SYSTEMIC HYPERTENSION

Left Ventricular Systolic Response to Exercise in Patients With Systemic Hypertension Without Left Ventricular Hypertrophy Timothy F. Christian, MD, Alan R. Zinsmeister, PhD, Todd Il. Miller, MD, Ian P. Clement& MD, and Raymond J. Gibbons, MD Supine exercise radionuclide angiography was perlonned in 367 men to assess left ventricular (LV) systolic response to exercise; 58 had systemic hypertension without LV hypertrophy on a resting ehtmcadogram and 309 were normotensive. All patients met the following criteria defining a low pretest likelihood of coronary artery disease: age 120 beats/min. Patlents taking &receptor Mockers were exduded. There were no significant differemes between hypertendve and normotensive groups in peak exercise heart rate, workload or exercise duration. However, hypertensive patients had significantly higher peak exercise systolic blood pressures and peak exercise rate-pressure products. There were no diirences between patients with and without hypertension in resting ejection fractii, peak exercise ejsction fraction (hypertensive patients 0.71 f 0.01, normotensive patients 0.70 f 0.05) or change in ejection fraction at peak exercise (hypertensive patients 0.07 f 0.01, nofmotensive patients 0.07 f 0.04). Diastolic and systolic ventricular vdumes tended to be smaller in the hypertenrive patients, but the difference was not statlstiiiy signiftcant. The change in systolic volume with exercise was similar in the 2 groups (hypertensive -10 l 3 ml/m*, normotensive -10 f 1 ml/m*). In the absence of electrocardiographic evidence of LV hypertrophy, systemic hypertension does not influence LV systdic response to exercise. (AmJCardid 1990;6%1204-1208)

From the Division of Cardiovascular Diseasesand Internal Medicine, Mayo Clinic, Rochester, Minnesota. Manuscript received November 28, 1989;revised manuscript receivedand acceptedJanuary 22,199O. Addressfor reprints: Raymond J. Gibbons, MD, Mayo Clinic, 200 First Street S.W., Rochester,Minnesota 55905.

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THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 65

here have been multiple conflicting reports concerning the effect of systemic hypertension on the left ventricular (LV) systolic responseto exercisein the absenceof coronary artery disease.1-6Consequently, the noninvasive evaluation of hypertensive patients for coronary artery diseaseusing exerciseradionuclide angiography has been questiomA4y6There have been similar conflicting reports regarding the utility of thallium-201 scintigraphy in the diagnosis of coronary artery diseasein hypertensivepatients.7-8Many of these studies have used inhomogenous groups with varying degreesof hypertension, LV hypertrophy and likelihood of coronary artery disease.In a population referred for catheterization, 75% of patients with hypertension and normal coronary arteriograms had an abnormal LV systolic responseduring exerciseradionuclide angiography while only 29% of patients without hypertension had an abnormal response.6In contrast, a secondstudy reported abnormal LV responsesin 0.50. The major clinical indication for these studies was patient reassurance,in individuals who were asymptomatic. The following were grounds for exclusion: a cardiac pacemaker;congenital or valvular heart disease;previous cardiac surgery; congestiveheart failure; previous myocardial infarction; hypertrophic cardiomyopathy in the absenceof known hypertension or valvular disease;mitral valve prolapse;or presenceof left bundle branch block. In addition, patients with LV hypertrophy on the resting electrocardio-

gram using the vector criteria of Romhilt et al9 were excluded. Patients receiving a P-receptor blocker within 48 hours of exercise testing were also excluded. The study group was composedof 367 patients who met these criteria. These patients were then divided into 2 groups on the basis of the presenceor absenceof hypertension. Hypertension was defined as a chronic elevation in systolic pressure > 140 mm Hg or diastolic pressure >90 mm Hg, or, a history of antihypertensive therapy for >l year. Using these criteria, 58 patients were defined as hypertensive and 309 as normotensive. Forty-five percent of hypertensive patients were receiving antihypertensive medication at the time of exercise testing. The majority of treated patients (58%) were receiving diuretics alone; 23% of patients on medication were receiving a vasodilator alone and 19%were receiving combination therapy. Exercise

protocols

and radionuclide

angiography:

Rest and exercise radionuclide angiograms were obtained in the supine position. The 12 standard electrocardiogram leads were continuously monitored and recorded every minute. Blood pressure was monitored indirectly in the right arm with the use of a sphygmomanometer. The patient’s erythrocytes were labeled with the use of 30 mCi of technetium-99m and the modified in vivo method of Callahan et al.‘O After rest imaging, supine exercise was performed on a bicycle ergometer table. The exerciseprotocol began at a workload of 300 kpm/min (49 watt-seconds). The workload was increased every 3 minutes in increments of 300 kpm/min. The usual exercise endpoints used in our laboratory include the following: severefatigue; moderate or severechest pain; severearrhythmia; and marked electrocardiographic changes(horizontal or downsloping ST-segmentdepressionLO.2 mV). No patient in our study had exercise discontinued becauseof severe arrhythmia or electrocardiographic abnormalities. Two patients stoppedexercisedue to chest pain and the remaining patients stopped due to severefatigue. Repeat blood pool imaging was obtained during the last 2 minutes of each exercisestage in the left anterior oblique views that best separatedthe ventricles. Acquisitions were gated to the patient’s electrocardiogram and collected at 16 frames/cardiac cycle with the use of standard gamma cameras. A blood sample was obtained immediately after exercise for cardiac volume determinations. Heart rate and systolic and diastolic blood pressureswere obtained at rest, in each increment of exercise workload and at peak exercise. Data processing: Radionuclide data were processed with the use of a commercially available dedicatedcomputer systemand software (Medical Data Systems)and previously reported techniques.*‘J* Ejection fraction was calculated from the background-corrected LV counts versustime curve by useof a commercially available operator interactive program. The change in ejection fraction was computed as peak exercise ejection fraction minus rest ejection fraction. End-diastolic and end-systolic volumes were determined with a countbased method’3 and a previously reported regression equation.14The end-diastolic volume index was deter-

TABLE I Patient Characteristics Hypertensive Patients

in Normotensive

and

Characteristic

Normotensive

Hypertensive

No. of pts Age Ws) Cigarette smokers Diabetes mellitus Chest pain None Nonanginal

309 41(1749) 61% 1%

58 45 (2249) 63% 5%

42% 57%

34% 64%

mined by dividing end-diastolic volume by body surface area. The correlation coefficients for end-diastolic and end-systolic volumes determined by this method compared with contrast ventriculography have been previously reported as 0.85 and 0.94, respectively.14Previous studies15have shown that a single rest blood sample may be used for volume measurementsbecause,with this labeling method, plasma activity is unchangedwith exercise. Oxygen consumption (VO2) at peak exercise and metabolic equivalents (METS) were estimated as previously described.16 Data analyds/statistiil methods: Multiple clinical, exercise and radionuclide angiographic variables were summarizedfor each group. A logistic regressionanalysis was used to assessthe univariate associationof these variables with the patient group. The cumulative distribution functions for change in ejection fraction and exercise ejection fraction were plotted for each group; such plots display the entire spectrum of data without requiring the identification of any “normal” criteria. RESULTS Three hundred sixty-seven patients fulfilled the study criteria; 58 were determined as hypertensive and 309 as normotensive. The groups were similar in age, smoking history and the presenceor absenceof diabetes (Table I). Exercise hemodynamks: Resting heart rate, peak exerciseheart rate, exerciseintensity and peak workload were not significantly different between the hypertensive and normotensivepatients (Table II). Rest and exercisesystolic blood pressureand rest and exerciseheart rate-blood pressureproduct were all significantly higher in the hypertensivepatients, as was the changein systolic pressurewith exercise. Radionuclide angiographic test variables: There was no significant difference between the 2 groups in any radionuclide angiographic parameter (Table III, Figures 1 and 2). The mean resting ejection fraction was nearly identical in the 2 groups. Hypertensive patients increasedLV ejection fraction by a mean of 0.07 to a mean peak exercise ejection fraction of 0.71; normotensive patients also increased LV ejection fraction by a mean of 0.07 to a mean of 0.70. Hypertensive and normotensive patients had a similar spectrum of LV ejection fraction responseto exercise (Figure 1). The percentage of patients who failed to increase ejection fraction with exercise was identical (16% of hypertensive patients, 16%of normotensivepatients). HypertenTHE AMERICAN JOURNAL OF CARDIOLOGY MAY 15, 1990

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TABLE

II Exercise

Hemodynamics

for Normotensive

and Hypertensive

Patients

Hypertensive (mean f SEM) 71 f2 139f2

Rest heart rate (beats/min) Rest systolic BP (mm Hg) Rest diastolic BP Rest HR X systolic BP (beats/min X mm Hg) Peak exercise heart rate (beats/min) Peak exercise systolic BP (mm Hg) Peak exercise HR X systolic BP (beats/min X mm Hg) Change in systolic BP (mm Hg) Exercise METS Peak bicycle workload (median, kpm/min) BP = blood pressure:

HR = heart rate; METS = metabolic

equivalents

Normotensive (mean f SEM) 70fl 126fl 80&

89fl

1 8,901 f 121 154f 1 197 f 1

9,968 f 324 150f2 215f3 32,416 f 720 76f3 7.2 f 0.2 9co of exercise;

NS = not significant;

sive and normotensive patients also had a similar spectrum of peak exerciseejection fractions (Figure 2). The percentageof patients attaining a peak exerciseejection fraction LO.60 was also similar between the 2 groups (hypertensive patients 90%,normotensivepatients 87%). Ventricular volumes tended to be smaller in the hypertensive patients in both systole (36 f 3 ml/m2) and diastole (118 f 7 ml/m2) compared to normotensive patients (42 f 2 and 135 f 3 ml/m2), respectively. These differences were not statistically significant (Ta-

30,390 f 300 71 f 1 8.6 f 0.4 900 SEM = standard

p Value NS