Advances in Feline Hypertrophic Cardiomyopathy (HCM): Diagnosis, Management, and Future Directions

Introduction

Hypertrophic cardiomyopathy (HCM) is the most frequently diagnosed cardiac condition in cats, affecting roughly 1 in 7 (14%), a rate far higher than what is seen in humans (1 in 300–500). The disease is characterized by abnormal thickening of the left ventricle, which results in impaired diastolic function. This myocardial hypertrophy involves disarrayed cardiomyocytes, fibrotic changes within the heart muscle, and compromised myocardial blood supply.

While HCM is thought to be predominantly genetic, a substantial number of cats with the disease do not carry any currently recognized mutations, underscoring the need for ongoing investigation. Several genetic variants have been associated with HCM in certain purebred breeds—most notably MYBPC3 mutations, including the A31P variant in Maine Coons, as well as mutations identified in Ragdolls.

Screening for HCM

Although prevalence is high, diagnosis of subclinical HCM can be challenging. Early detection offers the best opportunity to intervene.

Primary screening tools:

• Echocardiography: Gold standard for diagnosis and clinical staging of HCM.
• Auscultation: Heart murmurs are not sensitive or specific for HCM, although louder murmurs (≥3/6) warrant additional screening for HCM. Gallop sounds are a good indication of myocardial disease and should prompt echocardiography.
• Cardiac Biomarkers: NTproBNP is currently the best-performing biomarker. Quantitative testing is preferred when screening for subclinical disease. Values in excess of 50 pmol/L should prompt reevaluation and values over 100pmol/L should prompt immediate HCM screening by echocardiography.
• Electrocardiography: The presence of arrhythmias, predominantly ventricular, should prompt echocardiographic screening for HCM.
• Radiography: Not sensitive for early disease detection and thus not recommended for screening. However, if left atrial of ventricular enlargement is obvious on thoracic radiographs, echocardiography is recommended.

Breed screening recommendations:

• Maine Coon and Ragdoll cats should be genetically tested for known MYBPC3 mutations.
• Positive cats should begin annual NTproBNP or echo screening at 2–3 years.

Obstructive HCM (oHCM)

oHCM is a subtype of HCM involving left ventricular outflow tract obstruction, often from septal bulges or systolic anterior motion (SAM) of the mitral valve. Obstruction increases systolic left ventricular pressure and exacerbates hypertrophy. Cats with oHCM often have heart murmurs and thus may be more readily detected in the population.

Diagnosis of HCM

HCM is diagnosed by echocardiographic identification of left ventricular wall thickness exceeding 6 mm (excluding papillary muscles/ moderator bands) during diastole. For cats under 3 kg, a 5 mm threshold may be more appropriate.

HCM isn’t the only thing that causes left ventricular thickening - Phenocopies must be ruled out:

• Hyperthyroidism: Common in older cats; test total thyroxine in cats >6 years.
• Systemic hypertension: Screen via Doppler blood pressure and fundic exam.
• Other lookalikes: Aortic stenosis, acromegaly, transient thickening post severe stress, severe hypovolemia.

Staging of Feline HCM

Clinical manifestations range from asymptomatic to congestive heart failure (CHF), thromboemlism and/or sudden death. Myocardial ischemia and ventricular arrhythmias are common in more advanced stages.

Stage A: At-risk cats without evidence of disease (e.g., Maine Coon cat with MYBPC3 mutation). Recommend annual reevaluations.

Stage B1: Asymptomatic cats with LV hypertrophy but normal or minimally enlarged left atrial size. Annual rechecks advised.

Stage B2: LV hypertrophy with moderate left atrial enlargement or other obvious disease progression risk factors, but no clinical signs.

Stage C: Clinical signs (e.g., CHF, thromboembolic disease) present.

oHCM can occur at any of these stages and may come and go from evaluation to evaluation.

Treatment Overview

Subclinical HCM (Stages A and B1):

• No treatment is recommended for Stage A or B1 without obstruction.
• Atenolol: Occasionally used for moderate to severe oHCM. Theoretical benefits include reducing obstruction, arrhythmia prevention, improved myocardial perfusion, and cardioprotection. However, no study (although largely underpowered) has identified a survival benefit or improvement disease morbidity.
• Felycin™-CA1 (sirolimus delayed-release tablets): this delayed-release rapamycin product is now conditionally approved for the management of left ventricular hypertrophy in cats with subclinical HCM. It should be avoided in cats with diabetes and those with abnormal liver enzymes on routine biochemistry

Stage B2:

• Clopidogrel: Recommended to reduce thromboembolic risk due to left atrial enlargement. Though unproven for preventing first-time events, its safety and effcacy in secondary prevention supports its use.
• Resistance Testing: About 20% of cats are resistant to standard clopidogrel dosing which may be in part due to genetic variants. Consider genetic testing and/or adding rivaroxaban in high-risk cases such as those with severe atrial enlargement, obvious blood stasis or early clot formation in the left atrium.
• ACE Inhibitors (enalapril or benazepril): Sometimes used to mitigate remodeling and fluid retention in advanced stage B2. No survival benefit has been demonstrated.
• Felycin-CA1: this delayed-release rapamycin product is now conditionally approved for the management of left ventricular hypertrophy in cats with subclinical HCM. It should be avoided in cats with diabetes and those with abnormal liver enzymes on routine biochemistry

Stage C (CHF):

• Furosemide: Recommended first-line diuretic to manage fluid accumulation.
• Clopidogrel: Continued for thromboprophylaxis.
• ACE Inhibitors (enalapril or benazepril): Used to mitigate remodeling and fluid retention in cats with appropriate renal function.
• Spironolactone: Added in advanced CHF to further inhibit RAAS.
• Pimobendan: Frequently used in fi rst time or repeat CHF, especially in nonobstructive cases. It is shown to improve left atrial function in multiple studies and does not appear to cause harm.

Future Therapies

Therapeutic options for feline HCM have been limited for decades, but several medications under investigation are showing promise:

1. Delayed-Release Rapamycin (Felycin™-CA1): In a recent pilot study, rapamycin reduced or halted ventricular thickening in subclinical HCM. A conditionally approved product is now available and the fully approved product is awaiting results of larger clinical trials. A large, multicenter trial (HALT HCM Study) is underway. This represents the most promising advancement in feline cardiomyopathy management to date.
2. Sarcomere Contractility Inhibitors (e.g., Mavacamten/Afi camten): These appear effective in humans with HCM and oHCM. Both have shown appropriate pharmacologic activity in cats, but feline specific chronic dosing trials are lacking.

Conclusion

Feline HCM remains a complex, prevalent, and often-devastating disease. While cats can remain asymptomatic for years, progression to CHF or thromboembolism can be sudden. A structured approach to screening, staging, and individualized therapy is essential.

New therapies like rapamycin and myosin inhibitors hold the potential to fundamentally alter the HCM treatment landscape in cats. Continued research and clinical trial participation is critical to move the fi eld forward for this incredibly common feline disease.