National Institute of Health

Researchers examine association between protein misfolding and abnormal heart function

Light chain amyloidosis can damage multiple organs, including the heart. This can manifest as decreased left ventricular global longitudinal strain (LV GLS), a form of cardiac malfunction. In a new study, Samsung Medical Center researchers found a modest-yet-significant association between cardiac amyloid loads and LV GLS. In doing so, they established that LV GLS may be a useful biomarker to refine clinical risk stratification in cardiac amyloidosis.

Researchers from Samsung Medical Center, South Korea, examined and established a distinct correlation between light chain amyloidosis and left ventricular global longitudinal strain, a type of cardiac anomaly, suggesting that the latter may bestow additive prognostic value to the present risk stratification system of amyloidosis. The image shows amyloids in tissue samples from the heart of a patient with left ventricular global longitudinal strain.

Image courtesy: Eun-Seok Jeon, Samsung Medical Center

Proteins are necessary for our survival. However, the proper functioning of important proteins like enzymes and antibodies hinges on their accuracy of their structures. Misfolded proteins are highly problematic and can give rise to several serious diseases—Parkinson’s disease, Alzheimer’s disease, and Huntington’s disease, to name a few. These abnormal proteins can deposit in any organ in the form of aggregates known as “amyloid fibrils,” in process called amyloidosis.

In a recent study, biomedical researchers at Samsung Medical Center, South Korea, recently examined the likely association between cardiac amyloid loads and decreased left ventricular global longitudinal strain (LV GLS). Their findings were recently published in JACC: Cardiovascular Imaging. The study was supported by a fund (code: 2019ER690200) by Research of Korea Centers for Disease Control and Prevention.

Says lead investigator Dr. Darae Kim, “Cardiac amyloidosis is rare in occurrence, but it is also an overlooked cause of heart failure. Echocardiography (or 2D-echo as is usually referred to) is typically the first imaging technique used in the diagnosis of cardiac amyloidosis, and it also provides reliable prognostic information. Previous studies indicate that decreased LV GLS is associated with poor prognosis in cardiac amyloidosis. However, there are no detailed studies examining the association between reduced LV GLS and amyloid protein aggregates in the heart.”[A1] [A2] [A3] 

For the study, the team recruited 77 patients with cardiac disease. All patients underwent endomyocardial biopsy. In addition, 2D conventional transthoracic echocardiography was performed to evaluate the functioning of the heart.

The analyses included measurement of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and troponin T at the time of diagnosis. High levels of NT-proBNP indicate heart failure. Similarly, the presence of troponin T in the blood indicates damage to the cardiac muscles.

Next, the team immunohistochemically stained the extracted biopsy sample to estimate the amyloid load in the tissue. Meanwhile, patient mortality was documented and patients showing complete response, good partial response, or partial response to treatment were classified as “responders.” From the group of 77 patients, 40 patients were classified as responders.

The results were encouraging: LV GLS showed a modest but significant correlation with the amyloid protein aggregates detected in the heart tissue and the logarithm of the amount of NT-proBNP detected in the blood stream. Despite the modest association, the researchers considered LV GLS to have demonstrated significant additive prognostic value. Thus, the team successfully identified a new imaging-based biomarker for refining risk stratification of cardiac amyloidosis resulting not only from amyloid protein aggregates, but also from cardiotoxicity and fibrosis.

“Cardiac involvement is a critical prognostic factor in patients with light chain amyloidosis. If novel treatment options are made available for patients with light-chain amyloidosis, LV GLS could be used as an imaging biomarker to help better distinguish between patients with varying degrees of risk and also for monitoring prognosis ,”[A4] [A5]   notes Dr. Kim.   

Reference

About National Institute of Health in Korea 

The Korea National Institute of Health (KNIH), one of the major operating components of the Ministry of Health and Welfare, leads the nation’s medical research. Over the past seven decades, the KNIH has made unwavering efforts to enhance the public’s health and innovate biomedical research. The KNIH seeks to eradicate diseases and make people healthier. The KNIH establishes a scientific basis and evidence underlying health policy as well as provides national research infrastructures. We also promote public health research. To this end, we make efforts to enrich a health research environment by granting funds to research projects and keeping our resources, data, and facilities more open and accessible to researchers.

Website: http://www.nih.go.kr/NIH_ENG/ 

About Dr. Darae Kim

Dr. Darae Kim is an Assistant Professor of Cardiology at the Samsung Medical Center. She conducts research on heart failure, heart transplantation, and echocardiography. Her group is developing approaches to enhance screening for the early diagnosis of cardiac amyloidosis, in an attempt to improve management and survival of patients with this disease. Before joining Samsung Medical Center, she received her M.D. and Ph.D. degrees from Yonsei University College of Medicine. Dr. Kim finished her residency at Severance Hospital, Yonsei University College of Medicine.