Prognostic and predictive value of exertional hypotension in suspected coronary heart disease

The prognostic and predictive value of exertional hypotension was assessed in 1,241 patients having treadmill maximal exercise testing, coronary arteriography, and follow-up averaging 5.4 years. Medically treated patients with coronary artery disease (CAD) with exertional hypotension had poorer survival than did those without such hypotension; however, maximum systolic pressure during exercise was a more powerful predictor of survival. Patients with exertional hypotension had more extensive CAD and more left ventricular (LV) dysfunction than did patients who had an increase in blood pressure with exertion; these findings probably account for the impaired survival. However, exertional hypotension, was an insensitive indicator of significant left main coronary artery stenosis, 3-vessel disease, or severe resting LV dysfunction.     

Effect of beta-blockade on right ventricular performance in patients with and without right ventricular dysfunction due to coronary artery disease

To assess the effects of beta-blockade on right ventricular performance in patients with and without right ventricular dysfunction due to coronary artery disease, we performed radionuclide ventriculography on eight patients with normal right ventricular ejection fraction (RVEF greater than or equal to 35%) and 14 patients with mild to moderate right ventricular dysfunction (RVEF less than 35%) at rest. All patients had chronic stable angina pectoris, and nine patients had prior myocardial infarction. Radionuclide ventriculography was performed on placebo and during clinical beta-blockade (heart rate, 50 to 60 beats per minute and less than or equal to 20% increase in heart rate over baseline during stage I treadmill exercise, Bruce protocol) with the oral, cardioselective beta-blocking agent, betaxolol. The resting RVEF (mean +/- 1 SD) was 33% +/- 7% on placebo and 34% +/- 7% during clinical beta-blockade. Mean exercise RVEF was 40% +/- 8% on placebo and 39% +/- 8% during clinical beta-blockade. These differences were not statistically significant. Resting left ventricular ejection fraction ranged from 22% to 60% (mean, 42% +/- 8%). On placebo, one of eight patients with a resting RVEF greater than or equal to 35% had a normal exercise RVEF response (greater than or equal to 5% increment) whereas nine of 14 patients with resting RVEF less than 35% had normal exercise response. The discordant relationship between baseline RVEF and exercise response on placebo became less marked during clinical beta-blockade. We conclude that beta-blockade does not produce significant deterioration of right ventricular systolic function or right ventricular reserve either in patients with normal or in those with mild to moderately impaired resting right ventricular systolic function.     

Submaximal exercise testing early after myocardial infarction. Difficulty of predicting coronary anatomy and left ventricular performance

Impaired left ventricular function and extensive coronary artery disease are important determinants of prognosis after acute myocardial infarction. The ability of clinical and predischarge submaximal exercise test variables to predict multivessel coronary artery disease and impaired left ventricular function was assessed in 62 survivors of acute myocardial infarction. Abnormal exercise blood pressure response and short exercise performance were predictors of multivessel disease, but exercise induced ST segment changes and clinical variables were not. Q wave infarction, high grade Killip classification, and exercise induced ST segment elevation predicted statistically significant impairment of resting left ventricular function, whereas other clinical and exercise test variables did not. Exercise induced ST segment changes were therefore of little value in detecting extensive coronary disease, although exercise induced ST elevation was an indicator of poor resting left ventricular function. Although abnormal exercise haemodynamics may detect extensive coronary artery disease, other physiological markers of reversible myocardial ischaemia are probably necessary to plan optimal management in these patients.     

Submaximal exercise testing early after myocardial infarction. Difficulty of predicting coronary anatomy and left ventricular performance.

Impaired left ventricular function and extensive coronary artery disease are important determinants of prognosis after acute myocardial infarction. The ability of clinical and predischarge submaximal exercise test variables to predict multivessel coronary artery disease and impaired left ventricular function was assessed in 62 survivors of acute myocardial infarction. Abnormal exercise blood pressure response and short exercise performance were predictors of multivessel disease, but exercise induced ST segment changes and clinical variables were not. Q wave infarction, high grade Killip classification, and exercise induced ST segment elevation predicted statistically significant impairment of resting left ventricular function, whereas other clinical and exercise test variables did not. Exercise induced ST segment changes were therefore of little value in detecting extensive coronary disease, although exercise induced ST elevation was an indicator of poor resting left ventricular function. Although abnormal exercise haemodynamics may detect extensive coronary artery disease, other physiological markers of reversible myocardial ischaemia are probably necessary to plan optimal management in these patients.     

Effects of severity of mitral stenosis on left and right ventricular function at rest and during exercise

Few studies have assessed the effect of severity of mitral stenosis (MS) on ventricular function. Using equilibrium radionuclide ventriculography to measure ejection fraction and volume changes, 63 patients were studied during supine, symptom-limited exercise. To more carefully assess the 12 patients with MS and impaired left ventricular function, 2 groups of patients were formed. Group I (n = 51) had a normal (less than 50%) resting left ventricular (LV) ejection fraction (EF) and group II (n = 12) had an abnormally low (less than 50%) resting LVEF. Both groups were divided into mild (greater than 1.4 cm2), moderate (1.1-1.4 cm2) and severe (less than 1.0 cm2) MS. There were no differences in mean rest or exercise LVEF for group I. Exercise LVEF increased significantly (p less than 0.05) from rest with mild MS, but not with moderate or severe MS. The decrease in exercise LVEF was due to a decrease in exercise end-diastolic volume of 9 +/- 23% and 15 +/- 18% for moderate and severe MS, respectively. Exercise end-systolic volume decreased normally for all degrees of MS severity. Exercise right ventricular (RV)EF did not increase for any degree of MS severity due to an increase in end-systolic volume. All patients in group II had an RVEF of less than 40%. For this group, severity of MS had no effect on resting LVEF and the response to exercise was similar to group I. We conclude that in patients with MS, resting LVEF is unaffected by MS severity whereas exercise LVEF decreases with increased severity of MS due to impaired diastolic filling.(ABSTRACT TRUNCATED AT 250 WORDS)     

Haemodynamic dose-response actions of cicloprolol in left ventricular dysfunction due to ischaemic heart disease

Cicloprolol is a cardioselective beta-1 partial agonist; its haemodynamic and radionuclide (nuclear stethoscope) effects were determined in 22 patients with impaired left ventricular function due to coronary artery disease. Following a 20 min stable control period, the effects of four doses of cicloprolol (0.025, 0.025, 0.05 and 0.1 mg/kg at 10 min intervals) were measured at rest 5-10 min after each intravenous injection. The effects of the cumulative 0.2 mg/kg dosage were assessed during supine bicycle exercise and compared with a control exercise period. At rest there were significant increases in systolic arterial without change in mean blood pressure. The heart rate and cardiac index were unchanged. There was a significant increase in left ventricular ejection fraction with a reduction in filling pressure and volume. Patients with resting heart rate below 75 beats/min and with ejection fraction greater than 35% showed the greatest improvement. During supine bicycle exercise, ejection fraction was increased compared to control (31 +/- 2 to 36 +/- 2; P less than 0.01), cardiac volume reduced and exercise tachycardia attenuated. These data suggest that cicloprolol may be of value where beta-blockade is considered in the presence of underlying left ventricular dysfunction due to ischaemic heart disease.     

Interstudy variability of coronary flow reserve. Influence of heart rate, arterial pressure, and ventricular preload

To define the long-term variability of serial coronary flow reserve (CFR) measurements in humans and to evaluate the influence of changes in heart rate, mean arterial pressure, and left ventricular preload on CFR, 45 patients with normal left ventricular function (38 cardiac allograft recipients, five patients with normal coronary arteries, and two patients with minimal coronary artery disease [less than 50% diameter stenosis]) were studied. CFR (ratio of peak hyperemic [h] to resting [r] coronary blood flow velocity [CBFV]) was measured with a 3F coronary Doppler catheter and intracoronary papaverine. Initial CFR measurements were highly correlated with repeat measurements obtained 11 +/- 0.6 months later (r = 0.95; mean absolute difference, 0.3 +/- 0.1; n = 17). Differences in CFR between studies were related to changes in heart rate (r = 0.61, p = 0.01) but not to changes in mean arterial pressure (r = 0.25, p = 0.33). To define the effects of rapid changes in heart rate, mean arterial pressure, and preload on CFR, these variables were altered by atrial pacing, handgrip exercise, and volume expansion, respectively. Atrial pacing produced a rate-related increase in rCBFV but did not change hCBFV. Consequently, CFR was significantly reduced as heart rate was increased progressively from 76 +/- 2 in sinus rhythm (4.5 +/- 0.2) to 100 (3.8 +/- 0.2, p less than 0.05, n = 32) to 120 beats/min (3.2 +/- 0.1, p less than 0.05, n = 7). Despite a 19 +/- 2 mm Hg rise in mean arterial pressure during handgrip exercise, CFR was unchanged from baseline (3.7 +/- 0.3 vs. 3.7 +/- 0.4, p = NS, n = 7) because rCBFV rose proportionally with hCBFV. When pulmonary capillary wedge pressure was increased from 9 +/- 1 to 16 +/- 1 mm Hg after volume expansion, CFR was significantly decreased (from 3.8 +/- 0.2 to 2.9 +/- 0.2, p less than 0.05, n = 9) because rCBFV was increased while hCBFV remained unchanged. Hence, serial CFR measurements in humans are highly reproducible in the absence of conditions known to affect resting or hyperemic coronary blood flow. Increases in heart rate or preload reduced CFR because rCBFV was increased while hCBFV was unchanged. In contrast, changes in mean arterial pressure did not alter CFR. Proper interpretation of CFR measurements should take into account the hemodynamic conditions at which they are obtained.     

R wave amplitude during exercise. Relation to left ventricular function and coronary artery disease.

Change in R wave amplitude (mean delta R) was measured sequentially during and after 12 lead maximal treadmill exercise tests in 14 subjects with normal coronary arteries and 62 patients with coronary artery disease. In normal subjects mean delta R decreased maximally one minute after exercise and returned to control levels within three minutes. In contrast, mean delta R increased in patients with coronary artery disease, the greatest change occurring in patients with either triple vessel or left main disease or those with an akinetic region on the left ventriculogram. R wave amplitude returned to resting levels in five minutes. Increase in R wave amplitude was not directly related to changes in the ST segment. Changes in R wave amplitude during maximal treadmill exercise may improve the discrimination between patients with and without coronary artery disease and may help to identify those patients with abnormal left ventricular function.     

Lack of correlation between exercise capacity and indexes of resting left ventricular performance in heart failure

Symptoms of congestive heart failure occur most commonly during exercise, but cardiac performance is usually quantitated at rest. The relation between exercise capacity and measurements of cardiac performance at rest is little known. Treadmill exercise was performed in 21 patients with heart failure due to cardiomyopathy. Exercise duration averaged 9.1 ± 0.7 (standard error of the mean) minutes (normal value 12 or more minutes) and did not correlate with resting ejection fraction of 26.4 ± 2.7 percent (r = ?0.06). Left ventricular diastolic dimension of 6.6 ± 0.2 cm, mean velocity of circumferential fiber shortening and ratio of preejection period to left ventricular ejection time did not correlate with treadmill time (r = ?0.03). Repeat studies after treatment of heart failure also failed to show correlations between changes in exercise capacity and changes in left ventricular performance at rest. Thus, measures of left ventricular performance obtained at rest do not accurately reflect exercise tolerance and symptomatic status of patients with congestive heart failure.     

Left ventricular performance during exercise: Response of ear densitogram derivative

The peak derivative of the ear densitogram (PD) has been shown to track left ventricular (LV) function during exercise. Measured as percent change in amplitude from resting control, PD in normal subjects slowly and consistently increased throughout exercise and to 2 minutes of recovery, followed by return to control level. In contrast, PD in patients with coronary artery disease rapidly increased only to 1 minute of exercise, with no significant subsequent increase. Expressed as a percent change from control, the response of normal subjects differs significantly from that of patients with coronary artery disease at 1 and 4 minutes of exercise, and 2 minutes of recovery. The PD increase in normal subjects from end-exercise to 2 minutes of recovery may be attributable to the heart rate decreasing faster than venous return, associated with LV ejection time, which is significantly shorter than heart rate-predicted values 2 minutes after exercise.     

Position as a variable for cardiovascular responses during exercise

Twenty-one normal young male subjects underwent resting and exercise (bicycle) radionuclide angiography in the full supine and 70 degrees upright tilt positions in order to examine the effects of position on left ventricular size and performance, hemodynamics, and exercise duration. All subjects also underwent full (90 degrees) upright bicycle ergometry with respiratory gas analysis to establish the level of maximal exercise capacity for each. Body position significantly (p less than 0.05) affected resting and exercise cardiovascular parameters. End-diastolic and endsystolic left ventricular volumes and stroke volume were larger in the supine position, both at rest and during exercise. The cardiac output at rest and during exercise were comparable for the two positions; an increase in resting and exercise heart rate in the 70 degrees tilt position compensated for the reduced stroke volume of this posture. At maximal exercise, the 70 degrees upright position was associated with a greater response in left ventricular ejection fraction, otherwise this parameter was not position related. Exercise capacity, in terms of duration and workload, was significantly higher in the supine (1870 +/- 390 s) and full upright (1830 +/- 250 s) positions than in the 70 degrees tilt position (1730 +/- 260 s). Changes in body position significantly alter parameters of ventricular, cardiovascular, and exercise performance.     

Reversal of exertional hypotension after coronary bypass grafting.

A decrease in systolic blood pressure that occurs with treadmill exercise testing may be a sign of reversible ischemic left ventricular dysfunction. To test this hypothesis, we examined retrospectively the postoperative treadmill responses of 37 patients who had exertional hypotension (end exercise systolic blood pressure less than or equal to initial preexercise levels) before coronary arterial bypass grafting. This group of 37 patients was characterized preoperatively by an abnormal exercise electrocardiogram (36 patients), multiple vessel occlusive disease (36 patients) and a normal ejection fraction at rest (32 patients). Postoperative exercise tests showed improvement in hemodynamic and electrocardiographic changes with reversal of exertional hypotension (33 patients), and conversion to a normal exercise electrocardiogram (29 patients). Coronary bypass surgery can be expected to reverse exertional hypotension in patients with symptomatic angina pectoris and evidence of ischemia in the exercise electrocardiogram.     

Radionuclide angiographic evaluation of ventricular function in isolated congenitally corrected transposition of the great arteries

Eight asymptomatic patients (mean age 19 years, range 7 to 32) with congenitally corrected transposition of the great arteries (CCTGA) underwent equilibrium gated radionuclide angiocardiography at rest and during supine bicycle exercise to assess systemic (morphologic right) and pulmonary (morphologic left) ventricular function. Five patients had normal intracardiac hemodynamic values, 2 had trivial atrioventricular valve regurgitation and 1 patient had trivial pulmonary ventricular outflow tract obstruction. Average exercise duration was 11 +/- 1 minute, with limitation due only to fatigue. At peak exercise, heart rate increased 225% and systolic blood pressure 152% over the rest value. Pulmonary ventricular ejection fraction at rest was 51 +/- 3% (mean +/- standard error of the mean); it did not change significantly at peak stress, 53 +/- 2%. Systemic ventricular ejection fraction was 48 +/- 4% at rest and increased to 64 +/- 4% at peak exercise (p less than 0.01). Count-based volume changes for the pulmonary chamber showed no significant change in end-diastolic or systolic counts at peak exercise (109 +/- 8% and 106 +/- 9% of rest value, respectively). However, end-diastolic counts decreased 13% (87 +/- 3% of rest value) and end-systolic counts 34% (62 +/- 7% of rest value) at peak exercise in the systemic ventricle. These data suggest normal systemic and impaired pulmonary ventricular function in patients with congenitally corrected transposition of the great arteries unaccompanied by significant associated lesions. These findings have important clinical implications in the setting of complex congenital heart disease in patients in whom a morphologic right ventricle functions as the systemic pumping chamber. Despite the pulmonary ventricular dysfunction, symptoms were not apparent at rest or during exercise.     

Temporal evolution of changes in left ventricular function induced by cold pressor stimulation. An assessment with radionuclide angiography and gold 195m.

The evolutionary changes in left ventricular function induced by cold pressor stimulation were investigated at 90 second intervals by rapid sequential first pass radionuclide angiography using the short half life tracer gold 195m. The results in 12 subjects with normal coronary arteries were compared with those in 12 patients with coronary artery disease. Left ventricular ejection fraction fell significantly from resting values in both groups after 1 minute of cold pressor, but only in patients with coronary disease was the significant fall maintained at 2.5 and 4 minutes. In both groups, the maximum decrease in ejection fraction occurred after 1 minute, whereas the maximum rise in systolic blood pressure occurred after 2.5 minutes. New abnormalities of regional ventricular function developed in 10 normal subjects after 1 minute of cold, with a total of 12 new abnormal segments. Only two such segments were seen at the later stages of imaging. Twenty one new segments developed after 1 minute in the coronary disease group, and 13 segments remained abnormal after 4 minutes. Three patients, two of whom had left main stem stenoses, showed persistent abnormalities of ventricular function after 2 minutes of recovery from cold stimulation. Thus left ventricular function changes rapidly during a period of cold stimulation in both those without and those with coronary disease. When the cold pressor test is used with multiple gated equilibrium imaging, the timing of imaging may be crucial to the results and interpretation of the test. The discordance between functional changes and rise in blood pressure is further evidence that alterations in afterload are not solely responsible for cold induced abnormalities.     

Temporal evolution of changes in left ventricular function induced by cold pressor stimulation. An assessment with radionuclide angiography and gold 195m

The evolutionary changes in left ventricular function induced by cold pressor stimulation were investigated at 90 second intervals by rapid sequential first pass radionuclide angiography using the short half life tracer gold 195m. The results in 12 subjects with normal coronary arteries were compared with those in 12 patients with coronary artery disease. Left ventricular ejection fraction fell significantly from resting values in both groups after 1 minute of cold pressor, but only in patients with coronary disease was the significant fall maintained at 2.5 and 4 minutes. In both groups, the maximum decrease in ejection fraction occurred after 1 minute, whereas the maximum rise in systolic blood pressure occurred after 2.5 minutes. New abnormalities of regional ventricular function developed in 10 normal subjects after 1 minute of cold, with a total of 12 new abnormal segments. Only two such segments were seen at the later stages of imaging. Twenty one new segments developed after 1 minute in the coronary disease group, and 13 segments remained abnormal after 4 minutes. Three patients, two of whom had left main stem stenoses, showed persistent abnormalities of ventricular function after 2 minutes of recovery from cold stimulation. Thus left ventricular function changes rapidly during a period of cold stimulation in both those without and those with coronary disease. When the cold pressor test is used with multiple gated equilibrium imaging, the timing of imaging may be crucial to the results and interpretation of the test. The discordance between functional changes and rise in blood pressure is further evidence that alterations in afterload are not solely responsible for cold induced abnormalities.     

Long-term follow-up of cardiac function in patients with Hodgkin's disease treated with mediastinal irradiation and combination chemotherapy including doxorubicin

Among 41 evaluable patients whose first treatment for advanced Hodgkin's disease had consisted of alternating cycles of mechlorethamine, vincristine, prednisone, and procarbazine (MOPP), and doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), in addition to low-dose mediastinal irradiation, 19 underwent retrospective cardiac evaluation by routine posteroanterior and lateral chest x-ray, 12-lead ECG, M-mode echocardiogram, and ECG-gated left ventricular blood pool scan at rest and during exercise. Fifteen patients had unequivocally normal left ventricular function by all these parameters. Two patients had minimally reduced left ventricular ejection fraction (LVEF) at rest with a normal increment with exercise. In two other patients with high normal resting LVEF and subnormal increment with exercise, the elevated resting values implied initial measurement in a nonbasal state. A twentieth patient (the oldest; one of two with active Hodgkin's disease at the time of evaluation and the stimulus for this study) had markedly reduced LVEF as determined by radionuclide cardiac angiography and had developed clinical congestive heart failure shortly before evaluation. Despite this patient, the study indicates that treatment with MOPP/ABVD and low-dose mediastinal irradiation entails low risk for cardiac complications.     

Cardiac correlates of exercise induced pulmonary hypertension in patients with chronic heart failure due to left ventricular systolic dysfunction

BACKGROUND: Patients with chronic heart failure (CHF) due to left ventricular systolic dysfunction (LVSD) may develop pulmonary hypertension at rest and during exercise. The cardiac correlates of pulmonary hypertension have been ascertained in the resting state, but seldom during exercise in these patients. AIMS: We sought to determine the cardiac correlates of exercise induced pulmonary hypertension in patients with LVSD by monitoring the estimated pulmonary artery systolic pressure (PASP) by continuous Doppler echocardiography during semirecumbent bicycle exercise. METHODS: Eighty-five patients (mean age 57 +/- 13 years, 75% male) with CHF due to LVSD (LV ejection fraction [EF] <45%, mean LVEF 26 +/- 8%) were studied. RESULTS: Mitral effective regurgitant orifice area and E-wave were independent predictors of resting PASP. Resting PASP and exercise induced changes in PASP were unrelated (r =-0.08, P = 0.45). Decrease in LV end-systolic volume, increase in left atrial (LA) area, resting LV asynchrony, and decreased tricuspid annular plane systolic excursion (TAPSE) were independent predictors of exercise PASP. CONCLUSIONS: Resting LV asynchrony, impaired LV contractile reserve, and increase in LA dilatation correlate with the severity of exercise induced pulmonary hypertension in patients with CHF due to LVSD, while right ventricular systolic dysfunction is inversely related to the severity of exercise induced pulmonary hypertension.     

Left ventricular dysfunction in symptomatic mitral valve prolapse

Idiopathic MVP is characterized by a late systolic click or murmur from myxomatous mitral valvular dysfunction. It may be complicated by atypical chest pain, ventricular arrhythmias, and ECG changes that can mimic the symptoms of coronary artery disease. We prospectively performed radionuclide cineangiograms before and after stress tests in MVP patients with chest pain compared with asymptomatic MVP patients and symptomatic normal control patients. In ten patients with MVP, chest pain, and normal coronary anatomy, the LVEF remained essentially unchanged (increase of -0.5 +/- 4 percent) after exercise. In ten patients with MVP and no chest pain and in nine with normal cardiovascular system and chest pain, the exercise LVEF increased by 11.5 +/- 2 percent (p less than 0.05) and 17.4 +/- 3 percent (p less than 0.005), respectively. The resting LVEF was significantly lower (p less than 0.02) in the symptomatic MVP patients (59 +/- 3 percent) than in the asymptomatic MVP (76 +/- 5 percent) or symptomatic normal patient control subjects (70 +/- 3 percent). Patients with MVP and chest pain had a lower resting LVEF and an abnormal left ventricular functional response to exercise compared with asymptomatic MVP patients or symptomatic normal subjects. Therefore, exercise radionuclide ventriculography may not adequately differentiate between chest pain due to MVP or coronary artery disease.     

Influence of heart rate on stroke volume variability in atrial fibrillation in patients with normal and impaired left ventricular function

Both resting tachycardia and irregular ventricular rhythm may contribute to impaired cardiac performance in atrial fibrillation (AF). This study assesses the relation between resting heart rate and beat-to-beat changes in left ventricular (LV) ejection and filling in patients with normal and impaired LV systolic function. Beat-to-beat variation in LV outflow and inflow velocity-time integral was measured using pulsed Doppler ultrasound in 39 patients with chronic AF and normal (n = 22) or impaired (n = 17) LV systolic function. Aortic velocity-time integral variability increased with mean heart rate (p = 0.003) even though RR interval variability decreased (p <0.001). Aortic velocity-time integral was more sensitive to the duration of both the preceding (p <0.001) and prepreceding (p <0.001) RR intervals at higher heart rates. These relations were similar for patients with normal and impaired LV systolic function. The sensitivity of the filling velocity-time integral to RR interval variability also increased with heart rate (p <0.001). However, at higher heart rates the filling velocity-time integral (p = 0.009 ) and filling time (p = 0.005) were less sensitive to change in RR intervals in patients with impaired LV function. We conclude that beat-to-beat stroke volume variability in AF increases with heart rate. Stroke volume variability was not influenced by LV systolic function.