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ObjectivesThis study sought to determine whether changes in intra-abdominal pressure (IAP) with aggressive diuretic or vasodilator therapy are associated with improvement in renal function in acute decompensated heart failure (ADHF).BackgroundElevated IAP (≥8 mm Hg) is associated with intra-abdominal organ dysfunction. There is potential for ascites and visceral edema causing elevated IAP in patients with ADHF.MethodsForty consecutive patients admitted to a specialized heart failure intensive care unit for management of ADHF with intensive medical therapy were studied. The IAP was measured using a simple transvesical technique at time of admission and before removal of the pulmonary artery catheter.ResultsIn our study cohort (mean age 59 ± 13 years, mean left ventricular ejection fraction 19 ± 9%, baseline serum creatinine 2.0 ± 0.9 mg/dl), the mean baseline IAP was 8 ± 4 mm Hg, with 24 (60%) patients having elevated IAP. Elevated IAP was associated with worse renal function (p = 0.009). Intensive medical therapy resulted in improvement in both hemodynamic measurements and IAP. A strong correlation (r = 0.77, p < 0.001) was observed between reduction in IAP and improved renal function in patients with baseline elevated IAP. However, changes in IAP or renal function did not correlate with changes in any hemodynamic variable.ConclusionsElevated IAP is prevalent in patients with ADHF and is associated with impaired renal function. In the setting of intensive medical therapy for ADHF, changes in IAP were better correlated with changes in renal function than any hemodynamic variable.

OBJECTIVES We studied the outcome of diabetics enrolled in the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) V trial to assess whether the combination of half-dose reteplase and abciximab provides any propitious benefits over standard fibrinolytic therapy in diabetic patients. BACKGROUND Diabetics with acute ST-segment elevation myocardial infarction (MI) have a worse outcome compared with nondiabetics. Higher-risk patients are usually more likely to benefit from advances in medical therapy. METHODS We analyzed diabetic patients enrolled in the GUSTO V trial to assess the outcome of those randomized to the combination of half-dose reteplase and abciximab versus those randomized to reteplase. We also evaluated whether any differences existed in presentation and outcome of MI among the diabetics versus the nondiabetics enrolled in the study. RESULTS The trial enrolled 13,782 nondiabetics and 2,633 diabetics. Compared to nondiabetics, diabetics had a significantly higher mortality at 30 days (8.5% vs. 5.1%, p < 0.001) and at 1 year (12.7% vs. 7.5%, p < 0.001). Among the diabetic subset, no significant difference existed in the incidence of 30-day (8.8% vs. 8.2%, p = 0.52) or 1-year mortality (13.0% vs. 12.4%, p = 0.62) among patients randomized to reteplase compared to those receiving combination of abciximab and reteplase. The incidence of reinfarction (2.5% vs. 4.3%, p = 0.013), recurrent ischemia (11.8% vs. 14.9%, p = 0.017), and urgent revascularization (10.9% vs. 13.3%, p = 0.055) at seven days was lower in diabetics treated with the combination therapy. CONCLUSIONS Compared to nondiabetics, diabetics continue to have a worse outcome with MI. Although combination therapy did not provide a survival benefit, nonfatal ischemic outcomes, including reinfarction, recurrent ischemia, and urgent revascularization, were substantially reduced.

ObjectivesThe aim of this study was to investigate the use of durable mechanical circulatory support (MCS) in patients with chemotherapy-induced cardiomyopathy (CCMP) and determine their outcomes and survival in comparison to that of other patients with end-stage heart failure treated similarly.BackgroundPatients with end-stage heart failure as a result of CCMP from anthracyclines are often precluded from heart transplantation because of a history of cancer. In such patients, durable MCS may offer an important chance for life prolongation. Yet, there are no data to support the use of MCS in this increasingly prevalent group of patients.MethodsWe searched 3,812 MCS patients from June 2006 through March 2011 in the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) database for the diagnosis of CCMP. We compared characteristics, outcomes, and survival between CCMP patients and patients with nonischemic cardiomyopathy and ischemic cardiomyopathy.ResultsCompared with patients with nonischemic cardiomyopathy and ischemic cardiomyopathy, patients with CCMP were overwhelmingly female (72% vs. 24% vs. 13%, p = 0.001), had MCS more often implanted as destination therapy (33% vs. 14% vs. 22%, p = 0.03), required more right ventricular assist device support (19% vs. 11% vs. 6%, p = 0.006), and had a higher risk of bleeding (p = 0001). Survival of CCMP patients was similar to that of other groups.ConclusionsCCMP patients treated with MCS have survival similar to other MCS patients despite more frequent need for right ventricular assist device support and increased bleeding risk.

ObjectivesThis study sought to determine if the timing of hemoconcentration influences associated survival.BackgroundIndicating a reduction in intravascular volume, hemoconcentration during the treatment of decompensated heart failure has been associated with reduced mortality. However, it is unclear if this survival advantage stems from the improved intravascular volume or if healthier patients are simply more responsive to diuretics. Rapid diuresis early in the hospitalization should similarly identify diuretic responsiveness, but hemoconcentration this early would not indicate euvolemia if extravascular fluid has not yet equilibrated.MethodsConsecutive admissions at a single center with a primary discharge diagnosis of heart failure were reviewed (N = 845). Hemoconcentration was defined as an increase in both hemoglobin and hematocrit levels, then further dichotomized into early or late hemoconcentration by using the midway point of the hospitalization.ResultsHemoconcentration occurred in 422 (49.9%) patients (41.5% early and 58.5% late). Patients with late versus early hemoconcentration had similar baseline characteristics, cumulative in-hospital loop diuretic administered, and worsening of renal function. However, patients with late hemoconcentration versus early hemoconcentration had higher average daily loop diuretic doses (p = 0.001), greater weight loss (p < 0.001), later transition to oral diuretics (p = 0.03), and shorter length of stay (p < 0.001). Late hemoconcentration conferred a significant survival advantage (hazard ratio: 0.74 [95% confidence interval: 0.59 to 0.93]; p = 0.009), whereas early hemoconcentration offered no significant mortality benefit (hazard ratio: 1.0 [95% confidence interval: 0.80 to 1.3]; p = 0.93) over no hemoconcentration.ConclusionsOnly hemoconcentration occurring late in the hospitalization was associated with improved survival. These results provide further support for the importance of achieving sustained decongestion during treatment of decompensated heart failure.

ObjectivesWe sought to determine whether circulating soluble angiotensin-converting enzyme 2 (sACE2) is increased in the plasma of patients with heart failure (HF).BackgroundAngiotensin-converting enzyme 2 (ACE2) is an integral membrane protein that antagonizes the actions of angiotensin II and prevents the development of HF in animal models. However, because of the need for invasive cardiac tissue sampling, little is known about whether ACE2 is involved in the pathophysiology of HF in humans.MethodsWe developed a sensitive and specific assay to measure sACE2 activity in human plasma and screened a heterogeneous group of patients suspected of having clinical HF.ResultsIncreasing sACE2 plasma activity strongly correlated with a clinical diagnosis of HF (p = 0.0002), worsening left ventricular ejection fraction (p < 0.0001), and increasing B-type natriuretic peptide levels (p < 0.0001). Similar to B-type natriuretic peptide, sACE2 activity reflected the severity of HF, with increasing levels associated with worsening New York Heart Association functional class (p < 0.0001). These associations were independent of other disease states and medication use. We found that sACE2 activity was increased in patients with both ischemic and nonischemic cardiomyopathies and also in patients with clinical HF but a preserved left ventricular ejection fraction.ConclusionsSoluble ACE2 activity is increased in patients with HF and correlates with disease severity, suggesting that a cardioprotective arm of the renin-angiotensin-aldosterone system is active in HF.

ObjectivesThe purpose of this study was to describe the long-term course of left ventricular remodeling induced by cardiac resynchronization therapy (CRT), adjusting for the confounding effect of patient loss due to disease.BackgroundReverse remodeling has been identified as the primary mechanism of improved symptoms and outcome in heart failure patients.MethodsA total of 313 consecutive patients who underwent CRT with available baseline echocardiograms and subsequent clinical and echocardiographic follow-up were included in the analysis. Long-term follow-up included all-cause mortality, heart transplantation, and implantation of a left ventricular assist device. Longitudinal data analysis of left ventricular end-systolic volume index (LVESVi) was performed to adjust for the confounding effect of patient loss during follow-up.ResultsPatients with uneventful survival had a lower baseline LVESVi (Δ = 8.6 ml/m2, SE = 4.6 ml/m2, p < 0.0001) and a decreased LVESVi by −0.11 ml/m2/day during first 6 months, whereas the LVESVi remained unchanged in patients with adverse events (p < 0.0001). Beyond 6 months, the LVESVi remained unchanged in patients with uneventful survival, whereas the LVESVi continued to increase in those with adverse events at a rate of 0.01 ml/m2/day (p < 0.0001). Predictors of reverse remodeling were nonischemic etiology, female sex, and a wider QRS duration (p < 0.0001, p = 0.014, and p = 0.001, respectively). In the majority of patients, 6 months indicates a break point after which reverse remodeling becomes significantly less pronounced.ConclusionsCRT patients with uneventful survival show a significant decrease in the LVSVi at 6 months and generally maintain this response in the long term. Those with adverse outcomes are characterized by left ventricular dilation despite CRT.