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Glucagon-like peptide-1 agonists are effective weight loss treatments, yet few data are available regarding their use in patients with durable left ventricular assist devices. We report our single-center experience with glucagon-like peptide-1 agonist use in 21 patients with World Health Organization class I to III obesity on durable left ventricular assist device support. During therapy, patients experienced a median weight change of −12.4 (−20.0 to −2.9) kg and a −7.4% (−16.3 to −2.1) change in body weight with a median time on glucagon-like peptide-1 agonist therapy of 12 (6-22) months. Of these, 17 of 21 patients lost weight (median change −14.0kg [−21.8 to −5.3], −9.5% [−18.0 to −4.0] body weight) and 9 of 21 had a speed reduction. No major adverse events were attributed to glucagon-like peptide-1 agonist therapy. At our center, glucagon-like peptide-1 agonists use was well tolerated, safe, and associated with weight loss in patients with durable left ventricular assist devices.

Abstract Aims Patients with obesity and ischaemic heart failure may counter‐intuitively have better outcomes compared with patients with normal body weight due to an ‘obesity paradox’. This study sought to determine if body mass index (BMI) impacts the treatment effects or safety outcomes of the treatment of ischaemic heart failure with coronary artery bypass grafting (CABG). Methods and results We obtained and reviewed the Surgical Treatment of Ischaemic Heart Failure (STICHES) data for 1212 patients. We categorized obesity by the World Health Organization (WHO) classes to define baseline characteristics and test for treatment interactions for the primary and secondary STICHES outcomes by treatment groups. While CABG decreased the risk of death, there was no evidence of treatment interaction by BMI per 5 kg/m2 (P = 0.83) or WHO obesity class. For the overall cohort, there was no interaction by WHO obesity class for the cumulative incidence of death in either the medical therapy or CABG plus medical therapy (P‐interaction = 0.90). There was a non‐significant trend for higher BMI and a lower risk of death [hazard ratio 0.92, 95% confidence interval (CI) 0.85–1.00, P = 0.051]. Increasing body size (per 5 kg/m2) was associated with return to the operating room (odds ratio 2.48, 95% CI 1.45–4.26, P

Background Patient‐reported outcomes may be discordant to severity of illness as assessed by objective parameters. The frequency of this discordance and its influence on clinical outcomes in patients with heart failure is unknown. Methods and Results In HF‐ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training), participants (N=2062) had baseline assessment of health‐related quality of life via the Kansas City Cardiomyopathy Clinical Summary score (KCCQ‐CS) and objective severity by cardiopulmonary stress testing (minute ventilation [VE]/carbon dioxide production [VCO2] slope). We defined 4 groups by median values: 2 concordant (lower severity: high KCCQ‐CS and low VE/VCO2 slope; higher severity: low KCCQ‐CS and high VE/VCO2 slope) and 2 discordant (symptom minimizer: high KCCQ‐CS and high VE/VCO2 slope; symptom magnifier: low KCCQ‐CS and low VE/VCO2 slope). The association of group assignment with mortality was assessed in adjusted Cox models. Symptom magnification (23%) and symptom minimization (23%) were common. Despite comparable KCCQ‐CS scores, the risk of all‐cause mortality in symptom minimizers versus concordant–lower severity participants was increased significantly (hazard ratio [HR], 1.79; 95% CI, 1.27–2.50; P

Background Physical inactivity and low cardiorespiratory fitness (CRF) are associated with higher risk of heart failure. However, the independent contributions of objectively measured sedentary time, physical activity, and CRF toward left ventricular (LV) structure and function are not well established. Methods and Results We included 1368 participants from the DHS (Dallas Heart Study) (age, 49 years; 40% men) free of cardiovascular disease who had physical activity and sedentary time measured by accelerometer, CRF estimated from submaximal treadmill test, and cardiac magnetic resonance imaging performed using 3‐T magnetic resonance imaging. A series of linear regression models were constructed to evaluate the associations of sedentary time, moderate physical activity, vigorous physical activity, and CRF with LV parameters after adjustment for established cardiovascular risk factors. We observed a modest correlation between CRF levels and objectively measured moderate (correlation coefficient, 0.17; P

Background Duchenne muscular dystrophy (DMD) is a neuromuscular disorder caused by mutations within the dystrophin gene. DMD is characterized by progressive skeletal muscle degeneration and atrophy and progressive cardiomyopathy. It has been observed the severity of cardiomyopathy varies in patients with DMD. Methods and Results A cohort of male patients with DMD and female DMD carriers underwent whole exome sequencing. Potential risk factor variants were identified according to their functional annotations and frequencies. Cardiac function of 15 male patients with DMD was assessed by cardiac magnetic resonance imaging, and various cardiac magnetic resonance imaging parameters and circulating biomarkers were compared between genotype groups. Five subjects carrying potential risk factor variants in the cystic fibrosis transmembrane regulator gene demonstrated lower left ventricular ejection fraction, larger left ventricular end‐diastolic volume, and higher NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) levels compared with 10 subjects who did not carry the potential risk factor variants (P=0.023, 0.019 and 0.028, respectively). Conclusions This study revealed heterozygous cystic fibrosis transmembrane regulator gene missense variants were associated with worse cardiac function in patients with DMD. The cystic fibrosis transmembrane regulator gene may serve as a genetic modifier that accounts for more severe cardiomyopathy in patients with DMD, who would require more aggressive management of the cardiomyopathy.

Background Current strategies for cardiovascular disease (CVD) risk assessment focus on 10‐year or longer timeframes. Shorter‐term CVD risk is also clinically relevant, particularly for high‐risk occupations, but is under‐investigated. Methods and Results We pooled data from participants in the ARIC (Atherosclerosis Risk in Communities study), MESA (Multi‐Ethnic Study of Atherosclerosis), and DHS (Dallas Heart Study), free from CVD at baseline (N=16 581). Measurements included N‐terminal pro‐B‐type natriuretic peptide (>100 pg/mL prospectively defined as abnormal); high‐sensitivity cardiac troponin T (abnormal >5 ng/L); high‐sensitivity C‐reactive protein (abnormal >3 mg/L); left ventricular hypertrophy by ECG (abnormal if present); carotid intima‐media thickness, and plaque (abnormal >75th percentile for age and sex or presence of plaque); and coronary artery calcium (abnormal >10 Agatston U). Each abnormal test result except left ventricular hypertrophy by ECG was independently associated with increased 3‐year risk of global CVD (myocardial infarction, stroke, coronary revascularization, incident heart failure, or atrial fibrillation), even after adjustment for traditional CVD risk factors and the other test results. When a simple integer score counting the number of abnormal tests was used, 3‐year multivariable‐adjusted global CVD risk was increased among participants with integer scores of 1, 2, 3, and 4, by ≈2‐, 3‐, 4.5‐ and 8‐fold, respectively, when compared with those with a score of 0. Qualitatively similar results were obtained for atherosclerotic CVD (fatal or non‐fatal myocardial infarction or stroke). Conclusions A strategy incorporating multiple biomarkers and atherosclerosis imaging improved assessment of 3‐year global and atherosclerotic CVD risk compared with a standard approach using traditional risk factors.

Background Left ventricular assist devices (LVADs) improve outcomes in patients with end‐stage heart failure and are increasingly implanted for destination therapy. We describe dynamic estimates of event‐free survival with conditional survival probabilities in a destination therapy LVAD population. Methods and Results We studied 8245 adult patients in INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) implanted with a continuous‐flow destination therapy LVAD. The composite primary end point was death, device exchange or removal, or heart transplantation. Conditional survival probabilities were calculated and stratified by implantation characteristics and nonfatal adverse events experienced within the first year after implant. Probabilities of surviving an additional 1 to 3 years were numerically higher after longer prior event‐free survival. INTERMACS profile 1, extracorporeal membrane oxygenation support, prior or concomitant surgery, and dialysis within 48 hours of implantation were associated with significantly lower event‐free survival in the first year but did not impact event‐free survival beyond then. For patients who experienced a nonfatal adverse event within the first year, subsequent 1‐year conditional survival was lower than in the absence of that event for stroke (65% [95% CI, 57%–73%] versus 75% [95% CI, 73%–77%]; P

Background The prognostic interrelationship between natriuretic peptide (NP) levels and body mass index (BMI) among patients with chronic stable heart failure with preserved ejection fraction is not well characterized. Methods and Results Participants from the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial enrolled in the Americas meeting inclusion by the NP stratum were stratified into 4 data‐derived categories by BMI and standardized NP‐z score. Adjusted Cox‐proportional models determined the independent association of BMI, NP‐z score, and BMI/NP categories with composite primary end point, heart failure hospitalization, and all‐cause mortality. The study population included 997 participants. There was a U‐shaped relationship between BMI and NP with elevated NP levels noted at extremes of BMI distribution. There was also a U‐shaped relationship between BMI and risk of adverse clinical outcomes with the lowest risk among patients approximating a BMI of 25 kg/m2. In contrast, higher NP levels were linearly associated with higher risk of adverse clinical outcomes. For BMI/NP‐based categories, participants in the high BMI/high NP group had greater prevalence of cardiac structural and functional abnormalities and the highest risk of adverse clinical outcomes (hazard ratio for primary end point; 95% confidence interval: 2.29 [1.36–3.84] Reference: low BMI/low NP). Conclusions There is a U‐shaped association between BMI and NP levels among patients with chronic heart failure with preserved ejection fraction. Higher NP levels are independently associated with a higher risk of mortality across both high and low BMI strata. Among obese patients with heart failure with preserved ejection fraction, elevated NP levels identify a higher risk phenotype with a significantly increased incidence of both mortality and heart failure hospitalization.

BackgroundDuchenne muscular dystrophy (DMD) is frequently complicated by development of a cardiomyopathy. Despite significant medical advances provided to DMD patients over the past 2 decades, there remains a group of DMD patients who die prematurely. The current study sought to identify a set of prognostic factors that portend a worse outcome among adult DMD patients. Methods and ResultsA retrospective cohort of 43 consecutive patients was followed in the adult UT Southwestern Neuromuscular Cardiomyopathy Clinic. Clinical data were abstracted from the electronic medical record to generate baseline characteristics. The population was stratified by survival to time of analysis and compared with characteristics associated with death. The DMD population was in the early 20s, with median follow‐up times over 2 years. All the patients had developed a cardiomyopathy, with the majority of the patients on angiotensin‐converting enzyme inhibitors (86%) and steroids (56%), but few other guideline‐directed heart failure medications. Comparison between the nonsurviving and surviving cohorts found several poor prognostic factors, including lower body mass index (17.3 [14.8–19.3] versus 25.8 [20.8–29.1] kg/m2, P

BackgroundObesity may increase heart failure risk through cardiac remodeling. Cross‐sectional associations between adiposity and cardiac structure and function have been elucidated, but the impact of longitudinal changes in adiposity on cardiac remodeling is less well understood. Methods and ResultsParticipants in the Dallas Heart Study without cardiovascular disease or left ventricular dysfunction underwent assessment of body weight, anthropometrics, and cardiac magnetic resonance imaging at baseline and 7 years later. Associations between changes in indices of generalized and central adiposity with changes in left ventricular mass, volume, mass/volume ratio (concentricity), wall thickness, and ejection fraction were assessed using multivariable linear regression. The study cohort (n=1262) mean age was 44 years with 57% women, 44% black, and 36% obese participants. At follow‐up, 41% had ≥5% weight gain, and 15% had ≥5% weight loss. Greater weight gain was associated with younger age, lower risk factor burden, and lower body mass index at baseline. In multivariable models adjusting for age, sex, race, comorbid conditions at baseline and follow‐up, baseline adiposity, and cardiac measurement, increasing weight was associated with increases in left ventricular mass (β=0.10, P