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Post-transplant diabetes mellitus (PTDM) is common following heart transplant, impacting greater than 20% of patients with most cases occurring in the first year after transplant. PTDM is associated with multiple negative sequelae including increased post-operative infections, a higher rate of renal failure, and increased mortality. Compared with pre-transplant diabetes mellitus, PTDM has several unique risk factors and immunosuppressive medications play an important role in disease pathophysiology. Newer treatments for hyperglycemia, including glucagon like peptide-1 receptor agonists and sodium glucose cotransporter-2 inhibitors, may counter the mechanisms of immunosuppression-related hyperglycemia making them an appealing treatment option for patients with PTDM. Here, we review the definitions, incidence, risk factors, pathophysiology, clinical outcomes, treatment options, pharmacologic considerations, and future directions in PTDM.

This study aimed to evaluate hemodynamic correlates of inducible blood pressure (BP) pulsatility with exercise in heart failure with preserved ejection fraction (HFpEF), to identify relationships to outcomes, and to compare this with heart failure with reduced ejection fraction (HFrEF).In HFpEF, determinants and consequences of exercise BP pulsatility are not well understood.We measured exercise BP in 146 patients with HFpEF who underwent invasive cardiopulmonary exercise testing. Pulsatile BP was evaluated as proportionate pulse pressure (PrPP), the ratio of pulse pressure to systolic pressure. We measured pulmonary arterial catheter pressures, Fick cardiac output, respiratory gas exchange, and arterial stiffness. We correlated BP changes to central hemodynamics and cardiovascular outcome (nonelective cardiovascular hospitalization) and compared findings with 57 patients with HFrEF from the same referral population.In HFpEF, only age (standardized beta = 0.593; P 0.001), exercise stroke volume (standardized beta = 0.349; P 0.001), and baseline arterial stiffness (standardized beta = 0.182; P = 0.02) were significant predictors of peak exercise PrPP in multivariable analysis (R = 0.661). In HFpEF, lower PrPP was associated with lower risk of cardiovascular events, despite adjustment for confounders (HR:0.53 for PrPP below median; 95% CI: 0.28-0.98; P = 0.043). In HFrEF, lower exercise PrPP was not associated with arterial stiffness but was associated with lower peak exercise stroke volume (P = 0.013) and higher risk of adverse cardiovascular outcomes (P = 0.004).In HFpEF, greater inducible BP pulsatility measured using exercise PrPP reflects greater arterial stiffness and higher risk of adverse cardiovascular outcomes, in contrast to HFrEF where inducible exercise BP pulsatility relates to stroke volume reserve and favorable outcome.

Diabetes is characterized as an integrated condition of dysregulated metabolism across multiple tissues, with well-established consequences on the cardiovascular system. Recent advances in precision phenotyping in biofluids and tissues in large human observational and interventional studies have afforded a unique opportunity to translate seminal findings in models and cellular systems to patients at risk for diabetes and its complications. Specifically, techniques to assay metabolites, proteins, and transcripts, alongside more recent assessment of the gut microbiome, underscore the complexity of diabetes in patients, suggesting avenues for precision phenotyping of risk, response to intervention, and potentially novel therapies. In addition, the influence of external factors and inputs (eg, activity, diet, medical therapies) on each domain of molecular characterization has gained prominence toward better understanding their role in prevention. Here, the authors provide a broad overview of the role of several of these molecular domains in human translational investigation in diabetes.

Exercise intolerance is a principal feature of heart failure with preserved ejection fraction (HFpEF), whether or not there is evidence of congestion at rest. The degree of functional limitation observed in HFpEF is comparable to patients with advanced heart failure and reduced ejection fraction. Exercise intolerance in HFpEF is characterized by impairments in the physiological reserve capacity of multiple organ systems, but the relative cardiac and extracardiac deficits vary among individuals. Detailed measurements made during exercise are necessary to identify and rank-order the multiorgan system limitations in reserve capacity that culminate in exertional intolerance in a given person. We use a case-based approach to comprehensively review mechanisms of exercise intolerance and optimal approaches to evaluate exercise capacity in HFpEF. We also summarize recent and ongoing trials of novel devices, drugs, and behavioral interventions that aim to improve specific exercise measures such as peak oxygen uptake, 6-min walk distance, heart rate, and hemodynamic profiles in HFpEF. Evaluation during the clinically relevant physiological perturbation of exercise holds promise to improve the precision with which HFpEF is defined and therapeutically targeted.

Objectives This study evaluated whether plasma miRNAs were specifically associated with sudden cardiac and/or arrhythmic death (SCD) in a cohort of patients with coronary heart disease (CHD), most of whom were without primary prevention implantable cardioverter-defibrillators. Background Novel biomarkers for sudden death risk stratification are needed in patients with CHD to more precisely target preventive therapies, such as implantable cardioverter-defibrillators. miRNAs have been implicated in regulating inflammation and cardiac fibrosis in cells, and plasma miRNAs have been shown to predict cardiovascular death in patients with CHD. Methods We performed a nested case control study within a multicenter cohort of 5,956 patients with CHD followed prospectively for SCD. Plasma levels of 18 candidate miRNAs previously associated with cardiac remodeling were measured in 129 SCD cases and 258 control subjects matched on age, sex, race, and left ventricular ejection fraction. Results miR-150-5p, miR-29a-3p, and miR-30a-5p were associated with increased SCD risk (odds ratios and 95% confidence intervals: 2.03 [1.12 to 3.67]; p = 0.02; 1.93 [1.07 to 3.50]; p = 0.02; 0.55 [0.31 to 0.97]; p = 0.04, respectively, for third vs. first tertile miRNA level). Unfavorable levels of all 3 miRNAs was associated with a 4.8-fold increased SCD risk (1.59 to 14.51; p = 0.006). A bioinformatics-based approach predicted miR-150-5p, miR-29a-3p, and miR-30a-5p to be involved in apoptosis, fibrosis, and inflammation. Conclusions These findings suggest that plasma miRNAs may regulate pathways important for remodeling and may be useful in identifying patients with CHD at increased risk of SCD.

Background Abnormal pulmonary arterial pressure (PAP) responses to exercise have been described in select individuals; however, clinical and prognostic implications of exercise pulmonary hypertension (exPH) among broader samples remains unclear. Objectives This study sought to investigate the association of exPH with clinical determinants and outcomes. Methods The authors studied individuals with chronic exertional dyspnea and preserved ejection fraction who underwent cardiopulmonary exercise testing with invasive hemodynamic monitoring. Exercise pulmonary hypertension was ascertained using minute-by-minute PAP and cardiac output (CO) measurements to calculate a PAP/CO slope, and exPH defined as a PAP/CO slope >3 mm Hg/l/min. The primary outcome was cardiovascular (CV) hospitalization or all-cause mortality. Results Among 714 individuals (age 57 years, 59% women), 296 (41%) had abnormal PAP/CO slopes. Over a mean follow-up of 3.7 ± 2.9 years, there were 208 CV or death events. Individuals with abnormal PAP/CO slope had a 2-fold increased hazard of future CV or death event (multivariable-adjusted hazard ratio: 2.03; 95% confidence interval: 1.48 to 2.78; p Conclusions Exercise pulmonary hypertension is independently associated with CV event-free survival among individuals undergoing evaluation of chronic dyspnea. These findings suggest incremental value of exercise hemodynamic assessment to resting measurements alone in characterizing the burden of PH in individuals with dyspnea. Whether PH and PH subtypes unmasked by exercise can be used to guide targeted therapeutic interventions requires further investigation.

Patients with borderline personality disorder have high rates of comorbid mood, anxiety, substance use, and eating disorders. The longitudinal studies conducted on borderline patients over 10 years of prospective follow-up suggest that patients with borderline personality disorder experienced declining rates of Axis I disorders over time, but the rates of these disorders remained high compared with those with other personality disorders. In addition, patients whose borderline personality disorder remitted over time experienced a substantial decline in all comorbid Axis I disorders, but those whose borderline personality disorder did not remit over time, reported stable rates of comorbid disorders.

Coronary microvascular dysfunction (MVD) may contribute to the pathogenesis of heart failure with preserved ejection fraction (HFpEF). Using myocardial flow reserve (MFR) measured by positron emission tomography (PET) as an assessment of microvascular function, we hypothesized that abnormal MFR is associated with LV diastolic dysfunction (DD) and reduced LV and LA strain in patients with risk factors for HFpEF and normal epicardial perfusion on cardiac PET.Retrospective study of patients without heart failure who underwent cardiac rubidium-82 PET and echocardiography. Global MFR was calculated as the ratio of global stress to rest myocardial blood flow. Echocardiographic measures of diastolic function were recorded. Global longitudinal LA and LV strain were measured with a 2-dimensional speckle-tracking technique. Relationships among MFR and echocardiographic measures were assessed with linear regression, analysis of variance, and test for trend. Seventy-three patients (age 64 ± 11 years, 52% male) were identified with no epicardial perfusion defect on cardiac PET and an ejection fraction ≥50%. Decreased MFR was associated with LV DD (P = .02) and increased E/e', an estimation of LV filling pressure (low E/e' [8] vs. high E/e' [15], P.001). MFR was associated with LA strain independent of age, gender, and common comorbidities (adjusted β = 2.6% per unit MFR, P = 0.046); however, MFR was only marginally related to LV strain.In patients with risk factors for HFpEF, MVD assessed with MFR was associated with DD, increased estimated LV filling pressure, and abnormal LA strain.

Objectives: The study sought to determine the associations between local (pericardial) fat and incident cardiovascular disease (CVD) events and cardiac remodeling independent of markers of ...

Cardiovascular disease (CVD) is one of the main causes of mortality and morbidity worldwide. As an emerging population, South Asians (SAs) bear a disproportionately high burden of CVD relative to underlying classical risk factors, partly attributable to a greater prevalence of insulin resistance and diabetes and distinct genetic and epigenetic influences. While the phenotypic distinctions between SAs and other ethnicities in CVD risk are becoming increasingly clear, the biology of these conditions remains an area of active investigation, with emerging studies involving metabolism, genetic variation and epigenetic modifiers (e.g., extracellular RNA). In this review, we describe the current literature on prevalence, prognosis and CVD risk in SAs, and provide a landscape of translational research in this field toward ameliorating CVD risk in SAs.

While adiposity and hepatic steatosis are linked to cardiovascular risk in developed countries, their prevalence and impact in low-income countries are poorly understood. We investigated the association of anthropomorphic variables and hepatic steatosis with cardiometabolic risk profiles and subclinical cardiovascular disease (CVD) in a large rural Indian cohort.In 4691 individuals in the Birbhum Population Project in West Bengal, India, we performed liver ultrasonography, carotid ultrasound and biochemical and clinical profiling. We assessed the association of hepatic steatosis and anthropomorphic indices (BMI, waist circumference) with CVD risk factors (dysglycemia, dyslipidemia, hypertension) and subclinical CVD (by carotid intimal-medial thickness).Rural Indians exhibited a higher visceral adiposity index and pro-atherogenic dyslipidemia at a lower BMI than Americans. Individuals with any degree of hepatic steatosis by ultrasound had a greater probability of dysglycemia (adjusted odds ratio, OR=1.67, 95% CI 1.31-2.12, P0.0001) and pro-atherogenic dyslipidemia (OR=1.33, 95% CI 1.07-1.63, P=0.009). We observed a positive association between liver fat, adiposity and carotid intimal-medial thickness (CIMT) in an unadjusted model (β=0.02, P=0.0001); the former was extinguished after adjustment for cardiometabolic risk factors.In a large population of rural Indians, hepatic steatosis and waist circumference were associated with prevalent cardiometabolic risk and subclinical CVD at lower BMI relative to multi-ethnic Americans, though the association of the former with subclinical CVD was extinguished after adjustment. These results underscore the emerging relevance of hepatic steatosis and adiposity in the developing world, and suggest efforts to target these accessible phenotypes for cardiometabolic risk prevention.

Background and aims Understanding contributions of lean and fat tissue to cardiovascular and non-cardiovascular mortality may help clarify areas of prevention in older adults. We aimed to define distributions of lean and fat tissue in older adults and their contributions to cause-specific mortality. Methods and results A total of 1335 participants of the Cardiovascular Health Study (CHS) who underwent dual-energy x-ray absorptiometry (DEXA) scans were included. We used principal components analysis (PCA) to define two independent sources of variation in DEXA-derived body composition, corresponding to principal components composed of lean ("lean PC") and fat ("fat PC") tissue. We used Cox proportional hazards regression using these PCs to investigate the relationship between body composition with cardiovascular and non-cardiovascular mortality. Mean age was 76.2 ± 4.8 years (56% women) with mean body mass index 27.1 ± 4.4 kg/m 2 . A greater lean PC was associated with lower all-cause (HR = 0.91, 95% CI 0.84–0.98, P = 0.01) and cardiovascular mortality (HR = 0.84, 95% CI 0.74–0.95, P = 0.005). The lowest quartile of the fat PC (least adiposity) was associated with a greater hazard of all-cause mortality (HR = 1.24, 95% CI 1.04–1.48, P = 0.02) relative to fat PCs between the 25th–75th percentile, but the highest quartile did not have a significantly greater hazard (P = 0.70). Conclusion Greater lean tissue mass is associated with improved cardiovascular and overall mortality in the elderly. The lowest levels of fat tissue mass are linked with adverse prognosis, but the highest levels show no significant mortality protection. Prevention efforts in the elderly frail may be best targeted toward improvements in lean muscle mass.

Background The acute heart failure (AHF) Syndromes International Working Group proposed that dyspnea be assessed under standardized, incrementally provocative maneuvers and called for studies to assess the feasibility of this approach. We sought to assess the feasibility and statistical characteristics of a novel provocative dyspnea severity score (pDS) versus the traditional dyspnea visual analog scale (DVAS) in an AHF trial. Methods At enrollment, 24, 48 and 72hours, 230 ROSE-AHF patients completed a DVAS. Dyspnea was then assessed with 5-point Likert dyspnea scales administered during 4 stages (A: upright-with O 2 , B: upright-without O 2 , C: supine-without O 2 and D: exercise-without O 2 ). Patients with moderate or less dyspnea were eligible for the next stage. Results At enrollment, oxygen withdrawal and supine provocation were highly feasible (≥97%), provoking more severe dyspnea (≥1 Likert point) in 24% and 42% of eligible patients, respectively. Exercise provocation had low feasibility with 38% of eligible patients unable to exercise due to factors other than dyspnea. A pDS was constructed from Likert scales during the 3 feasible assessment conditions (A-C). Relative to DVAS, the distribution of the pDS was more skewed with a high "ceiling effect" at enrollment (23%) limiting sensitivity to change. Change in pDS was not related to decongestion or 60-day outcomes. Conclusions Although oxygen withdrawal and supine provocation are feasible and elicit more severe dyspnea, exercise provocation had unacceptable feasibility in this AHF cohort. The statistical characteristics of a pDS based on feasible provocation measures do not support its potential as a robust dyspnea assessment tool in AHF.

Hypertension is a leading cause of cardiovascular disease (CVD). Although resting blood pressure (BP) is accessible and predicts CVD, dynamic BP changes during normal living are also important. Relationships between exercise-based measures of altered vascular reserve (e.g., exercise BP) in young

Purpose The early post-heart transplantation (HT) period entails frequent biopsies, which poses a unique challenge to administration of therapeutic anticoagulation when indicated. Heightened sensitivity to enoxaparin has been described primarily in lung transplant recipients but has not been assessed in relation to anti-Xa levels specifically in HT recipients. Herein we report our institutional experience with a range of doses of enoxaparin relative to anti-Xa levels. Methods We examined HT recipients who received therapeutic anticoagulation with enoxaparin and included patients with steady state anti-Xa levels at appropriate post-dosing time intervals (i.e. 4 hours) and GFR > 30. Based on suspected heightened sensitivity to enoxaparin, we initiated doses below 1mg/kg every 12 hours (Q12). Spearman's rank correlation was used to relate non-parametric data. Results A total of 14 patients (2016-2019) were included. Average age at the time of enoxaparin exposure was 62 years, 71% were male. Four patients (29%) had a GFR 30-60 while 10 patients (71%) had a GFR > 60. Of 39 anti-Xa levels collected, levels correlated with dose of enoxaparin in mg/kg (rho=0.48, p=0.002, Figure) but not GFR (rho=0.04, p=0.80). Dosing of 1 mg/kg Q12 resulted in average anti-Xa levels above the therapeutic range (mean ± SEM: 1.13±0.23 IU/mL), whereas doses of 0.6mg/kg Q12 resulted in average levels of 0.75±0.07 IU/mL, the midpoint of the desired therapeutic anticoagulation range. Lower doses of enoxaparin (between 0.2-0.5 mg/kg Q12, including those used for prophylaxis) often resulted in anti-Xa levels approaching the therapeutic range (Figure). Conclusion In our small population of HT recipients requiring therapeutic anticoagulation, use of enoxaparin 0.6 mg/kg BID results in average anti-Xa levels at the midpoint of the therapeutic range (0.75 IU/mL) and represents a preferable dosing strategy to FDA-label dosing of 1mg/kg Q12.

Blood pressure (BP) is an inherently dynamic risk factor that can vary over time. Rather than representing random fluctuations, visit-to-visit BP variability is a reproducible measure that is associated with heart failure (HF). We tested the hypothesis that visit-to-visit BP variability was

Visit-to-Visit BP variability is a risk measure that is independently associated with the risk of cardiovascular disease (CVD). The mechanisms that link visit-to-visit BP variability to CVD are however incompletely studied. We examined the association between visit-to-visit BP variability in early

Our study aimed to evaluate the relationship between quantitative measures of myocardial perfusion (myocardial flow reserve [MFR] and stress myocardial blood flow [MBF]) and biomarkers of myonecrosis (high sensitivity troponin I [hsTnI]), vasoconstriction (endothelin-1[ET1]) and inflammation (

Extracorporeal membrane oxygenation (ECMO) is an increasingly used supportive measure for patients with refractory cardiogenic shock (CS). Despite its increasing use, there remain minimal data regarding which patients with refractory CS are most likely to benefit from ECMO. We retrospectively studied all patients (n = 123) who underwent initiation of ECMO for CS from February 2009 to September 2014 at a single center. Baseline patient characteristics, including demographics, co-morbid illness, cause of CS, available laboratory values, and patient outcomes were analyzed. Overall, 69 patients (56%) were weaned from ECMO, with 48 patients (39%) surviving to discharge. Survivors were younger (50 vs 60 years; p ≤0.0001), had a lower rate of previous smoking (27 vs 56%; p = 0.01) and chronic kidney disease (2% vs 13%; p = 0.03), and had lower lactate measured soon after ECMO initiation (3.1 vs 10.2 mmol/l; p = 0.01). Patients with pulmonary embolism (odds ratio 8.0, 95% confidence interval 2.00 to 31.99; p = 0.01) and acute cardiomyopathy (odds ratio 7.5, 95% confidence interval 1.69 to 33.27; p = 0.01) had a higher rate of survival than acute myocardial infarction, chronic cardiomyopathy, and miscellaneous etiologies compared to postcardiotomy CS as a referent. In conclusion, survival after ECMO initiation differs based on underlying cause of CS. Survival may be lower in older patients and those with early evidence of persistent hypoperfusion after initiation of ECMO for CS.

A standard ("core") implementation of American College of Cardiology/American Heart Association 2013 lipid guidelines (based on 10-year risk) dramatically increases the statin-eligible population in older Americans, raising controversy in the cardiovascular community. The guidelines also endorse a more "comprehensive" risk approach based in part on lifetime risk. The impact of this broader approach on statin eligibility remains unclear. We studied the impact of 2 different implementations of the new guidelines ("core" and "comprehensive") using the National Health and Nutrition Examination Survey. Although "core" guidelines led to 72.0 million subjects qualifying for statin therapy, the broader "comprehensive" application led to nearly a twofold greater estimate for statin-eligible subjects (121.2 million), with the greatest impact among those aged 21 to 45 years. Subjects indicated for statin therapy under comprehensive guidelines had a greater burden of cardiovascular risk factors and a higher lifetime risk of cardiovascular disease than those not indicated for statins. In particular, men aged 21 to 45 years had a 3.13-fold increased odds of being eligible for statin therapy only under the "comprehensive" guidelines (vs standard "core" guidelines; 95% confidence interval 2.82 to 3.47, p0.0001). There were no racial differences. In conclusion, the "comprehensive" approach to statin eligibility espoused by the American College of Cardiology/American Heart Association 2013 guidelines would increase the statin-eligible population to over 120 million Americans, particularly targeting younger men with high-risk factor burden.

Objectives This study sought to evaluate differential effects of visceral fat (VF) and subcutaneous fat and their effects on metabolic syndrome (MetS) risk across body mass index (BMI) categories. Background The regional distribution of adipose tissue is an emerging risk factor for cardiometabolic disease, although serial changes in fat distribution have not been extensively investigated. VF and its alterations over time may be a better marker for risk than BMI in normal weight and overweight or obese individuals. Methods We studied 1,511 individuals in the MESA (Multi-Ethnic Study of Atherosclerosis) with adiposity assessment by computed tomography (CT). A total of 253 participants without MetS at initial scan underwent repeat CT (median interval 3.3 years). We used discrete Cox regression with net reclassification to investigate whether baseline and changes in VF area are associated with MetS. Results Higher VF was associated with cardiometabolic risk and coronary artery calcification, regardless of BMI. After adjustment, VF was more strongly associated with incident MetS than subcutaneous fat regardless of weight, with a 28% greater MetS hazard per 100 cm 2 /m VF area and significant net reclassification (net reclassification index: 0.44, 95% confidence interval [CI]: 0.29 to 0.60) over clinical risk. In individuals with serial imaging, initial VF (hazard ratio: 1.24 per 100 cm 2 /m, 95% CI: 1.08 to 1.44 per 100 cm 2 /m, p = 0.003) and change in VF (hazard ratio: 1.05 per 5% change, 95% CI: 1.01 to 1.08 per 5% change, p = 0.02) were associated with MetS after adjustment. Changes in subcutaneous fat were not associated with incident MetS after adjustment for clinical risk and VF area. Conclusions VF is modestly associated with BMI. However, across BMI, a single measure of and longitudinal change in VF predict MetS, even accounting for weight changes. Visceral adiposity is essential to assessing cardiometabolic risk, regardless of age, race, or BMI, and may serve as a marker and target of therapy in cardiometabolic disease.

With an aging population and the emergence of transcatheter valve replacement [(1)][1], the evaluation of bioprosthetic valve anatomy and function is of increasing importance. Traditional “tried and true” methods of assessing bioprosthetic valve dysfunction have relied on 2-dimensional

The aim of this study was to investigate the association between major adverse cardiovascular events (MACEs) and inducible ischemia on regadenoson cardiac magnetic resonance (CMR) myocardial perfusion imaging (MPI) performed at 3.0 T. Regadenoson stress CMR MPI is increasingly used to assess patients with suspected ischemia; however, its value in patient prognostication and risk reclassification is only emerging. A total of 346 patients with suspected ischemia who were referred for regadenoson CMR were studied. The prognostic association of presence of inducible ischemia by CMR with MACEs was determined. In addition, we assessed the extent of net reclassification improvement by CMR beyond a clinical risk model. There were 52 MACEs during a median follow-up period of 1.9 years. Patients with inducible ischemia were fourfold more likely to experience MACEs (hazard ratio, 4.14, 95% confidence interval 2.37 to 7.24, p 10%) by CMR was 0.29 (95% confidence interval 0.15 to 0.44), and continuous net reclassification improvement was 0.58. In conclusion, in patients with clinical suspicion of myocardial ischemia, regadenoson stress CMR MPI provides robust risk stratification. CMR MPI negative for ischemia was associated with a very low annual rate of hard cardiac events. In addition, CMR MPI provides effective risk reclassification in a substantial proportion of patients.

Right heart failure is poorly understood and treated. In left heart failure, ventricular restraint can reverse pathologic left ventricular remodeling. The effect of restraint in right heart failure, however, is not known. We hypothesize that ventricular restraint can be applied selectively to the right ventricle (RV) to promote RV reverse remodeling.Right heart failure was induced by right coronary artery ligation in a sheep model. Eight weeks later, a saline-filled epicardial balloon was placed around the RV surface for restraint. Restraint level was defined by measuring balloon luminal pressure at end-diastole. Maximum balloon pressure was determined by the amount of balloon pressure required to decrease systemic mean arterial pressure by 10 mm Hg. We determined end-diastolic transmural myocardial pressure, indices of myocardial oxygen consumption, and RV diastolic compliance at 4 different restraint levels.After coronary ligation, RV ejection fraction (EF) decreased from 0.574±0.04 to 0.362±0.03 (p0.05). End-diastolic RV volume increased from 70.8 mL/m2±9 to 82.2 mL/m2±7 (p0.05) by magnetic resonance imaging. After application of restraint to the RV only, RV transmural pressure decreased significantly by 27%. Greater levels of restraint also improved RV EF (0.347±0.06 to 0.473±0.05) but did not change RV end-diastolic volume.A model of ischemic right heart failure was successfully created. Selective RV restraint results in improved mechanical efficiency, decreased wall stress, and improved EF. The benefits of restraint in right heart failure warrant further investigation.

Circulating biomarkers that directly reflect disease progression, hemodynamics, and ventricular remodeling at a molecular level are critical to risk stratification in heart failure (HF), affording unique insights into pathophysiology not fully captured by traditional risk markers. Despite the wealth of data confirming the importance of natriuretic peptides in HF diagnosis and prognosis, residual clinical risk in HF suggests that additional biomarkers complementary to natriuretic peptides may be useful. In this article, the current literature addressing the role of these biomarkers in the clinical diagnosis and risk stratification in HF is summarized.

Objective To define the relationship between body mass index (BMI) and mortality in heart failure (HF) across the world and identify specific groups in whom BMI may differentially mediate risk. Background Obesity is associated with incident heart failure (HF), but is paradoxically associated with better prognosis during chronic HF. Methods We studied 6,142 patients with acute decompensated HF from 12 prospective observational cohorts followed across 4 continents. Primary outcome was all-cause mortality. Cox proportional hazards models and net reclassification index (NRI) described associations of BMI with all-cause mortality. Results “Normal” weight patients (BMI 18.5-25 kg/m2) were older with more advanced HF and lower cardiometabolic risk. Despite worldwide heterogeneity in clinical features across obesity categories, a higher BMI remained associated with decreased 30-day and 1-year mortality (11% decrease at 30 days; 9% decrease at 1 year per 5 kg/m2; P75; HR=0.82, P=0.006), decreased cardiac function (ejection fraction < 50%; HR=0.85, P

Objectives This study aimed to test the characteristics of the myocardial extracellular volume fraction (ECV) derived from pre- and post-contrast T1 measurements among healthy volunteers. Background Cardiac magnetic resonance (CMR) T1 measurements of myocardium and blood before and after contrast allow quantification of the ECV, a tissue parameter that has been shown to change in proportion to the connective tissue fraction. Methods Healthy volunteers underwent standard CMR imaging with administration of gadolinium. T1 measurements were performed with a Look-Locker sequence followed by gradient-echo acquisition. We tested the segmental, interslice, inter-, intra-, and test-retest characteristics of the ECV, as well as the association of the ECV with other variables. Juvenile and aged mice underwent a similar protocol, and cardiac sections were harvested for measurement of fibrosis. Results In healthy volunteers (N = 32, 56% female; age 21 to 72 years), the ECV averaged 0.28 ± 0.03 (range 0.23 to 0.33). The intraclass coefficients for the intraobserver, interobserver, and test-retest absolute agreements of the ECV were 0.94 (95% confidence interval: 0.84 to 0.98), 0.93 (95% confidence interval: 0.80 to 0.98), and 0.95 (95% confidence interval: 0.52 to 0.99), respectively. In volunteers, the ECV was associated with age (r = 0.74, p Conclusions In healthy volunteers, the myocardial ECV ranges from 0.23 to 0.33, has acceptable test characteristics, and is associated with age, left atrial volume, and left ventricular mass. In mice, the ECV also increases with age and strongly correlates with the extent of myocardial fibrosis.

Objectives This study assessed whether impaired fasting glucose (IFG), insulin resistance, and waist-to-hip ratio (WHR) had effects on cardiac remodeling, independent of obesity, in the MESA (Multi-Ethnic Study of Atherosclerosis) trial. Background Recent studies have suggested that central obesity and insulin resistance may be primary mediators of obesity-related cardiac remodeling independent of body mass index (BMI). Methods We investigated 4,364 subjects without diabetes in the MESA trial. IFG (100 to 125 mg/dl) or insulin resistance (by homeostatic model assessment of insulin resistance [HOMA-IR]) and WHR were used for cardiometabolic phenotyping. Multivariate linear regression analysis was used to determine the effects of the cardiometabolic markers on left ventricular (LV) remodeling, assessed primarily through the LV mass-to-volume ratio obtained by cine cardiac magnetic resonance imaging. Results Individuals with IFG were more likely to be older and hypertensive, with increased prevalence of cardiometabolic risk factors regardless of BMI. In each quartile of BMI, subjects with above-median HOMA-IR, above-median WHR, or IFG had a higher LV mass-to-volume ratio (p Conclusions Insulin resistance and WHR were associated with concentric LV remodeling independent of BMI. These results support the emerging hypothesis that the cardiometabolic phenotype, defined by insulin resistance and central obesity, may play a critical role in LV remodeling independently of BMI.

We aimed to describe the cardiac magnetic resonance (CMR) findings and determine the prognostic variables in patients with a cardiomyopathy after treatment with anthracyclines. CMR imaging was performed in 91 patients (58% men, mean age 43 ± 18 years, and mean anthracycline dose of 276 ± 82 mg/m(2)) with a reduced ejection fraction after anthracycline-based chemotherapy. Major adverse cardiovascular events were defined as cardiovascular death, appropriate implantable cardioverter-defibrillator therapy, and admission for decompensated heart failure. Patients presented a median of 88 months (interquartile range 37 to 138) after chemotherapy and were followed for 27 months (interquartile range 22 to 38). Late gadolinium enhancement was an uncommon finding (5 patients, 6%) despite a reduced ejection fraction (36 ± 8%). An inverse association was found between the anthracycline dose and the indexed left ventricular (LV) mass by CMR (r = -0.67, p0.001). A total of 52 adverse cardiac events occurred (event rate of 22%/year). When the patients were grouped according to the presence or absence of a major adverse cardiovascular event, the indexed LV mass and glomerular filtration rate were lower and the anthracycline dose was greater among the patients who experienced an adverse event. In a multivariate model, the indexed LV mass demonstrated the strongest association with major adverse cardiovascular events (hazard ratio 0.89, chi-square 26, p0.001). In conclusion, myocardial scar by late gadolinium enhancement-CMR is infrequent in patients with anthracycline-cardiomyopathy despite a reduced ejection fraction, the event rate in patients with established anthracycline-cardiotoxicity is high, and indexed LV mass by CMR imaging is a predictor of adverse cardiovascular events.

Patients with diabetes and heart failure (HF) have worse clinical outcomes compared to patients with HF without diabetes after cardiac resynchronization therapy (CRT). Patients with HF and diabetes represent a growing population at high risk for cardiovascular events and are increasingly treated with CRT. Although patients with diabetes and HF appear to benefit from CRT, their clinical outcomes are worse than those of patients without diabetes after CRT. The aim of this study was to identify clinical predictors that explain the differential hazard in patients with diabetes. We studied 442 patients (169 with diabetes) with systolic HF referred to the Massachusetts General Hospital CRT clinic from 2003 to 2010 to identify predictors of outcomes after CRT in patients with HF and diabetes. Patients with diabetes were more likely to have ischemic causes of HF than those without diabetes, but there was no difference in the left ventricular ejection fraction or HF classification at implantation. Patients with diabetes had poorer event-free survival (death or HF hospitalization) compared to those without diabetes (log-rank p = 0.04). The presence of diabetes was the most important independent predictor of differential outcomes in the entire population (hazard ratio 1.65, 95% confidence interval 1.10 to 2.51). Patients with diabetes receiving insulin therapy had poorer survival, whereas those not receiving insulin therapy had similar survival to patients without diabetes. Patients with peri-implantation glycosylated hemoglobin >7% had worse outcomes, whereas patients with glycosylated hemoglobin ≤7% had improved survival (hazard ratio 0.36, 95% confidence interval 0.15 to 0.86) equivalent to that of patients without diabetes. In conclusion, although the presence of diabetes, independent of other variables, increases the hazard of worse outcomes after CRT, there is additional risk conferred by insulin use and suboptimal peri-implantation glycemic control.

Radiotherapy (RT) is a standard treatment for cancer; however, RT is associated with an increase in atherosclerotic cardiovascular events (ASCVD). Whether the primary prevention ACC/AHA and USPSTF statin guidelines, using the pooled cohort risk equation (PCE), predict ASCVD after RT is unknown.

Obesity is associated with left ventricular (LV) dysfunction and heart failure. We investigated the role of metabolic syndrome as an additive risk for LV systolic dysfunction among adolescents. Fourteen obese adolescents (n=5 with metabolic syndrome, OMS+, and n=9 without metabolic syndrome, OMS-)

Background Although renin-angiotensin system (RAS) inhibitors have little demonstrable effect on mortality in patients with heart failure and preserved ejection fraction (HF-PEF), some trials have suggested a benefit with regard to reduction in HF hospitalization. Methods and Results Here, we systematically review and evaluate prospective clinical studies of RAS inhibitors enrolling patients with HF-PEF, including the 3 major trials of RAS inhibition (Candesartan in Patients with Chronic Heart Failure and Preserved Left Ventricular Ejection Fraction [CHARM-Preserved], Irbesartan in Patients with Heart Failure and Preserved Ejection Fraction [I-PRESERVE], and Perindopril in Elderly People with Chronic Heart Failure [PEP-CHF]). We also conducted a pooled analysis of 8021 patients in the 3 major randomized trials of RAS inhibition in HF-PEF (CHARM-Preserved, I-PRESERVE, and PEP-CHF) in fixed-effect models, finding no clear benefit with regard to all-cause mortality (odds ratio [OR] 1.03, 95% confidence interval [CI], 0.92-1.15; P =.62), or HF hospitalization (OR 0.90, 95% CI 0.80-1.02; P =.09). Conclusions Although RAS inhibition may be valuable in the management of comorbidities related to HF-PEF, RAS inhibition in HF-PEF is not associated with consistent reduction in HF hospitalization or mortality in this emerging cohort.

Imaging the coronary venous (CV) tree to delineate the coronary sinus and its tributaries can facilitate electrophysiological procedures, such as cardiac resynchronization therapy (CRT) and catheter ablation. Venography also allows visualization of the left atrial (LA) veins, which may be a potential conduit for ablative or pacing strategies given their proximity to foci that can trigger atrial fibrillation.The aim of this study was to provide a detailed description of CV anatomy using rotational venography in patients undergoing CRT.Coronary sinus (CS) size and the presence, size, and angulation of its tributaries were determined from the analysis of rotational CV angiograms from 51 patients (age 68 +/- 11 years; n = 12 women) undergoing CRT.The CS, posterior veins, and lateral veins were identified in 100%, 76%, and 91% of patients. Lateral veins were less prevalent in patients with a history of lateral myocardial infarction than in patients without such a history (33% vs. 96%; P = .014). The diameters of the CS and its tributaries were fairly variable (7.3-18.9 mm for CS, 1.3-10.5 mm for CS tributaries). The CS was larger in men than in women and in cases of ischemic than in cases of nonischemic cardiomyopathy (all P.05). The vein of Marshall, the most constant LA vein, was identified in 37 patients; its diameter is 1.7 +/- 0.5 mm, and its takeoff angle is 154 degrees +/- 15 degrees , making the vein potentially accessible for cannulation.Differences in CV anatomy that are related to either gender or coronary artery disease could have important practical implications during the left ventricular lead implantation. The anatomical features of the vein of Marshall make it a feasible potential conduit for epicardial LA pacing.

Omega-3 fatty acid (PUFAs) may have a number of beneficial pleiotropic effects. One randomized trial demonstrated significant survival benefit for PUFAs following acute MI. We conducted a randomized, double-blinded, placebo controlled trial of PUFA supplementation post acute MI. 358 patients were

Major bleeding complications were investigated in 2,460 patients with 3,684 patient-years of warfarin exposure from 2000 to 2003. The most common indications for anticoagulation were atrial fibrillation (30%), venous thromboembolic disease (28%), and mechanical heart valve prosthesis (15%). Eleven patients had 12 nonfatal major bleeding complications, with no fatal bleeds during the study. The incidence of major bleeding complications was 0.12%/year; there were 0.32 bleeds/100 patient-years of coverage. Of the 12 bleeding events, 5 (42%) were intracranial hemorrhages. The average hospitalization cost per patient was dollar 15,988, and the average length of hospitalization was 6.0 days.

Background: Recent data suggests that patients with Type 2 Myocardial Infarction (T2-MI) have a worse prognosis than previously appreciated. Yet, little is known about the implications of having a T2-MI at a young age. Methods: Using clinical & billing data, we identified all patients presenting

Background: Patients with non-ischemic dilated cardiomyopathy NIDC are at risk of arrhythmias and sudden cardiac death (SCD). The likely arrhythmia substrate is myocardial ibrosis. We tested the hypothesis that the presence and extent of ibrosis characterized by late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) may help risk stratify patients with NIDC referred for an implantable cardioverter deibrillator (ICD) therapy for primary prevention of SCD. Methods: One hundred and nine patients ((61% male, mean age of 50±14 years, mean left ventricular ejection fraction of 25±9%) with a class 1 indication for ICD insertion for primary prevention of SCD at two institutions underwent an LGE-CMR study and were prospectively followed. Events of interest were deined as a combination of death and appropriate ICD therapy. Results: Myocardial ibrosis by LGE-CMR was identiied in 59 patients (54%). During the median follow-up period of 34 months there were 30 events (10 deaths and 20 appropriate ICD therapies). Univariate analysis showed that the presence and the extent of LGE demonstrated the strongest unadjusted association with cardiac events (LGE, hazard ratio (HR): 5.8, chi-squared 12.7, P 5.6% had an overall event rate of 23% per year. Conclusions: LGE is a powerful marker of risk in patients with NIDC who meet criteria for ICD insertion.