Effect of nicorandil on left ventricular end-diastolic pressure during exercise in patients with hypertrophic cardiomyopathy.

AIMS: Impaired coronary microcirculation is thought to contribute to myocardial ischaemia, causing an abnormal increase in left ventricular end-diastolic pressure during exercise in individuals with hypertrophic cardiomyopathy. The effects of nicorandil on left ventricular end-diastolic pressure during exercise were examined in patients with this condition. METHODS AND RESULTS: Left ventricular pressures and dimensions were measured simultaneously during supine bicycle exercise in 23 patients with nonobstructive hypertrophic cardiomyopathy, before and after intravenous injection of either nicorandil (0.1 mg/kg) or propranolol (0.15 mg/kg). Exercise thallium-201 scintigraphy was also performed. Patients were grouped according to the changes in left ventricular end-diastolic pressure during exercise before treatment. Group I comprised 13 patients in whom left ventricular end-diastolic pressure increased progressively to abnormal values during exercise; group II comprised 10 patients in whom left ventricular end-diastolic pressure changed biphasically. The extents of both left ventricular hypertrophy and ischemic burden during exercise were greater in group I than in group II. Of the eight group I patients who received nicorandil, four individuals exhibited biphasic changes in left ventricular end-diastolic pressure during exercise after its administration whereas four subjects showed no such effect of the drug. Left ventricular end-diastolic pressure increased progressively during exercise after propranolol treatment in all 6 group II patients given this drug. CONCLUSION: Nicorandil has a salutary effect on the changes in left ventricular end-diastolic pressure during exercise in patients with hypertrophic cardiomyopathy.     

Positive correlations between serum calcineurin activity and left ventricular hypertrophy

BACKGROUND: Among various intracellular signaling cascades associated with cardiac hypertrophy, the involvement of calcineurin (CaN; Ca2+-calmodulin dependent protein phosphatase) is gaining credence because of its enhanced activity in ventricular myocardium and the ability of CaN inhibitors to prevent pressure-overload hypertrophy. Since our recent findings attribute clinical significance to serum CaN, the present investigation was conducted to evaluate its significance in cardiac hypertrophy. METHODS: The study group comprised of patients diagnosed for hypertensive hypertrophy, hypertrophic cardiomyopathy, chronic coronary artery disease with compensatory left ventricular hypertrophy, dilated cardiomyopathy and acute myocardial infarction. Serum contents of CaN and calmodulin were determined and activities of CaN as well as of acid and alkaline phosphatases were assayed and correlated with 2D echocardiography findings. The results were compared with those obtained from age-matched healthy volunteers. RESULTS: Serum CaN activity, but not of acid or alkaline phosphatases, was significantly enhanced by 2-fold in hypertensive hypertrophy, 3-fold in hypertrophic cardiomyopathy and 3.75-fold in chronic coronary artery disease associated with left ventricular hypertrophy, unaccompanied by changes in serum contents of calmodulin and CaN. No such increases were observed in acute myocardial infarction and dilated cardiomyopathy. CONCLUSIONS: Positive correlations observed between serum CaN activity and enhanced left ventricular mass in cardiac hypertrophy suggest that assaying serum CaN activity may be useful in the diagnosis and management of left ventricular hypertrophy.     

Systolic compression of epicardial coronary and intramural arteries in children with hypertrophic cardiomyopathy

It has been suggested that systolic compression of epicardial coronary arteries is an important cause of myocardial ischemia and sudden death in children with hypertrophic cardiomyopathy. We examined the associations between sudden death, systolic coronary compression of intra- and epicardial arteries, myocardial perfusion abnormalities, and severity of hypertrophy in children with hypertrophic cardiomyopathy. We reviewed the angiograms from 57 children with hypertrophic cardiomyopathy for the presence of coronary and septal artery compression; coronary compression was present in 23 (40%). The left anterior descending artery was most often affected, and multiple sites were found in 4 children. Myocardial perfusion abnormalities were more frequently present in children with coronary compression than in those without (94% vs 47%, P = 0.002). Coronary compression was also associated with more severe septal hypertrophy and greater left ventricular outflow gradient. Septal branch compression was present in 65% of the children and was significantly associated with coronary compression, severity of septal hypertrophy, and outflow obstruction. Multivariate analysis showed that septal thickness and septal branch compression, but not coronary compression, were independent predictors of perfusion abnormalities. Coronary compression was not associated with symptom severity, ventricular tachycardia, or a worse prognosis. We conclude that compression of coronary arteries and their septal branches is common in children with hypertrophic cardiomyopathy and is related to the magnitude of left ventricular hypertrophy. Our findings suggest that coronary compression does not make an important contribution to myocardial ischemia in hypertrophic cardiomyopathy; however, left ventricular hypertrophy and compression of intramural arteries may contribute significantly.     

Acute myocardial infarction with diminutive right coronary artery and obstructive hypertrophic cardiomyopathy without significant coronary stenoses

Focal tissue abnormalities consistent with regional ischemia have been reported in patients with hypertrophic cardiomyopathy (HCM). Coronary microvascular dysfunction has been also reported to be present in patients with HCM despite normal epicardial coronary arteries. Moreover, it has been demonstrated that in the case of HCM and idiopathic left ventricular hypertrophy, hypoplastic coronary arteries as diminutive vessels are present and that obstructive hypertrophic cardiomyopathy is associated with enhanced thrombin generation and platelet activation. Previously, it has been described an acute myocardial infarction in a young athlete with non-obstructive hypertrophic cardiomyopathy and normal coronary arteries. We present a case of an acute myocardial infarction with diminutive right coronary artery and obstructive hypertrophic cardiomyopathy without significant coronary stenoses. To our knowledge, this is the first report of an acute myocardial infarction with diminutive right coronary artery and obstructive hypertrophic cardiomyopathy without significant coronary stenoses.     

Idiopathic hypertrophic subaortic stenosis: evaluation of anginal symptoms with thallium-201 myocardial imaging.

The evaluation of angina pectoris in patients with idiopathic hypertrophic subaortic stenosis is difficult in those in the age group prone to coronary artery disease. Ten patients with angina pectoris, normal coronary angiograms and idiopathic hypertrophic subaortic stenosis were studied with thallium-201 myocardial imaging performed in conjunction with submaximal treadmill exercise testing. The resting electrocardiogram demonstrated left ventricular hypertrophy with S-T segment abnormalities in seven patients, thereby vitiating the further increase in S-T segment abnormalities that developed in these patients during exercise or in the postexercise period. Of the three patients with a normal resting electrocardiogram, one had significant exercise-induced S-T segment depression. Thallium-201 myocardial imaging revealed no significant perfusion defects in 9 of the 10 patients (90 percent). In one patient with severe left ventricular hypertrophy significant perfusion defects developed after exercise that were not present at rest. Stress thallium-201 myocardial perfusion imaging is a useful noninvasive technique that assists in ruling out the presence of significant coronary artery disease in patients with idiopathic hypertrophic subaortic stenosis.     

Non-obstructive hypertrophic cardiomyopathy and systolic compression of 3 coronary arteries. Long-term improvement with verapamil

Systolic compression of the three main coronary vessels was observed during the investigation of a 23 year old African with hypertrophic cardiomyopathy. The patient was admitted in 1982 for evaluation of retrosternal chest pain and one syncopal attack during exercise. The ECG showed left ventricular hypertrophy with important ST-T wave changes which became more severe on exercise. Diffuse myocardial hypertrophy without obstruction was confirmed by echocardiography and cardiac catheterisation. Coronary angiography showed systolic compression of the three main coronary arteries. There was no coronary vasodilatory response to rapid atrial pacing; increased left ventricular end diastolic pressure confirmed the poor tolerance of exercise. The therapeutic failure of betablockers suggested a possible coronary spasm. Long-term (4 years) clinical improvement was obtained with calcium antagonists (Verapamil 360 mg/day) without significant regression of the hypertrophy. Coronary vasodilation under Verapamil led to improved tolerance of rapid atrial pacing. Control angiography showed only mild systolic compression of the three main coronary vessels. The improvement of this functional coronary insufficiency with Verapamil was attributed to its negative inotropic effects associated with improved myocardial relaxation and ventricular filling.     

Coronary artery dimensions in primary and secondary left ventricular hypertrophy

Background. Coronary artery enlargment has been previously described in left ventricular hypertrophy.Objectives. We sought to assess coronary artery dimensions and their relation to left ventricular muscle mass in primary and secondary hyperthropy.Methods. Cross-sectional area of the left and right coronary arteries was determined by quantitative coronary angiography in 52 patients: 12 control subjects and 40 patients (13 with hypertrophic cardiomyopathy, 12 with dilated cardiomyopathy and 15 with aortic valve disease). As a measure of left ventricular hypertrophy, angiographic left ventricular mass and equatorial cross-sectional muscle area were determined.Results. Cross-sectional area of both the left and right coronary arteries is increased in left ventricular hypertrophy (p < 0.05 vs. values in control subjects). There is a curvilinear relation between left coronary artery size and left ventricular muscle mass (r = 0.76) or cross-sectional muscle area (r = 0.75). However, normalization of coronary cross-sectional area for left ventricular muscle mass or muscle area shows insufficient enlargement of the coronary arteries in both primary and secondary hypertrophy.Conclusions. 1) Coronary artery size increases as left ventricular mass increases in both primary and secondary hypertrophy. 2) The enlargement of left coronary cross-sectional area is independent of the cause of the increase in left ventricular mass. 3) The size of the coronary arteries is inappropriate with regard to left ventricular hypertrophy. Thus, the stimulus for growth of the coronary arteries is not influenced by the underlying disease but appears to depend on the degree of left ventricular hypertrophy.     

The use of non-linear methods of statistical analysis in the differential electrocardiographic diagnosis of hypertrophic cardiomyopathy (data from precordial mapping)

An algorithm was proposed to make a differential diagnosis of hypertrophic cardiomyopathy by precordial ECG mapping in 35 leads (PECG-35) of 82 patients with hypertrophic cardiomyopathy and 339 matched patients: those with isolated left and right ventricular hypertrophy, concurrent ventricular hypertrophy, those with coronary heart disease having scars of various sites and having no cicatricial myocardial changes, including those in the presence of left ventricular hypertrophy, as well as 98 healthy individuals. Computer-aided analysis of their mapping was used to calculate the area of Q, R, S, T waves and ST segment and the prolongation of QRS complex. ECG parameters were analyzed by using cluster and dispersion analyses and the kNN method. The cluster analysis of PECG-35 made it possible to divide all the data on hypertrophic cardiomyopathy into 2 groups. For each the complexes of PECG-35 parameters were identified, in whose range the kNN method differentiated hypertrophic cardiomyopathy with a broad spectrum of abnormalities at a high sensitivity of 67-75% and a specificity of 86-90%.     

老年心尖肥厚型心肌病冠脉造影特征

目的了解老年心尖肥厚型心肌病(APH)患者冠脉造影及心室造影特征。方法对我科1996～2003年7例老年APH患者冠脉造影资料进行分析。结果所有患者左冠脉普遍增粗,肌桥形成,心室造影见左室“黑桃样”改变,5例合并冠脉狭窄。结论老年APH患者以冠脉普遍增粗、肌桥形成及左室“黑桃样”改变为特征性冠脉造影改变,且合并冠心病概率高。     

Myocardial bridging of the left anterior descending coronary artery without relation to the site of hypertrophy in hypertrophic cardiomyopathy

Myocardial bridging of the left anterior descending coronaryartey producing complete systolic occlusion was demonstratedin a patient with hypertrophic cardiomyopathy. who had lolcalizedmyocardial hypertrophy in the lateral left ventricular walloutside the territory of that artery. Although a case and effectrelationship between systolic compression of the coronary arteryand myocardial hypertrophy has previously been postulated inhypertrophic cardiomyopathy the lack of relation between thesite of the myocardial bridging and the region of the left ventricularhypertrophy in our patient suggests that the myocardial bridginigof the left anterior descending coronary artery may not be relatedto the pathogenesis of asymmetric septal hypertrophy.     

Impaired Response of Left Ventricular Relaxation to Exercise-Induced Adrenergic Stimulation in Patients With Hypertrophic Cardiomyopathy

Objectives. We investigated the effect of adrenergic stimulation on left ventricular relaxation in patients with hypertrophic cardiomyopathy.

Background. Exercise-induced decreases in acceleration of left ventricular relaxation have been observed in patients with hypertrophic cardiomyopathy. However, data on sequential changes in left ventricular relaxation during exercise are limited.

Methods. We measured right (fluid filled) and left (high fidelity micromanometer) ventricular pressures during moderate supine ergometer exercise and during rapid right atrial pacing in four groups of patients: 9 with severe hypertrophic cardiomyopathy, 9 with moderate hypertrophic cardiomyopathy, 10 with hypertension and moderate hypertrophy and 5 control subjects.

Results. There was a curvilinear relation between the time constant of relaxation (tau) and heart rate in all groups during exercise. There was no difference in the slope of this relation between the two hypertrophic cardiomyopathy subgroups. Although the slope of this relation between tau and heart rate was steeper in the hypertensive than the moderate hypertrophic cardiomyopathy group (p < 0.001, analysis of covariance), the decrease in tau during right atrial pacing was similar in both groups. There were no significant differences in plasma levels of catecholamines at rest or at peak exercise among groups or in maximal heart rate during pacing.

Conclusions. Pacing-induced changes in tau in hypertrophic cardiomyopathy were similar to those in hypertensive hypertrophy, but remarkable decreases in exercise-induced acceleration of tau were observed only in hypertrophic cardiomyopathy. Our results may indicate a depressed left ventricular relaxation response to exercise-induced adrenergic stimulation in hypertrophic cardiomyopathy.

(J Am Coll Cardiol 1996;28:1738–45)>     

Left ventricular ejection dynamics in apical hypertrophy, a form of hypertrophic nonobstructive cardiomyopathy

The left ventricular (LV) cineangiograms of ten patients with apical hypertrophy (AH, group I) as a form of hypertrophic nonobstructive cardiomyopathy (HNCM) were analyzed. The left ventricular ejection dynamics, the extent and pattern of left ventricular contraction were compared with eight patients with secondary myocardial hypertrophy due to arterial hypertension (group II) and eight normal subjects (group III). End-diastolic, end-systolic and stroke volumes were significantly lower in group I. The analysis of left ventricular ejection dynamics with frame-by-frame-analysis revealed the typical ejection pattern of hypertrophic nonobstructive cardiomyopathy: Left ventricular ejection was completed within two thirds of the systolic ejection period. This ejection pattern is of diagnostic value when compared with the dynamics in group II. Although the apical segment in group I shows a good fiber shortening, the overall contribution to systolic performance is low; systolic function in apical hypertrophy is maintained by a compensatory increase in regional wall motion of the basal and midzonal part of the left ventricular free wall. There is no striking difference between apical hypertrophy with and without giant negative T waves with respect to the ejection pattern. Within these subgroups, the only difference was the greater left ventricular mass in patients with giant T wave inversion. Thus, the ejection dynamics in apical hypertrophy is typical of hypertrophic nonobstructive cardiomyopathy. Global parameters of systolic left ventricular performance revealed supernormal values even though systolic function is impaired. Segmental analysis of ejection phase was most sensitive in establishing the diagnosis.     

A Primer on Arrhythmias in Patients with Hypertrophic Cardiomyopathy

Patients with hypertrophic cardiomyopathy are at risk of atrial and ventricular arrhythmias, yet treatment options for these patients are made almost solely by extrapolation from patients with other diseases. Heart block may be seen spontaneously but is especially prevalent following septal reduction strategies. Atrial fibrillation is the most common arrhythmia in patients with hypertrophic cardiomyopathy. The onset of atrial fibrillation often represents a turning point clinically for patients, marked by substantial functional deterioration and morbidity. Sudden cardiac death is the most common cause of death in the young patient, but still contributes to mortality in older patients. Major risk factors for sudden cardiac death include resuscitated sudden cardiac death, marked hypertrophy, syncope, and family history of sudden cardiac death due to hypertrophic cardiomyopathy. Minor risk factors for sudden cardiac death include nonsustained ventricular tachycardia, and hypotensive response to exercise. Emerging possible risk factors include atrial fibrillation, myocardial ischemia, left ventricular outflow tract obstruction, genetic mutations, left ventricular apical aneurysms, myocardial fibrosis, and end stage disease.     

Nuclear magnetic resonance in hypertrophic cardiomyopathy.

The large differences in the spin lattice relaxation times (T1) of blood and myocardium (measured by nuclear magnetic resonance) allow the heart to be visualised without the use of contrast media. The findings using nuclear magnetic resonance in 11 unselected patients with hypertrophic cardiomyopathy were compared with those in equal numbers of normal subjects and patients with electrocardiographic features of left ventricular hypertrophy. In patients with hypertrophic cardiomyopathy characteristic septal hypertrophy was noted together with variable and sometimes pronounced hypertrophy of the left ventricular free wall, which is consistent with the heterogeneous nature of this disease. The mean (SD) ratio of septal to free wall thickness was 1.5(0.8) for patients with hypertrophic cardiomyopathy, 0.8(0.2) for those with left ventricular hypertrophy, and 0.9(0.2) for normal subjects. Although septal measurements by nuclear magnetic resonance were greater than those obtained by echocardiography there was a significant correlation between the two. Septal and free wall area were significantly smaller in normal subjects. There were no differences in septal or free wall T1 values between the three groups. Non-gated nuclear magnetic resonance can detect septal and free wall hypertrophy. With the addition of multiple slice acquisition, rapid estimation of myocardial mass will be possible allowing the potentially important assessment of progression or regression of myocardial hypertrophy.     

Nuclear magnetic resonance in hypertrophic cardiomyopathy

The large differences in the spin lattice relaxation times (T1) of blood and myocardium (measured by nuclear magnetic resonance) allow the heart to be visualised without the use of contrast media. The findings using nuclear magnetic resonance in 11 unselected patients with hypertrophic cardiomyopathy were compared with those in equal numbers of normal subjects and patients with electrocardiographic features of left ventricular hypertrophy. In patients with hypertrophic cardiomyopathy characteristic septal hypertrophy was noted together with variable and sometimes pronounced hypertrophy of the left ventricular free wall, which is consistent with the heterogeneous nature of this disease. The mean (SD) ratio of septal to free wall thickness was 1.5(0.8) for patients with hypertrophic cardiomyopathy, 0.8(0.2) for those with left ventricular hypertrophy, and 0.9(0.2) for normal subjects. Although septal measurements by nuclear magnetic resonance were greater than those obtained by echocardiography there was a significant correlation between the two. Septal and free wall area were significantly smaller in normal subjects. There were no differences in septal or free wall T1 values between the three groups. Non-gated nuclear magnetic resonance can detect septal and free wall hypertrophy. With the addition of multiple slice acquisition, rapid estimation of myocardial mass will be possible allowing the potentially important assessment of progression or regression of myocardial hypertrophy.     

Symptomatic myocardial bridges in children: a case report with review of literature

Myocardial bridge is a rare congenital coronary anomaly in children, usually seen in the setting of hypertrophic cardiomyopathy and in left ventricular hypertrophy. Most myocardial bridges are believed to represent a benign anatomical variant; however, symptomatic myocardial bridge is a distinct subgroup of pathological variant, linked to myocardial ischaemia, ventricular arrhythmia, and sudden cardiac death. We present a case of a symptomatic myocardial bridge in a 5-year-old boy with mild hypertrophic cardiomyopathy who underwent supra-arterial myotomy, automatic defibrillator placement, and long-term Beta-blocker therapy. We also present 10 years of follow-up with a review of literature regarding symptomatic myocardial bridges in the paediatric age group.     

Two Cases of Apical Ballooning Syndrome Masking Apical Hypertrophic Cardiomyopathy

Apical akinesis and dilation in the absence of obstructive coronary artery disease is a typical feature of stress-induced (takotsubo) cardiomyopathy, whereas apical hypertrophy is seen in apical-variant hypertrophic cardiomyopathy. We report the cases of 2 patients who presented with takotsubo cardiomyopathy and were subsequently found to have apical-variant hypertrophic cardiomyopathy, after the apical ballooning from the takotsubo cardiomyopathy had resolved. The first patient, a 43-year-old woman with a history of alcohol abuse, presented with shortness of breath, electrocardiographic and echocardiographic features consistent with takotsubo cardiomyopathy, and no significant coronary artery disease. An echocardiogram 2 weeks later revealed a normal left ventricular ejection fraction and newly apparent apical hypertrophy. The 2nd patient, a 70-year-old woman with pancreatitis, presented with chest pain, apical akinesis, and a left ventricular ejection fraction of 0.39, consistent with takotsubo cardiomyopathy. One month later, her left ventricular ejection fraction was normal; however, hypertrophy of the left ventricular apex was newly noted. To our knowledge, these are the first reported cases in which apical-variant hypertrophic cardiomyopathy was masked by apical ballooning from stress-induced cardiomyopathy.     

Left ventricular hypertrophy in coronary artery disease. A cardiomyopathy syndrome following myocardial infarction

Eighty-five patients with ventricular dysfunction due to coronary disease and to nonobstructive cardiomyopathy were studied by biplane angiocardiography (12/sec) to determine the extent of hypertrophy and the distinguishing features between primary myocardial and coronary disease. Patients with cardiomyopathy and equally severe dysfunction due to coronary disease had identical end-diastolic, end-systolic and stroke volume and work per square meter, stroke work per gram of ventricular mass, end-diastolic pressure, peak equatorial wall stress, ejection fraction, peak circumferential shortening velocity, peak ventricular ejection rate, peak external pump power, left ventricular mass and mass to diastolic volume ratio. Hypertrophy develops after myocardial infarction in proportion to ventricular dilatation and may result in a syndrome of massive hypertrophy, hypokinesis and congestive failure quantitatively identical to that found in primary cardiomyopathy except for etiology. Hypertrophy is associated with normalization of wall stress in both coronary and primary myocardial disease and is thus not dependent on the type of insult to the contractile mechanism.     

Quantitative assessment of ultrasonic myocardial reflectivity in hypertrophic cardiomyopathy

The purpose of this study was to investigate the relation between acoustic properties of the myocardium and magnitude of left ventricular hypertrophy in patients with hypertrophic cardiomyopathy. An on-line radio frequency analysis system was used to obtain quantitative operator-independent measurements of the integrated backscatter signal of the ventricular septum and posterior free wall in 25 patients with hypertrophic cardiomyopathy and 25 normal age-matched control subjects. The integrated values of the radio frequency signal were normalized for the pericardial interface and expressed in percent. Tissue reflectivity was significantly increased in the hypertrophied ventricular septum, as well as in the nonhypertrophied posterior free wall, in patients with hypertrophic cardiomyopathy (58 +/- 15% and 37 +/- 12%, respectively) compared with values in normal subjects (33 +/- 10% and 18 +/- 5%, respectively; p less than 0.001). Furthermore, measurements of reflectivity of the septum or posterior free wall, or both, were beyond 2 SD of normal values in greater than 90% of the patients and were also abnormal in each of the five study patients who had only mild and localized left ventricular hypertrophy. No correlation was identified between myocardial tissue reflectivity and left ventricular wall thickness in the patients with hypertrophic cardiomyopathy (correlation coefficient r = 0.4; p = NS). These findings demonstrate that myocardial reflectivity is abnormal in most patients with hypertrophic cardiomyopathy and is largely independent of the magnitude of left ventricular hypertrophy. Moreover, quantitative analysis of ultrasonic reflectivity can differentiate patients with hypertrophic cardiomyopathy from normal subjects independently of clinical features and conventional echocardiographic measurements.     

Exercise-induced ST-segment depression and myocardial ischemia in patients with hypertrophic cardiomyopathy: myocardial scintigraphic study

OBJECTIVES: Patients with hypertrophic cardiomyopathy (HCM) sometimes develop myocardial ischemia during exercise in the absence of coronary lesions. The relationship between myocardial ischemia and ST-segment depression was investigated during exercise testing in patients with HCM. METHODS: Regional hypoperfusion and/or transient left ventricular cavity dilation, a parameter of subendocardial hypoperfusion, were assessed on exercise 99mTc-tetrofosmin myocardial scintigraphy in 42 patients with non-obstructive HCM. The scintigraphic results were further correlated with the ST-segment responses to exercise. RESULTS: Regional hypoperfusion or transient left ventricular cavity dilation were observed in 19 (45%) or 16(38%)patients with HCM, respectively. The incidence of ST-segment depression > or = 0.1 mV during exercise testing was similar in HCM patients with regional hypoperfusion, with transient left ventricular cavity dilation, and without hypoperfusion (42%, 38%, 38%, p = 0.95). Furthermore, exercise-induced ST-segment depression > or = 0.1 mV occurred similarly irrespective of symptoms, exercise tolerance, the degree or the site of hypertrophy, or the presence or absence of resting ST-segment depression. CONCLUSIONS: ST-segment depression during exercise testing was common in patients with HCM, but seems to be an unreliable marker of myocardial ischemia as assessed by exercise scintigraphy.