Dataset Information

The Feline Cardiomyopathies: 2. Hypertrophic cardiomyopathy.

ABSTRACT:

Practical relevance

Hypertrophic cardiomyopathy (HCM) is the most common form of feline cardiomyopathy observed clinically and may affect up to approximately 15% of the domestic cat population, primarily as a subclinical disease. Fortunately, severe HCM, leading to heart failure or arterial thromboembolism (ATE), only occurs in a small proportion of these cats.

Patient group

Domestic cats of any age from 3 months upward, of either sex and of any breed, can be affected. A higher prevalence in male and domestic shorthair cats has been reported.

Diagnostics

Subclinical feline HCM may or may not produce a heart murmur or gallop sound. Substantial left atrial enlargement can often be identified radiographically in cats with severe HCM. Biomarkers should not be relied on solely to diagnose the disease. While severe feline HCM can usually be diagnosed via echocardiography alone, feline HCM with mild to moderate left ventricular (LV) wall thickening is a diagnosis of exclusion, which means there is no definitive test for HCM in these cats and so other disorders that can cause mild to moderate LV wall thickening (eg, hyperthyroidism, systemic hypertension, acromegaly, dehydration) need to be ruled out.

Key findings

While a genetic cause of HCM has been identified in two breeds and is suspected in another, for most cats the cause is unknown. Systolic anterior motion of the mitral valve (SAM) is the most common cause of dynamic left ventricular outflow tract obstruction (DLVOTO) and, in turn, the most common cause of a heart murmur with feline HCM. While severe DLVOTO is probably clinically significant and so should be treated, lesser degrees probably are not. Furthermore, since SAM can likely be induced in most cats with HCM, the distinction between HCM without obstruction and HCM with obstruction (HOCM) is of limited importance in cats. Diastolic dysfunction, and its consequences of abnormally increased atrial pressure leading to signs of heart failure, and sluggish atrial blood flow leading to ATE, is the primary abnormality that causes clinical signs and death in affected cats. Treatment (eg, loop diuretics) is aimed at controlling heart failure. Preventive treatment (eg, antithrombotic drugs) is aimed at reducing the risk of complications (eg, ATE).

Conclusions

Most cats with HCM show no overt clinical signs and live a normal or near-normal life despite this disease. However, a substantial minority of cats develop overt clinical signs referable to heart failure or ATE that require treatment. For most cats with clinical signs caused by HCM, the long-term prognosis is poor to grave despite therapy.

Areas of uncertainty

Genetic mutations (variants) that cause HCM have been identified in a few breeds, but, despite valiant efforts, the cause of HCM in the vast majority of cats remains unknown. No treatment currently exists that reverses or even slows the cardiomyopathic process in HCM, again despite valiant efforts. The search goes on.

SUBMITTER: Kittleson MD

PROVIDER: S-EPMC8642168 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Practical relevanceThe feline cardiomyopathies are the most prevalent type of heart disease in adult domestic cats. Several forms have been identified (see Parts 2 and 3), with hypertrophic cardiomyopathy (HCM) being the most common. Clinically the cardiomyopathies are often indistinguishable. Cats with subclinical cardiomyopathy may or may not have characteristic physical examination findings (eg, heart murmur, gallop sound), or radiographic cardiomegaly. Cats with severe disease may develop signs of heart failure (eg, dyspnea, tachypnea) or systemic arterial thromboembolism (ATE; eg, pain and paralysis). Sudden death is possible. Treatment usually does not alter the progression from subclinical to clinical disease and often the treatment approach, once clinical signs are apparent, is the same regardless of the type of cardiomyopathy. However, differentiating cardiomyopathy from normal variation may be important prognostically.Patient groupDomestic cats of any age from 3 months upward, of either sex and of any breed, can be affected. Mixed-breed cats are most commonly affected but certain breeds are disproportionately prone to developing HCM.DiagnosticsSubclinical feline cardiomyopathies may be suspected based on physical examination findings, thoracic radiographs and cardiac biomarker results but often the disease is clinically silent. The definitive clinical confirmatory test is echocardiography. Left heart failure (pulmonary edema and/or pleural effusion) is most commonly diagnosed radiographically, but point-of-care ultrasound and amino terminal pro-B-type natriuretic peptide (NT-proBNP) biomarker testing can also be useful, especially when the stress of taking radiographs is best avoided.Key findingsKnowledge of pathophysiological mechanisms helps the practitioner identify the feline cardiomyopathies and understand how these diseases progress and how they manifest clinically (heart failure, ATE). Existing diagnostic tests have strengths and limitations, and being aware of these can help a practitioner deliver optimal recommendations regarding referral.ConclusionsSeveral types of feline cardiomyopathies exist in both subclinical (mild to severe disease) and clinical (severe disease) phases. Heart failure and ATE are the most common clinical manifestations of severe cardiomyopathy and are therapeutic targets regardless of the type of cardiomyopathy. The long-term prognosis is often guarded or poor once overt clinical manifestations are present.Areas of uncertaintySome cats with presumed cardiomyopathy do not have echocardiographic features that fit the classic cardiomyopathies (cardiomyopathy - nonspecific phenotype). Although no definitive treatment is usually available, understanding how cardiomyopathies evolve remains worthy of investigation.

Project description:Hypertrophic cardiomyopathy (HCM) is an inherited disease of the heart muscle characterized by otherwise unexplained thickening of the left ventricle. Left ventricular outflow tract (LVOT) obstruction is present in approximately two-thirds of patients and substantially increases the risk of disease complications. Invasive treatment with septal myectomy or alcohol septal ablation can improve symptoms and functional status, but currently available drugs for reducing obstruction have pleiotropic effects and variable therapeutic responses. New medical treatments with more targeted pharmacology are needed, but the lack of preclinical animal models for HCM with LVOT obstruction has limited their development. HCM is a common cause of heart failure in cats, and a subset exhibit systolic anterior motion of the mitral valve leading to LVOT obstruction. MYK-461 is a recently-described, mechanistically novel small molecule that acts at the sarcomere to specifically inhibit contractility that has been proposed as a treatment for HCM. Here, we use MYK-461 to test whether direct reduction in contractility is sufficient to relieve LVOT obstruction in feline HCM. We evaluated mixed-breed cats in a research colony derived from a Maine Coon/mixed-breed founder with naturally-occurring HCM. By echocardiography, we identified five cats that developed systolic anterior motion of the mitral valve and LVOT obstruction both at rest and under anesthesia when provoked with an adrenergic agonist. An IV MYK-461 infusion and echocardiography protocol was developed to serially assess contractility and LVOT gradient at multiple MYK-461 concentrations. Treatment with MYK-461 reduced contractility, eliminated systolic anterior motion of the mitral valve and relieved LVOT pressure gradients in an exposure-dependent manner. Our findings provide proof of principle that acute reduction in contractility with MYK-461 is sufficient to relieve LVOT obstruction. Further, these studies suggest that feline HCM will be a valuable translational model for the study of disease pathology, particularly LVOT obstruction.