- Email: [email protected]
Effect of alterations in ventricular rate on cardiac output in complete heart block
Effect of Alterations in Ventricular Cardiac Output in Complete PHILIP SAMET, M.D.,
F.A.c.c.,
\~TILLIAM
Rate on
Heart Block*
H. BERNSTEIN, M.D., F.A.c.c.,
AARON MEDOW,
M.D.
and DAVID A. NATHAN, M.D., F.A.C.C.
Miami
Beach, Florida
T
cause problems by passage of the tip forward into the pulmonary artery or back into the right atrium, as may occur with the first two types. These three kinds of catheters permit varying the ventricular rate from the idioventricular control rate, generally 30 to 40/ min., to upper rates of 120 to 130. Card& output was determined in all 17 patients by inscription of systemic arterial indicator-dilution curves with indocyanine green via a Gilford densitometer. A Cournand needle was inserted into a brachial or femoral artery for this purpose. In 10 of the 17 patients simultaneous pulmonary artery indicator-dilution curves were also inscribed via a second catheter passed into the pulmonary artery. The site of injection of the indocyanine green in most patients was the right atrium or superior vena cava via a third catheter passed into the vena caval chambers. Blood withdrawn from the pulmonary and systemic arterial trees was reinfused by a Harvard constant infusionwithdrawal unit. Cardiac output determinations were made at varying ventricular rates, as indicated in Table I.
HE development of present day therapy for patients with complete heart block and Stokes-Adams episodes has passed through many phases. Present emphasis is on various types of implantable electronic pacemakers for artificial stimulation. Such pacemakers vary in electronic and physiologic characteristics. The essential features of the latter relate to the potentialities for variation of ventricular rate and for synchronization of atrioventricular function. The evidence for the importance of the latter has been analyzed elsewhere.lg2 The purpose of this paper is to examine data on the effect of variations in ventricular rate on the cardiac output of patients with complete heart block. SUBJECTS AND METHODS The relation between ventricular rate and cardiac output was investigated in 17 patients with complete heart block complicating arteriosclerotic heart disease ; all but one were men. Their ages ra*lged from 54 to 82 years. Cardiac output studies were performed prior to insertion of a permanent implantable pacemaker. In the earlier cases an idioventricular fixedrate implantable pacemaker3 was utilized; more recently a synchronous P-wave pacer was employed.4 The initial step in these studies consisted of insertion of a right ventricular pacemaker electrode catheter. In the initial studies a unipolar electrode catheters was passed into the right ventricular outflow tract. The circuit was completed with a subcutaneous ground and a Medtronic portable unit. More recently, a bipolar electrode catheter6 was utilized, with the tip placed in the right ventricular outflow tract. Of late, another type of bipolar electrode catheter (U. S. Catheter Co.) has been employed. The tip is placed in the right pulmonary artery; the two electrodes are placed in the right ventricular outflow tract. This type of catheter is least prone to
RESULTS Cardiac Output: Five patterns of output response to alterations in ventricular rate were observed in our 17 cases (Table I). In the first group of 5 patients (Cases l-5) the rise in cardiac index with increasing ventricular rates was minimal, less than 10 per cent. In 6 patients (Cases 6-11) the output rose more than 10 per cent as the ventricular rate was increased ; however, a secondary fall in output developed as the ventricular rate further increased, resulting in a bell-shaped curve relating output and heart rate. Peak cardiac outputs were generally recorded at ventricular rates of 80 to 105/min., but maximal outputs were also noted at lower ventricular rates. In 1 patient (Case 12) cardiac index continued to
* From the Cardio-Pulmonary Laboratory, Department of Medicine, Mount Sinai Hospital, Miami Beach, Fla., and the Department of Medicine, University of Miami School of Medicine, Coral Gables, Fla. This study was supported in part by a grant from the National Heart Institute (H-4249). VOLUME
14,
OCTOBER
1964
477
Samet,
478
Bernstein,
Medow ‘I‘AWLI..
L
Cardiac Output and Ventricular
Case
Sites of Dye Iniection and S~mpl&
V.R. (per min.
1
R.A. to B.A.
43 48 54 60 102 103 126
2
Ceph. Vein to P.A. and F.A.
32 46 50 54 73 94 112 126 138
3
P.A. to F.A.
4
R.A. to P.A. and F.A.
35 49 63 77 93* 104*
5
R.A. to F.A.
45 45 57 78 93 104 117
6t
Ceph. Vein to P.A. and F.A.
36 39 49 51 59 67 68 81 97 109 120 134
7
P.A. to F.A.
1
and Nathan
Rate Relationships
C.I. (PA.) ~l,.,‘min./M’.)
C.I. (F.A.) (L./min./hiz.)
S.V. (PA.)
(ml.)
(ml.1
2.72 3.12 2.97 3.11 2.91 2.89 2.88 1.49 1.66 1.63 1.80 1.70 1.69
1.64 l’.;b 1’.68 1.75 1.57 1.55 1.51
1’.65 1 .62
107 110 94 98 49 48 39 92
83 65 58 60 42 32
‘54 ‘4; 33 25 23 20
‘24 21
1.75 1.85 1.92 1.78
47 48 60 73 1.61 1 83 1.88 1.85 1.64 1.58
1 62 1.87 1.73 1.61 1.64
66 69 57 43 79 64 52 42 30 26
80 66 48 36 30
1.89 2.08 2.08 1.81 2.14 1.96 1.74 3.56 3.70 4.46 4.41 4.93 4.63 5.11 5.27
3.69 3.63 4.22 4.33 4.65 4.50 4.92 5.57 3.65 3.05 3.03 2.53
3’. 48 3.09 2.79
32 39 42 50 56 68 84 104 116 126
S.V. (F.A.)
71 79 62 39 39 32 25 151 145 139 132 128 106 115 100
157 143 132 130 121 103 111 105 58 43 39 29
‘b; 39 32
1.87 1.99 2.04 2.15 2.23 2.35 2.41 2.64 2.25 2.14
112 98 93 82 76 66 55 48 37 32
* Chest pain during these output determinations. t Intravenous isopropylnorepinephrine infused throughout study. THE
AMERICAN
JOURNAL
OF
CARDIOLOGY
Ventricular
Rate
and Cardiac
Output
in Heart
479
Block
TABLE I (continued) Cardiac Output
Case
8
9
Sites of Dye Injection and Sampling R.A.
R.A.
to P.A. and F.A.
to P.A. and F.A.
and Ventricular
(pey’r%n.)
1.77 -
49 50 63 79 91 106 116
2.60 2.57 2.93
R.A.
to F.A.
44 48 70 91 99 107
11
R.A.
to P.A. and F.A.
51 52 66 84 94 106 124
12
S.V.C.
13
R.A.
14
V.R. artery; artery.
R.A.
to P.A. and F.A.
to P.A. and F.A.
(~~mi?$~.)
38 42 53 57 60 92 98 118
10
to F.A.
Rate Relationships
1.67 1.83 1.73 1’.87 1.82
C.I. (F.A.) (L./min./M*.)
1.57 1.72 1.61 1.71
91
81 80 59 59
. ..
‘G 37
2’.66 2.82
91 88 80
46 46 54 66 79 92 109 126 148
‘37
2.09 2.13
53 62 63 75 83 91 97 108 120
2.43
2..;3 2.32 2.33 2.41
2..39 2’:52 2.45 2.36 2.93 2.86
92 ‘72 61
2.58 2.38 3.00 2.94 2.90 2.99 2.47
2.04 2.19 2.16 2.34 2.30 2.34 2.20 2.25 2.47 2.23 2.29 2.63 2.64 2.28 2’. 74
‘42 35 72 71 55 51 39 39
78 74 81 57 54 48 33
85 77 77 59 52 48 34 65 69 55 49 39 37 30 28 25
1.69 1.81 1.67 1.83 1.73 1.92 1.87 2.01 2.06
64 76 75 90 91 100 113
‘44 39 39
‘55 Z.60 2.39 2.01 2.20 2.46 2.95 2.49 2.66
2.36 2.27 3.17 2.85 3.03 3.04 2.42
(F.A.)
(ml.)
2.08 1.95 1.77 2.64
S.V.
(ml.)
‘62 63 57
2..2 2’.53
S.V. (P.V.)
60 52 ‘48 47 43 39 98 ‘8; ‘65 58 52 58 51
59 53 53 48 46 43 36 91 86 76 66 G8 62 50 ‘49
= ventricular rate; C.I. = cardiac index; S.V. = stroke volume; P.A. = pulmonary artery; F.A. = femoral R.A. = right atrium; Ceph. Vein = cephalic vein; S.V.C. = superior vena cava; and B.A. = brachial
VOLUME 14, OCTOBER 1964
380
Samet,
Bernstein, ‘1‘01.E
C!ardiac output
Case
Sites of Dye injection and Sampling
15
R.:\. to PA.
16
17
and &‘.A.
Medow I (mntinucd)
and Ventricular
V.K. (per min.)
and Nathan
Rate Relationships
C.I. (PA.) il,.,‘min./M”.)
C.1. (F.A.) (l,.!min.!Ms.)
S.V. (PA.) (ml. 1
S.V. (F.A.)
(In].)
5, 58 65 84 87 95 105 125
2.04 2.31 2.23 2.26 2.59 2.47 2.42 2.53
2.09 1.98 -.3 33 2.32 2.35 2.29 2.27
76 77 66 52 57 50 45 39
78 66 66 53 52 47 42
R.A. to P.A. and F.A.
56 66 74 88 105 120
1.60 1.41 1.92 2.11 2.09
1.80 1.48 1.91 2.07 2.15 2.14
48 36 44 40 34
54 38 44 40 35 30
R.A. to F.A.
46 46 51 72 92 106 117 126
rise progressively (more than 10%) as the rate was increased. In 4 patients (Cases 13-16) the control cardiac index rose more than 10 per cent, with increasing ventricular rates, to a higher level, which remained constant as further increments in ventricular rate were induced. In 1 patient (Case 17) the maximal cardiac index was observed at the slowest ventricular rates of 46 to 5l/minute. At higher rates, more than a 10 per cent fall in cardiac index was noted, and it remained constant at this lower level as the ventricular rate was progressively increased. No relationship was discernible between the clinical condition of these various patients and the pattern of response in output to an increase in ventricular rate. In summary, therefore, increases in cardiac output were detected with increments of ventricular rate in 11 of the 17 patients studied. The ventricular rate associated with peak cardiac outputs varied from patient to patient. Prediction of the rate associated with maximal output in any one patient was therefore not possible. Stroke Volume: In all five groups of patients, regardless of the response of cardiac output to increments of ventricular rate, stroke volume decreased with increases in rate. Even when the cardiac output rose as the rate was increased,
.
1.94 1.96 1.94 1.61 1.63 1.72 1.57 1.60
73 74 66 39 31 28 23 22
stroke volume fell, indicating that the increase in output was proportionately less than the increase in rate. DISCUSSION The cardiac output is most frequently diminished in patients with complete heart block and slow idioventricular rhythm.‘** Both myocardial disease and the slow ventricular rate may contribute to the decrease in cardiac output. The increase in arterial-mixed venous oxygen difference that has been noted casts doubts on the concept that a low basal metabolic rate is the sole cause of the low cardiac output.s If the possible contribution of the slow ventricular rate per se to the diminution in cardiac output could be removed, the clinical status of the patient would, in all probability, be improved. It is, therefore, of considerable clinical interest to determine the effect of alterations in ventricular rate on cardiac output in patients with complete heart block and slow ventricular rates. The data reported in Table I clearly demonstrate that changes in rate are associated with increases in output in two of every three subjects studied at rest. Similar but not strictly comparable data in 24 patients (at rest) are available in the literature. Escher et a1.g studied 10 patients with complete heart block on 11 occasions, emTHE
AMERICAN
JOURNAL
OF CARDIOLOGY
Ventricular
Rate
and Cardiac
ploying a right ventricular outflow tract electrode catheter. In 9 of the 10 the control cardiac outputs were low. In 7 patients, output increments of 35 to 140 per cent were observed as the ventricular rate was increased. In 2 of the 7, a bell-shaped relation between output and rate was noted, with a secondary decrease in output as the ventricular rates were pushed to their maximal levels. In 3 of the 7 the output continued to increase as the ventricular rates were raised. In the remaining 2 output increased to a second level as the ventricular rate rose. A relation between cardiac stroke volume and heart rate was not observed. The data in individual patients in this series have not been published in detail. Wade and BishoplO have reported data in 8 patients with complete heart block (unpublished work by Segal and Hudson, 1961) in whom the relation between cardiac output and heart rate was explored at two levels of oxygen consumption, i.e., at rest and during exercise. The average control cardiac index in these patients was 2.1 L./min./Mz. (range 1.4-2.5). This level rose to 2.8 L./min./M2. (range 1.8-4.1) when the ventricular rate was increased to 70-90. The control ventricular rates were not given. Bevegard’l has made observations on 2 patients with complete heart block. The ventricles were paced by electrodes sutured into the myocardium. In the first subject the cardiac outputs (Fick) were 3.1, 3.7, 4.8, 6.1 and 5.5 L./min. at ventricular rates of 22, 31, 52, 74 and 109, respectively. In the second subject the outputs were 3.6, 4.4, 6.0, 6.7 and 6.3 L./ min. at rates of 28, 55, 72, 91 and 99, respectively. In both subjects, stroke volume progressively decreased as the ventricular rate increased, indicating that ventricular rate increased more rapidly than cardiac output. Lasry et a1.12 studied 1 patient with complete heart block treated by pacemaker implantation. Cardiac output was calculated by using indocyanine green as the indicator. As the heart rate was increased from a’ control rate of 62 to rates of 76, 80, 84, 92, 96 and 104 by adjustment with an external induction-coil mechanism, cardiac output increased only minimally and was 3.69, 3.74, 3.48, 3.69, 4.06, 3.81 and 4.09 L./min. at the respective ventricular rates. These changes are of limited significance. Stroke volume again progressively decreased with increments in heart rate. Muller and BelleP3 have also evaluated the role that ventricular rate plays in cardiac output VOLUME
14,
OCTOBER
1964
Output
in Heart
Block
481
levels. In a single patient with complete heart block the control cardiac output (F’ick) was 2.72 L./min. at a ventricular rate of 30. When the rate was elevated to 50 by a right ventricular outflow tract catheter, the output rose to 3.22 L./min. With further increases in ventricular rate to 70 output fell to 2.60. These investigators also report that in 4 other patients with complete heart block, cardiac output increased with rate increases up to a level of 50 to bO/min. Further increase in rate in these 4 patients was associated with decreases in cardiac output; the detailed data have not been reported. These observations, together with data demonstrating the importance of synchronous atrioventricular contraction, have produced dissatisfaction with the fixed-rate implantable idioventricular pacemaker. New pacemakers were developed to permit rate variations.i4+ Even the original Chardack unit has been modified to permit alteration of a preset ventricular rate. Haupt et al.” studied 2 patients after implantation of a variable rate idioventricular pacemaker. Cardiac output was determined with indocyanine green indicator. In the first patient, cardiac indices were 3.41, 4.66, 3.85 and 3.89 L./min./M2. at rates of 66, 84, 102 and 120, respectively. In the second subject the indices were 2.94, 3.17, 3.38 and 3.22 at rates of 66, 79, 97 and 119, respectively. Stroke volume fell with increasing ventricular rates. Experimental observations by Miller et al.‘* also support the thesis that cardiac output may be significantly altered by rate changes in the dog with complete heart block. The ventricular rate was controlled by a right ventricular outflow tract electrode catheter. Increasing the ventricular rate to 60 from the slower idioventricular level resulted in a progressive rise in output. Ventricular rates between 60 to 90 beats per minute resulted in more modest elevations in output. Between rates of 90 to 150, cardiac output remained fixed; above 150 beats per minute cardiac output decreased with increasing rates. In a similar fashion, study of the effect of varying ventricular rate during similar exercise loads has demonstrated an increment in output at the higher ventriculate rate during exercise.r0~ir~r7 These observations during idioventricular pacing point to the importance of variable-rate pacemakers for the therapy of complete heart block. The ventricular rate at which cardiac output is maximal cannot be predicted, and adequate evidence is available of the importance
Samet,
482
Bernstein.
of synchronous as opposed to asynchronous atrio\,entricular contraction.‘JVIY-Yt It is therefore our conviction that the pacemaker of’ choice at this time is the synchronous P-wave pacemaker (Cordis), in which the ventricular rate is determined bv the atria1 rate via an artificial electronic circuit. The latter unit The physical has been employed in 22 patients. characteristics of the unit and the clinical results have been presented in detail elsewhere.2 SUMMARY
Evidence is presented, both from a review of the literature and from original observations in this laboratory during cardiac catheterization in man, to demonstrate that the cardiac output in the majority of patients with complete heart block can be increased with increments in These data, especially when ventricular rate. considered in conjunction with the demonstrated importance of synchronous as opposed to asynchronous atrioventricular contraction, strongly suggest that synchronous P-wave pacemakers, such as the one developed by our group, are physiologically and clinically superior to idioventricular pacemakers of either the fixed or variable rate types. REFERENCES 1. SAMET, P., JACOBS, W., BERNSTEIN, W. H. and SHANE, R. Hemodynamic sequelae of idioventricular pacemaking in complete heart block. Am. J. Card&l., 11 : 594, 1963. 2. NATHAN, D. A., SAMET, P., CENTER, S. and WV, C. Y. Long term correction of complete heart block. Clinical and physiologic studies of a new type of implantable synchronous pacer. Prog. Cardiovas. Dis., 6~538, 1964. 3. CHARDACK, W. M., GAGE, A. A. and GREATBATCH, W. Correction of complete heart block by a selfcontained and subcutaneously implanted pacemaker. J. Thor&c & Cardiovas. Surg., 42: 814, 1961. 4. NATHAN, D. A., CENTER, S., Wu, C. Y. and KELLER, W. An implantable synchronous pacemaker for the long term correction of complete heart block. Am. J. Cardiol., 11: 362, 1963. 5. FURMAN, S. and SCHWEDEL, J. B. Intracardiac pacemaker for Stokes-Adams seizures. New England J. Med., 261: 943, 1959. 6. PARSONNET,V., ZUCKER,I. R., GILBERT,L. and ASA, M. An intracardiac bipolar electrode for interim Am. J. treatment of complete heart block. Cardiol.. 10: 261, 1962. 7. LEVINSON, D. C., GUNTHER, L., MEEHAN, J. P., GRIFFITH, G. C. and SPRITZLER, R. J. Hemo-
Medow
and Nathan
dynamic studies in five patients with heart block and slow ventricular rates. C’irculatio~l, 12: 739, 1955. 8. S-~ACK, M. F., KADER, B., SOROL, 15..I.,I:ARBER. S. J. and EICHNA, I,. W. Cardiovascular hemo-
dynamic functions in complete heart block and the effect of isopropylnorepinephrine. Circulation, 17: 526, 1958.
9. ESCHER, D. J. W., et al.
Cardiovascular dynamic responses to artificial pacing of patients in heart block. Circulation, 24: 928, 1961. 10. WADE, 0. L. and BISHOP, J. M. Cardiac Output and Regional Blood Flow, p. 183. Philadelphia, 1962. F. A. Davis Co. 11. BEVEGARD,S. Observations on the effect of varying ventricular rate on the circulation at rest and dur-
ing exercise in two patients with an artificial pacemaker. Acta med. scandinau., 172: 615, 1962.
12. LASRY, J. E., BENCHIMOL,A., BARONOFSKY,I. D. and DE CARVALNO, F. R. Cardiovascular hemo-
dynamics and the internally placed cardiac pacemaker. Am. J. Cardiol.. 11: 399. 1963.
13. MULLER, 0. F. and BEL~ET, S. ‘Treatment of intractable heart failure in the presence of complete atrioventricular block by the use of the internal cardiac pacemaker. New England J. Med., 265: 768, 1961. 14. GLENN, W. W. L., MAURO, L., LONGO, E., LAVIETAS, P. H. and MACKAY, F. J. Remote stimulation of the heart by radio-frequency transmission. Clinical application to a patient with Stokes-Adams syndrome. New England J. Med., 261: 948, 1959. 15. KANTROWITZ, A., COHEN, R., RAILLARD, H., SCHMIDT,J. and FELDMAN,D. S. The treatment of complete heart block with an implanted, controllable pacemaker. Surg. Gynec. @ Obst., 115: 417, 1962. 16. HICKMAN, D. M. et al. A portable miniature transistorized radio-frequency coupled cardiac pacemaker. IRE Tr. Bio-Med. Electron. B.M.E., 8: 258, 1961. 17. HAUPT, G. J., MYERS, R. N., DALY, J. W., and BIRKHEAD,N. C. Implanted cardiac pacemakers of variable frequency. J.A.M.A., 185: 87, 1963. 18. MILLER, D. E., GLEASON, W. L., WHALEN, R. E., MORRIS, .J. J. and MCINTOSH, H. D. Effect of ventricular rate on the cardiac output in the dog with chronic heart block. Circulation Res., 10: 658, 1962. 19. GILMORE, J. P., SARNOFF, S. J., MITCHELL, J. H. and LINDEN, R. J. Synchronicity of ventricular contraction: observations comparing haemodynamic effects of atria1 and ventricular pacing. Brit. Heart J., 25: 299, 1963. 20. SKINNER,N. S., JR., MITCHELL, J. H., WALLACE, A. G., and SARNOFF, S. J. Hemodynamic effects of altering the timing of atria1 systole. Am. J. Physiol., 205: 499, 1963. 21. MITCHELL, J. H., GILMORE,J. P. and SARNOFF, S. J. The transport function of the atrium. Factors influencing the relation between mean left atria1 pressure and left ventricular end diastolic pressure. Am. J. Cardiol., 9: 237, 1962.
THE AMERICANJOURNAL
OF CARDIOLOGY
F.A.c.c.,
\~TILLIAM
Rate on
Heart Block*
H. BERNSTEIN, M.D., F.A.c.c.,
AARON MEDOW,
M.D.
and DAVID A. NATHAN, M.D., F.A.C.C.
Miami
Beach, Florida
T
cause problems by passage of the tip forward into the pulmonary artery or back into the right atrium, as may occur with the first two types. These three kinds of catheters permit varying the ventricular rate from the idioventricular control rate, generally 30 to 40/ min., to upper rates of 120 to 130. Card& output was determined in all 17 patients by inscription of systemic arterial indicator-dilution curves with indocyanine green via a Gilford densitometer. A Cournand needle was inserted into a brachial or femoral artery for this purpose. In 10 of the 17 patients simultaneous pulmonary artery indicator-dilution curves were also inscribed via a second catheter passed into the pulmonary artery. The site of injection of the indocyanine green in most patients was the right atrium or superior vena cava via a third catheter passed into the vena caval chambers. Blood withdrawn from the pulmonary and systemic arterial trees was reinfused by a Harvard constant infusionwithdrawal unit. Cardiac output determinations were made at varying ventricular rates, as indicated in Table I.
HE development of present day therapy for patients with complete heart block and Stokes-Adams episodes has passed through many phases. Present emphasis is on various types of implantable electronic pacemakers for artificial stimulation. Such pacemakers vary in electronic and physiologic characteristics. The essential features of the latter relate to the potentialities for variation of ventricular rate and for synchronization of atrioventricular function. The evidence for the importance of the latter has been analyzed elsewhere.lg2 The purpose of this paper is to examine data on the effect of variations in ventricular rate on the cardiac output of patients with complete heart block. SUBJECTS AND METHODS The relation between ventricular rate and cardiac output was investigated in 17 patients with complete heart block complicating arteriosclerotic heart disease ; all but one were men. Their ages ra*lged from 54 to 82 years. Cardiac output studies were performed prior to insertion of a permanent implantable pacemaker. In the earlier cases an idioventricular fixedrate implantable pacemaker3 was utilized; more recently a synchronous P-wave pacer was employed.4 The initial step in these studies consisted of insertion of a right ventricular pacemaker electrode catheter. In the initial studies a unipolar electrode catheters was passed into the right ventricular outflow tract. The circuit was completed with a subcutaneous ground and a Medtronic portable unit. More recently, a bipolar electrode catheter6 was utilized, with the tip placed in the right ventricular outflow tract. Of late, another type of bipolar electrode catheter (U. S. Catheter Co.) has been employed. The tip is placed in the right pulmonary artery; the two electrodes are placed in the right ventricular outflow tract. This type of catheter is least prone to
RESULTS Cardiac Output: Five patterns of output response to alterations in ventricular rate were observed in our 17 cases (Table I). In the first group of 5 patients (Cases l-5) the rise in cardiac index with increasing ventricular rates was minimal, less than 10 per cent. In 6 patients (Cases 6-11) the output rose more than 10 per cent as the ventricular rate was increased ; however, a secondary fall in output developed as the ventricular rate further increased, resulting in a bell-shaped curve relating output and heart rate. Peak cardiac outputs were generally recorded at ventricular rates of 80 to 105/min., but maximal outputs were also noted at lower ventricular rates. In 1 patient (Case 12) cardiac index continued to
* From the Cardio-Pulmonary Laboratory, Department of Medicine, Mount Sinai Hospital, Miami Beach, Fla., and the Department of Medicine, University of Miami School of Medicine, Coral Gables, Fla. This study was supported in part by a grant from the National Heart Institute (H-4249). VOLUME
14,
OCTOBER
1964
477
Samet,
478
Bernstein,
Medow ‘I‘AWLI..
L
Cardiac Output and Ventricular
Case
Sites of Dye Iniection and S~mpl&
V.R. (per min.
1
R.A. to B.A.
43 48 54 60 102 103 126
2
Ceph. Vein to P.A. and F.A.
32 46 50 54 73 94 112 126 138
3
P.A. to F.A.
4
R.A. to P.A. and F.A.
35 49 63 77 93* 104*
5
R.A. to F.A.
45 45 57 78 93 104 117
6t
Ceph. Vein to P.A. and F.A.
36 39 49 51 59 67 68 81 97 109 120 134
7
P.A. to F.A.
1
and Nathan
Rate Relationships
C.I. (PA.) ~l,.,‘min./M’.)
C.I. (F.A.) (L./min./hiz.)
S.V. (PA.)
(ml.)
(ml.1
2.72 3.12 2.97 3.11 2.91 2.89 2.88 1.49 1.66 1.63 1.80 1.70 1.69
1.64 l’.;b 1’.68 1.75 1.57 1.55 1.51
1’.65 1 .62
107 110 94 98 49 48 39 92
83 65 58 60 42 32
‘54 ‘4; 33 25 23 20
‘24 21
1.75 1.85 1.92 1.78
47 48 60 73 1.61 1 83 1.88 1.85 1.64 1.58
1 62 1.87 1.73 1.61 1.64
66 69 57 43 79 64 52 42 30 26
80 66 48 36 30
1.89 2.08 2.08 1.81 2.14 1.96 1.74 3.56 3.70 4.46 4.41 4.93 4.63 5.11 5.27
3.69 3.63 4.22 4.33 4.65 4.50 4.92 5.57 3.65 3.05 3.03 2.53
3’. 48 3.09 2.79
32 39 42 50 56 68 84 104 116 126
S.V. (F.A.)
71 79 62 39 39 32 25 151 145 139 132 128 106 115 100
157 143 132 130 121 103 111 105 58 43 39 29
‘b; 39 32
1.87 1.99 2.04 2.15 2.23 2.35 2.41 2.64 2.25 2.14
112 98 93 82 76 66 55 48 37 32
* Chest pain during these output determinations. t Intravenous isopropylnorepinephrine infused throughout study. THE
AMERICAN
JOURNAL
OF
CARDIOLOGY
Ventricular
Rate
and Cardiac
Output
in Heart
479
Block
TABLE I (continued) Cardiac Output
Case
8
9
Sites of Dye Injection and Sampling R.A.
R.A.
to P.A. and F.A.
to P.A. and F.A.
and Ventricular
(pey’r%n.)
1.77 -
49 50 63 79 91 106 116
2.60 2.57 2.93
R.A.
to F.A.
44 48 70 91 99 107
11
R.A.
to P.A. and F.A.
51 52 66 84 94 106 124
12
S.V.C.
13
R.A.
14
V.R. artery; artery.
R.A.
to P.A. and F.A.
to P.A. and F.A.
(~~mi?$~.)
38 42 53 57 60 92 98 118
10
to F.A.
Rate Relationships
1.67 1.83 1.73 1’.87 1.82
C.I. (F.A.) (L./min./M*.)
1.57 1.72 1.61 1.71
91
81 80 59 59
. ..
‘G 37
2’.66 2.82
91 88 80
46 46 54 66 79 92 109 126 148
‘37
2.09 2.13
53 62 63 75 83 91 97 108 120
2.43
2..;3 2.32 2.33 2.41
2..39 2’:52 2.45 2.36 2.93 2.86
92 ‘72 61
2.58 2.38 3.00 2.94 2.90 2.99 2.47
2.04 2.19 2.16 2.34 2.30 2.34 2.20 2.25 2.47 2.23 2.29 2.63 2.64 2.28 2’. 74
‘42 35 72 71 55 51 39 39
78 74 81 57 54 48 33
85 77 77 59 52 48 34 65 69 55 49 39 37 30 28 25
1.69 1.81 1.67 1.83 1.73 1.92 1.87 2.01 2.06
64 76 75 90 91 100 113
‘44 39 39
‘55 Z.60 2.39 2.01 2.20 2.46 2.95 2.49 2.66
2.36 2.27 3.17 2.85 3.03 3.04 2.42
(F.A.)
(ml.)
2.08 1.95 1.77 2.64
S.V.
(ml.)
‘62 63 57
2..2 2’.53
S.V. (P.V.)
60 52 ‘48 47 43 39 98 ‘8; ‘65 58 52 58 51
59 53 53 48 46 43 36 91 86 76 66 G8 62 50 ‘49
= ventricular rate; C.I. = cardiac index; S.V. = stroke volume; P.A. = pulmonary artery; F.A. = femoral R.A. = right atrium; Ceph. Vein = cephalic vein; S.V.C. = superior vena cava; and B.A. = brachial
VOLUME 14, OCTOBER 1964
380
Samet,
Bernstein, ‘1‘01.E
C!ardiac output
Case
Sites of Dye injection and Sampling
15
R.:\. to PA.
16
17
and &‘.A.
Medow I (mntinucd)
and Ventricular
V.K. (per min.)
and Nathan
Rate Relationships
C.I. (PA.) il,.,‘min./M”.)
C.1. (F.A.) (l,.!min.!Ms.)
S.V. (PA.) (ml. 1
S.V. (F.A.)
(In].)
5, 58 65 84 87 95 105 125
2.04 2.31 2.23 2.26 2.59 2.47 2.42 2.53
2.09 1.98 -.3 33 2.32 2.35 2.29 2.27
76 77 66 52 57 50 45 39
78 66 66 53 52 47 42
R.A. to P.A. and F.A.
56 66 74 88 105 120
1.60 1.41 1.92 2.11 2.09
1.80 1.48 1.91 2.07 2.15 2.14
48 36 44 40 34
54 38 44 40 35 30
R.A. to F.A.
46 46 51 72 92 106 117 126
rise progressively (more than 10%) as the rate was increased. In 4 patients (Cases 13-16) the control cardiac index rose more than 10 per cent, with increasing ventricular rates, to a higher level, which remained constant as further increments in ventricular rate were induced. In 1 patient (Case 17) the maximal cardiac index was observed at the slowest ventricular rates of 46 to 5l/minute. At higher rates, more than a 10 per cent fall in cardiac index was noted, and it remained constant at this lower level as the ventricular rate was progressively increased. No relationship was discernible between the clinical condition of these various patients and the pattern of response in output to an increase in ventricular rate. In summary, therefore, increases in cardiac output were detected with increments of ventricular rate in 11 of the 17 patients studied. The ventricular rate associated with peak cardiac outputs varied from patient to patient. Prediction of the rate associated with maximal output in any one patient was therefore not possible. Stroke Volume: In all five groups of patients, regardless of the response of cardiac output to increments of ventricular rate, stroke volume decreased with increases in rate. Even when the cardiac output rose as the rate was increased,
.
1.94 1.96 1.94 1.61 1.63 1.72 1.57 1.60
73 74 66 39 31 28 23 22
stroke volume fell, indicating that the increase in output was proportionately less than the increase in rate. DISCUSSION The cardiac output is most frequently diminished in patients with complete heart block and slow idioventricular rhythm.‘** Both myocardial disease and the slow ventricular rate may contribute to the decrease in cardiac output. The increase in arterial-mixed venous oxygen difference that has been noted casts doubts on the concept that a low basal metabolic rate is the sole cause of the low cardiac output.s If the possible contribution of the slow ventricular rate per se to the diminution in cardiac output could be removed, the clinical status of the patient would, in all probability, be improved. It is, therefore, of considerable clinical interest to determine the effect of alterations in ventricular rate on cardiac output in patients with complete heart block and slow ventricular rates. The data reported in Table I clearly demonstrate that changes in rate are associated with increases in output in two of every three subjects studied at rest. Similar but not strictly comparable data in 24 patients (at rest) are available in the literature. Escher et a1.g studied 10 patients with complete heart block on 11 occasions, emTHE
AMERICAN
JOURNAL
OF CARDIOLOGY
Ventricular
Rate
and Cardiac
ploying a right ventricular outflow tract electrode catheter. In 9 of the 10 the control cardiac outputs were low. In 7 patients, output increments of 35 to 140 per cent were observed as the ventricular rate was increased. In 2 of the 7, a bell-shaped relation between output and rate was noted, with a secondary decrease in output as the ventricular rates were pushed to their maximal levels. In 3 of the 7 the output continued to increase as the ventricular rates were raised. In the remaining 2 output increased to a second level as the ventricular rate rose. A relation between cardiac stroke volume and heart rate was not observed. The data in individual patients in this series have not been published in detail. Wade and BishoplO have reported data in 8 patients with complete heart block (unpublished work by Segal and Hudson, 1961) in whom the relation between cardiac output and heart rate was explored at two levels of oxygen consumption, i.e., at rest and during exercise. The average control cardiac index in these patients was 2.1 L./min./Mz. (range 1.4-2.5). This level rose to 2.8 L./min./M2. (range 1.8-4.1) when the ventricular rate was increased to 70-90. The control ventricular rates were not given. Bevegard’l has made observations on 2 patients with complete heart block. The ventricles were paced by electrodes sutured into the myocardium. In the first subject the cardiac outputs (Fick) were 3.1, 3.7, 4.8, 6.1 and 5.5 L./min. at ventricular rates of 22, 31, 52, 74 and 109, respectively. In the second subject the outputs were 3.6, 4.4, 6.0, 6.7 and 6.3 L./ min. at rates of 28, 55, 72, 91 and 99, respectively. In both subjects, stroke volume progressively decreased as the ventricular rate increased, indicating that ventricular rate increased more rapidly than cardiac output. Lasry et a1.12 studied 1 patient with complete heart block treated by pacemaker implantation. Cardiac output was calculated by using indocyanine green as the indicator. As the heart rate was increased from a’ control rate of 62 to rates of 76, 80, 84, 92, 96 and 104 by adjustment with an external induction-coil mechanism, cardiac output increased only minimally and was 3.69, 3.74, 3.48, 3.69, 4.06, 3.81 and 4.09 L./min. at the respective ventricular rates. These changes are of limited significance. Stroke volume again progressively decreased with increments in heart rate. Muller and BelleP3 have also evaluated the role that ventricular rate plays in cardiac output VOLUME
14,
OCTOBER
1964
Output
in Heart
Block
481
levels. In a single patient with complete heart block the control cardiac output (F’ick) was 2.72 L./min. at a ventricular rate of 30. When the rate was elevated to 50 by a right ventricular outflow tract catheter, the output rose to 3.22 L./min. With further increases in ventricular rate to 70 output fell to 2.60. These investigators also report that in 4 other patients with complete heart block, cardiac output increased with rate increases up to a level of 50 to bO/min. Further increase in rate in these 4 patients was associated with decreases in cardiac output; the detailed data have not been reported. These observations, together with data demonstrating the importance of synchronous atrioventricular contraction, have produced dissatisfaction with the fixed-rate implantable idioventricular pacemaker. New pacemakers were developed to permit rate variations.i4+ Even the original Chardack unit has been modified to permit alteration of a preset ventricular rate. Haupt et al.” studied 2 patients after implantation of a variable rate idioventricular pacemaker. Cardiac output was determined with indocyanine green indicator. In the first patient, cardiac indices were 3.41, 4.66, 3.85 and 3.89 L./min./M2. at rates of 66, 84, 102 and 120, respectively. In the second subject the indices were 2.94, 3.17, 3.38 and 3.22 at rates of 66, 79, 97 and 119, respectively. Stroke volume fell with increasing ventricular rates. Experimental observations by Miller et al.‘* also support the thesis that cardiac output may be significantly altered by rate changes in the dog with complete heart block. The ventricular rate was controlled by a right ventricular outflow tract electrode catheter. Increasing the ventricular rate to 60 from the slower idioventricular level resulted in a progressive rise in output. Ventricular rates between 60 to 90 beats per minute resulted in more modest elevations in output. Between rates of 90 to 150, cardiac output remained fixed; above 150 beats per minute cardiac output decreased with increasing rates. In a similar fashion, study of the effect of varying ventricular rate during similar exercise loads has demonstrated an increment in output at the higher ventriculate rate during exercise.r0~ir~r7 These observations during idioventricular pacing point to the importance of variable-rate pacemakers for the therapy of complete heart block. The ventricular rate at which cardiac output is maximal cannot be predicted, and adequate evidence is available of the importance
Samet,
482
Bernstein.
of synchronous as opposed to asynchronous atrio\,entricular contraction.‘JVIY-Yt It is therefore our conviction that the pacemaker of’ choice at this time is the synchronous P-wave pacemaker (Cordis), in which the ventricular rate is determined bv the atria1 rate via an artificial electronic circuit. The latter unit The physical has been employed in 22 patients. characteristics of the unit and the clinical results have been presented in detail elsewhere.2 SUMMARY
Evidence is presented, both from a review of the literature and from original observations in this laboratory during cardiac catheterization in man, to demonstrate that the cardiac output in the majority of patients with complete heart block can be increased with increments in These data, especially when ventricular rate. considered in conjunction with the demonstrated importance of synchronous as opposed to asynchronous atrioventricular contraction, strongly suggest that synchronous P-wave pacemakers, such as the one developed by our group, are physiologically and clinically superior to idioventricular pacemakers of either the fixed or variable rate types. REFERENCES 1. SAMET, P., JACOBS, W., BERNSTEIN, W. H. and SHANE, R. Hemodynamic sequelae of idioventricular pacemaking in complete heart block. Am. J. Card&l., 11 : 594, 1963. 2. NATHAN, D. A., SAMET, P., CENTER, S. and WV, C. Y. Long term correction of complete heart block. Clinical and physiologic studies of a new type of implantable synchronous pacer. Prog. Cardiovas. Dis., 6~538, 1964. 3. CHARDACK, W. M., GAGE, A. A. and GREATBATCH, W. Correction of complete heart block by a selfcontained and subcutaneously implanted pacemaker. J. Thor&c & Cardiovas. Surg., 42: 814, 1961. 4. NATHAN, D. A., CENTER, S., Wu, C. Y. and KELLER, W. An implantable synchronous pacemaker for the long term correction of complete heart block. Am. J. Cardiol., 11: 362, 1963. 5. FURMAN, S. and SCHWEDEL, J. B. Intracardiac pacemaker for Stokes-Adams seizures. New England J. Med., 261: 943, 1959. 6. PARSONNET,V., ZUCKER,I. R., GILBERT,L. and ASA, M. An intracardiac bipolar electrode for interim Am. J. treatment of complete heart block. Cardiol.. 10: 261, 1962. 7. LEVINSON, D. C., GUNTHER, L., MEEHAN, J. P., GRIFFITH, G. C. and SPRITZLER, R. J. Hemo-
Medow
and Nathan
dynamic studies in five patients with heart block and slow ventricular rates. C’irculatio~l, 12: 739, 1955. 8. S-~ACK, M. F., KADER, B., SOROL, 15..I.,I:ARBER. S. J. and EICHNA, I,. W. Cardiovascular hemo-
dynamic functions in complete heart block and the effect of isopropylnorepinephrine. Circulation, 17: 526, 1958.
9. ESCHER, D. J. W., et al.
Cardiovascular dynamic responses to artificial pacing of patients in heart block. Circulation, 24: 928, 1961. 10. WADE, 0. L. and BISHOP, J. M. Cardiac Output and Regional Blood Flow, p. 183. Philadelphia, 1962. F. A. Davis Co. 11. BEVEGARD,S. Observations on the effect of varying ventricular rate on the circulation at rest and dur-
ing exercise in two patients with an artificial pacemaker. Acta med. scandinau., 172: 615, 1962.
12. LASRY, J. E., BENCHIMOL,A., BARONOFSKY,I. D. and DE CARVALNO, F. R. Cardiovascular hemo-
dynamics and the internally placed cardiac pacemaker. Am. J. Cardiol.. 11: 399. 1963.
13. MULLER, 0. F. and BEL~ET, S. ‘Treatment of intractable heart failure in the presence of complete atrioventricular block by the use of the internal cardiac pacemaker. New England J. Med., 265: 768, 1961. 14. GLENN, W. W. L., MAURO, L., LONGO, E., LAVIETAS, P. H. and MACKAY, F. J. Remote stimulation of the heart by radio-frequency transmission. Clinical application to a patient with Stokes-Adams syndrome. New England J. Med., 261: 948, 1959. 15. KANTROWITZ, A., COHEN, R., RAILLARD, H., SCHMIDT,J. and FELDMAN,D. S. The treatment of complete heart block with an implanted, controllable pacemaker. Surg. Gynec. @ Obst., 115: 417, 1962. 16. HICKMAN, D. M. et al. A portable miniature transistorized radio-frequency coupled cardiac pacemaker. IRE Tr. Bio-Med. Electron. B.M.E., 8: 258, 1961. 17. HAUPT, G. J., MYERS, R. N., DALY, J. W., and BIRKHEAD,N. C. Implanted cardiac pacemakers of variable frequency. J.A.M.A., 185: 87, 1963. 18. MILLER, D. E., GLEASON, W. L., WHALEN, R. E., MORRIS, .J. J. and MCINTOSH, H. D. Effect of ventricular rate on the cardiac output in the dog with chronic heart block. Circulation Res., 10: 658, 1962. 19. GILMORE, J. P., SARNOFF, S. J., MITCHELL, J. H. and LINDEN, R. J. Synchronicity of ventricular contraction: observations comparing haemodynamic effects of atria1 and ventricular pacing. Brit. Heart J., 25: 299, 1963. 20. SKINNER,N. S., JR., MITCHELL, J. H., WALLACE, A. G., and SARNOFF, S. J. Hemodynamic effects of altering the timing of atria1 systole. Am. J. Physiol., 205: 499, 1963. 21. MITCHELL, J. H., GILMORE,J. P. and SARNOFF, S. J. The transport function of the atrium. Factors influencing the relation between mean left atria1 pressure and left ventricular end diastolic pressure. Am. J. Cardiol., 9: 237, 1962.
THE AMERICANJOURNAL
OF CARDIOLOGY