The early recognition of incipient heart failure with preserved left ventricular function in diabetic patients

Background and relevance

The prevalence of heart failure (HF) in the Netherlands is rising to over 240,000 people; 6% of people aged >65 have HF. Approximately 50% has HF with preserved ejection fraction (HFpEF). HFpEF is particularly common in people with type 2 diabetes (T2D). Previous studies show that HFpEF and its precursor (diastolic dysfunction; DD) occur in approximately 19% and 42% of people with T2D. Moreover, the presence of T2D increases mortality risk of patients with HFpEF by 30%-50%.

Problem definition and objectives

Little is known about the course of early recognized DD and HFpEF. Earlier detection and treatment might give a better prognosis. Moreover, the causes of DD/HFpEF differ; it might be useful to tailor treatment to individual risk factors by better characterizing DD/HFpEF patients. This requires timely identification of people with T2D with increased risk of DD/HFpEF and to study possibly associated phenotypes.

The aim of this study is to investigate

  1. which risk factors can be identified for earlier recognition of DD/HFpEF-risk in people with T2D
  2. if subgroups of DD/HFpEF can be distinguished to which (preventive) treatment could be tailored
  3. if subgroups and stages of DD/HFpEF are associated with quality of life and health care utilization.

This project aims to provide general practitioners (GPs) with the means to recognize DD/HFpEF at an earlier stage and to offer potential options for more personalized treatment based on risk profiles to improve the outlook for people with DD/HFpEF.

Action plan and research design

The proposed project is an observational cohort study with a retrospective, cross-sectional and prospective component. Between 2019 and 2022, an echocardiogram was made in 850 people with T2D without known HF in the Diabetes Care System (DCS) cohort. We combine the DCS data of this group with the 'DIAMANT data infrastructure'. DIAMANT collects information from GP files of ±400,000 people with T2D and can link this with data from hospitals and pharmacies.

For aim 1 we will use retrospective data from DCS (since 1996) to construct a multivariate prediction model with the echo outcome measures (normal diastolic function, mild DD, HFpEF) in order establish DD/HFpEF risk factors with which these patients might be identified at an earlier phase. Available measurements include clinical variables (diabetes duration, co-morbidities, medication use), measurements (BMI, HbA1c, fasting glucose, lipids, blood pressure, renal function, NT-proBNP) and ECG parameters.

For aim 2 we shall perform hierarchical clustering to group patients and phenotype variables, to then determine the association between phenotype groups and outcome using multivariable Cox proportional risk models.

In the prospective analysis (aim 3), we will associate echocardiographic measurements with medication use, morbidity, hospital admissions and quality of life as outcomes over a 3-year follow-up period. We will take age and sex into account in our analyses. The number of people with a background other than native Dutch is very limited (± 2%), conclusions can only be drawn for a native Dutch population.

Intended results and impact

The theoretical rationale for this approach is that once we can distinguish phenotype subgroups, we can investigate whether treatment in early stages of HFpEF is meaningful and can be personalized. For example, if overweight and physical limitations are the main cause in a certain subgroup of patients, weight loss, exercise training, metformin and an SGLT2 inhibitor might be useful. On the other hand, if atrial fibrillation and left atrial myopathy are the main cause of (early) HFpEF, early use of antiarrhythmic drugs or surgery (ablation) might be helpful. At the end of the study, in consultation with a medical decision expert, we will propose a subgroup typification for the purpose of personalizing (research into) treatment options.

Features

Project number:
10060012210008
Duration: 49%
Duration: 49 %
2024
2026
Project lead and secretary:
dr. M.T. Blom
Responsible organisation:
Amsterdam UMC Locatie AMC
Afbeelding

General Practitioner care

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