Human heart
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A research team in Spain, reporting in the Journal of the American College of Cardiology, say they have identified five subtypes of dilated cardiomyopathy (DCM), and created the first risk stratification of disease development among symptom-free people who carry a genetic mutation that can cause it.

Estimates suggest that in 30 percent to 40 percent of people with dilated cardiomyopathy, the disease is caused by a specific genetic mutation, but little is known about which carriers of this mutation will go on to develop the disease, or at what age it is likely to occur if it does develop. Further, it is unknown what other factors might help identify those who are likely to show signs of the disease who could benefit from closer monitoring.

Dilated cardiomyopathy is the most frequent cause of heart failure among young people, and the leading cause of heart transplantation. It is characterized by an enlarged heart with a reduced capacity to pump blood, and people who have the disease are at high risk of arrhythmias and sudden death.

The study was led by Pablo García-Pavía, a researcher at the The National Center for Cardiovascular Research (CNIC), a group leader in the Spanish cardiovascular research network (CIBERCV), and a cardiologist at Hospital Universitario Puerta de Hierro. Twenty-five hospitals provided data for the study which collected data from 779 genetic carriers, from 300 families, all of whom had shown no signs of the disease prior to entering the study cohort.

After a median follow up period of 37 months, the investigators found that nearly 11 percent of the genetic carriers had developed the disease, and found that development of the disease was dependent on the specific type of genetic mutation present.

“We found that patients who develop the disease tended to share certain characteristics, such as older age, electrocardiogram alterations, and an enlarged heart with a weaker pumping action, albeit within the normal range,” noted García-Pavía. “The risk for developing the disease was also higher in patients with mutations in sarcomere genes or in those whose hearts showed signs of fibrosis detected by magnetic resonance imaging.”

Eva Cabrera-Romero, the first author of the study and a cardiologist at Hospital Universitario Puerta de Hierro added that the results of their work will allow for cardiologists to provide a more personalized approach to treating DCM in people identified as genetic carriers of the disease, but who show no symptoms.

Today, people who are genetic carriers of the disease receive similar care which typically consists of either annual or semi-annual checkups. With the new tool for stratification, Cabrera said that “Now, we can schedule check-ups to meet the specific needs of the individual patient: more spaced out for patients without risk factors, and more frequent for those at higher risk.”

The new risk stratification developed should also provide a roadmap of sorts for drug developers to target those specific mutations that make some people more susceptible to the development of CDM.

“Our findings are particularly relevant for future clinical trials with specific disease-modifying therapies, because data on penetrance and the factors associated with disease onset are crucial for the design of early intervention and prevention studies in the field of genetic cardiomyopathies,” the researchers wrote.

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