Epidemiology of heart failure in diabetes: a disease in disguise

Abstract

Left ventricular diastolic dysfunction (LVDD) without symptoms, and heart failure (HF) with preserved ejection fraction (HFpEF) represent the most common phenotypes of HF in individuals with type 2 diabetes mellitus, and are more common than HF with reduced ejection fraction (HFrEF), HF with mildly reduced ejection fraction (HFmrEF) and left ventricular systolic dysfunction (LVSD) in these individuals. However, diagnostic criteria for HF have changed over the years, resulting in heterogeneity in the prevalence/incidence rates reported in different studies. We aimed to give an overview of the diagnosis and epidemiology of HF in type 2 diabetes, using both a narrative and systematic review approach; we focus narratively on diagnosing (using the 2021 European Society of Cardiology [ESC] guidelines) and screening for HF in type 2 diabetes. We performed an updated (2016-October 2022) systematic review and meta-analysis of studies reporting the prevalence and incidence of HF subtypes in adults ≥18 years with type 2 diabetes, using echocardiographic data. Embase and MEDLINE databases were searched and data were assessed using random-effects meta-analyses, with findings presented as forest plots. From the 5015 studies found, 209 were screened using the full-text article. In total, 57 studies were included, together with 29 studies that were identified in a prior meta-analysis; these studies reported on the prevalence of LVSD (n=25 studies, 24,460 individuals), LVDD (n=65 studies, 25,729 individuals), HFrEF (n=4 studies, 4090 individuals), HFmrEF (n=2 studies, 2442 individuals) and/or HFpEF (n=8 studies, 5292 individuals), and on HF incidence (n=7 studies, 17,935 individuals). Using Hoy et al's risk-of-bias tool, we found that the studies included generally had a high risk of bias. They showed a prevalence of 43% (95% CI 37%, 50%) for LVDD, 17% (95% CI 7%, 35%) for HFpEF, 6% (95% CI 3%, 10%) for LVSD, 7% (95% CI 3%, 15%) for HFrEF, and 12% (95% CI 7%, 22%) for HFmrEF. For LVDD, grade I was found to be most prevalent. Additionally, we reported a higher incidence rate of HFpEF (7% [95% CI 4%, 11%]) than HFrEF 4% [95% CI 3%, 7%]). The evidence is limited by the heterogeneity of the diagnostic criteria over the years. The systematic section of this review provides new insights on the prevalence/incidence of HF in type 2 diabetes, unveiling a large pre-clinical target group with LVDD/HFpEF in which disease progression could be halted by early recognition and treatment.Registration PROSPERO ID CRD42022368035.

Keywords: Clinical research; Diabetes; Heart failure, diastolic; Heart failure, systolic; Lifestyle; Meta-analysis; Review; Systematic review.

Fig. 1

Schematic overview of diagnostic pathway for HF in people with type 2 diabetes, based on the 2021 ESC guidelines for the diagnosis and treatment of HF. HF can be categorised as HFrEF, HFmrEF or HFpEF. The diagnosis of HF requires the presence of cardinal symptoms (ia) and, occasionally, signs (ib). Supporting investigations (ii) include ECG, risk factor assessment (risk factors include medical history of cardiovascular events, older age [>70 years], sex and obesity) and analysis of NP levels (note that in individuals with atrial fibrillation [AF], diagnostic values are ≥365 pg/ml N-terminal pro–B-type NP [NT-proBNP] and ≥105 pg/ml brain NP [BNP]). Echocardiography (iii) allows for differentiation into different categories of HF. A reduced LVEF is needed to diagnose HFrEF and HFmrEF (≤40% for HFrEF and 41–49% for HFmrEF), and a preserved LVEF (≥50%) combined with echocardiographic functional and/or structural abnormalities and/or serological abnormalities is required for the diagnosis of HFpEF. Secondary diagnostic tests may include use of diagnostic algorithms, which are non-invasive. More invasive tests (e.g., exercise echocardiography, [exercise] right heart catheterisation and/or pulmonary artery wedge pressure) may be used if HF is suspected despite normal results for tests of echocardiographic functional and/or structural abnormalities and serological abnormalities, and if other comorbidities do not sufficiently explain symptoms/signs. F, female; M, male; SR, sinus rhythm. This figure is available as part of a downloadable slideset

Fig. 2

PRISMA flow chart showing the process for selection of relevant articles included in the systematic review and meta-analysis. This figure is available as part of a downloadable slideset

Fig. 3

Prevalence of LVSD in individuals with type 2 diabetes in the hospital and general population, categorised by new studies included in this updated meta-analysis and studies in the original meta-analysis by Bouthoorn et al. The combined prevalence of our and Bouthoorn et al’s meta-analyses is shown in bold black font. This figure is available as part of a downloadable slideset

Fig. 4

Prevalence of (a) HFmrEF and (b) HFrEF in individuals with type 2 diabetes in the hospital and general population. For HFrEF results are categorised by new studies included in this updated meta-analysis and studies in the original meta-analysis by Bouthoorn et al. The combined prevalence of our and Bouthoorn et al’s meta-analyses is shown in bold black font. NA, not applicable. This figure is available as part of a downloadable slideset

Fig. 5

Prevalence of LVDD in individuals with type 2 diabetes in the hospital population, general population and in populations that were not specified. Outcomes are categorised by new studies included in this updated meta-analysis and studies in the original meta-analysis by Bouthoorn et al. The combined prevalence of our and Bouthoorn et al’s meta-analyses is shown in bold black font. This figure is available as part of a downloadable slideset

Fig. 6

Prevalence of LVDD in individuals with type 2 diabetes in the hospital, general population and in populations that were not specified, categorised as (a) grade I, (b) grade II and (c) grade III based on ASE/EACVI recommendations. This figure is available as part of a downloadable slideset

Fig. 7

Prevalence of LVDD in individuals with type 2 diabetes in the hospital and general population, categorised as (a) indeterminate or (b) definitive based on ASE/EACVI recommendations. This figure is available as part of a downloadable slideset

Fig. 8

Prevalence of HFpEF in individuals with type 2 diabetes in the hospital and general population. Results are categorised by new studies included in this updated meta-analysis and studies in the original meta-analysis by Bouthoorn et al. The combined prevalence of our and Bouthoorn et al’s meta-analyses is shown in bold black font. This figure is available as part of a downloadable slideset

Fig. 9

Incidence of (a) HFpEF and (b) HFrEF in individuals with type 2 diabetes in the hospital population, general population and in populations that were not specified. This figure is available as part of a downloadable slideset