The patient with coronary heart disease at altitude: observations during acute exposure to 3100 meters

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1 Journal of Wilderness Medicine 1, (1990) The patient with coronary heart disease at altitude: observations during acute exposure to 3100 BJ. MORGAN!, J.K. ALEXANDER2*, S.A. NICOLI l and H.L. BRAMMELU JDivision of Cardiology, University of Colorado Health Sciences Center, Denver, Colorado, USA and 2Cardiology Section, Department ofmedicine, Baylor College ofmedicine, Houston, Texas, USA. Nine men with documented coronary artery disease who had exercise-induced angina and/or ST segment depression were studied by treadmill testing at 1600 m and during acute exposure to 3100 m altitude. Mean maximal oxygen uptake was reduced at altitude by 11% (range, 5-26%). Ventilation, heart rate, and systolic pressure at submaximal workloads were increased at 3100 m, but maximal values were unchanged. Oxygen saturation was reduced at rest, and during submaximal and maximal exercise (88.3 ± 14 vs 93.4 ± 0.7%). Angina and/or ST segment depression occurred at the same heart rate systolic pressure product, but at lower workloads. Systolic time intervals were unchanged at altitude. A target heart rate range of 70-85% of the ischemic end-point rate at lower altitude predicted an appropriate level of tolerable exercise at high altitude. We conclude that activity prescription for coronary patients with angina on arrival at high altitude should be based on heart rate rather than workload. Key words: altitude illness, coronary disease, heart disease Introduction Although the effects of altitude exposure on healthy persons have been studied extensively, little information is available concerning the response to altitude of persons with coronary heart disease. In normal subjects, acute exposure to high altitude is associated with increased heart rate, blood pressure, and ventilation, and decreased maximal oxygen consumption [1-4]. If similar effects take place in persons with coronary heart disease, myocardial ischemia and/or ventricular dysfunction might be precipitated with or without symptoms. We studied the cardiovascular and respiratory responses of nine patients with coronary disease to an acute exposure of 3100 m altitude. In addition, we evaluated commonly used methods of activity prescription to determine the safest and most appropriate means to provide activity guidelines during acute exposure to altitude. Materials and Methods Nine men (ages 50-75) residing in Colorado served as subjects. All had coronary artery disease which was documented by previous myocardial infarction, arteriography, or 20lTe scintigraphy. Subject selection criteria included: (1) Stable angina pectoris and/or electrocardiographic evidence of exercise-induced ischemia (ST depression). *To whom correspondence should be addressed at: 6550 Fannin, SM-1246, Houston, Texas /90 $ Chapman and Hall Ltd.

2 148 Morgan et al. (2) At least three months after clinical event of myocardial infarction, coronary artery bypass grafting, or unstable angina pectoris. (3) No significant pulmonary or musculoskeletal disease. Five of the nine subjects had previous myocardial infarction, and two of these had subsequently undergone coronary artery bypass graft surgery. Three subjects had stable angina pectoris without previous myocardial infarction. One subject had ST segment depression on the exercise electrocardiogram which was not associated with angina, but in whom an ischemic response was demonstrated by 201TQ scintigraphy. No subject had signs or symptoms of congestive heart failure at the time of entry into the study. Patient characteristics and medications are shown in Table 1. After providing informed consent, each subject underwent a cardiovascular physical examination and a complete blood count. Forced vital capacity and expired volume over the first second or forced expiration (FEV 1) were measured using a Stead-Wells Spirometer to rule out significant pulmonary disease. Table 1. Clinical data on nine men ages with coronary heart disease. Subject Clinical Ischemic endpoint Medications Angina ST depression CB* None No Yes None FB MI,CABG No Yes Sulfinpyrazone SB+ Angina Yes Yes Nitroglycerin p.r.n. DK MI Yes Yes 20 mg day-l RM MI,CABG No Yes Propranolol 120 mg day-l 20 mg day-l KM MI Yes Yes Nadolol 120 mg day-l CS MI Yes Yes Nadolol GS+ Angina Yes Yes Propranolol 1 LS+ Angina Yes Yes Propranolol MI: Myocardial Infarction; CABG: Coronary artery bypass grafts "'Exercise induced inferior wall perfusion deficit with redistribution on tomographic thallium imaging. +High grade stenosis of left anterior descending artery on arteriography.

3 Coronary heart disease at altitude 149 Subjects were evaluated by symptom-limited treadmill tests on two separate occasions in Denver (1600 m). During the treadmill evaluation, the 12-lead electrocardiogram (EKG) was monitored on a 3-channel electrocardiograph and recorded at the end of each minute of exercise. Blood pressure by cuff sphygmomanometry was measured and recorded at the same time intervals. Expired air was directed through a hot-wire anemometer and into a mixing chamber from which CO 2 and O 2 were measured by an LB-2 CO 2 analyzer (Beckman Instruments, Schiller Park, Illinois) and a fuel cell O 2 analyzer. The gas analysis equipment was on line to a micronova computer (Data General Corp., Southboro, MA) which printed oxygen consumption, carbon dioxide production, ventilation, tidal volume, respiratory rate, and respiratory quotient every 30 sec. A treadmill protocol was selected for each subject such that each symptom-limited test, which used 2 min stages, would require no more than 15 min of treadmill walking. For the more fit subjects, the protocol involved walking either 3.4 or 3.75 mph, with increases in grade of 2% per stage. The less fit subjects walked either 2.0 mph with 3.5% increase in grade per stage or 3.0 mph with 2.5% increase in grade per stage. The subjects reported the time at which angina first occurred during the treadmill exercise. The onset of polarization change was taken to be the time at which the ST segment became consistently depressed by 1.0 mm at 0.08 seconds after the J point. The onset of angina or ST segment depression, whichever came first, was identified as the ischemic endpoint. After onset of the ischemic endpoint, the patient was allowed to continue exercising to a symptom-limited maximal level. Measurement of blood oxygen saturation was done during treadmill exercise by an ear oximeter (472lOA Hewlett-Packard, Waltham, MA). Values for oxygen saturation were also printed every 10 sec. Systolic time intervals (QS2, LVET, PEP) were measured by simultaneous recording of the electrocardiogram, phonocardiogram, and carotid pulse tracing on a ContinueTrace 101 recorder (Irex Medical Systems, Ramsey, NJ). These measurements were made in the sitting position before and immediately after exercise. The Denver study evaluation protocol was repeated on a separate day in Leadville, Colorado (3100 m). All subjects travelled from Denver to Leadville by car (approximately 100 miles) and were studied within one hour of arrival. The laboratory equipment and personnel used for testing were transported between the two sites, and temperature was standardized in the two testing facilities. The time of day, time after a meal and time after medication were standardized for each subject. No subject required a change in the dose or type of medication during the course of the study. Paired t-tests were used to compare data secured at the two altitudes. P values of less than 0.05 were considered significant. Results Functional capacity Functional capacities of the nine subjects (measured at residence altitude of 1600 m) ranged from 12.6 to ml kg-1min- 1 (3.6 to 9.1 METs).

4 150 Morgan et al. Treadmill performance Exercise duration decreased from 10 ± 1 min (mean ± SEM) at 1600 m to 8 ± 1 min at 3100 m, p < Maximal oxygen uptake was reduced at the higher altitude (20.6 ± 2.6 vs 22.8 ± 2.2 ml kg- I min-l, p < 0.05) (Fig. 1). Oxygen uptake at comparable submaximal workloads was not different at the two altitudes. Treadmill exercise at altitude did not increase either the number or complexity of ventricular arrhythmias. 26 p< p< Max VO:! 22 (ml/kg/min) 20 Exercise 10 Duration (minutes) Fig. 1. Mean values and standard deviations for exercise maximal oxygen uptake and exercise duration at 1600 and 3100 m. Ventilation Minute ventilation was higher at 3100 m at the submaximal workload of 3 METs (33.1 ± 3.4 vs 26.2 ± 2.2 I min-l, p < 0.05). Minute ventilation at 5 METs showed a trend toward higher values at 3100 m (43.0 ± 2.6 vs 36.6 ± 1.8 I min-l, p = 0.12). Maximal ventilation, which occurred at a lower treadmill workload at 3100 m, was unchanged at the higher elevation (64.2 ± 5.4 vs 63.8 ± 5.3 I min-i). Arterial oxygen saturation Exposure to 3100 m resulted in decreases in saturation at rest (92.4 ± 1.5 vs 96.2 ± 1.0%, p < 0.01), during submaximal exercise at 3 METs (87.6 ± 2.3 vs 92 ± 2.9%, p < 0.05), at 5 METs (88.7 ± 1.1 vs 94.1 ± 1.08%, p < 0.01), and at maximal exercise (88.3 ± 1.4 vs 93.4 ± 0.7%, P <0.01). Hemodynamic variables Heart rate at rest and at 2 submaximal workloads (3 METs and 5 METs) was higher at 3100 m. There was no change, however, in maximum heart rate or heart rate at the onset of angina or ST segment depression (Table 2).

5 Coronary heart disease at altitude 151 Table 2. Heart rate, systolic blood pressure and heart rate systolic blood pressure product at 1600m and 3100m. Rest 3METs 5METs Maximal Ischemic exercise endpoint Heart Rate 1600m 59±4 96±6 110±5 135 ±9 119±7 (bpm) 3100m 64±4* 110±7* 124±8* 140±8 124±7 Systolic Blood 1600m 128±6 151±7 157±8 167±9 138±6 Pressure 3100m 129±7 164±7* 167 ±8* 171 ± ±7 (mm Hg) Heart Rate 1600m 7.6± ± ± ± ± 1.7 Blood Pressure 3100m 8.4± 1 18 ± 2.2* 20.8 ± ± ±2 Product (x 10-3 ) * = p< 0.05 Systolic blood pressure at rest was unchanged at 3100 m, as was systolic pressure at maximal exercise and at the onset of angina or ST segment depression. The systolic pressure at submaximal workloads was higher at 3100 m (Table 2). Heart rate, systolic blood pressure product at rest, maximal exercise, and onset of angina or ST segment depression were unchanged at the higher altitude (Table 2). However, the ischemic endpoint was reached at a lower workload, and thus after a shorter exercise period (Fig. 2). During submaximal work, heart rate systolic pressure product was higher at 3100 m, reflecting significant increases in both heart rate and systolic blood pressure. Diastolic blood pressure at rest and during exercise was unchanged at altitude n.s p< Minutes HR xsbp of x 10-2 Exercise at 150 at 6 Angina Angina erst' orst' Fig. 2. Mean values with standard deviation for heart rate systolic blood pressure product and minutes of exercise at the ischemic endpoint at 1600 and 3100 m.

6 152 Morgan et al. Systolic time intervals Duration of QS2 at rest (409.5 ± 8.3 vs ± 8.1 msec) and immediately after exercise ( vs loa msec) was unchanged at altitude. The PEP/LVET ratio at rest (DAD vs 0043 ± 0.02) and after exercise (0.26 ± 0.03 vs 0.27 ± 0.04) was also unchanged at altitude. Hematocrit and body weight Neither hematocrit (45.5 ± 1.2 vs 44.2 ± 0.8%) nor body weight (7.60 ± 4.5 kg) changed in response to acute altitude exposure. Pulmonary function Both forced vital capacity (304 ± 0.2 vs 3.8 ± 0.21, P < 0.05) and FEV1 (2.8 ± 0.1 vs 3.2 ± 0.11, P < 0.01) were reduced at 3100 m. Symptoms Two patients (FB and CS) reported shortness of breath after arrival at 3100 m. None of the other patients was symptomatic at altitude. Discussion At higher elevations, decreased atmospheric pressure is responsible for reduction in the partial pressure of oxygen in ambient and alveolar air. At sea level, alveolar oxygen tension is about 110 torr, while at 3000 m it falls to about 60 torr. Tissue oxygen requirements, however, are unchanged at high altitude. The adaptations which accompany short or long altitude exposure facilitate the delivery of oxygen to tissue. The responses of healthy persons have been characterized over a wide range of altitudes. These changes include an increase in heart rate at rest and at submaximal exercise workloads with no change in maximal heart rate [1]. A rise in systolic blood pressure at rest and with submaximal work has been documented. Minute ventilation has also been shown to increase at high altitudes at rest and at submaximal workloads, while maximal ventilation remains constant [4]. Arterial oxygen saturation decreases at rest and during submaximal exercise [2,4]. The study of patients with coronary heart disease showed similar responses to acute altitude exposure. The decrease in maximal body oxygen uptake that occurred in our subjects has also been well documented in healthy persons. Buskirk and co-workers have calculated the magnitude of the decrease to be approximately 3% for each 1000 feet of ascent above 5000 feet. Our subjects, who were exposed to a 5000 foot increase in altitude, demonstrated a mean reduction in maximal oxygen uptake of 11% (range, 5-26%). Exposure to altitude did not change the maximally tolerated heart rate systolic blood pressure product in our patients. However, since the maximally tolerated rate pressure product occurred at a lower external workload at altitude, exercise capacity and, therefore, maximal oxygen uptake were limited. The mechanisms by which maximal oxygen uptake is limited at altitude remain obscure. In our patients, reduced uptake did not appear to be due to a change in plasma and/or blood volume (indirectly assessed by hematocrit and body weight). Forced vital capacity and FEV1 were reduced at the higher altitude, but it is unlikely that this factor could limit oxygen uptake, since maximal ventilation was unchanged. Systolic ventricular

7 Coronary heart disease at altitude 153 function, assessed by systolic time intervals measured at rest and immediately after exercise, did not differ at the two altitudes. Therefore, left ventricular dysfunction did not appear to contribute to reduced exercise capacity at altitude in this acute setting. Ischemic endpoints (the onset of angina or abnormal repolarization) occurred at the same heart rate systolic blood pressure product at the two altitudes. However, the external workload at which the endpoint occurred was lower at 3100 m in eight of the nine patients (Fig. 2). This observation has relevance to activity counseling of the coronary artery disease patient who anticipates transient high altitude exposure, and suggests that a target heart rate range is a better guideline for safe activity levels at altitude than is an activity prescription based on workload alone. In view of the augmented sympathetic activity known to take place on ascent to altitude in normal subjects [5], and the preservation of systolic left ventricular function suggested by unchanged systolic time intervals, it seems probable that the effects we have observed are related to increased left ventricular afterload secondary to elevated catecholamines, rather than to global ventricular ischemia. Identifying an ischemic endpoint heart rate from a symptom-limited treadmill evaluation performed at the lower altitude and calculating a tolerable target heart rate range as 70-85% of the ischemic endpoint rate in all cases predicted an appropriate level for aerobic exercise at the high altitude. Because ischemic endpoints during exercise occurred at a lower workload at 3100 m than at 1600 m, activity guidelines based on the MET levels of tasks performed without symptoms at 1600 m would have resulted in heart rates at altitude in excess of those at which angina or ST segment changes occurred. We conclude that heart rate guidelines developed using the target heart rate method are more appropriate for patients with coronary heart disease on arrival at high altitude areas than are guidelines based on MET or workload. It must be noted that in addition to heart rate guidelines, other precautions are necessary, since activity at higher altitude may be associated with other stressors such as cold, wind, and isometric efforts which could precipitate symptoms. References 1. Consolazio, C.F., Nelson, RA., Matoush, L.a., et al. Energy metabolism at high altitude. J Appl PhysioI1966, 21, Hansen, J.E., Vogel, J.A., Stelter, G.P. and Consolazio, C.F. Oxygen uptake in man during exhaustive work at sea level and high altitude. J Appl Physiol1967, 23, Saltin, B., Grover, R.F., Blomqvist, C.G., et al Maximal oxygen uptake and cardiac output after 2 weeks at 4300 m. J Appl Physiol1968, 23, Grover, RF., Lufschanowski, R, Alexander, J.K. Alterations in the coronary circulation of man following ascent to 3100 m altitude. J Appl Physiol1976, 42, Cunningham, W.L., Becker, E.J., Kreuser, F. Catecholamines in plasma and urine at high altitude. J Appl Physiol1965, 20,