Exploring Health Care Disparities in Genetic Testing and Research for Hereditary Cardiomyopathy: Current State and Future Perspectives.

Background Hereditary cardiomyopathies are commonly occurring myocardial conditions affecting heart structure and function with a genetic or familial association, but the etiology is often unknown. Cardiomyopathies are linked to significant mortality, requiring robust risk stratification with genetic testing and early diagnosis. Hypothesis We hypothesized that health care disparities exist in genetic testing for hereditary cardiomyopathies within clinical practice and research studies. Methods In a narrative fashion, we conducted a literature search with online databases such as PubMed/MEDLINE, Google Scholar, EMBASE, and Science Direct on papers related to hereditary cardiomyopathies. A comprehensive analysis of findings from articles in English on disparities in diagnostics and treatment was grouped into four categories. Results Racial and ethnic disparities in research study enrollment and health care delivery favor White populations and higher socioeconomic status, resulting in differences in the development and implementation of effective genetic screening. Such disparities have shown to be detrimental, as minorities often suffer from disease progression to heart failure and sudden cardiac death. Barriers related to clinical genetic testing included insurance-related issues and health illiteracy. The underrepresentation of minority populations extends to research methodologies, as testing in ethnic minorities resulted in a significantly lower detection rate and diagnostic yield, as well as a higher likelihood of misclassification of variants. Conclusions Prioritizing minority-based participatory research programs and screening protocols can address systemic disparities. Diversifying research studies can improve risk stratification strategies and impact clinical practice.

Assessing the association between genetic and phenotypic features of dilated cardiomyopathy and outcome in patients with coronary artery disease.

AIMS: To examine the relevance of genetic and cardiovascular magnetic resonance (CMR) features of dilated cardiomyopathy (DCM) in individuals with coronary artery disease (CAD). METHODS AND RESULTS: This study includes two cohorts. First, individuals with CAD recruited into the UK Biobank (UKB) were evaluated. Second, patients with CAD referred to a tertiary centre for evaluation with late gadolinium enhancement (LGE)-CMR were recruited (London cohort); patients underwent genetic sequencing as part of the research protocol and long-term follow-up. From 31 154 individuals with CAD recruited to UKB, rare pathogenic variants in DCM genes were associated with increased risk of death or major adverse cardiac events (hazard ratio 1.57, 95% confidence interval [CI] 1.22-2.01, p < 0.001). Of 1619 individuals with CAD included from the UKB CMR substudy, participants with a rare variant in a DCM-associated gene had lower left ventricular ejection fraction (LVEF) compared to genotype negative individuals (mean 47 ± 10% vs. 57 ± 8%, p < 0.001). Of 453 patients in the London cohort, 63 (14%) had non-infarct pattern LGE (NI-LGE) on CMR. Patients with NI-LGE had lower LVEF (mean 38 ± 18% vs. 48 ± 16%, p < 0.001) compared to patients without NI-LGE, with no significant difference in the burden of rare protein altering variants in DCM-associated genes between groups (9.5% vs. 6.7%, odds ratio 1.5, 95% CI 0.4-4.3, p = 0.4). NI-LGE was not independently associated with adverse clinical outcomes. CONCLUSION: Rare pathogenic variants in DCM-associated genes impact left ventricular remodelling and outcomes in stable CAD. NI-LGE is associated with adverse remodelling but is not an independent predictor of outcome and had no rare genetic basis in our study.

Phenotype, outcomes and natural history of early-stage non-ischaemic cardiomyopathy.

AIMS: To characterize the phenotype, clinical outcomes and rate of disease progression in patients with early-stage non-ischaemic cardiomyopathy (early-NICM). METHODS AND RESULTS: We conducted a prospective observational cohort study of patients with early-NICM assessed by late gadolinium enhancement cardiovascular magnetic resonance (CMR). Cases were classified into the following subgroups: isolated left ventricular dilatation (early-NICM H-/D+), non-dilated left ventricular cardiomyopathy (early-NICM H+/D-), or early dilated cardiomyopathy (early-NICM H+/D+). Clinical follow-up for major adverse cardiovascular events (MACE) included non-fatal life-threatening arrhythmia, unplanned cardiovascular hospitalization or cardiovascular death. A subset of patients (n = 119) underwent a second CMR to assess changes in cardiac structure and function. Of 254 patients with early-NICM (median age 46 years [interquartile range 36-58], 94 [37%] women, median left ventricular ejection fraction [LVEF] 55% [52-59]), myocardial fibrosis was present in 65 (26%). There was no difference in the prevalence of fibrosis between subgroups (p = 0.90), however fibrosis mass was lowest in early-NICM H-/D+, higher in early-NICM H+/D- and highest in early-NICM H+/D+ (p = 0.03). Over a median follow-up of 7.9 (5.5-10.0) years, 28 patients (11%) experienced MACE. Non-sustained ventricular tachycardia (hazard ratio [HR] 5.1, 95% confidence interval [CI] 2.36-11.00, p < 0.001), myocardial fibrosis (HR 3.77, 95% CI 1.73-8.20, p < 0.001) and diabetes mellitus (HR 5.12, 95% CI 1.73-15.18, p = 0.003) were associated with MACE in a multivariable model. Only 8% of patients progressed from early-NICM to dilated cardiomyopathy with LVEF <50% over a median of 16 (11-34) months. CONCLUSION: Early-NICM is not benign. Fibrosis develops early in the phenotypic course. In-depth characterization enhances risk stratification and might aid clinical management.

The common pathobiology between coronary artery disease and calcific aortic stenosis: Evidence and clinical implications.

Calcific aortic valve stenosis (CAS), the most prevalent valvular disease worldwide, has been demonstrated to frequently occur in conjunction with coronary artery disease (CAD), the third leading cause of death worldwide. Atherosclerosis has been proven to be the main mechanism involved in CAS and CAD. Evidence also exists that obesity, diabetes, and metabolic syndrome (among others), along with specific genes involved in lipid metabolism, are important risk factors for CAS and CAD, leading to common pathological processes of atherosclerosis in both diseases. Therefore, it has been suggested that CAS could also be used as a marker of CAD. An understanding of the commonalities between the two conditions may improve therapeutic strategies for treating both CAD and CAS. This review explores the common pathogenesis and disparities between CAS and CAD, alongside their etiology. It also discusses clinical implications and provides evidence-based recommendations for the clinical management of both diseases.

Chemotherapy Induced Cardiotoxicity: A State of the Art Review on General Mechanisms, Prevention, Treatment and Recent Advances in Novel Therapeutics.

As medicine advances to employ sophisticated anticancer agents to treat a vast array of oncological conditions, it is worth considering side effects associated with several chemotherapeutics. One adverse effect observed with several classes of chemotherapy agents is cardiotoxicity which leads to reduced ejection fraction (EF), cardiac arrhythmias, hypertension and Ischemia/myocardial infarction that can significantly impact the quality of life and patient outcomes. Research into possible mechanisms has elucidated several mechanisms, such as ROS generation, calcium overload and apoptosis. However, there is a relative scarcity of literature detailing the relationship between the exact mechanism of cardiotoxicity for each anticancer agent and observed clinical effects. This review comprehensively describes cardiotoxicity associated with various classes of anticancer agents and possible mechanisms. Further research exploring possible mechanisms for cardiotoxicity observed with anticancer agents could provide valuable insight into susceptibility for developing symptoms and management guidelines. Chemotherapeutics are associated with several side effects. Several classes of chemotherapy agents cause cardiotoxicity leading to a reduced ejection fraction (EF), cardiac arrhythmias, hypertension, and Ischemia/myocardial infarction. Research into possible mechanisms has elucidated several mechanisms, such as ROS generation, calcium overload, and apoptosis. However, there is a relative scarcity of literature detailing the relationship between the exact mechanism of cardiotoxicity for each anticancer agent and observed clinical effects. This review describes cardiotoxicity associated with various classes of anticancer agents and possible mechanisms. Further research exploring mechanisms for cardiotoxicity observed with anticancer agents could provide insight that will guide management.

Prognostic factors of 10-year mortality after coronary artery bypass graft surgery: a secondary analysis of the arterial revascularization trial.

OBJECTIVES: The objective of this investigation was to determine the preoperative prognostic factors of long-term (10-year) mortality in patients treated with isolated coronary artery bypass graft surgery in the arterial revascularization trial (ART). METHODS: A post hoc analysis of the ART was conducted. Cumulative 10-year mortality was estimated using the Kaplan-Meier method. Prospectively collected preoperative data were used to determine the prognostic factors of 10-year all-cause mortality in patients who participated in the ART (Cox proportional hazards model). RESULTS: A total of 3102 patients who participated in the ART were included in the analysis. Ten-year follow-up was completed in 3040 patients (98%). A total of 644 patients (20.8%) had died by 10 years. Preoperative factors that were identified as statistically significant predictors of 10-year mortality in the multivariable analysis (all P ≤ 0.01) were: left ventricular ejection fraction, atrial fibrillation, age, diabetes, prior cerebrovascular event (stroke or transient ischaemic attack), serum creatinine and smoking status. The following variables were significantly associated in univariable models but did not retain significance in the multivariable model for mortality: non-Caucasian ethnicity, hypertension, peripheral vascular disease, chronic obstructive pulmonary disease and prior myocardial infarction. CONCLUSIONS: Independent predictors of 10-year mortality in the ART were multifactorial. Several key independent predictors of 10-year mortality in the ART were identified including: heart function, renal function, cerebrovascular disease, age, atrial fibrillation, smoking status and diabetes. Understanding which preoperative variables influence long-term outcome after coronary artery bypass grafting may help to target treatments to those at higher risk to reduce mortality.