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

MASOOD AHMAD, MD, FRCP(C), FACC l

STEVEN L. MERRY, MD

HELMUT HAIBACH, MD

Columbia, Missouri

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

From the Division of Cardiology and Department of Nuclear Medicine, University of Missouri Med- ical Center and Harry S. Truman Veterans Ad- ministration Hospital, Columbia, Missouri. Manu- script received September 24, 1980; revised manuscript received February 24, 1981, accepted May 21, 1981.

l Present address and address for reprints: Masood Ahmad, MD, University of Texas Medical Branch, Cardiology Division, JSH5A, Galveston, Texas 77550.

A transient narrowing of the left anterior descending coronary artery during systole occurs when a segment of this vessel dips into the myo- cardium for a variable distance. The intramyocardial portion of the vessel is squeezed during systole and the constriction disappears during dias- to1e.l Angina, either typical or atypical, may occur in some patients with this coronary anomaly.2 The role of systolic narrowing of the coronary artery in producing myocardial ischemia in the absence of associated atherosclerotic disease is not clear. This study was undertaken to eval- uate left ventricular function and myocardial perfusion at rest and during exercise in patients with isolated systolic coronary arterial narrowing.

Methods

Patient selection: A total of 589 coronary cineangiograms were reviewed in a search for systolic coronary arterial narrowing of the proximal or mid portion of the left anterior descending vessel. All studies had been performed at the Harry S. Truman Memorial Veterans Administration Hospital and the Uni- versity of Missouri Medical Center from 1977 to 1979. The catheterization lab- oratory protocol during this period called for routine sublingual administration of nitrates before performance of coronary cineangiography. The coronary and left ventricular cineangiograms were reviewed by two independent observers. Systolic coronary arterial narrowing, defined as transient narrowing of the coronary artery during systole with normal caliber during diastole, was detected in 38 patients (6.4 percent of the total series). A quantitative assessment of the degree of such narrowing was made by measuring with a ruler the transverse

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diameter of the vessel in diastole and systole. The projection showing the most severe degree of constriction (45O left an- terior oblique projection in all patients) was used for data analysis. The severity of percent narrowing was expressed according to the method of Greenspan et al.?

Diameter in diastole - Diameter in systole x 100

Diameter in diastole

The degree of constriction was graded from I to III with 50 percent constriction as grade I, 50 to 75 percent constriction as grade II and greater than 75 percent constriction as grade III. The length of the constricted segment was also measured in centimeters in the 45” left anterior oblique projection. There was no disagreement between the two independent observers regarding the degree, length and location of the systolic coronary arterial narrowing. The observers also agreed completely regarding the absence of significant (greater than 50 percent stenosis) atherosclerotic disease in all patients. Twenty-eight (73.3 percent) of the 38 patients with systolic coronary arterial narrowing had associated significant ath- erosclerotic disease and were excluded from this investigation. Seven of 10 patients with systolic coronary arterial narrowing of the left anterior descending vessel without associated sig- nificant atherosclerotic disease consented to participate in the study. The seven patients were men aged 35 to 63 years.

Imaging procedures: All seven patients underwent a symptom-limited maximal exercise stress test using Bruce’s multistage treadmill protocol.4 The heart rate, blood pressure and electrocardiogram (modified Vs electrode) were moni- tored throughout the exercise. Thallium-201 (1.5 to 2 milli- curies [mCi]) was injected at peak exercise. Five patients ex- ercised up to 60 seconds after the injection and two patients terminated exercise 30 seconds after the injection. Imaging was begun within 5 to 10 minutes of the termination of exer- cise. An Ohio Nuclear series 120 gamma camera and a high resolution collimator were used for imaging. Polaroid scinti- photographs, with counts of 300,000 to 400,000, were obtained in the anterior, 45’ left anterior oblique and left lateral views. Data were also recorded on a magnetic tape for subsequent analysis on a PDP-11 digital computer. Follow-up thallium- 201 scintigrams were obtained in the same projections 4 to 6 hours after the initial scintigrams. Images were processed by performing a 20 to 25 percent background subtraction. All interpretations were made from the original unprocessed scintiphotographs by two independent observers who were unaware of the clinical data, and the processed images were used to confirm these observations further. Images were in- terpreted as normal or abnormal and the location of the image defect was localized as anterior (anteromedial wedge in the left anterior oblique view), posterior (posterolateral wedge in the left anterior oblique view) and apical (the tip of the ven- tricle in the anterior view).5 Thallium-201 scintigrams were interpreted as abnormal if a discrete area of absent or de- creased activity was noted. A complete resolution of the scintigraphic defect from the exercise to the follow-up scan was required before the defect was labeled exercise-induced. The two observers were in complete agreement on thallium scintigraphic findings.

In a separate study, equilibrium cardiac blood pool images were obtained in 45’ left anterior oblique projection at rest and during exercise after the intravenous injection of 15 to 20 mCi of technetium-99m labeled to human serum albumin. Exercise was performed on a bicycle ergometer with an initial work load of 150 kilopond meters (kpm)/min with increments of 150 kpm/min every 3 minutes until a symptom-limited

maximum was achieved. Imaging was carried out by using an Ohio Nuclear series 120 camera equipped with a Leap colli- mator. All data were recorded on magnetic tape for subse- quent analysis on a PDP-11 computer. The regions of interest at end-diastole and at end-systole were defined by a single experienced observer. After the background counts were subtracted from an area inferoposterior to the left ventricular region of interest, the ejection fraction was calculated from the following formula:

Total counts at end-diastole - Total counts at end-systole Total counts at end-diastole

Regional left ventricular wall motion was evaluated by ex- amining the systolic and diastolic frames alternately in dy- namic mode, by superimposing the outlines of the diastolic and systolic regions of interest, and from the radioactivity seen in the subtracted image.

Results Table I summarizes the clinical, cineangiographic and

scintigraphic data in the seven patients studied. Two patients had typical effort-induced angina relieved by rest and nitroglycerin. Both patients were treated with nitrates. In five patients the chest pain was atypical for angina either in location or in its relation to exertion. Three of these five patients had relief of pain with ni- trates and one patient was treated with Inderalm. The total duration of symptoms in the seven patients ranged from 2 to 5 years. No patient had clinical evidence of left ventricular hypertrophy. The left ventricular cinean- giogram revealed normal function and wall motion in six patients. One patient had an area of apical hypoki- nesia and a prolapsing posterior mitral scallop without mitral regurgitation. Both resting and exercise elec- trocardiograms were within normal limits in all patients. One patient had typical angina at peak exercise. All three patients with grade II systolic narrowing had a normal thallium-201 scintigram (Table I). The length of the constricted segment ranged from 2 to 3.5 cm in these three patients. Three of the four patients with grade III systolic narrowing had stress-induced perfu- sion abnormalities in the distribution of the left anterior descending vessel. The length of the constricted seg- ment in the patient with grade III narrowing and a normal scintigram was approximately 2.5 cm. In the three patients with an abnormal scintigram, the length of constriction ranged from 2.5 to 4.5 centimeters.

Figure 1 shows a 45” left anterior oblique projection, diastolic and systolic frames, from the coronary cine- angiogram of a patient with greater than 75 percent systolic coronary arterial narrowing. Figure 2 shows 45” left anterior oblique thallium-201 scintigrams in the same patient. As seen, the perfusion deficit in the septal region in the stress image resolved completely in the follow-up scintigram. All three patients with grade II systolic narrowing and one patient with grade III sys- tolic narrowing had an increase in ejection fraction during exercise. In two patients with grade III narrow- ing, the response of the ejection fraction to exercise was blunted (less than 5 percent change), and one patient with a high ejection fraction at rest showed a decrease during exercise.

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SYSTOLIC CORONARY ARTERIAL NARROWING-AHMAD ET AL.

TABLE I

Clinical, Electrocardiographic, Cineangiographic and Scintigraphic Data In Seven Men With Isolated Systolic Coronary Arterial Narrowing

HR

Age Presenting Peak Case (yr) Symptoms R Ex

Exercise Stress Test Cineangiogram

Systolic Coronary BP Arterial TI-20 1

Narrowing Scintigram LVEF Peak

R Ex ECG Symptoms Site Grade Stress Follow-Up Rest Ex

1 33

2 35

3 41

4

5’

43

45

6 44

7 63

AFh;jcsrl 76

pain A;$ctal 68

At&@;;’ 65

pain Typical 48

angina Azh$;;l 75

pain Atypical 56

chest pain

Typical 62 angina

152 123170

166 128184

162 108/76

170 120/80

140 118180

168 130/70

165174 N Shortness of breath

168178 N Shortness of breath, fatigue

16Of90 N Shortness of breath

148190 N Angina

150180 N Shortness of breath

155/75 N Fatigue

156 120168 160/72 N Shortness of breath, fatigue

Prox LAD

Prox LAD

Prox LAD

Mid LAD

Mid LAD

Mid LAD

Prox LAD

II N N 70 78

Ill Abn (ant)

N 58 62

II N N 60 75

Ill Abn (ant)

II N

N 78 68

N 56 62

Ill N N 58 76

Ill Abn (ant)

N 55 58

+ This patient was taking Inderal, 40 mg orally/day. Abn = abnormal; ant = anterior; BP = blood pressure (mm Hg); ECG = electrocardiogram; Ex = exercise: HR = heart rate (beats/min); LVEF

= left ventricular ejection fraction; Mid LAD = left anterior descending coronary artery, immediately distal to first septal perforator: N = normal; Prox LAD = left anterior descending coronary artery, proximal to first septal perforator; R = rest.

Discussion

Incidence of systolic coronary arterial narrow- ing: The coronary arteries and their major branches course through the epicardial tissue of the human heart sending smaller branches into the myocardium along their paths. Occasionally, a major coronary artery may dip into the myocardium for a variable distance and

then return to its usual course in the epicardial fat. The submerged portion of the vessel is squeezed by the muscular contraction during systole and a normal cal- iber is restored during diastole. The incidence of systolic coronary arterial narrowing due to myocardial bridging varies among studies. In a postmortem series of 70 hearts, Polacek and Kraloves reported the incidence

FIGURE 1. A 45’ left anterior oblique projection, diastolic (A) and systolic (6) frames from the coronary cineangiogram of a patient with greater than 75 percent systolic coronary arterial narrowing. Arrows point to the area of systolic coronary arterial narrowing.

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SYSTOLIC CORONARY ARTERIAL NARROWING-AHMAD ET AL.

FIGURE 2. A 45’ left anterior oblique thallium-201 scintigram in the patient with greater than 75 percent systolic coronary arterial narrowing (Fig. 1). Arrows point to the area of decreased perfusion in the stress scintigram (A) with resolution in the follow-up scintigram (B).

rate of myocardial bridges to be as high as 85.7 percent. The reported incidence rate of systolic coronary arterial narrowing by coronary cineangiography is much lower, ranging from 0.71 percent in a series of 2,000 patients3 to 0.51 percent in a series of 5,250 patients.2 The higher rate of such narrowing (6.4 percent) in our series of 589 patients may be related to differences in patient pop- ulation and cineangiographic techniques. As a tertiary care referral center, our catheterization laboratory studies a number of patients with atypical symptom complexes for ischemic heart disease. This referral pattern may play a role in influencing the incidence of the various disease processes. The routine use of nitrates before coronary cineangiography in our laboratory may have contributed to a higher detection rate of the sys- tolic coronary arterial narrowing because nitrates are known to accentuate the degree of systolic coronary arterial constriction.7

Role in producing myocardial ischemia: The role of transient systolic coronary arterial narrowing due to myocardial bridging in producing ischemia is not clear. Because the coronary blood flow occurs predominantly in diastole, a transient systolic narrowing of the coro- nary arteries would not be expected to impede flow. However, some patients with such narrowing without associated significant atherosclerotic disease may present with angina of the typical or atypical variety.2 Noble et a1.2 have shown a decreased left ventricular lactate extraction during rapid atria1 pacing in patients with a high degree of systolic coronary arterial nar- rowing. Relief of angina and ventricular arrhythmias after resection of the myocardial bridge and bypass grafting of the left anterior descending vessel has been reported.8 In a recent paper, Morales et al.9 reported postmortem findings in three apparently healthy per- sons who died suddenly during strenuous exercise. All three patients had an intramural left anterior de- scending vessel, diminished vascularity to the posterior left ventricle and ventricular septum, and morphologic evidence of patchy, ischemic necrosis of the septum.

Thallium perfusion imaging: Preliminary data regarding thallium-201 myocardial imaging in patients with myocardial bridging have been reported by two different groups of investigators. Thallium-201 scinti- grams were reported to show normal findings in these patients in one study,3 and objective evidence of myo- cardial ischemia was demonstrated in the other study.‘O Raizner et al.iO have demonstrated resolution of thal- lium-201 myocardial perfusion deficits after successful bypass graft surgery in patients with myocardial bridging.

In our small series of seven patients, definite myo- cardial perfusion deficits were observed in the stress thallium-201 scintigrams in the distribution of the left anterior descending vessel in three patients with greater than 75 percent systolic narrowing. The length of the constricted segment in these three patients ranged from 2.5 to 4.5 cm. There was complete resolution of the perfusion deficits in the follow-up scintigrams indi- cating the reversible nature of ischemia. In one of these three patients typical angina developed during exercise. The left ventricular ejection fraction response to exer- cise was blunted in two of these patients, and in one patient there was reduction of the ejection fraction during exercise. The decrease or a lack of increase in ejection fraction during exercise is similar to the re- sponse observed in patients with coronary artery dis- ease,ll and lends further support to the abnormal thallium-201 scintigraphic findings in these patients. The exercise electrocardiograms did not show ischemic changes, indicating that thallium-201 imaging may be more sensitive in detecting ischemia in these patients. A higher detection rate of ischemic heart disease by using combined thallium-201 myocardial imaging and exercise electrocardiography is well known.12

Mechanism of impaired perfusion: The mecha- nism of impaired perfusion during exercise in patients with systolic coronary arterial narrowing remains speculative. It is possible that at high heart rates, there is a marked reduction in the total diastolic time avail-

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able for coronary flow, thus making the ordinarily small amount of systolic flow more important. A marked systolic constriction may somehow impair diastolic re- laxation of the vessel.2 Systolic compression of the first septal perforator vessel has been reported in association with left ventricular hypertrophy.13 However, none of the seven patients reported on in this study had evi- dence of left ventricular hypertrophy. The possible

presence of coronary spasm in association with rapid systolic coronary compression at high heart rates and its role in causing ischemia cannot be excluded.

On the basis of our data, we believe that thallium-201 myocardial imaging offers promise in detecting abnor- mal perfusion in patients with systolic coronary arterial constriction. Additional studies with a larger number of patients are needed to further confirm our results.

References

1. AmplaD K, Anderson R. Angiographic appearance of myocardial bridging of the coronary artery. Invest Radio1 1968;3:213-5.

2. Noble J, Bouraesa MG, Petitclerc R, Dyrda I. Myocardial bridging and milking effect of the left anterior descending coronary artery: normal variant or obstruction? Am J Cardiol 1978;37:993-9.

3. Greenspan M, lskandrian AS, Catherwood E, et al. Myocardial bridging of the left anterior descending artery: evaluation using exercise thallium-201 myocardial scintigraphy. Cathet Cardiovasc Diagn 1980;6: 173-80.

8. Faruqul AM, Maloy WC, Felner JM, et al. Symptomatic myocardial bridging of coronary artery. Am J Cardiol 1978;41:1305-10.

9. Morales AR, Romanelli R, Boucek RJ. The mural left anterior descending coronary artery, strenuous exercise, and sudden death. Circulation 1980:82:230-7.

10. Ralzner AE, lshlmori T, Veranl MS, et al. Surgical relief of myo- cardial ischemia due to myocardial bridges (abstr). Am J Cardiol 1980;45:417.

4. Bruce RA, Kusumle F, Hosmer D. Maximal oxygen intake and nomographic assessment of functional aerobic impairment in cardiovascular disease. Am Heart J 1973;85:548-62.

5. Rltchle JL, Hamllton GW. Wllliams DL, et al. Myocardial imaging with radionuclide-labeled particles. Radiology 1976;121:131-8.

8. Polacek P, Kralove H. Relation of myocardial bridges and loops on the coronary arteries to coronary occlusions. Am Heart J 1961;61:44-52.

11. Borer JS, Bacharach SL, Green MV, Kent KM, Epstein SE, Johnston GS. Real-time radionuclide cineangiography in the noninvasive evaluation of global and regional left ventricular function at rest and during exercise in patients with coronary artery disease. N Engl J Med 1977;296:839-44.

12. Rltchie JL, Trobaugh GB, Hamllton GW, et al. Myocardial imaging with thallium-201 at rest and during exercise: comparison with coronary artericgraphy and resting and stress electrocardiography. Circulation 1977;56:68-71.

7. lahlmori T, Raizner AE, Chahlne RA. et al. Myocardial bridges in 13. Kotls JB, Moreyra AE, Natarajan N, et al. The pathophysiology man: clinical correlations and angiographic accentuation with ni- and diverse etiology of septal perforator compression. Circulation troglycerine. Cathet Cardiovasc Diagn 1977;3:59-86. 1979;59:913-9.

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