Alteration of left ventricular performance by left bundle branch block simulated with atrioventricular sequential pacing

Alteration of Left Ventricular Performance by Left Bundle Branch Block Simulated with AtrioventricularSequential Pacing JOSEPH ASKENAZI,

MD, JAY H. ALEXANDER, MD, DAVID I. KOENIGSBERG, MD,

NENAD BELIC, MD, and MICHAEL LESCH, MD

The effects of atrioventricular (AV) sequential pacing-induced left bundle branch block (LBBB) on left ventricular (LV) performance were evaluated during cardiac catheterization in 9 randomly selected patients being investigated for chest pain. All patients were in normal sinus rhythm with a normal P-R interval and QRS duration. LV performance was assessed by both hemodynamic and angiographic measurements. The maximal rate of LV pressure increase (dP/dt), rate of maximal LV pressure decrease (-dP/dt), LV end-diastolic pressure (LVEDP), end-diastolic volume (LVEDV), end-systolic volume (LVESV), stroke volume and percent ejection (EF) were measured during right atrial and AV sequential pacing at a constant pacing rate. The average pacing rate was 97 f 3 beats/min (mean f standard error of the mean). In each patient, both decreased significantly (p dP/dt and -dP/dt
ml) or AV sequential pacing (137 f 14 ml). In contrast, the LVESV during AV sequential pacing was higher by 15 ml (23%) (from 48 f 10 to 63 f 12 ml) (p
The effects of the abnormal pattern of ventricular activation caused by left bundle branch block (LBBB) on left ventricular (LV) performance are incompletely defined and remain controversial. In studies of a patient with rate-related LBBB, Takeshita et al’ reported a

marked deterioration in ventricular function during periods of abnormal conduction; in contrast, Wong et al” found no apparent change in ventricular function during periods of LBBB. In a study of a large group of patients with LBBB, Haft et al:’ found that aberrant activation of the left ventricle due to LBBB had little effect on the cineangiographic patterns of contraction in the otherwise normal left ventricle. Williams et al,” in a study of 15 patients with chronic LBBB, could not confirm the data of Haft et al” and reported regional wall motion abnormalities, as measured angiographitally, to be often associated with isolated LBBB. Hemodynamic studies of LV function in animal prepara-

From the Department of Medicine, Section of Cardiology, Veterans Administration Lakeside Medical Center, and Northwestern Memorial Hospital, Northwestern University Medical School, Chicago, Illinois. Manuscript received July 5, 1983; revised manuscript received September 9, 1983, accepted September 19, 1983. Address for reprints: Joseph Askenazi, MD, Section of Cardiology, Veterans Administration Lakeside Medical Center, 333 East Huron Street, Chicago, Illinois 606 11.

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TABLE I

Baseline Hemodynamic Measurements in 9 Patients During Intrinsic Sinus Rhythm

Age (yr)

(beazmin)

PR (s)

(mlY;at)

0.13

1

LVSP (mm Hg)

LVEDP (mm Hg)

dP/dt (mm Hg/s)

-dP/dt (mm big/s)

110

15

1,500

1,700

5

5:

6’;

0.16 0.15

112 ;:

160 110

ia 10

1,550 1,100

1,175 1,550

s 6

:;

60 z:

58

0.12 0.14

105 101 94

122 145 120

10 a

z:

ia

1,020 1,370 1,200

1,050 1,480 1,200

; 9

!8 66

75 6”:

0.14 0.16 0.14

;z 67

195 134 200

20 :;

1,420 1,378 1,210

1,360 1,325 1,375

::

!“3

0.14 f0.01

:“3

143 f12

2’:

1,305 f61

1,357 f67

Mean fSEM

dP/dt = maximal rate of left ventricular (LV) pressure development during isovolumic contraction; -dP/dt = maximal rate of maximum LV pressure decline during isovolumic relaxation; HR = heart rate; LVEDP = LV end-diastolic pressure: LVSP = LV systolic pressure; PR = electrocardiographic PR interval; SEM = standard error of the mean; SV = stroke volume.

tions and human subjects5-g in whom acute LBBB was induced by right atrioventricular (AV) sequential pacing and compared with the intrinsic rhythm or atria1 pacing, or both, have also produced conflicting results. Classically, the physiologic determinants of myocardial performance are considered to be heart rate, preload, afterload and contractility.1° Although this is presumably true in isolated muscle preparations, the confusing array of data regarding the effects of LBBB raises the issue of whether the activation sequence of cardiac muscle in the intact heart is an additional variable that must be considered when describing global ventricular performance. To address this question, we have measured positive and negative dP/dt and LV end-systolic and end-diastolic volumes in a group of patients during right atrial, right AV sequential and right ventricular pacing at identical pacing rates at the time of diagnostic catheterization.

Methods Hemodynamic studies were performed in 9 selected men, aged 32 to 71 years (mean 58). All patients underwent cardiac catheterization and coronary angiography for stable angina pectoris and had consented to the investigational protocol. All patients were in normal sinus rhythm, had normal QRS intervals on standard ECGs and a normal PR interval. Seven patients had significant coronary artery disease by angiog-

PACING

RA

raphy (obstructive lesion 265% in diameter of 21 major coronary artery), 1 patient had mitral valve prolapse without mitral regurgitation and 1 had concentric LV hypertrophy. Under normal intraventricular conduction, 4 patients with coronary artery disease were noted during angiography to have regional wall abnormalities (akinetic segments); 5 had normal LV motion. Study protocol: After routine right-sided cardiac catheterization including cardiac output determination by thermodilution had been completed, the Swan-Ganz catheter was replaced by a hexapolar pacing catheter. The distal electrodes were placed at the right ventricular apex, or near it, and the proximal electrodes at the high lateral wall of the right atrium. Atria1 and ventricular capture was satisfactorily obtained using an American Optical bifocal AV sequential pacing generator with an adjustable PR interval. The left-sided cardiac studies were performed with a No. 8Fr pigtail catheter using the percutaneous technique through the femoral artery. Pacing was initiated at an average rate of 97 beats/min. The sequence of the pacing modes was randomly changed so that 5 patients were atrially paced first, followed by AV sequential and ventricular pacing, while the other 4 patients were paced first by the AV sequential pacing mode. Ventricular pacing was carried out at 2 times the diastolic threshold and the atria1 pacing at fixed high output (7 mA). Changes in pacing mode were accomplished by disconnecting or connecting the atria1 or ventricular connections at the generator site. Measurements: LV pressure was measured using a Statham 23Db pressure transducer placed at the midchest diameter point and recorded on an Electronics for Medicine

RA - RV

FIGURE cording negative RA-right changes dP/dt.

1. A composite figure illustrating a typical reof left ventricular (LV) pressure, positive and dP/dt during high right atrial (RA), sequential ventricular (RV), and RV pacing. There are in the QRS duration of lead Vs on the ECG and

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TABLE II

LVSP

AV sequential Ventricular

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Comparison of Hemodynamic and Left Ventricular (LV) Volumetric Results (Mean f Standard Error of the Mean) in 9 Patients During Atrial, Atrioventricular (AV) Sequential and Ventricular Pacing

(mm Hg) Atrial

THE AMERICAN JOURNAL

161 p 145 p 131

f 10
LVEDP (mm Hg)

dP/dt (mm Hg/s)

-dP/dt (mm Hg/s)

EDV (mi)

ESV (ml)

SV (ml/beat)

17f3 p = NS 16 f 2 p = NS 14f2

1,541 f 68 p
1,506 f 86 p -Co.01 1,276 f 92 p
135 f 13 p = NS 137 f 14

48f 14 p -Co.001 63f 14

87 f a p CO.01 74 f 6

66 f 5 p
1

dP/dt = maximal rate of LV pressure development during isovolumic contraction; -dP/dt = maximal rate of LV pressure decline during isovolumic relaxation: EDV = end-diastolic volume: EF = ejection fraction; ESV = end-systolic volume: LVEDP = LV end-diastolic pressure; LVSP = LV systolic pressure; NS = not significant; SV = stroke volume.

VR 16 multichannel photographic recorder in each pacing mode. Measurements of maximal positive and negative dP/dt were obtained through a differentiator that continuously processed the LV pressure signals. Left ventriculography was performed in the 30” right anterior oblique position for the atria1 and AV sequential pacing modes at the same rate without changing the distance between the x-ray tube and the patient. For each angiogram, 40 ml of Renografin-76s’ were injected over 4 to 5 seconds. The average elapsed time between injections was approximately 8 minutes; time required for the LV depressant effects of the first angiographic dye had fully dissipated. The LV volume at end-systole and end-diastole were calculated using the Sandler-Dodge area-length method’ 1with a correction factor for volumes obtained by the area grid method. Statistical significance was determined by performing the paired Student t test. The values are expressed as mean f standard error of the mean.

Results Hemodynamics: Baseline measurements of heart rate, PR interval, LV pressure, stroke volume and peak

Hg versus 145 f 10 mm Hg, p
positive and peak negative dP/dt for the 9 patients during intrinsic sinus rhythm are shown in Table I. The average pacing rate was 97 f 3 beatslmin with a PR interval averaging 0.16 second (range 0.13 to 0.19) for atria1 pacing and 0.12 second (range 0.09 to 0.13) for AV sequential pacing. Significant shortening in the PR interval during AV sequential pacing was required to assure that ventricular depolarization was not caused by conduction along the normal pathways. The QRS duration during ventricular pacing averaged 0.14 second and its duration and configuration were compatible with complete LBBB and identical to that seen during AV sequential pacing. In each patient, positive and negative dP/dt was significantly increased during atria1 pacing as compared with the intrinsic sinus rhythm at lower rates or the AV sequential and ventricular pacing modes at the same rate (range 86 to 108 beats/min). A typical recording comparing LV pressures in a patient during the various pacing modes at the same rate is shown in Figure 1. During AV sequential pacing, a decrease of 14% was observed in dP/dt, from an average of 1,541 f 68 mm/s to 1,319 f 56 mm/s (p
average of 1,319 to 1,238 mm/s) at the same pacing rate for each patient. A similar significant trend was detected for negative dP/dt (Table II and Fig. 2). LV systolic pressure decreased significantly when the atria1 and AV sequential pacing modes were compared (161 f 10 mm

FIGURE 2. The values of mean and standard error of positive and negative dP/dt in 9 patients during intrinsic normal sinus rhythm (NSR) and during right atrial (RA), atrioventricular sequential (AVS) and ventricular (V) pacing.

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AP @g

*“8

l P40.01 l * P
2oI

FIGURE 3. Angiographic left (EDV) and end-systolic (ESV) (SV) and ejection fraction (EF) (AP) and atrioventricular (AVS) f standard error.

ventricular end-diastolic volumes, stroke volume in 9 patients during atrial pacing. Values are mean

40

EOV

ESV

(InI)

hll

SV

EF

(ml)

tw

Discussion The 4 physiologic determinants of myocardial performance are classically listed as rate, preload, afterload and contractility.1° Although these determinants completely describe myocardial function in isolated muscle preparations, the possibility that additional variables may require consideration in the intact heart has not completely been ruled out. Although the effects of atria1 contraction and the temporal relation between atria1 and ventricular contraction (that is, PR interval) on ventricular function are presumably preload-mediated, alternative explanations for these effects have also been proposed. 5- g~12The importance of LBBB on LV function is controversial. Whether the activation sequence of cardiac muscle in the intact heart is a variable that must be considered remains undefined.

EF

w so

_

RA

80

00

70

70

60

20

50

50

40

40

30

30

FIGURE 4. Individual data and mean values of the ejection fraction (EF) in 9 patients during right atrial (RA) and atrioventricular sequential (AVS) pacing at the same heart rate.

Previous clinical studies addressing this issue have dealt primarily with symptomatic populations in which the prognosis and the measured variables of LV function were primarily dependent and determined by the associated cardiovascular diseases.sJ3J4 However, in patients with LBBB and without coronary artery disease, M-mode echocardiography has demonstrated asynergy of the interventricular septum.15J6 The ventriculographic assessment of 15 patients with chest pain and no angiographic evidence of coronary artery disease but with isolated LBBB demonstrated abnormalities of wall motion by qualitative and quantitative analysis of LV function4 Although it was speculated that a clinically occult structural abnormality was responsible for the segmental wall motion abnormalities, the possibility that an altered sequence of LV contraction was causally involved could not be discounted. In the present study, repeat analysis of LV function at a fixed heart rate under steady-state conditions during atrial pacing with normal ventricular conduction and during pacemaker-induced LBBB in the presence of atria1 systole was used to evaluate the contribution of altered LV activation on myocardial function. The contribution of atria1 systole to LV function is well established in experimental and clinical studies and presumably reflects an effect of altered preload.7TgJ7J8 If an appropriate and optimal AV interval is selected, AV sequential pacing can result in improved hemodynamics than those obtained with extremely short or long PR intervals.e,i9 This latter effect is thought to reflect the effect of atria1 systole on LV filling, that is, enddiastolic volume. The PR interval in our study during AV sequential pacing was significantly shorter than that during atria1 pacing. This shortening was required to prevent conduction through normal AV pathways. Although the shorter PR interval during AV sequential pacing might be expected to affect LV end-diastolic volume, this effect must have been trivial because similar end-diastolic volumes and pressures were observed during both states, thus allowing assessment of the effect of asynchronous ventricular contraction on ventricular performance at constant preload. Because peak systolic pressure was decreased during AV sequential pacing, this apparent decrease in afterload

January 1, 1984

should, if anything, improve myocardial function in this state. Finally, although angiographic dye is thought to depress contractility, the experimental protocol in which 4 patients were first studied in the AV sequential mode and the rest of the patients in the atria1 mode should eliminate altered contractility as an explanation for the observed results. The most significant change found during AV sequential pacing was an increase in end-systolic volume and a resultant diminished ejection fraction. The percentage change in stroke volume we found between atria1 and AV sequential pacing is similar to that observed by Waltson et al”” in an animal study. By using electromagnetic flow probes chronically implanted around the ascending aorta, they found an average decrease of 14% in LV stroke volume during sequential pacing as compared with atria1 pacing at the same rate. Our results conflict with the clinical study of Greenberg et a_l,sin which the stroke volume index during atrial and AV sequential pacing was identical. The rate of pacing in the 2 studies appeared to be similar; however, the PR interval during atria1 pacing in the latter study was prolonged at 0.22 second, whereas in our study it was shorter and averaged 0.16 second. In addition, the methods of measuring stroke volume in the 2 studies differ considerably. In the present study, LV volume analysis by contrast angiography was used, whereas thermodilution technique was used by Greenberg et a1.8 The maximal rate of LV pressure development was lowest during ventricular pacing and highest during atria1 pacing. The measurement of dP/dt with fluidfilled catheters has well known limitations and the absolute values obtained are of questionable significance. Nonetheless, despite these limitations, comparison of changes in dP/dt in a given patient who serves as an internal control during different states should be valid.“] Under conditions of constant heart rate, end-diastolic volume and end-diastolic pressure, the dP/dt approximates the LV contractile state.“‘-“” Because these requirements prevailed in the present study, a decrease in contractility may be inferred during AV sequential pacing. Peak negative dP/dt, a measurement that has been proposed to indicate some quantitative aspect of relaxation,Za was highest during atria1 pacing and decreased significantly during AV sequential and ventricular pacing. Our data do not indicate whether relaxation was indeed impaired during AV sequential as compared with atria1 pacing, because the smaller stroke volume noted during AV sequential pacing, caused by an increase in end-systolic volume, may have affected this variable. Thus, the hemodynamic changes observed during periods of altered LV conduction at the time of a normal temporal relation between atria1 and ventricular systole are presumably in part due to asynchronous LV contraction. Deterioration of ejection phase measures of LV performance, such as end-systolic volume, ejection fraction, stroke volume and peak systolic pressure, as well as the preejection phase measurement of dP/dt during AV sequential as compared with atria1 pacing,

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cannot be attributed to altered preload. contractility, afterload or heart rate. The effect of site of pacing on L\i’ performance, as judged by cardiac output and pressure, has been investigated. Wiggers”’ reported that apical L,V sites were superior to either left or right. basilar sites. ;Lister et al:J”i and other$-“” confirmed Wiggers’ observation that the LV apex was the superior pacing site. Other investigators:“‘m:lZused similar preparations of surgically induced atrioventricular block and found no significant differences in cardiac output during pacing from multiple lel’t and right ventricular sites. In a more recent study by Waltson et al,“” LV performance was assessed during both atria1 and sequential, and nonsequential ventric,ular pacing from multiple left and right ventricular epicardial sites, and no difference in hemodynamics among any of the vent,ricular pacing sites was found. Ectopic ventricular depolarizations alone during sequential or nonsequential ventricular pacing seemed to account for the depressed stroke volume, stroke work and peak power as compared with the results obtained during atria1 pacing. The LBBB pattern induced by right ventricular pacing may not represent the same pattern of complete LBBB seen in patients with proximal LBBB or a delav in depolarization in the distal branches of’ the left bundle. Echocardiographic studies indicate that at least 3 types of sept.al wall motion are associated with LBBB.lfi These findings may explain the observed effects of LBBB contraction. Our study using volume and pressure data does not corroborate findings that sequential AV pacing and atria1 pacing at the same ratts are “hemodynamically equivalent .“* Acknowledgment: Sumayya

preparation

We are indebted to &car L. Evans and Shabazz f’or the technical and secretarial work in of the manuscript.

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C11.

the maximal rate of rise of left ventricular pressure. Am J Physiol 1963; 205:30-36. 24. McLaurin LP, Rolett E, Grossman W. Impaired left ventricular relaxation during pacing induced ischemia. Am J Cardiol 1973;32:751-757. ^- Wfoaers Cl. The muscular reactions of the mammalian ventricle to artificial 13. su&e stimuli. Am J Physiol 1925;73:346-478. 26. Lister JW, Klotz DH, Jomaln SL, Jackson HS, Hoffman BF. Effect of pacemaker site on cardiac output and ventricular activation in dogs with complete heart block. Am J Cardiol 1964;14:494-503. 27. Vagnini FJ, Gourin A, Antell HI, Stuckey JH. Implantation sites of cardiac oacemaker electrodes and mvocardial contractilitv. Ann Thorac Sura i987;4:431-439. 20. Tyers GFO. Optimal electrode implantation site for asynchronous dipolar cardiac pacing. Ann Surg 1968;187:168-179. 29. Klotr DH, Lister JW. Jomain SL. Hoffman BF. Stuckev JH. lmolantation sites of pacemakers.after right ventriculotomy.and complete heart block. JAMA 1963;186:929-931, 30. Starri TE, Gaertner RA, Webb RC. The effects of repetitive electric cardiac stimulation in dogs with normal heart, complete heart block and experimental cardiac arrest. Circulation 1955;11:952-962. 31. William-Olsson G, Andersen MN. The effect of pacemaker electrode site on cardiac output. J Thorac Cardiovasc Surg 1963;45:618-621. 32. Fletcher FW, Theilen EO, Lawrence MS, Evans IW. Effect of pacemaker location on cardiac function in complete A-V heart block. Am J Physiol 1963;205:1232-1234.