|Year : 2011 | Volume
| Issue : 3 | Page : 112-117
Hypertrophic Cardiomyopathy in a Young Adult with RV Aneurysm: Report of a Rare Finding and Review of the Literature
Ahmed M Abdel-Razek, Leonard Y Lee, Robert Tozzi
Divisions of Cardiothoracic Surgery and Cardiology, Hackensack University Medical Center, Hackensack, NJ, USA
|Date of Web Publication||16-Apr-2012|
Ahmed M Abdel-Razek
Department of Cardiothoracic Surgery, Hackensack University Medical Center, 30 Prospect Avenue, Hackensack, NJ 07601
Source of Support: None, Conflict of Interest: None
| Abstract|| |
We report a case of a 22-year-old patient with a severe form of hypertrophic cardiomyopathy involving both ventricles, for which he underwent surgical treatment. Echocardiogram and magnetic resonance imaging confirmed the presence of an aneurysm in the inferior-anterior portion of the right ventricle.
Keywords: Hypertrophic cardiomyopathy, right ventricular aneurysm and left ventricular outflow tract
|How to cite this article:|
Abdel-Razek AM, Lee LY, Tozzi R. Hypertrophic Cardiomyopathy in a Young Adult with RV Aneurysm: Report of a Rare Finding and Review of the Literature. Heart Views 2011;12:112-7
|How to cite this URL:|
Abdel-Razek AM, Lee LY, Tozzi R. Hypertrophic Cardiomyopathy in a Young Adult with RV Aneurysm: Report of a Rare Finding and Review of the Literature. Heart Views [serial online] 2011 [cited 2020 Jul 5];12:112-7. Available from: http://www.heartviews.org/text.asp?2011/12/3/112/95067
| Introduction|| |
Hypertrophic cardiomyopathy (HCM) is a well-described but difficult to define disease. HCM is a collection of similar genetic diseases that can result from one or more sarcomere mutations in a single patient. Common accelerants of ventricular hypertrophy include obesity, sleep apnea, diabetes, hypertension and aortic stenosis. Right ventricular (RV) aneurysms are very rare to occur, and we believe that they have never been reported before in association with HCM.
| Case Report|| |
A 22-year-old male patient presented with a severe form of HCM involving both the ventricles. He had a history of right and left ventricular outflow tract obstruction which had required surgical intervention in the form of bilateral myectomy that was performed at the Mayo Clinic in 2004.
The patient's symptoms started at 1½years of age at which time he presented with tachycardia and hypertrophy and was diagnosed with HCM. At 8 years of age, the patient's tachycardia necessitated intervention at which time the patient underwent a successful ablation for ectopic atrial tachycardia at Boston Children's Hospital.
At 15 years of age, the condition progressed requiring surgical intervention. At Mayo Clinic, he underwent extended septal wall myomectomy that involved surgical excision of tissue from both right and left ventricles. The result was a dramatic improvement in symptoms.
Maintenance drug is Tenormin (50 mg in the morning and 25 mg at night). The family has been against the placement of an implantable cardioverter-defibrillator (ICD), and at 22 years of age, additional testing was performed to help with risk stratification. The Holter revealed ventricular ectopy but no runs of ventricular tachycardia. His stress test confirmed the presence of an abnormal fall in BP with exercise. Magnetic resonance imaging (MRI) demonstrated an RV aneurysm with no obvious thrombus [Figure 1] and [Figure 2].
|Figure 1: Inferior view of a transverse section of a MRI (Magnetic resonance imaging) showing the right ventricle (RV) and the aneurysm|
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|Figure 2: Inferior view of a transverse section of an Magnetic resonance imaging (MRI) showing the right ventricle (RV) during contraction and the hypokinetic aneurysm|
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On examination, the precordium was quiet with a normal S1 and S2. There was a 2-3/6 systolic ejection murmur present at the base with radiation to the back, head and neck.
The electrocardiogram showed voltage criteria for biventricular hypertrophy.
The echocardiogram confirmed the presence of a significant dilatation of inferior-anterior portion of the right ventricle. The aneurysm was well visualized with no obvious clot formation. There was mid-cavity obliteration in systole in the right ventricle. There was no significant left ventricular outflow tract (LVOT) obstruction. The sites of the previous myectomy were well visualized. There was minor mitral and tricuspid valve insufficiency.
| Discussion|| |
Review of literature
HCM is a well-described but difficult to define disease. HCM is a collection of similar genetic diseases that can result from one or more sarcomere mutations in a single patient. This is complicated by variable phenotypic expression from identified and yet to be discovered variants. Other causes of LV hypertrophy can confuse the diagnosis. Common accelerants of ventricular hypertrophy include obesity, sleep apnea, diabetes, hypertension and aortic stenosis. The diagnosis can be strengthened by confirmation of a known mutation on genetic testing. The characteristic findings on echocardiography include ventricular hypertrophy, symmetric or asymmetric (ratio of septum thickness to LV wall thickness, >1.3:1), presence of a narrow LVOT with a pressure gradient suggestive of obstruction, systolic anterior motion (SAM) of mitral valve or the chordae. 70% of patients with HCM have LVOT obstruction either at rest or with exercise. When outflow tract obstruction is present, then the patient is described as having hypertrophic obstructive cardiomyopathy.
MRI plays an important diagnostic role in visualizing areas of myocardium that are inadequately evaluated by ultrasound. 
HCM is inherited as autosomal dominant with variable penetrance and is caused by mutations in 11 genes encoding proteins of the cardiac sarcomere (13-15). These 11 genes are: beta-myosin heavy chain, cardiac myosin-binding protein C, cardiac troponin-T, troponin I, alpha-tropomyosin, myozenin 2 (calsarcin 1), myosin light chain, myosin light chain 2, alpha-actin, titin, and telethonin. There are other genes that are thought to have an association with HCM and are as follows: myosin light chain kinase 2, alpha-myocin heavy chain, cardiac troponin C, caveolin 3 and phopholamban. 
Although the LV is the predominant site of involvement, RV involvement may occur in apparent isolation or in association with left-sided involvement.  Younger people are likely to have a more severe form of HCM.  Most cases are familial conditions that are genetically transmitted, but the disease can also be a spontaneous mutation.
The most common cause for acquired cardiomyopathy is myocarditis due to viral infections. Other causes include: cocaine, interleukin 2 or viral infections (coxsackievirus, adenovirus, parvovirus, HIV), bacterial (diphtheria, meningococcus, psittacosis, streptococcus), rickettsial (typhus, Rocky Mountain spotted fever), fungal (aspergillosis, candidiasis), and parasitic (chagas disease, toxoplasmosis) and giant cell myocarditis. 
The causes of secondary cardiomyopathy include, but are not limited to, amyloidosis, Gaucher's disease; hemochromatosis, Fabry's; endomyocardial fibrosis and hypereosinophilic syndrome; sarcoidosis, Diabetes Mellitus; Noonan syndrome; Friedreich's ataxia and Duchenne-Becker muscular dystrophy; pellagra; systemic lupus erythematosis and scleroderma; doxorubicin and radiation. 
Thickening of the myocardium occurs most commonly at the inter-ventricular septum. The thickened septum may cause a narrowing that can block or reduce the blood flow from the LV to the aorta, a condition called "outflow tract obstruction" often mimicking aortic stenosis. This type of HCM may be called hypertrophic obstructive cardiomyopathy.
HCM is the most common genetic heart disease, the leading cause of sudden cardiac death in the young, and a cause of heart failure symptoms and death at any age. ,,,,,,
HCM can be considered obstructive or non obstructive, depending on the presence of LVOT gradient, either at rest or with provocative maneuvers.  Younger patients often have more diffuse hypertrophy and reversal of septal curvature, whereas older patients tend to have focal proximal septal hypertrophy, with a sigmoid septal morphology. ,[ 14],,, These may be two different disease processes because subjects with reversal of septal curvature were found to have an almost 80% yield for screening for HCM-associated mutations but those with a sigmoid septum had less than a 10% correlation. Hypertrophy often develops or worsens during the adolescent growth spurt. An apical variant of HCM also exists.
LV hypertrophy usually involves thickening of the proximal portion of the interventricular septum, resulting in narrowing of the LVOT.
SAM may occur if the mitral valve leaflets are pulled or dragged anteriorly toward the ventricular septum during ventricular contraction due to Bernoulli Effect. ,,, SAM results in LVOT obstruction and mitral regurgitation. Consequently, the left ventricle has to generate higher pressures to overcome the LVOT obstruction. Premature closure of the aortic valve may occur, caused by the decline in pressure distal to the LVOT obstruction. ,,
The obstruction that occurs with HCM is dynamic, therefore the degree of obstruction depends more on cardiac contractility and loading conditions than on fixed obstructions. An underfilled left ventricle results in greater obstruction because there is less space between the mitral valve and interventricular septum. Augmenting cardiac contractility also increases LVOT obstruction because a more vigorous contraction is more likely to cause the obstructing components to come together. Most patients with HCM have a favorable prognosis. ,,,,
HCM has a variable course in which most patients are asymptomatic. The most common symptom is dyspnea on exertion; others include chest pain on exertion, syncope and palpitations.
Diagnosis and treatment
- Chest radiograph may suggest LV hypertrophy.
- Electrocardiogram could show LV hypertrophy. 
- Echocardiography is the gold standard for diagnosing HCM. ,
- Transthoracic echocardiogram : The septum can be well visualized and measured in the parasternal long, apical long, apical four-chamber, and parasternal short axis views. ,,
- Stress echocardiography is performed in patients with HCM to assess the functional significance of LVOT obstruction.
- Transesophageal echocardiography can be conducted in subjects with technically limited imaging or as part of intraoperative monitoring during surgical intervention.
- MRI plays an important diagnostic role in its ability to visualize areas of myocardium that are inadequately evaluated by ultrasound.
HCM subjects should avoid strenuous activity because it will increase the afterload to the myocardium and can worsen hypertrophy,  and maintain adequate hydration.
are the first-line therapy for symptomatic HCM. Beta blockers decrease the contractile force which leads to decrease in the outflow gradient and decreased oxygen demand. Beta blockers also lengthen diastolic filling by slowing the heart rate. ,,,,,, Calcium channel blockers are second-line therapy because of their negative inotropic effect. ,,,,, The second-line agents are the Class IA antiarrhythmic agents that have negative inotropic effects. ,,, Surgical interventions and proceduresSeptal myectomy decreases LVOT gradients and improves the symptoms. ,,,,,,,,, Percutaneous alcohol septal ablation consideration is always second line because of formation of scar tissue in the myocardium.
| Conclusions|| |
RV aneurysms associated with HCM is a rare condition. The possible cause would be the pathologic process that causes myocyte disarray in HCM, increasing the thickness of the ventricular wall and also leading to local ventricular atrophy.  Regardless of the etiology, the treatment strategies remain the same.
Radionuclide imaging with analysis of viability utilizing Fluorine-18-Labeled Deoxyglucose Positron Emission Tomography (18F-FDG-PET) could provide additional information on the pathogenesis of RV aneurysm. Patients with RV aneurysms and HCM are at increased risk for life-threatening ventricular tachyarrhythmia and sudden death,  in which management strategies should be directed toward prevention of these risks.
| References|| |
|1.||Lauschke J, Maisch B. Athlete's heart or hypertrophic cardiomyopathy? Clin Res Cardiol 2009;98:80-8. |
|2.||Marian AJ. Hypertrophic cardiomyopathy: From genetics to treatment. Eur J Clin Invest 2010;40:360-9. |
|3.||Wigle ED, Sasson Z, Henderson MA, Ruddy TD, Fulop J, Rakowski H, et al. Hypertrophic cardiomyopathy. The importance of the site and the extent of hypertrophy. A review. Prog Cardiovasc Dis 1985;28:1-83. |
|4.||Maron BJ, Roberts WC, Epstein SE. Sudden death in hypertrophic cardiomyopathy: Profile of 78 patients. Circulation 1982;65:1388-94. |
|5.||Maron BJ, Towbin JA, Thiene G, Antzelevitch C, Corrado D, Arnett D, et al. Contemporary definitions and classification of the cardiomyopathies: An American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation 2006;113:1807-16. |
|6.||Maron BJ. Hypertrophic cardiomyopathy: A systematic review. JAMA 2002;287:1308-20. |
|7.||Spirito P, Seidman CE, McKenna WJ, Maron BJ. The management of hypertrophic cardiomyopathy. N Engl J Med 1997;336:775-85. |
|8.||Maron BJ, McKenna WJ, Danielson GK, Kappenberger LJ, Kuhn HJ, Seidman CE, et al. American college of cardiology/European society of cardiology. 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 2003;42:1687-713. |
|9.||Elliott PM, Poloniecki J, Dickie S, Sharma S, Monserrat L, Varnava A, et al. Sudden death in hypertrophic cardiomyopathy: Identification of high risk patients. J Am Coll Cardiol 2000;36:2212-8. |
|10.||Spirito P, Bellone P, Harris KM, Bernabo P, Bruzzi P, Maron BJ. Magnitude of left ventricular hypertrophy and risk of sudden death in hypertrophic cardiomyopathy. N Engl J Med 2000;342:1778-85. |
|11.||Wigle ED, Rakowski H, Kimball BP, Williams WG. Hypertrophic cardiomyopathy. Clinical spectrum and treatment. Circulation 1995;92:1680-92. |
|12.||Autore C, Bernabo P, Barilla CS, Bruzzi P, Spirito P. The prognostic importance of left ventricular outflow obstruction in hypertrophic cardiomyopathy varies in relation to the severity of symptoms. J Am Coll Cardiol 2005;45:1076-80. |
|13.||Braunwald E, Lambrew CT, Rockoff SD, Ross J Jr, Morrow AG. Idiopathic hypertrophic subaortic stenosis. A Description of the disease based upon an analysis of 64 patients. Circulation 1964;30: SUPPL 4:3-119. |
|14.||Maron BJ. Hypertrophic cardiomyopathy. Lancet 1997;350:127-33. |
|15.||Lewis JF, Maron BJ. Elderly patients with hypertrophic cardiomyopathy: A subset with distinctive left ventricular morphology and progressive clinical course late in life. J Am Coll Cardiol 1989;13:36-45. |
|16.||Lewis JF, Maron BJ. Clinical and morphologic expression of hypertrophic cardiomyopathy in patients greater than 65 years of age. Am J Cardiol 1994;73:1105-11. |
|17.||Lever HM, Karam RF, Currie PJ, Healy BP. Hypertrophic cardiomyopathy in the elderly. Distinctions from the young based on cardiac shape. Circulation 1989;79:580-9. |
|18.||Sherrid MV, Gunsburg DZ, Moldenhauer S, Pearle G. Systolic anterior motion begins at low left ventricular outflow tract velocity in obstructive hypertrophic cardiomyopathy. J Am Coll Cardiol 2000;36:1344-54. |
|19.||Sherrid MV, Chu CK, Delia E, Mogtader A, Dwyer EM Jr. An echocardiographic study of the fluid mechanics of obstruction in hypertrophic cardiomyopathy. J Am Coll Cardiol 1993;22:816-25. |
|20.||Sherrid MV. Dynamic left ventricular outflow obstruction in hypertrophic cardiomyopathy revisited: Significance, pathogenesis, and treatment. Cardiol Rev 1998;6:135-45. |
|21.||Jiang L, Levine RA, King ME, Weyman AE. Integrated mechanism for systolic anterior motion of the mitral valve in hypertrophic cardiomyopathy based on echocardiographic observations. Am Heart J 1987;113:633-44. |
|22.||Wigle ED, Adelman AG, Auger P, Marquis Y. Mitral regurgitation in muscular subaortic stenosis. Am J Cardiol 1969;24:698-706. |
|23.||Nihoyannopoulos P, Karatasakis G, Frenneaux M, McKenna WJ, Oakley CM. Diastolic function in hypertrophic cardiomyopathy: Relation to exercise capacity. J Am Coll Cardiol 1992;19:536-40. |
|24.||Bonow RO, Dilsizian V, Rosing DR, Maron BJ, Bacharach SL, Green MV. Verapamil-induced improvement in left ventricular diastolic filling and increased exercise tolerance in patients with hypertrophic cardiomyopathy: Short- and long-term effects. Circulation 1985;72:853-64. |
|25.||Bonow RO, Vitale DF, Maron BJ, Bacharach SL, Frederick TM, Green MV. Regional left ventricular asynchrony and impaired global left ventricular filling in hypertrophic cardiomyopathy: Effect of verapamil. J Am Coll Cardiol 1987;9:1108-16. |
|26.||Frank S, Braunwald E. Idiopathic hypertrophic subaortic stenosis. Clinical analysis of 126 patients with emphasis on the natural history. Circulation 1968;37:759-88. |
|27.||Maron BJ, Gottdiener JS, Epstein SE. Patterns and significance of distribution of left ventricular hypertrophy in hypertrophic cardiomyopathy. A wide angle, two dimensional echocardiographic study of 125 patients. Am J Cardiol 1981;48:418-28. |
|28.||Shapiro LM, McKenna WJ. Distribution of left ventricular hypertrophy in hypertrophic cardiomyopathy: A two-dimensional echocardiographic study. J Am Coll Cardiol 1983;2:437-44. |
|29.||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;26:1699-708. |
|30.||Maron BJ, Isner JM, McKenna WJ. 26th Bethesda conference: Recommendations for determining eligibility for competition in athletes with cardiovascular abnormalities. Task Force 3: hypertrophic cardiomyopathy, myocarditis and other myopericardial diseases and mitral valve prolapse. J Am Coll Cardiol 1994;24:880-5. |
|31.||Maron BJ, Bonow RO, Cannon RO 3rd, Leon MB, Epstein SE. Hypertrophic cardiomyopathy. Interrelations of clinical manifestations, pathophysiology, and therapy (1). N Engl J Med 1987;316:780-9. |
|32.||Maron BJ, Bonow RO, Cannon RO 3rd, Leon MB, Epstein SE. Hypertrophic cardiomyopathy. Interrelations of clinical manifestations, pathophysiology, and therapy (2). N Engl J Med 1987;316:844-52. |
|33.||Frank MJ, Abdulla AM, Canedo MI, Saylors RE. Long-term medical management of hypertrophic obstructive cardiomyopathy. Am J Cardiol 1978;42:993-1001. |
|34.||Adelman AG, Shah PM, Gramiak R, Wigle ED. Long-term propranolol therapy in muscular subaortic stenosis. Br Heart J 1970;32:804-11. |
|35.||Shah PM, Gramiak R, Adelman AG, Wigle ED. Echocardiographic assessment of the effects of surgery and propranolol on the dynamics of outflow obstruction in hypertrophic subaortic stenosis. Circulation 1972;45:516-21. |
|36.||Kaltenbach M, Hopf R, Kober G, Bussmann WD, Keller M, Petersen Y. Treatment of hypertrophic obstructive cardiomyopathy with verapamil. Br Heart J 1979;42:35-42. |
|37.||Rosing DR, Condit JR, Maron BJ, Kent KM, Leon MB, Bonow RO, et al. Verapamil therapy: A new approach to the pharmacologic treatment of hypertrophic cardiomyopathy: III. Effects of long-term administration. Am J Cardiol 1981;48:545-53. |
|38.||Rosing DR, Kent KM, Borer JS, Seides SF, Maron BJ, Epstein SE. Verapamil therapy: A new approach to the pharmacologic treatment of hypertrophic cardiomyopathy. I. Hemodynamic effects. Circulation 1979;60:1201-7. |
|39.||Rosing DR, Kent KM, Maron BJ, Epstein SE. Verapamil therapy: A new approach to the pharmacologic treatment of hypertrophic cardiomyopathy. II. Effects on exercise capacity and symptomatic status. Circulation 1979;60:1208-13. |
|40.||Bonow RO, Frederick TM, Bacharach SL, Green MV, Goose PW, Maron BJ, et al. Atrial systole and left ventricular filling in hypertrophic cardiomyopathy: Effect of verapamil. Am J Cardiol 1983;51:1386-91. |
|41.||Bonow RO, Ostrow HG, Rosing DR, Cannon RO 3rd, Lipson LC, Maron BJ, et al. Effects of verapamil on left ventricular systolic and diastolic function in patients with hypertrophic cardiomyopathy: Pressure-volume analysis with a nonimaging scintillation probe. Circulation 1983;68:1062-73. |
|42.||Bonow RO, Rosing DR, Bacharach SL, Green MV, Kent KM, Lipson LC, et al. Effects of verapamil on left ventricular systolic function and diastolic filling in patients with hypertrophic cardiomyopathy. Circulation 1981;64:787-96. |
|43.||Matsubara H, Nakatani S, Nagata S, Ishikura F, Katagiri Y, Ohe T, et al. Salutary effect of disopyramide on left ventricular diastolic function in hypertrophic obstructive cardiomyopathy. J Am Coll Cardiol 1995;26:768-75. |
|44.||Pollick C, Kimball B, Henderson M, Wigle ED. Disopyramide in hypertrophic cardiomyopathy. I. Hemodynamic assessment after intravenous administration. Am J Cardiol 1988;62:1248-51. |
|45.||Pollick C. Muscular subaortic stenosis: hemodynamic and clinical improvement after disopyramide. N Engl J Med. 1982 Oct 14; 307:997-9. |
|46.||Sherrid M, Delia E, Dwyer E. Oral disopyramide therapy for obstructive hypertrophic cardiomyopathy. Am J Cardiol 1988;62:1085-8. |
|47.||Cohn LH, Trehan H, Collins JJ Jr. Long-term follow-up of patients undergoing myotomy/myectomy for obstructive hypertrophic cardiomyopathy. Am J Cardiol 1992;70:657-60. |
|48.||Havndrup O, Pettersson G, Kjeldsen K, Bundgaard H. Outcome of septal myectomy in patients with hypertrophic obstructive cardiomyopathy. Scand Cardiovasc J 2000;34:564-9. |
|49.||Williams WG, Wigle ED, Rakowski H, Smallhorn J, LeBlanc J, Trusler GA. Results of surgery for hypertrophic obstructive cardiomyopathy. Circulation 1987;76:V104-8. |
|50.||McCully RB, Nishimura RA, Bailey KR, Schaff HV, Danielson GK, Tajik AJ. Hypertrophic obstructive cardiomyopathy: Preoperative echocardiographic predictors of outcome after septal myectomy. J Am Coll Cardiol 1996;27:1491-6. |
|51.||McCully RB, Nishimura RA, Tajik AJ, Schaff HV, Danielson GK. Extent of clinical improvement after surgical treatment of hypertrophic obstructive cardiomyopathy. Circulation 1996;94:467-71. |
|52.||McIntosh CL, Maron BJ. Current operative treatment of obstructive hypertrophic cardiomyopathy. Circulation 1988;78:487-95. |
|53.||Merrill WH, Friesinger GC, Graham TP Jr, Byrd BF 3rd, Drinkwater DC Jr, Christian KG, et al. Long-lasting improvement after septal myectomy for hypertrophic obstructive cardiomyopathy. Ann Thorac Surg 2000;69:1732-5. |
|54.||Schulte HD, Borisov K, Gams E, Gramsch-Zabel H, Lösse B, Schwartzkopff B. Management of symptomatic hypertrophic obstructive cardiomyopathy--long-term results after surgical therapy. Thorac Cardiovasc Surg 1999;47:213-8. |
|55.||Schulte HD, Bircks WH, Loesse B, Godehardt EA, Schwartzkopff B. Prognosis of patients with hypertrophic obstructive cardiomyopathy after transaortic myectomy. Late results up to twenty-five years. J Thorac Cardiovasc Surg 1993;106:709-17. |
|56.||Ten Berg JM, Suttorp MJ, Knaepen PJ, Ernst SM, Vermeulen FE, Jaarsma W. Hypertrophic obstructive cardiomyopathy. Initial results and long-term follow-up after Morrow septal myectomy. Circulation 1994;90:1781-5. |
|57.||Partanen J, Kupari M, Heikkila J, Keto P. Left ventricular aneurysm associated with apical hypertrophic cardiomyopathy. Clin Cardiol 1991;14:936-9. |
|58.||Paul M, Schafers M, Grude M, Reinke F, Juergens KU, Fischbach R, et al. Idiopathic left ventricular aneurysm and sudden cardiac death in young adults. Europace 2006;8:607-12. |
[Figure 1], [Figure 2]