Cardiomyopathy Management

Diagnosis and Pathophysiology

Hypertrophic cardiomyopathy (HCM) is defined as a disease state characterized by left ventricular hypertrophy in the absence of another cardiac, systemic, or metabolic disease, with a clinical diagnosis established by imaging showing a maximal end-diastolic wall thickness of ≥15 mm anywhere in the left ventricle, as defined by the American Heart Association/American College of Cardiology 1
Left ventricular outflow tract obstruction is common in HCM, often due to systolic anterior motion of the mitral valve, and diastolic dysfunction results from altered ventricular load, impaired LV compliance from hypertrophy and fibrosis, altered energetics, and microvascular ischemia 1
Mitral regurgitation can occur secondarily from SAM or primarily from leaflet abnormalities, and myocardial ischemia is due to mismatch between oxygen supply and demand, microvascular dysfunction, and impaired coronary flow reserve 1
The following table summarizes key diagnostic features of hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM):

Feature	Hypertrophic Cardiomyopathy	Dilated Cardiomyopathy
Definition	Heart muscle disease with unexplained LV hypertrophy, non-dilated ventricles, and preserved/increased ejection fraction	Heart muscle disease with LV dilatation and systolic dysfunction not attributable to abnormal loading conditions or CAD
Primary Structural Change	Increased wall thickness (≥15mm in adults)	Ventricular chamber enlargement
Sarcomere Changes	Addition of sarcomeres in parallel	Addition of sarcomeres in series
Histopathology	Myocyte hypertrophy, disarray, and interstitial fibrosis	Loss of myocytes and increased ECM
Genetics	Primarily sarcomeric mutations (MYBPC3, MYH7 most common)	Multiple genetic and acquired causes
Ejection Fraction	Preserved or increased	Reduced (<50%)	[2, 3]

The American College of Cardiology recommends surgical myectomy as the gold standard for patients with severe symptoms unresponsive to medical therapy, involving transaortic resection of the hypertrophied septum, which is very effective in reducing LVOTO and improving symptoms, with an operative mortality approximately 1% in experienced centers 4
Alcohol septal ablation is an alternative to surgery for selected patients, with success depending on septal artery anatomy, but has a higher rate of permanent pacemaker requirement and slightly higher mortality compared to myectomy 4
Beta-blockers (titrated to resting heart rate <60-65 bpm) are recommended as first-line pharmacotherapy for symptom control in patients with hypertrophic cardiomyopathy (HCM) without obstruction, by the American College of Cardiology 4, 5
Verapamil (up to 480 mg/day) can be used if beta-blockers are ineffective or contraindicated, as suggested by the American College of Cardiology 4
ACE inhibitors or ARBs may be considered for patients with HCM, though a 12-month trial of losartan showed no benefit on LV mass or fibrosis, according to the American College of Cardiology 5

Children with HCM have different diagnostic criteria, with a z-score >2.5 for those without family history and z-score >2 for those with family history or positive genetic test, as noted by the American Heart Association/American College of Cardiology 1
The European Society of Cardiology recommends risk stratification for DCM primarily based on ejection fraction, with additional factors including New York Heart Association (NYHA) class, QRS duration, and presence of left bundle branch block (LBBB) 3
Genetic testing is recommended for index cases of HCM, with a yield of 30-60% in probands, and primarily autosomal dominant sarcomeric mutations, according to the American Heart Association 2
Genetic testing in DCM has a lower yield (30-40%) and involves multiple genes beyond sarcomeric proteins, as noted by the European Society of Cardiology 3

Transthoracic echocardiography (TTE) is the cornerstone diagnostic test to assess the degree of cardiac enlargement, ventricular wall thickness, systolic and diastolic function, presence of valvular abnormalities, and potential causes of cardiomegaly, according to the American College of Cardiology 1
12-lead ECG can be used to evaluate for hypertrophy, conduction abnormalities, or arrhythmias, and cardiac MRI can be used when echocardiography is inconclusive or to better characterize tissue, as suggested by the American Heart Association 1

The following laboratory tests can be used to exclude phenocopies:

Test	Purpose
Hemoglobin	Exclude anemia
Renal function tests	Exclude renal disease
Liver transaminases	Exclude liver disease
Creatine phosphokinase	Exclude muscle disease
Alpha-galactosidase A	Exclude Fabry disease
Immunoglobulin free light chain assay	Exclude amyloidosis
Fasting glucose	Exclude diabetes
Brain natriuretic peptide and troponin T	Exclude cardiac disease
Thyroid function tests	Exclude thyroid disease

Regular clinical and imaging follow-up is recommended to monitor for progression in stable, mild ventriculomegaly without signs of increased intracranial pressure, as suggested by the American College of Cardiology 7
Endoscopic third ventriculostomy (ETV) with or without choroid plexus coagulation (CPC) is an effective alternative to shunting, especially in aqueductal stenosis, although it may result in persistent ventriculomegaly despite clinical improvement, as noted by the American College of Cardiology 7
The American College of Cardiology recommends implantable cardioverter-defibrillator (ICD) therapy for high-risk patients with HCM and for primary prevention in patients with DCM and an ejection fraction ≤35% despite optimal medical therapy 2, 3
Risk factors for sudden cardiac death in HCM include family history of sudden cardiac death, syncope, massive hypertrophy (≥30mm), non-sustained ventricular tachycardia, and abnormal blood pressure response to exercise, according to the American Heart Association 2