Type 2 Diabetes Mellitus and Heart Failure

Authors:
Dunlay SM, Givertz MM, Aguilar D, et al.
Citation:
Type 2 Diabetes Mellitus and Heart Failure: A Scientific Statement From the American Heart Association and the Heart Failure Society of America. Circulation 2019;Jun 6:[Epub ahead of print].

The following are key points to remember about this Scientific Statement from the American Heart Association and Heart Failure Society of America on type 2 diabetes mellitus (DM) and heart failure (HF):

  1. More than 29 million adults in the United States have noninsulin-dependent diabetes mellitus (DM), whereas 6.5 million have HF, and both conditions are expected to continue to increase in prevalence over time. In HF cohorts, including both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF), the prevalence of DM ranges from 10% to 47%. The prevalence of DM is higher in patients hospitalized with HF, with some reports of >40%. In patients with DM, the prevalence of HF is between 9% and 22%, which is 4 times higher than the general population, and the prevalence is even higher in patients with DM who are ≥60 years old.
  2. Observational studies have shown a two- to four-fold increased risk of HF in DM individuals compared with those without DM. The risk of HF is increased even with milder abnormalities in glucose regulation; for example, in one study of 18,084 people without DM at high risk for cardiovascular disease, a 1-mmol/L higher fasting plasma glucose was associated with a 1.23-fold increased risk of HF hospitalization (95% confidence interval, 1.03–1.47). Metabolic impairment is intrinsic to HF pathophysiology, and insulin resistance is present in up to 60% of patients with HF. DM can contribute to HF via systemic, myocardial, and cellular mechanisms resulting in ischemia/infarction, diabetic cardiomyopathy, impaired myocardial glucose metabolism, or left ventricular hypertrophy.
  3. Intensive glycemic control does not appear to reduce the risk of all-cause mortality, cardiovascular mortality, or stroke; however, it may reduce the risk of nonfatal myocardial infarction. The hemoglobin A1c goal should be individualized in patients with HF and DM based on the patient’s clinical/functional status (life expectancy, comorbidities, presence of complications of DM), history of hypoglycemia, self-management capacity and support system, and overall treatment burden.
  4. It is reasonable to use metformin in patients with DM at risk of or with established HF as long as estimated glomerular filtration rate (eGFR) exceeds 30 ml/min/1.73 m−2. Metformin should be discontinued in patients presenting with acute conditions associated with lactic acidosis, such as cardiogenic or distributive shock. Metformin and SGLT-2 (sodium glucose cotransporter type 2) inhibitors, are preferable to use of sulfonylurea drugs in patients at high risk for HF and those with established HF.
  5. Insulin is sometimes required to achieve adequate glycemic control in individuals with DM and HF. Insulin use is associated with weight gain and risk of hypoglycemia and should be used with caution and close monitoring. Other agents, such as metformin and SGLT-2 inhibitors, are preferred if adequate glycemic control can be achieved without insulin.
  6. Thiazolidinediones are not recommended in patients with established HF and may increase the risk of HF events in individuals with DM without HF. There is no evidence that dipeptidyl peptidase-4 (DPP-4) inhibitors provide cardiovascular benefit. In patients with DM at high cardiovascular risk, some DPP-4 inhibitors could increase the risk of HF hospitalization. On the basis of mechanistic studies, the risk-benefit balance for most DPP-4 inhibitors does not justify their use in patients with established HF or those at high risk for HF.
  7. SGLT-2 inhibitors are the first class of glucose-lowering agents demonstrated to reduce the risk of HF hospitalization in patients with DM. Cardiovascular benefits of SGLT-2 inhibitors should be balanced with their potential risks, including genital candidiasis and others, rare potential complications, such as euglycemic diabetic ketoacidosis, lower-limb amputation, and fractures (the latter two complications are only observed with canagliflozin).
  8. Management of DM and HF can be particularly challenging in patients with severely reduced renal function. In patients with eGFR <30 ml/min/1.73 m−2, insulin is safe to use but might require lower doses and frequent monitoring. Other selected agents including glimepiride, glipizide, DPP-4 inhibitors, and selected GLP-1 receptor agonists can be considered, but should be used with caution and might require dose adjustment.
  9. Given the strength of the data regarding benefits of renin-angiotensin-aldosterone system inhibitors, angiotensin receptor-neprilysin inhibitors, beta-blockers, ivabradine, and implantable cardioverter-defibrillators/cardiac resynchronization therapy in HFrEF regardless of DM status, these therapies should routinely be implemented in patients with DM and HFrEF who meet guideline indications. Because major HF trials of angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers excluded patients with severe renal dysfunction, little is known about their safety in this population.
  10. Exercise is safe and beneficial in patients with HF and DM. Patients referred to cardiac rehabilitation should be counseled on the importance of adherence to training. In patients with HFpEF and obesity, many of whom also have DM, a combined diet and exercise program can improve functional capacity.
  11. Approximately 18% of patients undergoing cardiac transplantation have DM. Approximately 30-40% of patients undergoing placement of a left ventricular assist device (LVAD) have DM. Most have demonstrated worse post-LVAD outcomes in patients with DM, including higher risk of mortality, persistently poor quality of life, and thromboembolic events. Similar to cardiac transplantation, DM with end-organ damage is a relative contraindication to durable mechanical circulatory support.
  12. Endocrinology consultation is strongly advised for patients with HF, DM, and poor glycemic control.

Perspective:

This scientific statement is an outstanding document with several clinical pearls—a must read for all clinicians managing HF in patients with type 2 DM.

Clinical Topics: Arrhythmias and Clinical EP, Cardiac Surgery, Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Prevention, Implantable Devices, SCD/Ventricular Arrhythmias, Cardiac Surgery and Arrhythmias, Cardiac Surgery and Heart Failure, Acute Heart Failure, Heart Transplant, Mechanical Circulatory Support, Diet

Keywords: Blood Glucose, Cardiac Rehabilitation, Cardiac Resynchronization Therapy, Defibrillators, Implantable, Diabetes Mellitus, Type 2, Diabetic Cardiomyopathies, Diabetic Ketoacidosis, Diet, Drug Therapy, Glomerular Filtration Rate, Heart Failure, Heart Transplantation, Heart-Assist Devices, Hypertrophy, Left Ventricular, Hypoglycemia, Insulin Resistance, Metabolic Syndrome X, Metformin, Myocardial Infarction, Obesity, Primary Prevention, Quality of Life, Risk Factors, Stroke, Stroke Volume


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