Hypertrophic cardiomyopathy medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Soroush Seifirad, M.D.[2]Cafer Zorkun, M.D. , Caitlin J. Harrigan ; Martin S. Maron, M.D.; Barry J. Maron, M.D.; Lakshmi Gopalakrishnan, M.B.B.S. [3]

Overview

The medical management of the patient with hypertrophic cardiomyopathy involves minimizing diastolic dysfunction, reducing left ventricular outflow tract obstruction, optimizing heart failure management, maintaining normal sinus rhythm, rate control and anticoagulation in the presence of atrial fibrillation, and implantation of an automatic implantable cardiac defibrillator in those patients who survive sudden cardiac death.

One of the fundamental goals of treatment is to relieve disabling dyspnea and improve exercise tolerance. It should be noted that the majority of patients do not have outflow tract obstruction, and therefore would not benefit from surgery. Medical therapy is, therefore, a mainstay of treatment. Given the limited number of patients with the condition, there are few randomized trials comparing strategies/agents in the management of HCM.

Initiation of Medical Therapy

Medical therapy is usually first initiated when signs and symptoms of exercise intolerance develop.

Diuretics

Treatment with diuretics (a mainstay of CHF treatment) will exacerbate symptoms in hypertrophic cardiomyopathy by decreasing ventricular volume and increasing outflow resistance.



Overview

In all patients with hypertrophic cardiomyopathy risk stratification is essential to attempt to ascertain which patients are at risk for sudden cardiac death [1] [2]. In those patients deemed to be at high risk the benefits and infrequent complications of defibrillator therapy are discussed; devices have been implanted in as many as 15% of patients at HOCM centers. Treatment symptoms of obstructive HOCM is directed towards decreasing the left ventricular outflow tract gradient and symptoms of dyspnea, chest pain and syncope.

Simple Supportive Measures

Avoid volume depletion

  • These patients should avoid volume depletion and dehydration which reduces Left ventricular volume and thereby exacerbates left ventricular outflow tract obstruction.

Avoid strenuous Activity

  • Strenuous activity has been associated with sudden cardiac death in these patients and for this reason these patients are counseled to avoid engaging in competitive sports.

Screening Relatives

  • This autosomal dominant disease has a high degree of penetrance and first degree relatives should be screened.

Pharmacotherapy

Medical therapy is successful in the majority of patients. The first medication that is routinely used is beta-blockade (metoprolol, atenolol, bisoprolol, propranolol)[1]. If symptoms and gradient persist disopyramide may be added to the beta-blocker [3]. Alternately a calcium channel blocker such as verapamil may be substituted for beta-blockade. It should be stressed that most patient's symptoms may be managed medically without needing to resort to inteventions such as surgical septal myectomy, alcohol septal ablation or pacing. Severe symptoms in non-obstructive HCM may actually be more difficult to treat because there is no obvious target (obstruction) to treat. Medical therapy with verapamil, beta-blockade may improve symptoms. Diuretics should be avoided, as they reduce the intravascular volume of blood, decreasing the amount of blood available to distend the left ventricular outflow tract, leading to an increase in the obstruction to the outflow of blood in the left ventricle [4].

As a summary:

  • The asymptomatic patient without risk factors for SCD (sudden cardiac death[) does not require therapy, even in the presence of NSVT. The symptomatic patient can be treated with negative inotropes such as calcium channel blockers and/or beta-blockers. Atrial fibrillation should be treated aggressively. Some use Disopyramide to maintain NSR (normal sinus rhythm) because of its negative inotropic effects. Amiodarone is the best medicine to maintain NSR and has been associated with symptomatic improvement in patients with HCM.

2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy (DO NOT EDIT)[5]

Pharmacologic Management in Symptomatic Patients (DO NOT EDIT)[5]

Class I
"1. Beta-blocking drugs are recommended for the treatment of symptoms (angina or dyspnea) in adult patients with obstructive or non-obstructive HCM but should be used with caution in patients with sinus bradycardia or severe conduction disease[6][7][8][1][9][10][11][12][13][14][15][16][17]. (Level of Evidence: B)"
"2. If low doses of beta-blocking drugs are ineffective for controlling symptoms (angina or dyspnea) in patients with HCM, it is useful to titrate the dose to a resting heart rate of less than 60 to 65 bpm (up to generally accepted and recommended maximum doses of these drugs)[6][7][8][10][11][12][13][14][15][16][17]. (Level of Evidence: B)"
"3. Verapamil therapy (starting in low doses and titrating up to 480 mg/d) is recommended for the treatment of symptoms (angina or dyspnea) in patients with obstructive or non-obstructive HCM who do not respond to beta-blocking drugs or who have side effects or contraindications to beta-blocking drugs. However, verapamil should be used with caution in patients with high gradients, advanced heart failure, or sinus bradycardia[7][8][1][18][19][20][21][22]. (Level of Evidence: B)"
"4. Intravenous phenylephrine (or another pure vasoconstricting agent) is recommended for the treatment of acute hypotension in patients with obstructive HCM who do not respond to fluid administration[8][23][24][25]. (Level of Evidence: B)"
Class IIa
"1. It is reasonable to combine disopyramide with a beta-blocking drug or verapamil in the treatment of symptoms (angina or dyspnea) in patients with obstructive HCM who do not respond to beta-blocking drugs or verapamil alone[7][8][1][26][27][28][29]. (Level of Evidence: B)"
"2. It is reasonable to add oral diuretics in patients with non-obstructive HCM when dyspnea persists despite the use of beta blockers or verapamil or their combination[2][9]. (Level of Evidence: C)"
Class IIb
"1. Beta-blocking drugs might be useful in the treatment of symptoms (angina or dyspnea) in children or adolescents with HCM, but patients treated with these drugs should be monitored for side effects, including depression, fatigue, or impaired scholastic performance. (Level of Evidence: C)"
"2. It may be reasonable to add oral diuretics with caution to patients with obstructive HCM when congestive symptoms persist despite the use of beta blockers or verapamil or their combination[7][8][1]. (Level of Evidence: C)"
"3. The usefulness of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in the treatment of symptoms (angina or dyspnea) in patients with HCM with preserved systolic function is not well established, and these drugs should be used cautiously (if at all) in patients with resting or provocable LVOT obstruction. (Level of Evidence: C)"
"4. In patients with HCM who do not tolerate verapamil or in whom verapamil is contraindicated, diltiazem may be considered. (Level of Evidence: C)"
Class III (Harm)
"1. Nifedipine or other dihydropyridine calcium channel-blocking drugs are potentially harmful for treatment of symptoms (angina or dyspnea) in patients with HCM who have resting or provocable LVOT obstruction. (Level of Evidence: C)"
"2. Verapamil is potentially harmful in patients with obstructive HCM in the setting of systemic hypotension or severe dyspnea at rest. (Level of Evidence: C)"
"3. Digitalis is potentially harmful in the treatment of dyspnea in patients with HCM and in the absence of AF[6][7][8][30][31][32]. (Level of Evidence: B)"
"4. The use of disopyramide alone without beta blockers or verapamil is potentially harmful in the treatment of symptoms (angina or dyspnea) in patients with HCM with AF because disopyramide may enhance atrioventricular conduction and increase the ventricular rate during episodes of AF[7][33][9][34][35][36][37][38][39]. (Level of Evidence: B)"
"5. Dopamine, dobutamine, norepinephrine, and other intravenous positive inotropic drugs are potentially harmful for the treatment of acute hypotension in patients with obstructive HCM[6][23][24][25][40][41][42][43]. (Level of Evidence: B)"

Management of Atrial Fibrillation in HCM (DO NOT EDIT)[44]

Class I
"1. Anticoagulation with vitamin K antagonists (ie, warfarin, to an international normalized ratio of 2.0 to 3.0) is indicated in patients with paroxysmal, persistent, or chronic AF and HCM[44][45][46]. (Anticoagulation with direct thrombin inhibitors [ie, dabigatran] may represent another option to reduce the risk of thromboembolic events, but data for patients with HCM are not available.)[47]. (Level of Evidence: C)"
"2. Ventricular rate control in patients with HCM with AF is indicated for rapid ventricular rates and can require high doses of beta antagonists and nondihydropyridine calcium channel blockers[44][46]. (Level of Evidence: C)"
Class IIa
"1. Disopyramide (with ventricular rate-controlling agents) and amiodarone are reasonable antiarrhythmic agents for AF in patients with HCM[44][48]. (Level of Evidence: B)"
"2. Radiofrequency ablation for AF can be beneficial in patients with HCM who have refractory symptoms or who are unable to take antiarrhythmic drugs[49][50][51][52][53]. (Level of Evidence: B)"
"3. Maze procedure with closure of left atrial appendage is reasonable in patients with HCM with a history of AF, either during septal myectomy or as an isolated procedure in selected patients. (Level of Evidence: C)"
Class IIb
"1. Sotalol, dofetilide, and dronedarone might be considered alternative antiarrhythmic agents in patients with HCM, especially in those with an ICD, but clinical experience is limited. (Level of Evidence: C)"

Sources

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 Maron BJ (2002). "Hypertrophic cardiomyopathy: a systematic review". JAMA. 287 (10): 1308–20. PMID 11886323.
  2. ↑ 2.0 2.1 Wigle ED, Rakowski H, Kimball BP, Williams WG (1995). "Hypertrophic cardiomyopathy. Clinical spectrum and treatment". Circulation. 92 (7): 1680–92. PMID 7671349.
  3. ↑ Sherrid MV, Barac I, McKenna WJ, Eliott M, Dickie S, Chojnowska L, Casey S, Maron BJ. Multicenter study of the efficacy and safety of disopyramide in obstructive hypertrophic cardiomyopathy. J Am College of Cardiol 2005; 45:1251–58
  4. ↑ Wynne J, Braunwald E. Hypertrophic cardiomyopathy. In: Braunwald E, ed. Heart disease: a textbook of cardiovascular medicine. 5th ed. Philadelphia: WB Saunders; 1997.
  5. ↑ 5.0 5.1 5.2 Gersh BJ, Maron BJ, Bonow RO, Dearani JA, Fifer MA, Link MS, Naidu SS, Nishimura RA, Ommen SR, Rakowski H, Seidman CE, Towbin JA, Udelson JE, Yancy CW (2011). "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 Developed in Collaboration With the American Association for Thoracic Surgery, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons". Journal of the American College of Cardiology. 58 (25): e212–60. doi:10.1016/j.jacc.2011.06.011. PMID 22075469. Retrieved 2011-12-19. Unknown parameter |month= ignored (help)
  6. ↑ 6.0 6.1 6.2 6.3 BRAUNWALD E, LAMBREW CT, ROCKOFF SD, ROSS J, MORROW AG (1964). "IDIOPATHIC HYPERTROPHIC SUBAORTIC STENOSIS. I. A DESCRIPTION OF THE DISEASE BASED UPON AN ANALYSIS OF 64 PATIENTS". Circulation. 30: SUPPL 4:3–119. PMID 14227306. Unknown parameter |month= ignored (help)
  7. ↑ 7.0 7.1 7.2 7.3 7.4 7.5 7.6 Maron BJ, McKenna WJ, Danielson GK; et al. (2003). "American College of Cardiology/European Society of Cardiology clinical expert consensus document on hypertrophic cardiomyopathy. A report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the European Society of Cardiology Committee for Practice Guidelines". J. Am. Coll. Cardiol. 42 (9): 1687–713. PMID 14607462. Unknown parameter |month= ignored (help)
  8. ↑ 8.0 8.1 8.2 8.3 8.4 8.5 8.6 Fifer MA, Vlahakes GJ (2008). "Management of symptoms in hypertrophic cardiomyopathy". Circulation. 117 (3): 429–39. doi:10.1161/CIRCULATIONAHA.107.694158. PMID 18212300. Unknown parameter |month= ignored (help)
  9. ↑ 9.0 9.1 9.2 Spirito P, Seidman CE, McKenna WJ, Maron BJ (1997). "The management of hypertrophic cardiomyopathy". N. Engl. J. Med. 336 (11): 775–85. doi:10.1056/NEJM199703133361107. PMID 9052657. Unknown parameter |month= ignored (help)
  10. ↑ 10.0 10.1 Adelman AG, Shah PM, Gramiak R, Wigle ED (1970). "Long-term propranolol therapy in muscular subaortic stenosis". Br Heart J. 32 (6): 804–11. PMC 487418. PMID 5212354. Unknown parameter |month= ignored (help)
  11. ↑ 11.0 11.1 Cohen LS, Braunwald E (1967). "Amelioration of angina pectoris in idiopathic hypertrophic subaortic stenosis with beta-adrenergic blockade". Circulation. 35 (5): 847–51. PMID 6067064. Unknown parameter |month= ignored (help)
  12. ↑ 12.0 12.1 Flamm MD, Harrison DC, Hancock EW (1968). "Muscular subaortic stenosis. Prevention of outflow obstruction with propranolol". Circulation. 38 (5): 846–58. PMID 4177137. Unknown parameter |month= ignored (help)
  13. ↑ 13.0 13.1 Frank MJ, Abdulla AM, Canedo MI, Saylors RE (1978). "Long-term medical management of hypertrophic obstructive cardiomyopathy". Am. J. Cardiol. 42 (6): 993–1001. PMID 569434. Unknown parameter |month= ignored (help)
  14. ↑ 14.0 14.1 HARRISON DC, BRAUNWALD E, GLICK G, MASON DT, CHIDSEY CA, ROSS J (1964). "EFFECTS OF BETA ADRENERGIC BLOCKADE ON THE CIRCULATION WITH PARTICULAR REFERENCE TO OBSERVATIONS IN PATIENTS WITH HYPERTROPHIC SUBAORTIC STENOSIS". Circulation. 29: 84–98. PMID 14105035. Unknown parameter |month= ignored (help)
  15. ↑ 15.0 15.1 Stenson RE, Flamm MD, Harrison DC, Hancock EW (1973). "Hypertrophic subaortic stenosis. Clinical and hemodynamic effects of long-term propranolol therapy". Am. J. Cardiol. 31 (6): 763–73. PMID 4735938. Unknown parameter |month= ignored (help)
  16. ↑ 16.0 16.1 Swanton RH, Brooksby IA, Jenkins BS, Webb-Peploe MM (1977). "Hemodynamic studies of beta blockade in hypertrophic obstructive cardiomyopathy". Eur J Cardiol. 5 (4): 327–41. PMID 196858. Unknown parameter |month= ignored (help)
  17. ↑ 17.0 17.1 Wigle ED, Adelman AG, Felderhof CH (1974). "Medical and surgical treatment of the cardiomyopathies". Circ. Res. 35 (2): suppl II:196–207. PMID 4858427. Unknown parameter |month= ignored (help)
  18. ↑ Bonow RO, Rosing DR, Bacharach SL; et al. (1981). "Effects of verapamil on left ventricular systolic function and diastolic filling in patients with hypertrophic cardiomyopathy". Circulation. 64 (4): 787–96. PMID 7196813. Unknown parameter |month= ignored (help)
  19. ↑ Epstein SE, Rosing DR (1981). "Verapamil: its potential for causing serious complications in patients with hypertrophic cardiomyopathy". Circulation. 64 (3): 437–41. PMID 7196300. Unknown parameter |month= ignored (help)
  20. ↑ Rosing DR, Kent KM, Maron BJ, Epstein SE (1979). "Verapamil therapy: a new approach to the pharmacologic treatment of hypertrophic cardiomyopathy. II. Effects on exercise capacity and symptomatic status". Circulation. 60 (6): 1208–13. PMID 574067. Unknown parameter |month= ignored (help)
  21. ↑ Rosing DR, Kent KM, Borer JS, Seides SF, Maron BJ, Epstein SE (1979). "Verapamil therapy: a new approach to the pharmacologic treatment of hypertrophic cardiomyopathy. I. Hemodynamic effects". Circulation. 60 (6): 1201–7. PMID 574066. Unknown parameter |month= ignored (help)
  22. ↑ Rosing DR, Condit JR, Maron BJ; et al. (1981). "Verapamil therapy: a new approach to the pharmacologic treatment of hypertrophic cardiomyopathy: III. Effects of long-term administration". Am. J. Cardiol. 48 (3): 545–53. PMID 7196690. Unknown parameter |month= ignored (help)
  23. ↑ 23.0 23.1 BRAUNWALD E, EBERT PA (1962). "Hemogynamic alterations in idiopathic hypertrophic subaortic stenosis induced by sympathomimetic drugs". Am. J. Cardiol. 10: 489–95. PMID 14015086. Unknown parameter |month= ignored (help)
  24. ↑ 24.0 24.1 WIGLE ED, DAVID PR, LABROOSE CJ, MCMEEKAN J (1965). "MUSCULAR SUBAORTIC STENOSIS; THE INTERRELATION OF WALL TENSION, OUTFLOW TRACT "DISTENDING PRESSURE" AND ORIFICE RADIUS". Am. J. Cardiol. 15: 761–72. PMID 14295867. Unknown parameter |month= ignored (help)
  25. ↑ 25.0 25.1 Haley JH, Sinak LJ, Tajik AJ, Ommen SR, Oh JK (1999). "Dynamic left ventricular outflow tract obstruction in acute coronary syndromes: an important cause of new systolic murmur and cardiogenic shock". Mayo Clin. Proc. 74 (9): 901–6. doi:10.4065/74.9.901. PMID 10488794. Unknown parameter |month= ignored (help)
  26. ↑ Kimball BP, Bui S, Wigle ED (1993). "Acute dose-response effects of intravenous disopyramide in hypertrophic obstructive cardiomyopathy". Am. Heart J. 125 (6): 1691–7. PMID 8498312. Unknown parameter |month= ignored (help)
  27. ↑ Pollick C, Kimball B, Henderson M, Wigle ED (1988). "Disopyramide in hypertrophic cardiomyopathy. I. Hemodynamic assessment after intravenous administration". Am. J. Cardiol. 62 (17): 1248–51. PMID 3195486. Unknown parameter |month= ignored (help)
  28. ↑ Pollick C (1988). "Disopyramide in hypertrophic cardiomyopathy. II. Noninvasive assessment after oral administration". Am. J. Cardiol. 62 (17): 1252–5. PMID 3057852. Unknown parameter |month= ignored (help)
  29. ↑ Sherrid M, Delia E, Dwyer E (1988). "Oral disopyramide therapy for obstructive hypertrophic cardiomyopathy". Am. J. Cardiol. 62 (16): 1085–8. PMID 3189171. Unknown parameter |month= ignored (help)
  30. ↑ Braunwald E, Bloodwell RD, Goldberg LI, Morrow AG (1961). "STUDIES ON DIGITALIS. IV. OBSERVATIONS IN MAN ON THE EFFECTS OF DIGITALIS PREPARATIONS ON THE CONTRACTILITY OF THE NON-FAILING HEART AND ON TOTAL VASCULAR RESISTANCE". J. Clin. Invest. 40 (1): 52–9. doi:10.1172/JCI104236. PMC 290689. PMID 16695846. Unknown parameter |month= ignored (help)
  31. ↑ BRAUNWALD E, BROCKENBROUGH EC, FRYE RL (1962). "Studies on digitalis. V. Comparison of the effects of ouabain on left ventricular dynamics in valvular aortic stenosis and hypertrophic subaortic stenosis". Circulation. 26: 166–73. PMID 13872647. Unknown parameter |month= ignored (help)
  32. ↑ Sonnenblick EH, Williams JF, Glick G, Mason DT, Braunwald E (1966). "Studies on digitalis. XV. Effects of cardiac glycosides on myocardial force-velocity relations in the nonfailing human heart". Circulation. 34 (3): 532–9. PMID 5922716. Unknown parameter |month= ignored (help)
  33. ↑ Wigle ED, Sasson Z, Henderson MA; et al. (1985). "Hypertrophic cardiomyopathy. The importance of the site and the extent of hypertrophy. A review". Prog Cardiovasc Dis. 28 (1): 1–83. PMID 3160067.
  34. ↑ Bergfeldt L, Schenck-Gustafsson K, Dahlqvist R (1992). "Comparative class 1 electrophysiologic and anticholinergic effects of disopyramide and its main metabolite (mono-N-dealkylated disopyramide) in healthy humans". Cardiovasc Drugs Ther. 6 (5): 529–37. PMID 1450096. Unknown parameter |month= ignored (help)
  35. ↑ Birkhead JS, Vaughan Williams EM (1977). "Dual effect of disopyramide on atrial and atrioventricular conduction and refractory periods". Br Heart J. 39 (6): 657–60. PMC 483295. PMID 884018. Unknown parameter |month= ignored (help)
  36. ↑ Jensen G, Uhrenholt A (1976). "Circulatory effects of intravenous disopyramide in heart failure". J. Int. Med. Res. 4 (1 Suppl): 42–5. PMID 1026527.
  37. ↑ Lara M, Oakley GD, Rowbotham D (1980). "Potentially dangerous effect of disopyramide on atrioventricular conduction in a patient on digitalis". Br Med J. 281 (6234): 198. PMC 1713674. PMID 7407521. Unknown parameter |month= ignored (help)
  38. ↑ Morady F, Scheinman MM, Desai J (1982). "Disopyramide". Ann. Intern. Med. 96 (3): 337–43. PMID 7036817. Unknown parameter |month= ignored (help)
  39. ↑ Robertson CE, Miller HC (1980). "Extreme tachycardia complicating the use of disopyramide in atrial flutter". Br Heart J. 44 (5): 602–3. PMC 482452. PMID 7437205. Unknown parameter |month= ignored (help)
  40. ↑ Elesber A, Nishimura RA, Rihal CS, Ommen SR, Schaff HV, Holmes DR (2008). "Utility of isoproterenol to provoke outflow tract gradients in patients with hypertrophic cardiomyopathy". Am. J. Cardiol. 101 (4): 516–20. doi:10.1016/j.amjcard.2007.09.111. PMID 18312769. Unknown parameter |month= ignored (help)
  41. ↑ KRASNOW N, ROLETT E, HOOD WBJr, YURCHAK PM, GORLIN R (1963). "Reversible obstruction of the ventricular outflow tract". Am. J. Cardiol. 11: 1–7. PMID 14035510. Unknown parameter |month= ignored (help)
  42. ↑ PIERCE GE, MORROW AG, BRAUNWALD E (1964). "IDIOPATHIC HYPERTROPHIC SUBAORTIC STENOSIS. 3. INTRAOPERATIVE STUDIES OF THE MECHANISM OF OBSTRUCTION AND ITS HEMODYNAMIC CONSEQUENCES". Circulation. 30: SUPPL 4:152+. PMID 14227305. Unknown parameter |month= ignored (help)
  43. ↑ WHALEN RE, COHEN AI, SUMNER RG, McINTOSH HD (1963). "Demonstration of the dynamic nature of idiopathic hypertrophic subaortic stenosis". Am. J. Cardiol. 11: 8–17. PMID 14000190. Unknown parameter |month= ignored (help)
  44. ↑ 44.0 44.1 44.2 44.3 44.4 Fuster V, Rydén LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA; et al. (2011). "2011 ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines". Circulation. 123 (10): e269–367. doi:10.1161/CIR.0b013e318214876d. PMID 21382897.
  45. ↑ Maron BJ, Olivotto I, Bellone P; et al. (2002). "Clinical profile of stroke in 900 patients with hypertrophic cardiomyopathy". J. Am. Coll. Cardiol. 39 (2): 301–7. PMID 11788223. Unknown parameter |month= ignored (help)
  46. ↑ 46.0 46.1 Olivotto I, Cecchi F, Casey SA, Dolara A, Traverse JH, Maron BJ (2001). "Impact of atrial fibrillation on the clinical course of hypertrophic cardiomyopathy". Circulation. 104 (21): 2517–24. PMID 11714644. Unknown parameter |month= ignored (help)
  47. ↑ Connolly SJ, Ezekowitz MD, Yusuf S; et al. (2009). "Dabigatran versus warfarin in patients with atrial fibrillation". N. Engl. J. Med. 361 (12): 1139–51. doi:10.1056/NEJMoa0905561. PMID 19717844. Unknown parameter |month= ignored (help)
  48. ↑ Tendera M, Wycisk A, Schneeweiss A, Poloński L, Wodniecki J (1993). "Effect of sotalol on arrhythmias and exercise tolerance in patients with hypertrophic cardiomyopathy". Cardiology. 82 (5): 335–42. PMID 8374931.
  49. ↑ Bunch TJ, Munger TM, Friedman PA; et al. (2008). "Substrate and procedural predictors of outcomes after catheter ablation for atrial fibrillation in patients with hypertrophic cardiomyopathy". J. Cardiovasc. Electrophysiol. 19 (10): 1009–14. doi:10.1111/j.1540-8167.2008.01192.x. PMID 18479329. Unknown parameter |month= ignored (help)
  50. ↑ Callans DJ (2008). "Ablation of atrial fibrillation in the setting of hypertrophic cardiomyopathy". J. Cardiovasc. Electrophysiol. 19 (10): 1015–6. doi:10.1111/j.1540-8167.2008.01230.x. PMID 18554205. Unknown parameter |month= ignored (help)
  51. ↑ Di Donna P, Olivotto I, Delcrè SD; et al. (2010). "Efficacy of catheter ablation for atrial fibrillation in hypertrophic cardiomyopathy: impact of age, atrial remodelling, and disease progression". Europace. 12 (3): 347–55. doi:10.1093/europace/euq013. PMID 20173211. Unknown parameter |month= ignored (help)
  52. ↑ Gaita F, Di Donna P, Olivotto I; et al. (2007). "Usefulness and safety of transcatheter ablation of atrial fibrillation in patients with hypertrophic cardiomyopathy". Am. J. Cardiol. 99 (11): 1575–81. doi:10.1016/j.amjcard.2006.12.087. PMID 17531584. Unknown parameter |month= ignored (help)
  53. ↑ Kilicaslan F, Verma A, Saad E; et al. (2006). "Efficacy of catheter ablation of atrial fibrillation in patients with hypertrophic obstructive cardiomyopathy". Heart Rhythm. 3 (3): 275–80. doi:10.1016/j.hrthm.2005.11.013. PMID 16500298. Unknown parameter |month= ignored (help)
  54. ↑ Gersh BJ, Maron BJ, Bonow RO, Dearani JA, Fifer MA, Link MS, Naidu SS, Nishimura RA, Ommen SR, Rakowski H, Seidman CE, Towbin JA, Udelson JE, Yancy CW (2011). "2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy: Executive Summary A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the American Association for Thoracic Surgery, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons". Journal of the American College of Cardiology. 58 (25): 2703–38. doi:10.1016/j.jacc.2011.10.825. PMID 22075468. Retrieved 2011-12-19. Unknown parameter |month= ignored (help)


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