What is the role of sirolimus in managing feline hypertrophic cardiomyopathy (HCM)?

Sirolimus (Rapamycin) in Feline Hypertrophic Cardiomyopathy Management

Sirolimus (rapamycin) shows promise as a disease-modifying therapy for feline hypertrophic cardiomyopathy (HCM), with evidence suggesting it may reduce left ventricular hypertrophy and improve cardiac remodeling when administered at low doses weekly. 1

Current Evidence for Sirolimus in Feline HCM

Sirolimus represents a novel approach to feline HCM management that targets the underlying pathophysiology rather than just symptoms:

• A 2023 pilot study demonstrated that low-dose (0.15 mg/kg) and high-dose (0.30 mg/kg) delayed-release oral rapamycin administered once weekly was well-tolerated in cats with naturally occurring hereditary HCM 1
• Transcriptomic analysis revealed dose-responsive suppressive effects on myocardial hypertrophy and stimulatory effects on autophagy
• Proteomic differences between treated and control cats suggested potential anti-coagulant/anti-thrombotic effects, cellular remodeling benefits, and metabolic improvements

Traditional Management of Feline HCM

Current standard therapies for feline HCM focus primarily on symptom management rather than disease modification:

• Beta-blockers are considered first-line therapy in human HCM to reduce contractility and outflow tract obstruction 2
• Non-dihydropyridine calcium channel blockers (diltiazem, verapamil) are alternative first-line agents, with diltiazem showing particular efficacy in cats 3
• Diuretics for volume overload in cats with congestive symptoms
• Anticoagulation for prevention of thromboembolism

However, a 2011 survey of veterinary cardiologists revealed that treatment decisions for feline HCM are often made with limited evidence basis, highlighting the need for more targeted therapies 4.

Emerging Approaches for HCM

Recent research has focused on targeting the underlying pathophysiology of HCM:

1. Sirolimus (rapamycin) - Shows promise for disease modification in feline HCM 1
2. Myosin inhibitors - A 2016 study demonstrated that MYK-461, a small molecule inhibitor of sarcomere contractility, acutely relieved left ventricular outflow tract obstruction in cats with HCM 5

Practical Approach to Sirolimus Use in Feline HCM

Based on the available evidence, a practical approach to sirolimus use in feline HCM would be:

1. Patient selection: Consider sirolimus for cats with:

   • Documented HCM on echocardiography
   • Subclinical or early-stage disease (before onset of congestive heart failure)
   • Non-obstructive HCM phenotype
   • Cases where disease modification is the goal

2. Dosing protocol:

   • Low-dose delayed-release oral sirolimus (0.15 mg/kg) once weekly
   • Monitor for tolerability and adjust as needed
   • Consider higher dose (0.30 mg/kg) if well-tolerated and inadequate response

3. Monitoring:

   • Regular echocardiographic assessment to evaluate changes in left ventricular wall thickness
   • Clinical evaluation for potential side effects
   • Continued assessment of cardiac biomarkers if available

Limitations and Considerations

• Sirolimus therapy for feline HCM is still investigational and not yet widely adopted in clinical practice
• The 2023 study was a small pilot study requiring further validation
• Long-term safety and efficacy data are still needed
• Sirolimus should be considered as part of a comprehensive management plan that may include traditional therapies

Conclusion

While traditional management of feline HCM has relied on symptomatic treatment with beta-blockers, calcium channel blockers, and diuretics, sirolimus represents a promising disease-modifying therapy that may address the underlying pathophysiology. The 2023 pilot study provides encouraging evidence that weekly low-dose sirolimus is well-tolerated and may have beneficial effects on cardiac remodeling in cats with HCM.