Markers of Decongestion, Dyspnea Relief, and Clinical Outcomes Among Patients Hospitalized With Acute Heart Failure

Background Congestion is a primary driver of symptoms in patients with acute heart failure (AHF), and relief of congestion is a critical goal of therapy. Monitoring of response to therapy through the assessment of daily weights and net fluid loss is the current standard of care, yet the relationship between commonly used markers of decongestion and both patient reported symptom relief and clinical outcomes are unknown. Methods and Results We performed a retrospective analysis of the randomized clinical trial -Diuretic Optimization Strategy Evaluation in Acute Heart Failure (DOSE-AHF), enrolling patients hospitalized with a diagnosis of acute decompensated heart failure (ADHF). We assessed the relationship between 3 markers of decongestion at 72 hours—weight loss, net fluid loss and % reduction in serum NT-proBNP level—and relief of symptoms as defined by the dyspnea visual analog scale area under the curve (VAS AUC). We also determined the relationship between each marker of decongestion and 60-day clinical outcomes defined as time to death, first re-hospitalization or ER visit. Mean age was 66 years, mean EF was 35% and 27% had EF ≥50%. Of the 3 measures of decongestion assessed, only % reduction in NT-proBNP was significantly associated with symptom relief (r=0.13, P = 0.04). There was no correlation between either weight loss or net fluid loss and symptom relief, (r=0.04, P=0.54 and r=0.07, P=0.27, respectively). Favorable changes in each of the 3 markers of decongestion were associated with improvement in time to death, re-hospitalization or ED visit at 60 days [weight: HR 0.91 (95% confidence interval 0.85, 0.97) per 4 lbs. weight lost; fluid HR 0.94 (0.90, 0.99) per 1000mL fluid loss; NT-proBNP HR 0.95 (0.91, 0.99) per 10% reduction]. These associations were unchanged after multivariable adjustment with the exception that % reduction in NT-proBNP was no longer a significant predictor (HR 0.97; 0.93, 1.02). Patients with 2 or 3 markers of decongestion (above the median value for each marker) had improved clinical outcomes versus those with 0 or 1 marker above the median value (39.0% versus 53.8%; P=0.03). Conclusions Weight loss, fluid loss and NT-proBNP reduction at 72 hours are poorly correlated with dyspnea relief. However, favorable improvements in each of the 3 markers were associated with improved clinical outcomes at 60 days. These data suggest the need for ongoing research to understand the relationships between symptom relief, congestion, and outcomes in patients with ADHF

International Variation in and Factors Associated With Hospital Readmission After Myocardial Infarction

Context ST-segment elevation myocardial infarction (STEMI) treatment has improved outcomes and shortened hospital stay. Recently, 30-day readmission rates have been proposed as a metric for care of patients with STEMI. However, international rates and predictors of 30-day readmission after STEMI have not been studied. Objective To determine international variation in and predictors of 30-day readmission rates after STEMI and country-level care patterns. Design, Setting, and Patients Post hoc analysis of the Assessment of Pexelizumab in Acute Myocardial Infarction trial that enrolled 5745 patients with STEMI at 296 sites in the United States, Canada, Australia, New Zealand, and 13 European countries from July 13, 2004, to May 11, 2006. Multivariable logistic regression analysis was used to identify independent predictors of all-cause and nonelective 30-day postdischarge readmission. Main Outcome Measures Predictors of 30-day postdischarge all-cause and nonelective readmissions. Results Of 5571 patients with STEMI who survived to hospital discharge, 631 (11.3%) were readmitted within 30 days. Thirty-day readmission rates were higher for the United States than other countries (14.5% vs 9.9%; P < .001). Median length of stay was shortest for US patients (3 days; interquartile range, 2-4 days) and longest for Germany (8 days; interquartile range, 6-11 days). In multivariable regression, the predictors of 30-day readmission included multivessel disease (odds ratio [OR], 1.97; 95% CI, 1.65-2.35) and US location (OR, 1.68; 95% CI, 1.37-2.07). Excluding elective readmission for revascularization, US enrollment was still an independent predictor of readmission (OR, 1.53; 95% CI, 1.20-1.96). After adjustment of the models for country-level median length of stay, US location was no longer an independent predictor of 30-day all-cause or nonelective readmission. Location in the United States was not a predictor of in-hospital death (OR, 0.88; 95% CI, 0.60-1.30) or 30-day postadmission death (OR, 1.0; 95% CI, 0.72-1.39). Conclusions In this multinational study, there was variation across countries in 30-day readmission rates after STEMI, with readmission rates higher in the United States than in other countries. However, this difference was greatly attenuated after adjustment for length of stay

Care Optimization Through Patient and Hospital Engagement Clinical Trial for Heart Failure: Rationale and design of CONNECT-HF

Many therapies have been shown to improve outcomes for patients with heart failure (HF) in controlled settings, but there are limited data available to inform best practices for hospital and post-discharge quality improvement initiatives. The CONNECT-HF study is a prospective, cluster-randomized trial of 161 hospitals in the United States with a 2×2 factorial design. The study is designed to assess the effect of a hospital and post-discharge quality improvement intervention compared with usual care (primary objective) on HF outcomes and quality-of-care, as well as to evaluate the effect of hospitals implementing a patient-level digital intervention compared with usual care (secondary objective). The hospital and post-discharge intervention includes audit and feedback on HF clinical process measures and outcomes for patients with HF with reduced ejection fraction (HFrEF) paired with education to sites and clinicians by a trained, nationally representative group of HF and quality improvement experts. The patient-level digital intervention is an optional ancillary study and includes a mobile application and behavioral tools that are intended to facilitate improved use of guideline-directed recommendations for self-monitoring and self-management of activity and medications for HFrEF. The effects of the interventions will be measured through an opportunity-based composite score on quality and time-to-first HF readmission or death among patients with HFrEF who present to study hospitals with acute HF and who consent to participate. The CONNECT-HF study is evaluating approaches for implementing HF guideline recommendations into practice and is one of the largest HF implementation science trials performed to date

Circulating T-Cell Subsets, Monocytes, and Natural Killer Cells in Peripartum Cardiomyopathy: Results From the Multicenter IPAC Study

•Immune cell subsets were examined in healthy postpartum and peripartum cardiomyopathy (PPCM) women.•In the early postpartum, PPCM women had lower NK and higher CD3+CD4–CD8–CD38+ T cell levels.•Levels largely normalized by 6 months postpartum. The aim of this work was to evaluate the hypothesis that the distribution of circulating immune cell subsets, or their activation state, is significantly different between peripartum cardiomyopathy (PPCM) and healthy postpartum (HP) women. PPCM is a major cause of maternal morbidity and mortality, and an immune-mediated etiology has been hypothesized. Cellular immunity, altered in pregnancy and the peripartum period, has been proposed to play a role in PPCM pathogenesis. The Investigation of Pregnancy-Associated Cardiomyopathy (IPAC) study enrolled 100 women presenting with a left ventricular ejection fraction of <0.45 within 2 months of delivery. Peripheral T-cell subsets, natural killer (NK) cells, and cellular activation markers were assessed by flow cytometry in PPCM women early (<6 wk), 2 months, and 6 months postpartum and compared with those of HP women and women with non–pregnancy-associated recent-onset cardiomyopathy (ROCM). Entry NK cell levels (CD3–CD56+CD16+; reported as % of CD3– cells) were significantly (P < .0003) reduced in PPCM (6.6 ± 4.9% of CD3– cells) compared to HP (11.9 ± 5%). Of T-cell subtypes, CD3+CD4–CD8–CD38+ cells differed significantly (P < .004) between PPCM (24.5 ± 12.5% of CD3+CD4–CD8– cells) and HP (12.5 ± 6.4%). PPCM patients demonstrated a rapid recovery of NK and CD3+CD4–CD8–CD38+ cell levels. However, black women had a delayed recovery of NK cells. A similar reduction of NK cells was observed in women with ROCM. Compared with HP control women, early postpartum PPCM women show significantly reduced NK cells, and higher CD3+CD4–CD8–CD38+ cells, which both normalize over time postpartum. The mechanistic role of NK cells and “double negative” (CD4–CD8–) T regulatory cells in PPCM requires further investigation