Sandbox/HCM

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mugilan Poongkunran M.B.B.S [2]

Overview

Hypertrophic cardiomyopathy (HCM), is a heterogeneous cardiac muscle disease characterized by unexplained LV hypertrophy associated with nondilated ventricular chambers in the absence any underlying disease that is capable of producing hypertrophy, or without overt hypertrophy in the presence of the HCM genetic substrate (genotype positive/phenotype negative or subclinical HCM). HCM is caused by autosomal dominant mutations in sarcomere genes which encode components of the contractile apparatus of the heart. The clinical manifestations of HCM individuals depends upon the site and extent of cardiac hypertrophy, having asymptomatic normal life expectancy without disability to severe symptomatic presentation due to LV outflow obstruction, heart failure, myocardial ischemia, arrhythmia, mitral regurgitation or sudden cardiac death. The diagnosis of HCM is made with cardiac imaging (echocardiography or cardiac MRI), showing maximal LV wall thickness ≥ 15 mm in adults or thickness ≥ 2 SD above the mean for age, sex, body size in children and with genetic testing. The management of HCM involves risk stratification to ascertain which patients are at risk for sudden cardiac death, treatment of comorbidities, ICDs for secondary or primary prevention, pharmacological therapy to control heart failure, surgical options for progressive and drug-refractory heart failure symptoms due to LV outflow tract (LVOT) obstruction and heart transplantation for systolic dysfunction with severe unrelenting symptoms.

Classification

Obstructive form of HCM

Defined when peak instantaneous LV outflow gradient ≥30 mm Hg under basal (resting) conditions. or with physiologic provocation.

Non-obstructive form of HCM

Defined when peak instantaneous LV outflow gradient <30 mm Hg at rest and with provocation.

Causes

Life Threatening Causes

Hypertrophic cardiomyopathy can be a life-threatening condition and must be treated as such irrespective of the underlying cause.

Common Causes

• Congenital: Autosomal dominant mutation in genes that encode sarcomere proteins or sarcomere-associated proteins.
  • Beta myosin heavy chain
  • Myosin binding protein C
  • Troponin T
  • Troponin I
  • Alpha tropomyosin
  • Actin
  • Regulatory light chain
  • Essential light chain
  • Actinin
  • Myozenin

FIRE: Focused Initial Rapid Evaluation

A Focused Initial Rapid Evaluation (FIRE) should be performed to identify patients in need of immediate intervention.

Boxes in red color signify that an urgent management is needed.

Complete Diagnostic Approach to Hypertrophic Obstructive Cardiomyopathy

A complete diagnostic approach should be carried out after a focused initial rapid evaluation is conducted and following initiation of any urgent intervention.

Complete Diagnostic Approach to Mitral Regurgitation

A complete diagnostic approach should be carried out after a focused initial rapid evaluation is conducted and following initiation of any urgent intervention.

Abbreviations: EKG: Electrocardiogram; LVOT: Left ventricle outflow tract;

Characterize the symptoms: ❑ Asymptomatic: ❑ Diagnosed as a result of family screening ❑ Diagnosed as a result of detection of a murmur during routine examination ❑ Diagnosed as a result of identification of an abnormal EKG ❑ Fatigue ❑ Dyspnea on exertion: Due to any of the following ❑ Diastolic dysfunction due to myocardial hypertrophy ❑ Impaired left ventricular emptying due to LVOT obstruction ❑ Systolic dysfunction in a patient with more extensive myocardial involvement ❑ Mitral regurgitation ❑ Paroxysmal nocturnal dyspnea (suggestive of heart failure) ❑ Orthopnea (suggestive of heart failure) ❑ Chest pain: Due to any of the following ❑ Increase in myocardial oxygen demand from hypertrophy ❑ Reduction in myocardial blood flow and oxygen supply ❑ Palpitations: Due to any of the following ❑ Atrial fibrillation ❑ Conduction abnormalities ❑ Syncope or pre-syncope: Due to any of the following ❑ LVOT obstruction ❑ Atrial fibrillation ❑ Conduction abnormalities ❑ Myocardial ischemia ❑ Ventricular baroreflex activation ❑ Abdominal distension (suggestive of right heart failure) ❑ Leg swelling (suggestive of right heart failure) ❑ Weakness (suggestive of an embolic event) ❑ Hemoptysis (suggestive of an embolic event)

Obtain a detailed history: ❑ Exercise history: ❑ Athlete's heart ❑ Past medical history: ❑ Cardiac arrest ❑ Ventricular tachycardia ❑ Ischemic heart disease ❑ Cardiomyopathy ❑ Hypertension ❑ Radiation exposure ❑ Collagen vascular disease ❑ Metabolic disorders ❑ Mitochondrial disease ❑ Family history: ❑ Premature sudden death ❑ Unexplained syncope ❑ LV thickness greater than or equal to 30 mm ❑ Nonsustained ventricular tachycardia ❑ Abnormal exercise blood pressure

Examine the patient: Vital signs: ❑ Pulse ❑ Pulsus bisferiens ❑ Irregularly irregular pulse (with onset of AF) ❑ Blood pressure ❑ Normotensive ❑ Abnormal blood pressure response to exercise ❑ Respiratory rate ❑ Tachypnea (in case of pulmonary edema) Skin: ❑ Peripheral edema (suggestive of right heart failure) Cardiovascular system: Palpation: ❑ Apical impulse: ❑ Diffuse and forceful LV apical impulse ❑ Parasternal lift (suggestive of significant mitral regurgitation and/or pulmonary hypertension) ❑ Systolic thrill at the apex or lower left sternal border ❑ Carotid pulse may be brisk in upstroke and bifid ❑ Due to the development of midsystolic obstruction to blood flow ❑ Due to partial closure of the aortic valve ❑ Jugular venous pulse ❑ Prominent "a" wave Auscultation: ❑ Heart sounds: ❑ Normal S1 ❑ Paradoxical splitting of S2 (suggestive of severe left ventricular outflow obstruction) ❑ S3 or S4 (common in young patients) ❑ Murmur: ❑ Systolic murmur due to LVOT obstruction: ❑ Harsh crescendo-decrescendo systolic murmur that begins slightly after S1 ❑ Similar to that of valvular aortic stenosis and subvalvular aortic stenosis ❑ Loudest at the left parasternal edge, 4th intercostal space, rather than in the aortic area ❑ Increases in intensity with the assumption of an upright posture from sitting or supine position and the Valsalva maneuver ❑ Decreases in intensity after going from a standing to a sitting or squatting position, with handgrip, and passive elevation of the legs ❑ Systolic murmur due to MR: ❑ Due to a combination of LV upper septal hypertrophy and systolic anterior motion (SAM) of the mitral valve ❑ Starts after S1 and continues up to and sometime beyond and obscuring A2 ❑ Holosystolic murmur heard loudest at the apex which radiates to the axilla ❑ Early diastolic murmur (due to large diastolic flow across severe MR) ❑ Mid systolic click (suggestive of mitral valve prolapse) Respiratory system: ❑ Crackles or rales (suggestive of pulmonary edema) ❑ Tachypnea Abdominal system: ❑ Hepatojugular reflex ❑ Hepatomegaly ❑ Ascites Neurological system: ❑ Stroke (in case of thromboembolism)

Order electrocardiogram: ❑ Prominent abnormal Q waves, particularly in the inferior (II, III, and aVF) and lateral leads (I, aVL, and V4-V6) ❑ Left axis deviation ❑ Deeply inverted T waves (giant negative T waves) from V2 through V4 in apical variant of HCM ❑ Findings of atrial fibrillation Apical hypertrophic cardiomyopathy with deeply inverted T waves in precordial leads V2-V6 and II, III, aVL. Order transthoracic echocardiography (TTE) (Level of Evidence: B): ❑ Confirmatory ❑ To determine LV hypertrophy ❑ To determine systolic anterior motion of the mitral valve ❑ To determine LVOT obstruction ❑ Cardiac MRI ❑ Provide additional information beyond that which is available from echocardiography ❑ Assessment of regional myocardial function ❑ Subtle structural abnormalities that may precede hypertrophy ❑ Identification and quantification of right ventricular hypertrophy ❑ Evidence of microvascular dysfunction Order lab tests: ❑ CBC ❑ Electrolytes ❑ ESR ❑ Serum cardiac troponin I and T ❑ Creatine kinase (CK-MB) ❑ Serum urea and creatinine Other tests: ❑ Transesophageal echocardiography (TEE): ❑ If TTE is inconclusive for clinical decision making about medical therapy ❑ To assess the feasibility of alcohol septal ablation ❑ To assess the strategy for myectomy, exclusion of subaortic membrane or mitral regurgitation ❑ Excercise testing: ❑ For risk stratification (ie, abnormal BP response to exercise) ❑ To assess LV outflow tract (LVOT) gradient ❑ Twenty four hour ambulatory (Holter) electrocardiographic monitoring: ❑ To detect ventricular tachycardia (VT) and identify patients who may be candidates for ICD therapy (Level of Evidence: B) ❑ Recommended when patient develop palpitations or lightheadedness (Level of Evidence: B) or when there is worsening of symptoms (Level of Evidence: C) ❑ Cardiac catheterization: ❑ In case of suspicion for LV outflow tract obstruction is present but the clinical and imaging data are discrepant ❑ In patients for whom invasive coronary angiography is being performed ❑ In patients for whom additional diagnosis of is being considered ❑ In patients for whom endomyocardial biopsy is indicated to exclude non-sarcomeric disease

Consider differential diagnosis: ❑ Hypertensive heart disease ❑ Athlete's heart ❑ Metabolic or infiltrative storage disorders in infants and children: ❑ Fabry disease ❑ Pompe disease ❑ Mitochondrial disease ❑ Danon disease ❑ Noonan syndrome ❑ Other causes of dilated cardiomyopathy

Treatment

HCM patients

Does the patient has signs of hemodynamic insatbility? ❑ Hypotension ❑ Tachycardia ❑ Cold extremities ❑ Peripheral cyanosis ❑ Mottling ❑ Altered mental status

Yes

No

Initiate resuscitative measures: ❑ Secure airway ❑ Administer O2 ❑ Establish 2 wide bore IV access ❑ Establish an arterial line ❑ Connect to ECG monitor ❑ Monitor vitals continuously ❑ Elevate the legs ❑ Administer intravenous fluids ❑ Normal saline 300-500 mL over 20-30 min ❑ Consider ICU admission

Treat Comorbidities: ❑ Hypertension ❑ Diabetes ❑ Hyperlipidemia ❑ Obesity

Initiate medical therapy: Intravenous phenylephrine: ❑ 10 mg (1 mL of 1 percent phenylephrine) of phenylephrine in 500 mL of dextrose in water ❑ Rate of 5 to 9 mL/min (or 100 to 180 drops/min if there are 20 drops/mL) ❑ Reduce the rate to 2 to 3 mL/min (40 to 60 drops/min) if BP stabilizes. Intravenous beta blockers: ❑ Propranolol: 1 mg OR ❑ Esmolol

Does the patient has left ventricular outflow tract (LVOT) obstruction?

Yes

No

Does the patient has heart failure symptoms or angina?

Does the patient has heart failure symptoms or angina?

Yes

No

Yes

No

Initiate medical therapy: Beta blockers: ❑ Start at low doses ❑ Titrate the dose to a resting heart rate of less than 60 to 65 bpm ❑ Caution in patients with sinus bradycardia or severe conduction disease OR Calcium channel blockers: ❑ Verapamil: ❑ For those who do not respond or have side effects or contraindications to beta blockers ❑ Start at low doses and titrate up to 480 mg/d ❑ Caution in patients with high gradients, advanced heart failure, or sinus bradycardia Avoid: ❑ Vasodialtor therpay AND ❑ High dose diuretic therapy

Annual clinical evaluation: ❑ ❑ ❑ ❑ ❑ ❑

Determine the systolic function (LVEF)

Annual clinical evaluation: ❑ Perform Genetic testing (Class IIa, Level of Evidence: B) ❑ Provide genetic counseling (Class I, Level of Evidence: B) ❑ Evaluate the familial inheritance (Class I, Level of Evidence: B) ❑ Clinical screening with or without genetic testing is recommended in first-degree relatives ❑ Dont perform genetic testing in relatives when the index patient does not have a definitive mutation ❑

Does the patient have persistent symptoms despite medical therapy?

LVEF < 50%

LVEF ≥ 50%

Yes

No

Click here for hear failure resident survival guide

Initiate medical therapy: ❑ Beta blockers ❑ Calcium channel blockers ❑ ACE inhibitors ❑ ARBs ❑ Diuretics

Acceptable surgical candidate?

Follow-up

Yes

No

Surgical momectomy or alcohol ablation

Alcohol ablation or pacing

Do's

However in equivocal cases, cardiac catheterization with isoproterenol infusion may further aid in eliciting a provocable gradient (82). Otherwise, routine invasive cardiac catheterization to document outflow gradients is necessary only when there are discordant data from Doppler echocardiography and the physical examination

Don'ts

Provocation with dobutamine infusion during Doppler echocardiography is no longer recommended as a strategy to induce outflow gradients in HCM.

• Don't perform genetic testing for relatives when the index patient does not have a definitive pathogenic mutation (Class IIb Level of Evidence:B).

References

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