HYPERTROPHIC CARDIOMYOPATHY
Mark Tuttle 2017
EPIDEMIOLOGY: Estimated to affect 0.2% of the world's population (1:500)1, equal occurrence in men and women2. NOMENCLATURE ● Hypertrophic cardiomyopathy (HCM) is the preferred term over hypertrophic obstructive cardiomyopathy (HOCM) since forms are known to exist without hemodynamic evidence of obstruction. ○ ⅓ of affected patients have no hemodynamic obstruction2. DEFINITION ● Left ventricular wall thickness ≥ 15 mm (13-14 is borderline) or ≥ 2 standard deviations above the mean in children ● Nondilated ventricular chambers ● No other cardiac or systemic diseases that itself would be capable of producing the magnitude of hypertrophy ○ Aortic valve stenosis ○ Systemic hypertension ○ Some expressions of physiologic “athlete’s heart” OR ● Genotype positive in the absence of phenotypic evidence of disease GENETICS ● Usually autosomal dominant, but other patterns of inheritance exist. ● 1,400 mutations have been identified in 13 genes coding for the sarcomere7 ○ 40% of all HCM cases have mutations in MYPBC3 and MYH7 genes, which code for the thick filament of the sarcomere7 ■ MYBPC3 (25% of cases): Older age of symptom onset, decreased risk of SCD, relatively asymptomatic clinical course7 ■ MYPBC3: Often develop symptoms in their 20s and 30s7 ● A given mutation may have variable expression ○ Family members with identical mutations may follow markedly different manifestations of disease and overall clinical courses7 DIAGNOSIS ● Transthoracic echocardiography ○ Outflow tract assessment: Pulsed wave doppler along the LV septum, velocity ≥2.7 m/s indicates ≥ 30 mmHg8 ○ Systolic anterior motion: Correlated with degree of LVOT obstruction9 ● Cardiac magnetic resonance imaging: May be useful if echocardiography is inconclusive or if an alternative diagnosis is suspected such as cardiac amyloidosis, Fabry disease, and genetic phenocopies such as LAMP2 cardiomyopathy1 CLINICAL FEATURES ● Hypertrophy: Defined as LV wall thickness ≥ 15 mm during diastole ○ Focal/diffuse4 ■ Focal (1-2 segments): 10% ■ Intermediate (3-7 segments): 35% ■ Diffuse (8-16 segments): 55% ○ Segment distribution5 ■ Anterior ventricular septum + posterior ventricular septum: 31% ■ Anterior ventricular septum only: 25% ■ Anterior ventricular septum, posterior ventricular septum, and lateral free wall: 17% ■ Anterior ventricular septum, posterior ventricular septum, lateral free wall, posterior free wall: 17% ■ Anterior ventricular septum, lateral free wall: 7% ■ Posterior ventricular septum: 1% ■ Apex: 1% ● Apical hypertrophic cardiomyopathy (AHC) or Yamaguchi Syndrome10, occurs in 25% of japanese patients with hypertrophic cardiomyopathy, but is uncommon outside of Japan6 ● Outflow obstruction: Defined as ≥ 30 mmHg ○ ⅓ have no obstruction, ⅓ have obstruction with provocation, and ⅓ have resting obstruction1 ○ Those with outflow obstruction have 4.4 relative risk of HCM-related death2 ● Abnormal ECG ○ 75-95% of affected patients have an abnormal ECG: most commonly Q waves or repolarization abnormalities1 ● Sudden death
MarkTuttleMD.com
HYPERTROPHIC CARDIOMYOPATHY
Mark Tuttle 2017
○ Overall: 1% annual risk1 ○ Secondary prevention (prior VT/VF): 10% annual risk1 ○ Primary prevention with risk factors: 4% annual risk1 PATHOPHYSIOLOGY ● Sarcomeric mutations lead to2: ○ Cardiomyocyte hypertrophy → Reduced capillary density ○ Interstitial fibrosis ○ Coronary microvascular dysfunction ○ Microvascular dysfunction → myocardial ischemia → replacement fibrosis → LV remodeling MANAGEMENT ● With outflow obstruction ○ All patients: ■ Avoid vasodilators (ex. Dihydropiridine CCB), high dose diuretics, and digoxin (except for AF.) ■ Avoid situations which may provoke obstruction (ex. hypovolemia) ○ If symptoms present: Verapamil, beta blocker, or disopyramide ■ If symptoms refractory, consider 1) surgical myomectomy, 2) alcohol ablation, or 3) DDD pacing (in order) ○ If no symptoms: Annual clinical evaluation ○ Acute hypotension: Fluid resuscitation, phenylephrine ● With heart failure symptoms ○ LVEF < 50%: According to heart failure guidelines ○ LVEF ≥ 50%: Verapamil, beta blockers, low-dose diuretics, ACEi/ARB ● Prevention of sudden death ○ The usefulness of genetic testing in the assessment of risk of SCD in HCM is uncertain. (Level of Evidence: B) ○ Indications for ICD ■ Prior cardiac arrest or sustained VT: Class I1 ■ Family history of sudden death in first degree relative: Class IIa1 ■ LV wall thickness ≥ 30mm: Class IIa1 ■ Recent unexplained syncope: Class IIa1 ■ Nonsustained VT or abnormal blood pressure response to exercise (failure to increase BP ≥ 20 mmHg or fall in BP ≥ 20 mmHg), with other risk factors: Class IIa1 ● CMR imaging with LGE. (Level of Evidence: C) ● Double and compound mutations (ie, >1). (Level of Evidence: C) ● Marked LVOT obstruction. (Level of Evidence: B) ● Screen relatives ○ First degree relatives: TTE or genetic testing (Level of Evidence: B)1 ■ Screening in genotype-positive, phenotype-negative relatives of affected patients. ● Age < 12: No screening unless symptomatic or a competitive athlete1 ● Age 12-21: Screen every 12-18 months or sooner if symptoms develop1 ● Age > 21: Screen every 5 years or sooner if symptoms develop1 SOURCES: 1. Gersh BJ, Maron BJ, Bonow RO, et al. 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2011;124(24):e783-831. 2. Mann DL, Braunwald E, Zipes DP et al. Braunwald's Heart Disease, A Textbook of Cardiovascular Medicine. Saunders; 2014. 3. Maron BJ, Maron MS. Hypertrophic cardiomyopathy. Lancet. 2013;381(9862):242-55. 4. Maron MS, Maron BJ, Harrigan C, et al. Hypertrophic cardiomyopathy phenotype revisited after 50 years with cardiovascular magnetic resonance. J Am Coll Cardiol. 2009;54(3):220-8. 5. Klues HG, Schiffers A, Maron BJ. Phenotypic spectrum and patterns of left ventricular hypertrophy in hypertrophic cardiomyopathy: morphologic observations and significance as assessed by two-dimensional echocardiography in 600 patients. J Am Coll Cardiol. 1995;26(7):1699-708. 6. Iskandar SB, Dittus K, Merrick D. Uncommon cause of a common disease. South Med J. 2003;96(8):828-31. 7. Sylvester J, Seidenberg P, Silvis M. The dilemma of genotype positive-phenotype negative hypertrophic cardiomyopathy. Curr Sports Med Rep. 2014;13(2):94-9.
MarkTuttleMD.com
HYPERTROPHIC CARDIOMYOPATHY
Mark Tuttle 2017
8. Otto CM. Textbook of Clinical Echocardiography, Expert Consult - Online and Print. Elsevier Health Sciences; 2013. 9. Lang R, Goldstein SA, Kronzon I et al. ASE’s Comprehensive Echocardiography. Elsevier Health Sciences; 2015. 10. Yamaguchi H, Ishimura T, Nishiyama S, et al. Hypertrophic nonobstructive cardiomyopathy with giant negative T waves (apical hypertrophy): ventriculographic and echocardiographic features in 30 patients. Am J Cardiol. 1979;44(3):401-12.
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