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Researchers find new GLIS model outperforms existing tests in identifying frailty and mortality risk in older adults with heart failure

As populations age worldwide, heart failure and sarcopenia—the loss of muscle mass and strength—pose growing risks to older adults. Existing diagnostic criteria for sarcopenia are inconsistent and may miss high-risk patients. Researchers from Japan analyzed older patients with heart failure in the FRAGILE-HF study and found that the new Global Leadership Initiative on Sarcopenia (GLIS) model identified impaired physical performance and predicted two-year all-cause mortality more accurately than the widely used AWGS2019 criteria.

Image title: GLIS Model Predicts Sarcopenia and Outcomes in Older Patients with Heart Failure

Image caption: Validation of the Global Leadership Initiative on Sarcopenia (GLIS) model in 891 older patients with heart failure shows strong links between sarcopenia, impaired physical performance, and higher two-year mortality, outperforming conventional AWGS2019 criteria. Early identification using GLIS may guide tailored rehabilitation and improve prognosis.

Image credit: Dr. Taisuke Nakade from Juntendo University Graduate School of Medicine, Tokyo, Japan

License type: Original content

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With populations aging rapidly worldwide, heart failure has become one of the most pressing medical and social challenges. Older patients face not only a high mortality risk but also losses in muscle strength, mobility, and independence. Clinicians frequently see people who, despite optimal cardiac care, still struggle with frailty and declining physical performance. Until now, different groups have proposed their own criteria: the AWGS criteria developed mainly by Asian experts, the EWGSOP criteria from Europe, and the SDOC statement from the United States. As a result, three different definitions and diagnostic methods have coexisted, creating a lack of consistency worldwide. Recognizing the need for a global standard, leading experts from these groups came together to form the Global Leadership Initiative on Sarcopenia (GLIS). The GLIS model introduced a new diagnostic approach based on muscle strength, muscle mass, and muscle-specific strength, while reclassifying physical performance tests such as the Short Physical Performance Battery (SPPB) not as diagnostic criteria but as outcomes of sarcopenia. However, it had remained unclear whether this new GLIS model could reliably predict prognosis in older patients with heart failure, or whether it truly reflects declines in physical performance.

Researchers from Juntendo University, Japan, led by Dr. Taisuke Nakade, together with Dr. Daichi Maeda, Dr. Yuya Matsue, Dr. Tohru Minamino, and colleagues from multiple hospitals and universities across Japan, have offered a solution to this puzzle. Their study, published in the European Journal of Preventive Cardiology on October 4, 2025, provides the first worldwide validation of the new GLIS model in older patients with heart failure.

“Our inspiration was to test whether this new model truly reflects what clinicians observe at the bedside—namely, functional decline and poor prognosis in older patients with heart failure—and to generate evidence that could influence both practice and international guidelines,” Dr. Nakade explains.

The GLIS model focuses on three core measures—muscle mass, grip strength, and muscle-specific strength—while treating walking speed and other functional tests as outcomes, thus separating diagnosis from performance. The study analyzed 891 patients aged 65 or older from the FRAGILE-HF registry, classifying them as non-sarcopenic, possible sarcopenic, or sarcopenic. Physical performance was assessed using walking speed, the five-chair stand test, the SPPB, and the six-minute walk test. Patients with sarcopenia or possible sarcopenia showed significantly worse performance across all measures.

Importantly, the GLIS model accurately identified patients with decreased physical performance. Over two years, mortality increased stepwise from non-sarcopenic to possible sarcopenic to sarcopenic patients. Even after adjusting for other risk factors, GLIS-defined sarcopenia was independently associated with a 3.4-fold higher risk of death. Compared to the conventional AWGS2019 criteria, GLIS provided superior risk reclassification, making it a more powerful tool for clinical decision-making.

The implications are clear. By diagnosing sarcopenia more accurately, clinicians can better identify those at high risk of physical decline and poor outcomes, even before symptoms become severe. The model also strengthens treatment planning, discharge decisions, and long-term care strategies. At a broader level, validating GLIS supports international standardization of sarcopenia diagnosis, promoting equitable care and paving the way for new diagnostic tools, screening devices, and digital health applications.

As Dr. Nakade emphasizes, “This study showed that the newly proposed international GLIS model for sarcopenia effectively reflects both impaired physical performance and poor prognosis in older patients with heart failure.”

In short, the GLIS model gives doctors a practical, evidence-based approach to detect sarcopenia early, improve patient outcomes, and address one of the most urgent challenges in aging societies.

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About Dr. Taisuke Nakade from Juntendo University

Dr. Taisuke Nakade is a Doctor of Medicine in the Department of Cardiovascular Biology and Medicine at the Juntendo University Graduate School of Medicine, Japan. He specializes in cardiology and geriatric medicine, with a focus on heart failure, sarcopenia, and frailty in older adults. His research also explores exercise-based cardiac rehabilitation, and he has published more than 15 articles in these areas. Dr. Nakade actively collaborates with multidisciplinary teams and is a member of leading professional societies, including the European Society of Cardiology (ESC) and its Heart Failure Association (HFA).