Tissue Doppler imaging in Fabry disease

PURPOSE OF REVIEW: The development of effective enzyme replacement/enhancement therapy makes of clinical relevance considering Fabry disease in the differential diagnosis of patients with hypertrophic cardiomyopathy. In particular the opportunity to significantly modify the clinical progression of the disease has reinforced the need for early diagnosis of Fabry cardiomyopathy. RECENT FINDINGS: The study with tissue Doppler of Fabry patients with endomyocardial biopsy-proven cardiac involvement showed a reduction of both diastolic and systolic myocardial velocities recorded at septal and lateral corners of mitral annulus. Tissue Doppler abnormalities were present not only in patients with left ventricular hypertrophy but also in younger patients with normal cardiac wall thickness and represent the first sign of myocardial damage. Furthermore tissue Doppler studies have been shown useful in detecting cardiac involvement in female carriers with no systemic manifestations of Fabry disease. In patients already submitted to enzyme-replacement therapy tissue Doppler and strain rate imaging represent useful noninvasive tools in assessing treatment efficacy. SUMMARY: Tissue Doppler imaging can provide early detection of cardiac involvement in Fabry disease and represents the most accurate and sensitive noninvasive tool for the diagnosis of myocardial dysfunction and for the assessment of cardiac improvement during enzyme replacement therapy. The detection of tissue Doppler abnormalities in female carriers may represent a hint for an invasive assessment of cardiac involvement.     

Magnetic resonance imaging early after acute myocardial infarction. A visual analysis of myocardial perfusion based on a 17 segment model

Magnetic resonance imaging allows an accurate calculation of the left ventricular ejection fraction and left ventricular volumes. Additionally, it makes possible to assess myocardial perfusion after gadolinium chelate injection. Late after the injection, the presence of a myocardial hyper-enhancement can be visualized. The present study has used the 17 segment standardized nomenclature for tomographic imaging of the heart as recommended for all cardiac imaging modalities. Sixty nine patients were studied after a revascularised myocardial infarction. All patients had Timi grade 3 flow in the infarct-related artery after therapy. Regional and global function was studied using cine MR short axis slices. The gadolinium chelate first pass was scored using a 5 level scale reflecting the transmural extent of the segmental myocardial enhancement. The delayed enhancement due to gadolinium accumulation in the myocardium 10 min post injection was scored in the same manner. Left ventricular ejection fraction was 51 +/- 13%. Segmental thickening parameters (systolic thickness, absolute thickening and relative thickening) appeared statistically related to the hypoperfusion and delayed enhancement scores. Absolute myocardial thickening varied from 4.8 +/- 2.7 mm in the myocardial segments free of any delayed enhancement to 2.4 +/- 2.1 mm in segments presenting with a transmural extent of the delayed hyper-enhancement. Scores obtained after gadolinium injection were also well correlated with the global left ventricular function (r = 0.65, p < 0.01 for late enhancement). Magnetic resonance imaging of the heart allows a precise characterisation of revascularised myocardium which makes this technique very attractive for evaluating the treatments designed to improve myocardial microperfusion.     

Six months of recombinant human GH therapy in patients with ischemic cardiac failure does not influence left ventricular function and mass

Beneficial effects of recombinant human GH on cardiac function have been reported in humans with GH deficiency and in patients with idiopathic dilated cardiomyopathy. No randomized controlled trial has been performed on the effects of recombinant human GH on cardiac function in patients with ischemic cardiac failure. We therefore randomly assigned 22 patients with ischemic cardiac failure (left ventricular ejection fraction, <40%; 19 men and 3 women; mean age, 64 yr) to receive 6 months of unblinded therapy with recombinant human GH (2.0 IU/d) or no treatment. Primary end points were left ventricular ejection fraction and left ventricular mass. Left ventricular end-diastolic volume, left ventricular end-systolic volume, and myocardial perfusion, both at rest and during exercise, were assessed as well. Cardiac imaging techniques were electrocardiographically gated single photon emission computer tomography and magnetic resonance imaging. In addition, biochemical and biometric measurements were performed. Nineteen patients completed the study (10 controls and 9 GH-treated subjects). IGF-I and IGF-binding protein-3 increased significantly after recombinant human GH treatment (+24% and +58%, respectively) compared with control values (-14% and +5%; P < 0.05). Left ventricular ejection fraction, left ventricular end-diastolic volume, left ventricular end-systolic volume, left ventricular mass, and myocardial perfusion were not influenced by recombinant human GH therapy. We conclude that 6 months of recombinant human GH treatment in patients with ischemic cardiac failure had no beneficial effect on left ventricular function and mass.     

Usefulness of pericardial effusion as new diagnostic criterion for noninvasive detection of myocarditis

Cardiovascular magnetic resonance (CMR) imaging holds promise for diagnosing myocarditis in vivo. The CMR diagnosis of myocarditis is determined by the ventricular morphology/function, late gadolinium enhancement, and T(2)-weighted imaging for myocardial edema. However, in routine clinical practice, we encounter patients with suspected myocarditis in the absence of left ventricular dysfunction, myocardial edema, or late gadolinium enhancement. In the present study, we sought to determine whether the presence of pericardial effusion could serve as a new diagnostic criterion and improve the sensitivity of CMR imaging to detect myocarditis. A total of 35 consecutive patients with biopsy proven virus-associated myocarditis, onset of clinical symptoms within the past 3 months, and normal left ventricular function were enrolled in the present study. All patients underwent echocardiography, CMR imaging, and endomyocardial biopsy for workup of myocarditis. Late gadolinium enhancement was present in 16 patients (46%). Myocardial edema on T(2)-weighted imaging was present in 4 patients, but in just 1, it was the only abnormal finding. Pericardial effusion was present in 14 patients (40%). In 7 patients with myocarditis (20%), pericardial effusion was the only abnormal finding. Pericardial effusion, used as an additional diagnostic criterion, improved the sensitivity of CMR imaging for myocarditis from 46% to 66% (p = 0.023). In conclusion, pericardial effusion detected by CMR imaging might serve as a new diagnostic criterion for the noninvasive diagnosis of myocarditis in patients with recent onset of clinical symptoms and normal left ventricular function.     

Myocardial enhancement on magnetic resonance imaging with gadolinium-diethylenetriamine pentaacetic acid and improvement of left ventricular function in patients with dilated cardiomyopathy

OBJECTIVES: This study evaluated the significance of myocardial gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) enhancement on magnetic resonance imaging for the improvement of left ventricular function in patients with dilated cardiomyopathy. METHODS: Twenty-seven patients with dilated cardiomyopathy (mean age 59 +/- 11 years) were studied. The magnitude of myocardial Gd-DTPA enhancement was quantitatively assessed using signal intensity ratio and compared to changes in left ventricular function and adverse cardiac events during a relatively long follow-up period. RESULTS: Regional high signal intensity ratio, defined as > or = mean + 2SD in seven normal subjects, was found in 14 patients: in three or more regions out of five myocardial regions analyzed in six patients (extensive enhancement) and in only one or two regions in eight patients (limited enhancement). The remaining 13 patients had no high signal ratio in any of the five regions analyzed (no enhancement). During the follow-up period of 3.9 +/- 1.9 years, four patients died of cardiac causes. The incidence of cardiac death was 33.3% in patients with extensive enhancement, 12.5% in those with limited enhancement and 7.7% in those without enhancement, but there was no statistical difference. Mild improvement in fractional shortening was observed in patients without enhancement during the follow-up (19 +/- 4%-->27 +/- 10%, p = 0.03). CONCLUSIONS: Evaluation of myocardial Gd-DTPA enhancement on magnetic resonance imaging may provide useful prognostic information for patients with dilated cardiomyopathy.     

Imaging and Impact of Myocardial Fibrosis in Aortic Stenosis

Aortic stenosis is characterized both by progressive valve narrowing and the left ventricular remodeling response that ensues. The only effective treatment is aortic valve replacement, which is usually recommended in patients with severe stenosis and evidence of left ventricular decompensation. At present, left ventricular decompensation is most frequently identified by the development of typical symptoms or a marked reduction in left ventricular ejection fraction <50%. However, there is growing interest in using the assessment of myocardial fibrosis as an earlier and more objective marker of left ventricular decompensation, particularly in asymptomatic patients, where guidelines currently rely on nonrandomized data and expert consensus. Myocardial fibrosis has major functional consequences, is the key pathological process driving left ventricular decompensation, and can be divided into 2 categories. Replacement fibrosis is irreversible and identified using late gadolinium enhancement on cardiac magnetic resonance, while diffuse fibrosis occurs earlier, is potentially reversible, and can be quantified with cardiac magnetic resonance T₁ mapping techniques. There is a substantial body of observational data in this field, but there is now a need for randomized clinical trials of myocardial imaging in aortic stenosis to optimize patient management. This review will discuss the role that myocardial fibrosis plays in aortic stenosis, how it can be imaged, and how these approaches might be used to track myocardial health and improve the timing of aortic valve replacement.     

Myocardial scars more frequent than expected: magnetic resonance imaging detects potential risk group.

OBJECTIVES: The aim of this study was to investigate the prevalence of clinically recognized myocardial infarctions (RMIs) and unrecognized myocardial infarctions (UMIs) in 70-year-old subjects, assessed with magnetic resonance imaging (MRI), and to relate the findings to cardiac function and morbidity. BACKGROUND: Late enhancement MRI identifies myocardial scars and thereby has the potential to detect UMI. METHODS: Cardiac MRI was performed on 259 randomly chosen 70-year-old subjects. Late enhancement and cine sequences were acquired, and the ejection fraction and left ventricular (LV) mass were calculated. Late enhancement involving the subendocardial layer was considered to represent myocardial infarction (MI) scars, and their volumes were calculated. Information on cardiac morbidity and risk factors was collected from medical records and from a health examination. Subjects with MI scars, with or without a hospital diagnosis of MI were classified as RMI or UMI, respectively. RESULTS: The images from 248 subjects (123 women, 125 men) were assessable. Myocardial infarction scars were found in 60 subjects (24.2%), in 49 of whom (19.8%) they were UMIs. The volumes of the UMIs were significantly smaller than those of the RMIs. There was an increased frequency of chest pain symptoms among the subjects with UMI or RMI compared with those without MI scars. Ejection fraction was significantly lower and LV mass significantly larger in the subjects with UMI or RMI than in those without MI scars. CONCLUSIONS: Unrecognized MI detected with MRI was more frequent than expected in 70-year-old subjects. The subjects displaying these UMIs may represent a previously unknown potential risk group for future cardiovascular events.     

Cardiovascular effects of mild hypothyroidism.

The cardiovascular risk is increased in patients with overt hypothyroidism, and several potential cardiovascular risk factors were similarly reported in patients with subclinical hypothyroidism. Only recently have more data become available about the effects of mild hypothyroidism on the cardiovascular system. An impaired left ventricular diastolic function, which is characterized by slowed myocardial relaxation and impaired ventricular filling, is the most consistent cardiac abnormality in patients with mild thyroid hormone deficiency. Impaired left ventricular diastolic function on effort was also documented by radionuclide ventriculography. Studies performed by ultrasonic myocardial textural analysis suggest an altered myocardial composition in patients with mild hypothyroidism. Moreover, pulsed tissue Doppler analysis revealed that patients with mild hypothyroidism had changes in myocardial time intervals in several left ventricular segments. Finally, alterations in cardiac hemodynamic were documented by cardiac magnetic resonance imaging in presence of mild disease. Vascular function is impaired in patients with mild and subclinical hypothyroidism, as documented by the increase in systemic vascular resistance and arterial stiffness and by the impaired endothelial function. The negative effect induced by mild hypothyroidism on cardiovascular system can be reverted restoring euthyroidism with levothyroxine (L-T4) therapy. Based on the data available, it appears that L-T4 replacement should be considered in patients with mild hypothyroidism in presence of associated cardiovascular risk factors in the attempt to reverse these negative prognostic factors and improve the cardiovascular risk.     

Intra-cardiac distribution of late gadolinium enhancement in cardiac sarcoidosis and dilated cardiomyopathy

Cardiac involvement of sarcoid lesions is diagnosed by myocardial biopsy which is frequently false-negative,and patients with cardiac sarcoidosis(CS) who have impaired left ventricular(LV) systolic function are sometimes diagnosed with dilated cardiomyopathy(DCM).Late gadolinium enhancement(LE) in magnetic resonance imaging is now a critical finding in diagnosing CS,and the novel Japanese guideline considers myocardial LE to be a major criterion of CS.This article describes the value of LE in patients with CS who have impaired LV systolic function,particularly the diagnostic and clinical significance of LE distribution in comparison with DCM.LE existed at all LV segments and myocardial layers in patients with CS,whereas it was localized predominantly in the midwall of basal to mid septum in those with DCM.Transmural(nodular),circumferential,and subepicardial and subendocardial LE distribution were highly specific in patients with CS,whereas the prevalence of striated midwall LE were high both in patients with CS and with DCM.Since sarcoidosis patients with LE have higher incidences of heart failure symptoms,ventricular tachyarrhythmia and sudden cardiac death,the analyses of extent and distribution of LE are crucial in early diagnosis and therapeutic approach for patients with CS.     

Effect of thyroid hormones on cardiac function, geometry, and oxidative metabolism assessed noninvasively by positron emission tomography and magnetic resonance imaging

Thyroid hormones influence cardiac performance directly and indirectly via changes in peripheral circulation. Little, however, is known about the effect on myocardial oxidative metabolism and its relation to cardiac function and geometry. Patients with a history of thyroidectomy for thyroid cancer present a unique model to investigate the cardiac effects of hypothyroidism. Ten patients without heart disease were investigated in the hypothyroid state and again 4-6 weeks later under euthyroid conditions. Myocardial oxidative metabolism was measured by positron emission tomography with [11C]acetate and the clearance constant k(mono). Cine magnetic resonance imaging was applied to determine left ventricular geometry. A stroke work index (SWI = stroke volume x systolic blood pressure/ventricular mass) was calculated. Then, to estimate myocardial efficiency, a work metabolic index [WMI = SWI x heart rate/k(mono)] was obtained. Compared to hormone replacement, systemic vascular resistance and left ventricular mass were significantly higher in hypothyroidism. Ejection fraction and SWI were significantly lower. Despite an additional reduction of k(mono), the WMI was significantly lower, too. In summary, cardiac oxygen consumption is reduced in hypothyroidism. This reduction is associated with increased peripheral resistance and reduced contractility. Estimates of cardiac work are more severely suppressed than those of oxidative metabolism, suggesting decreased efficiency. These findings may provide an explanation for development or worsening of heart failure in hypothyroid patients with preexisting heart disease.     

Detection of Myocardial Injury by CMR After Transcatheter Aortic Valve Replacement

Background

Myocardial injury after transcatheter aortic valve replacement (TAVR) is common, but its cause and relationship to the extent of myocardial tissue loss remain unclear.

Objectives

This study sought to examine the incidence and degree of ischemic myocardial damage using cardiac magnetic resonance imaging and myocardial biomarkers in patients undergoing TAVR.

Methods

Patients with severe aortic stenosis (n = 61) underwent cardiac magnetic resonance imaging before and after TAVR for the assessment of new myocardial injury. High-sensitivity cardiac troponin T and creatine kinase-myocardial band were measured before and at 24, 48, and 72 h after TAVR.

Results

After TAVR, new myocardial late enhancement (LE) with an ischemic pattern occurred in 11 patients (18%), with a mean mass of 3.7 g (interquartile range: 1.2 to 6 g) or 1.8% (interquartile range: 1.3% to 4.1%) of the left ventricular mass. Patients with new LE had a decreased left ventricular function (ejection fraction: pre, 55.5 ± 14.1% vs. post, 45.3 ± 14.9%; p = 0.001). In patients without new LE, no differences were observed (ejection fraction: pre, 53.9 ± 17.3% vs. post, 54.6 ± 16.3%; p = NS) after TAVR.

Conclusions

New ischemic-type myocardial LE after TAVR can be observed in a notable proportion of patients and is assumed to be of embolic origin. Patients with new LE feature a significant decrease in left ventricular function at discharge.     

Effect of isometric handgrip on systolic time intervals in patients with ischemic heart disease and cyclic amp phosphodiesterase inhibitor pretreatment.

The effect of cAMP phosphodiesterase inhibitor EG626 on the left ventricular function was studied in 23 patients with ischemic heart disease at rest and during the IHG test. Administration of a single dose of the substance produced changes in STIs indicating an increase in cardiac output and a possible enhancement of myocardial contractility during the IHG test. EG626 may have a beneficial effect on impaired left ventricular function in patients with ischemic heart disease.     

Cardiac findings after enzyme replacement therapy for mucopolysaccharidosis type I

Mucopolysaccharidosis type I is a lethal autosomal recessive storage disease caused by a deficiency of lysosomal alpha-L-iduronidase and the consequent systemic accumulation of glycosaminoglycan. Cardiomyopathy and valvar insufficiency occur as glycosaminoglycan accumulates in the myocardium, expands the spongiosa of cardiac valves, and proliferates within the myointima of the epicardial coronary arteries. Congestive heart failure and death occur within the first decade of life in the most severe cases. Allogeneic hematopoietic stem cell transplantation, used in severe forms of the disease, markedly prolongs survival, alleviates ventricular hypertrophy, and preserves cardiac function, but cardiac valves continue to thicken and valvular insufficiency progresses. Enzyme replacement therapy with human recombinant alpha-L-iduronidase has been proposed as an alternativee therapy for patients with mucopolysaccharidosis type I in whom the risk/benefit ratio of hematopoietic stem cell transplantation seems unfavorable. The investigators report the cardiac findings in a small series of 5 children with mucopolysaccharidosis type I who received enzyme replacement therapy for as long as 7 years. No deaths occurred during treatment. Left ventricular hypertrophy, which was present before therapy, resolved in all cases, and myocardial function remained normal. In contrast, the mitral and aortic valves remained thickened and, in some instances, developed progressive thickening and regurgitation. In conclusion, long-term enzyme replacement therapy has some clear benefits for the myocardium, but the cardiac valves appear unresponsive, and the ultimate effect on the coronary vasculature is unknown.     

POINT: A Prescription to Decrease Left Ventricular Function

The Courage Trial, published in 2007, has significantly reduced the incidence of treating stable angina with angioplasty. The investigators randomized 2297 patients with documented cardiac ischemia to conservative or invasive therapy and concluded that there was no difference in major events during a follow-up of 2.5 to 7 years and that the urge to open the narrowed artery was unjustified. Over the years it has been well documented by myocardial biopsy that repeated ischemic episodes result in replacement of myocardial cells by fibrous tissue, loss of mitochondria, and deterioration of left ventricular function. Ischemic episodes often occur in the absence of angina so that it is impossible to determine whether the therapy is reducing the magnitude or duration of the process. Also, in their study, 32% of the conservatively treated patients crossed over to invasive. The evidence indicated that conservative treatment may result in a progressive decrease in left ventricular function.     

A positive association between cardiomyocyte volume and serum malondialdehyde levels

Calcium sensitizers also improve cardiac function by increasing the contraction of the myocardium without significantly increasing intracellular calcium levels. Although right ventricular function is an important role for better cardiac global function, there is no study about effects of levosimendan on right ventricular function measured by tissue Doppler imaging. The aim of the present study was to evaluate changes of myocardial properties in patients with idiopathic dilated cardiomyopathy using tissue Doppler imaging after levosimendan infusion. This tissue Doppler study shows that levosimendan also affects myocardial especially systolic waves of right ventricle and those of left ventricle.     

Follow-up by cardiac magnetic resonance imaging in patients with hypertrophic cardiomyopathy who underwent percutaneous ventricular septal ablation

To evaluate myocardial infarction and describe the early to mid-term changes induced by percutaneous ventricular septal ablation (PVSA) in symptomatic patients with hypertrophic cardiomyopathy using cardiac magnetic resonance imaging. Cardiac magnetic resonance imaging was performed before and 1 week and 1 year after PVSA in 52 patients. The relation between the infarction size and other factors was determined. At 1 week after PVSA, regional hyperenhancement was visualized in the basal interventricular septum in all patients. The mean infarction size was 29.5 ± 15.9 g. The infarction size correlated well with the ethanol volume. The left ventricular myocardial mass decreased significantly from 196.1 ± 65.9 g at baseline to 183.4 ± 63.6 g 1 week after PVSA (p <0.001) and 164.1 ± 60.9 g within the 1-year follow-up period (p <0.001). In conclusion, cardiac magnetic resonance imaging allowed a detailed evaluation of the size and location of septal myocardial infarction induced by PVSA. The left ventricular myocardial mass decreased significantly during the follow-up period.     

直接经皮冠状动脉介入治疗对急性心肌梗死患者室壁瘤的阻抑效应和心功能改善作用

目的:研究经皮冠状动脉介入治疗(PCI)对急性心肌梗死(AMI)患者室壁瘤形成的阻抑效应及心功能改善作用。方法:发病12h以内急性前壁心肌梗死伴室壁瘤形成患者随机分为直接PCI(A组36例),溶栓治疗(B组:31例),常规药物治疗(C组31例);各组患者均在治疗后1周、24周分别行超声心动图和平衡法核素心室造影评价左室质量指数(LVMI)和局部室壁运动积分(RWMI)、心室收缩同步性(VSS)和心功能(HF)等参数的改善状况。结果:治疗后1周和24周时,A组RWMI、VSS和HF均优于B组和C组,均P<0.05。A组和B组24周时上述各参数均优于1周。C组VSS参数中相角程在24周时较1周有所改善,余各项结果比较差异无统计学意义。结论:PCI治疗和溶栓对AMI患者室壁瘤有阻抑作用且改善心功能,而直接PCI优于溶栓治疗。     

Mechanical bridging to improvement in severe acute "nonischemic, nonmyocarditis" heart failure

Improved myocardial function has been observed in patients with acute myocarditis who have had short-term support with a ventricular assist system. Additionally, a limited number of patients with nonischemic cardiomyopathy have undergone successful device explantation after their myocardial function improved during ventricular assist system support. The authors present their experience with four patients who had acute, severe heart failure without coronary artery disease or biopsy-proven myocarditis. After receiving prolonged ventricular assist system support, all four patients had significantly improved left ventricular function, returning to New York Heart Association functional class I without inotropic therapy. In each case, dobutamine stress echocardiography and invasive hemodynamic tests were performed to confirm improvement of cardiac function before device explantation was undertaken. In all four cases, device explantation was followed by early successful maintenance of left ventricular function. These cases reveal a unique clinical syndrome that may be successfully treated with early institution of ventricular assist system support followed by explantation after myocardial recovery.     

Myocardial structure and function in patients with aortic valve disease and their relation to postoperative results

Left ventricular angiographic studies were performed before and 6 months after aortic valve replacement with a Björk-Shiley prosthesis in 21 patients, 5 with aortic stenosis, 8 with mixed aortic valve lesions and 8 with aortic insufficiency. The degree of myocardial fibrosis and myocardial ultrastructural changes were evaluated from transmural needle biopsy specimens obtained from the left ventricular anterior free wall at operation. Twelve patients without heart disease served as control subjects for angiographic data. Patients with aortic valve disease had a significantly higher left ventricular mass before operation than control subjects and a lower ejection fraction and mean normalized systolic ejection rate. After operation left ventricular mass decreased considerably but did not reach normal level. Ejection fraction and mean normalized systolic ejection rate became normal in all patients with aortic valve disease. The percent fibrosis determined with morphometry was significantly higher in the subendocardium than in the subepicardium of pressure-overloaded hearts (predominant stenosis) (19 versus 13 percent) but equal in both layers of volume-overloaded hearts (predominant regurgitation) (19 versus 18 percent). Electron microscopy revealed significant intracell alterations of the nucleus, sarcomeres, mitochondria and cytoplasmic reticulum. When all patients, regardless of type of aortic valve lesion, were considered, there was no significant correlation before operation between percent fibrosis and ejection fraction (r 0.10) or mean normalized systolic ejection rate (r 0.02) but a significant inverse relation between left ventricular mass and ejection fraction (r 0.54) as well as mean normalized systolic ejection rate (r 0.49).These data suggest that (1) Depressed left ventricular function in aortic valve disease is associated with ultrastructural degenerative cell changes, but complete recovery of cardiac function after aortic valve replacement is not prevented by these changes. (2) Interstitial myocardial fibrosis is not a primary determinant of depressed cardiac function in aortic valve disease.     

Evidence of impaired myocardial perfusion and abnormal left ventricular function during exercise in patients with isolated systolic narrowing of the left anterior descending coronary artery

Seven men ranging in age from 35 to 63 years with a chest pain syndrome and cineangiographically documented systolic narrowing of the left anterior descending coronary artery underwent thallium-201 myocardial scintigraphy and gated cardiac blood pool imaging. Grade II (50 to 75 percent) systolic coronary arterial constriction was present in three patients and grade III constriction (greater than 75 percent) in four. Three of the four patients with grade III constriction had an exercise-induced perfusion abnormality in the thallium-201 scintigram and an impaired left ventricular ejection fraction response during exercise. (In two patients the left ventricular ejection fraction did not change and in one patient it decreased.) Each of the three patients with grade II constriction had normal thallium-201 perfusion and a normal increase in ejection fraction during exercise. These data provide evidence of abnormal myocardial perfusion and impaired left ventricular function during exercise in patients with high grade systolic coronary arterial narrowing.