© 2015, Wiley Periodicals, Inc. DOI: 10.1111/echo.12986
Echocardiography
Left Ventricular Apex Involvement in Hypertrophic Cardiomyopathy Vito Maurizio Parato, M.D.,* Iacopo Olivotto, M.D.,† Martin S. Maron, M.D.,‡ Navin C. Nanda, M.D.,§ and Natesa G. Pandian, M.D.‡ *Cardiology Unit and Echocardiography, Madonna del Soccorso Hospital, San Benedetto del Tronto and Politecnica delle Marche University, Ancona, Italy; †Referral Center for Cardiomyopathies, Careggi University Hospital, Florence, Italy; ‡Tufts Medical Center, Boston, Massachusetts; and §Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, Alabama
(Echocardiography 2015;32:1575–1580) Key words: hypertrophic cardiomyopathy, left ventricular apex, left ventricle aneurysm, atherosclerotic epicardial coronary disease, echocardiography, two-dimensional echocardiography, three-dimensional echocardiography Hypertrophic cardiomyopathy (HCM) is a genetically transmitted disease with broad morphologic and clinical spectrum.1–4 The most common presentation involves asymmetric basal anteroseptal left ventricular (LV) hypertrophy with outflow tract obstruction due to systolic anterior motion of the mitral valve. Less common variants are represented by midventricular and apical HCM. These forms are usually defined “sub-basal HCM” and have been associated with apical aneurysm formation.5 There is no universal classification of the LV hypertrophy pattern in HCM.6,7 According to a “four-patterns” model proposed by Helmy SM,8 four different patterns of LV hypertrophy are identified: Pattern 1 (P1) is characterized by septal hypertrophy alone; pattern 2 (P2) involves the septum and adjacent segments but spares the apex; pattern 3 (P3) involves the apex in combination with other LV segments; and pattern 4 (P4) consists of an apical hypertrophy alone (Fig. 1). Isolated apical HCM (pattern 4) is a rare variant in the nonJapanese population (1–2%).6 We present three patients with HCM in whom the LV apex was involved in various patterns, reflecting the atypical localization of hypertrophy or the consequences of the mid-ventricular obstruction, and discuss the clinical implications of these rare variants.
Clinical Cases: Case A: The patient was a 62-year-old male, with negative clinical history. He was diagnosed at our institution following electrocardiogram (ECG) for sport-related preparticipation screening, and was completely asymptomatic and event-free. The ECG showed T wave inversion and ST-T depression in leads V4–6, Lead 1 and aVL (Fig. 2A). Transthoracic echocardiography showed apical hypertrophy (maximum diastolic thickness: 22 mm) extending to the whole lateral wall (maximum diastolic thickness: 21 mm). There was no intraventricular obstruction. LV cavity volume was 64 ml/m2 (end-diastole) and 27 ml/m2 (end-systole) with LV ejection fraction (EF): 58% (Fig. 2B,C). Cardiac magnetic resonance (CMR) (Fig. 2D,E) confirmed the apical localization of hypertrophy and identified areas of late gadolinium enhancement (LGE) within the inferior wall which was hypokinetic. Because of this finding, the patient underwent computed tomographic coronary angiogram (CTA) that revealed a significant lesion of the proximal right coronary artery (RCA) and nonsignificant lesions of the circumflex and left anterior descending coronary artery (LAD). The proximal RCA lesion, confirmed by angiography, was treated by percutaneous intervention (PCI) because of a positive exercise stress echocardiogram. To date, he remains asymptomatic and in good health.
Address for correspondence and reprint requests: Vito Maurizio Parato, M.D., Madonna del Soccorso Hospital, 3-7, via Manara, 63074, San Benedetto del Tronto, Italy. Fax: +39-0735-793363; E-mail: [email protected]
Case B: The patient was a 63-year-old male, who presented to the emergency department (ED) with
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atic on antiplatelet agents, b-blockers, renin– angiotensin inhibitors, and statins.
Figure 1. The four different patterns (P1 to P4) of HCM as proposed by Sherif M. Helmy.8 P1: Septal hypertrophy alone. P2: Hypertrophy involves the septum and adjacent segments but spares the apex. P3: Hypertrophy involves the apex in combination with other LV segments. P4: It consists of an apical hypertrophy alone.
acute onset of chest pain. He was diagnosed with NSTEMI due to a left circumflex coronary artery (LCx) culprit lesion and treated by PCI. The ECG showed very high voltages and an impressive ST depression plus very deep T-wave inversion in the precordial leads (Fig. 3A). The echocardiographic picture (Fig. 3B,C) was that of an evident apical HCM, with a maximum diastolic thickness of 21 mm. There was a complete apical obliteration in systole, confirmed by cardiac magnetic resonance (CMR) (Fig. 3D,E). During follow-up, the patient required a further PCI and stenting procedure for critical stenosis of the LAD. After this procedure, the patient remained asymptom-
Case C: The patient was a 60-year-old female, with a negative clinical history. She presented to the ED because of chest pain, palpitation, and dyspnea. The ECG showed rapidly conducted atrial fibrillation, associated with hypotension (90/60) and mild TnT/hs elevation. Urgent DC shock cardioversion was performed. The ECG after cardioversion (Fig. 4A) showed ST elevation in leads V1–5. A transthoracic echocardiogram showed clear evidence of HCM with the septal width of 28 mm and systolic muscular apposition of the septum and LV free wall at the mid-ventricle associated with a pressure gradient between the apical and basal chambers (Fig. 4B,C). Mid-ventricular gradients were 13 mmHg in diastole and 60 mmHg in systole. An “hourglass” shaped LV with a large apical aneurysm (28 9 20 mm in size) was evident. The aneurysm was more clearly detectable by CMR (Fig. 4D,E), which also showed transmural late gadolinium enhancement (LGE) due to extensive myocardial scarring at this level. The basal LV cavity was enlarged with a concave appearance of the interventricular septum. The coronary angiogram showed normal epicardial vessels. The patient underwent intracardiac defibrillator (ICD) implantation for primary prophylaxis and was started on warfarin, amiodaron, beta-blocker, and a statin. She remained asymptomatic at 4 years of follow-up, with no further recurrence of atrial fibrillation.
Figure 2. Case A. A. Basal ECG. B. Transthoracic echocardiogram, four-chamber view, systolic phase. C. Transthoracic echocardiogram, four-chamber view, diastolic phase. D. CMR image (L-A). E. CMR image (S-A). F,G. CMR images (four-chamber, diastole).
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Figure 3. Case B. A. Basal ECG. B. TT-echocardiogram, four-chamber view, diastolic phase. C. TT- echocardiogram, fourchamber view, systolic phase. D. CMR image, four-chamber, diastolic phase. E. CMR image, four-chamber, systolic phase.
Figure 4. Case C. A.ECG during atrial fibrillation. B. Basal ECG in sinus rythm. C. TT-echocardiogram image, four-chamber view. D. CW-doppler: mid-ventricular gradient measurement. E,F. CMR images showing the apical aneurysm in diastolic (E, red arrow) and systolic (F, red arrow) phase.
Discussion: Hypertrophic cardiomyopathy patients with LV apex involvement represent an under-recognized subset in the heterogeneous HCM disease spectrum bearing important clinical implications. The detection of apical involvement often requires a high index of suspicion.9,10 CMR is often necessary to confirm the diagnosis, although contrast-enhanced echocardiography is an elegant bedside alternative to assess left ventricular apical segments.3
There are some special features of HCM with apex involvement. First, when the apex is involved, ECG evidence of LV hypertrophy is virtually always detectable. In Helmy’s study, it was present in 100% of patients with patterns 3 and 4.8 Likewise, in our patients the ECG was distinctively abnormal. This contains a clear message: in patients with ECG repolarization abnormalities without an obvious ischemic cause, routine echocardiography without contrast may not exclude apical 1577
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HCM. Definitive exclusion of this important diagnosis requires an echo contrast study with or without three-dimensional echocardiography or another noninvasive modality like CMR.3 Our first two patients had epicardial coronary disease as well. We do not know if this finding could have contributed to ECG abnormalities. Our first patient (case A) can be characterized as pattern 3 according to Helmy’s criteria.8 These forms are generally judged to have a favorable outlook, with a very low risk of developing obstruction or apical aneurysm. Patients usually are asymptomatic, and the diagnosis is made following routine ECG. Indeed, this patient had a critical RCA lesion treated with PCI/stenting. Our second patient (case B) can be labeled as having a pattern 4 (P4) which is associated with an elevated risk of apical aneurysm.10 Of note, the clinical course in this patient was also complicated by epicardial coronary disease, including an acute coronary syndrome (ACS) due to LCx lesion and subsequent PCI/stenting of LAD because of recurrent angina. These first two patients allow us to focus on coronary artery disease (CAD) associated with hypertrophic cardiomyopathy. Myocardial ischemia in the absence of epicardial coronary atherosclerosis is a well-recognized phenomenon in patients with HCM. Approximately 25% of patients with HCM have evidence of ischemia during daily activity.11 The presence of ischemia has been associated with a worse prognosis in HCM.12,13 The mechanisms of ischemia are complex and include distortion of the arteriolar architecture, intramural small-vessel disease, a high prevalence of myocardial bridging, impairment of endothelium-dependent vasodilation, and an imbalance of myocardial oxygen supply and demand due to the hypertrophied myocardium and ventricular loading conditions.13 There also is evidence that coronary blood flow is maximal or near maximal in most patients with HCM (i.e., impaired coronary reserve).14 As a result of ischemia, myocardial fibrosis in HCM is a progressive and rapid phenomenon and it can be identified by CMR—late gadolinium enhancement (LGE) detection. We know that LGE which is related to a worse clinical status is more extensive in apical hypertrophy than in other patterns.4,15,16 Adult patients with HCM may develop concomitant atherosclerotic epicardial CAD. Reports on the prevalence of CAD in HCM have varied, but up to 20% of adult HCM patients have been shown to have coexistent CAD.15 Epicardial CAD is one of several etiologic mechanisms that contribute to myocardial ischemia in patients with HCM.17 There is a paucity of data on the clinical outcomes of patients with HCM who have CAD. 1578
Sorajja’s investigation18 revealed an adverse prognosis for patients with HCM undergoing routine coronary angiography who were found to have severe CAD. Compared with HCM patients without severe CAD, those with severe CAD had a significantly greater risk of death that was evident despite a normal LV ejection fraction. Optimal treatment of these patients with combined disease remains to be determined as in Sorajja’s study there was no apparent survival benefit for revascularization (PCI or CABG) in comparison to those who were treated medically.18 The third patient (case C) had an apical aneurysm due to mid-ventricular obstruction (type 2 of Helmy’s patterns). This indirect apical involvement includes different and more serious clinical implications.10 An LV apical aneurysm may be defined as a discrete thin-walled dyskinetic or akinetic segment of the most distal portion of the chamber with a relatively wide communication to the LV cavity. The incidence of concealed apical aneurysm with mid-ventricular cavity obliteration is approximately 1–2% of all HCM cases.10 The mechanisms responsible for the formation of apical aneurysms in patients with HCM remain unresolved. Several causes have been hypothesized, such as an increased LV wall stress as a result of mid-cavitary LV obstruction and elevated intracavitary systolic pressures, genetic predisposition, and myocardial bridging of LAD. The massive hypertrophy of the LV apex alone (Helmy’s pattern 4) could be at risk of aneurysm formation probably due to microvascular myocardial ischemia causing myocardial scarring. In a previous study,10 32% of patients with apical aneurysm had distal hypertrophy alone. The formation of apical aneurysm in HCM represents a very serious complication. Often, LV systolic function is depressed and thrombi may develop inside the aneurysm leading to embolic events. Ventricular tachycardia arising from the scarred apical wall may also occur, predisposing to sudden death. High-risk HCM patient subgroups identified with CMR include those with thin-walled scarred LV apical aneurysms (which prior to CMR imaging in HCM remained largely undetected).14 We know that echocardiography without contrast has a low accuracy (57%) in detecting LV aneurysm.10 Recently, Thind et al. from University of Alabama’s group 19 found that three-dimensional transthoracic echocardiogram (3DTTE) is of incremental value to two-dimensional transthoracic echocardiogram (2DTTE) in the assessment of mid left ventricular cavity obstruction with apical aneurysm formation. In the patient studied by them, 3DTTE provided a more comprehensive assessment of the apical
A Series of Three HCM Patients with LV Apex Involvement
aneurysm as compared to 2DTTE, which provides at any given time only a thin slice of a structure being studied. With 3DTTE, the entire extent of the aneurysm was contained in the 3D dataset so that it could be more fully studied using multiple cross sections at any desired angulation. Measurements in 3 dimensions included the azimuthal dimension (z axis), as well as the volume of the aneurysm, which is a more precise parameter of size compared with just 2 dimensions provided by 2DTTE. This would allow for more accurate monitoring of the progression of the aneurysm over time.19 In the same patient, a more comprehensive assessment of the thrombus inside the aneurysm was also possible by 3DTTE. Echolucencies, meaning clot dissolution, could also be assessed by 3DTTE. 3DTTE also showed areas of hyperechogenicity in the region of aneurysm consistent with fibrosis/scar tissue which correlated well with late gadolinium enhancement on CMR study. Interestingly in this patient, the aneurysm was missed initially by transthoracic echocardiography even though retrospectively it had been previously detected by CMR. Off-axis apical imaging and use of an echo contrast agent was helpful in identifying the aneurysm. These authors also commented on the previously described paradoxic jet flow phenomenon found in patients with HCM and apical aneurysm. High velocity flow is noted from the aneurysm into the LV in early systole, followed by low velocity flow or practically no flow going into the LV during mid-systole, and this is then followed by high velocity flow and high gradient during the isovolumetric relaxation period and diastole.20 Thind et al.19 postulated that even though the apex is aneurysmal and thin, there has to be enough muscle still present to generate a fairly strong apical contraction to explain the high gradients found between the apex and the LV cavity in early systole. Later in systole, the mid-cavity essentially closes resulting in little or no flow into the LV. During diastole, LV cavity opens up as it relaxes and the LV apex is able to push blood again into ventricle. Specific complications are common in association with large or medium aneurysms: sudden death, LV systolic dysfunction, progressive heart failure symptoms, and embolic stroke from LV apical thrombus. Small aneurysms usually are free of complications. Patients with large apical aneurysm have a high risk of sudden death, and they need ICD implantation. Mid-ventricular obstruction may be treated by transaortic myectomy, transapical muscle resection, and a combined transaortic and transapical approach.21 A transapical approach allows an excellent exposure for midventricular myectomy and relief of intraventricu-
lar gradients and related symptoms.1 However, the correct treatment of these forms remains unresolved. Conclusions: In patients with ECG or transthoracic echocardiographic evidence of LV hypertrophy, it is very important to accurately investigate the LV apex especially if there is no evidence of systemic hypertension to explain LV hypertrophy. Contrast-enhanced transthoracic echocardiography22 or CMR23 improves the accuracy of LV apex assessment. They are the best techniques in apical HCM, and usually they are concordant. In patients with HCM, LV apex may be involved in different ways. Whereas apical hypertrophy together with any other segment involvement may be a benign condition, massive hypertrophy of the apex could be at risk of aneurysm formation and myocardial scarring with serious prognostic implications. Aneurysm formation is frequent in patients with a mid-ventricular obstruction. 3DTTE is of incremental value to 2DTTE in the assessment of these patients. 3DTTE may be the gold standard in the HCM-related LV aneurysm assessment. Only a correct diagnosis of the apical involvement allows us to plan a correct interventional strategy. References 1. Maron BJ, McKenna W, Danielson GK, et al: ACC/ESC clinical expert consensus document on hypertrophic cardiomyopathy: A report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents and the European Society of Cardiology Committee for Practice Guidelines. J Am Coll Cardiol 2003;42:1687–1713. 2. Braunwald E, Lambrew CT, Rockoff SD, et al: Idiopathic hypertrophic subaortic stenosis. I. A description of the disease based upon an analysis of 64 patients. Circulation 1964;30(Suppl 4):3–119. 3. Wigle ED, Rakowski H, Kimball BP, et al: Hypertrophic cardiomyopathy. Clinical spectrum and treatment. Circulation 1995;92:1680–1692. 4. Maron BJ: Hypertrophic cardiomyopathy: A systematic review. JAMA 2002;287:1308–1320. 5. Wever-Pinzon O: Dual chamber pacing relieves obstruction in Japanese-variant hypertrophic cardiomyopathy. Am J Ther 2013;20:588–590. 6. Maron MS, Maron BJ, Harrigan C, et al: Hypertrophic cardiomyopathy phenotype revisited after 50 years with cardiovascular magnetic resonance. J Am Coll Cardiol 2009;54:220–228. 7. 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;48:418–428. 8. Helmy Sherif M: Hypertrophic cardiomyopathy: Prevalence, hypertrophy patterns, and their clinical and ECG findings in a hospital at Qatar. Heart Views 2011;12: 143–149.
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9. Maron MS: Clinical utility of cardiovascular magnetic resonance in hypertrophic cardiomyopathy. J Cardiovasc Magn Reson 2012;14:13. 10. Maron MS, Finley JJ, Bos JM, et al: Prevalence, clinical significance and natural history of left ventricular apical aneurysm in Hypertrophic Cardiomyopathy. Circulation 2008;118:1541– 1549. 11. Elliott PM, Kaski JC, Prasad K, et al: Chest pain during daily life in patients with hypertrophic cardiomyopathy: An ambulatory electrocardiographic study. Eur Heart J 1996;17:1056–1064. 12. Dilsizian V, Bonow RO, Epstein SE, et al: Myocardial ischemia detected by thallium scintigraphy is frequently related to cardiac arrest and syncope in young patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 1993;22:796–804. 13. Lazzeroni E, Picano E, Morozzi L, et al: Dipyridamoleinduced ischemia as a prognostic marker of future adverse cardiac events in adult patients with hypertrophic cardiomyopathy. Circulation 1997;96:4268– 4272. 14. Hirasaki S, Nakamura T, Kuribayashi T, et al: Abnormal course, abnormal flow, and systolic compression of the septal perforator associated with impaired myocardial perfusion in hypertrophic cardiomyopathy. Am Heart J 1999;137:109–117. 15. Ahn HS, Kim HK, Park EA, et al: Coronary flow reserve impairment in apical vs asymmetrical septal hypertrophic cardiomyopathy. Clin Cardiol 2013;36:207–216. 16. Olivotto I, Cecchi F, Poggesi C, et al: Patterns of disease progression in Hypertrophyc Cardiomiopathy: An
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19.
20.
21.
22.
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individualized approach to clinical staging. Circ Heart Fail 2012;5:535–546. Cokkinos DV, Krajcer Z, Leachman RD: Coronary artery disease in hypertrophic cardiomyopathy. Am J Cardiol 1985;55:1437–1438. Sorajja P, Ommen SR, Nishimura RA, et al: Adverse prognosis of patients with hypertrophic cardiomyopathy who have epicardial coronary artery disease. Circulation 2003;108:2342–2348. Thind M, Joson M, Gaba S, et al: Incremental value of live/real time three- dimensional transthoracic echocardiography over two-dimensional echocardiography in hypertrophic cardiomyopathy with mid-ventricular obstruction and apical aneurysm. Echocardiography 2015;32:565–569. Hsieh BP, Tauras J, Taub C: Continuous apex to left ventricle blood flow pattern in hypertrophic cardiomyopathy with apical aneurysm and midventricular obstruction. Echocardiography 2012;29:E131–E133. Kunkala MR, Schaff HV, Nishimura RA, et al: Transapical approach to myectomy for midventricular obstruction in hypertrophi cardiomyopathy. Ann Thorac Surg 2013;96:564–570. Walpot J, Pasteuning WH, Shivalkar B, et al: Apical hypertrophic cardiomyopathy: Elegant use of contrastenhanced echocardiography in the diagnostic work-up. Acta Cardiol 2012;67:495–497. Todiere G, Aquaro GD, Piaggi P, et al: Progression of myocardial fibrosis assessed with cardiac magnetic resonance in hypertrophic cardiomyopathy. J Am Coll Cardiol 2012;60:922–929.
Echocardiography
Left Ventricular Apex Involvement in Hypertrophic Cardiomyopathy Vito Maurizio Parato, M.D.,* Iacopo Olivotto, M.D.,† Martin S. Maron, M.D.,‡ Navin C. Nanda, M.D.,§ and Natesa G. Pandian, M.D.‡ *Cardiology Unit and Echocardiography, Madonna del Soccorso Hospital, San Benedetto del Tronto and Politecnica delle Marche University, Ancona, Italy; †Referral Center for Cardiomyopathies, Careggi University Hospital, Florence, Italy; ‡Tufts Medical Center, Boston, Massachusetts; and §Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, Alabama
(Echocardiography 2015;32:1575–1580) Key words: hypertrophic cardiomyopathy, left ventricular apex, left ventricle aneurysm, atherosclerotic epicardial coronary disease, echocardiography, two-dimensional echocardiography, three-dimensional echocardiography Hypertrophic cardiomyopathy (HCM) is a genetically transmitted disease with broad morphologic and clinical spectrum.1–4 The most common presentation involves asymmetric basal anteroseptal left ventricular (LV) hypertrophy with outflow tract obstruction due to systolic anterior motion of the mitral valve. Less common variants are represented by midventricular and apical HCM. These forms are usually defined “sub-basal HCM” and have been associated with apical aneurysm formation.5 There is no universal classification of the LV hypertrophy pattern in HCM.6,7 According to a “four-patterns” model proposed by Helmy SM,8 four different patterns of LV hypertrophy are identified: Pattern 1 (P1) is characterized by septal hypertrophy alone; pattern 2 (P2) involves the septum and adjacent segments but spares the apex; pattern 3 (P3) involves the apex in combination with other LV segments; and pattern 4 (P4) consists of an apical hypertrophy alone (Fig. 1). Isolated apical HCM (pattern 4) is a rare variant in the nonJapanese population (1–2%).6 We present three patients with HCM in whom the LV apex was involved in various patterns, reflecting the atypical localization of hypertrophy or the consequences of the mid-ventricular obstruction, and discuss the clinical implications of these rare variants.
Clinical Cases: Case A: The patient was a 62-year-old male, with negative clinical history. He was diagnosed at our institution following electrocardiogram (ECG) for sport-related preparticipation screening, and was completely asymptomatic and event-free. The ECG showed T wave inversion and ST-T depression in leads V4–6, Lead 1 and aVL (Fig. 2A). Transthoracic echocardiography showed apical hypertrophy (maximum diastolic thickness: 22 mm) extending to the whole lateral wall (maximum diastolic thickness: 21 mm). There was no intraventricular obstruction. LV cavity volume was 64 ml/m2 (end-diastole) and 27 ml/m2 (end-systole) with LV ejection fraction (EF): 58% (Fig. 2B,C). Cardiac magnetic resonance (CMR) (Fig. 2D,E) confirmed the apical localization of hypertrophy and identified areas of late gadolinium enhancement (LGE) within the inferior wall which was hypokinetic. Because of this finding, the patient underwent computed tomographic coronary angiogram (CTA) that revealed a significant lesion of the proximal right coronary artery (RCA) and nonsignificant lesions of the circumflex and left anterior descending coronary artery (LAD). The proximal RCA lesion, confirmed by angiography, was treated by percutaneous intervention (PCI) because of a positive exercise stress echocardiogram. To date, he remains asymptomatic and in good health.
Address for correspondence and reprint requests: Vito Maurizio Parato, M.D., Madonna del Soccorso Hospital, 3-7, via Manara, 63074, San Benedetto del Tronto, Italy. Fax: +39-0735-793363; E-mail: [email protected]
Case B: The patient was a 63-year-old male, who presented to the emergency department (ED) with
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atic on antiplatelet agents, b-blockers, renin– angiotensin inhibitors, and statins.
Figure 1. The four different patterns (P1 to P4) of HCM as proposed by Sherif M. Helmy.8 P1: Septal hypertrophy alone. P2: Hypertrophy involves the septum and adjacent segments but spares the apex. P3: Hypertrophy involves the apex in combination with other LV segments. P4: It consists of an apical hypertrophy alone.
acute onset of chest pain. He was diagnosed with NSTEMI due to a left circumflex coronary artery (LCx) culprit lesion and treated by PCI. The ECG showed very high voltages and an impressive ST depression plus very deep T-wave inversion in the precordial leads (Fig. 3A). The echocardiographic picture (Fig. 3B,C) was that of an evident apical HCM, with a maximum diastolic thickness of 21 mm. There was a complete apical obliteration in systole, confirmed by cardiac magnetic resonance (CMR) (Fig. 3D,E). During follow-up, the patient required a further PCI and stenting procedure for critical stenosis of the LAD. After this procedure, the patient remained asymptom-
Case C: The patient was a 60-year-old female, with a negative clinical history. She presented to the ED because of chest pain, palpitation, and dyspnea. The ECG showed rapidly conducted atrial fibrillation, associated with hypotension (90/60) and mild TnT/hs elevation. Urgent DC shock cardioversion was performed. The ECG after cardioversion (Fig. 4A) showed ST elevation in leads V1–5. A transthoracic echocardiogram showed clear evidence of HCM with the septal width of 28 mm and systolic muscular apposition of the septum and LV free wall at the mid-ventricle associated with a pressure gradient between the apical and basal chambers (Fig. 4B,C). Mid-ventricular gradients were 13 mmHg in diastole and 60 mmHg in systole. An “hourglass” shaped LV with a large apical aneurysm (28 9 20 mm in size) was evident. The aneurysm was more clearly detectable by CMR (Fig. 4D,E), which also showed transmural late gadolinium enhancement (LGE) due to extensive myocardial scarring at this level. The basal LV cavity was enlarged with a concave appearance of the interventricular septum. The coronary angiogram showed normal epicardial vessels. The patient underwent intracardiac defibrillator (ICD) implantation for primary prophylaxis and was started on warfarin, amiodaron, beta-blocker, and a statin. She remained asymptomatic at 4 years of follow-up, with no further recurrence of atrial fibrillation.
Figure 2. Case A. A. Basal ECG. B. Transthoracic echocardiogram, four-chamber view, systolic phase. C. Transthoracic echocardiogram, four-chamber view, diastolic phase. D. CMR image (L-A). E. CMR image (S-A). F,G. CMR images (four-chamber, diastole).
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A Series of Three HCM Patients with LV Apex Involvement
Figure 3. Case B. A. Basal ECG. B. TT-echocardiogram, four-chamber view, diastolic phase. C. TT- echocardiogram, fourchamber view, systolic phase. D. CMR image, four-chamber, diastolic phase. E. CMR image, four-chamber, systolic phase.
Figure 4. Case C. A.ECG during atrial fibrillation. B. Basal ECG in sinus rythm. C. TT-echocardiogram image, four-chamber view. D. CW-doppler: mid-ventricular gradient measurement. E,F. CMR images showing the apical aneurysm in diastolic (E, red arrow) and systolic (F, red arrow) phase.
Discussion: Hypertrophic cardiomyopathy patients with LV apex involvement represent an under-recognized subset in the heterogeneous HCM disease spectrum bearing important clinical implications. The detection of apical involvement often requires a high index of suspicion.9,10 CMR is often necessary to confirm the diagnosis, although contrast-enhanced echocardiography is an elegant bedside alternative to assess left ventricular apical segments.3
There are some special features of HCM with apex involvement. First, when the apex is involved, ECG evidence of LV hypertrophy is virtually always detectable. In Helmy’s study, it was present in 100% of patients with patterns 3 and 4.8 Likewise, in our patients the ECG was distinctively abnormal. This contains a clear message: in patients with ECG repolarization abnormalities without an obvious ischemic cause, routine echocardiography without contrast may not exclude apical 1577
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HCM. Definitive exclusion of this important diagnosis requires an echo contrast study with or without three-dimensional echocardiography or another noninvasive modality like CMR.3 Our first two patients had epicardial coronary disease as well. We do not know if this finding could have contributed to ECG abnormalities. Our first patient (case A) can be characterized as pattern 3 according to Helmy’s criteria.8 These forms are generally judged to have a favorable outlook, with a very low risk of developing obstruction or apical aneurysm. Patients usually are asymptomatic, and the diagnosis is made following routine ECG. Indeed, this patient had a critical RCA lesion treated with PCI/stenting. Our second patient (case B) can be labeled as having a pattern 4 (P4) which is associated with an elevated risk of apical aneurysm.10 Of note, the clinical course in this patient was also complicated by epicardial coronary disease, including an acute coronary syndrome (ACS) due to LCx lesion and subsequent PCI/stenting of LAD because of recurrent angina. These first two patients allow us to focus on coronary artery disease (CAD) associated with hypertrophic cardiomyopathy. Myocardial ischemia in the absence of epicardial coronary atherosclerosis is a well-recognized phenomenon in patients with HCM. Approximately 25% of patients with HCM have evidence of ischemia during daily activity.11 The presence of ischemia has been associated with a worse prognosis in HCM.12,13 The mechanisms of ischemia are complex and include distortion of the arteriolar architecture, intramural small-vessel disease, a high prevalence of myocardial bridging, impairment of endothelium-dependent vasodilation, and an imbalance of myocardial oxygen supply and demand due to the hypertrophied myocardium and ventricular loading conditions.13 There also is evidence that coronary blood flow is maximal or near maximal in most patients with HCM (i.e., impaired coronary reserve).14 As a result of ischemia, myocardial fibrosis in HCM is a progressive and rapid phenomenon and it can be identified by CMR—late gadolinium enhancement (LGE) detection. We know that LGE which is related to a worse clinical status is more extensive in apical hypertrophy than in other patterns.4,15,16 Adult patients with HCM may develop concomitant atherosclerotic epicardial CAD. Reports on the prevalence of CAD in HCM have varied, but up to 20% of adult HCM patients have been shown to have coexistent CAD.15 Epicardial CAD is one of several etiologic mechanisms that contribute to myocardial ischemia in patients with HCM.17 There is a paucity of data on the clinical outcomes of patients with HCM who have CAD. 1578
Sorajja’s investigation18 revealed an adverse prognosis for patients with HCM undergoing routine coronary angiography who were found to have severe CAD. Compared with HCM patients without severe CAD, those with severe CAD had a significantly greater risk of death that was evident despite a normal LV ejection fraction. Optimal treatment of these patients with combined disease remains to be determined as in Sorajja’s study there was no apparent survival benefit for revascularization (PCI or CABG) in comparison to those who were treated medically.18 The third patient (case C) had an apical aneurysm due to mid-ventricular obstruction (type 2 of Helmy’s patterns). This indirect apical involvement includes different and more serious clinical implications.10 An LV apical aneurysm may be defined as a discrete thin-walled dyskinetic or akinetic segment of the most distal portion of the chamber with a relatively wide communication to the LV cavity. The incidence of concealed apical aneurysm with mid-ventricular cavity obliteration is approximately 1–2% of all HCM cases.10 The mechanisms responsible for the formation of apical aneurysms in patients with HCM remain unresolved. Several causes have been hypothesized, such as an increased LV wall stress as a result of mid-cavitary LV obstruction and elevated intracavitary systolic pressures, genetic predisposition, and myocardial bridging of LAD. The massive hypertrophy of the LV apex alone (Helmy’s pattern 4) could be at risk of aneurysm formation probably due to microvascular myocardial ischemia causing myocardial scarring. In a previous study,10 32% of patients with apical aneurysm had distal hypertrophy alone. The formation of apical aneurysm in HCM represents a very serious complication. Often, LV systolic function is depressed and thrombi may develop inside the aneurysm leading to embolic events. Ventricular tachycardia arising from the scarred apical wall may also occur, predisposing to sudden death. High-risk HCM patient subgroups identified with CMR include those with thin-walled scarred LV apical aneurysms (which prior to CMR imaging in HCM remained largely undetected).14 We know that echocardiography without contrast has a low accuracy (57%) in detecting LV aneurysm.10 Recently, Thind et al. from University of Alabama’s group 19 found that three-dimensional transthoracic echocardiogram (3DTTE) is of incremental value to two-dimensional transthoracic echocardiogram (2DTTE) in the assessment of mid left ventricular cavity obstruction with apical aneurysm formation. In the patient studied by them, 3DTTE provided a more comprehensive assessment of the apical
A Series of Three HCM Patients with LV Apex Involvement
aneurysm as compared to 2DTTE, which provides at any given time only a thin slice of a structure being studied. With 3DTTE, the entire extent of the aneurysm was contained in the 3D dataset so that it could be more fully studied using multiple cross sections at any desired angulation. Measurements in 3 dimensions included the azimuthal dimension (z axis), as well as the volume of the aneurysm, which is a more precise parameter of size compared with just 2 dimensions provided by 2DTTE. This would allow for more accurate monitoring of the progression of the aneurysm over time.19 In the same patient, a more comprehensive assessment of the thrombus inside the aneurysm was also possible by 3DTTE. Echolucencies, meaning clot dissolution, could also be assessed by 3DTTE. 3DTTE also showed areas of hyperechogenicity in the region of aneurysm consistent with fibrosis/scar tissue which correlated well with late gadolinium enhancement on CMR study. Interestingly in this patient, the aneurysm was missed initially by transthoracic echocardiography even though retrospectively it had been previously detected by CMR. Off-axis apical imaging and use of an echo contrast agent was helpful in identifying the aneurysm. These authors also commented on the previously described paradoxic jet flow phenomenon found in patients with HCM and apical aneurysm. High velocity flow is noted from the aneurysm into the LV in early systole, followed by low velocity flow or practically no flow going into the LV during mid-systole, and this is then followed by high velocity flow and high gradient during the isovolumetric relaxation period and diastole.20 Thind et al.19 postulated that even though the apex is aneurysmal and thin, there has to be enough muscle still present to generate a fairly strong apical contraction to explain the high gradients found between the apex and the LV cavity in early systole. Later in systole, the mid-cavity essentially closes resulting in little or no flow into the LV. During diastole, LV cavity opens up as it relaxes and the LV apex is able to push blood again into ventricle. Specific complications are common in association with large or medium aneurysms: sudden death, LV systolic dysfunction, progressive heart failure symptoms, and embolic stroke from LV apical thrombus. Small aneurysms usually are free of complications. Patients with large apical aneurysm have a high risk of sudden death, and they need ICD implantation. Mid-ventricular obstruction may be treated by transaortic myectomy, transapical muscle resection, and a combined transaortic and transapical approach.21 A transapical approach allows an excellent exposure for midventricular myectomy and relief of intraventricu-
lar gradients and related symptoms.1 However, the correct treatment of these forms remains unresolved. Conclusions: In patients with ECG or transthoracic echocardiographic evidence of LV hypertrophy, it is very important to accurately investigate the LV apex especially if there is no evidence of systemic hypertension to explain LV hypertrophy. Contrast-enhanced transthoracic echocardiography22 or CMR23 improves the accuracy of LV apex assessment. They are the best techniques in apical HCM, and usually they are concordant. In patients with HCM, LV apex may be involved in different ways. Whereas apical hypertrophy together with any other segment involvement may be a benign condition, massive hypertrophy of the apex could be at risk of aneurysm formation and myocardial scarring with serious prognostic implications. Aneurysm formation is frequent in patients with a mid-ventricular obstruction. 3DTTE is of incremental value to 2DTTE in the assessment of these patients. 3DTTE may be the gold standard in the HCM-related LV aneurysm assessment. Only a correct diagnosis of the apical involvement allows us to plan a correct interventional strategy. References 1. Maron BJ, McKenna W, Danielson GK, et al: ACC/ESC clinical expert consensus document on hypertrophic cardiomyopathy: A report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents and the European Society of Cardiology Committee for Practice Guidelines. J Am Coll Cardiol 2003;42:1687–1713. 2. Braunwald E, Lambrew CT, Rockoff SD, et al: Idiopathic hypertrophic subaortic stenosis. I. A description of the disease based upon an analysis of 64 patients. Circulation 1964;30(Suppl 4):3–119. 3. Wigle ED, Rakowski H, Kimball BP, et al: Hypertrophic cardiomyopathy. Clinical spectrum and treatment. Circulation 1995;92:1680–1692. 4. Maron BJ: Hypertrophic cardiomyopathy: A systematic review. JAMA 2002;287:1308–1320. 5. Wever-Pinzon O: Dual chamber pacing relieves obstruction in Japanese-variant hypertrophic cardiomyopathy. Am J Ther 2013;20:588–590. 6. Maron MS, Maron BJ, Harrigan C, et al: Hypertrophic cardiomyopathy phenotype revisited after 50 years with cardiovascular magnetic resonance. J Am Coll Cardiol 2009;54:220–228. 7. 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;48:418–428. 8. Helmy Sherif M: Hypertrophic cardiomyopathy: Prevalence, hypertrophy patterns, and their clinical and ECG findings in a hospital at Qatar. Heart Views 2011;12: 143–149.
1579
Parato, et al.
9. Maron MS: Clinical utility of cardiovascular magnetic resonance in hypertrophic cardiomyopathy. J Cardiovasc Magn Reson 2012;14:13. 10. Maron MS, Finley JJ, Bos JM, et al: Prevalence, clinical significance and natural history of left ventricular apical aneurysm in Hypertrophic Cardiomyopathy. Circulation 2008;118:1541– 1549. 11. Elliott PM, Kaski JC, Prasad K, et al: Chest pain during daily life in patients with hypertrophic cardiomyopathy: An ambulatory electrocardiographic study. Eur Heart J 1996;17:1056–1064. 12. Dilsizian V, Bonow RO, Epstein SE, et al: Myocardial ischemia detected by thallium scintigraphy is frequently related to cardiac arrest and syncope in young patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 1993;22:796–804. 13. Lazzeroni E, Picano E, Morozzi L, et al: Dipyridamoleinduced ischemia as a prognostic marker of future adverse cardiac events in adult patients with hypertrophic cardiomyopathy. Circulation 1997;96:4268– 4272. 14. Hirasaki S, Nakamura T, Kuribayashi T, et al: Abnormal course, abnormal flow, and systolic compression of the septal perforator associated with impaired myocardial perfusion in hypertrophic cardiomyopathy. Am Heart J 1999;137:109–117. 15. Ahn HS, Kim HK, Park EA, et al: Coronary flow reserve impairment in apical vs asymmetrical septal hypertrophic cardiomyopathy. Clin Cardiol 2013;36:207–216. 16. Olivotto I, Cecchi F, Poggesi C, et al: Patterns of disease progression in Hypertrophyc Cardiomiopathy: An
1580
17. 18.
19.
20.
21.
22.
23.
individualized approach to clinical staging. Circ Heart Fail 2012;5:535–546. Cokkinos DV, Krajcer Z, Leachman RD: Coronary artery disease in hypertrophic cardiomyopathy. Am J Cardiol 1985;55:1437–1438. Sorajja P, Ommen SR, Nishimura RA, et al: Adverse prognosis of patients with hypertrophic cardiomyopathy who have epicardial coronary artery disease. Circulation 2003;108:2342–2348. Thind M, Joson M, Gaba S, et al: Incremental value of live/real time three- dimensional transthoracic echocardiography over two-dimensional echocardiography in hypertrophic cardiomyopathy with mid-ventricular obstruction and apical aneurysm. Echocardiography 2015;32:565–569. Hsieh BP, Tauras J, Taub C: Continuous apex to left ventricle blood flow pattern in hypertrophic cardiomyopathy with apical aneurysm and midventricular obstruction. Echocardiography 2012;29:E131–E133. Kunkala MR, Schaff HV, Nishimura RA, et al: Transapical approach to myectomy for midventricular obstruction in hypertrophi cardiomyopathy. Ann Thorac Surg 2013;96:564–570. Walpot J, Pasteuning WH, Shivalkar B, et al: Apical hypertrophic cardiomyopathy: Elegant use of contrastenhanced echocardiography in the diagnostic work-up. Acta Cardiol 2012;67:495–497. Todiere G, Aquaro GD, Piaggi P, et al: Progression of myocardial fibrosis assessed with cardiac magnetic resonance in hypertrophic cardiomyopathy. J Am Coll Cardiol 2012;60:922–929.
