- Email: [email protected]
Improving Pacemaker Therapy in Congenital Heart Disease: Contractility and Resynchronization
Improving Pacemaker Therapy in Congenital Heart Disease: Contractility and Resynchronization Peter P. Karpawich Designed as effective therapy for patients with symptomatic bradycardia, implantable cardiac pacemakers initially served to improve symptoms and survival. With initial applications to the elderly and those with severe myocardial disease, extended longevity was not a major concern. However, with design technology advances in leads and generators since the 1980s, pacemaker therapy is now readily applicable to all age patients, including children with congenital heart defects. As a result, emphasis and clinical interests have advanced beyond simply quantity to quality of life. Adverse cardiac effects of pacing from right ventricular apical or epicardial sites with resultant left bundle branch QRS configurations have been recognized. As a result, and with the introduction of newer catheter-delivered pacing leads, more recent studies have focused on alternative or select pacing sites such as septal, outflow tract, and para-bundle of His. This is especially important in dealing with pacemaker therapy among younger patients and those with congenital heart disease, with expected decades of artificial cardiac stimulation, in which adverse myocellular changes secondary to pacing itself have been reported. As a correlate to these alternate or select pacing sites, applications of left ventricular pacing, either via the coronary sinus, intraseptal or epicardial, alone or in combination with right ventricular pacing, have gained interest for patients with heart failure. Although cardiac resynchronization pacing has, to date, had limited clinical applications among patients with congenital heart disease, the few published reports do indicate potential benefits as a bridge to cardiac transplant. Semin Thorac Cardiovasc Surg Pediatr Card Surg Ann 18:51-56 C 2015 Elsevier Inc. All rights reserved.
Introduction
D
esigned as effective therapy for patients with symptomatic bradycardia, cardiac pacemakers initially served to improve patient symptoms and survival. Any adverse hemodynamic consequences were not yet realized. Complications, as recognized, typically involved implant issues, device design, and physical effects of leads on valves and interactions of lead tip electrodes with cardiac tissue. Because of initial pacing lead design technologies, with no lead tip fixation capabilities, the ventricular apex and atrial appendages were chosen as secure anatomic sites that permitted ease of lead implant with limited dislodgement.1 Epicardial ventricular leads typically were
Section of Cardiology, Department of Pediatrics, The Children’s Hospital of Michigan, Wayne State University School of Medicine, Detroit, MI. Conflict of Interest: none Address Correspondence to Peter P. Karpawich, MSc, MD, Director, Cardiac Electrophysiology, The Children’s Hospital of Michigan, 3901 Beaubien Blvd., Detroit, MI 48201. E-mail: [email protected]
http://dx.doi.org/10.1053/j.pcsu.2014.12.002 1092-9126/& 2015 Elsevier Inc. All rights reserved.
placed anywhere on the anterior right ventricle, primarily for ease of implant and convenience.2 However, over time, further studies indicated that ventricular pacing itself, associated with inherent bundle branch block QRS morphologies and resultant altered ventricular contractility vectors, can be associated with adverse myocellular changes contributing to decreased function.3–7 With improvement in design technologies, the 1990s saw a re-thinking of pacing applications with an increase in applications to patients with repaired congenital heart disease (CHD). As part of ongoing investigations to improve paced myocardial contractility and maintain normalized right and left contractions, the concept of “alternative site” pacing evolved. Bundle of His, septal and ventricular outflow tract, as well as Bachmann’s bundle sites have been explored.8–11 As an offshoot to these investigations, dual ventricular leads or “biventricular” pacing, with two right ventricular leads or one lead in the right and the other in the left ventricle saw promise to improve an already abnormally contractile or “desynchronized” systemic ventricle caused by ischemia, congestive cardiomyopathy, CHD, and advanced heart failure.12–14 In 51
P.P. Karpawich
52
KEY POINTS Lead implant location and the initiation of pacing dictate myocardial contractility response.
Right ventricular apical pacing with an inherent left bundle branch block QRS morphology can adversely alter left ventricular function.
A proactive approach to optimize paced myocardial function, irrespective of pacing lead threshold/sensing issues, should be a part of every pacemaker implant.
Left ventricular apical is superior to right ventricular epicardial pacing, both for temporary and permanent lead implant.
Concerns for chronic vascular/valvular issues are still present when contemplating endocardial pacing in children.
Resynchronization pacing (CRT) can be applicable to some patients with congenital heart defects and heart failure, but none of the published guidelines for patient selection or implant values are applicable.
Detailed knowledge of anatomy and vascular issues among repaired CHD patients is mandatory prior to pacemaker/ ICD implant. cardiac “resynchronization” therapy (CRT) pacing, two ventricular leads in effect coerce the heart to contract between them, with more normal left-right “synchronization.” This is in deference to the left-right delay as represented by the typical pacing-induced bundle branch block QRS. This combined action ostensibly can realign disarranged myofibrils, improves electromechanical activation, and increases contractile efficiency. As a result, although not curing the underlying heart disease, CRT can improve the clinical expression of the failing heart.
pacing thresholds, have been stressed for decades. However, since the introduction of low-threshold and steroideluting endo- and epicardial pacing leads, such concerns have become less important.15–17 Since the 1920s, pacing electrode placement in close proximity to the normal conduction system has been known to offer the potential for improved ventricular function by optimizing biventricular contractility.18 More recently, various studies have demonstrated that pacing site, and therefore the initiation of ventricular contractility, is the prime contributor to function.19 However, just which parameters to measure to ascertain optimal paced ventricular contractility have not been resolved. Initially thought to have potential for a correlation with contractility, QRS duration does not appear to be that effective of a marker.20 This is especially true among patients with repaired congenital heart defects in whom abnormal QRS axis and morphologies are commonly found. Other more accurate measurements have included pressure-volume loops, as well as the first derivative of systolic pressure (dP/dt), which additionally has had pertinent impact with interest in resynchronization pacing for heart failure.21,22 Initial lead implant optimization with direct measurements of physiologic responses, especially among a patient population, such as repaired congenital heart, in whom pacing can be anticipated to be required for decades, is a prudent approach to medical care delivery. With the introduction of improved low threshold and steerable pacing lead designs permitting fixation at nearly any ventricular location, alternative right ventricular pacing (“septal,” “outflow tract”) sites have been demonstrated to offer improved response over the apex (Fig. 1). However, there is confusion in the literature as precise definition of these sites is
Optimizing Paced Ventricular Function Initiation of paced electrical impulse propagation from an apical or free wall epicardial region is associated more with muscle than His-Purkinje (H-P) conduction, causing asynchronous right and left ventricular contractility changes. The spiral orientation of ventricular muscle fibers favors optimal contractility when normal H-P conduction occurs. Anything else will realign stress vectors. Because ventricular function may be affected by rate, atrioventricular activation coupling intervals, and pacing site, each of these variables have found interest in both animal and clinical studies. Prevention of potential dysfunction by a more proactive approach to initial pacemaker application based on contractility response is a less-established clinical application than standard implant protocols, in which lead integrity and optimization of electrode-tissue interface reactivity to limit fibrotic capsule formation and assure low
Figure 1 Fluoroscopic appearance in the A-P projection of a endocardial right ventricular septal lead implant in a patient with a fractured previous epicardial pacing lead. Use of the deflectable introducing catheter (arrow) allows for precise lead implant at the septal site that demonstrates optimal contractility using a temporary quadripolar pacing catheter.
Improving Cardiac Pacing frequently lacking.23 One recent study has sought to better define potential ventricular implant sites with concomitant contractility indices.24 Although 38% of patients studied exhibited the most optimal paced contractility from the mid ventricular septum that approximated the region of the moderator band, interestingly, apical pacing, among certain repaired congenital heart patients, was found to be associated with the best contractility response. This was frequently found among patients with dyskinetic septal contractility following repaired septal defects. CHD anatomy and post-surgical residue of prosthetic patches, conduits, and valves add additional concerns that must be recognized and addressed whenever any cardiac implantable electronic device (CIED) therapy is contemplated.25 Because many repaired congenital heart patients require epicardial pacing, fortunately there are comparable animal and clinical studies that evaluate pacing responses between right and left ventricular epicardial sites, with the left ventricular epicardium demonstrating improved responses. In this respect, the concept that any epicardial left is preferential to any right ventricular site has been advocated. The lateral free wall of the left ventricle, an area between the left anterior descending coronary artery and diagonal coronary branches at a distance from the left atrial appendage, has been reported to be an excellent location for epicardial pacing in children.26 Other studies comparing potential epicardial left ventricular sites have reported that the apical region can be the most effective for optimal contractility responses both as a temporary or permanent lead implant location (Fig. 2).27,28 A common question, and one that has been the focus of many debates at scientific sessions, is the age-appropriateness of endocardial versus epicardial pacing leads. As an initial concept, especially to avoid potential thromboembolic
53 concerns, patients with single ventricle morphologies should receive an epicardial pacing system. It may also be prudent and perhaps most efficacious to implant an epicardial pacing system, if required, at the time of CHD surgical repair in a child. This can even apply to the implant of a permanent epicardial lead without generator in those instances of presumed temporary heart block, with the generator implanted later if the block does not resolve.29 The literature has reported safety of endocardial lead implant in children weighing from 2.3 to 20 kg, with a “ballpark” acceptable range typically of 15 to 20 kg.30–32 However, follow-up has been somewhat limited with mean values of about 6 years. There is probably no real debate that endocardial leads can and do perform well in regard to thresholds in children comparable to adults, especially in the current era of steroid eluting designs. However, a “save the veins and valves” approach may still be prudent. Patient growth and lead effects and performances remain a concern. Pacing leads are not completely thrombi-free and lead/tissue interactions do occur. Estimation of age-related venous diameters as well as lead lengths may be helpful in decision making.33,34 Lead extraction, however, is more complicated than implant. These issues need to be considered, especially when contemplating endocardial pacemaker implant in a patient with an anticipated 20 to 50 years of pacing. Eventually switching from an epi- to endocardial pacing system may have less morbidities than dealing with chronic endocardial leads once implanted in very young children. Adverse vascular/valvular effects are still found with endocardial leads. Venous occlusions have been reported in more than 20% of children and young adults.35 Although the newer 4.1 French diameter lead may be associated with less valvular damage than larger diameter leads, very long term follow-up studies are still lacking.36 As a result, an informed implanter must consider all potential variables and long-term consequences associated with both lead implant approaches.
Resynchronization Pacing
Figure 2 Radiographic appearance of left atrial and ventricular epicardial pacing leads.
In the past decade, there have been numerous studies encompassing thousands of patients on the potential applications of pacing therapy to improve dysfunctional ventricles in adults with congestive heart failure, typically caused by ischemic heart failure. These studies have been multi-center, collaborative reports with such now-established acronyms (PATH, MUSTIC, MIRACLE, CAREHF, COMPANION, to name a few). Patient pre-selection guidelines were established as indicated in ACC/AHA publications: symptomatic heart failure in spite of optimal medical management, NYHA Class III-IV, normal sinus rhythm, ventricular dyssynchrony with a QRS duration 4120 ms, and left ventricular ejection fraction o30%.12 However, in spite of such guidelines, the success or “responder” rate, although initially thought to be 60% to 70%, on more recent reviews may be closer to only 50% to 60%. Part of the discrepancy has been in what the different studies have used to define an endpoint for a positive response: improved 6 minute walk, less hospitalizations, 410% increase in ventricular stroke volume/ejection fraction, or quality-of-life
P.P. Karpawich
54 scores. Interestingly, CRT alone has not shown to improve mortality. For this reason the concept of CRT plus ICD (implantable cardiac defibrillator) therapy has gained interest. More recently, the issue that if CRT pacing arrests further deterioration of a pre-existing cardiac condition but does not show bona fide improvement, does this constitute a favorable response? Unfortunately, direct physiologic measurements to determine actual changes in hemodynamics are essentially lacking. Another conflicting concept is that although various implant sites on the right ventricle may be readily achieved, placement of a pacing lead in any one cardiac vein via the coronary sinus has not been uniform. In essence, there are no established guidelines concerning where the most effective biventricular lead implant sites are located. Because coronary sinus and cardiac vein morphologies can be very diverse, placement of pacing leads designed for venous implant is based more on lead positional stability than contractility response. Therefore, reviews of CRT pacing raise multiple questions of where to position leads, what variables to measure, and how to really define efficacy. Nevertheless, CRT pacing remains an established therapeutic option that may improve heart failure symptoms in some patients. However, in spite of the myriad of CRT-related publications dealing with patients with ischemic heart failure associated with a structurally normal heart, the multiple anatomic variations, surgical interventions, and functional heterogenicities of patients with repaired CHD preclude any real application of this information to these patients. For example, the ACC/AHA guidelines of a QRS 4120msec, ventricular ejection fraction o35%, sinus rhythm and NYHA class III-IV, is a rare combination among patients with CHD. In addition, many CHD patients have pre-existing pacemakers, an issue that is not included in any published guidelines. Other than case reports, to date, there are only a few publications dealing with CRT in patients with CHD, totaling just over 300 patients (mean age, 15 years), published from 2004 to 2013.37–41 Of these, two are multicenter studies encompassing more than 100 patients each. Unfortunately, none are prospective or randomized, most were retrospective, and clinical follow-up was limited to only a few months. Outcomes, as in most studies, were relatively subjective and concerned predominately with systemic ventricular function. In this regard, “responder rates” were greater (85% to 90%) than reported for older adults. Of note, several of these studies stressed the utilization of CRT as a bridge to delay orthoptic cardiac transplant among patients with CHD and intractable heart failure (40% of patients were removed from their respective transplant listing after CRT pacing). Considering the relatively young age (compared with studies in adults with heart failure) of these patients with CHD, that alone would indicate a potentially favorable application of CRT pacing. Based on these relatively few studies, some observations, however, can still be made considering CRT pacing among patients with CHD. 1) Patients with pre-existing ventricular pacemakers and associated ventricular dyssynchrony demonstrated the most improvement in systemic ventricular function.
2) Pre-existing left or right bundle branch block was not an important indicator for CRT pacing. 3) Cardiac ejection fraction improvement can be variable, ranging from 6% to 20%. 4) Most patients have been of a lower NYHA classification (II) than comparable patients with ischemic myocardial dysfunction. 5) Echocardiographic parameters or QRS duration, alone, were not valid predictors to select CHD patients for CRT pacing. 6) A systemic left ventricle morphology is associated with the best improvement in function. Currently, an ongoing study is pre-selecting prospective CRT recipients by direct evaluation of hemodynamic responses (pressures, contractility indices, QRS duration) to temporary biventricular pacing. An increase in ventricular dP/dt 415% with acute, temporary pacing over baseline demonstrates a favorable CRT response and assists in decision making to implant a CRT device.42 Probably one of the most important considerations when contemplating CRT pacing in a patient with CHD is anatomy. Systemic right ventricles, as in D- and L-transposition as well as univentricular hearts, pose obstacles to implant. In addition, reparative surgical procedures (Mustard, Senning, Fontan, bi-caval anastomosis) can create considerable technical challenges (Fig. 3). Access to the coronary sinus and cardiac veins may not be feasible from a transvenous approach. Often complete epicardial or a combination “hybrid” transvenous/epicardial lead implant is required, with anticipated associated co-morbidities, especially considering the need for a repeat thoracotomy. Recently, the Pediatric and Congenital Electrophysiology Society (PACES) and the Heart Rhythm Society (HRS) published an updated consensus statement on the management of arrhythmias among adults with CHD, including recommendations for CRT pacing. It is
Figure 3 Fluoroscopic appearance in the A-P projection of CRT pacing in a patient post d-TGA/Mustard with a SVC stent and epicardial (black arrow) as well as transvenous endocardial (white arrows) pacing leads. The epicardial lead is connected subcutaneously up to the implanted generator under the left clavicle.
Improving Cardiac Pacing an important addition to the literature for anyone caring for such patients.43
Conclusion Pacemaker therapy application to patients with congenital heart entails all of the risks/benefits as for any patient, but with significantly more issues. By virtue of anatomy, surgical repair procedures, and their sequelae, even simple device implant can be very complicated. Knowledge of anatomy is imperative. Also, if initiated in childhood, expected decades-long pacing therapy with any associated effects on myocardial function, can potentially increase patient morbidity. The past few decades have been associated with significant advances in implantable device designs, largely eliminating many of the earlier concerns associated with cardiac pacing. Future directions will entail improving chronically paced myocardial function to potentially prevent pacemaker-related heart failure, as well as to help improve the failed congenital heart by applications of resynchronization pacing. With the ever-increasing numbers of adults with repaired CHD, these challenges will continue long into the future. Although it can be an effective therapy for some patients with CHD and heart failure, CRT pacing may not be applicable to all patients. Improved patient selection criteria are needed. It is also not a procedure that should be undertaken by other than experienced device implanters with an excellent working knowledge of the many nuances of congenital heart and their associated surgical procedures and potential sequelae to vascular access.
References 1. Furman S, Schwedel JB: An intracardiac pacemaker for Stokes-Adams seizures. N Engl J Med 1959;261:943-948 2. Hunter SW, Roth NA, Bernandez D, et al: A bipolar myocardial electrode for complete heart block. Lancet 1959;79:506-508 3. Adomian GE: Myofibrillar disarray produced in normal hearts by chronic electrical pacing. Am Heart J 1986;112:79-83 4. Karpawich PP, Rabah R, Haas JE: Altered cardiac histology following apical right ventricular pacing in patients with congenital atrioventricular block. Pacing Clin Electrophysiol 1999;22:1372-1377 5. Prinzen FW, Augustijn CH, Arts T, et al: Redistribution of myocardial fiber strain and blood flow by asynchronous activation. Am J Physiol 1990;259:330-338 6. Tse HF, Lau CP: Long-term effect of right ventricular pacing on myocardial perfusion and function. J Am Coll Cardiol 1997;29:744-749 7. Tantengco MVT, Thomas RL, Karpawich PP: Left ventricular dysfunction after long-term right ventricular apical pacing in the young. J Am Coll Cardiol 2001;37:2093-2100 8. Karpawich PP, Gates J, Stokes K: Septal His-purkinje ventricular pacing in canines: a new endocardial electrode approach. Pacing Clin Electrophysiol 1992;15:2011-2015 9. Lieberman R, Grenz D, Mond H, et al: Selective Site Pacing: Defining and reaching the selected site. Pacing Clin Electrophysiol 2004;26:883-886 10. Deshmukh P, Romanyshyn M: Direct His-bundle pacing: Present and future. Pacing Clin Electrophysiol 2004;27:862-870 11. Manolis A: The deleterious consequences of right ventricular apical pacing: Time to seek alternate site pacing. Pacing Clin Electrophysiol 2006;29:298-315 12. Behan MW, Rinaldi CA: Cardiac resynchronization therapy for heart failure. Int J Clin Pract 2006;60:1107-1114
55 13. Birnie DH, Tang AS: The problem with non-response to cardiac resynchronization therapy. Curr Opin Cardiol 2006;21:20-26 14. Pires L, Abraham WT, Young JB, et al: Clinical predictors and timing of New York Heart Association class improvement with cardiac resynchronization therapy in patients with advanced heart failure: results from the Multicenter InSync Randomized Clinical Evaluation (MIRACLE) and Multicenter InSync ICD Randomized Clinical Evaluation (MIRACLEICD) trials. Am Heart J 2006;51:837-843 15. Karpawich PP, Hakimi M, Arciniegas E, et al: DL: Improved chronic epicardial pacing in children: steroid contribution to porous platinized electrodes. Pacing Clin Electrophysiol 1992;15:1151-1157 16. Horenstein MS, Karpawich PP: Chronic performance of steroid-eluting epicardial leads in a growing pediatric population: a 10-year comparison. Pacing Clin Electrophysiol 2003;26:1467-1471 17. Khan A, Zelin K, Karpawich PP: Performance of the Lumenless 4.1fr diameter pacing lead implanted at alternate pacing sites in congenital heart: a chronic 5 year comparison. Pacing Clin Electrophysiol 2010;33: 1467-1474 18. Wiggers J: The muscle reactions of the mammalian ventricles to artificial surface stimulation. Am J Physiol 1925;73:346-378 19. Padeletti L, Lieberman R, Valsecchi S, et al: Physiologic pacing: new modalities and pacing sites. Pacing Clin Electrophysiol 2006;29(suppl 2): S72-S77 20. Bleeker GB, Schalij MJ, Molhoek SG, et al: Relationship between QRS duration and left ventricular dyssynchrony in patients with end-stage heart failure. J Cardiovasc Electrophysiol 2004;15: 544-549 21. Lieberman R, Padeletti L, Schreuder J, et al: Ventricular pacing lead location alters systemic hemodynamics and left ventricular function in patients with and without reduced ejection fraction. J Am Coll Cardiol 2006;48:1634-1641 22. Mason D, Braunwald E, Covell J, et al: Assessment of cardiac contractility: the relation between the rate of pressure rise and ventricular pressure during isovolumic systole. Circulation 1971;44:47-58 23. Giudici M, Karpawich PP: Alternative site pacing: it’s time to define terms. Pacing Clin Electrophysiol 1999;22:551-553 24. Karpawich PP, Singh H, Zelin K: Optimizing paced ventricular function in patients with and without repaired congenital heart disease by contractility-guided lead implant. Pacing Clin Electrophysiol 2015;38:54–62 25. Mond H, Karpawich PP: Pacing options in the adult patient with congenital heart disease. Malden, MA: Blackwell-Futura; 2007 26. Dodge-Khatami A, Kadner A, Dave H, et al: Left heart atrial and ventricular epicardial pacing through a left lateral thoracotomy in children: a safe approach with excellent functional and cosmetic results. Eur J Cardio Thorac Surg 2005;28:541-545 27. Peschar M, de Swart H, Michels KJ, et al: Left ventricular septal and apex pacing for optimal pump function in canine hearts. J Am Coll Cardiol 2003;41:1218-1226 28. Silvetti MS, Di Carlo D, Ammirati A, et al: Left ventricular pacing in neonates and infants with isolated congenital complete or advanced atrioventricular block: short- and medium-term outcome. Europace 2014; http://dx.doi.org/10.1093/europace/euu180. 12 August 2014. pii: euu180 [Epub ahead of print] 29. Serwer GA, Mericle JM, Armstrong BE: Epicardial ventricular pacemaker electrode longevity in children. Am J Cardiol 1988;61: 104-106 30. Gillette PC, Ziegler V, Bragham GB, et al: Pediatric transvenous pacing: a concern for venous thrombosis? Pacing Clin Electrophysiol 1988;11: 1935-1939 31. Kanmmeraad JAE, Rosenthal E, Bostock J, et al: Endocardial pacemaker implantation in infants weighing o 10 kilograms. Pacing Clin Electrophysiol 2004;27:1466-1474 32. Stojanov PL, Savic DV, Zivkovic MB, et al: Permanent endovenous pediatric pacing: absence of lead failure – 20 years followup. Pacing Clin Electrophysiol 2008;31:495-498 33. Sanjeev S, Karpawich PP: Superior vena cava and innominate vein dimensions in growing children: an aid for interventional devices and transvenous leads. Pediatr Cardiol 2006;27:414-419
56 34. Antretter H, Hangler H, Colvin J, et al: Inferior vena caval loop of an endocardial pacing lead did not solve the growth problem in a child. Pacing Clin Electrophysiol 2001;24:1706-1709 35. Bar-Cohen Y, Berul CI, Alexander ME, et al: Age, size and lead factors alone do not predict venous obstruction in children and young adults with transvenous lead systems. J Cardiovasc Electrophysiol 2006;17:754-759 36. Bharmanee A, Zelin K, Singh H, et al: Comparative chronic effects on atrioventricular valve integrity between standard 5-7 French and the new 4.1 French diameter pacing leads in the young [abstract]. Circulation 2013;28:A12056 37. Janoušek J, van Geldorp IE, Krupičková S, et al: Permanent cardiac pacing in children: choosing the optimal pacing site: a multicenter study. Circulation 2013;127:613-623. (See comment in PubMed Commons below) 38. Dubin AM, Janousek J, Rhee E, et al: Resynchronization therapy in pediatric and congenital heart patients: an international multicenter study. J Am Coll Cardiol 2005;46:2277-2283
P.P. Karpawich 39. Khairy P, Fournier A, Thibault B, et al: Cardiac resynchronization therapy in congenital heart disease. Int J Cardiol 2006;109:160-168 40. Cecchin F, Frangini PA, Brown DW, et al: Cardiac resynchronization therapy (and multisite pacing) in pediatrics and congenital heart disease: Five years experience in a single institution. J Cardiovasc Electrophysiol 2009;20:58-65 41. Janousek J, Gebauer RA, Abdul-Khaliq H, et al: Cardiac resynchronisation therapy in paediatric and congenital heart disease: differential effects in various anatomical and functional substrates. Heart 2009;95: 1165-1117 42. Karpawich PP, Sanil Y, Bansal N, et al: Improved resynchronization pacing efficacy among congenital heart disease patients with refractory heart failure [abstract]. J Heart Dis 2014;11:9 43. Khairy P, Van Hare GF, Balaji S, et al. PACES/HRS expert consensus statement on the recognition and management of arrhythmias in adult congenital heart disease. Heart Rhythm 2014;11(10): e102–e165
Introduction
D
esigned as effective therapy for patients with symptomatic bradycardia, cardiac pacemakers initially served to improve patient symptoms and survival. Any adverse hemodynamic consequences were not yet realized. Complications, as recognized, typically involved implant issues, device design, and physical effects of leads on valves and interactions of lead tip electrodes with cardiac tissue. Because of initial pacing lead design technologies, with no lead tip fixation capabilities, the ventricular apex and atrial appendages were chosen as secure anatomic sites that permitted ease of lead implant with limited dislodgement.1 Epicardial ventricular leads typically were
Section of Cardiology, Department of Pediatrics, The Children’s Hospital of Michigan, Wayne State University School of Medicine, Detroit, MI. Conflict of Interest: none Address Correspondence to Peter P. Karpawich, MSc, MD, Director, Cardiac Electrophysiology, The Children’s Hospital of Michigan, 3901 Beaubien Blvd., Detroit, MI 48201. E-mail: [email protected]
http://dx.doi.org/10.1053/j.pcsu.2014.12.002 1092-9126/& 2015 Elsevier Inc. All rights reserved.
placed anywhere on the anterior right ventricle, primarily for ease of implant and convenience.2 However, over time, further studies indicated that ventricular pacing itself, associated with inherent bundle branch block QRS morphologies and resultant altered ventricular contractility vectors, can be associated with adverse myocellular changes contributing to decreased function.3–7 With improvement in design technologies, the 1990s saw a re-thinking of pacing applications with an increase in applications to patients with repaired congenital heart disease (CHD). As part of ongoing investigations to improve paced myocardial contractility and maintain normalized right and left contractions, the concept of “alternative site” pacing evolved. Bundle of His, septal and ventricular outflow tract, as well as Bachmann’s bundle sites have been explored.8–11 As an offshoot to these investigations, dual ventricular leads or “biventricular” pacing, with two right ventricular leads or one lead in the right and the other in the left ventricle saw promise to improve an already abnormally contractile or “desynchronized” systemic ventricle caused by ischemia, congestive cardiomyopathy, CHD, and advanced heart failure.12–14 In 51
P.P. Karpawich
52
KEY POINTS Lead implant location and the initiation of pacing dictate myocardial contractility response.
Right ventricular apical pacing with an inherent left bundle branch block QRS morphology can adversely alter left ventricular function.
A proactive approach to optimize paced myocardial function, irrespective of pacing lead threshold/sensing issues, should be a part of every pacemaker implant.
Left ventricular apical is superior to right ventricular epicardial pacing, both for temporary and permanent lead implant.
Concerns for chronic vascular/valvular issues are still present when contemplating endocardial pacing in children.
Resynchronization pacing (CRT) can be applicable to some patients with congenital heart defects and heart failure, but none of the published guidelines for patient selection or implant values are applicable.
Detailed knowledge of anatomy and vascular issues among repaired CHD patients is mandatory prior to pacemaker/ ICD implant. cardiac “resynchronization” therapy (CRT) pacing, two ventricular leads in effect coerce the heart to contract between them, with more normal left-right “synchronization.” This is in deference to the left-right delay as represented by the typical pacing-induced bundle branch block QRS. This combined action ostensibly can realign disarranged myofibrils, improves electromechanical activation, and increases contractile efficiency. As a result, although not curing the underlying heart disease, CRT can improve the clinical expression of the failing heart.
pacing thresholds, have been stressed for decades. However, since the introduction of low-threshold and steroideluting endo- and epicardial pacing leads, such concerns have become less important.15–17 Since the 1920s, pacing electrode placement in close proximity to the normal conduction system has been known to offer the potential for improved ventricular function by optimizing biventricular contractility.18 More recently, various studies have demonstrated that pacing site, and therefore the initiation of ventricular contractility, is the prime contributor to function.19 However, just which parameters to measure to ascertain optimal paced ventricular contractility have not been resolved. Initially thought to have potential for a correlation with contractility, QRS duration does not appear to be that effective of a marker.20 This is especially true among patients with repaired congenital heart defects in whom abnormal QRS axis and morphologies are commonly found. Other more accurate measurements have included pressure-volume loops, as well as the first derivative of systolic pressure (dP/dt), which additionally has had pertinent impact with interest in resynchronization pacing for heart failure.21,22 Initial lead implant optimization with direct measurements of physiologic responses, especially among a patient population, such as repaired congenital heart, in whom pacing can be anticipated to be required for decades, is a prudent approach to medical care delivery. With the introduction of improved low threshold and steerable pacing lead designs permitting fixation at nearly any ventricular location, alternative right ventricular pacing (“septal,” “outflow tract”) sites have been demonstrated to offer improved response over the apex (Fig. 1). However, there is confusion in the literature as precise definition of these sites is
Optimizing Paced Ventricular Function Initiation of paced electrical impulse propagation from an apical or free wall epicardial region is associated more with muscle than His-Purkinje (H-P) conduction, causing asynchronous right and left ventricular contractility changes. The spiral orientation of ventricular muscle fibers favors optimal contractility when normal H-P conduction occurs. Anything else will realign stress vectors. Because ventricular function may be affected by rate, atrioventricular activation coupling intervals, and pacing site, each of these variables have found interest in both animal and clinical studies. Prevention of potential dysfunction by a more proactive approach to initial pacemaker application based on contractility response is a less-established clinical application than standard implant protocols, in which lead integrity and optimization of electrode-tissue interface reactivity to limit fibrotic capsule formation and assure low
Figure 1 Fluoroscopic appearance in the A-P projection of a endocardial right ventricular septal lead implant in a patient with a fractured previous epicardial pacing lead. Use of the deflectable introducing catheter (arrow) allows for precise lead implant at the septal site that demonstrates optimal contractility using a temporary quadripolar pacing catheter.
Improving Cardiac Pacing frequently lacking.23 One recent study has sought to better define potential ventricular implant sites with concomitant contractility indices.24 Although 38% of patients studied exhibited the most optimal paced contractility from the mid ventricular septum that approximated the region of the moderator band, interestingly, apical pacing, among certain repaired congenital heart patients, was found to be associated with the best contractility response. This was frequently found among patients with dyskinetic septal contractility following repaired septal defects. CHD anatomy and post-surgical residue of prosthetic patches, conduits, and valves add additional concerns that must be recognized and addressed whenever any cardiac implantable electronic device (CIED) therapy is contemplated.25 Because many repaired congenital heart patients require epicardial pacing, fortunately there are comparable animal and clinical studies that evaluate pacing responses between right and left ventricular epicardial sites, with the left ventricular epicardium demonstrating improved responses. In this respect, the concept that any epicardial left is preferential to any right ventricular site has been advocated. The lateral free wall of the left ventricle, an area between the left anterior descending coronary artery and diagonal coronary branches at a distance from the left atrial appendage, has been reported to be an excellent location for epicardial pacing in children.26 Other studies comparing potential epicardial left ventricular sites have reported that the apical region can be the most effective for optimal contractility responses both as a temporary or permanent lead implant location (Fig. 2).27,28 A common question, and one that has been the focus of many debates at scientific sessions, is the age-appropriateness of endocardial versus epicardial pacing leads. As an initial concept, especially to avoid potential thromboembolic
53 concerns, patients with single ventricle morphologies should receive an epicardial pacing system. It may also be prudent and perhaps most efficacious to implant an epicardial pacing system, if required, at the time of CHD surgical repair in a child. This can even apply to the implant of a permanent epicardial lead without generator in those instances of presumed temporary heart block, with the generator implanted later if the block does not resolve.29 The literature has reported safety of endocardial lead implant in children weighing from 2.3 to 20 kg, with a “ballpark” acceptable range typically of 15 to 20 kg.30–32 However, follow-up has been somewhat limited with mean values of about 6 years. There is probably no real debate that endocardial leads can and do perform well in regard to thresholds in children comparable to adults, especially in the current era of steroid eluting designs. However, a “save the veins and valves” approach may still be prudent. Patient growth and lead effects and performances remain a concern. Pacing leads are not completely thrombi-free and lead/tissue interactions do occur. Estimation of age-related venous diameters as well as lead lengths may be helpful in decision making.33,34 Lead extraction, however, is more complicated than implant. These issues need to be considered, especially when contemplating endocardial pacemaker implant in a patient with an anticipated 20 to 50 years of pacing. Eventually switching from an epi- to endocardial pacing system may have less morbidities than dealing with chronic endocardial leads once implanted in very young children. Adverse vascular/valvular effects are still found with endocardial leads. Venous occlusions have been reported in more than 20% of children and young adults.35 Although the newer 4.1 French diameter lead may be associated with less valvular damage than larger diameter leads, very long term follow-up studies are still lacking.36 As a result, an informed implanter must consider all potential variables and long-term consequences associated with both lead implant approaches.
Resynchronization Pacing
Figure 2 Radiographic appearance of left atrial and ventricular epicardial pacing leads.
In the past decade, there have been numerous studies encompassing thousands of patients on the potential applications of pacing therapy to improve dysfunctional ventricles in adults with congestive heart failure, typically caused by ischemic heart failure. These studies have been multi-center, collaborative reports with such now-established acronyms (PATH, MUSTIC, MIRACLE, CAREHF, COMPANION, to name a few). Patient pre-selection guidelines were established as indicated in ACC/AHA publications: symptomatic heart failure in spite of optimal medical management, NYHA Class III-IV, normal sinus rhythm, ventricular dyssynchrony with a QRS duration 4120 ms, and left ventricular ejection fraction o30%.12 However, in spite of such guidelines, the success or “responder” rate, although initially thought to be 60% to 70%, on more recent reviews may be closer to only 50% to 60%. Part of the discrepancy has been in what the different studies have used to define an endpoint for a positive response: improved 6 minute walk, less hospitalizations, 410% increase in ventricular stroke volume/ejection fraction, or quality-of-life
P.P. Karpawich
54 scores. Interestingly, CRT alone has not shown to improve mortality. For this reason the concept of CRT plus ICD (implantable cardiac defibrillator) therapy has gained interest. More recently, the issue that if CRT pacing arrests further deterioration of a pre-existing cardiac condition but does not show bona fide improvement, does this constitute a favorable response? Unfortunately, direct physiologic measurements to determine actual changes in hemodynamics are essentially lacking. Another conflicting concept is that although various implant sites on the right ventricle may be readily achieved, placement of a pacing lead in any one cardiac vein via the coronary sinus has not been uniform. In essence, there are no established guidelines concerning where the most effective biventricular lead implant sites are located. Because coronary sinus and cardiac vein morphologies can be very diverse, placement of pacing leads designed for venous implant is based more on lead positional stability than contractility response. Therefore, reviews of CRT pacing raise multiple questions of where to position leads, what variables to measure, and how to really define efficacy. Nevertheless, CRT pacing remains an established therapeutic option that may improve heart failure symptoms in some patients. However, in spite of the myriad of CRT-related publications dealing with patients with ischemic heart failure associated with a structurally normal heart, the multiple anatomic variations, surgical interventions, and functional heterogenicities of patients with repaired CHD preclude any real application of this information to these patients. For example, the ACC/AHA guidelines of a QRS 4120msec, ventricular ejection fraction o35%, sinus rhythm and NYHA class III-IV, is a rare combination among patients with CHD. In addition, many CHD patients have pre-existing pacemakers, an issue that is not included in any published guidelines. Other than case reports, to date, there are only a few publications dealing with CRT in patients with CHD, totaling just over 300 patients (mean age, 15 years), published from 2004 to 2013.37–41 Of these, two are multicenter studies encompassing more than 100 patients each. Unfortunately, none are prospective or randomized, most were retrospective, and clinical follow-up was limited to only a few months. Outcomes, as in most studies, were relatively subjective and concerned predominately with systemic ventricular function. In this regard, “responder rates” were greater (85% to 90%) than reported for older adults. Of note, several of these studies stressed the utilization of CRT as a bridge to delay orthoptic cardiac transplant among patients with CHD and intractable heart failure (40% of patients were removed from their respective transplant listing after CRT pacing). Considering the relatively young age (compared with studies in adults with heart failure) of these patients with CHD, that alone would indicate a potentially favorable application of CRT pacing. Based on these relatively few studies, some observations, however, can still be made considering CRT pacing among patients with CHD. 1) Patients with pre-existing ventricular pacemakers and associated ventricular dyssynchrony demonstrated the most improvement in systemic ventricular function.
2) Pre-existing left or right bundle branch block was not an important indicator for CRT pacing. 3) Cardiac ejection fraction improvement can be variable, ranging from 6% to 20%. 4) Most patients have been of a lower NYHA classification (II) than comparable patients with ischemic myocardial dysfunction. 5) Echocardiographic parameters or QRS duration, alone, were not valid predictors to select CHD patients for CRT pacing. 6) A systemic left ventricle morphology is associated with the best improvement in function. Currently, an ongoing study is pre-selecting prospective CRT recipients by direct evaluation of hemodynamic responses (pressures, contractility indices, QRS duration) to temporary biventricular pacing. An increase in ventricular dP/dt 415% with acute, temporary pacing over baseline demonstrates a favorable CRT response and assists in decision making to implant a CRT device.42 Probably one of the most important considerations when contemplating CRT pacing in a patient with CHD is anatomy. Systemic right ventricles, as in D- and L-transposition as well as univentricular hearts, pose obstacles to implant. In addition, reparative surgical procedures (Mustard, Senning, Fontan, bi-caval anastomosis) can create considerable technical challenges (Fig. 3). Access to the coronary sinus and cardiac veins may not be feasible from a transvenous approach. Often complete epicardial or a combination “hybrid” transvenous/epicardial lead implant is required, with anticipated associated co-morbidities, especially considering the need for a repeat thoracotomy. Recently, the Pediatric and Congenital Electrophysiology Society (PACES) and the Heart Rhythm Society (HRS) published an updated consensus statement on the management of arrhythmias among adults with CHD, including recommendations for CRT pacing. It is
Figure 3 Fluoroscopic appearance in the A-P projection of CRT pacing in a patient post d-TGA/Mustard with a SVC stent and epicardial (black arrow) as well as transvenous endocardial (white arrows) pacing leads. The epicardial lead is connected subcutaneously up to the implanted generator under the left clavicle.
Improving Cardiac Pacing an important addition to the literature for anyone caring for such patients.43
Conclusion Pacemaker therapy application to patients with congenital heart entails all of the risks/benefits as for any patient, but with significantly more issues. By virtue of anatomy, surgical repair procedures, and their sequelae, even simple device implant can be very complicated. Knowledge of anatomy is imperative. Also, if initiated in childhood, expected decades-long pacing therapy with any associated effects on myocardial function, can potentially increase patient morbidity. The past few decades have been associated with significant advances in implantable device designs, largely eliminating many of the earlier concerns associated with cardiac pacing. Future directions will entail improving chronically paced myocardial function to potentially prevent pacemaker-related heart failure, as well as to help improve the failed congenital heart by applications of resynchronization pacing. With the ever-increasing numbers of adults with repaired CHD, these challenges will continue long into the future. Although it can be an effective therapy for some patients with CHD and heart failure, CRT pacing may not be applicable to all patients. Improved patient selection criteria are needed. It is also not a procedure that should be undertaken by other than experienced device implanters with an excellent working knowledge of the many nuances of congenital heart and their associated surgical procedures and potential sequelae to vascular access.
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56 34. Antretter H, Hangler H, Colvin J, et al: Inferior vena caval loop of an endocardial pacing lead did not solve the growth problem in a child. Pacing Clin Electrophysiol 2001;24:1706-1709 35. Bar-Cohen Y, Berul CI, Alexander ME, et al: Age, size and lead factors alone do not predict venous obstruction in children and young adults with transvenous lead systems. J Cardiovasc Electrophysiol 2006;17:754-759 36. Bharmanee A, Zelin K, Singh H, et al: Comparative chronic effects on atrioventricular valve integrity between standard 5-7 French and the new 4.1 French diameter pacing leads in the young [abstract]. Circulation 2013;28:A12056 37. Janoušek J, van Geldorp IE, Krupičková S, et al: Permanent cardiac pacing in children: choosing the optimal pacing site: a multicenter study. Circulation 2013;127:613-623. (See comment in PubMed Commons below) 38. Dubin AM, Janousek J, Rhee E, et al: Resynchronization therapy in pediatric and congenital heart patients: an international multicenter study. J Am Coll Cardiol 2005;46:2277-2283
P.P. Karpawich 39. Khairy P, Fournier A, Thibault B, et al: Cardiac resynchronization therapy in congenital heart disease. Int J Cardiol 2006;109:160-168 40. Cecchin F, Frangini PA, Brown DW, et al: Cardiac resynchronization therapy (and multisite pacing) in pediatrics and congenital heart disease: Five years experience in a single institution. J Cardiovasc Electrophysiol 2009;20:58-65 41. Janousek J, Gebauer RA, Abdul-Khaliq H, et al: Cardiac resynchronisation therapy in paediatric and congenital heart disease: differential effects in various anatomical and functional substrates. Heart 2009;95: 1165-1117 42. Karpawich PP, Sanil Y, Bansal N, et al: Improved resynchronization pacing efficacy among congenital heart disease patients with refractory heart failure [abstract]. J Heart Dis 2014;11:9 43. Khairy P, Van Hare GF, Balaji S, et al. PACES/HRS expert consensus statement on the recognition and management of arrhythmias in adult congenital heart disease. Heart Rhythm 2014;11(10): e102–e165