Prognostic Effect of the Dose of Loop Diuretic Over Five Years in Chronic Heart Failure

Background: High diuretic doses in chronic heart failure (HF) are potentially deleterious. We assessed the effect of dynamic furosemide dose on all-cause mortality among HF ambulatory patients. Methods and Results: A cohort of 560 ambulatory patients from an outpatient clinic specialized in HF, with median age 70 years, 67% male, and 89% with moderate-severely reduced ejection fraction, was retrospectively followed for up to 5 years. Dynamic furosamide exposure was categorized as low (0–59 mg/d), medium (60–119 mg/d), high (120–159 mg/d), and very high (≥160 mg/d). Extended Cox models were used to estimate the association between time-varying diuretic dose and mortality. A dose-dependent crude association between higher doses of furosemide and death (hazard ratio [HR] = 1.34, 95% confidence interval (CI): 1.06–2.16; HR = 2.09, 95% CI: 1.54–2.84, for high and very high dose, respectively) was totally explained by patients' characteristics and disease severity indicators (adjusted HR = 0.94, 95% CI: 0.63–1.38; HR = 1.10, 95% CI: 0.79–1.55, for high and very high dose, respectively). Conclusion: In this context, higher doses of diuretic did not impair survival, but rather indicated greater severity of the patient's condition.This study was funded by FEDER through the Operational Programme Competitiveness and Internationalization and national funding from the Foundation for Science and Technology– FCT (Portuguese Ministry of Science, Technology and Higher Education) (FCOMP-01-0124-FEDER-011019), under the project “A pharmacoepidemiological approach to the study of prognosis in acute and chronic heart failure” (Ref. FCT PTDC/SAU-ESA/107940/2008) and the Unidade de Investigação em Epidemiologia—Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (POCI-01-0145-FEDER-006862; Ref. UID/DTP/04750/2013)

Prognostic Value of Osteoprotegerin in Acute Heart Failure

Background: Osteoprotegerin (OPG) is promising as a predictor of adverse prognosis in patients with acute coronary syndromes and chronic heart failure. Its prognostic value in acute heart failure (AHF) is unknown. The aim of this study was to assess the prognostic value provided by serum OPG levels at discharge after an admission for AHF. Methods: In a prospective study, we enrolled 338 patients consecutively admitted with AHF to the internal medicine department of a tertiary care university hospital in Porto, Portugal between March 2009 and December 2010. OPG was measured using a commercial enzyme-linked immunosorbent assay and was both analyzed as a continuous variable and categorized by quartiles. Patients were followed for up to 6 months after discharge to ascertain the occurrence of all-cause death or hospital readmission resulting from AHF. Results: During follow-up, 119 patients died or were readmitted for AHF. A graded increase in the risk of the combined end point was observed across quartiles of OPG. At 6 months, the cumulative risk of the end point was 25% for the first quartile and 50% for the fourth quartile. The multivariable adjusted risk of death or hospitalization for AHF increased progressively across categories of OPG up to a statistically significant 2.44-fold increase in risk in the highest category (P for linear trend = 0.002, ie, by 5% per 10 pg/mL increase in OPG). Conclusions: Serum OPG was directly associated with a higher probability of death or readmission for AHF within 6 months, irrespective of other known prognostic markers. This was true both when the ejection fraction was preserved and when it was reduced