Association of Low Body Temperature and Poor Outcomes in Patients Admitted With Worsening Heart Failure

A Substudy of the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) Trial

Saeed Payvar; John A. Spertus; Alan B. Miller; S. Ward Casscells; Peter S. Pang; Faiez Zannad; Karl Swedberg; Aldo P. Maggioni; Kimberly J. Reid; Mihai Gheorghiade

Disclosures

Eur J Heart Fail. 2013;15(12):1382-1389. 

In This Article

Abstract and Introduction

Abstract

Aims Risk stratification in patients admitted with worsening heart failure (HF) is essential for tailoring therapy and counselling. Risk models are available but rarely used, in part because many require laboratory and imaging results that are not routinely available. Body temperature is associated with prognosis in other illnesses, and we hypothesized that low body temperature would be associated with worse outcomes in patients admitted with worsening HF.

Methods and results The Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial was an event-driven, randomized, double-blind, placebo-controlled study of tolvaptan in 4133 patients hospitalized for worsening HF with an EF <40%. Co-primary endpoints were all-cause mortality and cardiovascular (CV) death or HF rehospitalization. Body temperature was measured orally at randomization and entered in analyses both as a continuous variable and categorized into three groups (<36°C, 36–36.5°C, and >36.5°C) using Cox regression models. The composite of CV death or HF rehospitalization occurred in 1544 patients within 1 year. For every 1°C decrease in body temperature, the risk of adverse outcomes increased by 16% [hazard raio (HR) 1.16, 95% confidence interval (CI) 1.04–1.28], after adjustment for age, gender, race, systolic blood pressure, EF, blood urea nitrogen, and serum sodium. In fully adjusted analysis, the risk of adverse outcomes in the lowest body temperature group (<36°C) was 51% higher than that of the index group (>36.5°C) (HR 1.35, 95% CI 1.15–1.58).

Conclusions Low body temperature is an independent marker of poor cardiovascular outcomes in patients admitted with worsening HF and reduced EF.

Introduction

Chronic heart failure (HF) with reduced EF is a syndrome that is associated with significant morbidity and mortality. Therapeutic decisions and counselling for HF patients are based on risk assessment. Many biomarkers[1] and 39 co-morbid conditions[2] have been recognized to be associated with worse outcomes in HF patients. These have been incorporated into several risk profiles and models, such as the Seattle Heart Failure Model,[3] the Acute Decompensated Heart Failure National Registry tree model risk score,[4] the PROTECT in-hospital risk model,[5] and others.[6] However these tend to be complex and difficult to apply in routine clinical settings where some variables may not be routinely available.

Vital signs are readily available in clinical practice, and body temperature has been used for this purpose in other illnesses such as shock,[7] trauma,[8,9] and multiorgan failure.[10] Defining the relationship between body temperature and outcomes is important due to the simplicity and low cost of integrating it into a prognostic assessment. Body temperature has been found to be a predictor of outcomes in HF patients in smaller retrospective studies;[11,12] yet such an association has not been reported in any prospective studies. We hypothesized that in patients with reduced EF admitted for worsening HF, low body temperature would be associated with worse outcomes, and we tested this in a pre-specified manner in the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial, a large clinical trial of patients admitted with decompensated HF.

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