Cardiomyopathy

Cardiomyopathies are diseases of the muscle tissue of the heart. Types of cardiomyopathies include dilated, hypertrophic, restrictive, and arrhythmogenic right ventricular cardiomyopathy.

Dilated cardiomyopathy (DCM) is the most common type of cardiomyopathy. Although most cases are idiopathic, a number of conditions (e.g., coronary artery disease, wet beriberi), infections (e.g., Coxsackie B virus, Chagas disease), and substances (e.g., heavy drinking, cocaine) have been identified as causes. In DCM, the decreased ventricular contractility of the dilated left ventricle (LV) leads to failure of the left and eventually right heart with decreased ventricular output. Isolated dilation and subsequent decrease in contractility of right ventricle (RV) is rare. Dilation can be seen on echocardiography, the most important diagnostic tool for all cardiomyopathies. Therapy involves management of congestive heart failure and treatment of the underlying condition.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) primarily affects the right ventricle and is characterized by fibrofatty replacement of myocardium, which causes myocardial thinning and subsequent ventricular dilation. Although the hallmark finding is arrhythmia, symptoms are highly variable. Because management depends greatly on individual factors, such as the extent of the disease, there is no single best course of treatment. All patients should avoid strenuous exercise.

Arrhythmia-induced cardiomyopathy is a very rare type of cardiomyopathy. It is caused by long-standing arrhythmia and typically affects the left ventricle. Features include palpitations, syncope, and signs of arrhythmia on ECG. Progression to left heart failure is possible in severe cases. Treatment involves antiarrhythmics such as beta blockers for rhythmic control.

“Hypertrophic cardiomyopathy,” “Restrictive cardiomyopathy,” and “Peripartum cardiomyopathy” are described in their respective articles in more detail.

Epidemiology

• Incidence: 6/100,000 per year (most common cardiomyopathy)
• Sex: ♂ > ♀ (approx. 3:1)

Etiology ^[2]

• Idiopathic (∼ 50%)
• Genetic predisposition ^[3]
  • Gene mutations with familial incidence including:
    • Mutations of TTN gene, encoding for the intrasarcomeric protein titin (connectin)
    • Mutations of MYH7 gene, encoding for the β-myosin heavy chain
  • Hemochromatosis
  • Duchenne muscular dystrophy
• Secondary causes
  • Coronary heart disease (ischemic cardiomyopathy)
  • Arterial hypertension
  • Peripartum cardiomyopathy
  • Infection
    • Coxsackie B virus myocarditis (viral dilated cardiomyopathy)
    • Rheumatic heart disease
    • Chagas disease
    • HIV
  • Systemic lupus erythematosus; , sarcoidosis
  • Toxic substances
    • Alcohol use disorder (alcoholic cardiomyopathy)
    • Cocaine
    • Cardiotoxic drugs (anthracyclines such as doxorubicin, daunorubicin, AZT, and trastuzumab)
    • Inhalation of organic solvents (e.g., glue-sniffing)
  • Malnutrition
    • Thiamine deficiency (wet beriberi)
    • Selenium deficiency
  • Chronic tachycardia (e.g., atrial fibrillation)
  • Radiation
  • Endocrinopathies (e.g., pheochromocytoma, acromegaly, hyperthyroidism)
  • Valvular heart disease
    • Aortic valve stenosis
    • Aortic valve regurgitation
    • Mitral valve regurgitation

To remember some high-yield secondary causes of dilated cardiomyopathy, think ABCCCDD: Alcohol use, Beriberi, Cocaine, Coxsackie B virus, Chagas, Doxorubicin/Daunorubicin

Pathophysiology

• Causative factors decrease the contractility of myocardium → compensatory mechanisms (Frank-Starling law) are activated to maintain cardiac output → ↑ end-diastolic volume (preload) → myocardial remodeling → eccentric hypertrophy (sarcomeres added in series) and dilation of the ventricle ; → reduced myocardial contractility → systolic dysfunction and ↓ ejection fraction → heart failure
• ↓ LV contractility due to dilation leads to left heart failure and eventually right heart failure
  • Left heart failure: decreased LV output leads to clinical features of left-sided heart failure via the following mechanisms
    • Diminished systemic perfusion → decreased perfusion of end organs → forward failure (e.g., renal/cerebral dysfunction, cold extremities)
    • ↑ Pressure within the pulmonary circulation → pulmonary circulation congestion → impaired gas exchange and fluid extravasation into the interstitium and alveoli → backward failure with predominant pulmonary congestion (e.g., dyspnea, orthopnea, cardiac asthma)
  • Right heart failure : decreased right ventricular output → systemic circulation congestion → backward failure with predominant systemic congestion (see clinical features of right-sided heart failure)

Clinical features

• General symptoms: gradual development of CHF symptoms
  • Exertional dyspnea
  • Ankle edema, ascites
  • Angina pectoris
• Physical examination findings
  • Relative mitral valve regurgitation or tricuspid valve regurgitation (systolic murmur)
  • S3 gallop
  • Left ventricular impulse displacement
  • Jugular venous distention
  • Rales over both lung fields
  • Palpitations
  • Diffuse abdominal and peripheral edema

Diagnostics

Approach

• Diagnostic approach to DCM aims to:
  1. Investigate the underlying cause with confirming either the secondary cause or idiopathic disease
  2. Assess cardiac function
  3. Assess structural remodeling
• Specific investigations are guided by suspected underlying cause or complications

Investigations ^[4]

• Laboratory
  • ↑ BNP: in concomitant heart failure ^[5]
  • Troponin and CK-MB: to rule out myocardial infarction
• Echocardiography: used mainly for assessment of cardiac remodeling and function as it has a limited role in establishing etiology
  • Atrial and/or ventricular dilation
  • ↓ Left ventricular ejection fraction (LVEF)
  • Wall motion abnormalities (e.g., inferolateral hypokinesis in muscular dystrophy and acute myocarditis)
• Chest x-ray
  • Cardiomegaly: left-sided hypertrophy with a balloon appearance
  • Pulmonary edema: sign of left heart failure decompensation
• ECG: The following findings may be present but are not specific for DCM.
  • Disorders of conduction (e.g. AV block , left bundle branch block)
  • Atrial fibrillation, arrhythmias
  • Reduced QRS voltage
  • Change of cardiac axis

Pathology

• Histology (idiopathic DCM): mostly used to exclude other causes of cardiomyopathy
  • Interstitial fibrosis without interstitial inflammation
  • In particular, myocardial interstitial fibrosis is more extensive in the subendocardium because of its higher metabolic demand than the subepicardial layer.
  • Variation in the caliber of cardiomyocytes: cells may appear elongated and wavy with hypertrophy
  • Nuclear atypia

Treatment

• Treatment of the underlying disease
  • Avoid cardiotoxic agents.
  • Abstain from alcohol.
  • Treat endocrine disorders (e.g., beta blockers for the treatment of hyperthyroidism).
  • Treat infection (e.g., benznidazole for treatment of Chagas disease).
• Treatment of heart failure
  • Sodium restriction
  • ACE inhibitors, beta blockers, diuretics, digoxin, aldosterone receptor antagonists
  • See “Treatment” in “Congestive heart failure.”
• Anticoagulation: in the case of mechanical valves, intraventricular thrombus and/or atrial fibrillation (e.g., warfarin)
• Surgical treatment
  • If LVEF < 35%: AICD (to prevent sudden cardiac death caused by ventricular fibrillation)
  • If medical therapy fails: heart transplantation

Complications

• Progressive LV failure → global heart failure
• Systemic thromboembolism → stroke, pulmonary embolism, acute mesenteric ischemia
• Ventricular tachycardia → ventricular fibrillation
• Sudden cardiac death

Epidemiology

• Most common in young adults (mean age at diagnosis: ∼ 30 years) ^[6]
• Prevalence: 1:1,000–2,000 ^[7]

Etiology

• Mutations of various genes (e.g., JUP gene)
• Autosomal recessive or autosomal dominant inheritance ^[7][8]

Pathophysiology

• Right ventricular myocardial cell death (due to myocyte apoptosis, inflammation, and fatty/fibrotic tissue replacement) → thinning of the right ventricular wall → dilation of the ventricle → ventricular arrhythmia and dysfunction ^[6]
• The left ventricle can also be affected, but consequences are usually less severe.

Clinical features

• Highly variable
• Many patients remain asymptomatic.
• Angina pectoris
• Dyspnea
• Peripheral edema, ascites, hepatic and splenic congestion
• Palpitations, syncope, possibly sudden cardiac death (particularly during or after exercise)

Diagnostics ^[6][7][9]

Approach

ARVC is diagnosed based on the AHA criteria which include the following features:

1. Dysfunction and structural abnormalities of RV (can be revealed by echocardiography, MRI, or RV angiography)
2. Histological characteristics (require myocardial biopsy)
3. Abnormal repolarization (diagnosed with ECG)
4. Depolarization/conduction abnormalities (diagnosed with ECG)
5. Arrhythmias (diagnosed with ECG)
6. Family history (confirmation of ARVC in a relative either by criteria, pathological examination in surgery or autopsy, or by genetic testing)

Findings

• ECG
  • Repolarization disturbances in the right precordial leads (V_1-3)
    • Possibly epsilon wave (at the end of a widened QRS complex)
    • Highly specific for ARVC but only occurs in ∼ ⅓ of patients
  • Increased QRS duration
  • Ventricular tachycardia
  • Ventricular extrasystoles
• Echocardiography and cardiac MRI
  • RV enlargement
  • RV wall motion abnormalities
  • ↓ RV EF
  • Localized RV aneurysms
• Endomyocardial biopsy: fibrofatty replacement of myocardial tissue
• Genetic testing: Multiple genetic abnormalities that can cause ARVC have been identified (e.g., plakoglobin (JUP), desmoplakin (DSP), plakophilin-2 (PKP2), desmoglein-2 (DSG2), desmocollin (DSC2)). ^[8]

Management ^[9]

• Avoid intense physical exertion.
• Antiarrhythmic treatment
  • Pharmacologic: beta blockers (e.g., sotalol), amiodarone, calcium channel blockers
  • Invasive
    • AICD implantation (in high-risk patients, e.g., patients with left ventricular involvement)
    • Radiofrequency ablation (only as ancillary treatment)
• Heart transplant (in severe cases that are refractory to all other treatments)
• Screening and genetic counseling for first-degree relatives ^[10]

Left ventricular noncompaction ^[11]

• Definition: rare inherited cardiomyopathy which is associated with structural abnormalities of the left ventricular myocardium (prominent trabeculations and deep intertrabecular recesses)
• Clinical findings
  • Signs of heart failure and arrhythmia (e.g., dyspnea, edema, chest pain, palpitations, syncope)
  • Thromboembolisms
• Diagnostics: echocardiography and/or cardiac MRI: LV wall thickening, prominent trabecular meshwork, detection of abnormal flow (within the deep intertrabecular recesses)
• Treatment: no causal treatment available
  • Avoid intense physical exertion
  • Symptomatic treatment of complications (e.g., heart failure)
  • Prevention of thromboembolism
  • AICD
  • Heart transplant
  • Family and genetic counseling

Arrhythmia-induced cardiomyopathy ^[12][13]

• Definition: recurring or persistent atrial or ventricular arrhythmias causing structural cardiac changes and left ventricular dysfunction (potentially reversible)
• Etiology
  • Supraventricular tachyarrhythmias (i.e., tachycardia, atrial fibrillation, atrial flutter, supraventricular reentry tachycardia)
  • Ventricular tachyarrhythmia (less commonly than supraventricular tachyarrhythmias)
  • Atrial or ventricular ectopy (with or without tachycardia)
• Clinical features
  • Signs of underlying arrhythmia (e.g., palpitations, syncope)
  • Signs of left heart failure (e.g., dyspnea, chest pain, pulmonary edema)
• Diagnostics
  • ECG: tachyarrhythmia, ectopic foci
  • Cardiac monitoring (e.g., Holter monitor)
  • Echocardiography and/or cardiac MRI: to evaluate cardiac structure and function (e.g., LVEF measurement)
  • To exclude other causes (e.g., coronary heart disease via coronary angiography)
• Treatment
  • Beta blockers: management of CHF, rate control in tachyarrhythmias
  • Antiarrhythmics (e.g., amiodarone): rhythm control in tachyarrhythmias
  • Catheter ablation: rhythm control in tachyarrhythmias, ectopic foci

1. Cooper LT. Definition and classification of the cardiomyopathies. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/definition-and-classification-of-the-cardiomyopathies?source=search_result&search=dilated%20cardiomyopathy&selectedTitle=4~150#H6.Last updated: June 12, 2015. Accessed: February 20, 2017.
2. Sisakian H. Cardiomyopathies: Evolution of pathogenesis concepts and potential for new therapies. World Journal of Cardiology. 2014; 6 (6): p.478. doi: 10.4330/wjc.v6.i6.478 . | Open in Read by QxMD
3. Japp AG, Gulati A, Cook SA, Cowie MR, Prasad SK. The Diagnosis and Evaluation of Dilated Cardiomyopathy. J Am Coll Cardiol. 2016; 67 (25): p.2996-3010. doi: 10.1016/j.jacc.2016.03.590 . | Open in Read by QxMD
4. Colucci WS, Chen HH. Natriuretic peptide measurement in heart failure. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. http://www.uptodate.com/contents/natriuretic-peptide-measurement-in-heart-failure.Last updated: March 14, 2016. Accessed: February 20, 2017.
5. William J McKenna, MD. Arrhythmogenic right ventricular cardiomyopathy: Anatomy, histology, and clinical manifestations. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/arrhythmogenic-right-ventricular-cardiomyopathy-anatomy-histology-and-clinical-manifestations.Last updated: June 6, 2019. Accessed: July 8, 2019.
6. William J McKenna, MD. Arrhythmogenic right ventricular cardiomyopathy: Pathogenesis and genetics. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/arrhythmogenic-right-ventricular-cardiomyopathy-pathogenesis-and-genetics.Last updated: June 6, 2019. Accessed: July 5, 2019.
7. Arrhythmogenic Right Ventricular Dysplasia (ARVD). https://emedicine.medscape.com/article/163856-overview#a4. Updated: September 14, 2014. Accessed: July 8, 2019.
8. William J McKenna, MD. Arrhythmogenic right ventricular cardiomyopathy: Treatment and prognosis. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/arrhythmogenic-right-ventricular-cardiomyopathy-treatment-and-prognosis.Last updated: June 6, 2019. Accessed: July 8, 2019.
9. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: Executive Summary. Circulation. 2018; 138 (13): p.e210–e271. doi: 10.1161/cir.0000000000000548 . | Open in Read by QxMD
10. Arman Arghami, Joseph A. Dearani, Sameh M. Said, Patrick W. O’Leary, and Hartzell V. Schaff. Hypertrophic cardiomyopathy in children. Annals of Cardiothoracic Surgery. 2017 .
11. Connolly HM, Attenhofer-Jost CH. Isolated left ventricular noncompaction. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/isolated-left-ventricular-noncompaction.Last updated: September 12, 2016. Accessed: March 30, 2017.
12. Tracy CM. Arrhythmia-induced cardiomyopathy. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/arrhythmia-induced-cardiomyopathy.Last updated: July 6, 2016. Accessed: February 20, 2017.
13. Gopinathannair R, Etheridge SP, Marchlinski FE, Spinale FG, Lakkireddy D, Olshansky B. Arrhythmia-Induced Cardiomyopathies Mechanisms, Recognition, and Management. J Am Coll Cardiol. 2015; 66 (15): p.1714-1728. doi: 10.1016/j.jacc.2015.08.038 . | Open in Read by QxMD
14. Kasper DL, Fauci AS, Hauser SL, Longo DL, Lameson JL, Loscalzo J. Harrison's Principles of Internal Medicine. McGraw-Hill Education ; 2015
15. Agabegi SS, Agabegi ED. Step-Up To Medicine. Wolters Kluwer Health ; 2015
16. Le T, Bhushan V, Chen V, King M. First Aid for the USMLE Step 2 CK. McGraw-Hill Education ; 2015
17. Le T, Bhushan V, Bagga HS. First Aid for the USMLE Step 2 CK. McGraw-Hill Medical ; 2009
18. Fischer C. Master the Boards USMLE Step 2 CK. Kaplan Publishing ; 2015
19. Maron MS. Hypertrophic cardiomyopathy: Clinical manifestations, diagnosis, and evaluation. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/hypertrophic-cardiomyopathy-clinical-manifestations-diagnosis-and-evaluation?source=search_result&search=hypertrophic+cardiomyopathy&selectedTitle=1~150#H17.Last updated: December 15, 2016. Accessed: February 13, 2017.
20. Nguyen VQ, Celebi MM, Suleman A, Sander GE. Dilated Cardiomyopathy. Dilated Cardiomyopathy. New York, NY: WebMD. http://emedicine.medscape.com/article/152696-overview. Updated: January 20, 2017. Accessed: February 20, 2017.
21. Elliott PM, Anastasakis A, Borger MA et al. 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: The Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC) . Eur Heart J. 2014; 35 (39): p.2733-2779. doi: 10.1093/eurheartj/ehu284 . | Open in Read by QxMD
22. Maron MS. Patient education: Hypertrophic cardiomyopathy (Beyond the Basics). In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. http://www.uptodate.com/contents/hypertrophic-cardiomyopathy-beyond-the-basics.Last updated: November 18, 2015. Accessed: February 20, 2017.
23. 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 . J Thorac Cardiovasc Surg. 2011; 142 (6): p.e153-203. doi: 10.1016/j.jtcvs.2011.10.020 . | Open in Read by QxMD
24. Shah SN. Hypertrophic Cardiomyopathy. Hypertrophic Cardiomyopathy. New York, NY: WebMD. http://emedicine.medscape.com/article/152913-overview#a4. Updated: January 5, 2016. Accessed: February 20, 2017.
25. Maron MS. Hypertrophic cardiomyopathy: Gene mutations and clinical genetic testing. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. http://www.uptodate.com/contents/hypertrophic-cardiomyopathy-gene-mutations-and-clinical-genetic-testing?source=see_link.Last updated: December 14, 2016. Accessed: February 20, 2017.
26. Hypertrophic Cardiomyopathy. http://www.heart.org/HEARTORG/Conditions/More/Cardiomyopathy/Hypertrophic-Cardiomyopathy_UCM_444317_Article.jsp#.WKreI7bhC8p. Updated: July 6, 2016. Accessed: February 20, 2017.
27. Vainrib A, Viccellio AW, Goswami VJ. Restrictive Cardiomyopathy. Restrictive Cardiomyopathy. New York, NY: WebMD. http://emedicine.medscape.com/article/153062-overview. Updated: December 18, 2014. Accessed: February 20, 2017.
28. Tomich EB. Takotsubo Cardiomyopathy. In: Schraga ED, Takotsubo Cardiomyopathy. New York, NY: WebMD. http://emedicine.medscape.com/article/1513631-overview. Updated: January 17, 2017. Accessed: March 30, 2017.
29. Reeder GS, Prasad A. Clinical manifestations and diagnosis of stress (takotsubo) cardiomyopathy. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-stress-takotsubo-cardiomyopathy.Last updated: March 28, 2017. Accessed: March 30, 2017.
30. Reeder GS, Prasad A. Management and prognosis of stress (takotsubo) cardiomyopathy. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/management-and-prognosis-of-stress-takotsubo-cardiomyopathy.Last updated: October 2, 2015. Accessed: March 30, 2017.
31. Shavelle DM. Pathophysiology of stunned or hibernating myocardium. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/pathophysiology-of-stunned-or-hibernating-myocardium.Last updated: December 10, 2015. Accessed: March 30, 2017.
32. Cisneros S, Duarte R, Fernandez-perez GC, et al. Left ventricular apical diseases. Insights Imaging. 2011; 2 (4): p.471-482. doi: 10.1007/s13244-011-0091-6 . | Open in Read by QxMD
33. Le T, Bhushan V,‎ Sochat M, Chavda Y, Zureick A. First Aid for the USMLE Step 1 2018. McGraw-Hill Medical ; 2017
34. Van Diepen S, Katz JN, Albert NM, et al. Contemporary Management of Cardiogenic Shock: A Scientific Statement From the American Heart Association. Circulation. 2017; 136 (16). doi: 10.1161/cir.0000000000000525 . | Open in Read by QxMD
35. Nishimura RA, Seggewiss H, Schaff HV. Hypertrophic Obstructive Cardiomyopathy. Circ Res. 2017; 121 (7): p.771-783. doi: 10.1161/circresaha.116.309348 . | Open in Read by QxMD
36. Maron MS, Hauser TH, Dubrow E, et al. Right Ventricular Involvement in Hypertrophic Cardiomyopathy. Am J Cardiol. 2007; 100 (8): p.1293-1298. doi: 10.1016/j.amjcard.2007.05.061 . | Open in Read by QxMD
37. Christian Prinz, Dr. med., Martin Farr, Dr. rer. nat., Detlef Hering, Dr. med., Dieter Horstkotte, Prof. Dr. med, and Lothar Faber, Prof. Dr. med.. The Diagnosis and Treatment of Hypertrophic Cardiomyopathy. Deutsches Ärzteblatt. 2011 .
38. Martin S. Maron, MD; Ethan J. Rowin, MD; Barry J. Maron, MD. How to Image Hypertrophic Cardiomyopathy. Circulation: Cardiovascular Imaging. 2017 .
39. Dr. Irena Peovska Mitevksa. Focus on echocardiography in hypertrophic cardiomyopathy - fourth in series. ESC Council for Cardiology Practice. 2015 .
40. Veselka J, Anavekar NS, Charron P. Hypertrophic obstructive cardiomyopathy. Lancet. 2017; 389 (10075): p.1253-1267. doi: 10.1016/s0140-6736(16)31321-6 . | Open in Read by QxMD
41. Diagnosis of Hypertrophic Cardiomyopathy: What Every Cardiologist Needs to Know. https://www.acc.org/latest-in-cardiology/articles/2020/02/25/06/34/diagnosis-of-hypertrophic-cardiomyopathy. Updated: February 27, 2020. Accessed: March 22, 2020.
42. Lee PT, Dweck MR, Prasher S, et al. Left Ventricular Wall Thickness and the Presence of Asymmetric Hypertrophy in Healthy Young Army Recruits. Circulation: Cardiovascular Imaging. 2013; 6 (2): p.262-267. doi: 10.1161/circimaging.112.979294 . | Open in Read by QxMD
43. Afonso LC, Bernal J, Bax JJ, Abraham TP. Echocardiography in Hypertrophic Cardiomyopathy. J Am Coll Cardiol Img. 2008; 1 (6): p.787-800. doi: 10.1016/j.jcmg.2008.09.002 . | Open in Read by QxMD
44. Maron BJ. Clinical Course and Management of Hypertrophic Cardiomyopathy. N Engl J Med. 2018; 379 (7): p.655-668. doi: 10.1056/nejmra1710575 . | Open in Read by QxMD
45. Ammirati E, Contri R, Coppini R, Cecchi F, Frigerio M, Olivotto I. Pharmacological treatment of hypertrophic cardiomyopathy: current practice and novel perspectives. European Journal of Heart Failure. 2016; 18 (9): p.1106-1118. doi: 10.1002/ejhf.541 . | Open in Read by QxMD
46. Sherrid MV, Barac I, McKenna WJ, et al. Multicenter study of the efficacy and safety of disopyramide in obstructive hypertrophic cardiomyopathy. J Am Coll Cardiol. 2005; 45 (8): p.1251-1258. doi: 10.1016/j.jacc.2005.01.012 . | Open in Read by QxMD
47. Houston BA, Stevens GR. Hypertrophic cardiomyopathy: a review.. Clin Med Insights Cardiol. 2014; 8 (Suppl 1): p.53-65. doi: 10.4137/CMC.S15717 . | Open in Read by QxMD