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(Chest. 2000;117:60-64.)
© 2000 American College of Chest Physicians

Improved Left Ventricular Relaxation During Short-term Right Ventricular Outflow Tract Compared to Apical Pacing*

Theofilos M. Kolettis, MD; Zenon S. Kyriakides, MD; Dimitrios Tsiapras, MD; Todor Popov, MSc; Ioannis A. Paraskevaides, MD and Dimitrios Th. Kremastinos, MD

* From the 2nd Department of Cardiology, Onassis Cardiac Surgery Center, Athens, Greece.


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
 References
 
Study objectives: Pacing-induced asynchrony may deteriorate left ventricular function; however, limited data exists in humans. The aim of our study was to compare left ventricular hemodynamics during short-term atrioventricular sequential pacing from the right ventricular apex and from the outflow tract of the right ventricle.

Design: Three 5-min pacing intervals were applied in a random order, at a rate of 15 beats/min above the resting sinus rate. Atrioventricular sequential pacing from the two sites was compared with atrial pacing. During each pacing mode, left ventricular pressure was recorded, and cardiac output was calculated using Doppler echocardiography.

Setting: Cardiac catheterization laboratory.

Patients: Twenty patients (18 male, mean age 62 ± 11 years) without structural heart disease were studied.

Results: During atrial pacing, maximum negative first derivative of pressure (dp/dt) was 1,535 ± 228 mm Hg/s; during pacing from the apex it decreased to 1,221 ± 294 mm Hg/s (p = 0.0001), but was not significantly different during pacing from the outflow tract (1,431 ± 435 mm Hg/s, p > 0.05). Isovolumic relaxation time constant ({tau}) during atrial pacing was 39.7 ± 11.9 ms; during pacing from the apex, it increased to 47.9 ± 14.0 (p = 0.001), but was not significantly different during pacing from the outflow tract (42.5 ± 11.2, p > 0.05). Peak systolic pressure decreased significantly during atrioventricular sequential pacing from either site; however, it did not differ between the two sites. No differences in end-diastolic pressure, maximum positive dp/dt, or cardiac output could be demonstrated.

Conclusion: In patients with no structural heart disease, short-term right ventricular outflow tract pacing is associated with more favorable diastolic function, compared to right ventricular apical pacing.

Key Words: apex • diastolic function • hemodynamics • outflow tract • pacing


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 Conclusion
 References
 
Since the introduction of permanent pacing, the preferred site for ventricular stimulation has been almost exclusively the right ventricular apex, because this site provides excellent lead stability and low capture thresholds. However, such pacing results in an asynchronous ventricular contraction, associated with a deterioration in left ventricular systolic and diastolic function indexes.1 2 Pacing from the right ventricular outflow tract mimics the normal ventricular activation sequence, decreases the degree of pacing-induced asynchrony, and may produce less deterioration in left ventricular performance.3 However, there are no detailed hemodynamic data in humans with regard to atrioventricular dual-chamber sequential pacing (DDD) from the two sites. The purpose of our study was to compare the acute hemodynamic status during short-term DDD pacing from the apex vs the outflow tract of the right ventricle in patients with no structural heart disease.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 Conclusion
 References
 
Participants in our study were screened among patients referred for diagnostic cardiac catheterization and electrophysiologic study. Those with normal left ventricular function, normal 12-lead ECG, and absence of significant ischemia on thallium exercise scintigraphy were considered eligible for the study. All medications were discontinued 24 h before the study. Informed consent was obtained before entry into the study, and the protocol was approved by the Hospital Ethics Committee.

All patients underwent contrast left ventriculography, coronary arteriography, and electrophysiologic study, as clinically indicated. All studies were performed in the fasting, postabsorptive state, without the use of premedication. A standard percutaneous Seldinger technique was used to gain access to the femoral vein and artery. Patients with no significant coronary artery disease were enrolled in the study. For purposes of this study, "significant coronary artery disease" was defined as (1) any degree of stenosis in the left main stem, or (2) stenosis > 50% in diameter in any other coronary vessel.

Pacing Protocol
One electrode catheter was positioned in the right atrium and one in the right ventricle. Three pacing modes were applied: atrial pacing, DDD with ventricular pacing from the right ventricular apex, and DDD with ventricular pacing from the right ventricular outflow tract; the order was chosen randomly. Pacing was performed with a DDD temporary pulse generator (model 5346; Medtronic, Inc; Minneapolis, MN). During outflow tract pacing, the electrode was placed high in the outflow tract, almost to the pulmonary valve, and was pulled back until the tip pointed in a lateral direction on a posteroanterior fluoroscopic projection, as previously described.4 The position was confirmed in the right and left anterior oblique projections. After fine manipulations of the ventricular electrode, the pacing site producing the shortest QRS-complex duration was chosen as the final outflow tract pacing site. We have previously reported on this electrode positioning procedure in detail.5 To avoid fusion beats, atrioventricular delay was set at 60% of the intrinsic PR interval. The pacing rate was 15 beats/min higher than the resting sinus rate. Each pacing mode lasted for 5 min, with 3-min intervals between each mode.

Pressure Recordings
Left ventricular pressure was recorded during the last 30 s of each pacing protocol, using a high-fidelity, micromanometer-tipped pressure catheter (Millar Instruments; Houston, TX). All measurements were performed using a custom-made software program, and recordings were stored on a hard disk. This program, which allows accurate measurements of multiple variables on a beat-to-beat basis, has been described previously.6 Variables were measured during atrial pacing (AAI) and during DDD pacing from the two sites. To express steady-state values during the last 30 s of each pacing protocol, data were averaged from beats 10, 20, 30, 40, and 50.

Variables
The following hemodynamic variables were measured: left ventricular peak systolic pressure (SP), left ventricular end-diastolic pressure, maximum positive and maximum negative first derivative of pressure (dp/dt). Isovolumic relaxation time constant ({tau}) was calculated using a zero asymptote from peak negative rate of decrease of left ventricular pressure over time (dp/dt) to 5 mm Hg above the previous left ventricular end-diastolic pressure.7

Cardiac Output Measurements
At the end of each pacing protocol, cardiac output was measured using Doppler echocardiography. This method was favored over the Fick or thermodilution techniques because the Doppler technique is practical, reproducible, and accurate.8 9 The equipment used was the Sonos 2500 (Hewlett-Packard; Andover, MA) with a 3.5-MHz transducer. Measurements were performed using standard techniques.10 In brief, the highest audio signal and the sharpest outline with the maximal envelope were used to assess blood flow velocities in the ascending aorta from the apical five-chamber view. Measurements were performed off-line using a computer-assisted digitization system. The area under the Doppler flow velocity curve was determined by digitizing the signal from baseline to baseline. An average of three consecutive cycles was taken. Cardiac output was calculated as the systolic velocity integral times the aortic root area, times heart rate. The aortic root area was measured using the parasternal long-axis view. Heart rate was measured using two consecutive spikes on the ECG. All measurements were blindly performed by two experienced echocardiographers (DT and JAP).

QRS-complex Duration
QRS-complex duration was measured from hard copy recordings (at paper speed of 100 mm/s) using hand-held calipers. Measurements were performed at baseline and during each pacing sequence. QRS-complex duration was averaged from three consecutive complexes in the lead with the widest QRS complex.

Statistics
Differences in variables were compared using the analysis of variance for repeated measures (split plot design), utilizing the Statistica statistical software (version 5, 1997 edition; StatSoft; Tulsa, OK). Post hoc analysis was performed using Tukey’s multiple comparisons test. Values are expressed as mean± SD. Statistical significance was defined at an {alpha} level of 0.05. Percent changes from atrial pacing were calculated for DDD pacing from the two sites and were compared using the Student’s paired t test.


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 Conclusion
 References
 
Twenty patients (18 were male, 2 were female) with a mean age of 62 ± 11 years and a mean ejection fraction of 62 ± 8% were included in the study. Mean heart rate during pacing was 84 ± 7 beats/min.

Left Ventricular Pressure Data:
Left ventricular end-diastolic pressure and maximum positive dp/dt were comparable between the three pacing protocols. Significant variance was found for maximum negative dp/dt, {tau}, and for peak systolic pressure (Table 1 ). Compared to AAI pacing, maximum negative dp/dt decreased significantly during pacing from the apex (p = 0.0001), but was not statistically significantly different during pacing from the outflow tract (p > 0.05). When DDD pacing from the two sites was compared, maximum negative dp/dt was significantly higher during outflow tract, compared with apical pacing (p = 0.004). {tau} increased significantly during pacing from the apex (p = 0.01), but was not statistically significantly different during pacing from the outflow tract. When DDD pacing from the two sites was compared, {tau} was significantly lower during outflow tract, compared with apical pacing (p = 0.036).


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  		Table 1.. Hemodynamic Data*

 
DDD pacing from either site was associated with a significant drop in peak systolic pressure, but peak systolic pressure was not statistically significantly different between the two sites. The percent changes from atrial pacing for all variables are shown in Figure 1 .



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  		Figure 1.. Diagram depicting mean percent changes (± SEM) from AAI for EDP, SP, +dp/dt, -dp/dt, and {tau} (tau). See Table 1 for abbreviations.

 
No significant differences in cardiac output were found between pacing from the two sites. Compared with pacing from the apex, QRS-complex duration was consistently shorter during pacing from the right ventricular outflow tract (Table 1) .


   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
Conclusion
 References
 
The hemodynamic consequences of ectopic cardiac stimulation were first described by Wiggers in 1925.11 He believed that "a certain orderliness in the mode of contraction may be necessary in order to produce a maximal effect on intraventricular pressure." Ventricular contraction and relaxation are both impaired, and this impairment may be proportional to the left ventricular mass, which is activated by intraventricular conduction, as opposed to normal His-Purkinje conduction.11 12 However, these observations remained clinically irrelevant, because the right ventricular apex has been regarded as the "only" pacing site for many decades. Recently, pacing from the right ventricular outflow tract proved to be safe and feasible in regard to pacing and sensing thresholds.13 Thus, the interest in alternative pacing sites resurfaced.

Several experimental animal studies have indicated that, during pacing, a hemodynamic impairment occurs that is proportional to the degree of the pacing-induced wall motion asynchrony.1 2 3 14 15 Burkhoff et al1 paced isolated canine hearts at various sites, including the left ventricular apex, the left ventricular free wall, and the right ventricular free wall. Peak left ventricular pressure varied significantly between sites, being higher with shorter QRS complexes. In a similar experimental setting, pacing from the right ventricular lateral wall was associated with a significant decrease in maximum positive and negative dp/dt, compared with left ventricular apical pacing.14 Mabo et al15 showed that mean BP fell with right ventricular apical pacing but remained stable with pacing from the His-Purkinje bundle.

The results from the animal studies1 2 3 11 12 14 15 indicate that, during pacing, ventricular performance deteriorates in proportion to the extent of induced ventricular asynchrony. Our study tested the hypothesis that, compared to pacing from the apex, pacing from the outflow tract may be associated with more favorable left ventricular hemodynamics.

Giudici et al16 examined right ventricular outflow tract pacing acutely in 89 patients, and they noted a significant benefit in cardiac output measured by Doppler echocardiography. Similarly, de Cock et al17 studied 17 patients and reported a higher cardiac index during pacing from the right ventricular outflow tract at three pacing rates (85 beats/min, 100 beats/min, and 120 beats/min). However, these studies had three significant limitations: (1) in both studies,16 17 only ventricular pacing was evaluated; (2) although the hemodynamic results of pacing-induced ventricular asynchrony may vary in different patient subgroups,16 17 inhomogeneous groups of patients were included, with an apparently wide range of left ventricular function and a variation of the severity of coronary artery disease; (3) in both studies,16 17 only cardiac output was compared, and detailed hemodynamic data were not reported.

We compared systolic and diastolic left ventricular function indexes during pacing from the two sites in a homogeneous group of patients, ie, in patients with normal left ventricular function and absence of significant coronary artery disease. Furthermore, atrioventricular sequential pacing was examined. Such pacing is a more physiologic pacing mode, it results in substantial hemodynamic advantages,18 and it is widely used in the absence of atrial fibrillation.

Apical pacing is associated with an impairment in left ventricular relaxation.19 20 In the animal model, it has been shown that this impairment correlates with the degree of wall motion asynchrony.2 Compared with right ventricular apical pacing, outflow tract pacing may be associated with less ventricular asynchrony, resulting in higher positive and negative dp/dt, irrespective of the atrioventricular delay.3 In agreement with this concept, we report a lower {tau} and a higher peak negative dp/dt during outflow tract pacing, indicating more favorable left ventricular relaxation. This benefit could be attributed to shorter intraventricular conduction times during outflow tract pacing, evidenced by shorter QRS complexes. Previous studies20 21 22 have shown that indexes of isovolumic relaxation are independent of loading conditions, but are sensitive to pacing-induced changes in ventricular activation sequence. Our results confirm this notion, as comparable end-diastolic and peak systolic pressures were found during DDD pacing from the two sites.

In our study, we found no differences in cardiac output or in other systolic function indexes. Our results are in agreement with those of Buckingham et al,23 who compared the two ventricular pacing sites, in a study cohort very similar to ours; they reported no significant differences in cardiac output measured by Doppler echocardiography.23 In contrast, in patients with poor left ventricular function and low cardiac output, a pacing site that decreases pacing-induced asynchrony may be associated with a significant acute hemodynamic improvement.24

Limitations of the Study
We believe that our study contributes to the ongoing research on the optimum ventricular pacing site. However, a few limitations may be apparent.

First, our study examined the effects of pacing site on ventricular hemodynamics at the resting, supine position and not at the upright position or during exertion.

Second, an important caveat needs to be made: the acute hemodynamic changes produced by short-term pacing do not necessarily predict the long-term hemodynamic status. A recent report25 failed to show any symptomatic improvement or any hemodynamic benefit after chronic (3 months) pacing from the right ventricular outflow tract, by comparison with apical pacing.

Third, our results probably apply to a minority of patients requiring permanent pacing, namely patients with normal left ventricular function and absence of coronary artery disease.

Clinical Implications
It appears that right ventricular outflow tract pacing results in less ventricular asynchrony because of the proximity of this pacing site with the His-Purkinje conduction system.4 In patients with normal left ventricular systolic function, such pacing seems to result in better indexes of left ventricular relaxation. Further studies are necessary, in order to examine whether the acute hemodynamic changes are sustained and whether these changes are translated into a symptomatic benefit and/or an improved outcome.


   Conclusion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
References
 
We conclude that in patients with structurally normal hearts short-term right ventricular outflow tract pacing is associated with more favorable left ventricular diastolic function compared with apical pacing.


   Footnotes
 
Abbreviations: AAI = atrial pacing; DDD = atrioventricular dual-chamber sequential pacing; dp/dt = first derivative of pressure; SP = peak systolic pressure; {tau} = isovolumic relaxation time constant

Correspondence to: Theofilos M. Kolettis, MD, Onassis Cardiac Surgery Center, 356 Syngrou Ave, 176 74 Kallithea, Athens, Greece; e-mail: elbee@ath.forthnet.gr

Received for publication December 23, 1998. Accepted for publication July 15, 1999.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
 References
 

  1. Burkhoff, D, Oikawa, RY, Sagawa, K (1986) Influence of pacing site on canine left ventricular contraction. Am J Physiol 251,H428-H435
  2. Aoyagi, T, Iizuka, M, Takahashi, T, et al (1989) Wall motion asynchrony prolongs time constant of left ventricular relaxation. Am J Physiol 257,H883-H890[Abstract/Free Full Text]
  3. Rosenqvist, M, Bergfeldt, L, Haga, Y, et al (1996) The effect of ventricular activation sequence on cardiac performance during pacing. Pacing Clin Electrophysiol 19,1279-1286[CrossRef][Medline]
  4. Buckingham, TA (1997) Right ventricular outflow tract pacing. Pacing Clin Electrophysiol 20,1237-1242[CrossRef][Medline]
  5. Kolettis, TM, Kyriakides, ZS, Kremastinos, DT (1998) Coronary blood flow velocity during apical versus septal pacing. Int J Cardiol 66,203-205[CrossRef][ISI][Medline]
  6. Kyriakides, ZS, Kolettis, TM, Popov, T, et al (1998) Coronary blood flow changes during atrioventricular sequential pacing with different atrioventricular delays in normal individuals. J Intervent Cardiac Electrophysiol 2,163-169[CrossRef][ISI][Medline]
  7. Raff, GL, Glantz, SA (1981) Volume loading slows left ventricular isovolumic relaxation rate: evidence of load-dependent relaxation in the intact dog heart. Cir Res 48,813-824[Free Full Text]
  8. Espersen, K, Jensen, EW, Rosenborg, D, et al (1995) Comparison of cardiac output measurement techniques: thermodilution, Doppler, CO2-rebreathing and the direct Fick method. Acta Anaesthesiol Scand 39,245-251[ISI][Medline]
  9. Davies, JN, Allen, DR, Chant, AD (1991) Non-invasive Doppler-derived cardiac output: a validation study comparing this technique with thermodilution and Fick methods. Eur J Vasc Surg 5,497-500[CrossRef][Medline]
  10. Chandraratna, PA, Nanna, M, McKay, C, et al (1984) Determination of cardiac output by transcutaneous continuous-wave ultrasonic Doppler computer. Am J Cardiol 53,234-237[CrossRef][ISI][Medline]
  11. Wiggers, LJ (1925) The muscular reactions of the mammalian ventricles to artificial surface stimuli. Am J Physiol 73,346-378[Free Full Text]
  12. Lister, JW, Klotz, DH, Jomain, SL, et al (1964) Effect of pacemaker site on cardiac output and ventricular activation in dogs with complete heart block. Am J Cardiol 14,494-503[CrossRef][ISI][Medline]
  13. Barin, ES, Jones, SM, Ward, DE, et al (1991) The right ventricular outflow tract as an alternative permanent pacing site: Long-term follow-up. Pacing Clin Electrophysiol 14,3-6[CrossRef][Medline]
  14. Henning, RJ, Levy, MN (1991) Effects of autonomic nerve stimulation, asynchrony and load on dp/dtmax and dp/dtmin. Am J Physiol 260,H1290-H1298[Abstract/Free Full Text]
  15. Mabo, P, Scherlag, BJ, Munsif, A, et al (1994) Hemodynamic benefit of His pacing compared to right ventricular apex pacing in dual chamber modes [abstract]. Eur J Cardiol Pacing Electrophysiol 4,80
  16. Giudici, MC, Thornburg, GA, Buck, DL, et al (1997) Comparison of right ventricular outflow tract and apical lead permanent pacing on cardiac output. Am J Cardiol 79,209-212[CrossRef][ISI][Medline]
  17. de Cock, CC, Meyer, A, Kamp, O, et al (1998) Hemodynamic benefits of right ventricular outflow tract pacing: comparison with right ventricular apex pacing. Pacing Clin Electrophysiol 21,536-541[CrossRef][Medline]
  18. Samet, P, Castillo, C, Bernstein, WH (1968) Hemodynamic consequences of sequential atrioventricular pacing: subjects with normal hearts. Am J Cardiol 21,207-212[CrossRef][ISI][Medline]
  19. Bedotto, JB, Grayburn, PA, Black, WH, et al (1990) Alterations in left ventricular relaxation during atrioventricular pacing in humans. J Am Coll Cardiol 15,658-664[Abstract]
  20. Zile, MR, Blaustein, AS, Shimizu, G, et al (1987) Right ventricular pacing reduces the rate of left ventricular relaxation and filling. J Am Coll Cardiol 10,702-709[Abstract]
  21. Bahler, RC, Martin, P (1985) Effects of loading conditions and inotropic state on rapid filling phase of left ventricle. Am J Physiol 248,H523-533
  22. Blaustein, AS, Gaasch, WH (1983) Myocardial relaxation. VI. Effects of beta-adrenergic tone and asynchrony on LV relaxation rate. Am J Physiol 244,H417-H422
  23. Buckingham, TA, Candinas, R, Schlapfer, J, et al (1997) Acute hemodynamic effects of atrioventricular pacing at differing sites in the right ventricle individually and simultaneously. Pacing Clin Electrophysiol 20,909-215[CrossRef][Medline]
  24. Blanc, J-J, Etienne, Y, Gilard, M, et al (1997) Evaluation of different ventricular pacing sites in patients with severe heart failure. Circulation 96,3273-3277[Abstract/Free Full Text]
  25. Victor, F, Leclercq, C, Mabo, P, et al (1999) Optimal right ventricular pacing site in chronically implanted patients. A prospective randomized crossover comparison of apical and outflow tract pacing. J Am Coll Cardiol 33,311-316[Abstract/Free Full Text]



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