in molecular profiles.

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“…1.1 Patient Population: Our HCM Registry (JHH-HCM Registry) is approved by the Institutional Review Boards of the Johns Hopkins Hospital (JHH) and the University of California San Francisco (UCSF). Patients were enrolled in the JHH-HCM Registry during their first visit to the Johns Hopkins HCM-Center of Excellence [15] if they met the standard diagnostic criteria for HCM, namely, maximal LV wall thickness [? ]15 mm [16] in the absence of uncontrolled hypertension, valvular heart disease and HCM phenocopies (amyloidosis, storage disorders).…”

Section: Clinical Data and Outcomesmentioning

confidence: 99%

HCM-AF-Risk Model to Identify Cases and Predictors of Atrial Fibrillation in Hypertrophic Cardiomyopathy

Bhattacharya

Greenland

et al. 2020

Preprint

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Background AF in HCM is associated with high stroke risk despite low CHA2DS2-VASc scores. Hence, there is need to understand AF pathophysiology and predict AF in HCM. We develop/apply a data-driven, machine learning-based method to identify AF cases and clinical features associated with AF in HCM, using electronic health record (EHR) data. Methods Patients with documented paroxysmal/ persistent/permanent AF (n=191) were considered AF cases, and the remaining patients in sinus rhythm (n=640) were tagged as No-AF. We evaluated 93 clinical variables; the most informative variables useful for distinguishing AF from No-AF cases were selected based on the 2-sample t-test and information gain criterion. Results We identified 18 highly informative clinical variables: 11 are positively associated (e.g. LA-diameter, LV-diastolic dysfunction, LV-LGE), and 7 are negatively correlated (e.g. several exercise parameters) with AF in HCM. Next, patient records were represented via these 18 variables. Data imbalance resulting from the relatively low number of AF cases was addressed via a combination of over-and under-sampling strategies. We trained and tested multiple classifiers under this sampling approach, showing effective classification. Specifically, an ensemble of logistic regression and naïve Bayes classifiers, trained based on the 18 variables and corrected for data imbalance, proved most effective for separating AF from No-AF cases (sensitivity=0.74, specificity=0.72, C-index=0.80). Conclusions Our model (HCM-AF-Risk Model), the first machine learning-based method for identification of AF cases in HCM, demonstrates good performance, and suggests that AF is associated with a more severe cardiac HCM-phenotype.

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Sex-specific cardiac phenotype and clinical outcomes in patients with hypertrophic cardiomyopathy

Cited by 26 publications

References 59 publications

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

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

Differences in molecular phenotype in mouse and human hypertrophic cardiomyopathy

HCM-AF-Risk Model to Identify Cases and Predictors of Atrial Fibrillation in Hypertrophic Cardiomyopathy

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