Around 5.1 million Americans are suffering with heart failure. According to the CDC, about 50 percent of patients die within five years of their diagnoses. This condition is a contributing factor in one of every nine deaths. An estimated one of every 250 people has dilated cardiomyopathy (DCM), a leading source of inherited heart failure. International researchers discovered a genetic mutation that can cause DCM. This finding may promote genetic testing to improve treatments for high-risk heart failure patients.
Harvard experts advise that the key to avoiding dilated cardiomyopathy is preventing its contributing factors including:
Coronary artery disease
Heart inflammation (myocarditis)
Untreated thyroid conditions
Disorders that overload your heart with amyloid protein or iron
Lengthy excess alcohol consumption
Chemotherapy and radiation
To reduce your coronary artery disease chances:
Keep your blood pressure in the normal range by taking medication if necessary.
Eat a nutritious diet that includes plenty of fruits and vegetables.
Restrict alcoholic beverages to two per day. If your DCM risk is high, don’t drink any alcohol.
DCM symptoms may include:
Labored breathing, particularly during exertion
Breathing difficulties when lying down
Light-headedness or fainting
Even if you’re symptom free, schedule a medical evaluation if relatives developed inherited DCM. Besides a physical exam, tests may include:
Electrocardiogram (EKG), which records your heart’s electrical activity
Echocardiogram, which uses ultrasonic waves to produce a graphic record of your heart’s structures and cardiac output
If your doctor discovers DCM or heart failure, he may prescribe an ACE inhibitor like Accupril(Quinapril).
DNA Sequencing Detects Problematic Protein
Study subjects with this mutation produce shorter titin proteins that are essential muscle components. Titin truncation increases dilated cardiomyopathy severity more than other causes. It stretches, thins, and weakens the heart muscle’s walls, which reduces its elasticity while also enlarging that organ and hindering its blood-pumping ability. More preemptive therapy may be necessary, says study co-author and researcher Dr. Angharad Roberts. Beneficial outcomes could include screening these patients’ heart rhythm issues and implanting internal cardiac defibrillators.
The researchers ran genetic sequencing tests on 5267 subjects, which included DCM patients and healthy controls. They examined the gene that creates titin and analyzed its levels in heart tissue samples. Previous research identified genetically shortened titins as dilated cardiomyopathy’s main genetic cause, accounting for around of quarter of serious cases. But many of the numerous titin mutations don’t contribute to heart failure. Gene truncations are common with roughly one occurring among 50 people. Most are benign, which makes developing useful genetic tests difficult.
After weeding out harmless titins, the scientists focused on the dangerous variations occurring in DCM patients most often. Mutations that provoke DCM appeared at gene sequences’ far ends. In healthy subjects, the final proteins have tendencies not to include gene parts with mutations, so titins remain functional. One titin mutation type occurring in families increases dilated cardiomyopathy risk greatly. It’s the underlying cause of severe familial DCM cases 49 out of 50 times, Roberts says.
Unfortunately, the investigators also determined that this mutation is responsible for heart disease with much greater damaging effects. They used MRI scans to compare hearts of subjects with titin mutations to those without them and then followed their clinical progress, explains co-author and lecturer Dr. James Ware. Dilated cardiomyopathy was more severe in patients who developed it via titin mutations. Their heart rhythm problems were more life threatening while their survival rates were worse than other DCM patients.
Future Improvements to Come
Until now, genetic analysis for heart failure patients has been challenging. Interpreting which mutations may cause heart disease has been tricky, Roberts notes. Part of the problem is that titin is among the largest proteins, notes Dr. Jeremy Pearson. But finally, a study defines the problematic gene’s comprehensive mutations, which ones have dilated cardiomyopathy associations, and which ones are harmless. Such evidence gives doctors a reference to interpret their patients’ confusing DNA sequences. It could help physicians determine which patients ― especially those with family histories ― have greater heart failure risks.
This discovery changes DCM’s genetic testing landscape by accounting for a significantly higher case number than all other currently identified genes. Dr. Stuart Cook, the study’s lead researcher, says that the results explain DCM’s molecular basis in detail. Doctors can use that data to screen patients’ families. After identifying which members have risks for developing that disease, they can help them manage their conditions early.
Two professors agree. According to Dr. Dudley Pennell, this study separates bad genetic mutations from ones that are just bystanders. Besides benefitting current cardiomyopathy patients, it enables doctors to reassure their relatives who don’t have DCM that they can avoid expensive tests and anxiety. Pearson notes that this discovery adds tremendous value to diagnosing and treating future patients correctly as gene sequencing becomes more commonplace.
Further studies will hone in on how mutated titins compromise the heart, says geneticist Dr. Christine Seidman. Understanding those signals would help scientists identify how to attenuate or stop those signals. Cumulative data could help researchers create therapies that prevent or treat heart failure stemming from abbreviated titins.