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BACKGROUND: Patients with heart failure (HF) often have multiple chronic conditions that may impact health-related quality of life (HRQOL) despite HF therapy. We sought to determine the association between noncardiac comorbidities and HRQOL in ambulatory patients with advanced HF. METHODS: Baseline data from 373 subjects in Registry Evaluation of Vital Information for Ventricular Assist Devices (VADs) in Ambulatory Life were analyzed using multivariable general linear models to evaluate the relationship between comorbidities and HRQOL (EuroQol-visual analogue scale [EQ-VAS], EQ-5D-3L Index Score, and Kansas City Cardiomyopathy Questionnaire [KCCQ]). The primary independent variables were a comorbidity index (sum of 14 noncardiac conditions), a residual comorbidity index (without depression), and depression alone. The median (25(th)-75(th) percentile) number of comorbidities was 3 (2–4). RESULTS: Increasing comorbidity burden was associated with a reduction in generic (EQ-5D Index, p=0.005) and HF-specific (KCCQ, p=0.001) HRQOL. The residual comorbidity index was not associated with HRQOL when depression included in the model independently, while depression was associated with HRQOL across all measures. Participants with depression (vs. without) scored on average 13 points (95% confidence interval 8–17) lower on the EQ-VAS, 0.15 points (0.12–0.18) lower on the EQ-5D Index, and 24.9 points (21.2–28.5) lower on the KCCQ-overall summary score. CONCLUSIONS: While noncardiac comorbidities were prevalent in ambulatory advanced HF patients, only depression was associated with decreased generic and HF-specific HRQOL. Other than depression, the presence of noncardiac comorbidities should not impact expected gains in HRQOL following VAD, provided the conditions are not a contraindication to implant. REGISTRATION: Clinicaltrials.gov; Unique identifier: NCT01369407.

BackgroundThe basis for increased mortality after heart transplantation in African Americans and other non-Caucasian racial groups is poorly defined. We hypothesized that increased risk of adverse events is driven by biologic factors. To test this hypothesis in the Invasive Monitoring Attenuation through Gene Expression (IMAGE) study, we determined whether the event rate of the primary outcome of acute rejection, graft dysfunction, death, or retransplantation varied by race as a function of calcineurin inhibitor (CNI) levels and gene expression profile (GEP) scores.MethodsWe determined the event rate of the primary outcome, comparing racial groups, stratified by time after transplant. Logistic regression was used to compute the relative risk across racial groups, and linear modeling was used to measure the dependence of CNI levels and GEP score on race.ResultsIn 580 patients monitored for a median of 19 months, the incidence of the primary end point was 18.3% in African Americans, 22.2% in other non-Caucasians, and 8.5% in Caucasians (p < 0.001). There were small but significant correlations of race and tacrolimus trough levels to the GEP score. Tacrolimus levels were similar among the races. Of patients receiving tacrolimus, other non-Caucasians had higher GEP scores than the other racial groups. African American recipients demonstrated a unique decrease in expression of the FLT3 gene in response to higher tacrolimus levels.ConclusionsAfrican Americans and other non-Caucasian heart transplant recipients were 2.5-times to 3-times more likely than Caucasians to experience outcome events in the Invasive Monitoring Attenuation through Gene Expression study. The increased risk of adverse outcomes may be partly due to the biology of the alloimmune response, which is less effectively inhibited at similar tacrolimus levels in minority racial groups.

This study evaluated the Heartmate Risk Score (HMRS) and its potential benefits in clinical practice.The HMRS has been shown to correlate with mortality in the cohort of patients enrolled in the Heartmate II trials, but its validity in unselected, "real world" populations remains unclear.This study identified a cohort of 269 consecutive patients who received a Heartmate II left ventricular assist device at our institution, the Barnes-Jewish Hospital in St. Louis, Missouri, between June 2005 and June 2013. Ninety-day and 2-year mortality rates, as well as frequency of several morbid events, were compared by retrospectively assigned HMRS category groups. The analysis was repeated within the subgroup of INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) class 1 patients.Receiver operating curve analysis showed that the HMRS correlated with 90-day mortality with an area under the curve of 0.70. Stratification in low, mid, and high HMRS groups identified patients with increasing hazard of 90-day mortality, increasing long-term mortality, increasing rate of gastrointestinal bleeding events, and increasing median number of days spent in the hospital in the first year post implant. Within INTERMACS class 1 patients, those in the highest HMRS group were found to have a relative risk of 90-day mortality 5.7 times higher than those in the lowest HMRS group (39.1% vs. 6.9%, p = 0.029).HMRS is a valid clinical tool to stratify risk of morbidity and mortality after implant of Heartmate II devices in unselected patients and can be used to predict short-term mortality risk in INTERMACS class 1 patients.

We determined the role of donor-specific antibodies (DSA) and antibodies (Abs) to self-antigens, collagen-V (Col-V), and K-α1-Tubulin (KAT) in pathogenesis of acute antibody-mediated rejection (AMR) and cardiac allograft vasculopathy (CAV) after human heart transplantation (HTx).One hundred thirty-seven HTx recipients, with 60 early period (≤ 12 months) and 77 late period (12 months), were enrolled in this study. Circulating DSA was determined using LUMINEX. Abs against Col-I, II, IV, V, and KAT were measured using ELISA. Frequency of CD4+T helper cells (CD4+Th) secreting interferon (IFN)-γ, interleukin (IL)-5, -10, or -17 specific to self-antigens were determined using Enzyme Linked Immunosorbent Spot assay.A significant association between AMR and DSA was demonstrated. Development of DSA in AMR patients correlated well with the development of auto-Abs to Col-V (AMR[+]: 383 ± 72 μg/mL, AMR[-]: 172 ± 49 μg/mL, P=0.033) and KAT (AMR[+]: 252 ± 49 μg/mL, AMR[-]: 61 ± 21 μg/mL, P=0.014). Patients who developed AMR demonstrated increased frequencies of CD4+Th secreting IFN-γ and IL-5 with reduction in IL-10 specific for Col-V/KAT. Patients diagnosed with CAV also developed DSA and auto-Abs to Col-V (CAV[+]: 835 ± 142 μg/mL, CAV[-]: 242 ± 68 μg/mL, P=0.025) and KAT (CAV[+]: 768 ± 206 μg/mL, CAV[-]: 196 ± 72 μg/mL, P=0.001) with increased frequencies of CD4+Th secreting IL-17 with reduction in IL-10 specific for Col-V/KAT. CONCLUSIONS.: Development of Abs to human leukocyte antigens and self-antigens are associated with increases in CD4+Th secreting IFN-γ and IL-5 in AMR and IL-17 in CAV, with reduction in CD4+Th secreting IL-10 in both AMR and CAV.

Accumulation of triglycerides (TG) in heart tissue has been associated with changes in left ventricular function. Proton magnetic resonance spectroscopy is currently the only noninvasive in vivo method to measure myocardial triglycerides content. The primary aim of this study was to determine if these in vivo measurements are specific to myocardial triglycerides in human subjects. Thus, in vivo proton magnetic resonance spectroscopy measurements were conducted on orthotopic heart transplant patients (n = 8) immediately before they underwent routine biopsies and ex vivo measurements were made on the endomyocardial biopsy samples. The correlation coefficient between the two measurements was 0.97, with P0.005, demonstrating for the first time the specificity of the in vivo measurement in human heart. From accompanying reliability experiments, the standardized typical error for the in vivo proton magnetic resonance spectroscopy method was estimated to be 7.0%, with a 95% confidence interval from 5.5 to 9.4%. These results suggest that proton magnetic resonance spectroscopy provides a specific and reliable measurement of myocardial triglycerides content and is suitable for routine studies.

Humoral immune responses to mismatched donor human leukocyte antigen (HLA) and major histocompatibility complex (MHC) class I-related chain A (MICA) have been reported to contribute to immunopathogenesis of antibody-mediated rejection (AMR) in the early period and cardiac allograft vasculopathy (CAV) in the late period after cardiac transplantation (HTx). The goal of this study is to define the roles of donor-specific antibodies (DSA) and anti-MICA in AMR and CAV. A total of 95 post-HTx recipients were enrolled; 43 patients in the early period (≤ 12 months post-HTx) and 52 patients in the late period (12 months post-HTx). Development of DSA and anti-MICA were serially monitored using Luminex. Development of DSA (AMR+: n = 6/8.75%, AMR-: n = 4/35.11%, p = 0.009) and anti-MICA (AMR+: n = 5/8.63%, AMR-: n = 4/35.11%, p = 0.002) was significantly associated with AMR. AMR+DSA+ patients demonstrated increased anti-MICA levels compared with AMR+DSA- patients (p=0.01). Serial monitoring revealed DSA (2.7 ± 1.4 months) preceded development of anti-MICA (6.5 ± 2.1 months) in recipients diagnosed with AMR at 8.3 ± 2.5 months post-HTx. Development of DSA (CAV+: n = 8/12.67%, CAV-: n = 5/40.13%, p = 0.004) and anti-MICA (CAV+: n = 9/12.75%, CAV-: n = 5/40.13%, p = 0.001) was significantly associated with CAV. CAV+DSA+ patients demonstrated increased anti-MICA levels compared with CAV+DSA- patients (p = 0.01). Antibodies to HLA are associated with and precede development of anti-MICA in AMR and CAV. Therefore, DSA and anti-MICA can be used as noninvasive markers for monitoring AMR and CAV.

Hospitalizations for acute decompensated heart failure are increasing in the United States. Moreover, the prevalence of heart failure is increasing consequent to an increased number of older individuals, as well as to improvement in therapies for coronary artery disease and sudden cardiac death that have enabled patients to live longer with cardiovascular disease. The main treatment goals in the hospitalized patient with heart failure are to restore euvolemia and to minimize adverse events. Common in-hospital treatments include intravenous diuretics, vasodilators, and inotropic agents. Novel pharmaceutical agents have shown promise in the treatment of acute decompensated heart failure and may simplify the treatment and reduce the morbidity associated with the disease. This review summarizes the contemporary management of patients with acute decompensated heart failure.

The number of Left Ventricular Assist Devices (LVADs) implanted each year is rising. Nevertheless, there are minimal data on device acceptance after LVAD implant, and on its relationship with patient-reported outcomes. We designed a cross-sectional study to address this knowledge gap and test the hypothesis that low device acceptance is associated with poorer quality of life, depression and anxiety. Self-report questionnaires were administered to assess quality of life (12-item Kansas City Cardiomyopathy Questionnaire quality of life subscale), level of anxiety (7-item Generalized Anxiety Disorder; GAD-7), level of depression (9-item Patient Health Questionnaire; PHQ-9) and device acceptance (Florida Patient Acceptance Survey; FPAS) to 101 consecutive patients presenting to LVAD clinic. Regression analysis showed a strong correlation between device acceptance and both psychological distress (p