Laboratory Tests and Ancillaries
Laboratory tests help in identifying conditions that lead to or aggravate ventricular dysfunction (eg diabetes mellitus, thyroid disease, renal dysfunction) and organ dysfunction developing from advanced heart failure. Include complete blood count, fasting blood glucose, hemoglobin A1c, thyroid function tests, liver transaminases, renal function tests, creatine phosphokinase, electrolytes, troponin T, brain natriuretic peptide (BNP), N-terminal pro-BNP, urine and plasma protein, and lactic acid in the request.
Genetic Testing
All patients must be counseled before and after genetic testing to review and discuss its clinical significance. Genetic testing helps in the diagnosis, cascade genetic testing in the family, prognostication, therapeutic stratification, and reproductive management of the patient. This may be performed in patients with signs and symptoms suggestive of hypertrophic cardiomyopathy to verify diagnosis, those with an atypical clinical presentation of hypertrophic cardiomyopathy, or when hypertrophic cardiomyopathy cannot be accounted for solely by a non-genetic source. This identifies the gene mutation that causes the disease, which can be used for genetic testing and eventual early management of at-risk family members and may also help in decision-making regarding future reproduction. Female patients should be counseled regarding the risks associated with pregnancy and the risk of transmitting the disease to the fetus (ie preconceptional and prenatal reproductive and genetic counseling). A gene-positive detection rate of 40-50% may result from screening of the most common hypertrophic cardiomyopathy-causing genes.
Cardiac Biopsy
Cardiac biopsy is rarely performed but shows features of hypertrophic cardiomyopathy such as interstitial fibrosis and myocyte hypertrophy and disarray, though these are usually seen post-mortem. This may be considered in cases where myocardial inflammation, infiltration, or storage is suspected after evaluation with specialized tests.
Imaging
Multimodality imaging helps characterize the phenotype and identify abnormal ventricular morphology (eg hypertrophy, dilatation) and function (systolic/diastolic, global/regional) and detect abnormalities of tissue characterization (eg non-ischemic myocardial scar and fatty replacement).
For left ventricle (LV) structural and functional abnormalities, echocardiography and cardiac magnetic resonance imaging (MRI) can identify dilatation, hypertrophy, or ventricular function, while cardiac MRI also allows tissue characterization. For functional abnormalities, stress echocardiography may confirm valvular and dynamic gradients, whereas computed tomography (CT) coronary angiography or stress testing can evaluate myocardial ischemia. Additional studies include bone scintigraphy to detect amyloidosis and positron emission tomography (PET)-CT to assess myocardial inflammation.
Echocardiography
Echocardiography reliably confirms hypertrophic cardiomyopathy diagnosis. This aids in determining distribution and extent of hypertrophy, LV and RV systolic (global and regional) and LV diastolic function, severity of LV outflow tract obstruction (LVOTO), pathology of membranes or valves (ie mitral regurgitation), and evidence of abnormal or anomalous papillary muscles. LVOTO is a Doppler LV outflow tract gradient of ≥30 mmHg, with ≥50 mmHg as the threshold for advanced pharmacotherapy or invasive treatment.
The major criteria include LV wall thickness in the anterior septum of ≥13 mm or posterior septum or free wall of ≥15 mm and severe systolic anterior motion (SAM) of the mitral valve (septal-leaflet contact). Minor criteria include LV wall thickness in the anterior septum of 12 mm or posterior septum or free wall of 14 mm, moderate SAM (absent septal-leaflet contact), redundant leaflets of mitral valve. A diagnosis of familial hypertrophic cardiomyopathy is established by the presence of one major criterion or two minor echocardiographic criteria or one minor echocardiographic criterion plus two minor ECG criteria.
Transthoracic Echocardiography (TTE)
Transthoracic echocardiography (TTE) evaluates global and regional RV and LV anatomy and function as well as valve function and identifies the presence of dynamic LVOTO, pericardial effusion, pulmonary hypertension, or exercise-induced mitral regurgitation. This is recommended during baseline or screening examinations, for evaluation of prognosis during follow-up, and after developing new cardiac symptoms or a change in clinical status. In patients with hypertrophic cardiomyopathy with changes in clinical status or a new clinical event, a repeat TTE is recommended. In patients with hypertrophic cardiomyopathy without changes in clinical status, repeat TTE is recommended every 1-2 years. Transthoracic echocardiography with provocative maneuvers (eg Valsalva or squat-to-stand maneuver) is recommended in patients with hypertrophic cardiomyopathy and resting peak LVOT gradient <50 mmHg. If a symptomatic patient with hypertrophic cardiomyopathy does not have a resting or provocable outflow tract peak gradient ≥50 mmHg on TTE, it is recommended to perform an exercise TTE.
Transesophageal Echocardiography (TEE)
Hypertrophic Cardiomyopathy_Diagnostics 1Transesophageal echocardiography (TEE) aids in the evaluation of the mitral valve, ie mitral regurgitation, and exclusion of atrial thrombi related to atrial fibrillation if TTE results are uncertain. This is used when planning for invasive septal reduction or surgical myectomy and assessing post-surgical complications.
Contrast Echocardiography
Contrast echocardiography improves visualization of the endocardium and LV apex to identify apical hypertrophic cardiomyopathy. This helps guide alcohol localization during alcohol septal ablation.
Exercise Stress Echocardiography
Exercise stress echocardiography identifies provocable LVOTO in symptomatic patients with hypertrophic cardiomyopathy.
Cardiac Magnetic Resonance Imaging (MRI)
Cardiac MRI is indicated if echocardiography is inconclusive of hypertrophic cardiomyopathy. This aids in the diagnosis when findings are conflicting between an ECG and echocardiography. This further determines the distribution and severity of hypertrophy and fibrosis and systolic function. This helps in planning the use of an implantable cardiac defibrillator (ICD). The advantages of cardiac MRI over echocardiography include the ability to quantify myocardial fibrosis using late gadolinium enhancement (LGE) and evaluation of areas not well seen on echocardiography, such as apical hypertrophic cardiomyopathy. Phenotypic mimics of hypertrophic cardiomyopathy are diagnosed using cardiac MRI with LGE. Contrast-enhanced cardiac MRI may be considered to assess the extent and distribution of hypertrophy and myocardial fibrosis prior to alcohol septal ablation or myectomy. Minimal to no LGE is associated with a reduced risk of sudden cardiac death.
Cardiac Computed Tomography (CT) Scan
Cardiac CT may be considered for diagnosis and definition of coronary anatomy if echocardiogram is non-diagnostic and cardiac MRI is contraindicated or not available. The disadvantages include the use of radiation and radioiodine contrast and inferior temporal resolution compared with echocardiography.
Coronary Angiography (CT or Invasive)
Hypertrophic Cardiomyopathy_Diagnostics 2Coronary angiography is recommended in patients with symptomatic hypertrophic cardiomyopathy or evidence of myocardial ischemia. This is recommended prior to surgical myectomy in patients with hypertrophic cardiomyopathy at risk of coronary atherosclerosis. This aids in the assessment of septal anatomy prior to alcohol septal ablation.
Other Investigations
12-Lead Electrocardiography (ECG)
Hypertrophic Cardiomyopathy_Diagnostics 3A 12-lead ECG is performed during the initial evaluation of patients with hypertrophic cardiomyopathy; it is abnormal in 75-95% of such individuals. The major electrocardiographic criteria include left ventricular (LV) hypertrophy with repolarization changes, abnormal Q waves, and inversion of T waves. Minor criteria include LV leads showing complete bundle branch block, interventricular conduction defect or minor repolarization changes, deep S V2, unexplained syncope, chest pain, or dyspnea. A diagnosis of familial hypertrophic cardiomyopathy is established by the presence of one major ECG criterion or two minor ECG criteria plus one minor echocardiographic criterion.
Other findings may include the following: Changes in the P wave suggestive of LBBB, left axis deviation, or LA dilatation; a PR interval that is short and a QRS complex upstroke that is slurred, which may be seen in hypertrophic cardiomyopathy with no underlying accessory pathways; and atrial fibrillation that is persistent, which is associated with a high risk of thromboembolism.
Holter Monitor and Exercise Test
The diagnosis of hypertrophic cardiomyopathy may be confirmed, or the risk of sudden death may be established, with a 24- to 48-hour ambulatory Holter monitor or an exercise test that may be done with or without myocardial perfusion scanning or echocardiography; both tests can provide additional information on etiology and prognosis.
Holter monitoring may reveal non-sustained ventricular tachycardia or paroxysmal atrial fibrillation and may help identify candidates for implantable cardiac defibrillator (ICD) therapy. Extended ambulatory monitoring is recommended for atrial fibrillation screening (as part of initial evaluation and annual follow-up) in patients with hypertrophic cardiomyopathy who are considered to be at high risk for developing atrial fibrillation and who are eligible for anticoagulation. It is recommended to perform extended electrocardiographic monitoring or event recording in patients with hypertrophic cardiomyopathy with lightheadedness or palpitations to diagnose arrhythmia and for clinical correlation.
Hypertrophic Cardiomyopathy_Diagnostics 4Exercise tests may reveal ischemia or arrhythmia. Exercise stress testing is recommended to determine functional capacity and provide prognostic information in pediatric patients with hypertrophic cardiomyopathy, regardless of symptom status. Cardiopulmonary exercise stress testing should be done for quantification of degree of functional limitation and selection of patients for mechanical circulatory support or heart transplantation in patients with non-obstructive hypertrophic cardiomyopathy and New York Heart Association (NYHA) functional class III-IV heart failure.
Cardiac Catheterization
Cardiac catheterization is recommended for invasive hemodynamic assessment of patients with symptomatic hypertrophic cardiomyopathy in whom noninvasive imaging studies are uncertain for the presence or severity of LVOTO and when results will affect patient management.