Undiagnosed dysglycemia in patients hospitalized for worsening heart failure: not so sweet after all

Abstract

This article refers to ‘Long-term mortality is increased in patients with undetected prediabetes and type 2 diabetes hospitalized for worsening heart failure and reduced ejection fraction’ by Pavlović and colleagues, published in this issue of the journal. The syndrome of heart failure (HF) is the clinical manifestation of diverse underlying cardiac and noncardiac comorbidities, resulting in a heterogeneous patient population ranging from stable and ambulatory to decompensated and hospitalized. Among patients recently hospitalized for worsening HF, the mortality and readmission rates approach 27% and 44%, respectively, at 1 year. Despite this dismal prognosis, no specific disease-modifying therapy has been shown convincingly to improve post-discharge outcomes. HF and type 2 diabetes mellitus (T2DM) are the two great pandemics of contemporary practice. Furthermore, patients with HF and concomitant T2DM are at increased risk and may have a unique pathophysiology including hemodynamic and neurohormonal abnormalities. In the most recent pan-European registry, T2DM was found to be an independent predictor of death among ambulatory patients with heart failure with a reduced ejection fraction (HFrEF). Furthermore, in a recent meta-analysi, T2DM was more commonly found in the group of ambulatory HFrEF patients who do not improve ejection fraction over time as result of evidence-based interventions. In contrast, among patients hospitalized for acute HF, although the increased risk of morbidity and mortality conferred by known diabetic status is well established, the risk associated with newly diagnosed prediabetes and T2DM remains controversial. In addition, it is not entirely clear whether elevated blood glucose level in acute HF is a marker for risk or a mediator of adverse outcomes. In a large international cohort of acute HF patients, blood glucose concentrations at presentation were powerful prognostic indicators for short-term mortality even after adjusting for diabetes status, systolic function and other traditional risk factors. However, the association between the full spectrum of dysglycemia and long-term outcomes after hospitalization for acute HF has not been well studied. Three randomized control trials (RCTs) have addressed the prevalence and prognostic value of post-hoc characterization of glycemic abnormalities (i.e. prediabetes and newly diagnosed T2DM) but these studies were restricted to stable ambulatory HF patients. In this issue of the journal, Pavlović et al. present data from a prospective cohort study enrolling 150 patients hospitalized for worsening HFrEF and New York Heart Association functional class II–III symptoms. Based on fasting plasma glycemia and a standard 2-hour oral glucose tolerance test, patients were classified as: normoglycemic, prediabetes, and newly diagnosed T2DM. All patients were prospectively followed and outcomes, including all-cause and cardiovascular mortality, were reported at 1 year. Survival analysis was reported separately for patients with prediabetes and newly diagnosed T2DM. The Cox proportional hazard models were used to estimate the hazard ratios (HRs) for all-cause and cardiovascular mortality in patients with prediabetes and T2DM, with normoglycemic patients serving as the reference group. Cox regression models were adjusted for clinically relevant variables found to be significant on univariate analysis. The investigators found that among hospitalized HFrEF patients, dysglycemia was common, prediabetes and T2DM, respectively, were diagnosed in 43% and 19% of patients. Furthermore, dysglycemia, compared with normoglycemia, during hospitalization