Catheterization and Cardiovascular Diagnosis 3:37-45 (1977)
EXTERNAL COUNTERPULSATION: CORONARY HEMODYNAMICS AND USE IN TREATMENT OF PATIENTS WITH STABLE ANGINA PECTORIS Alain Solignac, M.D., Ronald J. Ferguson, Ph.D., and Martial G. Bourassa, M.D. External pressure counterpulsation (ECP) has been reported to improve the clinical status of patients with angina pectoris. To document the mechanisms for such an improvement left ventricular oxygen consumption and lactate metabolism, coronary sinus blood flow, and cardiac index were studied in 10 patients with angina pectoris 1) prior to and during ECP; and 2) during right atrial pacing beforeand after 4 consecutive 2-hour sessions of ECP treatment. During ECP peak early and mean arterial diastolic pressures were significantly raised above control values by 32 and 13% respectively. However, coronary sinus blood flow, left ventricular oxygen consumption and left ventricular lactate extraction, mean systolic arterial pressure and cardiac index were not significantly altered by ECP. Right atrial pacing at 140 beatslmlnIncreasedcoronary sinus blood flow 70% over control values and Inducedangina and ischemic STsegment changes in 8 patients before and after 4 consecutlvetreatments of ECP. ECP treatment did not significantly modify the above metabolic and hemodynamlcresponsesat rest or during atrial pacing. Although 5 patients reported improvement in angina symptoms the effect was transitory. No significant improvement over pre ECP-treatment exercise angina threshold was observed Immediately following or at 1 and 3 months post treatment. This method of noninvasive clrculatory assistance appears to be of doubtful value in the management of patients with stable angina pectoris. Key words: Coronary sinus blood flow, myocardial metabolism, right atrial pacing, exerciseinduced angina, St-t segment depression
From the Montreal Heart Institute, Montreal, Quebec, Canada This work is supported by Grant MA-5124, Medical Research Council of Canada, and by the University of Montreal, Alma Mater Fund.
Dr. Solignac is a recipient of a Canadian Heart Foundation Fellowship Grant. Reprint requests to: Martial G . Bourassa, M.D., Montreal Heart Institute, 5000 East. Belanger Street, Montreal, Quebec H1T 1C8, Canada Received April 16, 1976; revision accepted August 29, 1976
37
0 1 9 7 7 Alan R. Liss, Inc., 150 Fifth Avenue, New York, NY 10011
38
Solignac, Ferguson, and Bourassa
INTRODUCTION
The treatment of angina pectoris consists primarily of drug therapy and exercise conditioning which tend to reduce myocardial oxygen consumption, and of aortocoronary bypass surgery which increases myocardial blood supply. The latter has succeeded in improving or relieving angina in 60 to 80% of patients when the grafts remained patent (1,2). However, this surgery is of limited use in the presence of distal coronary atherosclerosis and/or significant impairment of left ventricular function (3-5). Recently, a noninvasive technique of external pressure counterpulsation (ECP) has been proposed as a means to improve the clinical status of patients with angina due to coronary artery disease (6,7). Like intra-aortic balloon pumping, ECP should theoretically increase coronary blood flow secondary to a raised arterial diastolic pressure and reduce myocardial oxygen consumption by a reduction in left ventricular afterload during systole. A simultaneous reduction in myocardial ischemia should occur. It has been suggested that after as few as 5 ECP treatments a long-lasting improvement may result secondary to an enhancement of the coronary collateral circulation (6,7). The purposes of the present study were: 1) to determine the immediate effect of ECP on arterial systolic and diastolic pressure, coronary sinus blood flow, left ventricular oxygen consumption, lactate extraction, and cardiac index; 2) to evaluate the effect of a series of ECP treatments on these aforementioned parameters at rest and during right atrial pacing; and 3) to evaluate the effect of ECP treatment on clinical status and treadmill exercise capacity over a 3-month period. METHODS Patient Selection
Ten patients, 8 males and 2 females, aged 35 to 57 (mean 42) years, with moderate to severe stable angina pectoris were investigated. None had severe left ventricular dysfunction, congestive heart failure, valvular disease, hypertension, diabetes, or significant pulmonary disease. Propranolol was discontinued 4 days prior to the first exercise test, and no patient was taking digitalis. All were functional class 111 according to NYHA criteria. Informed consent was obtained prior to the study. Selective coronary arteriography and left cineventriculography as previously described (8) were performed within 6 months prior to the study. All patients had at least 1 major coronary artery with obstruction equal to or greater than 70%. Nine patients had double vessel and 1 had triple vessel disease. All but I patient, with antero-apical akinesis, had normal or only slight impairment of left ventricular contraction. Measurements
ECP was performed using a Cardiassist apparatus (Medical Innovations Inc., Waltham, Mass.), which was placed over the legs and adjustedfor patient comfort. External positive pressure was activated during the first two-thirds of diastole by the QRS complex of the electrocardiogram, the peripheral arterial pulse pressure, and/or the arterial pulse obtained from a finger plethysmograph. The counterpulsation pressure ranged from 200 to 250 mmHg depending on the peak early diastolic pressure obtained and the patient’s comfort.
External Counterpulsation and Stable Angina
39
A 100 cm size 8F Ganz thermodilution cathetert was inserted from the right antecubital vein into the main coronary sinus. Pressures were recorded from a Statham P23Db transducer connected to an 18 gauge Amplatz needle inserted percutaneously in the right brachial artery. The zero reference level for arterial pressure was at the midchest position and recordings were made at 100 mm/sec on a multichannel Sanborn photographic recorder. Mean arterial pressure was obtained by electrical integration and mean systolic and diastolic pressures by planimetry. Peak early diastolic pressure was the highest pressure recorded during the first third of diastole (Fig. 1). Cardiac output was measured by the dye dilution technique (9) with a rapid injection of 5 mg of indocyanine green into the coronary sinus. Arterial blood was withdrawn through a Waters cuvette densitometer by a Harvard infusionwithdrawal pump at a constant speed of 20 mlhin. Coronary sinus blood flow was determined by the continuous thermodilution technique as described by Ganz et al. (10). Arterial and coronary sinus blood were sampled immediately after coronary sinus blood flow measures and analyzed for pH, pOz, pCOz, and lactate concentration. Left ventricular oxygen consumption (ml/min) was calculated from arterial-coronary sinus difference times coronary sinus blood flow. Left ventricular lactate extraction (%) was calculated as arterial minus coronary sinus over arterial lactate concentration (mg/l00 mi).
Procedure
Duplicate hemodynamic measurements were obtained at rest, after 8 min of right atrial pacing ( 140 beatshin), and during ECP. Catheterization was performed on the morning of day 1 with the subjects in the fasting state and without premedication. ECP was performed for 2 hr on each of days I through 4. Following ECP on CONIROL
DURMG E O
Fig. 1: PDP is peak early diastolic pressure. Mean diastolic pressure equals shaded area (a)/ tz-ts
?Supplied by Wilton Webster C o . , Altadena, California.
40
Solignac, Ferguson, and Bourassa
day 4 hemodynamic measurements were repeated at rest and during right atrial pacing. A 12-lead electrocardiogram was recorded during the control measures, each 30 sec during atrial pacing, and each min of the treadmill exercise test. An ischemic change was defined as J-point depression of at least 0.1 mV associated with a null or negative ST-segment slope for at least 0.08 sec. Maximal multistage treadmill exercise tests (1 1) were performed prior to day 1 within 3 days of, and at 1 and 3 months after, the last hemodynamic determinations. Clinical status was evaluated according to the NYHA functional classification before and at 1 and 3 months after ECP treatment. Statistical comparisons between resting and ECP data, resting data before and after ECP treatment, and right atrial pacing data before and after ECP treatment were made using the Student’s t-test for paired values. Comparisons of treadmill data before and after ECP treatment were made using analysis of variance for repeated measures (12). RESULTS
Effects of ECP
ECP significantly (p 0.05). ECP is external counterpulsation. Values are mean (standard error).
Control
During ECP
67 (4) 3.1 (0.2)
75 ( 6 ) 2.1 (0.2)
< 0.005
101 (3)
133 (5)
< 0.001
P*
NS
90 (4)
104 ( 6 )
< 0.01
102 (2)
106 (5)
NS
140 (5)
134 (6)
NS
1 1 5 (4)
120 (5)
NS
117 (14)
NS
13 (2) 35 (4)
NS NS
External Counterpulsation and Stable Angina
41
Control values for cardiac index (3.320.2 literdmin X m2), mean arterial pressure (96+5 mmHg), coronary sinus blood flow (108 ml/min), and left ventricular oxygen consumption (1252 ml/min) measured prior to right atrial pacing after ECP treatment were not significantly different from control values before ECP treatment. Left ventricular lactate extraction was normal in the control state in all patients before (35+4%) and after (3925%) ECP treatment. ECP Treatment
Right atrial pacing significantly (p 0.05). ECP is external counterpulsation. Values are mean (standard error).
Before ECP
After ECP
P* NS
NS NS NS
42
Solignac, Ferguson, and Bourassa
-
-2.0L 1 1 -3.0 -4.0
Fig. 2: Lactate extraction (filled circles) and production (open circles) during right atrial pacing (140lmin) before and after ECP treatment. TABLE Ill. Symptom-Limited Exercise Capacity Before and After ECP Treatment
n=8 Work time* (min) PRP X 10-3t Hedrt rate (beatslmin)
Before ECP
11.1 (2.3) 22.2 (2.5) 134 (11)
1--2 days
After ECP 1 month
11.9 (2.7) 21.9 (3.0) 143 (1 0)
12.7 (2.7) 23.8 (2.9) 138 (9)
3 months 13.1 (3.1) 23.5 (2.7) 132
(1 0 )
F$
NS NS NS
*Work time to the onset of angina pectoris. tPRP is systolic arterial pressure X heart rate. $Analysis of variance for repeated measures. Values are mean (standard error). NS is not significant (p > 0.05).
DISCUSSION Angina pectoris results from an imbalance between myocardial oxygen requirements and delivery. It has been hypothesized that external counterpulsation, like intra-aortic balloon counterpulsation, is a method of circulatory assistance which by 1) augmenting aortic diastolic pressure could increase coronary blood flow to critically stenosed (pressure-dependent) areas of the myocardium, and 2) by decreasing systolic aortic pressure could decrease left ventricular afterload and, thus, myocardial oxygen requirement.
External Counterpulsation and Stable Angina
43
The present data do not support these hypotheses. Despite the significant augmentation of peak early arterial diastolic pressure (32%) during ECP, coronary sinus blood flow was not increased. Singh et al. (13) found that ECP increased coronary sinus blood flow and mean diastolic arterial pressure to a lesser extent than intraaortic balloon counterpulsation in patients with myocardial infarction and shock. Mueller et al. (14) have reported increases in coronary sinus blood flow and peak diastolic pressure during ECP in patients with acute myocardial infarction without shock. Results to the contrary for left ventricular oxygen consumption and coronary sinus blood flow were reported for ECP by Parmley et al. (15) in 7 patients with acute myocardial infarction. Studies (16,17) on symptomatic coronary artery disease patients during ECP have failed to show increases in coronary sinus blood flow despite augmented diastolic arterial pressure. In particular, Loeb et al. (16) studied patients during pacing-induced ischemia with and without ECP. Besides having no effect on coronary sinus blood flow during pacing, ECP did not significantly modify lactate production, ST segment depression, or incidence of angina. It is apparent that significant increases in mean diastolic pressure do not consistently increase coronary blood flow. Since left ventricular work and oxygen demand are not significantly modified by ECP, the coronary circulation autoregulates to maintain a constant coronary blood flow despite the increased diastolic perfusion pressure (18). With the exception of Mueller et al. (14), available studies (15-17, 19) have shown no tendency for ECP to lower arterial pressure, thereby decreasing left ventricular afterload and left ventricular oxygen consumption. The present results obtained during ECP are in agreement with these studies. The small but significant increase in heart rate found during ECP in the present study has also been noted by Kahn et al. (17). Measures of total left ventricular blood flow during ECP might not indicate possible changes in the distribution of coronary blood flow to ischemic pressure-dependent areas of the myocardium. Techniques measuring regional flow would be warranted (16). In our study left ventricular lactate production, occurring in 4 patients during right atrial pacing, tended to be lower after ECP treatment. Although not significant as a group, 4 of the 8 patients studied by Loeb et al. (16) had improved left ventricular lactate metabolism during pacing with the simultaneous application of ECP. However, the lack of improvement in exercise-induced angina and ischemic ECG signs with ECP tends to diminish the importance of this hypothesis. The use of ECP as a treatment for chronic stable angina is suggested from the data of Banas et al. (6,7) who studied patients before and after 5 1-hr sessions of ECP. Angina was eliminated in the majority of patients, mean pressure time per min during pacing-induced angina was increased, and some patients showed increased coronary vascularity upon repeat coronary angiography 4-8 weeks after ECP treatment. The present hemodynamic, exercise testing, and clinical results do not confirm these data. Four consecutive 2-hour sessions of ECP treatment did not significantly modify any parameter of coronary hemodynamics, left ventricular oxygen consumption, or left ventricular lactate metabolism during the control period or upon right atrial pacing at 140 beatshin. No significant improvement over preECP treatment exercise angina threshold was observed immediately following or
44
Solignac, Ferguson, and Bourassa
up to 3 months post treatment. Although 5 patients reported improvement in symptoms of angina this was transitory and probably related to a placebo effect. However, Clapp et al. (20) have reported improvement in nitroglycerin usage and pressure times heart rate product during bicycle exercise after 5 2-hr sessions of ECP treatment. These results were not obtained when a sham ECP was performed. On the other hand, Johnson et al. (21) found no dramatic improvement in angina symptoms in 4 or more weeks following 5 I-hour sessions of ECP treatment, although there was a modest improvement in submaximal exercise tolerance. Although ECP may be of use in patients in acute myocardial infarction the present data obtained on patients with chronic stable angina pectoris fail to demonstrate any mechanism capable of reducing myocardial ischemia during ECP or following ECP treatment. The lack of objective and important clinical improvement suggests that ECP is of doubtful value in the treatment of patients with stable angina pectoris. REFERENCES 1. Johnson WD and Lepley D, Jr.: An aggressive surgical approach to coronary disease. J Thorac
Cardiovasc Surg 59: 128-135, 1970. 2. Spencer FC: Venous bypass grafts for occlusive disease of the coronary arteries. Am Heart J 79: 568-571, 1970. 3. Lesperance J , Bourassa MG, Biron P, Campeau L and Saltiel J: Aorta to coronary artery saphenous vein grafts. Preoperative angiographic criteria for successful surgery. Am J Cardiol 30: 459-465, 1972. 4. Shirey EK: Selection of the surgical candidate. Surg Clin North Am 51: 1023-1033, 1971. 5 . Bourassa MG: Left ventricular performance following direct myocardial revascularization. Circulation 48: 915-916, 1973. 6. Banas JS, Brilla A , Soroff HS and Levine HJ: Evaluation of external counterpulsation for t h e treatment of severe angina pectoris. (abstr) Circulation 46 (suppl 11): 11-74, 1972. 7. Banas JS, Brilla A and Levine HJ: Evaluation of external counterpulsation for the treatment of angina pectoris. (abstr) Am J Cardiol 31: 118, 1973. 8. Bourassa MG, Lesperance J and Campeau L: Selective coronary arteriography by the percutaneous femoral artery approach. Am J Roentgenol Rad Ther & Nucl Med 107: 377-383, 1969. 9. Williams JCP, O’Donovan TPB and Wood EH: A method for the calculation of areas under indicator-dilution curves. J Appl Physiol 21: 695-699, 1966. 10. Ganz W, Tamura K, Marcus HS, Donoso R, Yoshida S and Swan HJC: Measurement of coronary sinus blood flow by continuous thermodilution in man. Circulation 44: 181-195, 1971. I I . Naughton JP and Haider R: Methods of exercise testing. In (Naughton JP and Hellerstein HK, eds): Exercise Testing and Exercise Training in Coronary Heart Disease. New York: Academic Press, 1973, Chap. 6. 12. Winer BJ: Statistical Principles in Experimental Design. New York, McGraw Hill Book Co., 1%2. 13. Singh J , Mueller H and Ayres S: Invasive versus noninvasive cardiac assistance in myocardial infarction shock in man. (abstr) Circulation 50 (suppl 111): 111-108, 1974. 14. Mueller H , Evans R and Ayres S: External counterpulsation-a noninvasive form of cardiac assistance. (abstr) Am J Cardiol 33: 158, 1974. 15. Parmley WW, Chatterjee K , Charuzi Y and Swan HJC: Hemodynamic effects of noninvasive systolic unloading (nitroprusside) and diastolic augmentation (external counterpulsation) in pa1974. tients with acute myocardial infarction. Am J Cardiol 33: 81-25. 16. Loeb HS, Kahn M, Towne W and Gunnar RM: Effects of external counterpulsation on myocardial ischemia induced by atrial pacing. Circulation 49-50 (suppl 11): II:255-258, 1974. 17. Kahn M, Loeb HS, Towne W and Gunnar RM: Hemodynamic effects of external counterpulsation in patients with coronary artery disease. (abstr) Circulation 48 (suppl IV): IV-182, 1973.
External Counterpulsation and Stable Angina
45
18. Rubio R, Berne RM: Regulation of coronary blood flow. Prog Cardiovasc Dis 18: 105-122, 1975. 19. Michael TD, Bassen M, Chatterjee K. Forrester J, Parmley WW and Swan HJC: Hemodynamic and metabolic effects of noninvasive circulatory assist (Cardiassist). (abstr) Circulation 46 (suppl IT): 11-192, 1972. 20. Clapp JC, Banas JS, Stickley LP, Salem DN, Pollak RH and Levine HJ: Evaluation of sham and true external counterpulsation in patients with angina pectoris (abstr) Circulation 50 (suppl 111): 111-108, 1974. 21. Johnson S , Loeb HS, Kahn M, Towne W and Gunnar RM: Clinical response in patients with coronary artery disease to external counterpulsation. (abstr) Circulation 48 (suppl IV): IV-59, 1973.
EXTERNAL COUNTERPULSATION: CORONARY HEMODYNAMICS AND USE IN TREATMENT OF PATIENTS WITH STABLE ANGINA PECTORIS Alain Solignac, M.D., Ronald J. Ferguson, Ph.D., and Martial G. Bourassa, M.D. External pressure counterpulsation (ECP) has been reported to improve the clinical status of patients with angina pectoris. To document the mechanisms for such an improvement left ventricular oxygen consumption and lactate metabolism, coronary sinus blood flow, and cardiac index were studied in 10 patients with angina pectoris 1) prior to and during ECP; and 2) during right atrial pacing beforeand after 4 consecutive 2-hour sessions of ECP treatment. During ECP peak early and mean arterial diastolic pressures were significantly raised above control values by 32 and 13% respectively. However, coronary sinus blood flow, left ventricular oxygen consumption and left ventricular lactate extraction, mean systolic arterial pressure and cardiac index were not significantly altered by ECP. Right atrial pacing at 140 beatslmlnIncreasedcoronary sinus blood flow 70% over control values and Inducedangina and ischemic STsegment changes in 8 patients before and after 4 consecutlvetreatments of ECP. ECP treatment did not significantly modify the above metabolic and hemodynamlcresponsesat rest or during atrial pacing. Although 5 patients reported improvement in angina symptoms the effect was transitory. No significant improvement over pre ECP-treatment exercise angina threshold was observed Immediately following or at 1 and 3 months post treatment. This method of noninvasive clrculatory assistance appears to be of doubtful value in the management of patients with stable angina pectoris. Key words: Coronary sinus blood flow, myocardial metabolism, right atrial pacing, exerciseinduced angina, St-t segment depression
From the Montreal Heart Institute, Montreal, Quebec, Canada This work is supported by Grant MA-5124, Medical Research Council of Canada, and by the University of Montreal, Alma Mater Fund.
Dr. Solignac is a recipient of a Canadian Heart Foundation Fellowship Grant. Reprint requests to: Martial G . Bourassa, M.D., Montreal Heart Institute, 5000 East. Belanger Street, Montreal, Quebec H1T 1C8, Canada Received April 16, 1976; revision accepted August 29, 1976
37
0 1 9 7 7 Alan R. Liss, Inc., 150 Fifth Avenue, New York, NY 10011
38
Solignac, Ferguson, and Bourassa
INTRODUCTION
The treatment of angina pectoris consists primarily of drug therapy and exercise conditioning which tend to reduce myocardial oxygen consumption, and of aortocoronary bypass surgery which increases myocardial blood supply. The latter has succeeded in improving or relieving angina in 60 to 80% of patients when the grafts remained patent (1,2). However, this surgery is of limited use in the presence of distal coronary atherosclerosis and/or significant impairment of left ventricular function (3-5). Recently, a noninvasive technique of external pressure counterpulsation (ECP) has been proposed as a means to improve the clinical status of patients with angina due to coronary artery disease (6,7). Like intra-aortic balloon pumping, ECP should theoretically increase coronary blood flow secondary to a raised arterial diastolic pressure and reduce myocardial oxygen consumption by a reduction in left ventricular afterload during systole. A simultaneous reduction in myocardial ischemia should occur. It has been suggested that after as few as 5 ECP treatments a long-lasting improvement may result secondary to an enhancement of the coronary collateral circulation (6,7). The purposes of the present study were: 1) to determine the immediate effect of ECP on arterial systolic and diastolic pressure, coronary sinus blood flow, left ventricular oxygen consumption, lactate extraction, and cardiac index; 2) to evaluate the effect of a series of ECP treatments on these aforementioned parameters at rest and during right atrial pacing; and 3) to evaluate the effect of ECP treatment on clinical status and treadmill exercise capacity over a 3-month period. METHODS Patient Selection
Ten patients, 8 males and 2 females, aged 35 to 57 (mean 42) years, with moderate to severe stable angina pectoris were investigated. None had severe left ventricular dysfunction, congestive heart failure, valvular disease, hypertension, diabetes, or significant pulmonary disease. Propranolol was discontinued 4 days prior to the first exercise test, and no patient was taking digitalis. All were functional class 111 according to NYHA criteria. Informed consent was obtained prior to the study. Selective coronary arteriography and left cineventriculography as previously described (8) were performed within 6 months prior to the study. All patients had at least 1 major coronary artery with obstruction equal to or greater than 70%. Nine patients had double vessel and 1 had triple vessel disease. All but I patient, with antero-apical akinesis, had normal or only slight impairment of left ventricular contraction. Measurements
ECP was performed using a Cardiassist apparatus (Medical Innovations Inc., Waltham, Mass.), which was placed over the legs and adjustedfor patient comfort. External positive pressure was activated during the first two-thirds of diastole by the QRS complex of the electrocardiogram, the peripheral arterial pulse pressure, and/or the arterial pulse obtained from a finger plethysmograph. The counterpulsation pressure ranged from 200 to 250 mmHg depending on the peak early diastolic pressure obtained and the patient’s comfort.
External Counterpulsation and Stable Angina
39
A 100 cm size 8F Ganz thermodilution cathetert was inserted from the right antecubital vein into the main coronary sinus. Pressures were recorded from a Statham P23Db transducer connected to an 18 gauge Amplatz needle inserted percutaneously in the right brachial artery. The zero reference level for arterial pressure was at the midchest position and recordings were made at 100 mm/sec on a multichannel Sanborn photographic recorder. Mean arterial pressure was obtained by electrical integration and mean systolic and diastolic pressures by planimetry. Peak early diastolic pressure was the highest pressure recorded during the first third of diastole (Fig. 1). Cardiac output was measured by the dye dilution technique (9) with a rapid injection of 5 mg of indocyanine green into the coronary sinus. Arterial blood was withdrawn through a Waters cuvette densitometer by a Harvard infusionwithdrawal pump at a constant speed of 20 mlhin. Coronary sinus blood flow was determined by the continuous thermodilution technique as described by Ganz et al. (10). Arterial and coronary sinus blood were sampled immediately after coronary sinus blood flow measures and analyzed for pH, pOz, pCOz, and lactate concentration. Left ventricular oxygen consumption (ml/min) was calculated from arterial-coronary sinus difference times coronary sinus blood flow. Left ventricular lactate extraction (%) was calculated as arterial minus coronary sinus over arterial lactate concentration (mg/l00 mi).
Procedure
Duplicate hemodynamic measurements were obtained at rest, after 8 min of right atrial pacing ( 140 beatshin), and during ECP. Catheterization was performed on the morning of day 1 with the subjects in the fasting state and without premedication. ECP was performed for 2 hr on each of days I through 4. Following ECP on CONIROL
DURMG E O
Fig. 1: PDP is peak early diastolic pressure. Mean diastolic pressure equals shaded area (a)/ tz-ts
?Supplied by Wilton Webster C o . , Altadena, California.
40
Solignac, Ferguson, and Bourassa
day 4 hemodynamic measurements were repeated at rest and during right atrial pacing. A 12-lead electrocardiogram was recorded during the control measures, each 30 sec during atrial pacing, and each min of the treadmill exercise test. An ischemic change was defined as J-point depression of at least 0.1 mV associated with a null or negative ST-segment slope for at least 0.08 sec. Maximal multistage treadmill exercise tests (1 1) were performed prior to day 1 within 3 days of, and at 1 and 3 months after, the last hemodynamic determinations. Clinical status was evaluated according to the NYHA functional classification before and at 1 and 3 months after ECP treatment. Statistical comparisons between resting and ECP data, resting data before and after ECP treatment, and right atrial pacing data before and after ECP treatment were made using the Student’s t-test for paired values. Comparisons of treadmill data before and after ECP treatment were made using analysis of variance for repeated measures (12). RESULTS
Effects of ECP
ECP significantly (p 0.05). ECP is external counterpulsation. Values are mean (standard error).
Control
During ECP
67 (4) 3.1 (0.2)
75 ( 6 ) 2.1 (0.2)
< 0.005
101 (3)
133 (5)
< 0.001
P*
NS
90 (4)
104 ( 6 )
< 0.01
102 (2)
106 (5)
NS
140 (5)
134 (6)
NS
1 1 5 (4)
120 (5)
NS
117 (14)
NS
13 (2) 35 (4)
NS NS
External Counterpulsation and Stable Angina
41
Control values for cardiac index (3.320.2 literdmin X m2), mean arterial pressure (96+5 mmHg), coronary sinus blood flow (108 ml/min), and left ventricular oxygen consumption (1252 ml/min) measured prior to right atrial pacing after ECP treatment were not significantly different from control values before ECP treatment. Left ventricular lactate extraction was normal in the control state in all patients before (35+4%) and after (3925%) ECP treatment. ECP Treatment
Right atrial pacing significantly (p 0.05). ECP is external counterpulsation. Values are mean (standard error).
Before ECP
After ECP
P* NS
NS NS NS
42
Solignac, Ferguson, and Bourassa
-
-2.0L 1 1 -3.0 -4.0
Fig. 2: Lactate extraction (filled circles) and production (open circles) during right atrial pacing (140lmin) before and after ECP treatment. TABLE Ill. Symptom-Limited Exercise Capacity Before and After ECP Treatment
n=8 Work time* (min) PRP X 10-3t Hedrt rate (beatslmin)
Before ECP
11.1 (2.3) 22.2 (2.5) 134 (11)
1--2 days
After ECP 1 month
11.9 (2.7) 21.9 (3.0) 143 (1 0)
12.7 (2.7) 23.8 (2.9) 138 (9)
3 months 13.1 (3.1) 23.5 (2.7) 132
(1 0 )
F$
NS NS NS
*Work time to the onset of angina pectoris. tPRP is systolic arterial pressure X heart rate. $Analysis of variance for repeated measures. Values are mean (standard error). NS is not significant (p > 0.05).
DISCUSSION Angina pectoris results from an imbalance between myocardial oxygen requirements and delivery. It has been hypothesized that external counterpulsation, like intra-aortic balloon counterpulsation, is a method of circulatory assistance which by 1) augmenting aortic diastolic pressure could increase coronary blood flow to critically stenosed (pressure-dependent) areas of the myocardium, and 2) by decreasing systolic aortic pressure could decrease left ventricular afterload and, thus, myocardial oxygen requirement.
External Counterpulsation and Stable Angina
43
The present data do not support these hypotheses. Despite the significant augmentation of peak early arterial diastolic pressure (32%) during ECP, coronary sinus blood flow was not increased. Singh et al. (13) found that ECP increased coronary sinus blood flow and mean diastolic arterial pressure to a lesser extent than intraaortic balloon counterpulsation in patients with myocardial infarction and shock. Mueller et al. (14) have reported increases in coronary sinus blood flow and peak diastolic pressure during ECP in patients with acute myocardial infarction without shock. Results to the contrary for left ventricular oxygen consumption and coronary sinus blood flow were reported for ECP by Parmley et al. (15) in 7 patients with acute myocardial infarction. Studies (16,17) on symptomatic coronary artery disease patients during ECP have failed to show increases in coronary sinus blood flow despite augmented diastolic arterial pressure. In particular, Loeb et al. (16) studied patients during pacing-induced ischemia with and without ECP. Besides having no effect on coronary sinus blood flow during pacing, ECP did not significantly modify lactate production, ST segment depression, or incidence of angina. It is apparent that significant increases in mean diastolic pressure do not consistently increase coronary blood flow. Since left ventricular work and oxygen demand are not significantly modified by ECP, the coronary circulation autoregulates to maintain a constant coronary blood flow despite the increased diastolic perfusion pressure (18). With the exception of Mueller et al. (14), available studies (15-17, 19) have shown no tendency for ECP to lower arterial pressure, thereby decreasing left ventricular afterload and left ventricular oxygen consumption. The present results obtained during ECP are in agreement with these studies. The small but significant increase in heart rate found during ECP in the present study has also been noted by Kahn et al. (17). Measures of total left ventricular blood flow during ECP might not indicate possible changes in the distribution of coronary blood flow to ischemic pressure-dependent areas of the myocardium. Techniques measuring regional flow would be warranted (16). In our study left ventricular lactate production, occurring in 4 patients during right atrial pacing, tended to be lower after ECP treatment. Although not significant as a group, 4 of the 8 patients studied by Loeb et al. (16) had improved left ventricular lactate metabolism during pacing with the simultaneous application of ECP. However, the lack of improvement in exercise-induced angina and ischemic ECG signs with ECP tends to diminish the importance of this hypothesis. The use of ECP as a treatment for chronic stable angina is suggested from the data of Banas et al. (6,7) who studied patients before and after 5 1-hr sessions of ECP. Angina was eliminated in the majority of patients, mean pressure time per min during pacing-induced angina was increased, and some patients showed increased coronary vascularity upon repeat coronary angiography 4-8 weeks after ECP treatment. The present hemodynamic, exercise testing, and clinical results do not confirm these data. Four consecutive 2-hour sessions of ECP treatment did not significantly modify any parameter of coronary hemodynamics, left ventricular oxygen consumption, or left ventricular lactate metabolism during the control period or upon right atrial pacing at 140 beatshin. No significant improvement over preECP treatment exercise angina threshold was observed immediately following or
44
Solignac, Ferguson, and Bourassa
up to 3 months post treatment. Although 5 patients reported improvement in symptoms of angina this was transitory and probably related to a placebo effect. However, Clapp et al. (20) have reported improvement in nitroglycerin usage and pressure times heart rate product during bicycle exercise after 5 2-hr sessions of ECP treatment. These results were not obtained when a sham ECP was performed. On the other hand, Johnson et al. (21) found no dramatic improvement in angina symptoms in 4 or more weeks following 5 I-hour sessions of ECP treatment, although there was a modest improvement in submaximal exercise tolerance. Although ECP may be of use in patients in acute myocardial infarction the present data obtained on patients with chronic stable angina pectoris fail to demonstrate any mechanism capable of reducing myocardial ischemia during ECP or following ECP treatment. The lack of objective and important clinical improvement suggests that ECP is of doubtful value in the treatment of patients with stable angina pectoris. REFERENCES 1. Johnson WD and Lepley D, Jr.: An aggressive surgical approach to coronary disease. J Thorac
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18. Rubio R, Berne RM: Regulation of coronary blood flow. Prog Cardiovasc Dis 18: 105-122, 1975. 19. Michael TD, Bassen M, Chatterjee K. Forrester J, Parmley WW and Swan HJC: Hemodynamic and metabolic effects of noninvasive circulatory assist (Cardiassist). (abstr) Circulation 46 (suppl IT): 11-192, 1972. 20. Clapp JC, Banas JS, Stickley LP, Salem DN, Pollak RH and Levine HJ: Evaluation of sham and true external counterpulsation in patients with angina pectoris (abstr) Circulation 50 (suppl 111): 111-108, 1974. 21. Johnson S , Loeb HS, Kahn M, Towne W and Gunnar RM: Clinical response in patients with coronary artery disease to external counterpulsation. (abstr) Circulation 48 (suppl IV): IV-59, 1973.
