Type 2 diabetes mellitus (T2DM) and heart failure

Diabetes mellitus and heart failure

• diabetes mellitus is highly prevalent amongst patients with heart failure, especially those with heart failure and preserved ejection fraction (HFpEF), and patients with the two conditions have a higher risk of mortality compared with patients without diabetes or heart failure (1)
• the Framingham study estimated that men and women with DM have a two and four times, respectively, increased risk to develop HF compared with non-DM subjects (2)
• the pathophysiological mechanism for development of HF in T2DM is complex but may be related to abnormal cardiac handling of glucose and free fatty acids (FFAs), and because of the effect of the metabolic derangements of diabetes on the cardiovascular system
• epidemiological studies have confirmed this relationship and revealed that impaired glucose tolerance, increased serum glucose levels and glycated haemoglobin levels are associated not only with incidence of systolic HF but also with the prevalence of diastolic dysfunction - DM and metabolic syndrome are risk factors for HF (3)
  
  
• Characteristics of HF in T2DM:
  • myocardial dysfunction in T2DM usually is progressive with an early asymptomatic phase where the heart hypertrophies, leading to diastolic dysfunction in the setting of preserved LV ejection fraction (LVEF) (4)
    • followed by a late stage, which is characterized by alteration in microvasculature compliance, an increase in left ventricular size, and a decrease in cardiac performance leading to symptomatic HF
    • predictors for progression to late stage, which may take several years, include comorbidities often seen in T2DM such as CAD, hypertension, obesity, and microvascular changes
      
      
• the term diabetic cardiomyopathy was used to define either systolic or diastolic left ventricular dysfunction in otherwise healthy diabetic persons in the absence of clinically significant coronary, valvular or hypertensive disease (5)
• DM can be categorised in the stage A of the American College of Cardiology Foundation (ACCF)/American Heart Association (AHA) classification of HF, meaning that diabetic subjects are at high-risk for HF but without structural heart disease or symptoms of HF
  
  
• Clinical and Epidemiological Connections
  • DM predicts readmissions of HF patients (6)
  • DM increases mortality in subjects with left ventricular dysfunction (7)
  • in Type 2 DM, glycated haemoglobin significantly predicts future HF hospitalisation independently of baseline b-type natriuretic peptide (BNP) level or echocardiographic parameters (8)

Prediction of Incident Heart Failure in Pre-Diabetes and Diabetes (9)

• there is evidence of the effectiveness of a test based on 4 cardiac and inflammatory biomarkers in prediction of possible development of heart failure
  • an integer-based risk score: hs-cTnT>=6 ng/l; NT-proBNP>=125 pg/ml, hs-CRP>=3 mg/l, and left ventricular hypertrophy by ECG, with 1 point for each abnormal biomarker
• study results showed that:
  • 5-year risk of HF among subjects with a biomarker score of <= was low and comparable to participants with euglycemia (0.78%)
  • 5-year risk for HF increased in a graded fashion with an increasing biomarker score, with the highest risk noted among those with scores of >=3 (diabetes: 12.0%; pre-diabetes: 7.8%)
  • estimated number of HF events that could be prevented using a sodium-glucose cotransporter-2 inhibitor per 1,000 treated subjects over 5 years was 11 for all subjects with diabetes and ranged from 4 in the biomarker score zero group to 44 in the biomarker score >=3 group

Relationship between microvascular disease (MVD) with incident HF in individuals with T2DM

• evidence from the Look AHEAD (Action of Health in Diabetes) study showed MVD was associated with an elevated risk of developing HF in adults with T2DM. This association was independent of traditional risk factors, including CAD (10)

Reference:

• MacDonald MR, Petrie MC, Varyani F, et al. Impact of diabetes on outcomes in patients with low and preserved ejection fraction heart failure: an analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme. Eur Heart J 2008;29:1377–85.
• Kannel WB, Hjortland M, Castelli WP, Role of diabetes in congestive heart failure: the Framingham study, Am J Cardiol, 1974;34:29–34.
• Yancy CW, Jessup M, Bozkurt B, et al., 2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines, Circulation, 2013;128:1810–52.
• Ofstad AP et al. The heart failure burden of type 2 diabetes mellitus-a review of pathophysiology and interventions. Heart Fail Rev. 2018; 23(3): 303–323.
• Rutter MK, Parise H, Benjamin EJ, et al., Impact of glucose intolerance and insulin resistance on cardiac structure and function: sex-related differences in the Framingham Heart Study, Circulation, 2003;107:448–54.
• Krumholz HM, Chen YT, Wang Y, et al., Predictors of readmission among elderly survivors of admission with heart failure, Am Heart J, 2000;139:72–7.
• Shindler DM, Kostis JB, Yusuf S, et al., Diabetes mellitus, a predictor of morbidity and mortality in the Studies of Left Ventricular Dysfunction (SOLVD) Trials and Registry, Am J Cardiol, 1996;77:1017–20.
• Kishimoto I, Makino H, Ohata Y, et al., Hemoglobin A1c predicts heart failure hospitalization independent of baseline cardiac function or B-type natriuretic peptide level, Diabetes Res Clin Pract, 2014;104(2):257–65.
• Pandey A, Vaduganathan M, Patelet KV et al. Biomarker-Based Risk Prediction of Incident Heart Failure in Pre-Diabetes and Diabetes. JACC Heart Fail. 2020 Dec 24;S2213-1779(20)30591-6. doi: 10.1016/j.jchf.2020.10.013
• Kaze AD, Santhanam P, Erqou S, et al. Microvascular Disease and Incident Heart Failure Among Individuals With Type 2 Diabetes Mellitus J Am Heart Assoc. 2021;10:e018998. doi: 10.1161/JAHA.120.018998.