Hypertrophic cardiomyopathy

What it is

Hypertrophic cardiomyopathy (HCM) is a disease of the myocardium in which the left ventricle thickens (concentric hypertrophy) without a cause that explains it, such as systemic hypertension, hyperthyroidism or aortic stenosis. The thickened, fibrotic muscle relaxes poorly and becomes stiff (diastolic dysfunction): the ventricle needs a higher pressure to fill, and that pressure is transmitted to the left atrium, which dilates. When the pressure in the atrium and pulmonary veins rises enough, pulmonary oedema or pleural effusion appears. Blood flows slowly in the dilated atrium, where thrombi can form and embolise into the systemic arteries.

In some cats the thickened septum and systolic anterior motion of the mitral valve obstruct the left ventricular outflow tract (obstructive form). It is a heterogeneous disease: the 2020 ACVIM consensus classifies feline cardiomyopathies by phenotype (hypertrophic, restrictive, dilated, arrhythmogenic right ventricular and non-specific) and stages them as A (predisposed), B1 and B2 (no signs, with low or high risk of heart failure or thromboembolism), C (current or previous heart failure or thromboembolism) and D (refractory).

Who it affects

Adult cats of any age, more often males. It affects many non-pedigree domestic cats, and is inherited in some breeds: variants of the MYBPC3 gene (cardiac myosin binding protein C) with autosomal dominant inheritance have been identified in the Maine Coon and the Ragdoll. The British Shorthair, Sphynx, Persian and Bengal, among others, are also predisposed. A cat carrying the variant does not always develop the disease, and a cat without it can still be affected.

Anatomy involved

• Left ventricle: thickened free wall and interventricular septum, sometimes asymmetrically or segmentally; the cavity may be greatly reduced. The papillary muscles are often hypertrophied.
• Mitral valve and outflow tract: systolic anterior motion of the septal leaflet of the mitral valve causes dynamic obstruction and mitral regurgitation.
• Left atrium: dilates; a large atrium is the main indicator of risk for heart failure and thromboembolism. Spontaneous echo contrast ("smoke") or a thrombus in the auricle are sometimes seen.
• Lungs and pleural space: a cat with left-sided failure may present with pulmonary oedema, pleural effusion or both.

Clinical signs

Many cats show no signs for years. Examination may reveal a systolic murmur (often dynamic, increasing with heart rate), a gallop sound or arrhythmias, although a proportion of affected cats have no murmur and many cats with a murmur have a normal heart. Signs appear with heart failure: tachypnoea and dyspnoea, open-mouth breathing, lethargy and inappetence; cats rarely cough from heart failure. Stress, anaesthesia, fluid therapy or corticosteroids can trigger decompensation. Other presentations are acute, painful pelvic limb paresis from aortic thromboembolism, syncope and sudden death.

Diagnosis

• Echocardiography: the reference test. Diagnosis rests on an increased end-diastolic left ventricular wall thickness (usually ≥ 6 mm) after other causes of hypertrophy are excluded; it also measures left atrial size and function, detects systolic anterior motion and looks for thrombi.
• Exclusion of secondary causes: blood pressure and total T4 in older cats; acromegaly also causes hypertrophy.
• Thoracic radiographs: in heart failure, cardiomegaly (with a "valentine-shaped" heart on the dorsoventral view when the atria are dilated), patchy pulmonary oedema and pleural effusion.
• NT-proBNP: helps distinguish cardiac from respiratory dyspnoea and detect moderate to severe cardiomyopathy in cats without signs; a point-of-care test on blood or pleural fluid is useful in emergencies.
• Point-of-care ultrasound: in a dyspnoeic cat it shows an enlarged left atrium, pleural fluid and lung B-lines with little stress.
• Electrocardiogram: for arrhythmias. Genetic tests are available for the Maine Coon and Ragdoll.

Treatment

No treatment reverses primary hypertrophy. In cats without signs but with an enlarged left atrium (stage B2), thromboprophylaxis with clopidogrel is recommended. In acute heart failure: oxygen, furosemide, thoracocentesis for pleural effusion and minimal stress. In chronic heart failure: furosemide at the lowest effective dose, clopidogrel and, depending on the case, an ACE inhibitor or spironolactone; pimobendan is used in selected cases with systolic dysfunction, avoiding severe outflow tract obstruction. Beta-blockers (atenolol) can reduce dynamic obstruction, although they have not been shown to prolong survival. At home the resting respiratory rate is monitored to detect early decompensation. The prognosis varies widely: many cats in stage B1 live normally, while heart failure or thromboembolism markedly shortens survival.

Key studies

• ACVIM consensus (Luis Fuentes et al., 2020): the reference guideline. It classifies feline cardiomyopathies by phenotype and introduces a staging system that divides cats without signs into those at low and those at higher risk of life-threatening complications, with recommendations for diagnosis and management at each stage.
• Payne et al. (2015, CatScan), prospective echocardiographic screening of 780 apparently healthy cats in rehoming centres. The prevalence of HCM was 14.7% and rose with age. A murmur was heard in 40.8% of cats, 70.4% of them considered functional, and the positive predictive value of a murmur for HCM was only 17.9–42.6%. Male sex, older age, higher body condition score and a murmur were associated with HCM.
• Fox et al. (2018, REVEAL), retrospective multicentre cohort of 1730 cats from 21 countries: 1008 with preclinical HCM, obstructive or not, and 722 apparently healthy cats. Among the cats with HCM, 30.5% developed heart failure, thromboembolism or both, and 27.9% died of cardiovascular causes; the risk of cardiovascular death was 6.7% at 1 year, 22.8% at 5 years and 28.3% at 10 years. The obstructive form did not carry a worse prognosis. Once a complication appeared, survival was short (mean 1.3 years).
• Payne et al. (2015), retrospective study of 255 referred cats with HCM followed for 2 years: 17.3% died of heart failure, 9.0% with thromboembolism and 4.7% suddenly. Heart failure at presentation and reduced left ventricular fractional shortening predicted death from heart failure; previous thromboembolism and reduced left atrial fractional shortening predicted death from thromboembolism. Cats without signs had a lower risk of all three.
• Fox et al. (2011), prospective multicentre case-control study of 113 cats with occult cardiomyopathy and 114 healthy cats. Plasma NT-proBNP above 46 pmol/L separated the two groups with 85.8% sensitivity and 91.2% specificity. The cats came from referral centres, so performance in the general population is uncertain.
• Schober et al. (2021), double-blind, randomised, placebo-controlled trial of pimobendan in 83 cats with HCM and recently controlled heart failure. The proportion of cats completing 180 days without an increase in the furosemide dose did not differ between groups, nor did the time to dose increase or death. It was an exploratory study, sponsored by the manufacturer.