Published online before print May 5, 2003, doi: 10.1161/01.CIR.0000070930.33499.9F
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2003;107:2287.)
© 2003 American Heart Association, Inc.
Brief Rapid Communications |
Electrical Resynchronization
A Novel Therapy for the Failing Right Ventricle
From the Departments of Pediatrics (A.M.D., J.A.F., G.F.V.H., D.N.R.) and Cardiothoracic Surgery (V.M.R., F.L.H.), Stanford University, Stanford, Calif.
Correspondence to Anne M Dubin, MD, Associate Professor of Pediatrics, Stanford University, 750 Welch Rd, Suite #305, Stanford, CA 94304. E-mail amdubin{at}leland.stanford.edu
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Background— Many patients with congenital heart disease develop right ventricular (RV) failure due to anatomy and prior therapy. RV problems may include right bundle-branch block (RBBB), volume loading, and chamber enlargement. Because the failing RV may have regional dyskinesis, we hypothesized that resynchronization therapy might augment its performance.
Methods and Results— We studied 7 patients with RV dysfunction and RBBB, using a predefined pacing protocol. QRS duration, cardiac index (CI), and RV dP/dt were measured in 4 different pacing states. Atrioventricular pacing improved CI and RV dP/dtmax and decreased QRS duration as compared with atrial pacing or sinus rhythm.
Conclusions— Atrioventricular pacing in patients with RBBB and RV dysfunction augments RV and systemic performance. RV resynchronization is a promising novel therapy for patients with RV failure.
Key Words: pacing • heart defects, congenital • heart failure
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Right heart failure is an important cause of late morbidity in congenital heart disease.1–3 Whereas left ventricular (LV) failure is well studied, the therapeutic approach to right ventricular (RV) failure is largely empirical, and clinical trial data are nearly nonexistent.
Regional dyskinesis is common in LV systolic dysfunction, impeding global cardiac contractility and relaxation. Restoring mechanical synchronization with biventricular pacing improves hemodynamics and bioenergetics.4 Resynchronization improves cardiac contractility without the increase in oxygen demand that accompanies inotropic therapies.5 Trials have demonstrated improved exercise tolerance, although survival benefit is uncertain.6
In contrast to LV dysfunction, the failing RV is poorly understood. Prior surgery often produces right bundle-branch block (RBBB).7 Tricuspid or pulmonary insufficiency may cause RV enlargement. These alterations may decrease RV ejection fraction.8 The motion of the interventricular septum often becomes paradoxic in these circumstances, indicating an abnormal RV activation sequence.9 Thus, RV dyskinesis appears to be a reasonable therapeutic target. We hypothesized that there would be an acute hemodynamic benefit from electrical resynchronization of the failing RV.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
This was an unblinded, acute intervention. Eligibility criteria included RV dysfunction determined by echocardiography or angiography, sinus rhythm, and RBBB on the ECG (QRS
120 ms). Exclusion criteria were concomitant LV failure or anatomy precluding temporary pacing. Patients enrolled in this study had clinically indicated cardiac catheterization. The Stanford University Human Subjects Committee approved the protocol. Patients were sedated for study. A pressure-tip catheter (Millar Instruments) was placed in the RV. Pacing catheters were inserted transvenously into the right atrium and RV. Data from the Millar catheters were passed through an isolation amplifier, digitized with the use of Powerlab hardware (ADInstruments) at a sampling rate of 400 Hz, and analyzed using custom software written in Labview (National Instruments).
Data were collected under the following conditions: sinus rhythm, atrial pacing (AOO) at a rate 10% faster than baseline, atrioventricular pacing (DOO) at the same rate as atrial pacing at 3 different RV sites, and atrial pacing again (AOO) to ensure that the patient’s condition remained stable during the study. Condition order of DOO pacing at the different RV sites was randomly assigned. For DOO pacing, an atrioventricular delay of 90% of the PR interval was chosen to facilitate RV capture yet minimize the effect of a shortened AV delay on ventricular function. Three separate RV pacing sites were used: apex, outflow tract, and septum. All pacing conditions were maintained for 2 minutes to obtain a steady state before data collection.
The primary outcomes were change in cardiac index (CI) and change in RV dP/dtmax. CI was determined by using the Fick method, assuming constant oxygen consumption during the study. AOO pacing was used as the study baseline to eliminate the effect of heart rate alteration.
Data were analyzed by using repeated-measures ANOVA and 
2 as appropriate. A value of P=0.05 was taken as significant.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Patient Characteristics
Seven patients (4 males) were studied. Diagnoses included tetralogy of Fallot6 and aortic stenosis status after Ross procedure.1 Baseline characteristics are shown in the Table.
|
Hemodynamic Measures
The Table shows baseline data. CI was generally normal, aside from 1 patient in whom the CI was 1.12 L/min per m2. RV systolic and diastolic pressures were elevated.
Cardiac Index
CI was calculated in all patients for all states. Mean CI in sinus rhythm was 2.8±1.19 L/min per m2, with no significant change in CI from sinus rhythm to AOO pacing (mean increase of 8%; P=NS). The mean CI with DOO pacing was 3.4±1.4 L/min per m2, which represented an increase of 17±8% compared with AOO pacing (P=0.04; Figure). One patient increased CI by 44% during resynchronization. Six of the seven patients increased CI during resynchronization.
|
dP/dtmax
dP/dtmax did not change between sinus rhythm and AOO pacing (mean increase of 0%; P=NS). There was a highly significant increase in dP/dtmax during DOO pacing, from 289±149 to 354±188 mm Hg/s (mean increase of 22% with resynchronization pacing; P=0.01; Figure).
QRS Duration
The QRS duration at baseline was 163±39 ms (range 110 to 240 ms). This decreased for every patient during DOO pacing, with a statistically significant decrease overall to 126±31 ms (P=0.001). The pacing site that produced the narrowest QRS duration was associated with the greatest improvement in CI for 6 of 7 patients (P=0.01). There was no apparent relationship between the site that produced the narrowest QRS duration and the site that produced the best RV dP/dtmax.
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Heart failure due to LV dysfunction is an important cause of death and disability in the United States.10 LV resynchronization represents a major therapeutic advance for selected heart failure patients, with both hemodynamic and clinical benefits.
For many forms of congenital heart disease, it is RV failure rather than LV failure that is clinically important. Many congenital heart lesions lead to long-term complications of RV function, through a combination of volume loading, pressure loading, and surgically induced myocardial injury. As in the LV, RV dysfunction often manifests as dilatation and dyskinesis.
In contrast to the LV, RV failure is less well understood, particularly from a therapeutic perspective. In fact, to our knowledge, there is no therapy for RV dysfunction that is well supported by experimental evidence.
Our data demonstrate the feasibility of RV resynchronization. In a group of patients with moderate to severe RV dysfunction, improvement during at least one pacing condition was seen in all patients. Benefit was demonstrated by an increase in RV dP/dtmax, a well-validated index of ventricular systolic performance.11,12 We selected this as our primary RV outcome because it can be measured independently of ventricular geometry and is insensitive to changes in afterload. Although dP/dtmax is affected by alterations in preload, there is no reason to believe that the pacing intervention altered preload acutely, particularly because heart rate was held constant. Therefore, the change in RV dP/dtmax in this study most likely indicates an improvement in intrinsic contractility. The average increase in dP/dtmax was 22% in our patients. This is a somewhat greater change than was recently described for LV resynchronization (14%).4 To place this in perspective, Nelson and colleagues5 have recently shown that an infusion of 10 to 25 µg/kg per min of dobutamine produced an increase in LV dP/dtmax of 42%.
In addition to the benefit shown in RV performance, resynchronization of the RV consistently improved systemic CI. This finding has several potential explanations. RV resynchronization may have exerted a favorable effect on interventricular interaction, improving LV diastolic performance. Alternatively, the RV may have played a key role in limiting LV output in this group of patients. In either case, the improvement in CI reinforces the potential impact of this therapy on overall cardiovascular hemodynamics. This finding also illustrates a potential role of RV resynchronization in settings of acute RV failure, such as the patient undergoing surgical repair of tetralogy of Fallot.
In LV failure, QRS duration is a good indicator of potential benefit from resynchronization, but the change in QRS duration during pacing does not necessarily correlate with the magnitude of benefit achieved.13,14 In our series, there did not appear to be a good relationship between the site that optimized QRS duration and the site that optimized RV function. However, there was a strong relationship between the degree of QRS improvement and the increase in CI. This relationship needs confirmation in a larger series.
Limitations
This is a preliminary study with a small number of heterogeneous subjects. The role of atrioventricular delay, which has been shown to be important in some studies, was not investigated.15 Our data demonstrate acutely improved hemodynamics but do not prove that there will be clinical benefit in a more chronic setting.
Conclusion
RV resynchronization is a novel therapy that improves RV function acutely in selected patients. In view of the essential role of the RV in many forms of congenital heart disease, this therapy should be tested more comprehensively to determine the potential clinical benefit. Populations of particular interest include those with acute RV failure from surgical repair and patients with chronic RV failure due to underlying congenital heart disease.
|
Acknowledgments |
|---|
This study was supported by the Lucile Packard Foundation for Children’s Health.
Received February 13, 2003; revision received March 25, 2003; accepted March 26, 2003.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Helbing WA, Rebergen SA, Maliepaard C, et al. Quantification of right ventricular function with magnetic resonance imaging in children with normal hearts and with congenital heart disease. Am Heart J. 1995; 130: 828–837.[CrossRef][Medline] [Order article via Infotrieve]
2. Ishii M, Eto G, Tei C, et al. Quantitation of the global right ventricular function in children with normal heart and congenital heart disease: a right ventricular myocardial performance index. Pediatr Cardiol. 2000; 21: 416–421.[CrossRef][Medline] [Order article via Infotrieve]
3. Gatzoulis MA, Clark AL, Cullen S, et al. Right ventricular diastolic function 15 to 35 years after repair of tetralogy of Fallot: restrictive physiology predicts superior exercise performance. Circulation. 1995; 91: 1775–1781.
4. Butter C, Auricchio A, Stellbrink C, et al. Effect of resynchronization therapy stimulation site on the systolic function of heart failure patients. Circulation. 2001; 104: 3026–3029.
5. Nelson GS, Berger RD, Fetics BJ, et al. Left ventricular or biventricular pacing improves cardiac function at diminished energy cost in patients with dilated cardiomyopathy and left bundle-branch block. Circulation. 2000; 102: 3053–3059.
6. Abraham WT, Fisher WG, Smith AL, et al. Cardiac resynchronization in chronic heart failure. N Engl J Med. 2002; 346: 1845–1853.
7. Horneffer PJ, Zahka KG, Rowe SA, et al. Long-term results of total repair of tetralogy of Fallot in childhood. Ann Thorac Surg. 1990; 50: 179–183.[Abstract]
8. Abd El Rahman MY, Abdul-Khaliq H, Vogel M, et al. Relation between right ventricular enlargement, QRS duration, and right ventricular function in patients with tetralogy of Fallot and pulmonary regurgitation after surgical repair. Heart. 2000; 84: 416–420.
9. Hayabuchi Y, Matsuoka S, Kubo M, et al. Usefulness of color kinesis imaging for evaluation of regional right ventricular wall motion in patients with surgically repaired tetralogy of Fallot. Am J Cardiol. 1998; 82: 1224–1229.[CrossRef][Medline] [Order article via Infotrieve]
10. Anderson RN. Deaths: leading causes for 2000. Natl Vital Stat Rep. 2002; 50: 1–85.[Medline] [Order article via Infotrieve]
11. Mahler F, Ross J Jr, O’Rourke RA, et al. Effects of changes in preload, afterload and inotropic state on ejection and isovolumic phase measures of contractility in the conscious dog. Am J Cardiol. 1975; 35: 626–634.[CrossRef][Medline] [Order article via Infotrieve]
12. Furnival CM, Linden RJ, Snow HM. Inotropic changes in the left ventricle: the effect of changes in heart rate, aortic pressure and end-diastolic pressure. J Physiol. 1970; 211: 359–387.
13. Leclercq C, Cazeau S, Ritter P, et al. A pilot experience with permanent biventricular pacing to treat advanced heart failure. Am Heart J. 2000; 140: 862–870.[CrossRef][Medline] [Order article via Infotrieve]
14. Nelson GS, Curry CW, Wyman BT, et al. Predictors of systolic augmentation from left ventricular preexcitation in patients with dilated cardiomyopathy and intraventricular conduction delay. Circulation. 2000; 101: 2703–2709.
15. Auricchio A, Stellbrink C, Block M, et al. Effect of pacing chamber and atrioventricular delay on acute systolic function of paced patients with congestive heart failure: The Pacing Therapies for Congestive Heart Failure Study Group; The Guidant Congestive Heart Failure Research Group. Circulation. 1999; 99: 2993–3001.
This article has been cited by other articles:
 |
|
 |
|
  M. L. Handoko, R. R. Lamberts, E. M. Redout, F. S. de Man, C. Boer, W. S. Simonides, W. J. Paulus, N. Westerhof, C. P. Allaart, and A. Vonk-Noordegraaf Right ventricular pacing improves right heart function in experimental pulmonary arterial hypertension: a study in the isolated heart Am J Physiol Heart Circ Physiol, November 1, 2009; 297(5): H1752 - H1759. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. W.K. Peng, S. Lilley, B. Knight, J. Sinclair, F. Lyall, K. MacArthur, J. C.S. Pollock, and M. H.D. Danton Synergistic interaction between right ventricular mechanical dyssynchrony and pulmonary regurgitation determines early outcome following tetralogy of Fallot repair Eur. J. Cardiothorac. Surg., October 1, 2009; 36(4): 694 - 702. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Nour, G. Wu, Z. Zhensheng, J. C Chachques, A. Carpentier, and D. Payen The Forgotten Driving Forces in Right Heart Failure: New Concept and Device* Asian Cardiovasc Thorac Ann, October 1, 2009; 17(5): 525 - 530. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Bordachar, X. Iriart, J. Chabaneix, F. Sacher, S. Lafitte, P. Jais, M. Haissaguerre, J. Clementy, P. Dos Santos, and J.-B. Thambo Presence of ventricular dyssynchrony and haemodynamic impact of right ventricular pacing in adults with repaired Tetralogy of Fallot and right bundle branch block Europace, August 1, 2008; 10(8): 967 - 971. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Haddad, R. Doyle, D. J. Murphy, and S. A. Hunt Right Ventricular Function in Cardiovascular Disease, Part II: Pathophysiology, Clinical Importance, and Management of Right Ventricular Failure Circulation, April 1, 2008; 117(13): 1717 - 1731. [Full Text] [PDF]
|
|
|
|
 |
|
 R E Lane, J Mayet, N S Peters, D W Davies, and A W C Chow Comparison of temporary bifocal right ventricular pacing and biventricular pacing for heart failure: evaluation by tissue Doppler imaging Heart, January 1, 2008; 94(1): 53 - 58. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Byrne, R. H. Helm, S. Daya, N. F. Osman, H. R. Halperin, R. D. Berger, D. A. Kass, and A. C. Lardo Diminished Left Ventricular Dyssynchrony and Impact of Resynchronization in Failing Hearts With Right Versus Left Bundle Branch Block J. Am. Coll. Cardiol., October 9, 2007; 50(15): 1484 - 1490. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Uebing, D. G. Gibson, S. V. Babu-Narayan, G. P. Diller, K. Dimopoulos, O. Goktekin, M. S. Spence, K. Andersen, M. Y. Henein, M. A. Gatzoulis, et al. Right Ventricular Mechanics and QRS Duration in Patients With Repaired Tetralogy of Fallot: Implications of Infundibular Disease Circulation, October 2, 2007; 116(14): 1532 - 1539. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Authors/Task Force Members, P. E. Vardas, A. Auricchio, J.-J. Blanc, J.-C. Daubert, H. Drexler, H. Ector, M. Gasparini, C. Linde, F. B. Morgado, et al. Guidelines for cardiac pacing and cardiac resynchronization therapy: The Task Force for Cardiac Pacing and Cardiac Resynchronization Therapy of the European Society of Cardiology. Developed in Collaboration with the European Heart Rhythm Association Europace, October 1, 2007; 9(10): 959 - 998. [Full Text] [PDF]
|
|
|
|
 |
|
 Authors/Task Force Members, P. E. Vardas, A. Auricchio, J.-J. Blanc, J.-C. Daubert, H. Drexler, H. Ector, M. Gasparini, C. Linde, F. B. Morgado, et al. Guidelines for cardiac pacing and cardiac resynchronization therapy: The Task Force for Cardiac Pacing and Cardiac Resynchronization Therapy of the European Society of Cardiology. Developed in Collaboration with the European Heart Rhythm Association Eur. Heart J., September 2, 2007; 28(18): 2256 - 2295. [Full Text] [PDF]
|
|
|
|
|
|
E. P. Walsh Interventional Electrophysiology in Patients With Congenital Heart Disease Circulation, June 26, 2007; 115(25): 3224 - 3234. [Full Text] [PDF]
|
|
|
|
|
|
T. A. Quinn, G. Berberian, S. E. Cabreriza, L. J. Maskin, A. D. Weinberg, J. W. Holmes, and H. M. Spotnitz Effects of sequential biventricular pacing during acute right ventricular pressure overload Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2380 - H2387. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G.-P. Diller, D. Okonko, A. Uebing, S. Y. Ho, and M. A. Gatzoulis Cardiac resynchronization therapy for adult congenital heart disease patients with a systemic right ventricle: analysis of feasibility and review of early experience. Europace, April 1, 2006; 8(4): 267 - 272. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. P. Pham, S. Balaji, I. Shen, R. Ungerleider, X. Li, and D. J. Sahn Impact of Conventional Versus Biventricular Pacing on Hemodynamics and Tissue Doppler Imaging Indexes of Resynchronization Postoperatively in Children With Congenital Heart Disease J. Am. Coll. Cardiol., December 20, 2005; 46(12): 2284 - 2289. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Dubin Resynchronization in Pediatrics: Who Needs It? J. Am. Coll. Cardiol., December 20, 2005; 46(12): 2290 - 2291. [Full Text] [PDF]
|
|
|
|
|
|
H J Nesser, O-A Breithardt, and B K Khandheria Established and evolving indications for cardiac resynchronisation Heart, December 1, 2004; 90(suppl_6): vi5 - vi9. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Janousek, V. Tomek, V. Chaloupecky, O. Reich, R. A. Gebauer, J. Kautzner, and B. Hucin Cardiac resynchronization therapy: A novel adjunct to the treatment and prevention of systemic right ventricular failure J. Am. Coll. Cardiol., November 2, 2004; 44(9): 1927 - 1931. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Janousek, A. M. Dubin, J. A. Feinstein, G. F. Van Hare, D. N. Rosenthal, V. M. Reddy, and F. L. Hanley Electrical Resychronization of Failing Right Ventricle * Response Circulation, January 20, 2004; 109 (2): e5 - e5. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||