February 03, 2017

Raising Hope: New Heart Disease Drug May Help Both Cats and People

A new drug to treat hypertrophic cardiomyopathy (HCM) in cats has shown promising results in a proof-of-concept study. Because HCM is similar in cats and humans, the drug could also eventually be used in people.
By Laurie Anne Walden, DVM, ELS
A new drug to treat hypertrophic cardiomyopathy (HCM) in cats has shown promising results in a proof-of-concept study. Because HCM is similar in cats and humans, the drug could also eventually be used in people. Results of the study were recently published in PLOS One.
 
“This is an exciting discovery for both animals and humans—an excellent representation of the One Health concept in action,” said Joshua Stern, DVM, PhD, chief of cardiology at the University of California, Davis, School of Veterinary Medicine, on the UC Davis website.
 
HCM affects up to 1 in 7 cats and 1 in 500 people, causing similar pathology in both species. The disease leads to heart failure in some patients and increases the risk of thromboembolism and sudden death.
 
Left ventricular outflow tract (LVOT) obstruction exacerbates ventricular hypertrophy and worsens outcomes in people with HCM. LVOT obstruction occurs when mitral valve leaflets exhibit systolic anterior motion, touching the interventricular septum during systole. Some cats with HCM also have LVOT obstruction.
 
Current medical treatments for LVOT obstruction (beta-blockers, calcium-channel blockers, and disopyramide) relieve obstruction and reduce myocardial oxygen demand by reducing heart rate or contractility. However, studies have not shown that these treatments have a clear benefit on outcomes in people, and they do not specifically target the molecular cause of the disease. In cats, preventive treatments have not been shown to alter disease progression. Invasive septal reduction or ablation improves symptoms and prognosis in humans but does not address other abnormalities caused by the disease. Therefore, say the researchers, targeted therapies for HCM are needed.
 
MYK-461 is a small molecule that specifically inhibits sarcomere contractility. Studies in mice have shown that this molecule could potentially be used to treat HCM, but mice do not develop LVOT obstruction. Cats, say the researchers, are a more relevant animal model of HCM.
 
The investigators tested MYK-461 in five cats with HCM from a research colony. All five cats had LVOT obstruction at rest, verified by echocardiography performed with the cats awake. The researchers tested the effects of MYK-461 with the cats under anesthesia. “Anesthesia was necessary to accurately measure LVOT velocities from subcostal views poorly tolerated by conscious cats and to maintain consistent hemodynamic parameters, but did alter resting hemodynamics,” they write.
 
In all five cats, MYK-461 administration reduced fractional shortening and LVOT pressure gradients but did not alter the heart rate. The results show, say the authors, that sarcomere inhibitors like MYK-461 can treat LVOT obstruction by selectively reducing heart muscle contractility (without the chronotropic or vasoactive effects of the current medical treatments).
 
A limitation of the study was that general anesthesia alters cardiovascular physiology. The investigators gave the anesthetized cats isoproterenol to induce sustained LVOT pressure gradients during the trial. They report that the LVOT obstruction provoked by isoproterenol was comparable to the obstruction observed in the cats when awake. “This model may best reflect the LVOT gradients induced upon exercise provocation, which are present in approximately one in three human HCM patients,” they write.
 
The study illustrates the value of companion animals as models of human disease in translational studies, conclude the authors, and may lead to a new treatment for hypertrophic cardiopathy in both species. “There has been little to no progress in advancing the treatment of HCM in humans or animals for many years,” said Stern. “This study brings new hope for cats and people.”
 
 
Dr. Laurie Anne Walden received her doctorate in veterinary medicine from North Carolina State University. After an internship in small animal medicine and surgery at Auburn University, she returned to North Carolina, where she has been in small animal primary care practice for over 20 years. Dr. Walden is also a board-certified editor in the life sciences and owner of Walden Medical Writing, LLC. She works as a full-time freelance medical writer and editor and continues to see patients a few days each month.
 

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