OUTpatient intravenous LASix Trial in reducing hospitalization for acute decompensated heart failure (OUTLAST).

BACKGROUND: Hospitalization for acute decompensated heart failure (ADHF) remains a major source of morbidity and mortality. The current study aimed to investigate the feasibility, safety, and efficacy of outpatient furosemide intravenous (IV) infusion following hospitalization for ADHF. METHODS: In a single center, prospective, randomized, double-blind study, 100 patients were randomized to receive standard of care (Group 1), IV placebo infusion (Group 2), or IV furosemide infusion (Group 3) over 3h, biweekly for a one-month period following ADHF hospitalization. Patients in Groups 2/3 also received a comprehensive HF-care protocol including bi-weekly clinic visits for dose-adjusted IV-diuretics, medication adjustment and education. Echocardiography, quality of life and depression questionnaires were performed at baseline and 30-day follow-up. The primary outcome was 30-day re-hospitalization for ADHF. RESULTS: Overall, a total of 94 patients were included in the study (mean age 64 years, 56% males, 69% African American). There were a total of 14 (15%) hospitalizations for ADHF at 30 days, 6 (17.1%) in Group 1, 7 (22.6%) in Group 2, and 1 (3.7%) in Group 3 (overall p = 0.11; p = 0.037 comparing Groups 2 and 3). Patients receiving IV furosemide infusion experienced significantly greater urine output and weight loss compared to those receiving placebo without any significant increase creatinine and no significant between group differences in echocardiography parameters, KCCQ or depression scores. CONCLUSION: The use of a standardized protocol of outpatient IV furosemide infusion for a one-month period following hospitalization for ADHF was found to be safe and efficacious in reducing 30-day re-hospitalization.

Prevalence and Prognostic Significance of Left Ventricular Noncompaction in Patients Referred for Cardiac Magnetic Resonance Imaging.

BACKGROUND: Presence of prominent left ventricular trabeculation satisfying criteria for left ventricular noncompaction (LVNC) on routine cardiac magnetic resonance examination is frequently encountered; however, the clinical and prognostic significance of these findings remain elusive. This registry aimed to assess LVNC prevalence by 4 current criteria and to prospectively evaluate an association between diagnosis of LVNC by these criteria and adverse events. METHODS AND RESULTS: There were 700 patients referred for cardiac magnetic resonance: 42% were women, median age was 70 years (range, 45-71 years), mean left ventricular ejection fraction was 51% (±17%), and 32% had late gadolinium enhancement on cardiac magnetic resonance. The cohort underwent diagnostic assessment for LVNC by 4 separate imaging criteria-referenced by their authors as Petersen, Stacey, Jacquier, and Captur, with LVNC prevalence of 39%, 23%, 25% and 3%, respectively. Primary clinical outcome was combined end point of time to death, ischemic stroke, ventricular tachycardia/ventricular fibrillation, and heart failure hospitalization. Secondary clinical outcomes were (1) all-cause mortality and (2) time to the first occurrence of any of the following events: cardiac death, ischemic stroke, ventricular tachycardia/ventricular fibrillation, or heart failure hospitalization. During a median follow-up of 7 years, there were no statistically significant differences in assessed outcomes noted between patients with and without LVNC irrespective of the applied criteria. CONCLUSIONS: Current criteria for the diagnosis of LVNC leads to highly variable disease prevalence in patients referred for cardiac magnetic resonance. The diagnosis of LVNC, by any current criteria, was not associated with adverse clinical events on nearly 7 years of follow-up. Limited conclusions can be made for Captur criteria due to low observed prevalence.

Right atrial volume by cardiovascular magnetic resonance predicts mortality in patients with heart failure with reduced ejection fraction.

BACKGROUND: Right Atrial Volume Index (RAVI) measured by echocardiography is an independent predictor of morbidity in patients with heart failure (HF) with reduced ejection fraction (HFrEF). The aim of this study is to evaluate the predictive value of RAVI assessed by cardiac magnetic resonance (CMR) for all-cause mortality in patients with HFrEF and to assess its additive contribution to the validated Meta-Analysis Global Group in Chronic heart failure (MAGGIC) score. METHODS AND RESULTS: We identified 243 patients (mean age 60 ± 15; 33% women) with left ventricular ejection fraction (LVEF) ≤ 35% measured by CMR. Right atrial volume was calculated based on area in two- and four -chamber views using validated equation, followed by indexing to body surface area. MAGGIC score was calculated using online calculator. During mean period of 2.4 years 33 patients (14%) died. The mean RAVI was 53 ± 26 ml/m2; significantly larger in patients with than without an event (78.7±29 ml/m2 vs. 48±22 ml/m2, p<0.001). RAVI (per ml/m2) was an independent predictor of mortality [HR = 1.03 (1.01-1.04), p = 0.001]. RAVI has a greater discriminatory ability than LVEF, left atrial volume index and right ventricular ejection fraction (RVEF) (C-statistic 0.8±0.08 vs 0.55±0.1, 0.62±0.11, 0.68±0.11, respectively, all p<0.02). The addition of RAVI to the MAGGIC score significantly improves risk stratification (integrated discrimination improvement 13%, and category-free net reclassification improvement 73%, both p<0.001). CONCLUSION: RAVI by CMR is an independent predictor of mortality in patients with HFrEF. The addition of RAVI to MAGGIC score improves mortality risk stratification.

Review and Analysis of Publication Trends over Three Decades in Three High Impact Medicine Journals.

CONTEXT: Over the past three decades, industry sponsored research expanded in the United States. Financial incentives can lead to potential conflicts of interest (COI) resulting in underreporting of negative study results. OBJECTIVE: We hypothesized that over the three decades, there would be an increase in: a) reporting of conflict of interest and source of funding; b) percentage of randomized control trials c) number of patients per study and d) industry funding. DATA SOURCES AND STUDY SELECTION: Original articles published in three calendar years (1988, 1998, and 2008) in The Lancet, New England Journal of Medicine and Journal of American Medical Association were collected. DATA EXTRACTION: Studies were reviewed and investigational design categorized as prospective and retrospective clinical trials. Prospective trials were categorized into randomized or non-randomized and single-center or multi-center trials. Retrospective trials were categorized as registries, meta-analyses and other studies, mostly comprising of case reports or series. Study outcomes were categorized as positive or negative depending on whether the pre-specified hypothesis was met. Financial disclosures were researched for financial relationships and profit status, and accordingly categorized as government, non-profit or industry sponsored. Studies were assessed for reporting COI. RESULTS: 1,671 original articles were included in this analysis. Total number of published studies decreased by 17% from 1988 to 2008. Over 20 year period, the proportion of prospective randomized trials increased from 22 to 46% (p < 0.0001); whereas the proportion of prospective non-randomized trials decreased from 59% to 27% (p < 0.001). There was an increase in the percentage of prospective randomized multi-center trials from 11% to 41% (p < 0.001). Conversely, there was a reduction in non-randomized single-center trials from 47% to 10% (p < 0.001). Proportion of government funded studies remained constant, whereas industry funded studies more than doubled (17% to 40%; p < 0.0001). The number of studies with negative results more than doubled (10% to 22%; p<0.0001). While lack of funding disclosure decreased from 35% to 7%, COI reporting increased from 2% to 84% (p < 0.0001). CONCLUSION: Improved reporting of COI, clarity in financial sponsorship, increased publication of negative results in the setting of larger and better designed clinical trials represents a positive step forward in the scientific publications, despite the higher percentage of industry funded studies.

"Second" Primary Cardiac Sarcoma in a Patient With Ewing Sarcoma. Always Expect The Unexpected.

A high suspicion for relapsed metastatic disease must arise when an intracardiac mass is detected in a patient with a recent history of Ewing sarcoma. Nevertheless, the scenario may eventually turn out to be much more complex than expected, and the possibility that the intracardiac tumor may instead be a "second" primary sarcoma, although extremely rare, should also be considered. We describe the first case of concomitant diagnosis of Ewing sarcoma and low-grade myxoid spindle cell sarcoma in the same young patient.

Right Ventricular Dysfunction Impairs Effort Tolerance Independent of Left Ventricular Function Among Patients Undergoing Exercise Stress Myocardial Perfusion Imaging.

BACKGROUND: Right ventricular (RV) and left ventricular (LV) function are closely linked due to a variety of factors, including common coronary blood supply. Altered LV perfusion holds the potential to affect the RV, but links between LV ischemia and RV performance, and independent impact of RV dysfunction on effort tolerance, are unknown. METHODS AND RESULTS: The population comprised 2051 patients who underwent exercise stress myocardial perfusion imaging and echo (5.5±7.9 days), among whom 6% had echo-evidenced RV dysfunction. Global summed stress scores were ≈3-fold higher among patients with RV dysfunction, attributable to increments in inducible and fixed LV perfusion defects (all P≤0.001). Regional inferior and lateral wall ischemia was greater among patients with RV dysfunction (both P<0.01), without difference in corresponding anterior defects (P=0.13). In multivariable analysis, inducible inferior and lateral wall perfusion defects increased the likelihood of RV dysfunction (both P<0.05) independent of LV function, fixed perfusion defects, and pulmonary artery pressure. Patients with RV dysfunction demonstrated lesser effort tolerance whether measured by exercise duration (6.7±2.8 versus 7.9±2.9 minutes; P<0.001) or peak treadmill stage (2.6±0.9 versus 3.1±1.0; P<0.001), paralleling results among patients with LV dysfunction (7.0±2.9 versus 8.0±2.9; P<0.001|2.7±1.0 versus 3.1±1.0; P<0.001 respectively). Exercise time decreased stepwise in relation to both RV and LV dysfunction (P<0.001) and was associated with each parameter independent of age or medication regimen. CONCLUSIONS: Among patients with known or suspected coronary artery disease, regional LV ischemia involving the inferior and lateral walls confers increased likelihood of RV dysfunction. RV dysfunction impairs exercise tolerance independent of LV dysfunction.