Rare Variant Genetics and Dilated Cardiomyopathy Severity: The DCM Precision Medicine Study.

BACKGROUND: Dilated cardiomyopathy (DCM) can lead to advanced disease, defined herein as necessitating a durable left ventricular assist device or a heart transplant (LVAD/HT). DCM is known to have a genetic basis, but the association of rare variant genetics with advanced DCM has not been studied. METHODS: We analyzed clinical and genetic sequence data from patients enrolled between 2016 and 2021 in the US multisite DCM Precision Medicine Study, which was a geographically diverse, multiracial, multiethnic cohort. Clinical evaluation included standardized patient interview and medical record query forms. DCM severity was classified into 3 groups: patients with advanced disease with LVAD/HT; patients with an implantable cardioverter defibrillator (ICD) only; or patients with no ICD or LVAD/HT. Rare variants in 36 DCM genes were classified as pathogenic or likely pathogenic or variants of uncertain significance. Confounding factors we considered included demographic characteristics, lifestyle factors, access to care, DCM duration, and comorbidities. Crude and adjusted associations between DCM severity and rare variant genetic findings were assessed using multinomial models with generalized logit link. RESULTS: Patients' mean (SD) age was 51.9 (13.6) years; 42% were of African ancestry, 56% were of European ancestry, and 44% were female. Of 1198 patients, 347 had LVAD/HT, 511 had an ICD, and 340 had no LVAD/HT or ICD. The percentage of patients with pathogenic or likely pathogenic variants was 26.2%, 15.9%, and 15.0% for those with LVAD/HT, ICD only, or neither, respectively. After controlling for sociodemographic characteristics and comorbidities, patients with DCM with LVAD/HT were more likely than those without LVAD/HT or ICD to have DCM-related pathogenic or likely pathogenic rare variants (odds ratio, 2.3 [95% CI, 1.5-3.6]). The association did not differ by ancestry. Rare variant genetic findings were similar between patients with DCM with an ICD and those without LVAD/HT or ICD. CONCLUSIONS: Advanced DCM was associated with higher odds of rare variants in DCM genes adjudicated as pathogenic or likely pathogenic, compared with individuals with less severe DCM. This finding may help assess the risk of outcomes in management of patients with DCM and their at-risk family members. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03037632.

Effectiveness of the Family Heart Talk Communication Tool in Improving Family Member Screening for Dilated Cardiomyopathy: Results of a Randomized Trial.

BACKGROUND: Managing disease risk among first-degree relatives of probands diagnosed with a heritable disease is central to precision medicine. A critical component is often clinical screening, which is particularly important for conditions like dilated cardiomyopathy (DCM) that remain asymptomatic until severe disease develops. Nonetheless, probands are frequently ill-equipped to disseminate genetic risk information that motivates at-risk relatives to complete recommended clinical screening. An easily implemented remedy for this key issue has been elusive. METHODS: The DCM Precision Medicine Study developed Family Heart Talk, a booklet designed to help probands with DCM communicate genetic risk and the need for cardiovascular screening to their relatives. The effectiveness of the Family Heart Talk booklet in increasing cardiovascular clinical screening uptake among first-degree relatives was assessed in a multicenter, open-label, cluster-randomized, controlled trial. The primary outcome measured in eligible first-degree relatives was completion of screening initiated within 12 months after proband enrollment. Because probands randomized to the intervention received the booklet at the enrollment visit, eligible first-degree relatives were limited to those who were alive the day after proband enrollment and not enrolled on the same day as the proband. RESULTS: Between June 2016 and March 2020, 1241 probands were randomized (1:1) to receive Family Heart Talk (n=621) or not (n=620) within strata defined by site and self-identified race/ethnicity (non-Hispanic Black, non-Hispanic White, or Hispanic). Final analyses included 550 families (n=2230 eligible first-degree relatives) in the Family Heart Talk arm and 561 (n=2416) in the control arm. A higher percentage of eligible first-degree relatives completed screening in the Family Heart Talk arm (19.5% versus 16.0%), and the odds of screening completion among these first-degree relatives were higher in the Family Heart Talk arm after adjustment for proband randomization stratum, sex, and age quartile (odds ratio, 1.30 [1-sided 95% CI, 1.08-∞]). A prespecified subgroup analysis did not find evidence of heterogeneity in the adjusted intervention odds ratio across race/ethnicity strata (P=0.90). CONCLUSIONS: Family Heart Talk, a booklet that can be provided to patients with DCM by clinicians with minimal additional time investment, was effective in increasing cardiovascular clinical screening among first-degree relatives of these patients. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03037632.

Genetic Architecture of Dilated Cardiomyopathy in Individuals of African and European Ancestry.

Importance: Black patients with dilated cardiomyopathy (DCM) have increased familial risk and worse outcomes than White patients, but most DCM genetic data are from White patients. Objective: To compare the rare variant genetic architecture of DCM by genomic ancestry within a diverse population of patients with DCM. Design: Cross-sectional study enrolling patients with DCM who self-identified as non-Hispanic Black, Hispanic, or non-Hispanic White from June 7, 2016, to March 15, 2020, at 25 US advanced heart failure programs. Variants in 36 DCM genes were adjudicated as pathogenic, likely pathogenic, or of uncertain significance. Exposure: Presence of DCM. Main Outcomes and Measures: Variants in DCM genes classified as pathogenic/likely pathogenic/uncertain significance and clinically actionable (pathogenic/likely pathogenic). Results: A total of 505, 667, and 26 patients with DCM of predominantly African, European, or Native American genomic ancestry, respectively, were included. Compared with patients of European ancestry, a lower percentage of patients of African ancestry had clinically actionable variants (8.2% [95% CI, 5.2%-11.1%] vs 25.5% [95% CI, 21.3%-29.6%]), reflecting the lower odds of a clinically actionable variant for those with any pathogenic variant/likely pathogenic variant/variant of uncertain significance (odds ratio, 0.25 [95% CI, 0.17-0.37]). On average, patients of African ancestry had fewer clinically actionable variants in TTN (difference, -0.09 [95% CI, -0.14 to -0.05]) and other genes with predicted loss of function as a disease-causing mechanism (difference, -0.06 [95% CI, -0.11 to -0.02]). However, the number of pathogenic variants/likely pathogenic variants/variants of uncertain significance was more comparable between ancestry groups (difference, -0.07 [95% CI, -0.22 to 0.09]) due to a larger number of non-TTN non-predicted loss of function variants of uncertain significance, mostly missense, in patients of African ancestry (difference, 0.15 [95% CI, 0.00-0.30]). Published clinical case-based evidence supporting pathogenicity was less available for variants found only in patients of African ancestry (P < .001). Conclusion and Relevance: Patients of African ancestry with DCM were less likely to have clinically actionable variants in DCM genes than those of European ancestry due to differences in genetic architecture and a lack of representation of African ancestry in clinical data sets.

Subclinical Myocardial Injury and the Phenotype of Clinical Congestion in Patients With Heart Failure and Reduced Left Ventricular Ejection Fraction.

BACKGROUND: Clinical congestion is associated with adverse outcomes in patients with heart failure. The pathophysiological mediators of this association remain uncertain. METHODS AND RESULTS: We prospectively enrolled a cohort of patients with heart failure and reduced left ventricular ejection fraction and performed a detailed clinical examination followed on the same day by an invasive right heart catheterization and blood sampling for biomarkers. High-sensitivity troponin T and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were measured. A clinical congestion score was calculated based on jugular venous pressure (cm H20 <10 = 0, 10-14 = 1, >14 = 2 points), bendopnea (0 vs 1), a third heart sound (0 vs 1), or peripheral edema (0-2). Congestion was categorized into tiers as absent (0 points), mild (1 point), or moderate to severe (≥ 2 points). We tested for associations of high-sensitivity troponin T, NT-proBNP, and elevated ventricular filling pressures with clinical congestion in both univariate and multivariable analyses. Of 153 participants, 65 (42%) had absent, 35 mild (23%), and 53 (35%) had moderate to severe clinical congestion. Congestion tier was associated with higher NT-proBNP and hs-troponin levels, and the right atrial pressure and pulmonary capillary wedge pressure (P < .001 for each). Increased congestion tier was also associated with the coexistent presence of elevated troponin T (≥52 ng/L), NT-proBNP (≥1000 pg/mL), and pulmonary capillary wedge pressure (≥22 mm Hg). Specifically, 78% of those with absent clinical congestion had 0 to 1 of these findings, whereas 75% of those with moderate-severe congestion had 2 or all 3 of these abnormalities (P < .001). An elevated hs-troponin was associated with mild or greater clinical congestion (odds ratio 3, 95% confidence interval 1.2-7.5, P = .02) in multivariable analysis adjusting for potential confounders including the right atrial pressure, pulmonary capillary wedge pressure, and NT-proBNP levels. CONCLUSIONS: Clinical congestion is a phenotype in which there is a high coexistent presence of elevated ventricular filling pressures, elevated natriuretic peptide levels, and subclinical myocardial injury. An elevated troponin was associated with clinical congestion in multivariable models that adjusted for ventricular filling pressures and natriuretic peptide levels. These data strengthen the evidence base for an association of elevated troponin with clinical congestion, suggesting that subclinical myocardial injury may be an important contributor to the pathophysiology of the congested state.

Clinical Implications of the Amyloidogenic V122I Transthyretin Variant in the General Population.

BACKGROUND: The V122I variant in transthyretin (TTR) is the most common amyloidogenic mutation worldwide. The aim of this study is to describe the cardiac phenotype and risk for adverse cardiovascular outcomes of young V122I TTR carriers in the general population. METHODS AND RESULTS: TTR genotypes were extracted from whole-exome sequence data in participants of the Dallas Heart Study. Participants with African ancestry, available V122I TTR genotypes (N = 1818) and either cardiac magnetic resonance imaging (n = 1364) or long-term follow-up (n = 1532) were included. The prevalence of V122I TTR carriers (45 ± 10 years) was 3.2% (n/N = 59/1818). The V122I TTR carriers had higher baseline left ventricular wall thickness (8.52 ± 1.82 vs 8.21 ± 1.62 mm, adjusted P = .038) than noncarriers, but no differences in other cardiac magnetic resonance imaging measures (P > .05 for all). Although carrier status was not associated with amino terminal pro-B-type natriuretic peptide (NT-proBNP) at baseline (P = .79), V122I TTR carriers had a greater increase in NT-proBNP on follow-up than noncarriers (median 28.5 pg/mL, interquartile range 11.4-104.1 pg/mL vs median 15.9 pg/mL, interquartile range 0.0-43.0 pg/mL, adjusted P = .018). V122I TTR carriers were at a higher adjusted risk of heart failure (hazard ratio 3.82, 95% confidence interval 1.80-8.13, P < .001), cardiovascular death (hazard ratio 2.65, 95% confidence interval 1.14-6.15, P = .023), and all-cause mortality (hazard ratio 1.95, 95% confidence interval 1.08-3.51, P = .026) in comparison with noncarriers. CONCLUSIONS: V122I TTR carrier status was associated with a greater increase in NT-proBNP, slightly greater left ventricular wall thickness, and a higher risk for heart failure, cardiovascular death, and all-cause mortality. These findings suggest the need to develop amyloidosis screening strategies for V122I TTR carriers.

Biomarker-Based Assessment for Infectious Risk Before and After Heart Transplantation.

PURPOSE OF REVIEW: Survival outcomes for heart transplant recipients have improved in recent decades, but infection remains a significant cause of morbidity and mortality. In this review, we discuss several biological markers, or biomarkers, that may be used to monitor immunologic status in this patient population. RECENT FINDINGS: While modest, data on the utility of immune biomarkers in heart transplant recipients suggest correlation between low level of immune response and increased infection risk. More novel assays, such as the detection of circulating levels of pathogen cell-free DNA in plasma and the use of Torque teno virus load as a surrogate for net state of immunosuppression, have potential to be additional important biomarkers. Biomarker approaches to individualize immunosuppression therapy among heart transplant recipients is a promising area of medicine. However, additional studies are needed to inform the optimal protocol in which to incorporate these biomarkers into clinical practice.

Prevalence and Cumulative Risk of Familial Idiopathic Dilated Cardiomyopathy.

Importance: Idiopathic dilated cardiomyopathy (DCM) aggregates in families, and early detection in at-risk family members can provide opportunity to initiate treatment prior to late-phase disease. Most studies have included only White patients, yet Black patients with DCM have higher risk of heart failure-related hospitalization and death. Objective: To estimate the prevalence of familial DCM among DCM probands and the age-specific cumulative risk of DCM in first-degree relatives across race and ethnicity groups. Design, Setting, and Participants: A family-based, cross-sectional study conducted by a multisite consortium of 25 US heart failure programs. Participants included patients with DCM (probands), defined as left ventricular systolic dysfunction and left ventricular enlargement after excluding usual clinical causes, and their first-degree relatives. Enrollment commenced June 7, 2016; proband and family member enrollment concluded March 15, 2020, and April 1, 2021, respectively. Exposures: The presence of DCM in a proband. Main Outcomes and Measures: Familial DCM defined by DCM in at least 1 first-degree relative; expanded familial DCM defined by the presence of DCM or either left ventricular enlargement or left ventricular systolic dysfunction without known cause in at least 1 first-degree relative. Results: The study enrolled 1220 probands (median age, 52.8 years [IQR, 42.4-61.8]; 43.8% female; 43.1% Black and 8.3% Hispanic) and screened 1693 first-degree relatives for DCM. A median of 28% (IQR, 0%-60%) of living first-degree relatives were screened per family. The crude prevalence of familial DCM among probands was 11.6% overall. The model-based estimate of the prevalence of familial DCM among probands at a typical US advanced heart failure program if all living first-degree relatives were screened was 29.7% (95% CI, 23.5% to 36.0%) overall. The estimated prevalence of familial DCM was higher in Black probands than in White probands (difference, 11.3% [95% CI, 1.9% to 20.8%]) but did not differ significantly between Hispanic probands and non-Hispanic probands (difference, -1.4% [95% CI, -15.9% to 13.1%]). The estimated prevalence of expanded familial DCM was 56.9% (95% CI, 50.8% to 63.0%) overall. Based on age-specific disease status at enrollment, estimated cumulative risks in first-degree relatives at a typical US advanced heart failure program reached 19% (95% CI, 13% to 24%) by age 80 years for DCM and 33% (95% CI, 27% to 40%) for expanded DCM inclusive of partial phenotypes. The DCM hazard was higher in first-degree relatives of non-Hispanic Black probands than non-Hispanic White probands (hazard ratio, 1.89 [95% CI, 1.26 to 2.83]). Conclusions and Relevance: In a US cross-sectional study, there was substantial estimated prevalence of familial DCM among probands and modeled cumulative risk of DCM among their first-degree relatives. Trial Registration: ClinicalTrials.gov Identifier: NCT03037632.

Epidemiology and risk factors for varicella zoster virus reactivation in heart transplant recipients.

Heart transplant (HT) recipients are at higher risk of varicella zoster virus (VZV) reactivation. Risk factors for VZV reactivation are currently not well defined, impeding the ability to design and implement strategies to minimize the burden of this illness in this population. Automated data extraction tools were used to retrieve data from the electronic health record (EHR) of all adult HT recipients at our center between 2010 and 2016. Information from the Organ Procurement and Transplantation Network Standard Analysis and Research Files was merged with the extracted data. Potential cases were manually reviewed and adjudicated using consensus definitions. Cumulative incidence and risk factors for VZV reactivation in HT recipients were assessed by the Kaplan-Meier method and Cox modeling, respectively. In 203 HT recipients, the cumulative incidence of VZV reactivation at 8-years post-transplantation was 26.4% (95% CI: 17.8-38.0). The median time to VZV reactivation was 2.1 years (IQR, 1.5-4.1). Half (14/28) of the cases experienced post-herpetic neuralgia (PHN). Post-transplant CMV infection (HR 9.05 [95% CI: 3.76-21.77) and post-transplant pulse-dose steroids (HR 3.19 [95% CI: 1.05-9.68]) were independently associated with a higher risk of VZV reactivation in multivariable modeling. Identification of risk factors will aid in the development of targeted preventive strategies.

Letermovir successfully used for secondary prophylaxis in a heart transplant recipient with ganciclovir-resistant cytomegalovirus syndrome (UL97 mutation).

Letermovir was approved by the Food and Drug Administration (FDA) in November 2017 for use in adult cytomegalovirus (CMV)-seropositive allogeneic stem cell transplant (SCT) recipients for primary prophylaxis of CMV infection and disease. We report off-label use of letermovir for secondary prophylaxis of genotype-confirmed ganciclovir-resistant cytomegalovirus (CMV) syndrome (UL 97 mutation [C603W]) in a heart transplant recipient initially treated with intravenous cidofovir followed by foscarnet, both discontinued due to unacceptable toxicities.

Refining the classification of left ventricular hypertrophy to provide new insights into the progression from hypertension to heart failure.

PURPOSE OF REVIEW: Left ventricular hypertrophy (LVH), an important consequence of hypertension, is traditionally classified as either concentric or eccentric based on the presence or absence of increased relative wall thickness. In 2010, we proposed a novel four-tiered classification that accounted for LV dilatation in addition to LV wall thickness. The purpose of this review is to discuss the rationale for this revised classification and highlight subsequent studies that have assessed its utility. RECENT FINDINGS: A series of recent observational studies have tested whether the four-tiered classification identifies subphenotypes of LVH with differential risk of adverse outcomes, including incident heart failure. The majority have confirmed that eccentric hypertrophy can be subdivided into a high-risk and a low-risk group based on whether LV dilatation is present. Additional studies have shown that LV dilatation is an independent risk factor for the development of heart failure. SUMMARY: Incorporation of LV dilatation into the assessment of LVH identifies important subphenotypes within the standard two-tiered classification that have differential risk. Such refinements in the classification of LVH may yield new insights into how LVH progresses to heart failure, help identify risk factors for this transition, and improve therapeutic efforts to prevent its occurrence.

Alterations in brain-stem auditory evoked potentials among drug addicts. A cross-sectional study.

OBJECTIVE: To compare the absolute latencies, the interpeak latencies, and amplitudes of different waveforms of brainstem auditory evoked potentials (BAEP) in different drug abusers and controls, and to identify early neurological damage in persons who abuse different drugs so that proper counseling and timely intervention can be undertaken. METHODS: In this cross-sectional study, BAEP`s were assessed by a data acquisition and analysis system in 58 male drug abusers in the age group of 15-45 years as well as in 30 age matched healthy controls. The absolute peak latencies and the interpeak latencies of BAEP were analyzed by applying one way ANOVA and student t-test. The study was carried out at the GGS Medical College, Faridkot, Punjab, India between July 2012 and May 2013. RESULTS: The difference in the absolute peak latencies and interpeak latencies of BAEP in the 2 groups was found to be statistically significant in both the ears (p<0.05). However, the difference in the amplitude ratio in both the ears was found to be statistically insignificant. CONCLUSION: Chronic intoxication by different drugs has been extensively associated with prolonged absolute peak latencies and interpeak latencies of BAEP in drug abusers reflecting an adverse effect of drug dependence on neural transmission in central auditory nerve pathways.

In-hospital cardiopulmonary arrests in patients with left ventricular assist devices.

UNLABELLED: Background: Basic and advanced cardiac life support guidelines do not address resuscitation of patients with continuous-flow (CF) left ventricular assist devices (LVADs). As the population of LVAD patients increases, it becomes important to understand how to provide emergency care to such patients. METHODS AND RESULTS: We retrospectively reviewed a consecutive series of patients with an implanted CF-LVAD who had an in-hospital cardiopulmonary arrest at our medical center from January 2011 to October 2013. We compared them with a matched cohort of patients without LVADs who had an inhospital cardiopulmonary arrest during the same time period. Code documentation was used to determine arrest characteristics, perfusion assessment techniques, and time to cardiopulmonary resuscitation (CPR) initiation. There were 415 in-hospital arrests during the study period, and 4% (n 5 16) occurred in patients with CF-LVADs. Response teams used various approaches to assess arterial perfusion, including palpation or Doppler of the arterial pulse and measurement of blood pressure by Doppler or arterial line. Nine of the 16 patients required CPR, but only 5 (56%) received CPR in !2 minutes. In the control group (n 5 32) of patients without an LVAD, 22 received CPR, which was initiated within 2 minutes in all (100%) of the patients. CONCLUSIONS: Cardiopulmonary arrests in LVAD patients accounted for 4% of all arrests in our center. We identified important time delays in CPR initiation, highlighting the need to develop resuscitation guidelines for this patient population.

Associations Between Cardiac Function and Brain Health in Diverse Middle-Aged Adults: The Dallas Heart Study-2.

Background: Previous studies have linked cardiovascular risk factors during midlife to cognitive function in later life. However, few studies have looked at the association between cardiac function, brain structure, and cognitive function and even less have included diverse middle-aged populations. Objectives: The objective of this study was to determine associations between cardiac and brain structure and function in a multiethnic cohort of middle-aged adults. Methods: A cross-sectional study was conducted in participants of the Dallas Heart Study phase 2 (N = 1,919; 46% Black participants). Left ventricular (LV) mass, LV ejection fraction, LV concentricity, and peak systolic strain (LV Ecc) were assessed by cardiac magnetic resonance imaging. White matter hyperintensities (WMH) volume was measured by fluid attenuated inversion recovery magnetic resonance imaging. The Montreal Cognitive Assessment was used to measure cognitive functioning. Associations between cardiac and brain measures were determined using multivariable linear regression after adjusting for cardiovascular risk factors, education level, and physical activity. Results: LV ejection fraction was associated with total Montreal Cognitive Assessment score (ß = 0.06 [95% CI: 0.003-0.12], P = 0.042) and LV Ecc was associated with WMH volume (ß = 0.08 [95% CI: 0.01-0.14], P = 0.025) in the overall cohort without significant interaction by race/ethnicity. Higher LV mass and concentricity were associated with larger WMH volume in the overall cohort (ß = 0.13 [95% CI: 0.03-0.23], P = 0.008 and 0.10 [95% CI: 0.03-0.17], P = 0.005). These associations were more predominant in Black than White participants (ß = 0.17 [95% CI: 0.04-0.30] vs ß = -0.009 [95% CI: -0.16 to 0.14], P = 0.036 and ß = 0.22 [95% CI: 0.13-0.32] vs ß = -0.11 [95% CI: -0.21 to -0.01], P < 0.0001, for LV mass and concentricity, respectively). Conclusions: Subclinical cardiac dysfunction indicated by LVEF was associated with lower cognitive function. Moreover, LV mass and concentric remodeling were associated with higher WMH burden, particularly among Black individuals.

Circulating transthyretin and retinol binding protein 4 levels among middle-age V122I TTR carriers in the general population.

BACKGROUND: Hereditary transthyretin cardiac amyloidosis (ATTRv-CA) has a long latency phase before clinical onset, creating a need to identify subclinical disease. We hypothesized circulating transthyretin (TTR) and retinol binding protein 4 (RBP4) levels would be associated with TTR carrier status and correlated with possible evidence of subclinical ATTRv-CA. METHODS: TTR and RBP4 were measured in blood samples from V122I TTR carriers and age-, sex- and race-matched non-carrier controls (1:2 matching) among Dallas Heart Study participants (phases 1 (DHS-1) and 2 (DHS-2)). Multivariable linear regression models determined factors associated with TTR and RBP4. RESULTS: There were 40 V122I TTR carriers in DHS-1 and 54 V122I TTR carriers in DHS-2. In DHS-1 and DHS-2, TTR was lower in V122I TTR carriers (p < .001 for both), and RBP4 in DHS-2 was lower in V122I TTR carriers than non-carriers (p = .002). Among V122I TTR carriers, TTR was negatively correlated with markers of kidney function, and limb lead voltage (p < .05 for both) and TTR and RBP4 were correlated with atrial volume in DHS-2 (p < .05). CONCLUSIONS: V122I TTR carrier status is independently associated with lower TTR and RBP4 in comparison with non-carriers. These findings support the hypothesis that TTR and RBP4 may correlate with evidence of subclinical ATTRv-CA.

Hybrid Majority Voting: Prediction and Classification Model for Obesity.

Because it is associated with most multifactorial inherited diseases like heart disease, hypertension, diabetes, and other serious medical conditions, obesity is a major global health concern. Obesity is caused by hereditary, physiological, and environmental factors, as well as poor nutrition and a lack of exercise. Weight loss can be difficult for various reasons, and it is diagnosed via BMI, which is used to estimate body fat for most people. Muscular athletes, for example, may have a BMI in the obesity range even when they are not obese. Researchers from a variety of backgrounds and institutions devised different hypotheses and models for the prediction and classification of obesity using different approaches and various machine learning techniques. In this study, a majority voting-based hybrid modeling approach using a gradient boosting classifier, extreme gradient boosting, and a multilayer perceptron was developed. Seven distinct machine learning algorithms were used on open datasets from the UCI machine learning repository, and their respective accuracy levels were compared before the combined approaches were chosen. The proposed majority voting-based hybrid model for prediction and classification of obesity that was achieved has an accuracy of 97.16%, which is greater than both the individual models and the other hybrid models that have been developed.

Screening for Dilated Cardiomyopathy in At-Risk First-Degree Relatives.

BACKGROUND: Cardiovascular screening is recommended for first-degree relatives (FDRs) of patients with dilated cardiomyopathy (DCM), but the yield of FDR screening is uncertain for DCM patients without known familial DCM, for non-White FDRs, or for DCM partial phenotypes of left ventricular enlargement (LVE) or left ventricular systolic dysfunction (LVSD). OBJECTIVES: This study examined the yield of clinical screening among reportedly unaffected FDRs of DCM patients. METHODS: Adult FDRs of DCM patients at 25 sites completed screening echocardiograms and ECGs. Mixed models accounting for site heterogeneity and intrafamilial correlation were used to compare screen-based percentages of DCM, LVSD, or LVE by FDR demographics, cardiovascular risk factors, and proband genetics results. RESULTS: A total of 1,365 FDRs were included, with a mean age of 44.8 ± 16.9 years, 27.5% non-Hispanic Black, 9.8% Hispanic, and 61.7% women. Among screened FDRs, 14.1% had new diagnoses of DCM (2.1%), LVSD (3.6%), or LVE (8.4%). The percentage of FDRs with new diagnoses was higher for those aged 45 to 64 years than 18 to 44 years. The age-adjusted percentage of any finding was higher among FDRs with hypertension and obesity but did not differ statistically by race and ethnicity (16.2% for Hispanic, 15.2% for non-Hispanic Black, and 13.1% for non-Hispanic White) or sex (14.6% for women and 12.8% for men). FDRs whose probands carried clinically reportable variants were more likely to be identified with DCM. CONCLUSIONS: Cardiovascular screening identified new DCM-related findings among 1 in 7 reportedly unaffected FDRs regardless of race and ethnicity, underscoring the value of clinical screening in all FDRs.

Association of Number of Live Births With Electrocardiographic and Cardiac Structural Changes.

Background Pregnancy is a major life event unique to women and leads to significant hemodynamic, hormonal, and metabolic changes. The purpose of this study was to use the DHS (Dallas Heart Study), a multiethnic population-based cohort study of Dallas county adults, to evaluate the association between number of live births and cardiac magnetic resonance imaging and ECG parameters later in life. Methods and Results Women were included if they had data on self-reported live births and ECG or cardiac magnetic resonance imaging measurements. The 3014 women were stratified by number of live births: 0, 1, 2, 3, 4, and ≥5. Higher number of live births was associated with larger left ventricular (LV) end-diastolic volume (ß, 1.31±0.41; P<0.01), LV end-systolic volume (ß, 0.83±0.24; P<0.01), and LV mass (ß, 1.13±0.49; P=0.02) and lower LV ejection fraction (ß, -0.004±0.0014; P<0.01). Increasing parity was associated with longer PR intervals (ß, 1.07±0.38; P<0.01). Subgroup analysis by race demonstrated that the association between number of live births and magnetic resonance imaging parameters (LV end-diastolic volume, LV end-systolic volume, and LV ejection fraction) only remained significant in Black women (P value for interaction <0.05). Conclusions Increasing number of live births was associated with electrocardiographic and cardiac structural changes in a multiethnic population. When stratified by race and ethnicity, magnetic resonance imaging structural changes only remained significant in Black participants. Whether these changes are pathologic and increase the risk of heart failure or arrhythmias in multiparous women warrants further investigation.

Comparison of Accuracy of Estimation of Cardiac Output by Thermodilution Versus the Fick Method Using Measured Oxygen Uptake.

The thermodilution (TD) method is routinely used for the estimation of cardiac output (Q̇C). However, its accuracy, compared with the gold-standard Fick method, where systemic oxygen uptake (V̇O2) is directly measured, and Q̇C calculated from V̇O2 and the arterio-venous oxygen difference ("direct" Fick), has not been well validated. The present study determined the agreement between TD and Fick methods in consecutive patients who underwent pulmonary artery catheterization for a broad range of clinical conditions. This is a subanalysis of a previous study comparing the indirect versus Fick method based on a prospective, consecutive patient registry of 253 patients who underwent pulmonary artery catheterization for clinical indications at a single center between 1999 and 2005. We included patients that had an estimation of Q̇C both by the Fick method using measured V̇O2 by exhaled gas analyses from timed Douglas bag collections and by TD. Cardiac index was classified as low when ≤2.2 L/min/m2 or normal when >2.2 L/min/m2. The median (25th, 75th percentile) age of the cohort was 59 (50,67) years, and 50% were female. A total of 43.5% had normal left ventricular function by ventriculography, and 25.7% had ischemic heart disease. Median overall Fick and TD Q̇C were 4.4 (3.5, 5.5) and 4.3 (3.7, 5.2) L/min, respectively (p = 0.04). The median absolute percent error between Fick and TD Q̇C was 17.5 (7.7, 28.4)%, with a typical error of 0.88 L/min (95% confidence interval [CI] 0.82 to 0.95). Median absolute percent error was comparable in the low (n = 118) and normal Q̇CI (n = 135) groups (16.9% vs 18.9%, respectively, p = 0.88). typical error was 0.3 (95% CI 0.27 to 0.33) and 0.49 (95% CI 0.45 to 0.55) L/min/m2 in that comparison. Percent error >25% between Fick and TD Q̇C was observed in over 30% of patients. Overall, Fick and TD Q̇C modestly correlated (Rs = 0.64, p <0.001), with a nondirectional error introduced by TD Q̇C [mean bias of 0.21 (-2.2, 2.7) L/min]. There was poor agreement between TD and the gold-standard Fick method, highlighting the limitations of making clinical decisions based on TD.