- Email: [email protected]
Comparative angiographic right and left ventricular volumes
Volume Number
5.
6.
7. 8.
9.
10.
109 2
Acebutotot/propranoloL
of two beta-blocking agents, acebutolol and propranolol, in essential hypertension. Curr Ther Res 28:964, 1980. Watson RDS, Stallard TJ, Littler WA: Comparison of once and twice daily administration of acebutolol in hypertension. Br J Clin Pharmacol 9:209, 1980. Martin MA, Phillips CA, Smith AJ: Acebutolol in hypertension: A double-blind trial against placebo. Br J Clin Pharmaco1 6:351, 1978. Dunlop D, Shanks RG: Selective blockade of adrenoceptive beta receutors in the heart. Br J Pharmacol 32:201. 1968. Buhler FR, Burkart F, Lutold BE, Kung M, Marbet G, Pfisterer M: Antihypertensive beta blocking action as related to renin and age: A pharmacologic tool to identify pathogenetic mechanisms in essential hypertension. Am J Cardiol 36:653, 1975. Hollifield JW, Sherman K, Slaton P: Age, race, and sex as a determinant of successful antihypertensive therapy. Prev Med 7:88, 1978. Woods JW, Pittman AW, Pulliam CC, Werk EE Jr, Waider W, Allen CA: Renin profiling in hypertension and its use in
Comparative angiographic ventricular volumes
11. 12. 13.
14.
15. 16. 17.
in hypertension
treatment with propranolol and chlorthalidone. N Engl J Med 294:1137, 1976. Humphries DG, Delvin DC: Ineffectiveness of propranolol in hypertensive Jamaicans. Br Med J 2:601, 1968. Oli JM: Acebutolol in the management of hypertension in Nigerians. Curr Ther Res 30:477, 1981. Zaman R, Jack DB, Kendall MJ: The penetration of acebuto101 and its major metabolite, diacetolol, into human cerebrospinal fluid and saliva. Br J Clin Pharmacol 12:427, 1981. Nair S, Maguire WC, Laddu AR: The effect of acebutolol, a beta-adrenergic blocking agent, and placebo on pulmonary functions in asthmatics. Int J Clin Pharmacol Toxic01 19519. 1981. Wilson JD: Antinuclear antibodies and cardiovascular drugs. Drugs 19:292, 1980. Lee SL, Chase PH: Drug-induced systemic lupus erythematosus: A critical review. Semin Arthritis Rheum 5:83, 1975. Wilson JD, Bullock JY, Sutherland DC, Main C, O’Brien KP: Antinuclear antibodies in patients receiving non-practolol beta-blockers. Br Med J 1:14, 1978.
right and left
Comparative angiographic right and left ventricular volumes and right and left ventricular ejection fractions have been reported in the same normal infants and children. This relationship was assessed in adult patients to determine if these pediatric observations persist in later life. Seventeen adults, who had both right and left ventricular angiograms and who had no demonstrable organic heart disease, were studied. Right ventricular end-diastolic volume ranged from 54 to 98 (76 * 14, mean * SD) cc/m* and left ventricular end-diastolic volume ranged from 48 to 90 (70 f 12) cc/m2; p < 0.03. Right ventricular end-systolic volume ranged from 22 to 47 (33 + 8.0) cc/m* and left ventricular end-systolic volume ranged from 13 to 34 (22 * 5.3) cc/mz; p < O.OOW5. Calculated right ventricular stroke volume ranged from 31 to 60 (43 i 8.3) cc/m2 and left ventricular stroke volume ranged from 29 to 70 (48 2 11) cc/m2; p = NS. Calculated right ventricular ejection fraction ranged from 0.48 to 0.62 (0.57 + 0.04) and the left ventricular ejection fraction ranged from 0.57 to 0.84 (0.68 f 0.07; p < 0.00005. Both right ventricular end-systolic and end-diastolic volumes were greater than left ventricular end-systolic and end-diastolic volumes. This resulted in decreased right ventricular ejection fraction compared to left ventricular ejection fraction. The difference between the two ventricles may be due to compliance, muscle mass, and anatomic configuration with a net result of one chamber more completely emptying than the other. Thus it appears that the relationships between right and left ventricular volumes noted in infancy and childhood persist in adult life. (AM HEART J 109:321, 1985.)
Raymond J. Pietras, M.D., George T. Kondos, Wilfred Lam, M.D. Chicago, Ill.
From the Section of Cardiology, of Illinois at Chicago. Received accepted
for publication duly 2, 1984.
March
Department 15, 1984;
of Medicine revision
received
M.D., David
of the University June
Reprint requests: Raymond J. Pietras, M.D., Cardiology Section, ty of Illinois at Chicago, PO Box 6998, Chicago, IL 60680.
1, 1984; Universi-
Kaplan,
B.S., and
Clinical evaluation of ventricular function has recently focused on both the right and left ventricle in heart disease of varied etiology.1-5 Although normal pressure relationships between right and left ventricles are well described, the normal relation321
322
Pietras
et al.
ship between right and left ventricular volume lacks definition. There are several reports of normal angiographic values for right and left ventricular vo1ume;6-g however, few comparisons of normal right ventricular volumes and left ventricular volumes in the same patient exist. 1o-1sClinical studies comparing right and left ventricular volume have mostly been reported in infants and children, except for one study in a small number of adults.‘” Since some results of comparative volume studies conflict and this relationship has virtually been unstudied in adults the following investigation was performed. METHODS
Seventeen patients, who had no demonstrable organic heart disease (except for arrhythmia) and who had technically adequate biplane right and left ventriculography, were studied. Clinical evaluation included history, physical examination, resting ECG, posteroanterior and lateral chest x-ray, and M-mode echocardiogram. All patients had cardiac catheterization to evaluate recurrent arrhythmia and/or chest pain syndromes. Cardiac catheterization. Prior to cardiac catheterization patients were premeditated with diazepam and Benadryl. All patients were in sinus rhythm at the time of study. Intracardiac pressure was recorded at rest from the right and left heart chambers through fluid-filled catheters, using midchest as the zero reference level. Mean right atria1 and right ventricular end-diastolic pressure <8 mm Hg and mean pulmonary capillary wedge pressure and left ventricular end-diastolic pressure <13 mm Hg were considered normal. Cardiac output was estimated by the Fick method in 15 patients and by the thermodilution method in the remaining two patients. A pigtail (Cook Laboratories, Bloomington, Ind.) catheter was used to record aortic and left ventricular pressure and to perform left ventriculography. After pressures were recorded and cardiac output was estimated, angiography was performed. The sequence was left ventriculography followed by right ventriculography in 16 patients and right ventriculography followed by left ventriculography in one patient. The time interval between right and left ventricular angiography was 15.2 i 5.3 (mean 2 SD) minutes. Right and left ventriculography. All patients had 40 to 45 cc of radiopaque contrast material (Renografin 76) injected into the left ventricle and into the right ventricle at a rate of 12 cc/set. Left and right ventriculograms were obtained with biplane cineangiography at a film speed of 33 or 48 frames/set. The distance of the x-ray and image tube to a table-mounted cradle was fixed. The distance between the palpable cardiac apex and the vertical image tube and between the midsternal line and the lateral image tube was measured before left ventriculography. The distance between the midaxillary line and the vertical image tube and between the midsternal line and lateral image tube was measured before right ventriculography. A 1 x 1 cm lead grid was filmed at each of the distances measured between patient and vertical image tube and patient and lateral image tube to correct magnification of
American
February, 1985 Heart Journal
the opacified ventricular chamber. Ventricular ectopic beats and postventricular ectopic beats were rejected for analysis. Ventricular end-diastolic and end-systolic frames were indentified by scanning a cardiac cycle for the largest and smallest ventricular image, respectively. The perimeter of the ventricular image was traced to imclude all the trabecular intersticies. Ventricular end-diastolic and end-systolic volumes were calculated with a computer (Echo Comp, Digisonics, Houston, Tex.) programmed for the modified area-length method of Dodge for the left ventricle”’ and programmed for Simpson’s rule method of analysis where the ventricle is assumed to be an elliptical cylinder for the right ventricle. Ventricular stroke volume was calculated as the difference between end-diastolic and end-systolic volume. Ventricular ejection fraction was calculated from stroke volume divided by end-diastolic volume. Left ventriculograms were obtained during held inspiration with biplane cineangiography with a table-mounted cradle in 30-degree right anterior oblique and 60-degree left anterior oblique projections. Left ventricular volume was corrected for true volume with the regression equation of Wynne et al.” Biplane right ventricular angiography was performed in the posteroanterior and lateral projections with radiopaque contrast material int,roduced during held expiration through a right ventricular pigtail catheter (Cook Inc, Bloomington, Ind.) (14 patients), Berman angiographic balloon catheter (Critikon. Tampa, Fla.) (two patients), or National Institutes of Health catheter (USC1 Ballirica, Mass.) (one patient). The measured volumes were corrected with a regression equation developed in our laboratory based on 19 right ventricular casts of animal hearts with a range of volumes from 16 to 95 cc filmed in the same projection. Linear repression analysis of paired data was performed. The regression equation obtained was: true volume = 0.789 calculated volume + 0.3 cc, r = 0.9, p < 0.00005, SEE = 9.1 cc. This correction for true volume is similar to that reported by Gentzier et al.” Ventricular regional wall motion was qualitatively assessed by three observers (R. P., W. L., and G. K.). Mitral and/or tricuspid valve prolapse was diagnosed when ventriculography revealed a scalloped atrioventricular valve bulging in systole into the left or right atrium, respectively. Selective coronary arteriography was performed in 14 patients by means of either a femoral or brachial artery approach. Student’s paired t test was used to assess significance of differences between right and left ventricular volumes. RESULTS Clinical characteristics. Patients ranged in age from 17 to 63 (38.3 -t 13.8, mean f SD) years. Eleven patients (65%) were female and six patients (35%) were male. Eleven patients with arrhythmia had symptoms which included one or more of the following: palpitations (9), syncope (4), dyspnea (4), and chest pain (4). Four other patients presented with chest pain, one of whom had paroxysmal supraven-
Volume Number
Table
109 2
Comparative
RV and LV volumes
PCW
LVS
L VED
10 10 10 4 10
160 150 105 135 105 102 127 100 92 96 120 115 108 106 120 120 140 118 19
10 10 10 8 8 8 5 3 8 4 12 9 10 5 5 10 10 7.9 2.6
323
I. Right and left ventricular hemodynamic findings
Patient No.
RA
RVS
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Mean SD-+
5 4 7 0 3 4 5 2 2 2 3 6 5 1 0 2 4 3.2 2.0
24
R VED (mm Hd 6 -
22 20 20 26 32 20 19 18 24 20 19 13 18 24 24 21 4.2
8 2 3 6 8 4 4 2 4 4 2 3 3 4 4 4.2 1.9
10 5 4 9 7 7 3 6 6 10 7.4 2.6
CI (Llminlm’) 3.4 3.3 2.6 4.2 3.7 3.2 3.8 3.3 3.0 2.9 4.6 3.4 3.1 3.1 2.5 3.4 2.8 3.3 0.5
Abbreviations: RA = mean right atria1 pressure; RVS = systolic right ventricular pressure; RVED = right ventricular end-diastolic pressure; PCW = mean pulmonary capillary wedge pressure; LVS = systolic left ventricular pressure; LVED = left ventricular end-diastolic pressure; CI = cardiac index.
Table
II. Comparative ventricular volumes
Patient No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Mean SD* P
RVSVI (cclm”)
LVSVI (cclm’)
R VED VI
L VED VI
(cclm’)
(cclm’)
(cclm?
(cclm’)
R VEF
L VEF
36 42 50 43 48 48 38 33 31 33 44 43 57 52 44 38 60 43 8.3
39 29 62 46 65 45 63 41 40 44 32 48 52 45 51 47 70 48 11
72 88 94 78 95 77 70 55 54 57 68 73 98 90 74 66 95 76 14
66 51 89 71 86 71 76 58 60 64 48 76 86 65 72 63 90 70 12
36 46 44 35 47 29 32 22 23 24 24 29 41 38 29 28 35 33.0 8.0
27 22 27 25 21 26 13 17 20 20 16 28 34 20 21 16 22 22.0 5.3
0.50 0.48 0.53 0.55 0.50 0.62 0.54 0.60 0.57 0.58 0.64 0.59 0.58 0.58 0.60 0.58 0.62 0.57 0.04
0.59 0.57 0.70 0.64 0.76 0.63 0.84 0.71 0.67 0.64 0.75 0.64 0.59 0.69 0.71 0.76 0.68 0.68 0.07
<0.07
<0.03
RVESVI
L VES VI
<0.00005
<0.00005
Abbreviations: RVSVI = right ventricular stroke volume; LVSVI = left ventricular stroke volume; RVEDVI = right ventricular end-diastolic volume: LVEDVI = left ventricular end-diastolic volume; RVESVI = right ventricular end-systolic volume; LVESVI = left ventricular end-systolic volume; RVEF = right ventricular ejection fraction; LVEF = left ventricular ejection fraction; SD = standard deviation.
tricular tachycardia. One patient with left bundle branch block and syncope and another with frequent asymptomatic ventricular premature depolarizations were studied. There were no significant murmurs or extra cardiac sounds found on physical examination. Excluding the occurrence of arrhyth-
mia the ECGs in 10 patients were normal. Of the remaining seven patients, five had nonspecific ST-T wave changes, one had left bundle branch block, and one had left ventricular hypertrophy. By study design no patient had cardiomegaly on chest x-ray examination and M-mode echocardiogram was nor-
324
Pietras et al.
American
ml/m*
%
‘OOr
\
1100
n = 17 Q=(msan+ SD)
80
- 80
P
60-
p-co.03
- 60 - 50
p < 0.00005 I
f
IO
p<0.00005 t
RV -1-1
EDV Fig.
P
p
LV
RV
LV
ESV
RV
LV
sv
RV
LV
EF
1. Comparative right and left ventricular volume in
the same patient normalized for body surface area. EF = ejection fraction; EDV = end-diastolic volume; ESV = end-systolic volume; RV = right ventricle; LV = left ventricle; SV = stroke volume.
ma1 in the 16 patients in whom it was performed. The precatheterization diagnosis in eight patients was ischemic heart disease, in one other patient the diagnosis was mitral valve prolapse, and in another diagnosis was cardiomyopathy. The remaining seven patients had no demonstrable organic heart disease (excluding arrhythmia) before catheterization. Cardiac catheterization data (Table I). By study design intracardiac pressure, cardiac output, valve function, wall motion, and coronary arteriograms were normal. Right atria1 mean pressure ranged from 0 to 7 (3.2 ? 2.0) mm Hg. Right ventricular systolic pressure ranged from 13 to 32 (21 -t 4.2) mm Hg. Right ventricular end-diastolic pressure ranged from 2 to 8 (4.2 ? 1.9) mm Hg. Mean pulmonary capillary wedge pressure ranged from 3 to 10 (7.4 f 2.6) mm Hg. Left ventricular systolic pressure ranged from 92 to 160 (118 * 19) mm Hg. Left ventricular end-diastolic pressure ranged from 3 to 12 (7.9 +- 2.6) mm Hg. Cardiac output ranged from 2.6 to 4.6 (3.3 f 0.5) L/min/m2. No transvalvular gradient or intracardiac shunt was detected. Coronary arteriograms in 14 patients were normal. There were absolutely no data to suggest ischemic
February. 1985 Heart Journal
heart disease in the remaining three patients who had not undergone coronary angiography. Right and left ventricular angiography. Regional wall motion was normal on visual inspection of biplane right and left ventricular angiograms. There was no evidence of tricuspid or mitral valve prolapse or insufficiency, except that which was catheter or arrhythmia induced. Right ventricular end-systolic volume ranged from 22 to 47 (33 -t 8.0) cc/m2 (Table II). Right ventricular end-diastolic volume ranged from 54 to 98 (76 ? 14) cc/m’. Calculated right ventricular stroke volume ranged from 31 to 60 (43.5 f 8.3) cc/m2 and right ventricular ejection fraction ranged from 0.48 to 0.62 (0.57 t 0.04). Left ventricular end-systolic volume ranged from 13 to 34 (22 t 5.3) cc/m2 and left ventricular enddiastolic volume ranged from 48 to 90 (70 + 12) cc/m2. Calculated left ventricular stroke volume ranged from 29 to 70 (48 rt 11) cc/m” and left ventricular ejection fraction ranged from 0.57 to 0.84 (0.68 +- 0.07). Comparison
of ventricular
volumes
(Table
II and Fig.
1). The heart rate during right ventricular angiography was 79.5 + 13.5 bpm and during left ventricular angiography was 80.6 -t 13.6 bpm, p = NS. Right ventricular end-diastolic volume”was slightly larger than left ventricular end-diastolic volume (p < 0.03) and right ventricular end-systolic volume was always greater than left ventricular end-systolic volume (p < 0.00005). The calculated right and left ventricular stroke volumes were not significantly different. Left ventricular ejection fraction was always greater than right ventricular ejection fraction (p < 0.00005). DISCUSSION
With present-day angiographic methods direct comparison of right and left ventricular volume in the same heart is difficult, since both ventriculograms are rarely performed in patients with normal ventricles. Therefore, in a group of adult patients who were clinically and hemodynamically screened to exclude organic heart disease, comparative right and left ventricular volumes were studied. In all patients left ventricular end-systolic volume was less than right ventricular end-systolic volume. Left ventricular end-diastolic volume was less than right ventricular end-diastolic volume in 12 of 17 patients studied. Although there were individual differences in right and left ventricular stroke volume, there was no statistical difference when the stroke volume of the right and left ventricle for the entire study group was compared. As a result of these volume
Volume
109
Number
2
relationships, left ventricular ejection fraction exceeded right ventricular ejection fraction in all instances. Right and left ventricular angiography. Angiographic studies comparing right and left ventricular volumes with one exception have appeared in the pediatric reports.‘O-l5 One hundred twenty-four “normal” patients form the basis of these reports. Most investigators found left ventricular ejection fraction to be greater than right ventricular ejection fraction, right ventricular end-systolic volume to be greater than left ventricular end-systolic volume, and right ventricular end-diastolic volume to be greater than left ventricular end-diastolic volume. However, Graham et al.” found no difference in right and left ventricular ejection fraction, end-systolic volume, and enddiastolic volume. Boak et a1.,15in a small number of adults, also found no difference between right and left ventricular end-diastolic volume. Although most investigators found no difference in right and left ventricular stroke volume, both Boak et a1.15and Carlsson et al.‘O reported differences. The latter group corrected right ventricular stroke volume for ectopy that occurred on right ventricular injection of contrast material by multiplying the observed right ventricular stroke volume by right ventricular diastolic filling period divided by left ventricular diastolic filling period to achieve equality between the two ventricular outputs. Many of the previous pediatric studies used sufficient sedation to produce rapid heart rates and possible depression of the inotropic state. Some were based on mixed populations of normal patients and patients with “mild” congenital heart defects. Levophase angiography of the left ventricle was common, which in adults and older children has been reported to underestimate left ventricular ejection fraction and alter stroke volume.18 It is possible that methodology may have influenced the volume relationships between the two ventricles in some of the previous studies. Fetal ventricular volumes. Experimental studies in humans and animals have shown that in the fetal state right ventricular end-diastolic volume is much greater than left ventricular end-diastolic volume and the right ventricular stroke volume is twice left ventricular stroke volume.1g Change in right and left ventricular volumes is stated to occur within 24 hours after birth. However, in a recent longitudinal echocardiographic study of the normal human fetus, similarities between right and left ventricular sizes, wall thicknesses, and free wall weights have been reported and do not support the theory of right ventricular dominance during gestation.20 Angiographic limitations. This study and all angio-
Comparative
RV and LV volumes
325
graphic studies have limitations in sampling and loading conditions. Only a few cardiac cycles are available to obtain end-diastolic volume and endsystolic volume. Cineangiographic images were obtained on inspiration or expiration to eliminate the diaphragm and improve quality of image. Respiratory maneuvers can inadvertently produce the Valsalva or Muller effect altering ventricular volume. It has been shown that even normal respiration mildly affects the two ventricles with changes in right ventricular stroke volume preceding left ventricular stroke volume by one cardiac cycle.21 Prior ectopic contractions and volume expansion of contrast material also influence loading conditions.10~22-25In our study the sequence of right and left ventriculography was not randomly varied and the interval between right and left ventriculography was not the same in all patients. This could produce larger volumes and decreased ejection fractions secondary to the negative inotropic effect of the contrast media. Fortuitously some of these effects are small in magnitude or opposite in direction negating their overall influence, and the normal ventricular response is a rapid return to steady state. Radionuclide angiographic studies. Two radionuelide angiographic studies, where both right and left ventricular ejection fractions were assessed in the same patient, support our angiographic findings. Berger et a1.26studied 50 “normal” adults with the first-pass radionuclide method and obtained a right ventricular ejection fraction of 0.45 to 0.71 (0.55 +0.10) and a left ventricular ejection fraction of 0.58 to 0.70 (0.69 +- 0.10). Right ventricular ejection fraction was less than left ventricular ejection fraction in 44 of 50 patients. Korr et a1.27studied 20 “normal” subjects with equilibrium-gated radionuclide angiography, whose right ventricular ejection fraction ranged from 0.42 to 0.67 (0.53 ? 0.06) and left ventricular ejection fraction range from 0.55 to 0.85 (0.71 f 0.10). In no radionuclide angiographic study were right and left ventricular volumes compared in the same patient. It has been suggested that at end diastole the less muscular right ventricle has a larger volume than the left ventricle because of its increased distensibility. 28The left ventricle with a greater muscle mass and a different mode of contraction more completely empties its contents. The right ventricle, however, achieves the same stroke output as the left ventricle from higher levels of end-diastolic and end-systolic volume resulting in a lower right ventricular ejection fraction than the left ventricular ejection fraction. Our results support most earlier pediatric observations of the relationship between right and left
February,
326
Pietras et al.
American
ventricular volume and the persistence of this association in adult life. We gratefully acknowledge the technical Ehler and Jonas Juska and the secretarial Jefferson.
assistance assistance
14.
of Donna of Frances
REFERENCES
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Heart
1985 Journal
volume in congenital heart disease. Am J Cardiol 36:67, 1975. Lange PE, Onnasch DL, Farr FL, Heintzen PH: Angiocardiographic right ventricular volume determination. Accuracy, as determined from human casts, and clinical application. Eur J Cardiol 8:477, 1978. Boak JG, Bove AA, Kreulen T, Spann JF: A geometric basis for calculation of right ventricular volume in man. Cathet Cardiovasc Diagn 3:217, 1977. Dodge HT, Sandler H, Ballew DW, Lord JD .Jr: The use of biplane angiocardiography for the measurement of left ventricular volume in man. AM HEART J 60:762, 1960. Wynne J, Green LH, Mann T, Levin D, Grossman W: Estimation of left ventricular volumes in man from biplane cineangiograms filmed in oblique projections. Am J Cardiol 41~726, 1978. Ferlinz J, Herman MV, Cohn PF, Gorlin R: Comparison of selective left ventriculograms with levophase (“forward”) ventriculograms in patients with coronary artery disease. AM HEART J 91:721, 1976. Erath HG, Jr, Graham TP, Smith CW. Thompson SL, Hammon JW: Comparative right and left ventricular volumes and pump function in the newborn lamb. Am .J Cardiol 47:855, 1981. St. John Sutton MG, Gewitz MH, Shah B, Cohen A, Reichek N, Gabbe S, Huff DS: Quantitative assessment of growth and function of the cardiac chambers in the normal human fetus: A prospective longitudinal study. Circulation 69:645, 1984. Franklin DL, Van Citters RL, Rushmer RF: Balance between right and left ventricular output. Circ Res 10:17, 1962. Iseri LT, Kaplan MA, Evans MJ, et al: Effect of concentrated contrast media during angiography on plasma volume and plasma osmolality. AM HEART J 69:154, 1965. Hallerman FJ, Rastelli GC, Swan HJC: Effects of rapid injection of heparinized blood into right and left ventricles in dogs. Radiology 83:647, 1964. Mullins CB, Leshin SJ, Mierzwiak DS, Alsobrook HD, Mitchell dH: Changes in left ventricular function produced by the injection of contrast media. AM HEART J 83:373, 1972. Hammermeister KE, Warbasse JR: Immediate hemodynamic effects of cardiac angiography in man. Am J Cardiol 31:307, 1973. Berger HJ, Matthay RA, Loke J, Marshall RC, Gottschalk A, Zaret BL: Assessment of cardiac performa, ce with quanitative radionuclide angiography: Right ve’itricular ejection fraction with reference to findings in chronic obstructive pulmonary disease. Am J Cardiol 41:897, 1978. Korr KS, Gandsman EJ, Winkler ML, Shulman RS, Bough EW: Hemodynamic correlates of right ventricular ejection fraction measured with gated radionuclide angiography. Am J Cardiol 49:71, 1982. Arcilla RA, Tsai P, Thilenlus 0, Ranniger K: Angiographic method for volume estimation of right and left ventricles. Chest 60:446, 1971.
5.
6.
7. 8.
9.
10.
109 2
Acebutotot/propranoloL
of two beta-blocking agents, acebutolol and propranolol, in essential hypertension. Curr Ther Res 28:964, 1980. Watson RDS, Stallard TJ, Littler WA: Comparison of once and twice daily administration of acebutolol in hypertension. Br J Clin Pharmacol 9:209, 1980. Martin MA, Phillips CA, Smith AJ: Acebutolol in hypertension: A double-blind trial against placebo. Br J Clin Pharmaco1 6:351, 1978. Dunlop D, Shanks RG: Selective blockade of adrenoceptive beta receutors in the heart. Br J Pharmacol 32:201. 1968. Buhler FR, Burkart F, Lutold BE, Kung M, Marbet G, Pfisterer M: Antihypertensive beta blocking action as related to renin and age: A pharmacologic tool to identify pathogenetic mechanisms in essential hypertension. Am J Cardiol 36:653, 1975. Hollifield JW, Sherman K, Slaton P: Age, race, and sex as a determinant of successful antihypertensive therapy. Prev Med 7:88, 1978. Woods JW, Pittman AW, Pulliam CC, Werk EE Jr, Waider W, Allen CA: Renin profiling in hypertension and its use in
Comparative angiographic ventricular volumes
11. 12. 13.
14.
15. 16. 17.
in hypertension
treatment with propranolol and chlorthalidone. N Engl J Med 294:1137, 1976. Humphries DG, Delvin DC: Ineffectiveness of propranolol in hypertensive Jamaicans. Br Med J 2:601, 1968. Oli JM: Acebutolol in the management of hypertension in Nigerians. Curr Ther Res 30:477, 1981. Zaman R, Jack DB, Kendall MJ: The penetration of acebuto101 and its major metabolite, diacetolol, into human cerebrospinal fluid and saliva. Br J Clin Pharmacol 12:427, 1981. Nair S, Maguire WC, Laddu AR: The effect of acebutolol, a beta-adrenergic blocking agent, and placebo on pulmonary functions in asthmatics. Int J Clin Pharmacol Toxic01 19519. 1981. Wilson JD: Antinuclear antibodies and cardiovascular drugs. Drugs 19:292, 1980. Lee SL, Chase PH: Drug-induced systemic lupus erythematosus: A critical review. Semin Arthritis Rheum 5:83, 1975. Wilson JD, Bullock JY, Sutherland DC, Main C, O’Brien KP: Antinuclear antibodies in patients receiving non-practolol beta-blockers. Br Med J 1:14, 1978.
right and left
Comparative angiographic right and left ventricular volumes and right and left ventricular ejection fractions have been reported in the same normal infants and children. This relationship was assessed in adult patients to determine if these pediatric observations persist in later life. Seventeen adults, who had both right and left ventricular angiograms and who had no demonstrable organic heart disease, were studied. Right ventricular end-diastolic volume ranged from 54 to 98 (76 * 14, mean * SD) cc/m* and left ventricular end-diastolic volume ranged from 48 to 90 (70 f 12) cc/m2; p < 0.03. Right ventricular end-systolic volume ranged from 22 to 47 (33 + 8.0) cc/m* and left ventricular end-systolic volume ranged from 13 to 34 (22 * 5.3) cc/mz; p < O.OOW5. Calculated right ventricular stroke volume ranged from 31 to 60 (43 i 8.3) cc/m2 and left ventricular stroke volume ranged from 29 to 70 (48 2 11) cc/m2; p = NS. Calculated right ventricular ejection fraction ranged from 0.48 to 0.62 (0.57 + 0.04) and the left ventricular ejection fraction ranged from 0.57 to 0.84 (0.68 f 0.07; p < 0.00005. Both right ventricular end-systolic and end-diastolic volumes were greater than left ventricular end-systolic and end-diastolic volumes. This resulted in decreased right ventricular ejection fraction compared to left ventricular ejection fraction. The difference between the two ventricles may be due to compliance, muscle mass, and anatomic configuration with a net result of one chamber more completely emptying than the other. Thus it appears that the relationships between right and left ventricular volumes noted in infancy and childhood persist in adult life. (AM HEART J 109:321, 1985.)
Raymond J. Pietras, M.D., George T. Kondos, Wilfred Lam, M.D. Chicago, Ill.
From the Section of Cardiology, of Illinois at Chicago. Received accepted
for publication duly 2, 1984.
March
Department 15, 1984;
of Medicine revision
received
M.D., David
of the University June
Reprint requests: Raymond J. Pietras, M.D., Cardiology Section, ty of Illinois at Chicago, PO Box 6998, Chicago, IL 60680.
1, 1984; Universi-
Kaplan,
B.S., and
Clinical evaluation of ventricular function has recently focused on both the right and left ventricle in heart disease of varied etiology.1-5 Although normal pressure relationships between right and left ventricles are well described, the normal relation321
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et al.
ship between right and left ventricular volume lacks definition. There are several reports of normal angiographic values for right and left ventricular vo1ume;6-g however, few comparisons of normal right ventricular volumes and left ventricular volumes in the same patient exist. 1o-1sClinical studies comparing right and left ventricular volume have mostly been reported in infants and children, except for one study in a small number of adults.‘” Since some results of comparative volume studies conflict and this relationship has virtually been unstudied in adults the following investigation was performed. METHODS
Seventeen patients, who had no demonstrable organic heart disease (except for arrhythmia) and who had technically adequate biplane right and left ventriculography, were studied. Clinical evaluation included history, physical examination, resting ECG, posteroanterior and lateral chest x-ray, and M-mode echocardiogram. All patients had cardiac catheterization to evaluate recurrent arrhythmia and/or chest pain syndromes. Cardiac catheterization. Prior to cardiac catheterization patients were premeditated with diazepam and Benadryl. All patients were in sinus rhythm at the time of study. Intracardiac pressure was recorded at rest from the right and left heart chambers through fluid-filled catheters, using midchest as the zero reference level. Mean right atria1 and right ventricular end-diastolic pressure <8 mm Hg and mean pulmonary capillary wedge pressure and left ventricular end-diastolic pressure <13 mm Hg were considered normal. Cardiac output was estimated by the Fick method in 15 patients and by the thermodilution method in the remaining two patients. A pigtail (Cook Laboratories, Bloomington, Ind.) catheter was used to record aortic and left ventricular pressure and to perform left ventriculography. After pressures were recorded and cardiac output was estimated, angiography was performed. The sequence was left ventriculography followed by right ventriculography in 16 patients and right ventriculography followed by left ventriculography in one patient. The time interval between right and left ventricular angiography was 15.2 i 5.3 (mean 2 SD) minutes. Right and left ventriculography. All patients had 40 to 45 cc of radiopaque contrast material (Renografin 76) injected into the left ventricle and into the right ventricle at a rate of 12 cc/set. Left and right ventriculograms were obtained with biplane cineangiography at a film speed of 33 or 48 frames/set. The distance of the x-ray and image tube to a table-mounted cradle was fixed. The distance between the palpable cardiac apex and the vertical image tube and between the midsternal line and the lateral image tube was measured before left ventriculography. The distance between the midaxillary line and the vertical image tube and between the midsternal line and lateral image tube was measured before right ventriculography. A 1 x 1 cm lead grid was filmed at each of the distances measured between patient and vertical image tube and patient and lateral image tube to correct magnification of
American
February, 1985 Heart Journal
the opacified ventricular chamber. Ventricular ectopic beats and postventricular ectopic beats were rejected for analysis. Ventricular end-diastolic and end-systolic frames were indentified by scanning a cardiac cycle for the largest and smallest ventricular image, respectively. The perimeter of the ventricular image was traced to imclude all the trabecular intersticies. Ventricular end-diastolic and end-systolic volumes were calculated with a computer (Echo Comp, Digisonics, Houston, Tex.) programmed for the modified area-length method of Dodge for the left ventricle”’ and programmed for Simpson’s rule method of analysis where the ventricle is assumed to be an elliptical cylinder for the right ventricle. Ventricular stroke volume was calculated as the difference between end-diastolic and end-systolic volume. Ventricular ejection fraction was calculated from stroke volume divided by end-diastolic volume. Left ventriculograms were obtained during held inspiration with biplane cineangiography with a table-mounted cradle in 30-degree right anterior oblique and 60-degree left anterior oblique projections. Left ventricular volume was corrected for true volume with the regression equation of Wynne et al.” Biplane right ventricular angiography was performed in the posteroanterior and lateral projections with radiopaque contrast material int,roduced during held expiration through a right ventricular pigtail catheter (Cook Inc, Bloomington, Ind.) (14 patients), Berman angiographic balloon catheter (Critikon. Tampa, Fla.) (two patients), or National Institutes of Health catheter (USC1 Ballirica, Mass.) (one patient). The measured volumes were corrected with a regression equation developed in our laboratory based on 19 right ventricular casts of animal hearts with a range of volumes from 16 to 95 cc filmed in the same projection. Linear repression analysis of paired data was performed. The regression equation obtained was: true volume = 0.789 calculated volume + 0.3 cc, r = 0.9, p < 0.00005, SEE = 9.1 cc. This correction for true volume is similar to that reported by Gentzier et al.” Ventricular regional wall motion was qualitatively assessed by three observers (R. P., W. L., and G. K.). Mitral and/or tricuspid valve prolapse was diagnosed when ventriculography revealed a scalloped atrioventricular valve bulging in systole into the left or right atrium, respectively. Selective coronary arteriography was performed in 14 patients by means of either a femoral or brachial artery approach. Student’s paired t test was used to assess significance of differences between right and left ventricular volumes. RESULTS Clinical characteristics. Patients ranged in age from 17 to 63 (38.3 -t 13.8, mean f SD) years. Eleven patients (65%) were female and six patients (35%) were male. Eleven patients with arrhythmia had symptoms which included one or more of the following: palpitations (9), syncope (4), dyspnea (4), and chest pain (4). Four other patients presented with chest pain, one of whom had paroxysmal supraven-
Volume Number
Table
109 2
Comparative
RV and LV volumes
PCW
LVS
L VED
10 10 10 4 10
160 150 105 135 105 102 127 100 92 96 120 115 108 106 120 120 140 118 19
10 10 10 8 8 8 5 3 8 4 12 9 10 5 5 10 10 7.9 2.6
323
I. Right and left ventricular hemodynamic findings
Patient No.
RA
RVS
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Mean SD-+
5 4 7 0 3 4 5 2 2 2 3 6 5 1 0 2 4 3.2 2.0
24
R VED (mm Hd 6 -
22 20 20 26 32 20 19 18 24 20 19 13 18 24 24 21 4.2
8 2 3 6 8 4 4 2 4 4 2 3 3 4 4 4.2 1.9
10 5 4 9 7 7 3 6 6 10 7.4 2.6
CI (Llminlm’) 3.4 3.3 2.6 4.2 3.7 3.2 3.8 3.3 3.0 2.9 4.6 3.4 3.1 3.1 2.5 3.4 2.8 3.3 0.5
Abbreviations: RA = mean right atria1 pressure; RVS = systolic right ventricular pressure; RVED = right ventricular end-diastolic pressure; PCW = mean pulmonary capillary wedge pressure; LVS = systolic left ventricular pressure; LVED = left ventricular end-diastolic pressure; CI = cardiac index.
Table
II. Comparative ventricular volumes
Patient No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Mean SD* P
RVSVI (cclm”)
LVSVI (cclm’)
R VED VI
L VED VI
(cclm’)
(cclm’)
(cclm?
(cclm’)
R VEF
L VEF
36 42 50 43 48 48 38 33 31 33 44 43 57 52 44 38 60 43 8.3
39 29 62 46 65 45 63 41 40 44 32 48 52 45 51 47 70 48 11
72 88 94 78 95 77 70 55 54 57 68 73 98 90 74 66 95 76 14
66 51 89 71 86 71 76 58 60 64 48 76 86 65 72 63 90 70 12
36 46 44 35 47 29 32 22 23 24 24 29 41 38 29 28 35 33.0 8.0
27 22 27 25 21 26 13 17 20 20 16 28 34 20 21 16 22 22.0 5.3
0.50 0.48 0.53 0.55 0.50 0.62 0.54 0.60 0.57 0.58 0.64 0.59 0.58 0.58 0.60 0.58 0.62 0.57 0.04
0.59 0.57 0.70 0.64 0.76 0.63 0.84 0.71 0.67 0.64 0.75 0.64 0.59 0.69 0.71 0.76 0.68 0.68 0.07
<0.07
<0.03
RVESVI
L VES VI
<0.00005
<0.00005
Abbreviations: RVSVI = right ventricular stroke volume; LVSVI = left ventricular stroke volume; RVEDVI = right ventricular end-diastolic volume: LVEDVI = left ventricular end-diastolic volume; RVESVI = right ventricular end-systolic volume; LVESVI = left ventricular end-systolic volume; RVEF = right ventricular ejection fraction; LVEF = left ventricular ejection fraction; SD = standard deviation.
tricular tachycardia. One patient with left bundle branch block and syncope and another with frequent asymptomatic ventricular premature depolarizations were studied. There were no significant murmurs or extra cardiac sounds found on physical examination. Excluding the occurrence of arrhyth-
mia the ECGs in 10 patients were normal. Of the remaining seven patients, five had nonspecific ST-T wave changes, one had left bundle branch block, and one had left ventricular hypertrophy. By study design no patient had cardiomegaly on chest x-ray examination and M-mode echocardiogram was nor-
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ml/m*
%
‘OOr
\
1100
n = 17 Q=(msan+ SD)
80
- 80
P
60-
p-co.03
- 60 - 50
p < 0.00005 I
f
IO
p<0.00005 t
RV -1-1
EDV Fig.
P
p
LV
RV
LV
ESV
RV
LV
sv
RV
LV
EF
1. Comparative right and left ventricular volume in
the same patient normalized for body surface area. EF = ejection fraction; EDV = end-diastolic volume; ESV = end-systolic volume; RV = right ventricle; LV = left ventricle; SV = stroke volume.
ma1 in the 16 patients in whom it was performed. The precatheterization diagnosis in eight patients was ischemic heart disease, in one other patient the diagnosis was mitral valve prolapse, and in another diagnosis was cardiomyopathy. The remaining seven patients had no demonstrable organic heart disease (excluding arrhythmia) before catheterization. Cardiac catheterization data (Table I). By study design intracardiac pressure, cardiac output, valve function, wall motion, and coronary arteriograms were normal. Right atria1 mean pressure ranged from 0 to 7 (3.2 ? 2.0) mm Hg. Right ventricular systolic pressure ranged from 13 to 32 (21 -t 4.2) mm Hg. Right ventricular end-diastolic pressure ranged from 2 to 8 (4.2 ? 1.9) mm Hg. Mean pulmonary capillary wedge pressure ranged from 3 to 10 (7.4 f 2.6) mm Hg. Left ventricular systolic pressure ranged from 92 to 160 (118 * 19) mm Hg. Left ventricular end-diastolic pressure ranged from 3 to 12 (7.9 +- 2.6) mm Hg. Cardiac output ranged from 2.6 to 4.6 (3.3 f 0.5) L/min/m2. No transvalvular gradient or intracardiac shunt was detected. Coronary arteriograms in 14 patients were normal. There were absolutely no data to suggest ischemic
February. 1985 Heart Journal
heart disease in the remaining three patients who had not undergone coronary angiography. Right and left ventricular angiography. Regional wall motion was normal on visual inspection of biplane right and left ventricular angiograms. There was no evidence of tricuspid or mitral valve prolapse or insufficiency, except that which was catheter or arrhythmia induced. Right ventricular end-systolic volume ranged from 22 to 47 (33 -t 8.0) cc/m2 (Table II). Right ventricular end-diastolic volume ranged from 54 to 98 (76 ? 14) cc/m’. Calculated right ventricular stroke volume ranged from 31 to 60 (43.5 f 8.3) cc/m2 and right ventricular ejection fraction ranged from 0.48 to 0.62 (0.57 t 0.04). Left ventricular end-systolic volume ranged from 13 to 34 (22 t 5.3) cc/m2 and left ventricular enddiastolic volume ranged from 48 to 90 (70 + 12) cc/m2. Calculated left ventricular stroke volume ranged from 29 to 70 (48 rt 11) cc/m” and left ventricular ejection fraction ranged from 0.57 to 0.84 (0.68 +- 0.07). Comparison
of ventricular
volumes
(Table
II and Fig.
1). The heart rate during right ventricular angiography was 79.5 + 13.5 bpm and during left ventricular angiography was 80.6 -t 13.6 bpm, p = NS. Right ventricular end-diastolic volume”was slightly larger than left ventricular end-diastolic volume (p < 0.03) and right ventricular end-systolic volume was always greater than left ventricular end-systolic volume (p < 0.00005). The calculated right and left ventricular stroke volumes were not significantly different. Left ventricular ejection fraction was always greater than right ventricular ejection fraction (p < 0.00005). DISCUSSION
With present-day angiographic methods direct comparison of right and left ventricular volume in the same heart is difficult, since both ventriculograms are rarely performed in patients with normal ventricles. Therefore, in a group of adult patients who were clinically and hemodynamically screened to exclude organic heart disease, comparative right and left ventricular volumes were studied. In all patients left ventricular end-systolic volume was less than right ventricular end-systolic volume. Left ventricular end-diastolic volume was less than right ventricular end-diastolic volume in 12 of 17 patients studied. Although there were individual differences in right and left ventricular stroke volume, there was no statistical difference when the stroke volume of the right and left ventricle for the entire study group was compared. As a result of these volume
Volume
109
Number
2
relationships, left ventricular ejection fraction exceeded right ventricular ejection fraction in all instances. Right and left ventricular angiography. Angiographic studies comparing right and left ventricular volumes with one exception have appeared in the pediatric reports.‘O-l5 One hundred twenty-four “normal” patients form the basis of these reports. Most investigators found left ventricular ejection fraction to be greater than right ventricular ejection fraction, right ventricular end-systolic volume to be greater than left ventricular end-systolic volume, and right ventricular end-diastolic volume to be greater than left ventricular end-diastolic volume. However, Graham et al.” found no difference in right and left ventricular ejection fraction, end-systolic volume, and enddiastolic volume. Boak et a1.,15in a small number of adults, also found no difference between right and left ventricular end-diastolic volume. Although most investigators found no difference in right and left ventricular stroke volume, both Boak et a1.15and Carlsson et al.‘O reported differences. The latter group corrected right ventricular stroke volume for ectopy that occurred on right ventricular injection of contrast material by multiplying the observed right ventricular stroke volume by right ventricular diastolic filling period divided by left ventricular diastolic filling period to achieve equality between the two ventricular outputs. Many of the previous pediatric studies used sufficient sedation to produce rapid heart rates and possible depression of the inotropic state. Some were based on mixed populations of normal patients and patients with “mild” congenital heart defects. Levophase angiography of the left ventricle was common, which in adults and older children has been reported to underestimate left ventricular ejection fraction and alter stroke volume.18 It is possible that methodology may have influenced the volume relationships between the two ventricles in some of the previous studies. Fetal ventricular volumes. Experimental studies in humans and animals have shown that in the fetal state right ventricular end-diastolic volume is much greater than left ventricular end-diastolic volume and the right ventricular stroke volume is twice left ventricular stroke volume.1g Change in right and left ventricular volumes is stated to occur within 24 hours after birth. However, in a recent longitudinal echocardiographic study of the normal human fetus, similarities between right and left ventricular sizes, wall thicknesses, and free wall weights have been reported and do not support the theory of right ventricular dominance during gestation.20 Angiographic limitations. This study and all angio-
Comparative
RV and LV volumes
325
graphic studies have limitations in sampling and loading conditions. Only a few cardiac cycles are available to obtain end-diastolic volume and endsystolic volume. Cineangiographic images were obtained on inspiration or expiration to eliminate the diaphragm and improve quality of image. Respiratory maneuvers can inadvertently produce the Valsalva or Muller effect altering ventricular volume. It has been shown that even normal respiration mildly affects the two ventricles with changes in right ventricular stroke volume preceding left ventricular stroke volume by one cardiac cycle.21 Prior ectopic contractions and volume expansion of contrast material also influence loading conditions.10~22-25In our study the sequence of right and left ventriculography was not randomly varied and the interval between right and left ventriculography was not the same in all patients. This could produce larger volumes and decreased ejection fractions secondary to the negative inotropic effect of the contrast media. Fortuitously some of these effects are small in magnitude or opposite in direction negating their overall influence, and the normal ventricular response is a rapid return to steady state. Radionuclide angiographic studies. Two radionuelide angiographic studies, where both right and left ventricular ejection fractions were assessed in the same patient, support our angiographic findings. Berger et a1.26studied 50 “normal” adults with the first-pass radionuclide method and obtained a right ventricular ejection fraction of 0.45 to 0.71 (0.55 +0.10) and a left ventricular ejection fraction of 0.58 to 0.70 (0.69 +- 0.10). Right ventricular ejection fraction was less than left ventricular ejection fraction in 44 of 50 patients. Korr et a1.27studied 20 “normal” subjects with equilibrium-gated radionuclide angiography, whose right ventricular ejection fraction ranged from 0.42 to 0.67 (0.53 ? 0.06) and left ventricular ejection fraction range from 0.55 to 0.85 (0.71 f 0.10). In no radionuclide angiographic study were right and left ventricular volumes compared in the same patient. It has been suggested that at end diastole the less muscular right ventricle has a larger volume than the left ventricle because of its increased distensibility. 28The left ventricle with a greater muscle mass and a different mode of contraction more completely empties its contents. The right ventricle, however, achieves the same stroke output as the left ventricle from higher levels of end-diastolic and end-systolic volume resulting in a lower right ventricular ejection fraction than the left ventricular ejection fraction. Our results support most earlier pediatric observations of the relationship between right and left
February,
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ventricular volume and the persistence of this association in adult life. We gratefully acknowledge the technical Ehler and Jonas Juska and the secretarial Jefferson.
assistance assistance
14.
of Donna of Frances
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