The Prognostic Significance of Diabetes and Microvascular Complications in Patients With Heart Failure With Preserved Ejection Fraction

Sandesara, Pratik B.; O’Neal, Wesley T.; Kelli, Heval Mohamed; Samman‐Tahhan, Ayman; Hammadah, Muhammad; Quyyumi, Arshed A.; Sperling, Laurence

doi:10.2337/dc17-0755

Cited by 95 publications

(64 citation statements)

References 16 publications

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“…T2D is itself associated with a number of structural abnormalities such as left ventricular hypertrophy, a common finding in HFpEF which is thought to be of pathophysiological importance . Recent studies have shown that MiVD in patients with T2D and diagnosed HFpEF is highly prevalent and associated with HF severity and worse outcome; however, ours is the first to show the independent prognostic association between MiVD and development of HFpEF. Echocardiographic studies have shown that T2D is associated with abnormalities of diastolic function independent of the presence of coronary artery disease .…”

Section: Discussionmentioning

confidence: 56%

Microvascular disease and heart failure with reduced and preserved ejection fraction in type 2 diabetes

et al. 2020

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Aims Identification of patients with type 2 diabetes (T2D) at increased risk of incident heart failure (HF) beyond traditional risk factors such as prior myocardial infarction (MI) might allow selection of patients who would benefit from preventative treatment. Microvascular disease (MiVD) is thought to play a pathophysiological role in the development of HF in T2D; however, its association with new-onset HF with reduced or preserved ejection fraction has not been specifically defined. Methods and results Patients in the Genetics of Diabetes Audit and Research Tayside Scotland study were linked to echocardiography, prescriptions, and clinical outcomes. In total, 9141 patients with T2D were identified for analysis. Clinical variables and the presence of retinopathy, nephropathy, and neuropathy were assessed. Cumulative incidence was calculated for the association of both individual and the total number of MiVD states and incident HF. Median follow-up was 9.3 years. In total, there were 900 HF events. The presence of any MiVD was independently associated with both HF with reduced ejection fraction (hazard ratio 1.40; 95% confidence interval 1.11-1.76, P = 0.004) and HF with preserved ejection fraction (hazard ratio 1.38; 95% confidence interval 1.10-1.72, P = 0.005), with a stepwise association between the number of MiVD states and risk of incident HF (P for trend <0.001). Similar associations were found in sensitivity analyses limited to patients without a prior MI, and using competing risks analysis. Conclusions Individuals with T2D and with MiVD are at risk of incident HF independent of a history of prior HF or MI. Patients with MiVD could benefit from screening for HF and individualized therapy with treatments that lower HF risk.

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Section: Discussionmentioning

confidence: 56%

Microvascular disease and heart failure with reduced and preserved ejection fraction in type 2 diabetes

et al. 2020

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“…Of more interest is a recent study in patients with heart failure and preserved ejection fraction (HFpEF). In the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial (TOPCAT), 32% of patients were reported to have a microvascular complication (neuropathy in 21%, retinopathy in 15% and nephropathy in 11% of participants with diabetes) . Patients in TOPCAT were on average approximately 7 years older than participants in the present study and a similar proportion in the two trials were treated with insulin (38% in TOPCAT vs. 41% in BEST).…”

Section: Discussionmentioning

confidence: 59%

Microvascular complications in diabetes patients with heart failure and reduced ejection fraction—insights from the Beta‐blocker Evaluation of Survival Trial

Kristensen

Rørth

Jhund

et al. 2018

European J of Heart Fail

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“…In addition to worse patient‐reported outcomes, individuals with diabetes, especially those treated with insulin, had worse clinical outcomes compared to patients without diabetes. Although a few studies have examined outcomes in HFpEF patients according to diabetes status, individually they have been too small to compare insulin‐treated patients to those not receiving insulin, could not adjust for all other important prognostic markers (particularly natriuretic peptides), or had both limitations . We found that, even after adjustment for NT‐proBNP and other key prognostic variables, use of insulin to treat diabetes was associated with around a doubling in risks for the composite of HF hospitalization or CV death, its individual components, and all‐cause mortality, and a 50% higher risk of these outcomes when other glucose‐lowering therapies were employed.…”

Section: Discussionmentioning

confidence: 83%

Insulin treatment and clinical outcomes in patients with diabetes and heart failure with preserved ejection fraction

Shen

Rørth

Cosmi³

et al. 2019

European J of Heart Fail

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Aims Insulin causes sodium retention and hypoglycaemia and its use is associated with worse outcomes in heart failure (HF) with reduced ejection fraction. We have investigated whether this is also the case in HF with preserved ejection fraction (HFpEF). Methods and results We examined the association between diabetes/diabetes treatments and the risk of the primary composite of cardiovascular death or HF hospitalization, as well as other outcomes in adjusted analyses in CHARM‐Preserved (left ventricular ejection fraction ≥ 45%), I‐Preserve and TOPCAT (Americas) pooled. Of 8466 patients, 2653 (31%) had diabetes, including 979 (37%) receiving insulin. Patients receiving insulin were younger, had a higher body mass index, prevalence of ischaemic aetiology, N‐terminal pro‐B‐type natriuretic peptide and use of diuretics, worse New York Heart Association class and signs and symptoms, and worse quality of life and renal function, compared to patients with diabetes not on insulin. Among the 1398 patients with echocardiographic data, insulin use was associated with higher left ventricular end‐diastolic pressure and more diastolic dysfunction than in other participants. The primary outcome occurred at a rate of 6.3 per 100 patient‐years in patients without diabetes, and 10.2 and 17.1 per 100 patient‐years in diabetes patients without and with insulin use, respectively [fully adjusted hazard ratio (aHR) insulin‐treated diabetes vs. other diabetes: 1.41, 95% confidence interval (CI) 1.23–1.63, P < 0.001]. The adjusted HR is 1.67 (95% CI 1.20–2.32, p = 0.002) for sudden death (insulin‐treated diabetes vs. other diabetes). Conclusions Insulin use is associated with poor outcomes in HFpEF. Although we cannot conclude a causal association, the safety of insulin and alternative glucose‐lowering treatments in HF needs to be evaluated in clinical trials.

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The Prognostic Significance of Diabetes and Microvascular Complications in Patients With Heart Failure With Preserved Ejection Fraction

Abstract: Diabetes is associated with adverse cardiovascular outcomes in HFpEF, and the inherent risk of adverse outcomes in HFpEF patients with diabetes varies by the presence of microvascular complications.

Cited by 95 publications

References 16 publications

Microvascular disease and heart failure with reduced and preserved ejection fraction in type 2 diabetes

Microvascular disease and heart failure with reduced and preserved ejection fraction in type 2 diabetes

Microvascular complications in diabetes patients with heart failure and reduced ejection fraction—insights from the Beta‐blocker Evaluation of Survival Trial

Insulin treatment and clinical outcomes in patients with diabetes and heart failure with preserved ejection fraction

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