Biventricular Pacing in Pediatric Patients

Given the inherent differences in cardiac pathology seen in adult and pediatric patients, simply extrapolating data from large multicenter trials in adults with heart failure is not always relevant to the management of young patients. Biventricular pacing in pediatrics was a topic of discussion at a recent symposium hosted by The Sibley Heart Center at Children s Healthcare of Atlanta. The 5th International Pediatric Cardiac Symposium: Management of Complex Congenital Heart Disease from Infancy to Adulthood was held June 23-26, 2005, at the Ritz-Carlton on Amelia Island, Florida. Indications for Biventricular Pacing The traditional indications for biventricular pacing/resynchronization therapy in adult patients with congestive heart failure include optimized medical therapy, NYHA class III or IV heart failure, reduced left ventricular ejection fraction and ventricular dysynchrony. Early data has suggested an approximately 30% non-responder rate, though advances in non-invasive imaging have further refined the evaluation of ventricular dysynchrony in an attempt to improve selection success rates. Moreover, these criteria are generalized for adult patients with heart failure and have not necessarily proven useful in pediatric patients. A study out of Boston Children s Hospital3 evaluated a cohort of pediatric patients with ventricular dysfunction, looking specifically at eligibility for biventricular pacing based upon criteria used in adult patients. These researchers found that only 2 of 95 patients with underlying congenital heart disease and 4 of 58 with primary cardiomyopathy met the "adult" criteria for resynchronization therapy. It was evident that simply applying the "adult" criteria in young patients with a more heterogeneous substrate was not practical. In addition to heterogeneity in diagnosis, there are a number of other issues encountered in pediatric pacing that must be considered when determining patient eligibility. Small patient size and structural heart disease with potential for intracardiac shunting often preclude the use of transvenous pacing leads. The unknowns associated with the long-term placement of a coronary sinus lead in a child are also of concern. For these reasons, epicardial lead placement may be preferable in many pediatric patients. Applications of Biventricular Pacing in Pediatrics Despite the difficulty with patient selection, biventricular/resynchronization pacing has proven beneficial in select pediatric patients, both in the acute post-operative setting and as chronic therapy. Biventricular epicardial pacing has demonstrated a beneficial hemodynamic effect in young patients recovering from congenital heart surgery.^4,5 In some patients, this pacing strategy has been used to wean patients successfully from cardiopulmonary bypass. Many patients with repaired and/or palliated congenital heart disease are at risk of developing ventricular dysfunction in the long-term. In some, it is the right ventricle that is in need of restoration of synchrony, such as those with repaired tetralogy of Fallot. Dubin, et al.⁶ evaluated the acute effects of right ventricular pacing as a means of improving ventricular synchrony and function in a cohort of patients with right ventricular failure related to their congenital heart disease. In the acute setting, these patients demonstrated improvements in systemic and right ventricular performance, suggesting that RV resynchronization may be a useful tool in select patients. Strieper, et al.⁷ reported the early experience with resynchronization pacing in young patients with congenital heart disease. This cohort had been referred for consideration of cardiac transplantation given their severe ventricular dysfunction. All but one of these patients was subsequently removed from consideration of transplantation following the initiation of biventricular pacing. Interestingly, all of these patients had required long-term single-site ventricular pacing prior to presenting with heart failure. While the underlying cardiac disease likely played a role in the development of ventricular dysfunction in these patients, one must also consider the causal role of chronic dysynchronous ventricular activation. Detrimental Effects of Single-Site Ventricular Pacing The idea that chronic single-site ventricular pacing is detrimental to myocardial performance has been shown in animal pacing models and human clinical evaluations. Our work in an animal model of AV block evaluated the acute effects of various epicardial pacing modes on myocardial performance.⁸ In the mature canine, epicardial biventricular pacing was superior to single-site ventricular pacing from the right ventricular apex (RVA) and left ventricular apex (LVA). The biventricular combination of RVA and LVA was the most beneficial pacing modality. We have recently completed an acute evaluation of epicardial biventricular pacing on an immature animal model. The findings in the immature animal suggest that single-site ventricular pacing from the LVA and biventricular pacing (RVA/LVA) are superior to standard single-site ventricular pacing from the RVA. This recent finding corresponds with the results of an acute pacing trial in children following repair for congenital heart disease. Vanagt, et al.⁹ performed acute epicardial pacing (RVA, LVA, and LV free wall) on children immediately after their cardiac surgery. These investigators found that single-site pacing from the LVA resulted in the most significant improvement in LV dP/dt max and aortic pulse pressure. Biventricular pacing was not assessed in this study. The detrimental effects of single-site ventricular pacing were quite clear in the DAVID trial¹⁰ and a study evaluating the effects of atrial and dual chamber pacing in patients with sick sinus syndrome.¹¹ The later study compared atrial pacing, dual chamber pacing with a short AV delay, and dual chamber pacing with a long AV delay in patients with sick sinus syndrome. The patients with atrial pacing and dual chamber pacing with a long AV delay (less ventricular pacing) had fewer episodes of atrial fibrillation and improved ventricular function as compared to the patients programmed dual chamber with a long AV delay. The DAVID trial evaluated patients with an indication for ICD, comparing DDDR pacing and VVI backup pacing. The increased mortality and heart failure hospitalizations in the DDDR group resulted in early termination of this study. The authors concluded that in patients with no indication for pacing, dual chamber pacing offers no clinical advantage over ventricular backup pacing and may be detrimental. Prosynchronization Pacing Unlike the patients in the aforementioned clinical trials, young patients with congenital or acquired AV block typically do not have a choice of whether or not to pace. The underlying rhythm in these patients is often a junctional escape with a narrow QRS complex signaling a synchronous depolarization pattern. Standard single-site ventricular pacing results in a dysynchronous ventricular activation pattern that may, in the long-term, result in ventricular dysfunction. Recent data suggests that while many of these patients are asymptomatic, this lack of symptoms is relative. When matched against healthy age-matched controls, a group of young adults who had been paced for 10 ±3 years for congenital AV block had decreased exercise performance by treadmill testing and increased markers of ventricular dysynchrony based on tissue Doppler imaging.¹² Concerns have been raised on a cellular level as well. Karpawich studied a group of patients with congenital AV block, performing RV endomyocardial biopsies prior to and approximately 5 years after the initiation of single-site ventricular pacing.¹³ The initial specimens revealed no degenerative changes at baseline, though there were varying degrees of cellular disarray at follow-up. Given the concerns regarding chronic single-site ventricular pacing, it is reasonable to consider alternate pacing sites and combinations in children who will potentially require decades of artificial stimulation. As most of these patients have a normal, synchronous ventricular activation pattern at the initiation of pacing, the use of biventricular or alternate site pacing in these patients can be thought of as prosynchronization pacing. The goal of prosynchronization pacing is to maintain a normal ventricular activation pattern and potentially avoid the development of long-term ventricular dysfunction. The difficulty lies in determining which patients would benefit from a treatment that will require novel lead placement. Conclusion As pediatric electrophysiologists, we are faced with many pacing challenges in young patients. Patient size, underlying cardiac pathology and the need for long-term (life-long) vascular access often preclude the use of transvenous leads. In those patients deemed adequate for transvenous pacing, the unknowns associated with chronic lead placement in the coronary sinus make this option for biventricular pacing less attractive as well. However, placing multiple epicardial leads, and using this approach well beyond the typical age/size may not be ideal. It is clear that our standard modes of pacing, while often adequate, may not be the optimal approach in young patients. However, the potential obstacles to chronic biventricular or alternate site pacing in young patients should not be taken lightly. As we consider new approaches, we must proceed cautiously, with collaborative research leading the way.