Effect of Torsemide Versus Furosemide on Symptoms and Quality of Life Among Patients Hospitalized for Heart Failure: The TRANSFORM-HF Randomized Clinical Trial.

BACKGROUND: Loop diuretics are a primary therapy for the symptomatic treatment of heart failure (HF), but whether torsemide improves patient symptoms and quality of life better than furosemide remains unknown. As prespecified secondary end points, the TRANSFORM-HF trial (Torsemide Comparison With Furosemide for Management of Heart Failure) compared the effect of torsemide versus furosemide on patient-reported outcomes among patients with HF. METHODS: TRANSFORM-HF was an open-label, pragmatic, randomized trial of 2859 patients hospitalized for HF (regardless of ejection fraction) across 60 hospitals in the United States. Patients were randomly assigned in a 1:1 ratio to a loop diuretic strategy of torsemide or furosemide with investigator-selected dosage. This report examined effects on prespecified secondary end points, which included Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS; assessed as adjusted mean difference in change from baseline; range, 0-100 with 100 indicating best health status; clinically important difference, ≥5 points) and Patient Health Questionnaire-2 (range, 0-6; score ≥3 supporting evaluation for depression) over 12 months. RESULTS: Baseline data were available for 2787 (97.5%) patients for KCCQ-CSS and 2624 (91.8%) patients for Patient Health Questionnaire-2. Median (interquartile range) baseline KCCQ-CSS was 42 (27-60) in the torsemide group and 40 (24-59) in the furosemide group. At 12 months, there was no significant difference between torsemide and furosemide in change from baseline in KCCQ-CSS (adjusted mean difference, 0.06 [95% CI, -2.26 to 2.37]; P=0.96) or the proportion of patients with Patient Health Questionnaire-2 score ≥3 (15.1% versus 13.2%: P=0.34). Results for KCCQ-CSS were similar at 1 month (adjusted mean difference, 1.36 [95% CI, -0.64 to 3.36]; P=0.18) and 6-month follow-up (adjusted mean difference, -0.37 [95% CI, -2.52 to 1.78]; P=0.73), and across subgroups by ejection fraction phenotype, New York Heart Association class at randomization, and loop diuretic agent before hospitalization. Irrespective of baseline KCCQ-CSS tertile, there was no significant difference between torsemide and furosemide on change in KCCQ-CSS, all-cause mortality, or all-cause hospitalization. CONCLUSIONS: Among patients discharged after hospitalization for HF, a strategy of torsemide compared with furosemide did not improve symptoms or quality of life over 12 months. The effects of torsemide and furosemide on patient-reported outcomes were similar regardless of ejection fraction, previous loop diuretic use, and baseline health status. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03296813.

Causes and hemodynamic findings in chronic severe pulmonary regurgitation.

Severe pulmonary regurgitation (PR) most commonly occurs as a sequelae of treatment of pulmonic stenosis or Tetralogy of Fallot with fewer cases of primary pulmonic valvular regurgitation. The amount of PR is influenced by valvular integrity, right ventricular (RV) size, and RV diastolic pressures. In chronic severe PR, the RV remodels to accommodate the regurgitant flow and RV stroke volume increases to maintain effective forward blood flow. Hemodynamic changes include a widened pulmonary artery (PA) pulse pressure and low PA diastolic pressures. As the amount of regurgitation increases, RV end diastolic pressure becomes elevated and systemic cardiac output is reduced, especially with exercise. "Ventricularization" of the PA pressure tracing, in which the contour of the PA pressure is similar to the contour of the RV pressure, is a specific but not sensitive finding in severe PR. © 2015 Wiley Periodicals, Inc.

The role of heart failure pharmacotherapy after left ventricular assist device support.

Left ventricular assist devices (LVADs) are an increasingly common treatment for end-stage systolic heart failure. However, there are limited data on how to best treat patients pharmacologically after LVAD implantation, resulting in uncertainty about which heart failure medications provide the most benefit. Still, some evidence exists that certain medical therapies can prevent remodeling and improve right ventricular and, possibly, left ventricular function. This article reviews the current literature for medical heart failure therapy in LVAD patients, and possible future treatment strategies.

Heart failure with preserved ejection fraction: an ongoing enigma.

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome based on traditional heart failure symptoms with documentation of increased left ventricular filling pressures and preserved left ventricular ejection fraction. The exact mechanisms that induce HFpEF are not known. End-diastolic ventricular stiffness does not seem to be acting alone. Substantial mortality exists compared with healthy age-matched controls, as well as significant health care expenditures on hospitalizations and readmissions. This article reviews the epidemiology, pathophysiology, and treatment of heart failure with preserved ejection fraction (HFpEF). Current practice guidelines focus on remedying volume overload, aggressively controlling hypertension, and treatment of comorbid conditions that contribute to decompensation.

Effect of body mass index, physical activity, depression, and educational attainment on high-sensitivity C-reactive protein in patients with atrial fibrillation.

Atherosclerosis development is a complex process, with inflammation, indicated by elevated high-sensitivity C-reactive protein (hs-CRP), as a potential mediator. Obesity, physical activity, and depression have all been reported to affect hs-CRP. However, these factors are interconnected, and their relative individual importance remains unclear. From a separate prospective cohort study, 289 patients were selected for the present substudy. We assessed the relation of a variety of potential predictors and hs-CRP. Obesity, physical activity, and depression, in addition to several other potential factors, were analyzed in bivariate and multivariate linear regression models, adjusting for potential confounders. In unadjusted analyses, mild-to-moderate and severe depression were associated with increased hs-CRP compared to no or minimal depression. Vigorous physical activity was associated with decreased hs-CRP compared to no physical activity. All classes of obesity were associated with increased hs-CRP. In addition, attaining a college or graduate degree was associated with decreased hs-CRP compared to high school or less educational attainment. On multivariate analysis, depression was no longer associated with increased hs-CRP. Physical activity remained associated with decreased hs-CRP but only at vigorous levels. Educational attainment also remained associated but only at the collegiate or professional education level. Ultimately, obesity remained the greatest absolute predictor of elevated hs-CRP. In conclusion, in analyses of multiple factors potentially predictive of elevated hs-CRP in a large population of patients with subclinical coronary heart disease, we found the most important predictor to be obesity.

Decreased expression of gastrokine 1 and the trefoil factor interacting protein TFIZ1/GKN2 in gastric cancer: influence of tumor histology and relationship to prognosis.

PURPOSE: Transcriptional profiling showed decreased expression of gastrokine 1 (GKN1) and the related trefoil factor interacting protein (TFIZ1/GKN2) in Helicobacter pylori infection. Decreased GKN1 and GKN2 mRNA expression has been reported in gastric adenocarcinoma. We have examined GKN1 and GKN2 protein expression in a large gastric cancer series, correlated expression with tumor subtype, and evaluated their utility as prognostic biomarkers. EXPERIMENTAL DESIGN: GKN1, GKN2, and the trefoil factors TFF1 and TFF3 were examined in tissue microarrays from 155 distal gastric adenocarcinomas. Immunohistochemical expression was correlated with clinical outcome. GKN1 and GKN2 expression was measured by real-time PCR and Western analysis in samples of gastric cancer and adjacent nonneoplastic mucosa. RESULTS: GKN1 was lost in 78% of diffuse and 42% of intestinal cancers (P < 0.0001, diffuse versus intestinal). GKN2 expression was lost in 85% of diffuse and 54% of intestinal type cancers (P < 0.002). GKN1 and GKN2 down-regulation were confirmed by Western and real-time PCR analysis. Loss of either protein was associated with significantly worse outcome in intestinal-type tumors by univariate analysis; and GKN2 loss remained a predictor of poor outcome in multivariate analysis (P < 0.033). TFF1 was lost in >70%, and TFF3 was expressed in approximately 50% of gastric cancers. CONCLUSIONS: Loss of GKN1 and GKN2 expression occurs frequently in gastric adenocarcinomas, especially in the diffuse subtype. GKN1 and GKN2 loss are associated with shorter overall survival in the intestinal subtype.