PHOTOS COURTESY SARAH MILLER, DVM, DACVIM (CARDIOLOGY) In a twist, a version of a medication in clinical trials to extend the healthy lifespan of dogs was conditionally approved in March by the U. S. Food and Drug Administration (FDA)1 to treat hypertrophic cardiomyopathy (HCM) in cats. It is expected to be available this summer for veterinarians to manage the disease, which affects one in seven cats, or about 15 percent. At the Feline Cardiology Symposium in April, presented by EveryCat Health Foundation (EHF) and North Carolina State College of Veterinary Medicine, veterinarians, veterinary technicians, and cat owners gathered to hear a dozen speakers on the future of feline cardiology, ranging from screening and diagnostics to therapies for feline arterial thromboembolism to nutrition, as well as topics for pet owners, such as recognizing respiratory distress, managing constipation and navigating end-of-life decisions. Here are some of the main takeaways for primary care veterinarians. Medication news Veterinarians and cat owners will rejoice that the new medication, felycin-CA1 (the CA1 stands for conditional approval) from TriviumVet, requires only weekly dosing. That eases the burden on both patient and pet parent, says Brian J. Peters, DVM, owner of Petology Animal Hospital in Naples, Fla., and a member of the EHF education committee. Historically, HCM has had few treatment options. It often goes undiagnosed, with the first sign being sudden death. Barriers to treatment of HCM include owners’ financial constraints to pursue cardiology referral and the limited availability of board-certified cardiologists—fewer than 500—in the U. S., according to Dr. Peters. “We will now have a therapy available that may minimize the risk of the catastrophic and fatal complications of this disease process,” he says. While it is not yet being used in cats, a new drug in the human market, aficamten,2 reduces cardiac contractility and may one day help cats with HCM. How the drug was developed A formulation of rapamycin—a naturally occurring compound that has been used to help prevent organ transplant rejection, among other things—is the basis of felycin-CA1, studied in a randomized double-blind clinical trial3 directed by Joshua A. Stern, DVM, PhD, ACVIM (Cardiology) carried out at University of California (UC), Davis, and North Carolina State University (NCSU), where Stern is currently associate dean. The study showed that in cats diagnosed with HCM, hypertrophy slowed. Rapamycin affects pathways involving protein synthesis, muscle development, and cellular turnover. The compound has been looked at in diseases that resemble HCM, including mouse studies showing that rapamycin prevents the heart muscle from thickening or reverses thickening over time, Dr. Stern says in his lecture on the future of HCM therapy. “Lots and lots of evidence in the literature pointed in this direction,” Stern says. “The data was there, just waiting for us to look at it and connect the dots.” The 43 cats enrolled in the study had subclinical HCM. They received the drug or a placebo once a week and underwent three cardiac ultrasounds over a six-month period. “Thank goodness we had some compliant cats,” Stern says. One important question was whether rapamycin could be used safely in cats. Because it is typically used in humans at much higher doses to prevent organ transplant rejection, there was concern that it might negatively affect immune function. “We didn’t see any evidence of that,” Stern says. “We’re using a lower dose at a very infrequent schedule, so we didn’t see any safety concerns in terms of bone marrow suppression or immune suppression. We didn’t see any GI side effects.” Cats that received the placebo worsened over time. One developed a urethral obstruction. Cats that received the study drug experienced no disease progression or a reduction in thickness of the heart wall, even at a low dose. “That’s the best news,” Stern says. “It’s the lowest dose we can give once a week that we are going to be using.” Blood clots are a problem in cats with HCM, but tissue testing of the drug found it had positive impacts on complement and coagulation cascades. Research teams continue to study this drug effect. That does not mean there were no adverse events. One cat that was pre-diabetic developed diabetic ketoacidosis and died, so rapamycin is not an option for cats at risk of diabetes or those that are already diabetic. Two cats, despite receiving the drug, progressed to left-sided congestive heart failure, and one experienced sudden death after syncope/seizure. Currently, researchers are seeking cats with subclinical HCM to be enrolled in the HALT Study,4 which aims to continue over a longer period to study the effectiveness of delayed-release rapamycin in managing ventricular hypertrophy in cats with subclinical HCM. This study is also randomized and double-blinded. Cats can be enrolled at one of approximately 22 sites across the country. “These cats will get a lot of free monitoring and help us understand how this drug is working in this longer study period,” Stern says. In older cats with heart murmurs, gallop sounds, or arrhythmias, it is recommended to check serum T4 concentration and blood pressure. Screening and diagnostics It is important to identify cats at risk early on. While most cats with HCM are non-pedigreed males, any cat—especially cats six to eight years old or older—can develop it, and certain breeds are predisposed. These include Maine coons, ragdolls, British shorthairs, Persians, Bengals, sphynx, Norwegian forest cats, and Birmans. Genetic testing is available for Maine coons and ragdolls. In these breeds, screening can influence breeding practices. “If we are better able to understand the underlying pathophysiology or genetics of this disease in a larger population of cats, we might be better able to prevent passing on these genetic mutations to future offspring,” says Joanna Kaplan, DVM, DACVIM (Cardiology), who spoke on screening for feline heart disease. For any cat, though, early detection and monitoring are important. Dr. Kaplan says, “In the ideal world, we would be able to catch this disease early before a cat develops any signs or symptoms and be able to intervene early. For a long time, we haven’t had excellent options to intervene in the preclinical setting. This may change with the new delayed-release formulation of rapamycin by Trivium. However, the pathophysiology of HCM is complex and not necessarily the same in all cats. Therefore, there is still much to learn about how we might be able to intervene early to delay progression or onset of HCM.” It is also important to rule out secondary conditions that can mimic HCM, as treating these may lead to partial or complete reversal of left ventricular hypertrophy, Dr. Kaplan says. The two most common secondary causes include systemic hypertension and hyperthyroidism, but other underlying causes to consider, depending on the clinical picture, include reduced preload in a severely dehydrated cat, transient myocardial thickening, acromegaly, or neoplastic infiltration. For instance, Kaplan says, “If you have a severely dehydrated cat, the walls might look thicker and the heart chamber sizes small. If you give fluids to that cat, then those left ventricular walls might measure normal again.” Another example is a more recently recognized phenomenon: transient myocardial thickening. This may be seen more commonly in younger cats who have experienced a sudden stressful event, such as construction in the home or a big party with many guests. Typically, the cat presents with respiratory distress and is diagnosed with and treated for heart failure. Over time, left ventricular wall thickness and left atrial size normalize and the situation resolves. Ideally, echocardiography is performed by board-certified veterinary cardiologists in unsedated cats in quiet conditions, and cats should be handled with minimal restraint. Adequate echocardiographic images are most commonly performed in lateral recumbency. Unfortunately, lack of physical examination findings can make diagnosing HCM in the occult setting difficult. For example, up to 80 percent and 19 percent of cats with HCM may have a cardiac murmur or gallop sound on physical examination, respectively. However, a large proportion of cats with HCM have no auscultation abnormalities on physical exam, and these cats are more likely to be missed in the early stages of disease. In addition, murmurs can be dynamic and may not be present at all veterinary visits. “They might have it on one day when they’re quite stressed and they might not have it on another day,” Kaplan says. “They might have it in a clinical setting but not at home.” A murmur or gallop sound is not conclusive for HCM, and other conditions can cause a murmur, including congenital heart disease, severe anemia, and hyperthyroidism. Regardless, Kaplan recommends an echocardiogram in any cat with a cardiac murmur, gallop sound, or arrhythmia detected on physical examination. A cardiac ultrasound or echocardiogram is the most accurate means of diagnosing hypertrophic cardiomyopathy and determining prognosis in cats. The American College of Veterinary Internal Medicine (ACVIM) has consensus statement guidelines5 for diagnosis, classification, and management of cardiomyopathies in cats. Establishing a diagnosis can call for the following: History and physical exam Echocardiogram Total T4 for cats older than six years Doppler BP Point of care ultrasound Genetic testing for Maine coon and ragdoll cats NTproBNP (blood biomarker) cTnl ECG Thoracic radiographs More details are available in the ACVIM guidelines. The ability to predict HCM is still in the future, but the ability to do so could permit disease-modifying therapies to be started earlier and improve understanding of factors driving disease penetrance and progression, says Jose Novo Matos, DVM, PhD, DECVIM (Cardiology), professor and head of cardiology at University of Cambridge, in his talk “HCM and Predicting the Future.” “The holy grail is precision medicine where we can tailor treatment to individual cats, using different drugs or changing environment.” Kim Campbell Thornton has been writing about dogs, cats, wildlife, and marine life since 1985, and is a recipient of multiple awards for her articles and books from the Cat Writers Association, Dog Writers Association of America, and American Society of Journalists and Authors. References https://www.fda.gov/animal-veterinary/cvm-updates/fda-conditionally-approves-drug-management-ventricular- hypertrophy-cats https://www.nature.com/articles/s44161-024-00503-2 https://avmajournals.avma.org/view/journals/javma/261/11/javma.23.04.0187.xml https://www.hcmincats.com/halt https://onlinelibrary.wiley.com/doi/10.1111/jvim.15745
