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Atrial contribution to cardiac output in complete heart block
The American Volume
Journal JULY
16
Clinical Atria1
of Cardiology .Turnber
1965
1
Studies Contribution Complete
to Cardiac Heart
Output
in
Block*
&MET, M.D., F.A.c.c., WILLIAM H. BERNSTEIN, M.D., F.A.c.c., DAVID A. NATHAN, M.D., F.A.C.C. and ALFREDO LOPEZ, M.D.
PHILIP
Miami
Beach, Florida
T
METHODS AND MATERIALS Six patients with complete heart block
HE influence of alterations in ventricular rate upon cardiac output in complete heart block has been reported in both the experimental The value of these data is animal and man.‘-’ limited by the variable temporal relationships between atria1 and ventricular activity in these The contribution of atria1 systole to studies.8 cardiac output has been analyzed both experimentallyg-13 and in man;2~7~14-18 however, the observations in man are very limited. The purpose of this study is to explore the relationship between heart rate, synchronous and asynchronous atrioventricular activity and cardiac output in 6 patients with complete heart Analyses were made during idioventricblock. ular ventricular pacing at the patient’s own resting slow ventricular rate, during idioventricular pacing induced by a right ventricular electrode catheter pacer, during synchronous atrioventricular pacing employing a Cordis synchronizing unit at the patient’s own atria1 rate, and during atria1 synchronous pacing. The latter was achieved by two bipolar electrode catheters, one placed in the atrium and one in the ventricle. The atrium was paced at rates above the control sinus rates during atria1 synchronous pacing.
were Two Goetz bipolar electrode catheters were studied. employed ; one was placed in the right ventricular A outflow tract and the other in the right atrium. third catheter was placed in the pulmonary artery or right atrium for pressure registration and as a means of indocyanine green injection for determination of cardiac output. Dye curves were recorded from the cannulated femoral artery via a Gilford densitometer, Harvard withdrawal-infusion apparatus and an Electronics for Medicine 8 channel recorder. Three dye concentrations in the subject’s blood were utilized for calibration. The experimental protocol was as follores: After recording control pressures and cardiac output at the patient’s own slow ventricular rate (idioventricular, nodal or His-bundle rhythm), the right ventricular bipolar catheter was employed to pace the heart at a rate above the control ventricular rate but below the The Cordis Synchrocor is used as control sinus rate. an idioventricular pacer for this purpose. Repeat physioIogic observations were then made at the patient’s control sinus rate by synchronization of the atrial and ventricular contraction. A Cordis Synchrocor furnished the means of atrioventricular synchronization via the two Goetz bipolar catheters. Further observations were made by atria1 pacing (with the atria1 bipolar catheter and a Medtronic pacer) at rates above the sinus rate (atria1 s),nchronous
* From the Section of Cardiology, Department of Medicinz, Mount Sinai Section of Cardiology, Department of Medicine, University of Miami School study was supported by a grant from the National Heart Institute, HE-08503-1 1
Hospital, Miami Beach, Fla., and thr of Medicine, Coral Gahlrs, Fla. This
Samet,
Bernstein,
Nathan
and L6pez
SYNCHROCOR Workable
parameter
synchronous and
pcicer
analyzers
FIXED-RATE PACER
FIG. 1. Graphic representation of the arrangement to produce ventricular or atria1 synchronous pacing via a bipolar catheter in the atrium and another in the right ventricle, employing a fixed rate pacer for atria1 pacing and a Synchrocor for synchronous pacing or ventricular pacing.
A \
6 I
G FIG. 2.
Details of function of the Synchrocor unit (see text). THE
AMERICAN
JOURNAL
OF
CARDIOLOGY
Atria1 Contribution
FIG. 3.
Cast
1.
Electrocardiogram
to Cardiac
demonstrating
3
Output
complrtc
heart block.
FIG. 4. Case 1. Idioventricular pacing by the right ventricular outflow tract catheter electrode, and synchronous pacing at the patient’s own control sinus rate. Femoral (F.A.) and pulmonary (P.A.) arterial curves are also illustrated. SC = Cordis Synchrocor stimulus.
paehg) ; the stimulus
produced by the Medtronic unit, also used to pace the right atrium, was detected by the Synchrocor unit, amplified and used to stimulate the right ventricle by a second bipolar catheter in the right ventricular outflow tract. Synchronous atrioventricular activity was thus produced at any desired atria1 rate. Usually observations were made at a series of atria1 rates above the sinus control rate. At each such rate, data were obtained both during atrioventricular synchronization and during right ventricular idioventricular pacing; the atria1 pacer was shut off during idioventricular pacing and the ventricles stimulated by the Cordis pacer. Synchronized atrioventricular contraction was achieved at all rates of atria1 synchronous pacing in the 6 patients. However, synchronous pacing was not uniformly obtained at the patient’s own atria1 rate, probably because the P waves were of low amplitude. Indicator dilution curves of cardiac output were VOLUME
16,
JULY
1965
usually recorded 1 to 3 min. after institution of a given rate and rhythm. The Cordis Synchrocor utilized in these studies deserves further comment. The process of atrioventricular synchronization during atria1 pacing is diagrammed in Figure 1. Details of the unit are shown in Figure 2. It is a variable parameter cardiac pacer. Selective circuits are utilized to vary the atrioventricular delay (P-R interval), refractory period duration, output pulse rate, and output current by dial control. The circuits consist of a selector switch (A) which permits biopolar stimulation at positions B1 and Bz or unipolar stimulation at positions CL and Uz. The battery strength meter is also activated at B1 and Bz for battery testing. The Synchrocor will function properly only when the milliampere reading is more than 0.6 ma. (B in Fig. 2). The sensitivity control (C) for the incoming atria1 signal ranges from 0.7 to 16 mv. The maximal synchronous rate (D) is
4
Samet,
Bernstein,
Nathan
TABLE Relation
and L6pez
I
Between Pacing Site and Cardiac Output in Six Patients with Complete Heart Block
Vent. Control
V.R.
C.I.
S.V.
44 49 66 51 56 74 88 95 105 118
1.85 2.02 2.18 2.23 2.09 2.51 2.37 2.69 2.66 2.60
76 75 60 80 68 62 49 52 46 40
42 59 63 72 90 108 120
3.45 3.53 3.47 3.46 3.99 3.79 3.63
46 63 74 65 81 100 111 120 131 102 84
Vent. Control
V.R.
C.I.
S.V.
V.P. (Idio) V.P. (Idio) S.P. S.P. V.P. V.P. V.P. V.P. V.P. V.P.
44 49 66 51 57 70 82 99 110 121
1.85 2.02 2.18 2.23 2.19 2.31 2.30 2.01 2.08 1.93
76 75 60 80 70 60 51 37 34 29
145 105 97 85 78 62 53
V.P. (Idio) V.P. A.S.P. A.S.P. A.S.P. A.S.P. A.S.P.
42 59 58 72 88 105 120
3.45 3.53 3.79 4.07 3.81 3.52 3.15
145 105 115 99 76 59 46
2.48 2.34 2.29 2.36 2.60 2.67 3.01 3.03 3.07 2.86 2.74
98 67 56 65 58 48 49 46 42 51 59
V.P. (Idio) V.P. V.P. S.P. A.S.P. A.S.P. A.S.P. A.S.P. A.S.P.
46 63 74 66 81 103 112 123 126
2.48 2.34 2.29 2.97 3.10 3.30 3.30 3.01 3.02
98 67 56 81 69 58 53 44 43
35 34 51 68 78 90 102 114 124
2.09 2.04 2.38 2.50 2.44 2.57 2.72 2.51 2.68
80 80 63 49 42 38 36 30 29
V.P. (Idio) V.P. (Idio) V.P. A.S.P. A.S.P. A.S.P. A.S.P. A.S.P. A.S.P.
35 34 51 68 73 90 103 111 120
2.09 2.04 2.38 2.80 2.81 3.33 3.08 3.10 3.10
80 80 63 55 52 50 40 37 35
37 48 74 84
1.80 2.14 2.57 2.48
97 89 69 59
110 121
2.27 2.60
41 43
V.P. (Idio) A.S.P. A.S.P. A.S.P. A.S.P. A.S.P. A.S.P.
37 48 77 83 100 108 119
1.80 2.14 2.80 2.81 2.71 2.73 2.64
97 89 73 68 54 50 44
Case 1 V.P. (Idio) V.P. (Idio) S.P. S.P. A.S.P. A.S.P. A.S.P. A.S.P. A.S.P. A.S.P. Case 2 (Sublingual V.P. (Idio) V.P. V.P. V.P. V.P. V.P. V.P.
Isuprel)
Case 3 V.P. (Idio) V.P. V.P. V.P. V.P. V.P. V.P. V.P. V.P. V.P. (A.R. 100) V.P. (A.R. 85) Case 4 V.P. (Idio) V.P. (Idio) V.P. V.P. V.P. V.P. V.P. V.P. V.P. Case 5 V.P. (Idio) V.P. V.P. V.P. V.P. V.P.
Vent. = ventricular; V.R. = ventricular rate; C.I. = cardiac index; S.V. = stroke volume; V.P. (Idio) = A.S.P. = atria1 synchronous pacing; and S.P. = synchronous pacing; control rate; V.P. = ventricular pacing; Nodal = nodal rhythm. THE
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JOURNAL
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Atria1 Contribution
to Cardiac
Output
3
TABLEI (continued) Vent. Control
vent. Control Case 6 Nodal Nodal V.P.
V.P. V.P. V.P. V.P. V.P.
V.R.
C.I.
58 57 71
1.90 1.95 2.04
56 47
99 105 115 125 136
2.29 2.24 2.45 2.48 2.44
38 35 35 32 29
_
S.V.
53
P-R P-R P-R
= 0.12 = 0.18 = 0.22
calibrated by a variable refractory delay. The atrioventricular delay may be varied between 20 and 300 msec. (E). The latter delay is the interval between receipt of an atrial signal and the time of the ventricular output stimulus. The automatic rate (F) regulates fixed rate idioventricular pacing when the sensitivity of the atria1 pickup circuit (C) is reduced and the Synchrocor does not respond to the atria1 signal. The output control (G) regulates the ventricular stimulus current, from 0.1 to 17 ma. The connector (H) permits union of the Synchrocor with various lead systems during pacing. The light at J flashes with each stimulus. The adapter plug (L) attached to the connector (H) contains red unipolar (Ur and Us), blue atria1 and black ground terminals. Ib achieve atrioventricular spchronization, the P wave or atria1 Medtronic stimulus is picked up by setting the millivolt sensitivity (C) below the amplitude of the P wave or atria1 stimulus, by setting the automatic rate (F) to the minimal value, by setting the synchronous rate control (D) to below the atria1 rate to prevent pacer atrioventricular block, and by selecting the desired atrioventricular delay, 0.12 sec. in this study unless otherwise specified. When idioventricular pacing at the same rate as the prior atria1 synchronous pacing rate is desired, the Medtronic atria1 pacing unit is turned off. and the automatic rate (F) is set at the desired idioventricular rate. At this point the atria1 rate is controlled by the sinus node and the ventricular rate by the Cordis unit.
RESULTS The control electrocardiogram in Case 1, a 71 year old white man, is shown in Figure 3. Complete heart block is evident with an atria1 rate of 54 and a ventricular rate of 27. The processes of idioventricular cardiac catheter synchronous pacing and atria1 synpacing, chronous pacing in this patient are illustrated in Figures 4 and 5. In the first method, the Cordis VOLUME
16,
JULY
1965
V.R.
C.I.
S.V.
Nodal Nodal
58 57
1.90 1.95
33 56
S.P. A.S.P. A.S.P. A.S.P. A.S.P. A.S.P.
86 98 108 114 122 130
~_.
sec. sec. sec.
A.S.P. A.S.P. A.S.P.
2.53 2.37 2.61 2.61 2.88 2.65 P-R in above = 0.12 sec. 108 2.61 108 2.97 108 2.72
48 39 39 37 38 33 39 45 41
stimulus (Cs) precedes each QRS complex; the P wave is temporally unrelated to both during idioventricular pacing. On the other hand, during synchronous pacing each P wa1.e is followed by a Cordis stimulus and in turn both are followed by a QRS complex produced by the right ventricular electrode catheter. In the third method (atria1 synchronized pacing), the right atriurn is stimulated by the Medtronic unit The MS (Ms) ; a small P wave follows. stimulus is detected by the Cordis synchrocor. The Cordis stimulus (Cs) follows and stimulates the right ventricle via the right ventricular bipolar catheter. The cardiac output data in the (, cases arc outlined in Table I. In Case 1 a significant ArtrioiSynchr+$dPacing
FIG. 5. Case 1. Ahal synchronizrrl’ r/r).//m. ‘lk atrium is stimulated by the fiixrd rate Medtronic pacer (M,) to produce P waves; the Medtronic stimulus is detected by the Cordis unit. which in turn causes vrntricular depolarization (C,), rrsulting in s)-nchrono~~s atrioventricular activity at any desired rate abow the patient’s own sinus rate.
Samet,
Bernstein,
FIG. 6. Comparison of cardiac indexes during idioventricular catheter electrode pacing and during synchronous atrioventricular activity at the same ventricular rate in 6 patients. Thirty-four pairs of indexes are plotted.
difference between outputs during atria1 and ventricular pacing developed at the higher ventricular rates. Cardiac index increments at higher rates were noted primarily during atria1 pacing. In Case 2 (the patient was on chronic administration of sublingual Isuprel@) the increases in flow during atria1 pacing were modest and most evident at rates of 60 to 70. At higher rates, atria1 synchronous indexes were Synsmaller than ventricular pacing flows. chronous pacing was clearly superior to idioventricular pacing at ventricular rates below 100 In the fourth case, blood flow was in Case 3. higher during atria1 synchronous than during ventricular pacing at all the heart rates studied. In Case 5 atria1 pacing was productive of a At the higher cardiac index at moderate rates. highest ventricular rate, indexes were similar In Case 6 modest during both kinds of pacing. increments in cardiac output were evident during atria1 pacing. Changes in the P-R interval resulted in small changes in cardiac outputs with a maximal flow at a P-R interval of 0.18 sec. The over-all data on cardiac index are graphed in Figure 6. Comparable atria1 and ventricular output data are available in 34 paired The average determinations in the 6 patients. level of cardiac index during ventricular pacing was 2.63 L./min./M2.; during synchronous or atria1 synchronous pacing, the average output The average difference was 2.90 L./min./M2. is thus 10 per cent and is highly significant (~<0.001). However, it must be emphasized
Nathan
and
L6pez
that a uniform response was not obtained in these 6 patients and that the averaged data tend to obscure larger changes in some patients. The significance of 10 per cent average difference between atria1 and ventricular pacing must thus be considered in light of the nonuniform response, i.e., not all patients exhibited similar data, and in light of a comparison of 400 paired outputs obtained by indicator dilution curves during 400 consecutive catheterizaIn this latter tions in patients in sinus rhythm. group, dye injections were made into the right heart with systemic arterial sampling in all instances. The first determination averaged 2.72, the second 2.74 L./min./M2., less than a 1 per cent average difference (Fig. 7). The difference between the mean difference for the two determinations of these 400 paired values and the mean difference between 34 paired output studies during atria1 and ventricular pacing in the 6 patients is highly significant (p
aortic
stenosis
studied
during
transient
Elevation of left ventricular A-V dissociation. end-diastolic pressure without elevation of mean left atria1 pressure was observed in a group of patients with ventricular hypertrophy without THE
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OF
CARDIOLOGY
Atria1 Contribution
to Cardiac
7
Output
a. 4.44-4.50 b. 4.53-4.63 c. 4.39-4.67 d. 4.38-4.31 e. 5.09-5.14 f. 4.41-4.65 g. 5.95-6.10 h. 4.61-4.49 i.4.58-4.42 i.6.19-6.06 I 2!.
I
I
I
I 3.10 I
1
I
' 410
I
I
FIG. 7. ~eprod~~6~~ityof indocyanine gmn indicator-dilution outputs via 330 paired determinaThere is no systematic difference between the tions in patients with normal sinus rhythm. An additional 10 pairs are given in the lower right hand fist and second determinations. (Indicator-dye injection into right heart with sampling at systemic corner of the figure. artery.)
FIG. 8. Femoral artery and left atria1 (L.A.) p resswe cwws during sinus rhythm and during Systemic arterial pressures are higher during sinus right ventricular outflow tract pacing. rhythm. Mitral insufficiency is evident during ventricular pacing.
dilatation.
recent publication, In a more Braunwald” has altered his position somewhat by noting that atria1 contraction does not elevate left ventricular end-diastolic pressure VOLUME
16, JULY 1965
above mean left atria1 pressure in the presence of ventricular dilatation rather than hyperThe question of whether the function trophy. of a diseased, chronically fibrillating atrium can
Samet,
Bernstein,
Nathan
and L6pez
NSR
VP
0.2 set
FIG. 9. ject
with
0.2 Set
Mitral insujiciency is again a Starr
mitral
valve
FIG. 10. Tricuspid ins@cimcv is evident during sinus rhythm.
evident prosthesis.
in right
atria1
during NSR
ventricular = normal
pressure
be restored by conversion to sinus rhythm was Braunwald concluded by stating that raised. “carefully controlled studies in the experimental physiological laboratory have shown the potential importance of atria1 contraction. However, the clinician must be wary of applying such physiologic data obtained in the setting of the experimental animal laboratory directly to the treatment of his patients with cardiac arrhythmia.” Burchell” has expressed similar views, stating that “in the fundamental regulatory mechanism controlling the volume of the circulation (or cardiac output) atria1 contraction is not intimately involved.” The recently published study of Graettinger et al.rg in which conversion of atria1 fibrillation to normal sinus rhythm in 20 patients (by transthoracic, directcurrent shock) failed to increase cardiac output unless a decrease in heart rate occurred after conversion, provides further support for the
curve
pacing (VP) sinus rhythm.
(R.A.)
during
in another
ventricular
sub-
pacing
but is absent
concept that the atria1 transport function is not of fundamental import for cardiovascular function. However, other studies have revealed significant increase in cardiac output after conversion of atria1 fibrillation to sinus rhythm, especially in those patients with heart and particularly during exercise.20-25 failure, Ferrer and Harveyz6 have reviewed other data on the importance of atria1 systole in the preservation of competency of the atrioventricular valves. Although not an invariable result of atria1 fibrillation, this rhythm is commonly inassociated with tricuspid or mitral sufficiency.l1,‘5~27,28 Variations in the optimal P-R interval may even be associated with such atrioventricular valvular insufficiency.27 Unpublished data in this laboratory have clearly shown marked alterations highly suggestive of tricuspid and mitral insufficiency during ventricular pacing at rates above the sinus rate in THE
AMERICAN
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Atria1
Contribution
to Cardiac
9
Output
1:x0. 11. Effect of atria1systole on left ventricular end-diastolic pressure (L.V.). The latter pressure is considerably lower when ventricular activity is not preceded by atria1 systole. B.A. = brachial xtvry pressure curve.
patients with normal sinus rhythm. The mean atria1 pressure is also elevated during ventricular pacing (Fig. 8-10). The role of atria1 systole in elevation of left ventricular end-diastolic pressure during normal sinus rhythm with ventricular premature beats is clearly shown in Figure 11. During the former rhythm, the enddiastolic pressure varies from 31 to 37 mm. Hg but falls to 19 to 21 in the absence of atrioventricular s)mchronization. Other aspects of this problem were recently reviewe‘d.18 The output data in this report make available for the first time comparative values of cardiac index during atria1 and ventricular pacing at similar rates in the same patients. Thirtyfour such paired sets of data are reported in the 6 patients w%th complete heart block. Similar comparisons have been made in 55 patients with normal sinus rhythm studied during atria1 and ventricular pacing at rates above the sinus rhythm. The details will be reported elsewhere; 153 paired sets are available. The mean cardiac index during atria1 pacing was 2.72 L. min.,, M2. ; the corresponding average index during ventricular pacing was 2.29. These data together with the observations in patients with heart block clearly establish the role of atria1 systole in maintenance of blood flow in man with various types of heart disease.
Synchrocor unit. The latter two rhythms are defined as those with P wave, ventricular stimulus and QRS complex sequences, and atria1 stimulus, P wave, ventricular stimulus and QRS Thirty-four complex sequences, respectively. paired observations were made during equal atria1 and ventricular pacing rates in these patients. The importance of atria1 systole for maintenance of cardiac output is clearly demonstrated by these data. REFERENCES 1. MILLER, D. E.. GLEASON, W. L.,
2.
3.
4.
5.
SUMMARY Cardiac output studies were performed in 6 patients with complete heart block during four kinds of ventricular rhythm. These include ventricular or His-bundle pacing at the control rate, right ventricular outflow tract catheter electrode pacing, and both synchronous and atria1 synchronous pacing by means of a Cordis VOLUME 16, JULY 1965
6.
7.
8.
LYHALEN, 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 RPS., 10: 658, 1962. ESCHER, D. J. W., SCHWEDEL, J. B., SCHWARTZ: L. S. and SOLOMON, N. Transvenous electrical stimulation of the heart-n. .4nn. Nerv York Acad. SC., 111 : 981, 1964. SAMET, P., BERNSTEIN, W. H., MEDOW, A. and NATHAN, D. A. Effect of alterations in ventricular rate upon cardiac output in complete heart block. Am. ./. Cardml.. 14: 477, 1964. SEGEL, N., HUDSON, W. A., HARRIS, P. and BISHOP, .I. M. The circulatory effects of electrically induced changes in ventricular rate at rest and during exercise in complete heart block. J. Clin. Inwst., 43: 1541, 1964. MCGREGOR, M. and KLASSEN, G. A. Observations on the effect of heart rate on cardiac output in patients with complete heart block at rest and exercise. Circulation Res., 14 (Supp. 2): 215, 1964. SOWTON, E. Haemodynamic studies in patients with artificial pacemakers. &it. Hear/ .J., 26: 737, 1964. JUDGE, R. D., WILSON, W. S. and SIEGEL, J. H. Hemodynamic studies in patients with implanted cardiac pacemakers. Nero Eqland J. Med., 270: 1391, 1964. SAMET, P., JACOBS, W., BERNSTEIN. W. H. and
10
9.
10.
11.
12.
13.
14.
15.
16. 17.
18.
19.
Samet, Bernstein, SHANE, R. Hemodynamic sequelae of idioventricular pacing in complete heart block. Am. J. Cardial., 11: 594, 1363. 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. 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. Dynamic function of atria1 conBROCKMAN,S. K. traction in regulation of cardiac performance. Am. J. Physiol., 205: 499, 1963. STEPHENSON,S. E., JR. and BROCKMAN,S. K. Pwave synchrony. Ann. New York Acad. SC., 111: 907, 1964. SELLERS, F. J., DONALD, D. E. and WOOD, E. H. Atria1 contribution to stroke volume in dogs with chronic cardiac denervation. Physiologist, 5 : 211, 1962. BRAUNWALD, E. and FRAHM, C. J. Studies on Starling’s law of the heart. IV. Observations on the hemodynamic functions of the left atrium in man. Circulation, 24: 633, 1961. GRANT, C., GREENE, D. G. and BUNNELL, I. L. The valve closing function of the right atrium. Am. J. Med., 34: 325, 1963. BURCHELL, H. B. A clinical appraisal of atria1 transport function. Lancet, 1: 775, 1964. on cardiac arrhyBRAUNWALD, E. Symposium thmias. Introduction. With comments on the hemodynamic significance of atria1 systole. Am. J. Med., 37: 665, 1964. SAMET, P., BERNSTEIN,W. H. and LEVINE, S. Significance of the atria1 contribution to ventricular filling. Am. J. Cardiol., 15: 195, 1965. GRAETTINGER,J. S., CARLETON, R. A. and MUEN-
Nathan
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21.
22.
23.
24.
25.
26.
27.
28.
and L6pez
STER, J. J. Circulatory consequences of changes in cardiac rhythm produced in patients by transthoracic direct-current shock. J. Clin. Invest., 43: 2290, 1964. HECHT, H. H., OSHER, W. J. and SAMUELS,A. J. Cardiovascular adjustments in subjects with organic heart disease before and after conversion of atria1 fibrillation to normal sinus rhythm. J. C/in. Invest., 30: 647, 1951. Cardiac output KORY, R. C. and MENEELY, G. R. in auricular fibrillation with observations on the effect of conversion to normal sinus rhythm. J. Clin. Invest., 30: 653, 1951. BROCH, 0. J. and MULLER, 0. Haemodynamic studies during auricular fibrillation and after restoration of sinus rhythm. Brit. Heart J., 19: 222, 1957. GILBERT, R., EICH, R. H., SMULYAN, H., KEIGHLEY, J. and AUCHINCLOSS,J. H., JR. Effect on circulation of conversion of atria1 fibrillation to sinus rhythm. Circulation, 27: 1079, 1963. MORRIS, J. J., JR., ENTMAN, M. L., THOMPSON, H. K., JR., NORTH, W. C. and MCINTOSH, H. D. Cardiac output in atria1 fibrillation and sinus rhythm. Circulation, 28: 772, 1963. KAHN, D. R., WILSON, W. S., WEBER, W. and SLOAN, H. Hemodynamic studies before and after cardioversion. J. Thoracic S&g., 48: 898, 1964. The value of FERRER, M. I. and HARVEY, R. M. converting atria1 fibrillation to sinus rhythm (Edit.). Am. Heart J., 68: 725, 1964. SKINNER,S. N., MITCHELL, J. H., WALLACE, A. G. and SARNOFF, S. J. Hemodynamic effects of atria1 systole timing. Am. J. Physiol., 205: 499, 1963. SKINNER,S. N., MITCHELL, J. H., WALLACE, A. G. and SARNOFF, S. J. Hemodynamic consequences of atria1 fibrillation at constant ventricular rates. Am. J. Med., 36: 342, 1964.
THE AMERICANJOURNAL OF CARDIOLOGY
Journal JULY
16
Clinical Atria1
of Cardiology .Turnber
1965
1
Studies Contribution Complete
to Cardiac Heart
Output
in
Block*
&MET, M.D., F.A.c.c., WILLIAM H. BERNSTEIN, M.D., F.A.c.c., DAVID A. NATHAN, M.D., F.A.C.C. and ALFREDO LOPEZ, M.D.
PHILIP
Miami
Beach, Florida
T
METHODS AND MATERIALS Six patients with complete heart block
HE influence of alterations in ventricular rate upon cardiac output in complete heart block has been reported in both the experimental The value of these data is animal and man.‘-’ limited by the variable temporal relationships between atria1 and ventricular activity in these The contribution of atria1 systole to studies.8 cardiac output has been analyzed both experimentallyg-13 and in man;2~7~14-18 however, the observations in man are very limited. The purpose of this study is to explore the relationship between heart rate, synchronous and asynchronous atrioventricular activity and cardiac output in 6 patients with complete heart Analyses were made during idioventricblock. ular ventricular pacing at the patient’s own resting slow ventricular rate, during idioventricular pacing induced by a right ventricular electrode catheter pacer, during synchronous atrioventricular pacing employing a Cordis synchronizing unit at the patient’s own atria1 rate, and during atria1 synchronous pacing. The latter was achieved by two bipolar electrode catheters, one placed in the atrium and one in the ventricle. The atrium was paced at rates above the control sinus rates during atria1 synchronous pacing.
were Two Goetz bipolar electrode catheters were studied. employed ; one was placed in the right ventricular A outflow tract and the other in the right atrium. third catheter was placed in the pulmonary artery or right atrium for pressure registration and as a means of indocyanine green injection for determination of cardiac output. Dye curves were recorded from the cannulated femoral artery via a Gilford densitometer, Harvard withdrawal-infusion apparatus and an Electronics for Medicine 8 channel recorder. Three dye concentrations in the subject’s blood were utilized for calibration. The experimental protocol was as follores: After recording control pressures and cardiac output at the patient’s own slow ventricular rate (idioventricular, nodal or His-bundle rhythm), the right ventricular bipolar catheter was employed to pace the heart at a rate above the control ventricular rate but below the The Cordis Synchrocor is used as control sinus rate. an idioventricular pacer for this purpose. Repeat physioIogic observations were then made at the patient’s control sinus rate by synchronization of the atrial and ventricular contraction. A Cordis Synchrocor furnished the means of atrioventricular synchronization via the two Goetz bipolar catheters. Further observations were made by atria1 pacing (with the atria1 bipolar catheter and a Medtronic pacer) at rates above the sinus rate (atria1 s),nchronous
* From the Section of Cardiology, Department of Medicinz, Mount Sinai Section of Cardiology, Department of Medicine, University of Miami School study was supported by a grant from the National Heart Institute, HE-08503-1 1
Hospital, Miami Beach, Fla., and thr of Medicine, Coral Gahlrs, Fla. This
Samet,
Bernstein,
Nathan
and L6pez
SYNCHROCOR Workable
parameter
synchronous and
pcicer
analyzers
FIXED-RATE PACER
FIG. 1. Graphic representation of the arrangement to produce ventricular or atria1 synchronous pacing via a bipolar catheter in the atrium and another in the right ventricle, employing a fixed rate pacer for atria1 pacing and a Synchrocor for synchronous pacing or ventricular pacing.
A \
6 I
G FIG. 2.
Details of function of the Synchrocor unit (see text). THE
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JOURNAL
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CARDIOLOGY
Atria1 Contribution
FIG. 3.
Cast
1.
Electrocardiogram
to Cardiac
demonstrating
3
Output
complrtc
heart block.
FIG. 4. Case 1. Idioventricular pacing by the right ventricular outflow tract catheter electrode, and synchronous pacing at the patient’s own control sinus rate. Femoral (F.A.) and pulmonary (P.A.) arterial curves are also illustrated. SC = Cordis Synchrocor stimulus.
paehg) ; the stimulus
produced by the Medtronic unit, also used to pace the right atrium, was detected by the Synchrocor unit, amplified and used to stimulate the right ventricle by a second bipolar catheter in the right ventricular outflow tract. Synchronous atrioventricular activity was thus produced at any desired atria1 rate. Usually observations were made at a series of atria1 rates above the sinus control rate. At each such rate, data were obtained both during atrioventricular synchronization and during right ventricular idioventricular pacing; the atria1 pacer was shut off during idioventricular pacing and the ventricles stimulated by the Cordis pacer. Synchronized atrioventricular contraction was achieved at all rates of atria1 synchronous pacing in the 6 patients. However, synchronous pacing was not uniformly obtained at the patient’s own atria1 rate, probably because the P waves were of low amplitude. Indicator dilution curves of cardiac output were VOLUME
16,
JULY
1965
usually recorded 1 to 3 min. after institution of a given rate and rhythm. The Cordis Synchrocor utilized in these studies deserves further comment. The process of atrioventricular synchronization during atria1 pacing is diagrammed in Figure 1. Details of the unit are shown in Figure 2. It is a variable parameter cardiac pacer. Selective circuits are utilized to vary the atrioventricular delay (P-R interval), refractory period duration, output pulse rate, and output current by dial control. The circuits consist of a selector switch (A) which permits biopolar stimulation at positions B1 and Bz or unipolar stimulation at positions CL and Uz. The battery strength meter is also activated at B1 and Bz for battery testing. The Synchrocor will function properly only when the milliampere reading is more than 0.6 ma. (B in Fig. 2). The sensitivity control (C) for the incoming atria1 signal ranges from 0.7 to 16 mv. The maximal synchronous rate (D) is
4
Samet,
Bernstein,
Nathan
TABLE Relation
and L6pez
I
Between Pacing Site and Cardiac Output in Six Patients with Complete Heart Block
Vent. Control
V.R.
C.I.
S.V.
44 49 66 51 56 74 88 95 105 118
1.85 2.02 2.18 2.23 2.09 2.51 2.37 2.69 2.66 2.60
76 75 60 80 68 62 49 52 46 40
42 59 63 72 90 108 120
3.45 3.53 3.47 3.46 3.99 3.79 3.63
46 63 74 65 81 100 111 120 131 102 84
Vent. Control
V.R.
C.I.
S.V.
V.P. (Idio) V.P. (Idio) S.P. S.P. V.P. V.P. V.P. V.P. V.P. V.P.
44 49 66 51 57 70 82 99 110 121
1.85 2.02 2.18 2.23 2.19 2.31 2.30 2.01 2.08 1.93
76 75 60 80 70 60 51 37 34 29
145 105 97 85 78 62 53
V.P. (Idio) V.P. A.S.P. A.S.P. A.S.P. A.S.P. A.S.P.
42 59 58 72 88 105 120
3.45 3.53 3.79 4.07 3.81 3.52 3.15
145 105 115 99 76 59 46
2.48 2.34 2.29 2.36 2.60 2.67 3.01 3.03 3.07 2.86 2.74
98 67 56 65 58 48 49 46 42 51 59
V.P. (Idio) V.P. V.P. S.P. A.S.P. A.S.P. A.S.P. A.S.P. A.S.P.
46 63 74 66 81 103 112 123 126
2.48 2.34 2.29 2.97 3.10 3.30 3.30 3.01 3.02
98 67 56 81 69 58 53 44 43
35 34 51 68 78 90 102 114 124
2.09 2.04 2.38 2.50 2.44 2.57 2.72 2.51 2.68
80 80 63 49 42 38 36 30 29
V.P. (Idio) V.P. (Idio) V.P. A.S.P. A.S.P. A.S.P. A.S.P. A.S.P. A.S.P.
35 34 51 68 73 90 103 111 120
2.09 2.04 2.38 2.80 2.81 3.33 3.08 3.10 3.10
80 80 63 55 52 50 40 37 35
37 48 74 84
1.80 2.14 2.57 2.48
97 89 69 59
110 121
2.27 2.60
41 43
V.P. (Idio) A.S.P. A.S.P. A.S.P. A.S.P. A.S.P. A.S.P.
37 48 77 83 100 108 119
1.80 2.14 2.80 2.81 2.71 2.73 2.64
97 89 73 68 54 50 44
Case 1 V.P. (Idio) V.P. (Idio) S.P. S.P. A.S.P. A.S.P. A.S.P. A.S.P. A.S.P. A.S.P. Case 2 (Sublingual V.P. (Idio) V.P. V.P. V.P. V.P. V.P. V.P.
Isuprel)
Case 3 V.P. (Idio) V.P. V.P. V.P. V.P. V.P. V.P. V.P. V.P. V.P. (A.R. 100) V.P. (A.R. 85) Case 4 V.P. (Idio) V.P. (Idio) V.P. V.P. V.P. V.P. V.P. V.P. V.P. Case 5 V.P. (Idio) V.P. V.P. V.P. V.P. V.P.
Vent. = ventricular; V.R. = ventricular rate; C.I. = cardiac index; S.V. = stroke volume; V.P. (Idio) = A.S.P. = atria1 synchronous pacing; and S.P. = synchronous pacing; control rate; V.P. = ventricular pacing; Nodal = nodal rhythm. THE
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Atria1 Contribution
to Cardiac
Output
3
TABLEI (continued) Vent. Control
vent. Control Case 6 Nodal Nodal V.P.
V.P. V.P. V.P. V.P. V.P.
V.R.
C.I.
58 57 71
1.90 1.95 2.04
56 47
99 105 115 125 136
2.29 2.24 2.45 2.48 2.44
38 35 35 32 29
_
S.V.
53
P-R P-R P-R
= 0.12 = 0.18 = 0.22
calibrated by a variable refractory delay. The atrioventricular delay may be varied between 20 and 300 msec. (E). The latter delay is the interval between receipt of an atrial signal and the time of the ventricular output stimulus. The automatic rate (F) regulates fixed rate idioventricular pacing when the sensitivity of the atria1 pickup circuit (C) is reduced and the Synchrocor does not respond to the atria1 signal. The output control (G) regulates the ventricular stimulus current, from 0.1 to 17 ma. The connector (H) permits union of the Synchrocor with various lead systems during pacing. The light at J flashes with each stimulus. The adapter plug (L) attached to the connector (H) contains red unipolar (Ur and Us), blue atria1 and black ground terminals. Ib achieve atrioventricular spchronization, the P wave or atria1 Medtronic stimulus is picked up by setting the millivolt sensitivity (C) below the amplitude of the P wave or atria1 stimulus, by setting the automatic rate (F) to the minimal value, by setting the synchronous rate control (D) to below the atria1 rate to prevent pacer atrioventricular block, and by selecting the desired atrioventricular delay, 0.12 sec. in this study unless otherwise specified. When idioventricular pacing at the same rate as the prior atria1 synchronous pacing rate is desired, the Medtronic atria1 pacing unit is turned off. and the automatic rate (F) is set at the desired idioventricular rate. At this point the atria1 rate is controlled by the sinus node and the ventricular rate by the Cordis unit.
RESULTS The control electrocardiogram in Case 1, a 71 year old white man, is shown in Figure 3. Complete heart block is evident with an atria1 rate of 54 and a ventricular rate of 27. The processes of idioventricular cardiac catheter synchronous pacing and atria1 synpacing, chronous pacing in this patient are illustrated in Figures 4 and 5. In the first method, the Cordis VOLUME
16,
JULY
1965
V.R.
C.I.
S.V.
Nodal Nodal
58 57
1.90 1.95
33 56
S.P. A.S.P. A.S.P. A.S.P. A.S.P. A.S.P.
86 98 108 114 122 130
~_.
sec. sec. sec.
A.S.P. A.S.P. A.S.P.
2.53 2.37 2.61 2.61 2.88 2.65 P-R in above = 0.12 sec. 108 2.61 108 2.97 108 2.72
48 39 39 37 38 33 39 45 41
stimulus (Cs) precedes each QRS complex; the P wave is temporally unrelated to both during idioventricular pacing. On the other hand, during synchronous pacing each P wa1.e is followed by a Cordis stimulus and in turn both are followed by a QRS complex produced by the right ventricular electrode catheter. In the third method (atria1 synchronized pacing), the right atriurn is stimulated by the Medtronic unit The MS (Ms) ; a small P wave follows. stimulus is detected by the Cordis synchrocor. The Cordis stimulus (Cs) follows and stimulates the right ventricle via the right ventricular bipolar catheter. The cardiac output data in the (, cases arc outlined in Table I. In Case 1 a significant ArtrioiSynchr+$dPacing
FIG. 5. Case 1. Ahal synchronizrrl’ r/r).//m. ‘lk atrium is stimulated by the fiixrd rate Medtronic pacer (M,) to produce P waves; the Medtronic stimulus is detected by the Cordis unit. which in turn causes vrntricular depolarization (C,), rrsulting in s)-nchrono~~s atrioventricular activity at any desired rate abow the patient’s own sinus rate.
Samet,
Bernstein,
FIG. 6. Comparison of cardiac indexes during idioventricular catheter electrode pacing and during synchronous atrioventricular activity at the same ventricular rate in 6 patients. Thirty-four pairs of indexes are plotted.
difference between outputs during atria1 and ventricular pacing developed at the higher ventricular rates. Cardiac index increments at higher rates were noted primarily during atria1 pacing. In Case 2 (the patient was on chronic administration of sublingual Isuprel@) the increases in flow during atria1 pacing were modest and most evident at rates of 60 to 70. At higher rates, atria1 synchronous indexes were Synsmaller than ventricular pacing flows. chronous pacing was clearly superior to idioventricular pacing at ventricular rates below 100 In the fourth case, blood flow was in Case 3. higher during atria1 synchronous than during ventricular pacing at all the heart rates studied. In Case 5 atria1 pacing was productive of a At the higher cardiac index at moderate rates. highest ventricular rate, indexes were similar In Case 6 modest during both kinds of pacing. increments in cardiac output were evident during atria1 pacing. Changes in the P-R interval resulted in small changes in cardiac outputs with a maximal flow at a P-R interval of 0.18 sec. The over-all data on cardiac index are graphed in Figure 6. Comparable atria1 and ventricular output data are available in 34 paired The average determinations in the 6 patients. level of cardiac index during ventricular pacing was 2.63 L./min./M2.; during synchronous or atria1 synchronous pacing, the average output The average difference was 2.90 L./min./M2. is thus 10 per cent and is highly significant (~<0.001). However, it must be emphasized
Nathan
and
L6pez
that a uniform response was not obtained in these 6 patients and that the averaged data tend to obscure larger changes in some patients. The significance of 10 per cent average difference between atria1 and ventricular pacing must thus be considered in light of the nonuniform response, i.e., not all patients exhibited similar data, and in light of a comparison of 400 paired outputs obtained by indicator dilution curves during 400 consecutive catheterizaIn this latter tions in patients in sinus rhythm. group, dye injections were made into the right heart with systemic arterial sampling in all instances. The first determination averaged 2.72, the second 2.74 L./min./M2., less than a 1 per cent average difference (Fig. 7). The difference between the mean difference for the two determinations of these 400 paired values and the mean difference between 34 paired output studies during atria1 and ventricular pacing in the 6 patients is highly significant (p
aortic
stenosis
studied
during
transient
Elevation of left ventricular A-V dissociation. end-diastolic pressure without elevation of mean left atria1 pressure was observed in a group of patients with ventricular hypertrophy without THE
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Atria1 Contribution
to Cardiac
7
Output
a. 4.44-4.50 b. 4.53-4.63 c. 4.39-4.67 d. 4.38-4.31 e. 5.09-5.14 f. 4.41-4.65 g. 5.95-6.10 h. 4.61-4.49 i.4.58-4.42 i.6.19-6.06 I 2!.
I
I
I
I 3.10 I
1
I
' 410
I
I
FIG. 7. ~eprod~~6~~ityof indocyanine gmn indicator-dilution outputs via 330 paired determinaThere is no systematic difference between the tions in patients with normal sinus rhythm. An additional 10 pairs are given in the lower right hand fist and second determinations. (Indicator-dye injection into right heart with sampling at systemic corner of the figure. artery.)
FIG. 8. Femoral artery and left atria1 (L.A.) p resswe cwws during sinus rhythm and during Systemic arterial pressures are higher during sinus right ventricular outflow tract pacing. rhythm. Mitral insufficiency is evident during ventricular pacing.
dilatation.
recent publication, In a more Braunwald” has altered his position somewhat by noting that atria1 contraction does not elevate left ventricular end-diastolic pressure VOLUME
16, JULY 1965
above mean left atria1 pressure in the presence of ventricular dilatation rather than hyperThe question of whether the function trophy. of a diseased, chronically fibrillating atrium can
Samet,
Bernstein,
Nathan
and L6pez
NSR
VP
0.2 set
FIG. 9. ject
with
0.2 Set
Mitral insujiciency is again a Starr
mitral
valve
FIG. 10. Tricuspid ins@cimcv is evident during sinus rhythm.
evident prosthesis.
in right
atria1
during NSR
ventricular = normal
pressure
be restored by conversion to sinus rhythm was Braunwald concluded by stating that raised. “carefully controlled studies in the experimental physiological laboratory have shown the potential importance of atria1 contraction. However, the clinician must be wary of applying such physiologic data obtained in the setting of the experimental animal laboratory directly to the treatment of his patients with cardiac arrhythmia.” Burchell” has expressed similar views, stating that “in the fundamental regulatory mechanism controlling the volume of the circulation (or cardiac output) atria1 contraction is not intimately involved.” The recently published study of Graettinger et al.rg in which conversion of atria1 fibrillation to normal sinus rhythm in 20 patients (by transthoracic, directcurrent shock) failed to increase cardiac output unless a decrease in heart rate occurred after conversion, provides further support for the
curve
pacing (VP) sinus rhythm.
(R.A.)
during
in another
ventricular
sub-
pacing
but is absent
concept that the atria1 transport function is not of fundamental import for cardiovascular function. However, other studies have revealed significant increase in cardiac output after conversion of atria1 fibrillation to sinus rhythm, especially in those patients with heart and particularly during exercise.20-25 failure, Ferrer and Harveyz6 have reviewed other data on the importance of atria1 systole in the preservation of competency of the atrioventricular valves. Although not an invariable result of atria1 fibrillation, this rhythm is commonly inassociated with tricuspid or mitral sufficiency.l1,‘5~27,28 Variations in the optimal P-R interval may even be associated with such atrioventricular valvular insufficiency.27 Unpublished data in this laboratory have clearly shown marked alterations highly suggestive of tricuspid and mitral insufficiency during ventricular pacing at rates above the sinus rate in THE
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Atria1
Contribution
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9
Output
1:x0. 11. Effect of atria1systole on left ventricular end-diastolic pressure (L.V.). The latter pressure is considerably lower when ventricular activity is not preceded by atria1 systole. B.A. = brachial xtvry pressure curve.
patients with normal sinus rhythm. The mean atria1 pressure is also elevated during ventricular pacing (Fig. 8-10). The role of atria1 systole in elevation of left ventricular end-diastolic pressure during normal sinus rhythm with ventricular premature beats is clearly shown in Figure 11. During the former rhythm, the enddiastolic pressure varies from 31 to 37 mm. Hg but falls to 19 to 21 in the absence of atrioventricular s)mchronization. Other aspects of this problem were recently reviewe‘d.18 The output data in this report make available for the first time comparative values of cardiac index during atria1 and ventricular pacing at similar rates in the same patients. Thirtyfour such paired sets of data are reported in the 6 patients w%th complete heart block. Similar comparisons have been made in 55 patients with normal sinus rhythm studied during atria1 and ventricular pacing at rates above the sinus rhythm. The details will be reported elsewhere; 153 paired sets are available. The mean cardiac index during atria1 pacing was 2.72 L. min.,, M2. ; the corresponding average index during ventricular pacing was 2.29. These data together with the observations in patients with heart block clearly establish the role of atria1 systole in maintenance of blood flow in man with various types of heart disease.
Synchrocor unit. The latter two rhythms are defined as those with P wave, ventricular stimulus and QRS complex sequences, and atria1 stimulus, P wave, ventricular stimulus and QRS Thirty-four complex sequences, respectively. paired observations were made during equal atria1 and ventricular pacing rates in these patients. The importance of atria1 systole for maintenance of cardiac output is clearly demonstrated by these data. REFERENCES 1. MILLER, D. E.. GLEASON, W. L.,
2.
3.
4.
5.
SUMMARY Cardiac output studies were performed in 6 patients with complete heart block during four kinds of ventricular rhythm. These include ventricular or His-bundle pacing at the control rate, right ventricular outflow tract catheter electrode pacing, and both synchronous and atria1 synchronous pacing by means of a Cordis VOLUME 16, JULY 1965
6.
7.
8.
LYHALEN, 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 RPS., 10: 658, 1962. ESCHER, D. J. W., SCHWEDEL, J. B., SCHWARTZ: L. S. and SOLOMON, N. Transvenous electrical stimulation of the heart-n. .4nn. Nerv York Acad. SC., 111 : 981, 1964. SAMET, P., BERNSTEIN, W. H., MEDOW, A. and NATHAN, D. A. Effect of alterations in ventricular rate upon cardiac output in complete heart block. Am. ./. Cardml.. 14: 477, 1964. SEGEL, N., HUDSON, W. A., HARRIS, P. and BISHOP, .I. M. The circulatory effects of electrically induced changes in ventricular rate at rest and during exercise in complete heart block. J. Clin. Inwst., 43: 1541, 1964. MCGREGOR, M. and KLASSEN, G. A. Observations on the effect of heart rate on cardiac output in patients with complete heart block at rest and exercise. Circulation Res., 14 (Supp. 2): 215, 1964. SOWTON, E. Haemodynamic studies in patients with artificial pacemakers. &it. Hear/ .J., 26: 737, 1964. JUDGE, R. D., WILSON, W. S. and SIEGEL, J. H. Hemodynamic studies in patients with implanted cardiac pacemakers. Nero Eqland J. Med., 270: 1391, 1964. SAMET, P., JACOBS, W., BERNSTEIN. W. H. and
10
9.
10.
11.
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13.
14.
15.
16. 17.
18.
19.
Samet, Bernstein, SHANE, R. Hemodynamic sequelae of idioventricular pacing in complete heart block. Am. J. Cardial., 11: 594, 1363. 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. 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. Dynamic function of atria1 conBROCKMAN,S. K. traction in regulation of cardiac performance. Am. J. Physiol., 205: 499, 1963. STEPHENSON,S. E., JR. and BROCKMAN,S. K. Pwave synchrony. Ann. New York Acad. SC., 111: 907, 1964. SELLERS, F. J., DONALD, D. E. and WOOD, E. H. Atria1 contribution to stroke volume in dogs with chronic cardiac denervation. Physiologist, 5 : 211, 1962. BRAUNWALD, E. and FRAHM, C. J. Studies on Starling’s law of the heart. IV. Observations on the hemodynamic functions of the left atrium in man. Circulation, 24: 633, 1961. GRANT, C., GREENE, D. G. and BUNNELL, I. L. The valve closing function of the right atrium. Am. J. Med., 34: 325, 1963. BURCHELL, H. B. A clinical appraisal of atria1 transport function. Lancet, 1: 775, 1964. on cardiac arrhyBRAUNWALD, E. Symposium thmias. Introduction. With comments on the hemodynamic significance of atria1 systole. Am. J. Med., 37: 665, 1964. SAMET, P., BERNSTEIN,W. H. and LEVINE, S. Significance of the atria1 contribution to ventricular filling. Am. J. Cardiol., 15: 195, 1965. GRAETTINGER,J. S., CARLETON, R. A. and MUEN-
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24.
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26.
27.
28.
and L6pez
STER, J. J. Circulatory consequences of changes in cardiac rhythm produced in patients by transthoracic direct-current shock. J. Clin. Invest., 43: 2290, 1964. HECHT, H. H., OSHER, W. J. and SAMUELS,A. J. Cardiovascular adjustments in subjects with organic heart disease before and after conversion of atria1 fibrillation to normal sinus rhythm. J. C/in. Invest., 30: 647, 1951. Cardiac output KORY, R. C. and MENEELY, G. R. in auricular fibrillation with observations on the effect of conversion to normal sinus rhythm. J. Clin. Invest., 30: 653, 1951. BROCH, 0. J. and MULLER, 0. Haemodynamic studies during auricular fibrillation and after restoration of sinus rhythm. Brit. Heart J., 19: 222, 1957. GILBERT, R., EICH, R. H., SMULYAN, H., KEIGHLEY, J. and AUCHINCLOSS,J. H., JR. Effect on circulation of conversion of atria1 fibrillation to sinus rhythm. Circulation, 27: 1079, 1963. MORRIS, J. J., JR., ENTMAN, M. L., THOMPSON, H. K., JR., NORTH, W. C. and MCINTOSH, H. D. Cardiac output in atria1 fibrillation and sinus rhythm. Circulation, 28: 772, 1963. KAHN, D. R., WILSON, W. S., WEBER, W. and SLOAN, H. Hemodynamic studies before and after cardioversion. J. Thoracic S&g., 48: 898, 1964. The value of FERRER, M. I. and HARVEY, R. M. converting atria1 fibrillation to sinus rhythm (Edit.). Am. Heart J., 68: 725, 1964. SKINNER,S. N., MITCHELL, J. H., WALLACE, A. G. and SARNOFF, S. J. Hemodynamic effects of atria1 systole timing. Am. J. Physiol., 205: 499, 1963. SKINNER,S. N., MITCHELL, J. H., WALLACE, A. G. and SARNOFF, S. J. Hemodynamic consequences of atria1 fibrillation at constant ventricular rates. Am. J. Med., 36: 342, 1964.
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