Arrhythmias following cardiac transplantation
- Howard J Eisen, MD
Howard J Eisen, MD
- Thomas J Vischer Professor of Medicine
- Drexel University College of Medicine
- Luke S Kusmirek, MD, FACC
Luke S Kusmirek, MD, FACC
- Assistant Professor of Medicine
- Director, Drexel Atrial Arrhythmia Center
- Division of Cardiology
- Section Editors
- Sharon A Hunt, MD
Sharon A Hunt, MD
- Editor-in-Chief — Cardiovascular Medicine
- Section Editor — Heart Transplantation
- Professor of Medicine
- Stanford University School of Medicine
- Leonard I Ganz, MD, FHRS, FACC
Leonard I Ganz, MD, FHRS, FACC
- Section Editor — Cardiac Arrhythmias
- Director of Cardiac Electrophysiology
- Heritage Valley Health System
Cardiac arrhythmias are common in the orthotopic heart transplant recipient, particularly in the early postoperative period. Premature atrial complexes and premature ventricular complexes are especially frequent, with a reported incidence of over 60 percent. Fortunately, these arrhythmias have little clinical importance. However, other cardiac arrhythmia, such as sinus node dysfunction and ventricular tachycardia, may result in significant morbidity or mortality.
There are several mechanisms for arrhythmogenesis in the transplanted heart, with early postoperative arrhythmia resulting from different mechanisms than those occurring later. Surgical trauma to the sinoatrial and atrioventricular nodes, ischemia during preservation, surgical suture lines, and, over the long term, rejection and accelerated atherosclerosis may contribute to the formation of an arrhythmogenic substrate. As an example, one autopsy study of 18 hearts found that acute rejection involved the conduction system as severely as the myocardium . With chronic rejection, there was often obstructive vasculopathy of the sinus node artery.
In occasional cases, severe rejection isolated to the conduction system with sparing of the rest of the myocardium occurs and presents as bradycardia with syncope .
In addition, the denervated donor heart has increased sensitivity to sympathetic amines, adenosine, and acetylcholine, which may contribute to both tachyarrhythmias and bradyarrhythmias [3-5]. The sympathetic effect may be presynaptic in origin; it is not due to increased beta receptor density [3,4]. Because of this increased sensitivity, adenosine should not be used (as it often is) to slow the rate in supraventricular tachyarrhythmias to elucidate the underlying arrhythmia mechanism. Such use can result in prolonged bradycardia or a period of asystole.
In the denervated heart, the normal resting sinus rate is usually greater than 80 bpm and may exceed 100 bpm in hearts transplanted from young donors. The heart rate is higher than in normals because of the loss of vagal neural inputs, which have a negative chronotropic effect. (See "Sinus tachycardia: Evaluation and management".)
- Calzolari V, Angelini A, Basso C, et al. Histologic findings in the conduction system after cardiac transplantation and correlation with electrocardiographic findings. Am J Cardiol 1999; 84:756.
- Knight CS, Tallaj JA, Rayburn BK, et al. Bradycardia and syncope as a presentation of cardiac allograft rejection involving the conducting system. Cardiovasc Pathol 2010; 19:117.
- Cannom DS, Rider AK, Stinson EB, Harrison DC. Electrophysiologic studies in the denervated transplanted human heart. II. Response to norepinephrine, isoproterenol and propranolol. Am J Cardiol 1975; 36:859.
- Yusuf S, Theodoropoulos S, Mathias CJ, et al. Increased sensitivity of the denervated transplanted human heart to isoprenaline both before and after beta-adrenergic blockade. Circulation 1987; 75:696.
- Ellenbogen KA, Thames MD, DiMarco JP, et al. Electrophysiological effects of adenosine in the transplanted human heart. Evidence of supersensitivity. Circulation 1990; 81:821.
- Burke MN, McGinn AL, Homans DC, et al. Evidence for functional sympathetic reinnervation of left ventricle and coronary arteries after orthotopic cardiac transplantation in humans. Circulation 1995; 91:72.
- Squires RW, Leung TC, Cyr NS, et al. Partial normalization of the heart rate response to exercise after cardiac transplantation: frequency and relationship to exercise capacity. Mayo Clin Proc 2002; 77:1295.
- Wilson RF, Johnson TH, Haidet GC, et al. Sympathetic reinnervation of the sinus node and exercise hemodynamics after cardiac transplantation. Circulation 2000; 101:2727.
- Gallego-Page JC, Segovia J, Alonso-Pulpón L, et al. Re-innervation after heart transplantation: a multidisciplinary study. J Heart Lung Transplant 2004; 23:674.
- Bengel FM, Ueberfuhr P, Ziegler SI, et al. Serial assessment of sympathetic reinnervation after orthotopic heart transplantation. A longitudinal study using PET and C-11 hydroxyephedrine. Circulation 1999; 99:1866.
- Arrowood JA, Minisi AJ, Goudreau E, et al. Absence of parasympathetic control of heart rate after human orthotopic cardiac transplantation. Circulation 1997; 96:3492.
- Bernardi L, Valenti C, Wdowczyck-Szulc J, et al. Influence of type of surgery on the occurrence of parasympathetic reinnervation after cardiac transplantation. Circulation 1998; 97:1368.
- Heinz G, Hirschl M, Buxbaum P, et al. Sinus node dysfunction after orthotopic cardiac transplantation: postoperative incidence and long-term implications. Pacing Clin Electrophysiol 1992; 15:731.
- Jacquet L, Ziady G, Stein K, et al. Cardiac rhythm disturbances early after orthotopic heart transplantation: prevalence and clinical importance of the observed abnormalities. J Am Coll Cardiol 1990; 16:832.
- Mackintosh AF, Carmichael DJ, Wren C, et al. Sinus node function in first three weeks after cardiac transplantation. Br Heart J 1982; 48:584.
- Heinz G, Kratochwill C, Koller-Strametz J, et al. Benign prognosis of early sinus node dysfunction after orthotopic cardiac transplantation. Pacing Clin Electrophysiol 1998; 21:422.
- Wellmann P, Herrmann FE, Hagl C, Juchem G. A Single Center Study of 1,179 Heart Transplant Patients-Factors Affecting Pacemaker Implantation. Pacing Clin Electrophysiol 2017; 40:247.
- Woodard DA, Conti JB, Mills RM Jr, et al. Permanent atrial pacing in cardiac transplant patients. Pacing Clin Electrophysiol 1997; 20:2398.
- Mason JW, Harrison DC. Electrophysiology and electropharmacology of the transplanted human heart. In: Cardiac Arrhythmias: Electrophysiology, Diagnosis and Management, Narula OS (Ed), Williams & Wilkins, Baltimore 1979. p.66.
- DiBiase A, Tse TM, Schnittger I, et al. Frequency and mechanism of bradycardia in cardiac transplant recipients and need for pacemakers. Am J Cardiol 1991; 67:1385.
- Dreyfus G, Jebara V, Mihaileanu S, Carpentier AF. Total orthotopic heart transplantation: an alternative to the standard technique. Ann Thorac Surg 1991; 52:1181.
- Sarsam MA, Campbell CS, Yonan NA, et al. An alternative surgical technique in orthotopic cardiac transplantation. J Card Surg 1993; 8:344.
- Aziz TM, Burgess MI, El-Gamel A, et al. Orthotopic cardiac transplantation technique: a survey of current practice. Ann Thorac Surg 1999; 68:1242.
- Deleuze PH, Benvenuti C, Mazzucotelli JP, et al. Orthotopic cardiac transplantation with direct caval anastomosis: is it the optimal procedure? J Thorac Cardiovasc Surg 1995; 109:731.
- el Gamel A, Yonan NA, Grant S, et al. Orthotopic cardiac transplantation: a comparison of standard and bicaval Wythenshawe techniques. J Thorac Cardiovasc Surg 1995; 109:721.
- Rothman SA, Jeevanandam V, Combs WG, et al. Eliminating bradyarrhythmias after orthotopic heart transplantation. Circulation 1996; 94:II278.
- Davies RR, Russo MJ, Morgan JA, et al. Standard versus bicaval techniques for orthotopic heart transplantation: an analysis of the United Network for Organ Sharing database. J Thorac Cardiovasc Surg 2010; 140:700.
- Heinz G, Ohner T, Laufer G, et al. Demographic and perioperative factors associated with initial and prolonged sinus node dysfunction after orthotopic heart transplantation. The impact of ischemic time. Transplantation 1991; 51:1217.
- Miyamoto Y, Curtiss EI, Kormos RL, et al. Bradyarrhythmia after heart transplantation. Incidence, time course, and outcome. Circulation 1990; 82:IV313.
- Cantillon DJ, Tarakji KG, Hu T, et al. Long-term outcomes and clinical predictors for pacemaker-requiring bradyarrhythmias after cardiac transplantation: analysis of the UNOS/OPTN cardiac transplant database. Heart Rhythm 2010; 7:1567.
- Redmond JM, Zehr KJ, Gillinov MA, et al. Use of theophylline for treatment of prolonged sinus node dysfunction in human orthotopic heart transplantation. J Heart Lung Transplant 1993; 12:133.
- Ellenbogen KA, Szentpetery S, Katz MR. Reversibility of prolonged chronotropic dysfunction with theophylline following orthotopic cardiac transplantation. Am Heart J 1988; 116:202.
- Cook LS, Will KR, Moran J. Treatment of junctional rhythm after heart transplantation with terbutaline. J Heart Transplant 1989; 8:342.
- Rothman SA, Jeevanandam V, Seeber CP, et al. Electrophysiologic effects of intravenous aminophylline in heart transplant recipients with sinus node dysfunction. J Heart Lung Transplant 1995; 14:429.
- Rothman SA, Jeevanandam V, Hsia H, et al. A comparison of the electrophysiologic effects of aminophylline and terbutaline in heart transplant recipients with sinus node dysfunction (abstract). Circulation 1995; 92(Suppl 1):I.
- Melton IC, Gilligan DM, Wood MA, Ellenbogen KA. Optimal cardiac pacing after heart transplantation. Pacing Clin Electrophysiol 1999; 22:1510.
- Mariani JA, McDonald MA, Nanthakumar K, et al. Cardiac resynchronization therapy after atrioventricular node ablation for rapid atrial fibrillation in a heart transplant recipient with late allograft dysfunction. J Heart Lung Transplant 2010; 29:704.
- Villa AE, de Marchena EJ, Myerburg RJ, Castellanos A. Comparisons of paired orthotopic cardiac transplant donor and recipient electrocardiograms. Am Heart J 1994; 127:70.
- Leonelli FM, Pacifico A, Young JB. Frequency and significance of conduction defects early after orthotopic heart transplantation. Am J Cardiol 1994; 73:175.
- Koller-Strametz J, Kratochwill C, Grabenwöger M, et al. PR interval adaptation in the denervated transplanted heart. Pacing Clin Electrophysiol 1997; 20:1247.
- Heinz G, Kratochwill C, Hirschl M, et al. Normal AV node function in patients with sinus node dysfunction after cardiac transplantation. J Card Surg 1993; 8:417.
- Markewitz A, Schmoeckel M, Nollert G, et al. Long-term results of pacemaker therapy after orthotopic heart transplantation. J Card Surg 1993; 8:411.
- Ruben S, Hsia H, Mather P, et al. Etiology and prognostic implications of post-transplant conduction system disease (abstract). J Heart Lung Transplant 1996; 15:S60.
- Little RE, Kay GN, Epstein AE, et al. Arrhythmias after orthotopic cardiac transplantation. Prevalence and determinants during initial hospitalization and late follow-up. Circulation 1989; 80:III140.
- Scott CD, Dark JH, McComb JM. Arrhythmias after cardiac transplantation. Am J Cardiol 1992; 70:1061.
- Romhilt DW, Doyle M, Sagar KB, et al. Prevalence and significance of arrhythmias in long-term survivors of cardiac transplantation. Circulation 1982; 66:I219.
- Creswell LL, Schuessler RB, Rosenbloom M, Cox JL. Hazards of postoperative atrial arrhythmias. Ann Thorac Surg 1993; 56:539.
- Pavri BB, O'Nunain SS, Newell JB, et al. Prevalence and prognostic significance of atrial arrhythmias after orthotopic cardiac transplantation. J Am Coll Cardiol 1995; 25:1673.
- Ahmari SA, Bunch TJ, Chandra A, et al. Prevalence, pathophysiology, and clinical significance of post-heart transplant atrial fibrillation and atrial flutter. J Heart Lung Transplant 2006; 25:53.
- Macdonald P, Hackworthy R, Keogh A, et al. Atrial overdrive pacing for reversion of atrial flutter after heart transplantation. J Heart Lung Transplant 1991; 10:731.
- Rivinius R, Helmschrott M, Ruhparwar A, et al. Long-term use of amiodarone before heart transplantation significantly reduces early post-transplant atrial fibrillation and is not associated with increased mortality after heart transplantation. Drug Des Devel Ther 2016; 10:677.
- Cohn WE, Gregoric ID, Radovancevic B, et al. Atrial fibrillation after cardiac transplantation: experience in 498 consecutive cases. Ann Thorac Surg 2008; 85:56.
- Dasari TW, Pavlovic-Surjancev B, Patel N, et al. Incidence, risk factors, and clinical outcomes of atrial fibrillation and atrial flutter after heart transplantation. Am J Cardiol 2010; 106:737.
- Arenal A, Almendral J, Muñoz R, et al. Mechanism and location of atrial flutter in transplanted hearts: observations during transient entrainment from distant sites. J Am Coll Cardiol 1997; 30:539.
- Pinski SL, Bredikis AJ, Winkel E, Trohman RG. Radiofrequency catheter ablation of atrial flutter after orthotopic heart transplantation: insights into the redefined critical isthmus. J Heart Lung Transplant 1999; 18:292.
- Marine JE, Schuger CD, Bogun F, et al. Mechanism of atrial flutter occurring late after orthotopic heart transplantation with atrio-atrial anastomosis. Pacing Clin Electrophysiol 2005; 28:412.
- Li YG, Grönefeld G, Israel C, et al. Radiofrequency catheter ablation in patients with symptomatic atrial flutter/tachycardia after orthotopic heart transplantation. Chin Med J (Engl) 2006; 119:2036.
- Nof E, Stevenson WG, Epstein LM, et al. Catheter ablation of atrial arrhythmias after cardiac transplantation: findings at EP study utility of 3-D mapping and outcomes. J Cardiovasc Electrophysiol 2013; 24:498.
- Goy JJ, Kappenberger L, Turina M. Wolff-Parkinson-White syndrome after transplantation of the heart. Br Heart J 1989; 61:368.
- Gallay P, Albat B, Thevenet A, Grolleau R. Direct current catheter ablation of an accessory pathway in a recipient with refractory reciprocal tachycardia. J Heart Lung Transplant 1992; 11:442.
- Neuzner J, Friedl A, Pitschner HF. Radiofrequency catheter ablation of a concealed accessory atrioventricular pathway after heart transplantation. Pacing Clin Electrophysiol 1994; 17:1778.
- Thompson E, Steinhaus D, Long N, Borkon AM. Preexcitation syndrome in a donor heart. J Heart Transplant 1989; 8:177.
- Rothman SA, Hsia HH, Bove AA, et al. Radiofrequency ablation of Wolff-Parkinson-White syndrome in a donor heart after orthotopic heart transplantation. J Heart Lung Transplant 1994; 13:905.
- Ott P, Kelly PA, Mann DE, et al. Tachycardia-induced cardiomyopathy in a cardiac transplant recipient: treatment with radiofrequency catheter ablation. J Cardiovasc Electrophysiol 1995; 6:391.
- Park JK, Hsu DT, Hordof AJ, Addonizio LJ. Arrhythmias in pediatric heart transplant recipients: prevalence and association with death, coronary artery disease, and rejection. J Heart Lung Transplant 1993; 12:956.
- Alexopoulos D, Yusuf S, Bostock J, et al. Ventricular arrhythmias in long term survivors of orthotopic and heterotopic cardiac transplantation. Br Heart J 1988; 59:648.
- Berke DK, Graham AF, Schroeder JS, Harrison DC. Arrhythmias in the denervated transplanted human heart. Circulation 1973; 48:III112.
- de Jonge N, Jambroes G, Lahpor JR, Woolley SR. Ventricular fibrillation during acute rejection after heart transplantation. J Heart Lung Transplant 1992; 11:797.
- Uretsky BF, Kormos RL, Zerbe TR, et al. Cardiac events after heart transplantation: incidence and predictive value of coronary arteriography. J Heart Lung Transplant 1992; 11:S45.
- Grinstead WC, Smart FW, Pratt CM, et al. Sudden death caused by bradycardia and asystole in a heart transplant patient with coronary arteriopathy. J Heart Lung Transplant 1991; 10:931.
- Tsai VW, Cooper J, Garan H, et al. The efficacy of implantable cardioverter-defibrillators in heart transplant recipients: results from a multicenter registry. Circ Heart Fail 2009; 2:197.
- SINUS RATE
- SINUS NODE DYSFUNCTION
- Prevalence and causes
- Treatment of sinus bradycardia
- CONDUCTION DISTURBANCES
- SUPRAVENTRICULAR ARRHYTHMIAS
- Atrial premature beats
- Atrial fibrillation or flutter
- Supraventricular tachycardias
- VENTRICULAR ARRHYTHMIAS
- Ventricular premature beats and nonsustained ventricular tachycardia
- Sustained ventricular arrhythmias and sudden cardiac death
- SOCIETY GUIDELINE LINKS
- INFORMATION FOR PATIENTS