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Vectorcardiographic Detection of Early Hemodynamic Abnormalities in Chronic Obstructive Pulmonary Disease* John R. Wilson, Robert John J. Picken, The M.D.; Ulysses G. Mason, III, C. Bahler, M.D., F.C.C.P.; M.D., F.C.C.P.; Edward and Gerald ability of the vectorcardiogram M.D.; H. Chester, M.D., L. Baum, M.D., to detect mild F.C.C.P.; F.C.C.P. ± 10.7 percent) or group 3 ( 1 7 . 8 ± 14.8 percent). Sixty- circulatory abnormalities in patients with chronic ob- five percent (13) of the 2 0 patients with hemodynamic structive pulmonary disease (COPD) is unclear. There- abnormalities had rightward terminal QRS forces of 15 fore, vectorcardiographic changes were correlated with percent or more, whereas only 8 percent (one) of the hemodynamic measurements made at rest and during 12 patients with normal hemodynamic data had such supine exercise in 3 2 patients with COPD and no clini- forces of 15 percent or more. The mean of the right- cal or electrocardiographic evidence of right ventricu- ward terminal QRS forces in 2 7 age-matched normal lar hypertrophy. Twelve patients had normal hemody- subjects was 5.0 ± namic data (group 1), nine had abnormal hemodynamic had forces of 15 percent or more. We conclude that data only during exercise (group 2 ) , and 1 1 had abnor- hemodynamic abnormalities are frequent mal hemodynamic exercise with COPD and no clinical evidence of right ventricu- (group 3 ) . The extent of rightward terminal QRS forces lar hypertrophy and that the vectorcardiogram provides noted on the vectorcardiogram was significantly less in an indirect method of detecting these abnormalities. data at rest and during 5.4 percent, and only one subject in patients group 1 (5.5 + 8.7 percent) than in either group 2 ( 1 9 . 0 T T e m o d y n a m i c abnormalities of the pulmonary circulation are found in over 50 percent of the Based on these correlations, we identified a simple vectorcardiographic criterion for detecting mild patients with chronic obstructive pulmonary disease hemodynamic abnormalities of the pulmonary circu- (COPD). lation in patients with C O P D . 1 - 8 These abnormalities range from nor- mal resting hemodynamics with abnormal circulatory responses to exercise " 1 monary hypertension. 4 The to severe resting pulclinical examination, MATERIALS AND METHODS Ambulatory patients with C O P D and a forced expiratory volume in one second ( F E V - J that was 7 5 percent or less of the predicted value were identified by reviewing data from pulmonary function tests and clinical records at Cleveland Metropolitan General Hospital and Cleveland Veterans Administration Hospital. Patients with intrinsic heart disease, hypertension, clinical signs of pulmonary hypertension, or prior episodes of respiratory failure were excluded. Thirtytwo patients agreed to participate in this study. Written informed consent was obtained. Twenty of these patients were also part of a multidisciplinary study on the treatment of C O P D . 1 2 electrocardiogram, 9 and vectorcardiogram 10,11 usu- ally allow detection of those patients with moderate or severe pulmonary hypertension; however, the detection of patients with mild hemodynamic abnormalities presently requires cardiac catheterization. T h e purpose of this study was to determine if the vectorcardiogram can also identify this latter group of patients. By comparing hemodynamic and vectorcardiographic data in a group of patients with C O P D , we found that a single vectorcardiographic measurement, the extent of rightward terminal QRS forces, correlated with hemodynamic measurements. * F r o m the Departments of Medicine, Cleveland Metropolitan General Hospital, the Veterans Administration Hospital, and Case Western Reserve University School of Medicine, Cleveland. Supported in part by grant 1 3 - P - 5 5 3 2 4 / 5 from the Social and Rehabilitation Services of the US Department of Health, Education, and Welfare. Manuscript received August 7; revision accepted February 1. Reprint requests: Dr. Bahler, Cleveland Metropolitan General Hospital, Cleveland 44109 160 1 3 Twelve-lead E C G s and vectorcardiograms using the Frank lead system were obtained. E a c h patient also underwent right heart catheterization on the same day or within a few days of the vectorcardiogram. Therapy with all medications was discontinued a minimum of 2 4 hours prior to hemodynamic study. At catheterization, the mean pulmonary arterial pressure, the pulmonary capillary pressure, and the cardiac output (indicator-dilution method with either indocyanine green or iced saline solution as the indicator) were measured at rest and again during the final minute of three to seven minutes of supine exercise on a bicycle ergometer set at between 1 5 0 and 3 0 0 kilopond • meters. Total pulmonary resistance was calculated as the mean pulmonary arterial WILSON ET AL Downloaded From: http://publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21056/ on 05/13/2017 CHEST, 76: 2, AUGUST, 1979 pressure divided by the cardiac output, and the pulmonary vascular resistance was calculated as the mean pulmonary arterial pressure minus the mean pulmonary capillary wedge pressure divided by the cardiac output. The E C G s were reviewed using the following criteria for right ventricular hypertrophy: ( 1 ) S j - Q pattern; ( 2 ) right axis deviation of 1 0 0 " or more; ( 3 ) Sj-S^Sg pattern; and ( 4 ) R/S ratio of one or less in leads V or V . Right ventricular hypertrophy was considered to be present if two criteria were met.T h e vectorcardiograms were classified into five types of horizontal loops, as shown in Figure 1A. T h e maximum QRS vector, the half-area QRS vector, the posterior/anterior ratio of millivolts, and the percentage of area of e a c h quadrant were measured on all horizontal and inferior loops as described previously. Only the extent of rightward terminal QRS forces was found to correlate with the hemodynamic m e a surements. This report will be confined to a discussion of this variable. The rightward terminal QRS force was calculated by using a plastic grid to measure the percentage area in both the right posterior quadrant in the horizontal loop and in the right inferior quadrant in the frontal loop ( s h a d e d areas, Fig I B ) . The rightward terminal QRS force was defined as the greater of these two measurements. The patients were divided into the following three groups based on the hemodynamic findings: ( 1 ) group 1, normal mean pulmonary arterial pressure or normal total pulmonary resistance both at rest and during exercise; ( 2 ) group 2, normal mean pulmonary arterial pressure or normal total pulmonary resistance at rest, with clearly elevated values for either or both with exercise; and ( 3 ) group 3, elevated mean pulmonary arterial pressure and total pulmonary resistance both at rest and during exercise. The normal value for resting mean pulmonary arterial pressure is 15 mm Hg (range, 10 to 18 mm H g ) and for resting total pulmonary resistance is 2 . 5 6 ± 0.64 u n i t s . ' During modest levels of exercise, the mean pulmonary arterial pressure normally rises to 2 0 mm Hg (range, 15 to 2 9 3 5 6 1 4 11 1 5 mm H g ) , while the total pulmonary resistance remains unchanged or decreases slightly. Normal subjects over 6 0 years of age may have mild elevations in total pulmonary resistance during e x e r c i s e . Criteria for the detection of abnormal hemodynamics were evaluated using the following two f o r m u l a s : ( 1 ) sensitivity equals the true-positives divided by the sum of the truepositives plus the false-negatives times 100; and ( 2 ) specificity equals the true-negatives divided by the sum of the false-positives plus the true-negatives times 100. F o r comparison, vectorcardiograms obtained from 27 agematched normal subjects were also analyzed for the extent of the rightward terminal QRS force. None of these subjects had smoked more than five years or within the past 15 years, and no subject had clinical or electrocardiographic evidence of cardiac or pulmonary disease. Statistical analysis was performed using standard least-squares methods for linear regression and Student's nonpaired f - t e s t . 17 1 9 20 21 22 RESULTS The characteristics of the 32 patients are noted in the following tabulation, showing the mean values (with ranges in parentheses): Age, yr 51(37-69) F E V , / (percent predicted) 47 ( 1 8 - 7 5 ) Arterial oxygen pressure ( P a 0 ) , m m H g 2 73 (54-98) Arterial carbon dioxide tension ( P a C O , ) , m m H g 3 5 ( 2 8 - 4 9 ) Electrocardiographic data Frontal-plane QRS axis, degrees Frontal-plane P axis, degrees S wave in lead V , m V 6 66(30-130) 70(59-90) 0.12(0-7) 1 6 F I G U R E 1. A (top), F i v e types of horizontal loops. Loops of types 1, 2, and 3 are oriented posteriorly, while types 4 and 5 have anterior orientation. B (bottom), Method for determining rightward terminal QRS forces. These were defined as greater of following two measurements: ( 1 ) percentage area in right posterior quadrant (horizontal l o o p ) ; and ( 2 ) percentage area in right inferior quadrant (frontal l o o p ) . One patient had an R / S ratio of less than one in lead Ve, and one patient had an S1-Q3 pattern. No patient had a Q R S duration exceeding 110 msec or electrocardiographic evidence of right ventricular hypertrophy. The results of catheterization and vectorcardiographic analysis are shown in Table 1 and Figures 2 and 3. There was no statistical difference in the mean age, Pa02, or F E V i among the three hemodynamic groups. Loops of types 1, 2, 3, 4, and 5 were found in 15, 8, 3, 1, and 5 patients, respectively. An initial anterior rightward (septal) force of greater then 10 msec was found in only 17 patients (53 percent). There was no correlation between hemodynamic variables and either the absence of a normal septal force or the type of vectorcardiographic loop. There was no correlation between terminal rightward Q R S forces and hemodynamic data when all 32 patients were considered; however, in patients with posteriorly oriented horizontal loops (types 1 to 3 ) , there was a linear correlation between terminal rightward Q R S forces and the mean pulmonary arterial pressure during exercise (r = 0.54; P < 0.01) (Fig 4 ) and the total pulmonary vascular CHEST, 76: 2, AUGUST, 1979 VCG DETECTION OF EARLY ABNORMALITIES IN COPD Type I Type Type 2 3 14 iZ Type Horizontal 4 Loop Type 5 Frontal Loop Downloaded From: http://publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21056/ on 05/13/2017 161 Table 1—Hemodynamic and Vectorcardiographic Group 1 Group 2 Group 3 50 52 52 F E V i , percent 51 + 18 51 ± 1 5 40 + 16 P a 0 , mm Hg Rest Exercise** 77 ± 1 3 72 ± 9 72 ± 8 71 ± 7 71 ± 7 62 + 10 Data Age, yr Pulmonary capillary wedge pressure, mm Hg Rest Exercise T o t a l pulmonary resistance, units f Rest Exercise Resting 50 Exercise Normal Normal range mean cn 4 0 2 Pulmonary arterial pressure, mm Hg Rest Exercise 60 Data* T" _1_ CZ t E -— 16±3 24 ± 3 17±3 34 ± 4 23 ± 4 40 ± 8 30 \< |o- 2 0 10 7±2 11 ± 3 7±2 14±2 10 + 4 18 + 7 0 Groupl ( n = 12) 2.71+0.54 2.72 ± 0 . 4 8 T e r m i n a l rightward Q R S forces, percent 5.5 ± 8.7 3.19 ± 0 . 4 6 4.30 ± 1 . 0 3 4.16±0.84 5.25 ± 1 . 2 0 19.0±10.7 17.8 ± 1 4 . 8 * T a b l e values are means ± S D . **Obtained in only six patients in each group. fArbitrary units, where total pulmonary resistance equals mean pulmonary arterial pressure divided by cardiac output. resistance during exercise (r = 0.41; P < 0.05) but not with resting mean pulmonary arterial pressure, resting total pulmonary resistance, or pulmonary vascular resistance. When only patients with type-1 loops were considered, the correlation between the rightward terminal QRS force and both the mean pulmonary arterial pressure during exercise and the total pulmonary resistance during exercise (r = 0.70; P < 0.01) was improved. Regardless of the configuration of the loops, vectorcardiograms in group 1 had significantly less terminal rightward QRS force (5.5 ± 8.7 percent) (P < 0.01) than either group 2 (19.0 ± 10.7 percent) or group 3 (17.8 ± 14.8 percent). Eighty-five percent ( 1 7 ) of the 20 patients with hemodynamic abnormalities had rightward terminal QRS forces of 5 percent or more, and 65 percent ( 1 3 ) had such forces of 15 percent or more. In contrast, only 25 percent (three) of the 12 patients with normal hemodynamic data had a rightward terminal QRS force of 5 percent or more, and only 8 percent (one) had a rightward terminal QRS force of 15 percent or more. When the presence of a rightward terminal QRS force of 5 percent or more was used to identify patients with abnormal hemodynamics, 85 percent of the patients in groups 2 and 3 were properly identified, with a specificity of 75 percent. By using a Group H ( n = 9) Group IE ( n • II) F I G U R E 2. Mean pulmonary arterial pressure ( P A ) at rest and during supine exercise for three groups. rightward terminal QRS force of 15 percent or more to identify these patients, the sensitivity dropped to 65 percent, although the specificity increased to 92 percent. In the 26 patients with loops of types 1 to 3, these same criteria were more sensitive, although the specificity remained approximately the same. In these 26 patients, when the criterion of a rightward terminal QRS force of 5 percent or more was used, 80 Resting Exercise 7 8 c o in 5 0 Normal range Normal mean 6 0 50 o> DC r5 c o 4.0 E r> 3 . 0 Q_ 0 0 Groupl Groupl GroupIU. (n=l2) (n-9) (n=ll) F I G U R E 3. Total pulmonary resistance at rest and during supine exercise is expressed in arbitrary units ( U ) , where total pulmonary resistance equals mean pulmonary arterial pressure divided by cardiac output. 162 WILSON ET AL Downloaded From: http://publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21056/ on 05/13/2017 CHEST, 76: 2, AUGUST, 1979 saturation correlated with hemodynamic data, although a trend toward a lower Pa02 during exercise was noted in group 3. These observations suggest that the development of right ventricular hypertrophy in COPD can begin at a time when resting pulmonary hemodynamics and arterial oxygenation are both relatively normal. Apparently, an abnormal increase in right ventricular work, even if it is only during exertion, is sufficient to bring about mild hypertrophy. 60 ,—, 50 O) X E £• < 0- 40 • 30 </) u L_ 0) X 20 Hi 0 '0 10 20 30 40 50 60 Rightward Terminal Forces (%) FIGURE 4 . Correlation of rightward terminal Q R S forces with mean pulmonary arterial pressure (PA) during exercise. Open circles indicate type -1 loops; solid circles indicate loops of types 2 and 3 ( n = 2 6 ; r = 0 . 5 4 ; P < 0 . 0 1 ) . the sensitivity was 94 percent, and the specificity was 70 percent; when the criterion of a rightward terminal QRS force of 15 percent or more was used, the sensitivity was 81 percent, and the specificity was 90 percent. The ages of the 27 normal subjects (range, 34 to 59 years) did not differ significantly from the patients. Only one subject had a rightward terminal QRS force of 15 percent or more, and the mean (5.0 ± 5.4 percent) was comparable to group 1. DISCUSSION This study demonstrates that the vectorcardiogram offers a simple noninvasive method of detecting mild hemodynamic abnormalities in patients with COPD. By superimposing a plastic grid over a patient's horizontal-plane and frontal-plane vectorcardiographic loops, the extent of terminal rightward QRS forces is easily calculated. Based on the measured value for such forces and the criteria outlined previously, one can determine the likelihood that a patient has abnormalities of the pulmonary circulation. The basis for this increased workload is an abnormal increase in pulmonary arterial pressure during exercise, rather than any excessive increase in cardiac output. Why there is an abnormal exertional increase in pressure is unclear. Previous investigators have demonstrated that hypoxia, hypercapnia, and acidosis are partially responsible for elevation of the pulmonary arterial pressure during exercise in patients with moderate to severe pulmonary hypertension; - ' * however, it is unlikely that the pulmonary hypertension during exertion seen in our patients, particularly in those in group 2, was due to such chemical stimuli, since we observed only minimal changes in Pa02, PaC02, and pH during exercise in most of the patients. 1 5 2 It is also unlikely that left ventricular dysfunction was responsible for the pulmonary hypertension. Although several patients did have an elevated pulmonary capillary pressure during exercise, none of the patients had any clinical or electrocardiographic evidence of left ventricular disease, and none had an elevated pulmonary capillary pressure at rest. Furthermore, an exercise-induced increase in pulmonary capillary pressure has been observed in many patients with C O P D . This increase is thought to be due to mechanical factors related to the pulmonary disease. " For example, Lim and Brownlee demonstrated a good correlation between pulmonary capillary pressure and intraesophageal pressure during exercise in patients with COPD, thus demonstrating that the marked fluctuation in intrathoracic pressures commonly observed in patients with COPD clearly influences the observed pressures in the pulmonary circulation. 3,4 25 27 5 In our patients, these abnormalities could not be anticipated with either resting arterial blood gas levels or pulmonary function tests. Although significant correlations between the mean pulmonary arterial pressure and both the arterial oxygen saturation ' and the F E V i have been reported, such correlations are obtained only when patients with moderate to severe pulmonary hypertension are included in the group under study. In our patients, neither the F E V i nor the resting oxygen Regardless of the actual stimulus to the pulmonary hypertension, it is clear from our study that the vectorcardiogram is more sensitive than originally thought to mild abnormalities of the pulmonary circulation. Previous investigators correlated the vectorcardiogram with the resting pulmonary arterial pressure in patients with COPD and known pulmonary hypertension or clinically suspected right ventricular hypertrophy. Our study extends the use of the vectorcardiogram to a group of patients with CHEST, 76: 2, AUGUST, 1979 VCG DETECTION OF EARLY ABNORMALITIES IN COPD 163 9 13 23 2 S 10 11 Downloaded From: http://publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21056/ on 05/13/2017 COPD in whom abnormalities of the pulmonary circulation were not known to be present and confirms that the presence of a rightward terminal Q R S force of 15 percent or more is a sensitive and specific indicator of abnormal pulmonary hemodynamics. W e have also shown that in patients without marked pulmonary hypertension, vectorcardiographic changes correlated more closely with exertional than with resting hemodynamic measurements. Consequently, correlation of the vectorcardiogram with only resting hemodynamic data will underestimate the ability of the vectorcardiogram to detect hemodynamic abnormalities. This apparent sensitivity of the vectorcardiogram to altered pulmonary hemodynamics makes it necessary to exclude smokers from a "normal" population when defining the normal vectorcardiogram. Inclusion of some smokers with subclinical COPD and associated abnormalities of the pulmonary circulation could bias the data. This is supported by the rarity of an increased rightward terminal Q R S force in our age-matched control group. In conclusion, mild hemodynamic abnormalities are frequently present in patients with COPD and no clinical evidence of pulmonary hypertension. The vectorcardiogram appears to provide an effective noninvasive method of detecting these abnormalities. Moreover, it appears that the extent of the rightward terminal Q R S force may represent a more sensitive index of excessive right ventricular work than do resting hemodynamic measurements. Therefore, the vectorcardiogram may offer a sensitive method of detecting patients who are at risk to develop cor pulmonale and of following the effects of therapeutic methods, such as long-term therapy with supplemental oxygen, that are used to reduce right ventricular work. A C K N O W L E D G M E N T : W e thank Dr. Charles Duncan, who greatly assisted in the initial aspects of the study. REFERENCES 1 Burrows B, Kettel L J , Niden AH, et al: Patterns of cardiovascular dysfunction in chronic obstructive lung disease. N Engl J Med 2 8 6 : 9 1 2 - 9 1 8 , 1 9 7 2 2 Riley R L , Himmelstein A, Motley H L , et al: Studies of the pulmonary circulation at rest and during exercise in normal individuals and in patients with chronic pulmonary disease. Am J Physiol 1 5 2 : 3 7 2 - 3 8 2 , 1948 3 Jezek V, Schrijen F, Sadoul P: Right ventricular function and pulmonary hemodynamics during exercise in patients with chronic obstructive bronchopulmonary disease. 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Clin Sci 3 7 : 5 0 3 - 5 1 7 , 1969 VI ASIA-PACIFIC CONGRESS ON DISEASES OF THE CHEST Sponsored by the International Academy of Chest Physicians and Surgeons, affiliated with the American College of Chest Physicians Bombay, India Host: The Indian Chapters President: Raman Viswanathan, M.D. Symposia subjects: Cardiomyopathy Valvular surgery Rheumatic heart disease (medical and surgical management) Surgical management of coronary artery disease Pulmonary hypertension Surgery of the heart in infants Hypertension Noninvasive diagnostic techniques in cardiology Myocardial preservation Guest lectures Free papers November 18-22,1979 Organizers: Western India Chapter Honorary President: K. K. Datey, M.D. Early diagnosis and management of lung cancer Shortterm chemotherapy of pulmonary TB Acute respiratory failure Pathogenesis and management of COLD Immunology of lung diseases Lung infestations Surgery of the mediastinum Occupational Lung diseases Social Program Post-congress Tours For information and registration forms, write to: Dr. Aspi R. Billimoria Secretary General, VI APCDC L. D. Ruparel Medical Centre Dr. Annie Besant Road Worli, Bombay 400 025, India Silver Jubilee Session, East India Chapter, ACCP A three-day scientific program will be presented by the East India Chapter of ACCP to commemorate their Silver Jubilee. The meeting will take place at the Park Hotel, Calcutta, India, November 11-13. For information, contact Dr. S. K. Bose, Secretary General, 190/B Rashbehari Avenue, Calcutta 700 029, India CHEST, 76: 2, AUGUST, 1979 VCG DETECTION OF EARLY ABNORMALITIES IN COPD Downloaded From: http://publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21056/ on 05/13/2017 165