American Journal of Therapeutics 23, e276–e282 (2016)
Sudden Cardiac Arrest in a Patient With Apical Hypertrophic Cardiomyopathy: Case Report and a Brief Review of Literature Tanush Gupta, MD,1 Neha Paul, MD,1 Chandrasekar Palaniswamy, MD,2 Nivas Balasubramaniyam, MD,2 Wilbert S. Aronow, MD,2* Dhaval Kolte, MD, PhD,1 Sahil Khera, MD,1 Amar B. Shah, MD,3 and Alan Gass, MD2
Apical hypertrophic cardiomyopathy (HCM) is a phenotypic variant of nonobstructive HCM, in which hypertrophy of the myocardium predominantly involves the left ventricular apex. It is common in Japanese and other Asian populations but is rare in the United States. Apical HCM has a relatively benign prognosis in terms of cardiovascular mortality; however, morbid events such as ventricular aneurysms, apical thrombi, diastolic dysfunction, atrial fibrillation, and myocardial infarction are not uncommon. We report a case of an 18-year-old white man who presented to our hospital after an out-of-hospital cardiac arrest. The patient had a witnessed collapse while playing basketball in the field. He was found to be pulseless and unresponsive by his coach, and cardiopulmonary resuscitation was immediately started. Upon arrival of emergency medical services, an automated external defibrillator advised shock and he was defibrillated thrice. Return of spontaneous circulation was achieved in 15 minutes. He was intubated for airway protection and was brought to the hospital. Therapeutic hypothermia was initiated. He demonstrated good neurological status after active rewarming. Subsequent cardiac magnetic resonance imaging was suggestive of apical HCM with right ventricular involvement. The patient underwent an implantable cardioverter defibrillator placement for secondary prevention and was subsequently discharged. In conclusion, apical HCM can rarely be associated with adverse cardiovascular events. The diagnosis may be missed on transthoracic 2-dimensional cardiac echocardiogram, and cardiac magnetic resonance imaging should be considered to exclude apical HCM in young patients who present after sudden cardiac arrest. Keywords: apical hypertrophic cardiomyopathy, cardiac arrest, cardiac magnetic resonance imaging
INTRODUCTION 1
Department of Medicine, New York Medical College, Valhalla, NY; 2Division of Cardiology, New York Medical College, Valhalla, NY; and 3Department of Radiology, New York Medical College, Valhalla, NY. The authors have no conflicts of interest to declare. *Address for correspondence: Division of Cardiology, New York Medical College, Macy Pavilion, Room 138, Valhalla, NY 10595. E-mail: [email protected]
Hypertrophic cardiomyopathy (HCM) is an autosomal dominant, heterogeneous cardiovascular disease with an overall prevalence of approximately 1 in 500 (0.2%) in the general population.1 It is an important cause of sudden death, heart failure, and atrial fibrillation.2 The diagnosis of HCM requires the presence of a hypertrophied nondilated left ventricle (LV) without evidence of any other cardiac or systemic disease (eg, hypertension, aortic stenosis, or metabolic cardiomyopathy)
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Apical Hypertrophic Cardiomyopathy
that could produce the extent of hypertrophy evident.2,3 Apical HCM is a relatively rare variant of nonobstructive HCM, which is localized to the LV apex.4 Although common in Asian populations, where it accounts for 13%–41% of HCM cases,5–7 apical HCM is rare in the United States with prevalence as low as 3% of all HCM cases.6 The diagnosis of apical HCM depends on the detection of localized apical hypertrophy by imaging.8 Echocardiography has limitations for visualizing the apex and may not detect apical HCM9,10; use of echocardiographic contrast media (Definity, Optison, etc) may improve the visualization of the apex. In the recent years, cardiac magnetic resonance imaging (CMR) has emerged as the diagnostic modality of choice.11 Right ventricular (RV) involvement in HCM, and apical HCM in particular, has not been well characterized.12 Apical HCM carries a benign prognosis in Asian populations with cardiovascular morbidity and mortality being relatively uncommon as compared with other forms of HCM.4,13,14 A study in a North American population reported favorable outcomes with an annual cardiovascular mortality of 0.1%.15 We report a case of a young white male athlete who was brought to our hospital after resuscitation for an out-of-hospital cardiac arrest and was subsequently diagnosed to have apical HCM with RV involvement.
CASE REPORT An 18-year-old adolescent man was brought to the emergency department (ED) after he had a sudden cardiac arrest during a basketball practice session. The patient was witnessed to suddenly collapse while playing basketball and was found to be pulseless and unresponsive by his coach. Cardiopulmonary resuscitation (CPR) was started immediately, and emergency medical services were called. Upon arrival of emergency medical services, the patient continued to be unresponsive and cardiopulmonary resuscitation was continued. An automated external defibrillator was placed, and it advised shock for pulseless ventricular tachycardia. He received 3 cycles of shock. Return of spontaneous circulation was achieved in 15 minutes. An electrocardiogram (ECG) showed sinus tachycardia at 107 beats per minute (bpm), tall R waves in leads V3-V5, ST segment depressions in leads V3-V5, and T wave inversions in leads V4-V5 (Figure 1). He was intubated for airway protection, and amiodarone infusion was started en route to the hospital. Upon arrival to the ED, his blood pressure was 156/97 mmHg, the heart rate 87 bpm, temperature 35.6°C, respiratory rate 22, and an oxygen saturation 97% on 100% oxygen delivered through an endotracheal tube. Physical www.americantherapeutics.com
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examination was unremarkable except for bilateral rhonchi on lung auscultation. Therapeutic hypothermia was initiated in the ED, and the patient was transferred to the Coronary Care Unit. The patient was previously healthy, with the only known medical history of attention-deficit/hyperactivity disorder, for which he was administered methylphenidate 2 months ago. Before starting this medication, the patient was advised to get a routine ECG, which showed tall R waves in precordial leads and 3–4 mm T wave inversions in leads V3-V5, which was suggestive of left ventricular hypertrophy (Figure 2). He was subsequently referred to a cardiologist and a 2-dimensional (2-D) transthoracic echocardiogram was performed, which showed normal LV size and thickness. There was no evidence of either systolic or diastolic dysfunction, and no valvular abnormalities were found. He did not have any history of substance abuse; his family history was unknown as he was adopted. The complete blood count and comprehensive metabolic panel were unremarkable except for leukocytosis (total white blood cell count of 20,000 per cubic millimeter). Troponin I was mildly elevated at 0.03 ng/mL, subsequently peaking at 0.57 ng/mL. Urine toxicology screen was negative. A portable chest radiograph showed bilateral diffuse airspace disease and a small left apical pneumothorax (Figure 3). A leftsided chest tube was inserted. He was empirically started on antibiotics for presumed aspiration pneumonia. A 2-D echocardiogram was suboptimal because of poor acoustic windows, and LV wall thickness or function could not be estimated. He was actively rewarmed after therapeutic hypothermia for 24 hours. The patient returned to baseline neurological status once the sedation was weaned off, and he was extubated on day 2 of the hospital course. Given the high suspicion for HCM and nondiagnostic echocardiogram, CMR was performed with intravenous gadolinium contrast. The findings were highly suggestive of an apical variant of HCM with apical RV involvement. The LV cavity size was normal. The anterior, inferior, septal, and lateral walls of the LV were thickened at the apex. The maximum LV thickness at the apex was 20 mm. Also, there was a patchy increase in T2 signal and delayed enhancement involving the apical segment. The RV myocardium was thickened at the apex and along its free wall at the apical level. Both the left and the right ventricle had hyperdynamic systolic function (Figure 4). The final diagnosis was apical HCM with RV involvement. The patient had no further arrhythmic events during the hospital course and demonstrated good clinical recovery. The chest tube was removed, and empiric antibiotics were discontinued. An American Journal of Therapeutics (2016) 23(1)
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FIGURE 1. ECG showing tall R waves in leads V3-V5 with left ventricular strain pattern.
implantable cardioverter defibrillator (ICD) was placed for secondary prevention, and he was subsequently discharged home with outpatient cardiology follow-up.
DISCUSSION Apical HCM, also known as Yamaguchi syndrome, was first described in 1976 in a series of Japanese patients with deep precordial T wave inversions.16 It has
historically been considered a disease of Asian populations and is quite rare in the United States.5 HCM is caused by more than 1400 unique mutations in 11 or more genes encoding proteins of the cardiac sarcomere.3 However, a positive genotype is found less frequently in apical HCM as compared with the other morphological variants of HCM. The most common mutations in apical HCM involve the myosinbinding protein C 3 (MYBC3) and b-myosin heavy chain 7 (MYH7) genes.17 Patients with positive genotype are more likely to have a positive family history
FIGURE 2. ECG showing tall R waves in precordial leads, ST depressions, and T wave inversions in leads V3-V5. American Journal of Therapeutics (2016) 23(1)
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FIGURE 3. Chest radiograph showing bilateral diffuse airspace disease and a left apical pneumothorax.
for HCM.17 Histological examination of apical HCM shows a severe myofibrillar disarray similar to other forms of HCM.18 Pathophysiological abnormalities in apical HCM include an impaired LV diastolic function with a decreased rate of early diastolic filling. Systolic function is usually normal or even hyperdynamic.19,20 HCM is predominantly considered a disease of LV, and the prevalence and extent of RV involvement has not been well described.12 This can partly be attributed to the fact that assessment of RV thickness with conventional 2-D echocardiography can be difficult because of its low spatial resolution.21 CMR provides complete tomographic coverage of both ventricles with better spatial resolution and is technically well suited for evaluation of RV.22 A study by Maron et al,23 which used CMR to evaluate frequency of RV involvement in 46 patients with HCM, reported that RV wall thickness and/or mass was increased in onethird of patients with HCM, including approximately 10% with extreme RV hypertrophy. RV involvement in HCM seems to be variable, with mild concentric RV hypertrophy being most common. Other reported patterns include heterogeneous hypertrophy of the RV apex, mid septum, basal septum, and/or free wall, with RV outflow tract obstruction being extremely rare.21,24–27 The data on RV involvement in apical HCM are limited.28 Almost half of the patients with apical HCM are mildly symptomatic or asymptomatic and many are diagnosed only when deep T wave inversions are noticed incidentally on routine ECG.8,29 Atypical chest www.americantherapeutics.com
pain is the most common symptom; typical angina may also occur because of reduced coronary flow reserve, similar to patients with asymmetric septal hypertrophy or other forms of HCM. Other presenting complaints can be palpitations, dyspnea, fatigue, presyncope, or syncope.19 In the absence of dynamic subaortic obstruction, most patients do not have a heart murmur.30 Typical ECG changes are signs of LV hypertrophy and giant negative T waves (typically . 10 mm) in precordial leads. However, studies have shown that patients in the United States are less likely to have giant negative T waves as compared with their Japanese counterparts.6 Also, ECG criteria for diagnosis of LV hypertrophy are less specific in the younger population. When increased voltage is associated with strain pattern in a young male, evaluation for LV hypertrophy should be strongly considered. Echocardiography is the first imaging modality for patients with suspected HCM; however, the apex may occasionally be difficult to visualize with conventional 2-D echocardiography.31 Significant narrowing toward the apex of the LV without involvement of other segments is usually seen.32 Subtle abnormalities of diastolic dysfunction may be present.33 Moon et al34 showed that 2-D echocardiogram could be insensitive in diagnosing apical HCM, and contrast echocardiography or CMR may be necessary to exclude this diagnosis. CMR can image in any plane, and contrast magnetic resonance imaging results in greater resolution and appreciation of cardiac morphology, resulting in accurate imaging of the myocardial apex.35–37 American Journal of Therapeutics (2016) 23(1)
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FIGURE 4. CMR with gadolinium contrast. A, 2-chamber balanced steady-state free precision sequence showing increased left ventricular (LV) thickness at the apex. B, Short axis balanced steady-state free precision sequence showing hypertrophy at the LV apex. C, 4-chamber balanced steady-state free precision sequence showing increased thickening at the right ventricular apex. D, Short axis T2-STIR showing patchy increase in signal at the LV apex. E, 2-chamber view showing delayed enhancement at the LV apex. F, 4-chamber view showing delayed enhancement at the LV apex.
Multiple clinical studies have validated the superiority of CMR over echocardiography in diagnosing apical HCM.15,38 Left ventriculography classically shows spade-like (“ace of spades”) morphology of the LV characterized by a relatively normal cavity size at the base American Journal of Therapeutics (2016) 23(1)
but marked narrowing at the apex. There may also be obliteration of the distal cavity at end systole.16 However, again, patients in the United States tend to have less localized involvement of the distal apex; as a result, the typical spade-like configuration is less commonly seen.15 www.americantherapeutics.com
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Apical Hypertrophic Cardiomyopathy
As compared with patients with asymmetric hypertrophic hypertrophy, patients with apical HCM have a benign outcome, and sudden cardiac death is rare, especially in the Asian population. In a study of 31 patients with apical HCM, Sakamoto et al13 reported zero mortality during a follow-up period ranging from 24 to 156 months. Similarly, other recent studies in Asian populations have reported favorable outcomes.39,40 Furthermore, studies in Western populations with apical HCM have reported low mortality but a higher incidence of cardiovascular morbidity.15 In their study of 105 patients with apical HCM, Eriksson et al15 reported an annual cardiovascular mortality of 0.1%. However, almost one-third of the patients had major morbid events, the most common being atrial fibrillation (12%) and myocardial infarction (10%). In a more recent study of 193 patients with apical HCM, Binder et al41 reported relatively worse outcomes. During a mean follow-up of 8 years, sudden cardiac death, resuscitated cardiac arrest, or appropriate ICD therapy was observed in 6% of the patients. Atrial fibrillation (28%), ventricular tachycardia (20%), and stroke (11%) were also common.41 This may warrant screening and risk stratification similar to other forms of HCM. 34 Other morbid sequelae of apical HCM include diastolic heart failure, apical outpouching and aneurysms, and apical thrombi with subsequent embolic events.8 Patients with apical HCM who have a myocardial infarction usually lack evidence of significant coronary disease on cardiac catheterization, with infarction being a result of either impaired coronary flow due to reduced diastolic compliance or small vessel disease.15 There is a paucity of data about the management of apical HCM. Most patients are asymptomatic and do not require any specific treatment. Patients with angina, palpitations, or tachyarrhythmias may benefit from beta-blockers or calcium channel blockers. No particular treatment has been proven to be effective in patients with diastolic dysfunction.19 An ICD must be considered in patients with conventional risk factors for sudden cardiac death in HCM, such as patients with history of cardiac arrest or sustained ventricular tachycardia, family history of sudden death due to HCM, unexplained recent syncope, multiple episodes of nonsustained ventricular tachycardia, hypotension, or attenuated blood pressure response to exercise, massive LV hypertrophy, and extensive and diffuse late gadolinium enhancement.3 In conclusion, although rare, apical HCM can be a cause of sudden cardiac arrest. Conventional echocardiography may not be diagnostic, and CMR must be considered to exclude this diagnosis in young www.americantherapeutics.com
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patients with unexplained cardiac arrest and ECG changes suggestive of LV hypertrophy.
REFERENCES 1. Maron BJ, Gardin JM, Flack JM, et al. Prevalence of hypertrophic cardiomyopathy in a general population of young adults. Echocardiographic analysis of 4111 subjects in the CARDIA Study. Coronary artery risk development in (young) adults. Circulation. 1995;92:785–789. 2. Maron BJ. Hypertrophic cardiomyopathy: a systematic review. JAMA. 2002;287:1308–1320. 3. Maron BJ, Maron MS. Hypertrophic cardiomyopathy. Lancet. 2013;381:242–255. 4. Sakamoto T, Tei C, Murayama M, et al. Giant T wave inversion as a manifestation of asymmetrical apical hypertrophy (AAH) of the left ventricle. Echocardiographic and ultrasono-cardiotomographic study. Jpn Heart J. 1976;17:611–629. 5. Chikamori T, Doi YL, Akizawa M, et al. Comparison of clinical, morphological, and prognostic features in hypertrophic cardiomyopathy between Japanese and western patients. Clin Cardiol. 1992;15:833–837. 6. Kitaoka H, Doi Y, Casey SA, et al. Comparison of prevalence of apical hypertrophic cardiomyopathy in Japan and the United States. Am J Cardiol. 2003;92: 1183–1186. 7. Ho HH, Lee KL, Lau CP, et al. Clinical characteristics of and long-term outcome in Chinese patients with hypertrophic cardiomyopathy. Am J Med. 2004;116:19–23. 8. Sakamoto T. Apical hypertrophic cardiomyopathy (apical hypertrophy): an overview. J Cardiol. 2001;37(Suppl 1): 161–178. 9. Suzuki Y, Kadota K, Nohara R, et al. Recognition of regional hypertrophy in hypertrophic cardiomyopathy using thallium-201 emission-computed tomography: comparison with two-dimensional echocardiography. Am J Cardiol. 1984;53:1095–1102. 10. Vacek JL, Davis WR, Bellinger RL, et al. Apical hypertrophic cardiomyopathy in American patients. Am Heart J. 1984;108:1501–1506. 11. Casolo GC, Trotta F, Rostagno C, et al. Detection of apical hypertrophic cardiomyopathy by magnetic resonance imaging. Am Heart J. 1989;117:468–472. 12. Mozaffarian D, Caldwell JH. Right ventricular involvement in hypertrophic cardiomyopathy: a case report and literature review. Clin Cardiol. 2001;24:2–8. 13. Sakamoto T, Amano K, Hada Y, et al. Asymmetric apical hypertrophy: ten years experience. Postgrad Med J. 1986; 62:567–570. 14. Sakamoto T, Suzuki J. Apical hypertrophic cardiomyopathy [in Japanese]. Nihon Rinsho. 2000;58:93–101. 15. Eriksson MJ, Sonnenberg B, Woo A, et al. Long-term outcome in patients with apical hypertrophic cardiomyopathy. J Am Coll Cardiol. 2002;39:638–645. 16. Yamaguchi H, Ishimura T, Nishiyama S, et al. Hypertrophic nonobstructive cardiomyopathy with giant negative American Journal of Therapeutics (2016) 23(1)
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T waves (apical hypertrophy): ventriculographic and echocardiographic features in 30 patients. Am J Cardiol. 1979;44:401–412. Gruner C, Care M, Siminovitch K, et al. Sarcomere protein gene mutations in patients with apical hypertrophic cardiomyopathy. Circ Cardiovasc Genet. 2011;4:288–295. Maron BJ, Bonow RO, Seshagiri TN, et al. Hypertrophic cardiomyopathy with ventricular septal hypertrophy localized to the apical region of the left ventricle (apical hypertrophic cardiomyopathy). Am J Cardiol. 1982;49: 1838–1848. Ibrahim T, Schwaiger M. Diagnosis of apical hypertrophic cardiomyopathy using magnetic resonance imaging. Heart. 2000;83:E1. Webb JG, Sasson Z, Rakowski H, et al. Apical hypertrophic cardiomyopathy: clinical follow-up and diagnostic correlates. J Am Coll Cardiol. 1990;15:83–90. McKenna WJ, Kleinebenne A, Nihoyannopoulos P, et al. Echocardiographic measurement of right ventricular wall thickness in hypertrophic cardiomyopathy: relation to clinical and prognostic features. J Am Coll Cardiol. 1988;11:351–358. Lima JA, Desai MY. Cardiovascular magnetic resonance imaging: current and emerging applications. J Am Coll Cardiol. 2004;44:1164–1171. Maron MS, Hauser TH, Dubrow E, et al. Right ventricular involvement in hypertrophic cardiomyopathy. Am J Cardiol. 2007;100:1293–1298. Maron BJ, McIntosh CL, Klues HG, et al. Morphologic basis for obstruction to right ventricular outflow in hypertrophic cardiomyopathy. Am J Cardiol. 1993;71: 1089–1094. Stierle U, Sheikhzadeh A, Shakibi JG, et al. Right ventricular obstruction in various types of hypertrophic cardiomyopathy. Jpn Heart J. 1987;28:115–125. Butz T, Horstkotte D, Langer C, et al. Significant obstruction of the right and left ventricular outflow tract in a patient with biventricular hypertrophic cardiomyopathy. Eur J Echocardiogr. 2008;9:344–345. Krecki R, Lipiec P, Piotrowska-Kownacka D, et al. Predominant, severe right ventricular outflow tract obstruction in hypertrophic cardiomyopathy. Circulation. 2007; 116:e551–e553. Comella A, Magnacca M, Gistri R, et al. Right ventricular involvement in hypertrophic cardiomyopathy. A case report and brief review of the literature [in Italian]. Ital Heart J Suppl. 2004;5:154–159.
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Gupta et al 29. Wigle ED. Cardiomyopathy: the diagnosis of hypertrophic cardiomyopathy. Heart. 2001;86:709–714. 30. Siewe D, Nichols KB, Furney SL, et al. King of hearts for ace of spades: apical hypertrophic cardiomyopathy. Am J Med. 2014;127:31–33. 31. Maron BJ, Spirito P, Green KJ, et al. Noninvasive assessment of left ventricular diastolic function by pulsed Doppler echocardiography in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol. 1987;10:733–742. 32. Keren G, Belhassen B, Sherez J, et al. Apical hypertrophic cardiomyopathy: evaluation by noninvasive and invasive techniques in 23 patients. Circulation. 1985;71:45–56. 33. Nihoyannopoulos P, Karatasakis G, Frenneaux M, et al. Diastolic function in hypertrophic cardiomyopathy: relation to exercise capacity. J Am Coll Cardiol. 1992;19: 536–540. 34. Moon JC, Fisher NG, McKenna WJ, et al. Detection of apical hypertrophic cardiomyopathy by cardiovascular magnetic resonance in patients with non-diagnostic echocardiography. Heart. 2004;90:645–649. 35. Soler R, Rodriguez E, Rodriguez JA, et al. Magnetic resonance imaging of apical hypertrophic cardiomyopathy. J Thorac Imaging. 1997;12:221–225. 36. Suzuki J, Watanabe F, Takenaka K, et al. New subtype of apical hypertrophic cardiomyopathy identified with nuclear magnetic resonance imaging as an underlying cause of markedly inverted T waves. J Am Coll Cardiol. 1993;22:1175–1181. 37. Thiele H, Nagel E, Paetsch I, et al. Functional cardiac MR imaging with steady-state free precession (SSFP) significantly improves endocardial border delineation without contrast agents. J Magn Reson Imaging. 2001;14:362–367. 38. Pons-Llado G, Carreras F, Borras X, et al. Comparison of morphologic assessment of hypertrophic cardiomyopathy by magnetic resonance versus echocardiographic imaging. Am J Cardiol. 1997;79:1651–1656. 39. Lee CH, Liu PY, Lin LJ, et al. Clinical features and outcome of patients with apical hypertrophic cardiomyopathy in Taiwan. Cardiology. 2006;106:29–35. 40. Chen CC, Lei MH, Hsu YC, et al. Apical hypertrophic cardiomyopathy: correlations between echocardiographic parameters, angiographic left ventricular morphology, and clinical outcomes. Clin Cardiol. 2011;34:233–238. 41. Binder J, Attenhofer Jost CH, Klarich KW, et al. Apical hypertrophic cardiomyopathy: prevalence and correlates of apical outpouching. J Am Soc Echocardiogr. 2011;24: 775–781.
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Sudden Cardiac Arrest in a Patient With Apical Hypertrophic Cardiomyopathy: Case Report and a Brief Review of Literature Tanush Gupta, MD,1 Neha Paul, MD,1 Chandrasekar Palaniswamy, MD,2 Nivas Balasubramaniyam, MD,2 Wilbert S. Aronow, MD,2* Dhaval Kolte, MD, PhD,1 Sahil Khera, MD,1 Amar B. Shah, MD,3 and Alan Gass, MD2
Apical hypertrophic cardiomyopathy (HCM) is a phenotypic variant of nonobstructive HCM, in which hypertrophy of the myocardium predominantly involves the left ventricular apex. It is common in Japanese and other Asian populations but is rare in the United States. Apical HCM has a relatively benign prognosis in terms of cardiovascular mortality; however, morbid events such as ventricular aneurysms, apical thrombi, diastolic dysfunction, atrial fibrillation, and myocardial infarction are not uncommon. We report a case of an 18-year-old white man who presented to our hospital after an out-of-hospital cardiac arrest. The patient had a witnessed collapse while playing basketball in the field. He was found to be pulseless and unresponsive by his coach, and cardiopulmonary resuscitation was immediately started. Upon arrival of emergency medical services, an automated external defibrillator advised shock and he was defibrillated thrice. Return of spontaneous circulation was achieved in 15 minutes. He was intubated for airway protection and was brought to the hospital. Therapeutic hypothermia was initiated. He demonstrated good neurological status after active rewarming. Subsequent cardiac magnetic resonance imaging was suggestive of apical HCM with right ventricular involvement. The patient underwent an implantable cardioverter defibrillator placement for secondary prevention and was subsequently discharged. In conclusion, apical HCM can rarely be associated with adverse cardiovascular events. The diagnosis may be missed on transthoracic 2-dimensional cardiac echocardiogram, and cardiac magnetic resonance imaging should be considered to exclude apical HCM in young patients who present after sudden cardiac arrest. Keywords: apical hypertrophic cardiomyopathy, cardiac arrest, cardiac magnetic resonance imaging
INTRODUCTION 1
Department of Medicine, New York Medical College, Valhalla, NY; 2Division of Cardiology, New York Medical College, Valhalla, NY; and 3Department of Radiology, New York Medical College, Valhalla, NY. The authors have no conflicts of interest to declare. *Address for correspondence: Division of Cardiology, New York Medical College, Macy Pavilion, Room 138, Valhalla, NY 10595. E-mail: [email protected]
Hypertrophic cardiomyopathy (HCM) is an autosomal dominant, heterogeneous cardiovascular disease with an overall prevalence of approximately 1 in 500 (0.2%) in the general population.1 It is an important cause of sudden death, heart failure, and atrial fibrillation.2 The diagnosis of HCM requires the presence of a hypertrophied nondilated left ventricle (LV) without evidence of any other cardiac or systemic disease (eg, hypertension, aortic stenosis, or metabolic cardiomyopathy)
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Apical Hypertrophic Cardiomyopathy
that could produce the extent of hypertrophy evident.2,3 Apical HCM is a relatively rare variant of nonobstructive HCM, which is localized to the LV apex.4 Although common in Asian populations, where it accounts for 13%–41% of HCM cases,5–7 apical HCM is rare in the United States with prevalence as low as 3% of all HCM cases.6 The diagnosis of apical HCM depends on the detection of localized apical hypertrophy by imaging.8 Echocardiography has limitations for visualizing the apex and may not detect apical HCM9,10; use of echocardiographic contrast media (Definity, Optison, etc) may improve the visualization of the apex. In the recent years, cardiac magnetic resonance imaging (CMR) has emerged as the diagnostic modality of choice.11 Right ventricular (RV) involvement in HCM, and apical HCM in particular, has not been well characterized.12 Apical HCM carries a benign prognosis in Asian populations with cardiovascular morbidity and mortality being relatively uncommon as compared with other forms of HCM.4,13,14 A study in a North American population reported favorable outcomes with an annual cardiovascular mortality of 0.1%.15 We report a case of a young white male athlete who was brought to our hospital after resuscitation for an out-of-hospital cardiac arrest and was subsequently diagnosed to have apical HCM with RV involvement.
CASE REPORT An 18-year-old adolescent man was brought to the emergency department (ED) after he had a sudden cardiac arrest during a basketball practice session. The patient was witnessed to suddenly collapse while playing basketball and was found to be pulseless and unresponsive by his coach. Cardiopulmonary resuscitation (CPR) was started immediately, and emergency medical services were called. Upon arrival of emergency medical services, the patient continued to be unresponsive and cardiopulmonary resuscitation was continued. An automated external defibrillator was placed, and it advised shock for pulseless ventricular tachycardia. He received 3 cycles of shock. Return of spontaneous circulation was achieved in 15 minutes. An electrocardiogram (ECG) showed sinus tachycardia at 107 beats per minute (bpm), tall R waves in leads V3-V5, ST segment depressions in leads V3-V5, and T wave inversions in leads V4-V5 (Figure 1). He was intubated for airway protection, and amiodarone infusion was started en route to the hospital. Upon arrival to the ED, his blood pressure was 156/97 mmHg, the heart rate 87 bpm, temperature 35.6°C, respiratory rate 22, and an oxygen saturation 97% on 100% oxygen delivered through an endotracheal tube. Physical www.americantherapeutics.com
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examination was unremarkable except for bilateral rhonchi on lung auscultation. Therapeutic hypothermia was initiated in the ED, and the patient was transferred to the Coronary Care Unit. The patient was previously healthy, with the only known medical history of attention-deficit/hyperactivity disorder, for which he was administered methylphenidate 2 months ago. Before starting this medication, the patient was advised to get a routine ECG, which showed tall R waves in precordial leads and 3–4 mm T wave inversions in leads V3-V5, which was suggestive of left ventricular hypertrophy (Figure 2). He was subsequently referred to a cardiologist and a 2-dimensional (2-D) transthoracic echocardiogram was performed, which showed normal LV size and thickness. There was no evidence of either systolic or diastolic dysfunction, and no valvular abnormalities were found. He did not have any history of substance abuse; his family history was unknown as he was adopted. The complete blood count and comprehensive metabolic panel were unremarkable except for leukocytosis (total white blood cell count of 20,000 per cubic millimeter). Troponin I was mildly elevated at 0.03 ng/mL, subsequently peaking at 0.57 ng/mL. Urine toxicology screen was negative. A portable chest radiograph showed bilateral diffuse airspace disease and a small left apical pneumothorax (Figure 3). A leftsided chest tube was inserted. He was empirically started on antibiotics for presumed aspiration pneumonia. A 2-D echocardiogram was suboptimal because of poor acoustic windows, and LV wall thickness or function could not be estimated. He was actively rewarmed after therapeutic hypothermia for 24 hours. The patient returned to baseline neurological status once the sedation was weaned off, and he was extubated on day 2 of the hospital course. Given the high suspicion for HCM and nondiagnostic echocardiogram, CMR was performed with intravenous gadolinium contrast. The findings were highly suggestive of an apical variant of HCM with apical RV involvement. The LV cavity size was normal. The anterior, inferior, septal, and lateral walls of the LV were thickened at the apex. The maximum LV thickness at the apex was 20 mm. Also, there was a patchy increase in T2 signal and delayed enhancement involving the apical segment. The RV myocardium was thickened at the apex and along its free wall at the apical level. Both the left and the right ventricle had hyperdynamic systolic function (Figure 4). The final diagnosis was apical HCM with RV involvement. The patient had no further arrhythmic events during the hospital course and demonstrated good clinical recovery. The chest tube was removed, and empiric antibiotics were discontinued. An American Journal of Therapeutics (2016) 23(1)
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FIGURE 1. ECG showing tall R waves in leads V3-V5 with left ventricular strain pattern.
implantable cardioverter defibrillator (ICD) was placed for secondary prevention, and he was subsequently discharged home with outpatient cardiology follow-up.
DISCUSSION Apical HCM, also known as Yamaguchi syndrome, was first described in 1976 in a series of Japanese patients with deep precordial T wave inversions.16 It has
historically been considered a disease of Asian populations and is quite rare in the United States.5 HCM is caused by more than 1400 unique mutations in 11 or more genes encoding proteins of the cardiac sarcomere.3 However, a positive genotype is found less frequently in apical HCM as compared with the other morphological variants of HCM. The most common mutations in apical HCM involve the myosinbinding protein C 3 (MYBC3) and b-myosin heavy chain 7 (MYH7) genes.17 Patients with positive genotype are more likely to have a positive family history
FIGURE 2. ECG showing tall R waves in precordial leads, ST depressions, and T wave inversions in leads V3-V5. American Journal of Therapeutics (2016) 23(1)
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FIGURE 3. Chest radiograph showing bilateral diffuse airspace disease and a left apical pneumothorax.
for HCM.17 Histological examination of apical HCM shows a severe myofibrillar disarray similar to other forms of HCM.18 Pathophysiological abnormalities in apical HCM include an impaired LV diastolic function with a decreased rate of early diastolic filling. Systolic function is usually normal or even hyperdynamic.19,20 HCM is predominantly considered a disease of LV, and the prevalence and extent of RV involvement has not been well described.12 This can partly be attributed to the fact that assessment of RV thickness with conventional 2-D echocardiography can be difficult because of its low spatial resolution.21 CMR provides complete tomographic coverage of both ventricles with better spatial resolution and is technically well suited for evaluation of RV.22 A study by Maron et al,23 which used CMR to evaluate frequency of RV involvement in 46 patients with HCM, reported that RV wall thickness and/or mass was increased in onethird of patients with HCM, including approximately 10% with extreme RV hypertrophy. RV involvement in HCM seems to be variable, with mild concentric RV hypertrophy being most common. Other reported patterns include heterogeneous hypertrophy of the RV apex, mid septum, basal septum, and/or free wall, with RV outflow tract obstruction being extremely rare.21,24–27 The data on RV involvement in apical HCM are limited.28 Almost half of the patients with apical HCM are mildly symptomatic or asymptomatic and many are diagnosed only when deep T wave inversions are noticed incidentally on routine ECG.8,29 Atypical chest www.americantherapeutics.com
pain is the most common symptom; typical angina may also occur because of reduced coronary flow reserve, similar to patients with asymmetric septal hypertrophy or other forms of HCM. Other presenting complaints can be palpitations, dyspnea, fatigue, presyncope, or syncope.19 In the absence of dynamic subaortic obstruction, most patients do not have a heart murmur.30 Typical ECG changes are signs of LV hypertrophy and giant negative T waves (typically . 10 mm) in precordial leads. However, studies have shown that patients in the United States are less likely to have giant negative T waves as compared with their Japanese counterparts.6 Also, ECG criteria for diagnosis of LV hypertrophy are less specific in the younger population. When increased voltage is associated with strain pattern in a young male, evaluation for LV hypertrophy should be strongly considered. Echocardiography is the first imaging modality for patients with suspected HCM; however, the apex may occasionally be difficult to visualize with conventional 2-D echocardiography.31 Significant narrowing toward the apex of the LV without involvement of other segments is usually seen.32 Subtle abnormalities of diastolic dysfunction may be present.33 Moon et al34 showed that 2-D echocardiogram could be insensitive in diagnosing apical HCM, and contrast echocardiography or CMR may be necessary to exclude this diagnosis. CMR can image in any plane, and contrast magnetic resonance imaging results in greater resolution and appreciation of cardiac morphology, resulting in accurate imaging of the myocardial apex.35–37 American Journal of Therapeutics (2016) 23(1)
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FIGURE 4. CMR with gadolinium contrast. A, 2-chamber balanced steady-state free precision sequence showing increased left ventricular (LV) thickness at the apex. B, Short axis balanced steady-state free precision sequence showing hypertrophy at the LV apex. C, 4-chamber balanced steady-state free precision sequence showing increased thickening at the right ventricular apex. D, Short axis T2-STIR showing patchy increase in signal at the LV apex. E, 2-chamber view showing delayed enhancement at the LV apex. F, 4-chamber view showing delayed enhancement at the LV apex.
Multiple clinical studies have validated the superiority of CMR over echocardiography in diagnosing apical HCM.15,38 Left ventriculography classically shows spade-like (“ace of spades”) morphology of the LV characterized by a relatively normal cavity size at the base American Journal of Therapeutics (2016) 23(1)
but marked narrowing at the apex. There may also be obliteration of the distal cavity at end systole.16 However, again, patients in the United States tend to have less localized involvement of the distal apex; as a result, the typical spade-like configuration is less commonly seen.15 www.americantherapeutics.com
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Apical Hypertrophic Cardiomyopathy
As compared with patients with asymmetric hypertrophic hypertrophy, patients with apical HCM have a benign outcome, and sudden cardiac death is rare, especially in the Asian population. In a study of 31 patients with apical HCM, Sakamoto et al13 reported zero mortality during a follow-up period ranging from 24 to 156 months. Similarly, other recent studies in Asian populations have reported favorable outcomes.39,40 Furthermore, studies in Western populations with apical HCM have reported low mortality but a higher incidence of cardiovascular morbidity.15 In their study of 105 patients with apical HCM, Eriksson et al15 reported an annual cardiovascular mortality of 0.1%. However, almost one-third of the patients had major morbid events, the most common being atrial fibrillation (12%) and myocardial infarction (10%). In a more recent study of 193 patients with apical HCM, Binder et al41 reported relatively worse outcomes. During a mean follow-up of 8 years, sudden cardiac death, resuscitated cardiac arrest, or appropriate ICD therapy was observed in 6% of the patients. Atrial fibrillation (28%), ventricular tachycardia (20%), and stroke (11%) were also common.41 This may warrant screening and risk stratification similar to other forms of HCM. 34 Other morbid sequelae of apical HCM include diastolic heart failure, apical outpouching and aneurysms, and apical thrombi with subsequent embolic events.8 Patients with apical HCM who have a myocardial infarction usually lack evidence of significant coronary disease on cardiac catheterization, with infarction being a result of either impaired coronary flow due to reduced diastolic compliance or small vessel disease.15 There is a paucity of data about the management of apical HCM. Most patients are asymptomatic and do not require any specific treatment. Patients with angina, palpitations, or tachyarrhythmias may benefit from beta-blockers or calcium channel blockers. No particular treatment has been proven to be effective in patients with diastolic dysfunction.19 An ICD must be considered in patients with conventional risk factors for sudden cardiac death in HCM, such as patients with history of cardiac arrest or sustained ventricular tachycardia, family history of sudden death due to HCM, unexplained recent syncope, multiple episodes of nonsustained ventricular tachycardia, hypotension, or attenuated blood pressure response to exercise, massive LV hypertrophy, and extensive and diffuse late gadolinium enhancement.3 In conclusion, although rare, apical HCM can be a cause of sudden cardiac arrest. Conventional echocardiography may not be diagnostic, and CMR must be considered to exclude this diagnosis in young www.americantherapeutics.com
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patients with unexplained cardiac arrest and ECG changes suggestive of LV hypertrophy.
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