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Myocardial stunning in hypertrophic cardiomyopathy: Recovery predicted by single photon emission computed tomographic thallium-201 scintigraphy
1415
JACC Vol. 13, No. 6 May 1989:1415-8
CASE REPORTS
Myocardial Stunning in Hypertrophic Cardiomyopathy: Recovery Predicted by Single Photon Emission Computed Tomographic Thallium-201 Scintigraphy DAVID G. FINE, Rochester,
MD: IAN P. CLEMENT&
MD, FACC, MARK J. CALLAHAN,
Minnesota
A young woman with hypertrophic cardiomyopathy confirmed by echocardiography and cardiac catheterization presented with chest pain and features of a large left ventricular aneurysm. The initial diagnosis was myocardial ischemia with either an evolving or an ancient myocardial infarction. Subsequently, verapamil therapy was associated with complete resolution of the extensive left ventricular wall motion abnormalities, normalization of left ventricular ejection fraction and a minimal myocardial infarction.
Hypertrophic cardiomyopathy is characterized by asymmetric myocardial hypertrophy, myofibrillar disarray, dynamic left ventricular outflow obstruction and decreased left ventricular compliance (1). The electrocardiogram (ECG) frequently shows abnormal Q waves suggestive of myocardial infarction. Although patients with this disorder are prone to sudden death (2) and have described symptoms of dyspnea, syncope, palpitation and chest pain, myocardial infarction has been described only rarely. We describe extensive spontaneous ischemia with subsequent resolution of the ischemia and associated severe wall motion abnormalities in a young woman with hypertrophic cardiomyopathy and angiographically normal coronary arteries.
Case Report A 32 year old white woman was admitted because of vague substernal heaviness associated with generalized weakness and exertional dyspnea lasting 12 h. She described three similar episodes in the past. The first was 1 year earlier after she received oxytocin and methylergonovine in the
From the Division of Cardiovascular Diseases and Internal Medicine. Mayo Clinic and Mayo Foundation, Rochester, Minnesota. Manuscript received June 20, 1988;revised manuscript received November 7, 1988,accepted December 5. 1988. -for Ian P. Clements. MD, Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, 200 First Street Southwest. Rochester, Minnesota 55905. 01989
MD, FACC
by the American
College
of
Cardiology
Normal thallium uptake on single photon emission computed tomographic scintigraphy early in the hospital course predicted myocardial viability in the region of the aneurysm. Thus, orally administered verapamil may reverse spontaneous extensive myocardial ischemia in hypertrophic cardiomyopathy and possibly limit the extent of myocardial infarction in such circumstances. (.I Am Co11Cardioll989;13:1415-8)
immediate postpartum period. That episode was associated with hypotension, bradycardia and dizziness. An ECG at that time showed small Q waves in the inferolateral leads and ST-T wave abnormalities. The patient recovered spontaneously and did’well until 3 weeks before admission, when she had an episode of nonexertional chest heaviness lasting about 2 h. Another brief episode occurred the night before admission. Many years earlier, she had been told she had a heart murmur. There was no history of hypertension, hyperlipidemia, diabetes, tobacco use, alcohol or drug abuse, oral contraceptive use, syncope or palpitation and there was no family history of cardiac disease. Physical examination. The patient, a tall, slender woman, had a blood pressure of 92/60 mm Hg, a heart rate of 64 beatsimin and a respiratory rate of 14 breathslmin. The apex beat was enlarged and dyskinetic. The jugular venous pressure was estimated to be 11 cm H,O. The first and second heart sounds were normal. A third heart sound was present. There was a grade 316apical systolic murmur that radiated to the left sternal border and axilla. The remainder of the findings were normal. Sublingual nitroglycerin exacerbated the patient’s chest discomfort. Initial evaluation. The ECG showed normal sinus rhythm and evidence suggesting an acute inferolateral myocardial infarction (Fig. 1). A chest radiograph was normal. An echocardiogram (Fig. 2) revealed an apical aneurysm, asymmetric septal hypertrophy, hyperdynamic basal left ventric0735.1097/89/$3,50
1416
FINE ET AL. MYOCARDIAL
STUNNING
JACC Vol. 13, No. 6 May 1989:1415-8
IN CARDIOMYOPATHY
Figure 1. Electrocardiogram on admission.
ular function, systolic anterior motion of the mitral valve and premature aortic valve closure. Doppler examination of the left ventricular outflow tract was consistent with a dynamic obstruction with a peak gradient of 10 to IS mm Hg. Mild mitral regurgitation was also recorded. The overall left ventricular cavity size was normal, and the ejection fraction was estimated to be approximately 45%. The findings were consistent with hypertrophic obstructive cardiomyopathy with an apical left ventricular aneurysm. Review of an echocardiogram recorded at another institution 3 years earlier showed findings of hypertrophic cardiomyopathy with no left ventricular wall motion abnormalities. Serumenzymes. Serum creatine kinase was 79 III/liter on admission (normal, 15 to 57) with 8% MB fraction, lactate dehydrogenase peaked at 72 IUiliter (normal, 48 to 115)with isoenzyme I greater than II (33% and 31%, respectively) and aspartate aminotransferase was 42 IUiliter (normal, 12 to 31). Hospital course. Because of further episodes of chest discomfort and further evolution of ECG changes (Fig. 3), cardiac catheterization was performed. Left ventriculography confirmed the asymmetric septal hypertrophy and dyskinetic anterolateral, apical, apical septal and diaphragmatic segments. The left ventricular end-diastolic pressure was 26
Figure 3. Secondelectrocardiogramshowingprogressionwith possible inferolateral myocardial infarction.
mm Hg. A mean intraventricular gradient of 22 mm Hg at rest was found. This increased to 45 mm Hg after ventricular premature beats and after amyl nitrite. The epicardial coronary arteries were entirely normal. Marked systolic compression of septal perforator vessels was seen. Oral administration of verapamil was begun, and the dose was increased to tolerance (360 mglday). Radionuclide angiography showed a large apical aneurysm and asymmetric septal hypertrophy. On the 8th hospital day, an echocardiogram showed a persistent aneurysm but improvement in global left ventricular function. Single photon emission computed tomographic thallium-201 scintigraphy performed 13 days after admission showed only slight inferoapical thinning, which was within normal limits (Fig. 4). Posthospital course. Radionuclide angiography performed 6 weeks after hospital discharge showed an ejection fraction of 83% and no evidence of aneurysm. Serial echocardiographic examinations over 4 months demonstrated gradual resolution of all regional wall motion abnormalities (Fig. 5). The patient has remained free of symptoms for more than a year since hospital dismissal.
Discussion Figure 2. Admission echocardiogram (end-systolic frame) demonstrating asymmetric septal hypertrophy and an apical aneurysm. LA = left atrium; LV = left ventricle; RA = right atrium; RV = right
ventricle.
Myocardial ischemia and infarction in hypertrophic cardiomyopathy. This case demonstrates that spontaneous myocardial ischemia can result in marked wall motion abnormalities mimicking extensive myocardial infarction in hypertrophic cardiomyopathy despite normal epicardial coronary arteries. The subsequent resolution of the wall motion abnormality with only a slight cardiac enzyme elevation demonstrated that the ischemia was reversible. This pa-
Figure 4. Single photon emission computed tomographic thallium201 scintigraphic scan performed before hospital discharge is within normal limits. Selected horizontal long-axis (left), vertical long-axis (center) and short-axis (right)images are shown.
JACC Vol. 13. No. 6 May 1989:1415-11
Figure5.
Echocardiogram obtained 4.5 months after hospital discharge (end-systolic frame). The aneurysm present on the initial examination (Fig. 2) has resolved. Abbreviations as in Figure 2.
recovery, which may have been presaged by the normal thallium uptake in the ischemic region, was associated with the use of verapamil. Exertional chest pain in patients with hypertrophic cardiomyopathy is a common symptom, even in the absence of epicardial coronary artery disease (1). Evidence that this may represent myocardial ischemia comes from atrial pacing studies in which increased lactate production, increased filling pressures and signs of inadequate coronary reserve have been demonstrated (3-6) and from exercise studies showing inducible thallium perfusion defects (7). Maron (8) and Wailer (9) and their coworkers found transmural infarction in seven necropsy cases of hypertrophic cardiomyopathy in which the epicardial coronary arteries were normal. Had the ischemia not been reversed, our patient likely would have been left with significant myocardial dysfunction. Perhaps this was the mechanism by which rapidly progressing congestive heart failure with ventricular dilation developed in six of the seven patients in the series of Maron et al. (8). Indeed, O’Gara et al. (7) showed that 93% of patients with hypertrophic cardiomyopathy and depressed left ventricular function had evidence of myocardial scarring or severe ischemia with exercise thallium testing. Most patients in that study had reversible thallium defects after exercise, an indication that myocardial ischemia had disappeared. The findings in our patient support the hypothesis that spontaneous myocardial ischemia in hypertrophic cardiomyopathy is reversible. Although no thallium scan was performed while the patient was symptomatic and no simultaneous regional wall motion assessment was performed. the abundant uptake of thallium in the region of the mechanically “stunned” myocardium at a time when the patient was asymptomatic appeared to foreshadow the eventual complete myocardial recovery. tient’s
MYOCARDIAL
STUNNING
FINE ET AI.. IN CARDIOMYOPATHY
1417
Possible causes of acute iscbemia. The cause of acute myocardial ischemia in patients with hypertrophic cardiomyopathy and normal coronary arteries is unknown. Cases demonstrating coronary emboli (8) and coronary spasm (10) have been reported. Myocardial compression of septal perforator branches, as seen in this patient, is not uncommon in hypertrophic cardiomyopathy (I I). It could result in significant ischemia in these patients, who characteristically have a prolonged systolic ejection time, so that greater dependence of myocardial perfusion is placed on the relatively shortened diastole (6, I I). Abnormalities in diastolic relaxation could be responsible for impairment of early filling of the coronary reservoir (12-14). Inadequate capillary density in relation to the increased myocardial mass present (14) may result in further decreased oxygen extraction (5). These microcirculatory changes may be due to replacement by abnormal myocellular architecture or fibrosis (15). Increased left ventricular filling pressure during ischemia could result in further decrease in oxygen delivery secondary to microcirculatory compression (5). In the series of Maron et al. (16). 83% of the patients with hypertrophic cardiomyopathy had disease of the small intramural coronary arteries that was strongly associated with areas of fibrosis. Such small vessel disease could cause ischemia by reducing coronary reserve (17,lS). Tillmanns et al. (19) found evidence that ergometrine constricted the microvascular prearteriolar vessels. Cannon et al. (20) showed that patients with normal coronary arteries in whom ergonovine induced chest pain experienced chest pain after infusion of dipyridamole despite a more than doubling of the transmural flow. presumably because of abnormal small coronary vessels. It could be postulated that the methylergonovine received preceding the postpartum episode of our patient resulted in coronary spasm of either the small or the large coronary vessels. Subendocardial and possibly transmural ischemia may occur with left ventricular hypertrophy of other causes, although the mechanisms may not be identical. It has been shown that in other patients with left ventricular hypertrophy. the small vessel coronary abnormalities are not as prevalent or as marked (16) and septal perforator compression is not present (II). Additionally, the presence of an outflow tract obstruction seems to play a role in coronary reserve (6). Therapeuticissues. Therapy for ischemia in hypertrophic cardiomyopathy is no better defined than is the etiology. The most commonly advocated therapeutic goals have been to improve ventricular filling and to avoid inotropic agents. As in other ischemic syndromes, agents affecting the autonomic nervous system have been advocated by some because of its influence on inotropy, chronotropy and circulatory tone. Studies (3,13) in hypertrophic cardiomyopathy have shown propranolol to primarily affect heart rate and systolic ejec-
1418
FINE ET AL. MYOCARDIAL STUNNING
JACC Vol. 13, No. 6 May 1989:1415-8
IN CARDIOMYOPATHY
tion rate. Verapamil has been advocated because of its ability to improve diastolic filling (14). One study (21) showed it to increase cardiac output in some patients with outflow tract obstruction. Recent studies have shown ejection fraction to remain the same (13) or decrease (14) when verapamil is used. Verapamil may also be beneficial if vasospasm is a factor. Conclusions. Hypertrophic cardiomyopathy can be associated with myocardial ischemia and infarction despite normal epicardial coronary arteries. The clinical occurrence is rare, and the cause is uncertain. This is, to our knowledge, the first report of documented reversal of a large amount of ischemic myocardium in the setting of an apparent acute myocardial infarction in a patient with hypertrophic cardiomyopathy and normal coronary arteries. Treatment of such patients with verapamil may alleviate ischemia and may improve regional wall motion to a greater degree than that seen in patients with typical coronary artery disease. Thallium scanning may have an important prognostic role in these patients.
References I. Braunwald E, Lambrew CT. Rockoff SD. Ross J Jr, Morrow AG. Idiopathic hypertrophic subaortic stenosis. I. A description of the disease based upon an analysis of 64 patients. Circulation 1964:3Otsuppl lVl:IV-3119. 2. Maron BJ, Roberts WC, Edwards JE. McAllister HA Jr. Foley DD. Epstein SE. Sudden death in patients with hypertrophic cardiomyopathy: characterization of 26 patients without functional limitations. Am J Cardiol 1978;41:803-10. 3. Thompson DS, Naqvi N. Juul SM, et al. Effects of propranolol on myocardial oxygen consumption. substrate extraction. and haemodynamits in hypertrophic obstructive cardiomyopathy. Br Heart J 1980:44:48898. 4. Cannon RO III, Rosing DR. Maron BJ, et al. Myocardial ischemia in patients with hypertrophic cardiomyopathy: contribution of inadequate vasodilator reserve and elevated left ventricular filling pressures. Circulation 1985;71:234-43.
7. O’Gara PT. Bonow RO. Maron BJ, et al. Myocardial perfusion abnormalities in patients with hypertrophic cardiomyopathy: assessment with thallium-201 emission computed tomography. Circulation 1987;76:1214-23. 8. Maron BJ, Epstein SE, Roberts WC. Hypertrophic cardiomyopathy and transmural myocardial infarction without significant atherosclerosis of the extramural coronary arteries. Am J Cardiol 1979;43: 1086-102. 9. Wailer BF, Maron BJ, Epstein SE, Roberts WC. Transmural myocardial infarction in hypertrophic cardiomyopathy: a cause of conversion from left ventricular asymmetry to symmetry and from normal-sized to dilated left ventricular cavity. Chest 1981;79:461-5. IO. Nishimura K. Nosaka H, Saito T, Nobuyoshi M. Another possible mechanism of angina in hypertrophic cardiomyopathy (abstr). Circulation 1983:68(suppl 111):111-162. II.
Pichard AD, Meller J, Teichholz LE. Lipnik S, Gorlin R, Herman MV. Septal perforator compression (narrowing) in idiopathic hypertrophic subaortic stenosis. Am J Cardiol 3977:40:310-4.
12. St John Sutton MG, Tajik AJ, Smith HC, Ritman EL. Angina in idiopathic hypertrophic subaortic stenosis: a clinical correlate of regional left ventricular dysfunction: a videometric and echocardiographic study. Circulation 1980:61:561-8. 13. Bonow RO. Rosing DR. Bacharach SL, et al. Effects of verapamil on left ventricular systolic function and diastolic filling in patients with hypertrophic cardiomyopathy. Circulation 1981;64:787-%. 14. Bonow RO, Ostrow HG, Rosing DR. 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. 15. Maron BJ. Roberts WC. Quantitative analysis of cardiac muscle cell disorganization in the ventricular septum of patients with hypertrophic cardiomyopathy. Circulation 1979;59:689-706. 16. Maron BJ, Wolfson JK, Epstein SE, Roberts WC. Intramural (“small vessel”) coronary artery disease in hypertrophic cardiomyopathy. J Am Coll Cardiol 1986:8:545-57. 17. Opherk D, Zebe H, Weihe E. et al. Reduced coronary dilatory capacity and ultrastructural changes of the myocardium in patients with angina pectoris but normal coronary arteriograms. Circulation 1981;63:817-25. 18. Cannon RO III, Watson RM, Rosing DR. Epstein SE. Angina caused by reduced vasodilator reserve of the small coronary arteries. J Am Coll Cardiol 1983;1:1359-73. 19. Tillmanns H. Mdller P, Dart AM, Steinhausen M, Parekh N, Ktlbler W. Changes in myocardial microvascular tone during ergometrine provocation (abstr). Circulation 1983;68(suppl llI):I11-33.
5. Pasternac A, Noble J, Streulens Y. Elie R. Henschke C. Bourassa MG. Pathophysiology of chest pain in patients with cardiomyopathies and normal coronary arteries. Circulation 1982;65:778-89.
20. Cannon RO, Leon MB, Rosing DR, Urquhart J, Epstein SE. Limited vasodilator reserve after dipyridamole in patients with ergonovineinduced abnormal vasodilator reserve (abstr). J Am Coil Cardiol 1985;5: 443.
6. Cannon RO III, Schenke WH, Maron BJ, et al. Differences in coronary flow and myocardial metabolism at rest and during pacing between patients with obstructive and patients with nonobstructive hypertrophic cardiomy opathy. J Am Coll Cardiol 1987:10:53-62.
21. 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.
JACC Vol. 13, No. 6 May 1989:1415-8
CASE REPORTS
Myocardial Stunning in Hypertrophic Cardiomyopathy: Recovery Predicted by Single Photon Emission Computed Tomographic Thallium-201 Scintigraphy DAVID G. FINE, Rochester,
MD: IAN P. CLEMENT&
MD, FACC, MARK J. CALLAHAN,
Minnesota
A young woman with hypertrophic cardiomyopathy confirmed by echocardiography and cardiac catheterization presented with chest pain and features of a large left ventricular aneurysm. The initial diagnosis was myocardial ischemia with either an evolving or an ancient myocardial infarction. Subsequently, verapamil therapy was associated with complete resolution of the extensive left ventricular wall motion abnormalities, normalization of left ventricular ejection fraction and a minimal myocardial infarction.
Hypertrophic cardiomyopathy is characterized by asymmetric myocardial hypertrophy, myofibrillar disarray, dynamic left ventricular outflow obstruction and decreased left ventricular compliance (1). The electrocardiogram (ECG) frequently shows abnormal Q waves suggestive of myocardial infarction. Although patients with this disorder are prone to sudden death (2) and have described symptoms of dyspnea, syncope, palpitation and chest pain, myocardial infarction has been described only rarely. We describe extensive spontaneous ischemia with subsequent resolution of the ischemia and associated severe wall motion abnormalities in a young woman with hypertrophic cardiomyopathy and angiographically normal coronary arteries.
Case Report A 32 year old white woman was admitted because of vague substernal heaviness associated with generalized weakness and exertional dyspnea lasting 12 h. She described three similar episodes in the past. The first was 1 year earlier after she received oxytocin and methylergonovine in the
From the Division of Cardiovascular Diseases and Internal Medicine. Mayo Clinic and Mayo Foundation, Rochester, Minnesota. Manuscript received June 20, 1988;revised manuscript received November 7, 1988,accepted December 5. 1988. -for Ian P. Clements. MD, Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, 200 First Street Southwest. Rochester, Minnesota 55905. 01989
MD, FACC
by the American
College
of
Cardiology
Normal thallium uptake on single photon emission computed tomographic scintigraphy early in the hospital course predicted myocardial viability in the region of the aneurysm. Thus, orally administered verapamil may reverse spontaneous extensive myocardial ischemia in hypertrophic cardiomyopathy and possibly limit the extent of myocardial infarction in such circumstances. (.I Am Co11Cardioll989;13:1415-8)
immediate postpartum period. That episode was associated with hypotension, bradycardia and dizziness. An ECG at that time showed small Q waves in the inferolateral leads and ST-T wave abnormalities. The patient recovered spontaneously and did’well until 3 weeks before admission, when she had an episode of nonexertional chest heaviness lasting about 2 h. Another brief episode occurred the night before admission. Many years earlier, she had been told she had a heart murmur. There was no history of hypertension, hyperlipidemia, diabetes, tobacco use, alcohol or drug abuse, oral contraceptive use, syncope or palpitation and there was no family history of cardiac disease. Physical examination. The patient, a tall, slender woman, had a blood pressure of 92/60 mm Hg, a heart rate of 64 beatsimin and a respiratory rate of 14 breathslmin. The apex beat was enlarged and dyskinetic. The jugular venous pressure was estimated to be 11 cm H,O. The first and second heart sounds were normal. A third heart sound was present. There was a grade 316apical systolic murmur that radiated to the left sternal border and axilla. The remainder of the findings were normal. Sublingual nitroglycerin exacerbated the patient’s chest discomfort. Initial evaluation. The ECG showed normal sinus rhythm and evidence suggesting an acute inferolateral myocardial infarction (Fig. 1). A chest radiograph was normal. An echocardiogram (Fig. 2) revealed an apical aneurysm, asymmetric septal hypertrophy, hyperdynamic basal left ventric0735.1097/89/$3,50
1416
FINE ET AL. MYOCARDIAL
STUNNING
JACC Vol. 13, No. 6 May 1989:1415-8
IN CARDIOMYOPATHY
Figure 1. Electrocardiogram on admission.
ular function, systolic anterior motion of the mitral valve and premature aortic valve closure. Doppler examination of the left ventricular outflow tract was consistent with a dynamic obstruction with a peak gradient of 10 to IS mm Hg. Mild mitral regurgitation was also recorded. The overall left ventricular cavity size was normal, and the ejection fraction was estimated to be approximately 45%. The findings were consistent with hypertrophic obstructive cardiomyopathy with an apical left ventricular aneurysm. Review of an echocardiogram recorded at another institution 3 years earlier showed findings of hypertrophic cardiomyopathy with no left ventricular wall motion abnormalities. Serumenzymes. Serum creatine kinase was 79 III/liter on admission (normal, 15 to 57) with 8% MB fraction, lactate dehydrogenase peaked at 72 IUiliter (normal, 48 to 115)with isoenzyme I greater than II (33% and 31%, respectively) and aspartate aminotransferase was 42 IUiliter (normal, 12 to 31). Hospital course. Because of further episodes of chest discomfort and further evolution of ECG changes (Fig. 3), cardiac catheterization was performed. Left ventriculography confirmed the asymmetric septal hypertrophy and dyskinetic anterolateral, apical, apical septal and diaphragmatic segments. The left ventricular end-diastolic pressure was 26
Figure 3. Secondelectrocardiogramshowingprogressionwith possible inferolateral myocardial infarction.
mm Hg. A mean intraventricular gradient of 22 mm Hg at rest was found. This increased to 45 mm Hg after ventricular premature beats and after amyl nitrite. The epicardial coronary arteries were entirely normal. Marked systolic compression of septal perforator vessels was seen. Oral administration of verapamil was begun, and the dose was increased to tolerance (360 mglday). Radionuclide angiography showed a large apical aneurysm and asymmetric septal hypertrophy. On the 8th hospital day, an echocardiogram showed a persistent aneurysm but improvement in global left ventricular function. Single photon emission computed tomographic thallium-201 scintigraphy performed 13 days after admission showed only slight inferoapical thinning, which was within normal limits (Fig. 4). Posthospital course. Radionuclide angiography performed 6 weeks after hospital discharge showed an ejection fraction of 83% and no evidence of aneurysm. Serial echocardiographic examinations over 4 months demonstrated gradual resolution of all regional wall motion abnormalities (Fig. 5). The patient has remained free of symptoms for more than a year since hospital dismissal.
Discussion Figure 2. Admission echocardiogram (end-systolic frame) demonstrating asymmetric septal hypertrophy and an apical aneurysm. LA = left atrium; LV = left ventricle; RA = right atrium; RV = right
ventricle.
Myocardial ischemia and infarction in hypertrophic cardiomyopathy. This case demonstrates that spontaneous myocardial ischemia can result in marked wall motion abnormalities mimicking extensive myocardial infarction in hypertrophic cardiomyopathy despite normal epicardial coronary arteries. The subsequent resolution of the wall motion abnormality with only a slight cardiac enzyme elevation demonstrated that the ischemia was reversible. This pa-
Figure 4. Single photon emission computed tomographic thallium201 scintigraphic scan performed before hospital discharge is within normal limits. Selected horizontal long-axis (left), vertical long-axis (center) and short-axis (right)images are shown.
JACC Vol. 13. No. 6 May 1989:1415-11
Figure5.
Echocardiogram obtained 4.5 months after hospital discharge (end-systolic frame). The aneurysm present on the initial examination (Fig. 2) has resolved. Abbreviations as in Figure 2.
recovery, which may have been presaged by the normal thallium uptake in the ischemic region, was associated with the use of verapamil. Exertional chest pain in patients with hypertrophic cardiomyopathy is a common symptom, even in the absence of epicardial coronary artery disease (1). Evidence that this may represent myocardial ischemia comes from atrial pacing studies in which increased lactate production, increased filling pressures and signs of inadequate coronary reserve have been demonstrated (3-6) and from exercise studies showing inducible thallium perfusion defects (7). Maron (8) and Wailer (9) and their coworkers found transmural infarction in seven necropsy cases of hypertrophic cardiomyopathy in which the epicardial coronary arteries were normal. Had the ischemia not been reversed, our patient likely would have been left with significant myocardial dysfunction. Perhaps this was the mechanism by which rapidly progressing congestive heart failure with ventricular dilation developed in six of the seven patients in the series of Maron et al. (8). Indeed, O’Gara et al. (7) showed that 93% of patients with hypertrophic cardiomyopathy and depressed left ventricular function had evidence of myocardial scarring or severe ischemia with exercise thallium testing. Most patients in that study had reversible thallium defects after exercise, an indication that myocardial ischemia had disappeared. The findings in our patient support the hypothesis that spontaneous myocardial ischemia in hypertrophic cardiomyopathy is reversible. Although no thallium scan was performed while the patient was symptomatic and no simultaneous regional wall motion assessment was performed. the abundant uptake of thallium in the region of the mechanically “stunned” myocardium at a time when the patient was asymptomatic appeared to foreshadow the eventual complete myocardial recovery. tient’s
MYOCARDIAL
STUNNING
FINE ET AI.. IN CARDIOMYOPATHY
1417
Possible causes of acute iscbemia. The cause of acute myocardial ischemia in patients with hypertrophic cardiomyopathy and normal coronary arteries is unknown. Cases demonstrating coronary emboli (8) and coronary spasm (10) have been reported. Myocardial compression of septal perforator branches, as seen in this patient, is not uncommon in hypertrophic cardiomyopathy (I I). It could result in significant ischemia in these patients, who characteristically have a prolonged systolic ejection time, so that greater dependence of myocardial perfusion is placed on the relatively shortened diastole (6, I I). Abnormalities in diastolic relaxation could be responsible for impairment of early filling of the coronary reservoir (12-14). Inadequate capillary density in relation to the increased myocardial mass present (14) may result in further decreased oxygen extraction (5). These microcirculatory changes may be due to replacement by abnormal myocellular architecture or fibrosis (15). Increased left ventricular filling pressure during ischemia could result in further decrease in oxygen delivery secondary to microcirculatory compression (5). In the series of Maron et al. (16). 83% of the patients with hypertrophic cardiomyopathy had disease of the small intramural coronary arteries that was strongly associated with areas of fibrosis. Such small vessel disease could cause ischemia by reducing coronary reserve (17,lS). Tillmanns et al. (19) found evidence that ergometrine constricted the microvascular prearteriolar vessels. Cannon et al. (20) showed that patients with normal coronary arteries in whom ergonovine induced chest pain experienced chest pain after infusion of dipyridamole despite a more than doubling of the transmural flow. presumably because of abnormal small coronary vessels. It could be postulated that the methylergonovine received preceding the postpartum episode of our patient resulted in coronary spasm of either the small or the large coronary vessels. Subendocardial and possibly transmural ischemia may occur with left ventricular hypertrophy of other causes, although the mechanisms may not be identical. It has been shown that in other patients with left ventricular hypertrophy. the small vessel coronary abnormalities are not as prevalent or as marked (16) and septal perforator compression is not present (II). Additionally, the presence of an outflow tract obstruction seems to play a role in coronary reserve (6). Therapeuticissues. Therapy for ischemia in hypertrophic cardiomyopathy is no better defined than is the etiology. The most commonly advocated therapeutic goals have been to improve ventricular filling and to avoid inotropic agents. As in other ischemic syndromes, agents affecting the autonomic nervous system have been advocated by some because of its influence on inotropy, chronotropy and circulatory tone. Studies (3,13) in hypertrophic cardiomyopathy have shown propranolol to primarily affect heart rate and systolic ejec-
1418
FINE ET AL. MYOCARDIAL STUNNING
JACC Vol. 13, No. 6 May 1989:1415-8
IN CARDIOMYOPATHY
tion rate. Verapamil has been advocated because of its ability to improve diastolic filling (14). One study (21) showed it to increase cardiac output in some patients with outflow tract obstruction. Recent studies have shown ejection fraction to remain the same (13) or decrease (14) when verapamil is used. Verapamil may also be beneficial if vasospasm is a factor. Conclusions. Hypertrophic cardiomyopathy can be associated with myocardial ischemia and infarction despite normal epicardial coronary arteries. The clinical occurrence is rare, and the cause is uncertain. This is, to our knowledge, the first report of documented reversal of a large amount of ischemic myocardium in the setting of an apparent acute myocardial infarction in a patient with hypertrophic cardiomyopathy and normal coronary arteries. Treatment of such patients with verapamil may alleviate ischemia and may improve regional wall motion to a greater degree than that seen in patients with typical coronary artery disease. Thallium scanning may have an important prognostic role in these patients.
References I. Braunwald E, Lambrew CT. Rockoff SD. Ross J Jr, Morrow AG. Idiopathic hypertrophic subaortic stenosis. I. A description of the disease based upon an analysis of 64 patients. Circulation 1964:3Otsuppl lVl:IV-3119. 2. Maron BJ, Roberts WC, Edwards JE. McAllister HA Jr. Foley DD. Epstein SE. Sudden death in patients with hypertrophic cardiomyopathy: characterization of 26 patients without functional limitations. Am J Cardiol 1978;41:803-10. 3. Thompson DS, Naqvi N. Juul SM, et al. Effects of propranolol on myocardial oxygen consumption. substrate extraction. and haemodynamits in hypertrophic obstructive cardiomyopathy. Br Heart J 1980:44:48898. 4. Cannon RO III, Rosing DR. Maron BJ, et al. Myocardial ischemia in patients with hypertrophic cardiomyopathy: contribution of inadequate vasodilator reserve and elevated left ventricular filling pressures. Circulation 1985;71:234-43.
7. O’Gara PT. Bonow RO. Maron BJ, et al. Myocardial perfusion abnormalities in patients with hypertrophic cardiomyopathy: assessment with thallium-201 emission computed tomography. Circulation 1987;76:1214-23. 8. Maron BJ, Epstein SE, Roberts WC. Hypertrophic cardiomyopathy and transmural myocardial infarction without significant atherosclerosis of the extramural coronary arteries. Am J Cardiol 1979;43: 1086-102. 9. Wailer BF, Maron BJ, Epstein SE, Roberts WC. Transmural myocardial infarction in hypertrophic cardiomyopathy: a cause of conversion from left ventricular asymmetry to symmetry and from normal-sized to dilated left ventricular cavity. Chest 1981;79:461-5. IO. Nishimura K. Nosaka H, Saito T, Nobuyoshi M. Another possible mechanism of angina in hypertrophic cardiomyopathy (abstr). Circulation 1983:68(suppl 111):111-162. II.
Pichard AD, Meller J, Teichholz LE. Lipnik S, Gorlin R, Herman MV. Septal perforator compression (narrowing) in idiopathic hypertrophic subaortic stenosis. Am J Cardiol 3977:40:310-4.
12. St John Sutton MG, Tajik AJ, Smith HC, Ritman EL. Angina in idiopathic hypertrophic subaortic stenosis: a clinical correlate of regional left ventricular dysfunction: a videometric and echocardiographic study. Circulation 1980:61:561-8. 13. Bonow RO. Rosing DR. Bacharach SL, et al. Effects of verapamil on left ventricular systolic function and diastolic filling in patients with hypertrophic cardiomyopathy. Circulation 1981;64:787-%. 14. Bonow RO, Ostrow HG, Rosing DR. 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. 15. Maron BJ. Roberts WC. Quantitative analysis of cardiac muscle cell disorganization in the ventricular septum of patients with hypertrophic cardiomyopathy. Circulation 1979;59:689-706. 16. Maron BJ, Wolfson JK, Epstein SE, Roberts WC. Intramural (“small vessel”) coronary artery disease in hypertrophic cardiomyopathy. J Am Coll Cardiol 1986:8:545-57. 17. Opherk D, Zebe H, Weihe E. et al. Reduced coronary dilatory capacity and ultrastructural changes of the myocardium in patients with angina pectoris but normal coronary arteriograms. Circulation 1981;63:817-25. 18. Cannon RO III, Watson RM, Rosing DR. Epstein SE. Angina caused by reduced vasodilator reserve of the small coronary arteries. J Am Coll Cardiol 1983;1:1359-73. 19. Tillmanns H. Mdller P, Dart AM, Steinhausen M, Parekh N, Ktlbler W. Changes in myocardial microvascular tone during ergometrine provocation (abstr). Circulation 1983;68(suppl llI):I11-33.
5. Pasternac A, Noble J, Streulens Y. Elie R. Henschke C. Bourassa MG. Pathophysiology of chest pain in patients with cardiomyopathies and normal coronary arteries. Circulation 1982;65:778-89.
20. Cannon RO, Leon MB, Rosing DR, Urquhart J, Epstein SE. Limited vasodilator reserve after dipyridamole in patients with ergonovineinduced abnormal vasodilator reserve (abstr). J Am Coil Cardiol 1985;5: 443.
6. Cannon RO III, Schenke WH, Maron BJ, et al. Differences in coronary flow and myocardial metabolism at rest and during pacing between patients with obstructive and patients with nonobstructive hypertrophic cardiomy opathy. J Am Coll Cardiol 1987:10:53-62.
21. 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.