Noncardiac Comorbidities in Heart Failure With Reduced Versus Preserved Ejection Fraction | Ten Points to Remember

Mentz RJ, Kelly JP, von Lueder TG, et al.
J Am Coll Cardiol 2014;64:2281-2293.
Study Question: What are the comorbidities associated with heart failure with preserved ejection fraction (HFpEF) versus heart failure with reduced ejection fraction (HFrEF)?
This review is based on discussions between scientists, clinical trialists, and regulatory and industry representatives at the 10th Global CardioVascular Clinical Trialists Forum in Paris, France on December 6, 2013.

The following are 10 points to remember:

1. Patients hospitalized with HFpEF tend to be 4-8 years older than those with HFrEF, and are more often female.

2. Overall, HFpEF is associated with morbidity and mortality that is similar to that of HFrEF.

3. Chronic obstructive pulmonary disease (COPD) has been identified to cause a proinflammatory substrate that causes endothelial and cardiomyocyte dysfunction, which can lead to myocardial fibrosis in HFpEF. In a recent study that was reviewed, COPD was an independent predictor of mortality in both groups.

4. Anemia is more frequent in HFpEF patients than in HFrEF patients, and the prevalence tends to be higher in women. The optimal treatment of anemia in HF patients requires further studies.

5. Diabetes mellitus leads to myocardial changes that result from insulin resistance and hyperglycemia through increased fatty acid concentration, mitochondrial dysfunction, abnormal calcium homeostasis, renin-angiotensin-aldosterone system activation, oxidative stress, and advanced glycation endproducts.

6. Renal dysfunction is prevalent in both HFrEF and HFpEF with an increased risk associated with comorbidity in both patient groups.

7. HFpEF patients tend to have more obstructive sleep apnea and HFrEF patients tend to have more central sleep apnea, whereas men in both groups are more likely to have sleep disordered breathing. The long-term impact of these disorders on HF is not well defined yet.

8. The obesity paradox exists in HF of both types; a high weight may be better associated with improved outcomes in HF patients compared to cardiac cachexia; however, its association with metabolic syndrome and glucose intolerance has been shown to be related to adverse events.

9. Frailty and arthritis have been shown to be associated with adverse outcomes in HF. Further research on depression, myopathy, and liver disease is needed to assess outcomes in both types of HF.

10. An emerging topic of research will be polypharmacy in HFpEF versus HFrEF.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Prevention, Lipid Metabolism, Acute Heart Failure, Stress, Sleep Apnea

Keywords: Anemia, Arthritis, Cachexia, Calcium, Comorbidity, Diabetes Mellitus, Fatty Acids, France, Glucose Intolerance, Heart Failure, Insulin Resistance, Metabolic Syndrome X, Obesity, Oxidative Stress, Paris, Pulmonary Disease, Chronic Obstructive, Renin-Angiotensin System, Sleep Apnea, Central, Sleep Apnea, Obstructive

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