Advances in feline hypertrophic cardiomyopathy (HCM): Diagnosis, management, and future directions

This content is sponsored by PRN Pharmacal.

Introduction

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

Although 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 and mutations identified in Ragdolls.

Screening for HCM

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

Primary screening tools:

• Echocardiography: This is considered the 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 100 pmol/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 or 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 to 3 years.

Obstructive HCM

Obstructive HCM (oHCM) is a subtype of HCM involving left ventricular outflow tract obstruction, often from septal bulges or systolic anterior motion 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 also be ruled out:

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

Staging of feline HCM

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

Stage A: At-risk cats without evidence of disease (eg, Maine coon cat with MYBPC3 mutation); recommend annual reevaluations.

Stage B1: Asymptomatic cats with left ventricular hypertrophy but normal or minimally enlarged left atrial size; annual rechecks advised.

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

Stage C: Clinical signs (eg, CHF, thromboembolic disease) are 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, preventing arrhythmias, improving myocardial perfusion, and cardioprotection. However, no study (although largely underpowered) has identified a survival benefit or improvement in disease morbidity.
• Sirolimus delayed-release tablets (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 B2

• Clopidogrel: Recommended to reduce thromboembolic risk due to left atrial enlargement. Though unproven for preventing first-time events, its safety and efficacy in secondary prevention support its use.
• Resistance testing: Approximately 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.
• 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 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 first-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 the results of larger clinical trials. A large, multicenter trial (HALT HCM) is underway. This represents the most promising advancement in feline cardiomyopathy management to date.
2. Sarcomere contractility inhibitors (eg, mavacamten/aficamten): 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. Although 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, such as rapamycin and myosin inhibitors, hold the potential to fundamentally alter the HCM treatment landscape in cats. Continued research and clinical trial participation are critical to move the field forward for this incredibly common feline disease.