Study suggests global longitudinal strain is a powerful independent predictor of adverse outcomes in patients with heart failure and diabetes

Most heart failure (HF) cases in recent history have been recorded in the Asian continent. Based on the Asian Sudden Cardiac Death in Heart Failure (ASIAN-HF) records, about 43% of individuals who suffered from HF had diabetes. Interestingly, this prevalence was found to be higher in higher-income countries, such as Hong Kong, Thailand, and Singapore. 

The Global longitudinal strain (GLS) is a simple parameter associated with myocardial deformation analysis. Although plasma concentrations of specific biomarkers like such as soluble ST2 (sST2), growth differentiation factor-15 (GDF-15), and galectin 3 (Gal-3) provide prognostic information in HF patients, their prognostic relevance in HF patients with diabetes has not been established.

Study: Global longitudinal strain ahttps://www.medrxiv.org/content/10.1101/2023.03.20.23287472v2nd plasma biomarkers for prognosis in heart failure complicated by diabetes. Image Credit: mi_viri / Shutterstock.com

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

A recent study posted on the medRxiv* preprint server investigates the prognostic significance of GLS by cardiac magnetic resonance (CMR) and identifies several novel HF plasma biomarkers linked with fibrosis and inflammation in individuals with HF and diabetes.

Background

Several structural abnormalities, such as myocyte hypertrophy, diffuse interstitial myocardial fibrosis, and impaired coronary microvascular perfusion, have been associated with diabetic hearts, as well as diastolic and systolic dysfunction. Diabetes complicates the prognosis of HF and leads to worse clinical outcomes.

CMR imaging is used to determine HF due to its capacity to assess myocardial tissue characteristics, cardiac morphology, and function. In the context of CMR, technicians often use late gadolinium enhancement (LGE) to visualize myocardial fibrosis. T1 mapping pre- and postgadolinium contrast is used to measure myocardial extracellular volume fraction (ECV), which is a biomarker of myocardial diffuse interstitial fibrosis.

GLS refers to changes in the left ventricle (LV) myocardial length between diastole and systole divided by the original end-diastolic length. The quantitative measure of LV systolic function provided by CMR resembles GLS measured by echocardiography.

Many individuals with diabetes exhibit impaired GLS and higher myocardial fibrosis, the latter of which is determined based on ECV and histology. GLS by CMR offers prognostic value in HF, irrespective of whether the cause of HF was ischemic or nonischemic.

Although several studies have established the prognostic value of GLS in asymptomatic patients with diabetes, there remains a lack of studies on the prognostic utility of GLS in diabetes patients with confirmed HF.

About the study

The current study hypothesized that GLS has an incremental prognostic association in HF patients with diabetes that is beyond plasma HF biomarkers, CMR markers of myocardial fibrosis, and LV ejection fraction.

Patients diagnosed with HF were recruited from six tertiary cardiac centers in Singapore. However, those with severe valve disease, acute coronary syndrome, acute pulmonary edema, and renal disease were excluded from the study.

Blood samples were collected to analyze plasma biomarker levels. The primary outcomes included the time of either first hospitalization for HF or all-cause mortality. CMR imaging data of all participants were assessed using CVI42 software.

Study findings

A total of 315 patients, which included 159 diabetics and 156 non-diabetics, fulfilled all study criteria and were included in this study. Notably, patients with diabetes were older and were more likely to have a history of hypertension, coronary artery disease, and worse NYHA Functional Class as compared to patients without diabetes. 

Diabetic patients had higher creatinine levels and elevated cardiac biomarkers, N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin T(hs-TnT), GDF-15, sST2, and Gal-3. Both groups exhibited similar LV ejection fraction and GLS. Although a higher prevalence of LGE was observed in the diabetic group with a higher rate of ischemic LGE, both groups exhibited a similar prevalence of non-ischemic LGE.

Diabetes patients were associated with a higher native time to inversion (TI), which reflects interstitial expansion due to myocardial fibrosis or myocardial edema impacting the cellular and interstitial compartments.

HF patients with diabetes exhibited worse CMR markers of myocardial injury, fibrosis, and inflammation. After adjusting for confounding factors like sex, age, coronary artery disease, and hypertension, diabetes was independently associated with increased ECV and LGE.

Over the follow-up period of 23 months, 74 patients, irrespective of the groups, experienced the primary outcome of hospitalization due to HF and all cause death. Of these 75 patients, 50 patients were diabetics. Circulating biomarkers that were associated with the primary outcome included GDF-15, NT-proBNP, sST2, and Gal-3.

Conclusions

Patients with diabetes had worse CMR and plasma markers of inflammation, injury, and fibrosis, which indicated an adverse prognosis. In HF patients with diabetes, GDF-15 and sST2 revealed incremental prognostic value beyond NT-proBNP. GLS was identified to be an independent and vital prognostic marker for HF patients with diabetes.

In the future, more research is needed to determine whether GLS-guided risk stratification and management can improve the clinical outcomes of these patients.

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Dr. Priyom Bose

Priyom holds a Ph.D. in Plant Biology and Biotechnology from the University of Madras, India. She is an active researcher and an experienced science writer. Priyom has also co-authored several original research articles that have been published in reputed peer-reviewed journals. She is also an avid reader and an amateur photographer.