Findings published in Biological Psychiatry point to new therapeutic pathways to protect this at-risk population from heart failure and improve life expectancy

Philadelphia, August 19, 2025 – Cardiovascular disease is the leading cause of premature deaths in patients with bipolar disorder worldwide. In a novel study in young adults (aged 20-45) with bipolar disorder researchers were able to detect subtle (subclinical) abnormalities in how their heart muscle functions and pumps blood before the onset of heart failure by measuring peak systolic strain and myocardial work. The findings in Biological Psychiatry, published by Elsevier, point to new avenues for therapeutic development aimed at preventing progression to heart failure in this at-risk population.

Despite accumulating evidence that cardiovascular disease risk increases during the early stages of bipolar disorder, few studies have investigated cardiac dysfunction in the early course of the illness. This study is the first to uncover that myocardial dysfunction is already evident in patients with bipolar disorder under 45 years of age before the onset of heart failure, suggesting a possible link to underlying coronary vascular dysfunction.

By using indicators sensitive to early detection of subclinical cardiac dysfunction before the onset of heart failure, this study showed that both global and regional peak systolic strain (measuring how much the heart muscle deforms or shortens during a contraction [systole]) and myocardial work (assessing the total work the heart muscle does to pump blood, taking into account both how much it contracts and the pressure it has to pump against) were impaired across left ventricular segments in young adults with bipolar disorder compared to individuals of similar age without psychiatric disorders.

Because the investigators measured regional peak systolic strain and regional myocardial work in accordance with the American Heart Association (AHA) 17-segment model based on the perfusion territories, specific areas of heart muscle supplied with blood by each of the main coronary arteries (i.e., the left anterior descending, left circumflex, and right coronary arteries), the findings of this study suggest an impaired cardiac function in relation to aberrant coronary vascular perfusion in the early course of bipolar disorder.

“Because no study has previously evaluated regional peak systolic strain and regional myocardial work in patients with bipolar disorder using the AHA 17-segment model, this hypothesis-generating study was designed to identify patterns and formulate potential hypotheses for further investigation into the heart–bipolar disorder link,” explains lead investigator Pao-Huan Chen, MD, PhD, Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University; and Department of Psychiatry, and Psychiatric Research Center, Taipei Medical University Hospital.

First author Cheng-Yi Hsiao, MD, Division of Cardiology, Department of Internal Medicine, and Cardiovascular Research Center, Taipei Medical University Hospital; and Taipei Heart Institute and School of Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, adds. “Although there is much evidence suggesting elevated cardiovascular risk in individuals with bipolar disorder, we are still surprised by the findings that even in this young population with bipolar disorder, the myocardial dysfunction extensively involves the left ventricular segments across the perfusion territories of the three major coronary arteries.”

Bipolar disorder is a severe mental illness that often manifests during adolescence and young adulthood. Population-based cohort studies and large-scale meta-analyses have revealed that in addition to experiencing the lifelong burden of mood symptoms, patients are at an approximately two-fold higher risk of heart failure, which is one of the main causes of premature cardiovascular mortality in patients with bipolar disorder.

To clarify the pathophysiology of heart failure in patients with bipolar disorder, future studies should explore the mechanistic pathways leading to coronary vascular dysfunction in this population.

“Following replication in future studies across different samples, the peak systolic strain and myocardial work indices should be incorporated into the cardiovascular assessment for patients with bipolar disorder. This assessment would provide an opportunity to identify and manage cardiac dysfunction as early as possible before the progression of heart failure, while laying a strong foundation for the development of new therapeutics to avoid heart failure and improve life expectancy,” advises Dr. Chen.

John Krystal, MD, Editor of Biological Psychiatry, comments, “Individuals with bipolar disorder have reduced life expectancy relative to the general population by nine to 20 years, and some of this risk may be related to increased risk for cardiovascular disease. This study raises important questions about this risk and potential genetic links between bipolar disorder and cardiac disease, the cardiac impact of psychotropic medications and other environmental factors like diet, exercise, stress, and substance use. It will also be important to understand why women were affected to a greater extent than men."