Relation of electrocardiographic R-wave amplitude to changes in left ventricular chamber size and position in normal subjects

MISCELLANEOUS TOPICS

Relation of Electrocardiographic R-Wave Amplitude to Changes in Left Ventricular Chamber Size and Position in Normal Subjects TED FELDMAN, MD, KENNETH M. BOROW, MD, ALEX NEUMANN, BS, ROBERTO M. LANG, MD, and RORY W. CHIDERS,

MD

Although exercise-induced changes in electrocardiographic R-wave amplitude have been ascribed to changes in left ventricular (LV) size, QRS axis, heart rate and ischemia, the physiologic mechanism remains unclear. To clarify the relation between R-wave amptitude and changes in LV size and position, simultaneous O-lead electrocardiograms and targeted M-mode echocardiograms were recorded from 15 normal subjects. Recordings were made at rest, during Valsalva maneuver and during methoxamine infusion. LV diastolic dimension increased with methoxamine and decreased with Vaisalva maneuver (p
change in LV dimension was 0.81 (p
Changes in electrocardiographic QRS amplitude have been noted during dynamic exercise. Although these changes may improve the predictive value of exercise testing for the diagnosis of coronary artery disease,1-5 their physiologic mechanism is complex. It has long been suggestedthat conditions that causechangesin left ventricular (LV) chamber size cause alterations in the electrocardiographic QRS complex amplitude.6 This has been inferred from the observation that QRS voltage increases after the pause following a ventricular premature complex, after infusion of saline solution and during elevation of the legs. All of these maneuvers cause an increase in cardiac blood volume.6-10 This phenomenon has been linked to the Brody effect7 De-

spite these findings, the relation between QRS complex amplitude and LV chamber size remains controversial.11-20Factors such as ischemia,21 QRS-axis shifts,22 or changes in intramyocardial conductioni have been suggested as major determinants of R-wave amplitude changes. During exercise, R-wave amplitude changes may be further influenced by a change in respiratory pattern, the position of the heart in the thorax and the amount of air or blood in the lungs.23 This study examines R-wave amplitude changes in the absence of these confounding factors.

From the Cardiology Section, Department of Medicine, University of Chicago Medical Center, Chicago, Illinois. This study was supported in part by Training Grant ,2-T32-HL07381 from the National Heart, Lung, and Blood Institute, Bethesda, Maryland. Manuscript received November 9, 1984; revised manuscript received December 20, 1984, accepted December 31, 1984. Address for reprints: Ted Feldman, MD, University of Chicago Hospital, 950 East 59th Street, Box 250, Chicago, Illinois 60637.

(Am J Cardiol 1985;55:1188-1174)

Methods The study population consisted of healthy men, aged 21 to 33 years. All subjects had normal intracardiac anatomy and LV performance on 2-dimensional(2-D) echocardiographic study as well as a normal scalar electrocardiogram. Scalar electrocardiograms, 2-D and targeted M-mode echocardiograms, and calibrated carotid pulse tracings were recorded simultaneously from 10 subjects. Recordings were madeunder resting conditions, during Valsalva maneuver,24 and at peak pressor effect induced by the al-adrenergic agonist methoxamine.25*26 In 8 subjects simultaneous targeted

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M-mode echocardiograms and electrocardiograms were recorded at end-expiration in the supine and left lateral decubitus positions under baseline conditions at rest without other interventions. Electrocardiograms were recorded during held end-expiration on a Marquette Electronics MAC II microcomputeraugmented cardiograph. This system records simultaneously 10 seconds of the unipolar chest leads, and derives the frontal plane electrocardiogram from 2 of its constituent leads. Leads Vz, Vs and Vd were not recorded to allow echocardiographic imaging during the electrocardiographic recording. The electrocardiographic recorder was programmed to average R-wave amplitude from all QRS complexes in a given lead. In this manner variations in R-wave amplitude during any single recording were minimized. R-wave amplitude was measured as the vertical distance from the PR segment to the peak of the R wave. The experimental protocol used for echocardiographic recording in this study has been described in detai1.2s-27Simultaneous recordings of the targeted LV M-mode echocardiogram, phonocardiogram, electrocardiogram, indirect carotid pulse tracing and blood pressure measurements were performed at held end-expiration under baseline conditions. Peak systolic and diastolic blood pressure determinations were made with the Dinamap”” 1846P Vital Signs Monitor (Critikon). This device estimates accurately central aortic pressure over a wide range of systolic and diastolic blood pressures independent of the patient’s cardiac index, systemic vascular resistance, LV ejection fraction and body surface area.zs12s All recordings were repeated at the peak effect of the strain phase of a Valsalva maneuver, when the LV end-diastolic dimension was smallest. All subjects then received 0.01 mg/kg of atropine sulfate intravenously 10 minutes before an intravenous infusion of methoxamine (infusion rate 1 mg/min). When peak systolic blood pressure had increased by 30 to 60 mm Hg above baseline (depending on baseline blood pressure observations), the methoxamine infusion was discontinued. The peak pressor effect lasted 2 to 5 minutes, during which time another set of end-expiratory echocardiographic, phonocardiographic, calibrated carotid pulse and electrocardiographic recordings was made.

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LV dimensions and wall thicknesses were measured as previously described from targeted M-mode echocardiograms recorded on a Hewlett-Packard ultrasound imaging system (model 77020A).2”27 In addition, the distance from the chest wall to the leading edge of the right septal surface and from the chest wall to the leading edge of the LV posterior epicardial surface were measured. Distance from the chest wall (adjacent to the Vs electrocardiographic electrode) to the LV apical endocardium was measured from targeted M-mode echocardiograms performed with the transducer in the apical 4-chamber position. This distance was measured from the first chest wall echo to the trailing edge of the LV apical endocardium. LV meridional wall stress at end systole was calculated using a previously validated formula.2a-2s All echocardiographic measurements were taken as the average of 3 to 5 cardiac cycles. Echocardiographic tracings were digitized and analyzed on a Franklin Quantic 1200 analog-to-digital computer. Statistical analysis: Paired t tests were performed to compare baseline values with data obtained at peak Valsalva and methoxamine effects. A p value <0.05 was considered statistically significant. To test the relation between 2 variables, correlation coefficients were calculated by least-squares linear regression analysis. Group data are expressed as mean f standard deviation.

Results Changes in left ventricular chamber size: In all subjects, LV dimension decreased at peak Valsalva maneuver and increased at peak methoxamine effect (p
PCG

FIGURE 1. Targeted M-mode echocardiographic recordings of the left ventricle from a subject under resting conditions and at peak Valsalva and methoxamine effects. Left ventricular chamber (LV) size decreased during Valsalva maneuver, and increased at peak methoxamine effect compared with resting conditions. CPT = carotid pulse tracing; LSS = left septal surface; LVP = LV posterior endocardiun; PCG = phonocardiogram; RSS = right septal surface; RV = right ventricular chamber.

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FIGURE 2. A, left ventricular (LV) enddiastolic dimensions (Ded) and endsystolic dimensions (Des) decreased during Valsalva maneuver (dots) and increased at peak methoxamine effect (squares). B, in all cases LV enddiastolic dimension decreased during Valsalva maneuver and increased at peak methoxamine effect.

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Changes in R-wave amplitude: During interventions, R-wave amplitude did not change consistently in electrocardiographic leads I, II, III, aVR, aVL, aVF or VI. Significant R-wave amplitude changes did occur in precordial leads V5 and Vs (Fig. 3 and 4). For each subject the lead showing the greatest change was used in this analysis. There was a 21% increase in R-wave amplitude with methoxamine infusion and a 17% decrease with Valsalva maneuver (p
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V6 -J FIGURE 3. Electrocardiographic recording of leads Vs and Vs from a typical subject. Compared with baseline (B), there was an increase in R-wave amplittxle with methoxamine infusion (M) and a decrease during Valsalva maneuver (V).

with LV dimension at end-diastole. In every case, interventions resulted in directionally similar changes in R-wave amplitude and LV end-diastolic dimension (r = 0.65, p
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FIGURE 4. A, electrocardiographic R-wave amplitude decreased during Valsalva maneuver (dots) and increased with methoxamine infusion (squares). B, changes in R-wave amplitude paralleled changes in left ventricular dimension in all subjects.

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FIGURE 5. Effects of supine and left lateral patient position. A, electrocardiographic R-wave amplitude increased significantly with movement of the left ventricle toward the chest wall in the left lateral position. B, this increase in R-wave amplitude was not associated with a change in left ventricular end-diastolic dimension. NS = not significant; SD = standard deviation.

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significant increase in R-wave amplitude was noted in electrocardiographic leads I, II, III, aVR, aVL, aVF or Vi. In addition, the frontal-plane QRS axis did not change. There was no concomitant change in LV enddiastolic dimension (0.0 f 0.1 cm) and no significant change in distance from the chest wall to LV posterior wall (0.5 f 0.4 cm). Changes in heart rate: Mean heart rate increased 19 f 18 beats/min with Valsalva maneuver and 11 f 18 beats/min at peak methoxamine effect (p CO.01and p <0.05, respectively). The correlation between R-wave amplitude and heart rate was poor (r = -0.08, p = not significant). Discussion Electrocardiographic R-wave amplitude correlated well with the distance of the heart from the chest wall as LV dimensions varied. Distance from the LV to the precordial recording electrodes thus appears to be a major determinant of R-wave amplitude. In addition, the distance from the LV apical endocardium to the lateral precordial electrocardiographic leads was associated with marked changes in Vs and Vs R-wave amplitude, without any significant change in the frontal leads or Vi R-wave amplitude. These changes were seen without change in LV chamber size, and demonstrate the importance of proximity of the LV to the chest wall as a determinant of R-wave amplitude independent of LV chamber size. Relation of left ventricular volume to R-wave amplitude: Brody,7 using a mathematical model, suggested that intracardiac blood, a highly conductive mass, augments the electrocardiographic surface potential if the progress of myocardial excitation is radial to the blood mass. The present study demonstrates a close linear correlation between R-wave amplitude and

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METHOXAMINE FIGURE 6. Left ventricular chamber size and position as they relate to the location of the lateral precordiai electrocardiographic leads. During Vaisaiva maneuver the left ventricle moves away from the lateral precordium as ventricular dimension decreases. Methoxamine infusion results in increased left ventricular size and increased proximity of the chamber to the lateral chest wail. in the left lateral position the heart moves toward the chest wail without any change in chamber size from baseline. A = anterior; L = left; P = posterior; R = right.

changes in LV dimension. Since LV dimension and volume closely parallel one another,“0 especially in subjects without regional wall motion abnormalities, changes in the LV intracavitary blood volume would also be a major determinant of R-wave amplitude. This supports the concept of a Brody effect. However, a change in LV intracavitary blood volume alters the proximity of the left ventricle to the precordial electrocardiographic recording electrodes (Fig. 6). The effect of change in proximity of the left ventricle to the chest wall, rather than change in the electrical effect of the LV blood mass, may be responsible for changes in R-wave amplitude. Distance from the left ventricle to the chest wall: Distance of the heart from the chest wall was considered a major determinant of R-wave amplitude in a study by LaMonte and Freiman31 of the electrocardiogram after mastectomy. These investigators noted increased precordial R-wave amplitude after left mastectomy and less prominent increases in left precordial voltage after right mastectomy. Changes in left precordial leads after right mastectomy suggest that the electrical properties of the chest wall, in addition to distance of the heart from the chest wall, are important determinants of R-wave size. With mastectomy, as in the present study, no significant changes were seen in the frontal leads. This latter finding further supports the contention that distance between the left ventricle and the chest wall is an important determinant of R-wave amplitude, since the major effects of this distance are reflected in the horizontal plane. The Valsalva maneuver resulted in a decreasein right ventricular chamber size and subsequent movement of the right septal surface toward the anterior chest wall. Movement of the LV posterior wall toward the anterior chest wall and away from the lateral chest wall during VaIsalva maneuver reflects the combined effects of a decrease in both left and right ventricular end-diastolic dimensions (Fig. 6). With methoxamine infusion, no change in right ventricular size was noted, consistent with the fact that LV afterload challenge in normal subjects does not alter right ventricular hemodynamics.32Finally, LV size increased at peak methoxamine effect, increasing the distance from the anterior chest wall to the LV posterior wall and moving the left ventricle closer to the lateral chest wall (Fig. 6). The position of the heart relative to the lateral chest wall was measured by echocardiogram with the transducer near the Vs electrode. The distance from the chest wall near the V5 electrode to the LV apical endocardium was correlated with R-wave amplitude. A striking increase in R-wave amplitude was evident simply by turning subjects into the left lateral position. These changes were not associated with changes in LV dimensions (Fig. 5). Furthermore, no significant change in R-wave amplitude was noted in the frontal leads or in lead Vi. Since distance from the chest wall varied with changes in LV chamber size caused by both Valsalva maneuver and methoxamine infusion, the change in proximity to the chest wall, rather than a volume change, may explain the observed R-wave amplitude

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changes. Thus, the distance from the LV to the chest wall appears to be a major determinant of R-wave amplitude independent of LV chamber size. Effects of heart rate and exercise: Dynamic exercise is associated with changes in sympathetic tone, heart rate, respiratory pattern and the volume of air and blood in the lungs. Because the subjects in our investigation were studied under controlled conditions without the use of dynamic exercise, most of these variables could be effectively eliminated as confounding factors. During dynamic exercise or atria1 pacing, alterations in LV chamber size are heart rate-dependent.“” In our study, heart rate increased with both Valsalva maneuver and methoxamine challenge, while R-wave amplitude moved in opposite directions. This clearly demonstrates that heart rate alone is not a major determinant of Rwave amplitude. Electrocardiographic factors: We observed prominent R-wave amplitude changes in leads V5 and Vs. However, no significant changes were noted in the frontal leads or in lead Vi. This suggests that failure to record multiple electrocardiographic leads may leave a change undetected. The averaging of R-wave amplitude from many planar leads may mask a change in a single lead, especially since the duration of R-wave amplitude change is brief. The use of an electrocardiographic recording system that acquires multiple leads simultaneously during an intervention, rather than recording single leads sequentially after an intervention, is essential for detection of transient R-wave amplitude variations. Shifts in QRS axis have been suggested as a mechanism of R-wave amplitude change.22We did not observe any change in the frontal-plane QRS axis. Effect of ischemia: Electrocardiographic R-wave amplitude changes resulting from myocardial ischemia may result from precipitation of ventricular asynergy, changes in intramyocardial conduction,l7 or by a change in LV chamber size.35R-wave amplitude changes noted during exercise or atria1 pacing may be influenced by both LV size and the presence of myocardial ischemia. In this study the effects of change in chamber size could be evaluated independent of the influence of ischemia. Methodologic considerations: Several studies have failed to demonstrate a relation between R-wave amplitude and LV size.12-lg This may be because singlelead electrocardiographic systems were used, QRS amplitudes were averaged from many leads, the influence of myocardial ischemia, or the varied physiologic effects of dynamic exercise.12-l” Studies using pacing or exercise compare LV volumes at rest to the decreased volumes associated with significant tachycardia.sJs When patients with ischemic heart disease are studied, the resting condition is compared with increased LV size associated with LV dysfunction. The present investigation eliminates the confounding effects of ischemia and the problems associated with exercise in comparing variations in LV chamber size alone to R-wave amplitude change. Clinical implications: LV chamber size and distance of the heart from the chest wall may influence R-wave

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amplitude in numerous clinical settings including cardiac transplant rejection, acute myocardial infarction, dynamic exercise testing and the pharmacologic treatment of systemic hypertension. When factors such as ischemia, LV systolic or diastolic dysfunction, or the many effects of dynamic exercise are present, the relative contribution of each to R-wave amplitude is complicated further. Thus, the importance of LV chamber size and position relative to the precordial recording electrodes must be considered when assessing the importance of changes in R-wave amplitude. References 1. Bonorls PE, Greenberg PS, Castellanet MJ, Ellestad MH. Significance of changes in R wave amplitude durina treadmill stress testing: angiographic correlation. Am J Cardiol 1978;41:846-851. 2. Bono& PE, Greenberg PS, Chrlstlson GW, Castettanet MJ, Etlestad MH. Evaluation of R wave amplitude changes versus ST segment depression in stress testing. Circulation 1978;57:904-910. 3. Chrtsttson GW, Bonorts PE, Greenberg PE, Castellanat MJ, Eltestad MH. Predicting coronary artery disease with treadmill stress testing: changes in R wave amplitude compared with ST segment depression. J Electrocardiol 1979:12:179-85. 4. Greenberg PS, Ellestad MH. Ability of R wave change during stress testing to accurately detect coronary disease in the presence of left bundle branch block at rest. Angiology 1980;31:230-237. 5. Uhl OS, Hopklrk JA. Analysis of exercise induced R wave amplitude changes in detection of coronary artery disease in asymptomatic men with left bundle branch block. Am J Cardiol 1979;44:1247-1250. 6. Lepeschkln E, Wllson FN. f&darn Electrocardiography. Baltimore: Williims 8 Wilkins, 1955:234-235. 7. Brody DA. A theoretical analysis of intracavitary blood mass influence on the heart-lead relationship. Circ Res 1956;4:731-738. 8. Rudy Y, Plonsey R, Leibman J. The effects of variations in conductivity and geometrical parameters on the electrocardiogram, using an electrical spheres model. Circ Res 1979;44:104-111. 9. Danlels S, Iskandrlan AS, Hakkl AH, Kane SA, Bemls CE, Horowitz LN, Greenspan AM, Segat BL. Correlation between changes in R wave amplitude and left ventricular volume induced bv. raoid atrial pacing. Am Heart J 1984;107:711-716. 10. Battler A, Froellcher VF, Gallagher KP, Kumada T, McKown D. Effects of changes in ventricular size on reaional and surface QRS amplitudes in the conscious dog. Circulation 198662:174-80. 11. Ellestad MH. The mechanism of exercise induced R wave amplitude changes coronary Arch Intern Med .__._ in___ ___ heart disease: still controversial. 12. tskandrlan AS, Hakki A, Mlntz GS, Anderson GJ, Kane SA, Segal BL. Changes in R wave during exercise: a correlation with left ventricular function and volumes. Cardiovasc Rev Rep 1983;3:245-352. 13. Davld DD, Kttchen JG, Michelson EL, Nafto M, Sawln HS, Chen CC. R wave amplitude responses to rapid atrial pacing; a marker for myocardial ischemia. Am Heart J 1984;107:53-81. 14. Deanfleld JE, Davles 0, Mongtadl F, Savage C, Selwyn AP, Fox KM. Factors influencing R wave amplitude in patients with ischaemic heart disease. Br Heart J 1983:49:8-14. 15. Battler A, Froellcher V, Slutsky R, Ashburn W. Relationship of QRS amplitude changes during exercise to lefl ventricular function and volumes and the diagnosis of coronary artery disease. Circulation 1979;60: 1004-1013. Amrnn K, UchlyAmA I. KAwAhArA 16. acute changes in&h ventricular size ’.” ’ ‘aQ”‘“-3:279-292. II”G,L. =abe Y, Chen CC, Morganroth J, _._I conduction; a major determinant mvocardial ischemia. Circulation 1982;65:161-167. 10. Davtd D, Nalto M, Chen CC, Michelson EL, Morganroth J, Schaffenburg M. R wave amplitude variations during acute experimental myocardial ischemia: an inadequate index for changes in intracardiac volume. Circulation 1981;63:1364-1371. lg. Tatbot S, Kllpatrlck D, Jonathan A, Raphael MJ. QRS voltage of the electrocardiogram and Frank vectorcardiogram in relation to ventricular volume. Br Heart J 1977;39:1109-1113. 20. Lekven J, Chatterjee K, Tyberg JV, Parmtay WW. Reduction in endocardial and epicardial potentials during acute increments in left ventricular dimensions. Am Heart J 1979;98:200-206. 21. Holland RP, Brooks H: The QRS complex during myocardial ischemia. J Clin Invest 1978;57:541-550. 22. Watanabe K, Bhargava V, Froellcbar VF. Tha relationship between exercise induced R wave amplitude changes and QRS vector loops. J Electrocardiol 1981:14:129-38. 23. Froelkher VF. Exercise Testing and Training. Chicago: Year Bock Medical, 1983:45-49. 24. Paris1 AF, Harrlngton JJ, Askenazi J, Pratt RC, McIntyre KM. Echocardiographic evaluation of the valsalva maneuver in healthy subjects and patients with and without heart failure. Circulation 1978:54:921-927. 25. Borow KM, Neumann A, Wynne J. Sensitivity of end systolic pressuredimension and pressure-volume relations to the inotropic state in humans. -...

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