Thick heart poses big risk

NEW HAVEN — A new study of almost 4,600 patients with a disease that causes a thickened heart muscle shows the genetically caused disorder is more dangerous than previously thought.

Dr. Daniel Jacoby, a co-author of the study, which is online and will be published in the Oct. 2 issue of the journal Circulation, said the understanding of hypertrophic cardiomyopathy until now has underestimated how lethal a disease it can be if not monitored and treated. Jacoby is director of the Comprehensive Heart Failure Program at Yale New Haven Hospital and a co-author of the paper.

“It’s a totally different understanding of the condition, and the implication is pretty significant,” Jacoby said of the study, which involved eight international medical centers over several years and was based on the Sarcomeric Human Cardiomyopathy Registry (known as SHaRe). “People need to be monitored and we need disease-altering therapy. This is not a benign condition that can be managed adequately with current therapies.”

Jacoby said HCM is the most common inherited cardiomyopathy, which refers to a group of diseases that makes it harder for the heart to pump blood. According to the Hypertrophic Cardiomyopathy Association, it affects one in 500 people or more than 700,000 Americans, but Jacoby said the rate may be as high as one in 350.

SHaRe was launched in 2014 by the biopharmaceutical company MyoKardia, which is developing a medication to treat the disease. Jacoby said all that can be done now is to limit the squeezing of the heart muscle, relaxing it with beta blockers or calcium channel blockers, and treating illnesses caused or exacerbated by cardiomyopathy: heart failure (a major symptom is shortness of breath), atrial fibrillation and ventricular tachycardia, which are forms of irregular heartbeat. According to the paper, “sudden cardiac death” is also a threat to those with the disease.

This is the first analysis of

the SHaRe data to be published. “The previous information had suggested that the mortality might be similar to the general population or even slightly lower than the general population,” Jacoby said.

A normal heart muscle is 1 centimeter thick, but in a person with HCM it may be 50 percent thicker. “It can be so thick that it can block blood flow out of the heart,” Jacoby said. “It can lead to increased stiffness of the heart.”

He said the new findings were important because “up until very recently, existing treatments were thought to be probably adequate to normalize quality of life and life expectancy with patients with HCM.

“This publication confirms our clinical observations that more needs to be done to help patients with this condition in order to avoid complications from it later in life,” he said.

According to the study, which examined more than 24,000 patient-years, the risk of death was three times greater among those with HCM than in those without the disease, at similar ages. And the younger a patient is diagnosed, the greater the chance of other illnesses occurring as the patient ages, so early diagnosis is vital, Jacoby said. Most complications appear between the ages of 50 and 70.

Atrial fibrillation is an irregular heartbeat coming from the top of the heart, which can result in palpitations and stroke, Jacoby said, while ventricular tachycardia is “a very, very fast heart rhythm arising from the

bottom chambers of the heart that makes it impossible for the heart to pump sufficient blood to the brain.”

Most threatening is that, as a result of ventricular tachycardia, “HCM is the No. 1 cause of sudden cardiac death in otherwise healthy young people,” he said.

Jacoby said that for about half the patients, the genes causing the disease can be identified, but that “there are multiple genes that can cause this condition.” Someone with a family member who has HCM should see a heart specialist, he said.

“One impact of knowing this is we can determine which patients need to be followed more closely and which don’t need as close follow-up,” he said.

There are other causes of a thickened heart muscle, such as uncontrolled high blood pressure, Jacoby said. Over time, the organ continues “to remodel … to change and adapt to the condition,” he said. That “may involve progressive stiffening of the heart muscle or additional scarring of the heart.”

Because of its seriousness, “we need to monitor for development of new problems, treat them symptomatically, and we need to develop new medications to prevent this process from happening,” Jacoby said. While there is no treatment for HCM itself, the related heart ailments can be treated.

“If you have hypertrophic cardiomyopathy, there is no doubt that you [should] have a minimum yearly checkup at an expert center,” such as Yale New Haven, he said. The hospital has been designated one of 29 Centers of Excellence by the Hypertrophic Cardiomyopathy Association, the only one in Connecticut to have earned the designation. “We have reduced mortality in our program,” Jacoby said.

At Yale New Haven’s Heart and Vascular Center, doctors will “screen you and your family, help you understand the genetic impact of this condition on your family … and monitor for these complications and provide therapy when necessary,” he said.

Signs that a person has hypertrophic cardiomyopathy are “a heart murmur, an abnormal EKG, symptoms or a family member is affected by the condition,” Jacoby said.

The drug that MyoKardia is testing in clinical trials is called mavacamten. The aim is to “normalize that squeezing power” in the heart, Jacoby said. Mavacamten “may slow or reverse this disease process and it certainly improves symptoms in some patients already.”

The eight heart centers that participate in SHaRe are from the United States, Italy, the Netherlands and Brazil. The lead author is Dr. Carolyn Ho, medical director of the Cardiovascular Genetics Center at Brigham and Women’s Hospital in Boston.

“Clinicians around the world have always known that this is a serious condition, but it hasn’t been until the international collaboration that came about through the SHaRe registry that we were able to understand the exact level of risk associated with this condition,” Jacoby said.