Pacing for bradycardia

Heart block seen in the setting of congenital cardiac malformations can be congenital, or present later in life. Lesions particularly associated with inherent abnormalities of the conduction system include atrioventricular septal defects with common atrioventricular junction, visceral heterotaxy in the setting of isomeric atrial appendages, and lesions with discordant atrioventricular connections, as typically seen in congenitally corrected transposition.^{1, 2} Individuals with these lesions should be frequently evaluated for progression of disease afflicting the conduction system, even if they appear to have normal atrioventricular conduction at birth. The conduction system is thought to be vulnerable due to anatomic factors, such as the anterior and superior displacement of the atrioventricular node leading to a longer course of the bundle of His.^{3, 4} Patients with discordant atrioventricular connections have been reported to have a prevalence of complete heart block at birth of 3.6 percent–5.2 percent, and a risk of 2 percent per year of spontaneously developing heart block.^{1, 5, 6} Additionally, patients who undergo surgical repair of congenital heart disease are at risk of postoperative heart block, with the level of risk varying with the location of the lesion. Infectious and metabolic aetiologies can also lead to heart block and a need for pacing. Indications for pacing in the children and the overall population of patients with congenital cardiac disease have been reviewed in the guidelines published in 2002 by a joint committee of the American College of Cardiology, American Heart Association, and North American Society of Pacing and Electrophysiology, the latter group now known as the Heart Rhythm Society.⁷

When faced with a child, or a patient with congenital cardiac disease who may require pacing, consideration must be given to several factors, such as the size of the patient, venous and cardiac anatomy, haemodynamics, and the state of the conduction system. All of these will contribute to the decision of single versus dual chamber devices, desired programmable options, as well as surgical approach. The discussion over the benefits of single versus dual chamber pacing has existed in the electrophysiologic community for years. Dual chamber devices offer the ability to maintain constant atrioventricular synchrony and sinus-based chronotropy, but may increase the amount of ventricular pacing, which has been associated with adverse outcomes in adults.⁸ No clear resolution to this question has been arrived at in the literature, but new modes of pacing that promote intrinsic conduction, and allow for back-up ventricular pacing, are offering clinicians more flexibility in programming the pacemakers.⁹ For patients with complete heart block, chronotropy is important, and can be created with either atrial based pacing or rate-responsive pacemakers, which have been found to perform well in children.^{10, 11} Size and cardiac anatomy are generally the primary determinants of surgical approach in these patients. Although transvenous implantation has been shown to be feasible in infants,^{12, 13} concerns remain regarding risk of long term vascular compromise in those weighing less than 10 kilograms.^{12, 14} Epicardial systems are most frequently used in infants, and both single and dual chamber systems can be implanted using these techniques. The epicardial approach is also commonly utilized in patients with structural cardiac disease and intracardiac shunting, as intravascular leads can be associated with thrombosis, embolism and stroke in this group of patients. Steroid eluting leads are now used whenever possible, and with these the incidence of pacemaker lead exit block, an inflammatory-mediated process, is significantly reduced.^{15, 16} Determination of the ideal pacing system for any given child must consider all of these factors, and therapy should be individualized for each patient. Additional thought should be given to the need for antitachycardia therapies, such as antitachycardia pacing or defibrillation, as well as cardiac resynchronization therapies, as will be reviewed in the remainder of our discussion.

Resynchronization therapy

The failing and dilated heart often has an associated delay in intraventricular conduction. This delay may cause dyssynchronous activation and contraction of the ventricles, which can lead to depressed systolic function, shorter diastolic filling times, abnormal morphologic changes, and ultimately to decreased cardiac output. Resynchronization therapy uses pacing techniques to stimulate regions of the heart prematurely, in an effort to restore electrical and mechanical synchrony. Resynchronization therapy using biventricular pacing in adults with dilated cardiomyopathy and left bundle branch block has been shown to improve symptoms from heart failure, quality of life, increase exercise tolerance, and improve overall survival.^{17, 18}

Resynchronization therapy has recently been extended to the populations with congenital cardiac disease. These populations, however, are very different from the population of adults for which resynchronization therapy was initially developed. Patients with congenital cardiac disease frequently have right bundle branch block, while left bundle branch block is relatively rare. In addition, it is often the morphologically right ventricle, either as the subpulmonary ventricle as in tetralogy of Fallot, or as the systemic ventricle in congenitally corrected transposition, that fails in such patients. An additional level of complexity is added by patients with functionally univentricular physiology, who are also at risk for heart failure. The population of patients with congenital cardiac disease also provides challenges for implantation of pacemakers in terms of the size of the patient, vascular access, and venous anatomy. The applicability of resynchronization therapy in this population, therefore, is currently the subject of much interest.

Initial experience with resynchronization therapy in this population was in the acute postoperative setting following surgery for congenital cardiac disease.^{19, 20} In these studies, temporary epicardial pacing leads were placed at various ventricular locations, such as the right and left ventricle, multiple right ventricular locations, or multiple systemic ventricular locations in patients with a functionally single ventricle. These studies showed that resynchronization therapy could decrease the duration of the QRS complex, increase systolic blood pressure, and increase cardiac output.^{19, 20} Zimmerman et al.²⁰ demonstrated in two patients that intraoperative pacing was able to help facilitate weaning from cardiopulmonary bypass.²⁰ A more recent study demonstrated that resynchronization therapy decreased mechanical dyssynchrony as assessed by tissue Doppler imaging, as well as increased cardiac index in the post-operative patient.²¹

In another study, electrical resynchronization using right ventricular pacing was described in 7 patients with chronic right ventricular dysfunction and right bundle branch block.²² The study was an unblinded, acute intervention in which pacing leads were placed into the right atrium and at various locations within the right ventricle. Atrioventricular sequential pacing produced a decrease in the duration of the QRS complex, an increase in cardiac index, and an increase in right ventricular dP/dt when compared to atrial pacing.²² Interestingly, the site of pacing in the right ventricle that produced the narrowest QRS duration correlated to the site with the greatest improvement in cardiac output, but did not correlate to the site with the greatest increase in dP/dt.²²

Since these initial experiences, several case series, and one large multicentric report, have been published describing the use of resynchronization therapy in patients with congenital heart disease. Strieper et al.²³ described 7 patients, with a mean age of 11 years, who were referred for consideration of cardiac transplantation because of refractory heart failure. They underwent resynchronization therapy as part of upgrading their pacemaker, or as new therapy. Over a follow-up period of 19 months, there was a significant increase in ejection fraction and significant decrease in left ventricular end diastolic dimension and QRS duration. During follow-up, 5 patients were removed from consideration for transplantation because of symptomatic improvement. Janousek et al.²⁴ described 8 patients, with a mean age of 15 years, all with a systemic morphologically right ventricle and delay in right ventricular conduction, either due to spontaneous right bundle branch block or induced by left ventricular-pacing, who underwent treatment by chronic resynchronization. Over a period of 17 months, the patients demonstrated an increase in ejection fraction and improvement in echocardiographic indexes of synchrony and cardiac performance. Khairy et al.²⁵ reported experience with resynchronization in 13 patients, having a mean age of 7 years, and with having a systemic morphologically right ventricle. Over a period of follow-up of 16 months, all patients undergoing follow-up demonstrated improved haemodynamics with either an increased ejection fraction or increased dP/dt.

Dubin et al.²⁶ recently reported the largest multicentric collaborative experience of chronic resynchronization in children. They evaluated 103 patients from 22 centres. The median age at the start of resynchronization was 12.8 years, with a median follow-up of 4 months. Just over seven-tenths of the patients had congenital cardiac disease, with one-tenth of these having functionally univentricular physiology, one-sixth had cardiomyopathy, and one-eighth had congenital complete heart block with cardiomyopathy. Following initiation of resynchronization, the duration of the QRS complex decreased, and ejection fraction increased. Of the patients, 11 were considered nonresponders, and had either an unchanged or worsened ejection fraction in response to resynchronization. Adverse events occurred in just under three-tenths of the overall group, issues with the lead in the coronary sinus being the most common complication. The overall mortality rate was 5 percent.

To date, therefore, the accumulated evidence regarding the use of resynchronization for patients with congenitally malformed hearts has mostly been positive. Yet many challenges remain. Determining who will best respond to resynchronization, and how to measure that response, is hotly debated by those dealing with adults, and will surely have relevance for the treatment of children. Furthermore, while the retrospective data has been encouraging, there is a clear need for prospective multicentric trials to evaluate this novel technology.

Implantable cardioverter-defibrillators

Implantable cardioverter-defibrillators have been shown to be extremely effective in treating and preventing sudden death in children and young adults with congenitally malformed hearts. The use of such devices in this population has grown significantly in the last several years. One of the most common diagnoses for young patients with implantable cardioverter-defibrillators is repaired congenital cardiac disease, including tetralogy of Fallot, transposition, and left sided obstructive lesions, among others. Other diagnoses seen include primary electrical disease, such as the long QT syndrome, catecholaminergic ventricular tachycardia, and idiopathic ventricular fibrillation, as well as hypertrophic and dilated cardiomyopathies.^{27, 28} General consensus exists regarding indications of use of the devices for secondary prevention, including patients resuscitated from near-miss sudden death with documented ventricular arrhythmia, and documented haemodynamically significant ventricular tachycardia requiring cardioversion or defibrillation. Unexplained syncope in the setting of repaired congenital heart disease, and repeated syncope despite adequate treatment of primary electrical disease, may also fit into this category. Indications for primary prevention, such as malignant family history, positive ventricular extrastimulus testing, and thickened ventricular septums in patients with hypertrophic cardiomyopathy, are still the subject of much debate. The lack of randomized clinical trials to determine who will derive a benefit in terms of survival following implantation of a cardioverter-defibrillator in this population leaves clinicians with ongoing discussions regarding appropriate indications for implantation.

Multiple retrospective studies from single centres have demonstrated a high incidence of appropriate defibrillation therapies in children, with effective results in one- to three-quarters of the patients.^{27, 28} In two recent studies,^{29, 30} the rate of implantable cardioverter-defibrillator therapies in patients with congenital heart disease was stratified on the basis of primary as opposed to secondary prevention. In one study, an equivalent rate of appropriate therapies was found in the two groups.²⁹ In the second study, equivalence was found between the group undergoing secondary prevention and those having primary prevention in the setting of a positive ventricular stimulation study, while those receiving primary prevention without a positive ventricular stimulation study had a lower rate of appropriate therapies.³⁰ Both studies demonstrated an equivalent rate of inappropriate shocks between the patients having devices implanted for primary and secondary prevention.

The incidence of inappropriate therapies is, unfortunately, relatively high in children, being found in up to half of the population.^{27, 28} The majority of inappropriate therapies are due to rapidly conducting supraventricular tachycardia, including sinus tachycardia, or failure of the leads.^{27, 28, 31} Prevention of most inappropriate therapies due to supraventricular tachycardia can be achieved by determining upper intrinsic rate with exercise testing, using beta-blockers, increasing the detection time or rate, programming discriminating algorithms, or placing an atrial lead to enhance the capability to discriminate.³¹ In one study, using multivariate predictive models, it was shown that somatic growth was significantly correlated with lead failure.²⁷ Once a lead has failed, frequently the only option is to remove the lead prior to implantation of a new device. Cooper et al.³² recently demonstrated that it is possible to extract leads safely, and with minimal morbidity, when an experienced operator uses a laser sheath retrieval system.³²

Routine follow-up of patients with implantable cardioverter-defibrillators typically has included interval defibrillation threshold testing. This has been thought to be especially important in children, since they have a relatively high incidence of lead failure. Recent evidence has suggested that, even though defibrillation thresholds increase over time, routine threshold testing may not significantly alter clinical practice. In the study coordinated by the first author of this review,³³ it was shown that almost nine-tenths of routine tests of defibrillation threshold led to no clinical changes. Conversely, half of threshold tests performed in patients in whom there was a clinical concern led to important programming or hardware modifications. Clinical concern was prompted by changes in sensing or pacing characteristics of the lead, changes in lead position on X-ray, ablation or surgery near the existing lead, or inappropriate shocks. The authors³³ proposed that routine testing of the defibrillation threshold may not be necessary, but that important clinical changes should be evaluated with consideration of repeated testing.

In the population of patients with congenitally malformed hearts, implantation of cardioverter-defibrillators may be limited due to the specific cardiac anatomy or the size of the patient. Epicardial patches have been used in some of these patients, but require a thoracotomy and may lead to a restrictive pericardial process. Recently, alternative configurations have been developed to allow implantation in patients with intracardiac shunting, or those who are too small for traditional transvenous implantation. Descriptions of these configurations were first published in 2001, when three centres described cases where epicardial ventricular sensing leads were combined with a subcutaneously implanted high voltage coil, and the active generator was placed in an abdominal position.^34–36 Another alternative configuration uses a transvenous high voltage lead placed in an epicardial position, again with an abdominally positioned active generator. Both of these alternative configurations have been used successfully in children, but the patients require close monitoring and follow-up, including routine testing of the defibrillation threshold, as they are new technologies. As such, they are prone to possible unanticipated complications.³⁷

Conclusions

Although patients with congenitally malformed hearts account for less than one percent of all implantations of pacemakers and cardioverter-defibrillators, electrophysiologic abnormalities represent a major cause of morbidity and mortality in this population. Recent advances in the technologies available, as well as novel applications of those technologies, have improved the ability of the paediatric cardiologist to care for these complex patients. The continued innovation and miniaturization of the devices will allow us to progress towards the fundamental goal of restoring the electrical systems of the heart, thus protecting and improving the quality of life of our patients.