Abstract
Heart failure (HF) in diabetes is an emerging topic both in epidemiological and in clinical and basic research. Over the last 12 months, Diabetes and Vascular Disease Research already published two editorials on ‘heart failure and diabetes’1,2 and continuing this theme in the present issue highlights the need for action.
The term ‘diabetic cardiomyopathy’ was brought up in 1972 by Rubler et al. 3 defining a ‘myocardial dysfunction in patients with diabetes in the absence of coronary artery disease hypertrophy of valvular disease’. Over the last four decades, dozens of publications have presented data on this topic and discussed a direct role of diabetes in myocardial changes unrelated to associated risk factors and other cardiac diseases; still, as of yet it is a matter of debate whether diabetic cardiomyopathy exists as a separate disease entity. Despite these debates and discussions, the clinical presentation of HF in diabetes with its prognostic implications has been underestimated by both diabetologists and cardiologists. Only over the last 15 years, it became evident that HF incidence and prevalence is high in patients with ‘pre-diabetes’ and diabetes. Data from various large epidemiological studies suggest that diabetes is associated with an increased risk for incident HF with a rate of 20–35 per 1000 patient-years reflecting a 10%–12% incidence over 3 years.4,5 In addition, a very elegant study published by Shah et al. 6 last year suggests that in subjects with type 2 diabetes, HF is the second frequent reason for initial clinical presentation for cardiovascular disease. Interestingly, the presentation with HF is more frequent than stable angina or non-fatal myocardial infarction. Of note, the most frequent reason is peripheral artery disease.
Once HF is present diabetes, these patients exhibit a higher mortality compared to HF patients without diabetes and up to 50% of all patients with diabetes hospitalized for congestive HF die within 3 years. 7 Apart from this, the risk of hospitalization for HF in patients with diabetes is by far higher than in subjects without diabetes – a finding that became evident in various large HF trials published over the last decades (e.g. SAVE, VALIANT, CHARM). 8
The recognition of the prognostic impact of HF in diabetes was paralleled by a better understanding of the different HF phenotypes dichotomizing patients in those with reduced (HFrEF) and preserved ejection fraction (HFpEF). No matter whether patients with diabetes suffer from HFrEF or HFpEF, their prognosis is worse than in HF patients without diabetes. Despite these striking data on HF in diabetes, HF itself has not been included as a primary endpoint in the recent large cardiovascular outcome trials in diabetes. Only the recently published EMPA-REG OUTCOME (Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes) trial with its surprising finding of a very rapid and highly significant reduction in hospitalization of HF by empagliflozin versus placebo 9 has shifted our attention away from the classical atherosclerotic endpoints myocardial infarction and stroke towards the clinically similarly meaningful endpoints of hospitalization for HF and HF death. The implementation of platelet inhibition, angiotensin-converting enzyme (ACE) inhibitors and statins in patients with diabetes has led to a robust reduction of coronary endpoints like myocardial infarction and hospitalization for unstable angina over the last decades, but we have been less successful in the improvement of HF endpoints in diabetes especially in HFpEF. This may be due to the fact that we need a better phenotyping of our HF patients to improve the taxonomy of HF in diabetes. Thus, we have to employ bio-informatics, cluster analyses and modern big-data approaches to better characterize HF patients with diabetes with the aim to develop more individualized and tailored therapies.
Given the increasing prevalence of diabetes and HF and the bad prognosis of HF patients with diabetes, we need a better understanding of the pathophysiology of HF in these patients, a more sophisticated phenotyping employing modern technology and – based on this – the development of tailored strategies to address this emerging problem in our patients.