EASD/ESC Symposium: heart failure in type 2 diabetes
M. Louis Handoko, MD
Department of Cardiology, Vrije Universiteit Medical Centre, Amsterdam, The Netherlands Javed Butler, MD, MPH, MBA
University of Mississippi Medical Centre, Jackson, MI, USA
Heart failure (HF) has a major impact on prognosis and management in patients with diabetes.
Screening for HF using history, symptoms and signs, and lab tests (NT-proBNP/BNP) should be performed along with specialist referral when appropriate.
Early HF with preserved ejection fraction (HFpEF) can be missed when relying only on lab tests and trans-thoracic echocardiography (TTE); exercise right heart catheterisation is the gold standard for diagnosis of HFpEF.
New glucose-lowering agents reduce the rate of HF events and mortality.
Various mechanisms contribute to the impairment in systolic and diastolic function in patients with diabetes, and there is an increased recognition that these patients develop HF independent of the presence of coronary artery disease or its associated risk factors. Epidemiologic and clinical data from the last 2 decades have shown that the prevalence of HF in diabetes is very high, and the prognosis for patients with HF is worse in those with diabetes than in those without diabetes. Recent data has highlighted the importance of diagnosis and screening for HF in patients with diabetes as well as taking preventive measures. This is of substantial relevance since about 20% of patients with type 2 diabetes will have comorbid HF, which accordingly has a substantial impact on the quality of life, prognosis and management.
The ideal screening tool for HF should be sensitive and specific, as well as readily available and simple to interpret.
Current diagnostic work-up for HF includes evaluation of patient characteristics, medical history, signs, symptoms and lab tests (NT-proBNP/BNP), which can be performed by an internist or general practitioner.
Electrocardiogram and instrumental chest exams may also be needed, which are usually interpreted by a cardiologist.
Some simplified screening tools have been developed, which can help the general practitioner address the patient for specialist care when positive.
Caution should be used when diagnosing HFpEF, since the sensitivity of natriuretic peptides is somewhat low, and TTE has difficulties in detecting subtle but possibly relevant left ventricular diastolic dysfunction.
Importantly, normal natriuretic peptide levels and a normal TTE do not exclude HFpEF in symptomatic patients.
HFpEF can be unmasked by more sophisticated techniques such as exercise right heart catheterisation.
Indeed, in patients with suspected HFpEF, invasive exercise testing substantially improves prediction of long-term mortality.
Exercise testing using both invasive and noninvasive hemodynamic assessments can thus greatly aid in confirming or refuting a diagnosis of HFpEF.
Taken together, HF is highly prevalent in type 2 diabetes, and the presence of HF has major implications for prognosis and management.
Active screening for HF is warranted (≥2 items): history, symptoms and signs, and lab tests (NT-proBNP/BNP) are sufficient.
TTE is required to establish a definite diagnosis of HF, and identification of the underlying cause is mandatory.
Early HFpEF can be missed when relying only on lab tests and TTE.
In this regard, the H2FPEF score relies on simple clinical characteristics and echocardiography, enables discrimination of HFpEF from noncardiac causes of dyspnea and can assist in determination of the need for further diagnostic testing in the evaluation of patients with unexplained exertional dyspnoea.
Lastly, exercise right heart catheterisation should be considered as the gold standard for diagnosis in challenging cases.
In the general population, the lifetime risk for developing chronic HF is 21% for men and 20.3% for women, with poor long-term survival.
In patients with diabetes, the presence of HF increases mortality by 10-fold compared to patients with diabetes without HF.
Costs for care of patients with HF are also high, reaching nearly $40 billion in the US alone, and projected to reach $160 billion in costs of direct care by 2030.
Given this scenario, it is unfortunate that prevention of HF is a neglected area and is rarely the subject of research and grants.
In most cardiovascular trials, it is often left out of primary endpoints, and the American College of Cardiology (ACC)/ American Heart Association (AHA), Heart Failure Society of America (HFSA), European Society of Cardiology (ESC) and American College of Physicians (ACP) have no guidelines on prevention of HF.
Some older studies have shown that inhibition of angiotensin converting enzyme can reduce HF as the primary cause for hospitalisation or death, and that antihypertensive medication also has a beneficial effect, as well as combination treatment with diuretics and ACE-inhibitors in patients ≥80 years old.
The benefits of intensive blood pressure control were later verified in the SPRINT trial where it was found that among patients at high risk for cardiovascular events but without diabetes, targeting a systolic blood pressure of less than 120 mmHg, compared with less than 140 mmHg, was associated in lower rates of fatal and nonfatal major cardiovascular events and death from any cause.
The presence of diabetes markedly increases the risk of developing new onset HF by 2-4 fold, which subsequently increases the risk of mortality even when conventional therapies are applied.
Recent studies have indicated, however, that the choice of pharmacological agent can markedly impact the risk of HF risk and associated outcomes.
A meta-analysis carried out in 2015 reported that in patients with or at risk for diabetes, compared with standard care, glycaemic lowering by various drugs or strategies might increase the risk of HF, with the magnitude of risk dependent on the method of glucose lowering and, potentially, weight gain.
More recently, there has been intense interest in the use of newer glucose-lowering agents such as sodium-glucose cotransporter 2 (SGLT2) inhibitors.
Early studies seemed to confirm the benefits of an SGLT2 inhibitor on outcomes including hospitalisation for HF and cardiovascular death, in patients both with and without HF at baseline.
The robustness of the HF results has later been confirmed across multiple outcomes and studies, confirming that SGLT2 inhibitors can provide robust prevention of HF in patients with diabetes, regardless of existing atherosclerotic cardiovascular disease or a history of HF.
Glucagon-like peptide 1 (GLP-1) receptor agonists and SGLT2 inhibitors have also been shown to be associated with lower mortality than dipeptidyl peptidase 4 (DPP-4) inhibitors or placebo or no treatment.
Considering the recent evidence, HF can now be considered to be preventable.
Early modification of risk factors can reduce the risk of HF, and the recommendation of appropriate medical interventions to patients with risk factors provides the earliest opportunity to reduce the impact of HF.
Indication of HF prevention for cardiovascular therapies should be prioritised and given equal or even greater weight than major adverse cardiovascular events.
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Zelniker TA, Wiviott SD, Raz I, et al. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet 2019 Jan 5;393(10166):31-9
Zheng SL, Roddick AJ, Aghar-Jaffar R, et al. Association Between use of sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 agonists, and dipeptidyl peptidase 4 inhibitors with all-cause mortality in patients with type 2 diabetes: a systematic review and meta-analysis. JAMA 2018 Apr 17;319(15):1580-91
Presenter disclosure: M.L. Handoko: AstraZeneca, Boehringer Ingelheim, Corvia Medical, Novartis, Vifor Pharma; no relationships exist relevant to the contents of this presentation. J. Buttler: Adrenomed, Amgen, Array, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CVRx, G3 Pharmaceutical, Innolife, Janssen, LinaNova, Luitpold, Medtronnic, Merck, Novartis, Relypsa, Roche, Sanofi, Vifor.
Medical writer: Patrick Moore, PhD
Reviewer: Marco Gallo, MD
Local reviewers: Marco Gallo, MD (Italia); Anna Novials Sardá, MD, PhD (España); Eric Renard, MD, PhD (France); Peter Schwarz, MD, PhD (Deutschland)