Publicado

2017-07-01

Electrocardiographic alterations associated with heart transplantation. Triggers, mechanisms and meaning

Alteraciones electrocardiográficas en el paciente con trasplante cardíaco. Desencadenantes, mecanismos y su significado

DOI:

https://doi.org/10.15446/revfacmed.v65n3.57498

Palabras clave:

Heart transplantation, Arrhythmias, Cardiac, Bradycardia, Tachycardia (en)
Trasplante de corazón, Arritmia cardíaca, Bradicardia, Taquicardia (es)

Autores/as

  • David Mauricio Figueroa-Bohórquez Universidad Nacional de Colombia - Bogotá Campus - Faculty of Medicine - Department of Surgery - Human Organ and Tissue Transplantation Group - Bogotá D.C. - Colombia. https://orcid.org/0000-0003-2858-0118
  • Xiomara Benavides Universidad Nacional de Colombia - Bogotá Campus - Faculty of Medicine - Department of Surgery - Human Organ and Tissue Transplantation Group - Bogotá D.C. - Colombia. https://orcid.org/0000-0002-3646-1795
  • Luz Garzón Universidad Nacional de Colombia - Bogotá Campus - Faculty of Medicine - Department of Surgery - Human Organ and Tissue Transplantation Group - Bogotá D.C. - Colombia.
  • Daniel Espinel Universidad Nacional de Colombia - Bogotá Campus - Faculty of Medicine - Department of Surgery - Human Organ and Tissue Transplantation Group - Bogotá D.C. - Colombia. https://orcid.org/0000-0003-4182-3057
  • Luis Suarez Universidad Nacional de Colombia - Bogotá Campus - Faculty of Medicine - Department of Surgery - Human Organ and Tissue Transplantation Group - Bogotá D.C. - Colombia. https://orcid.org/0000-0002-0776-1334
  • María Uribe Universidad del Rosario - Faculty of Medicine - Bogotá D.C. - Colombia.
  • Linda Gómez-Aristizabal Universidad Nacional de Colombia - Bogotá Campus - Faculty of Medicine - Department of Surgery - Human Organ and Tissue Transplantation Group - Bogotá D.C. - Colombia.
  • Eyner Lozano Márquez Universidad Nacional de Colombia - Bogotá Campus - Faculty of Medicine - Department of Surgery - Human Organ and Tissue Transplantation Group - Bogotá D.C. - Colombia.

Introduction: Heart rhythm disorders are associated with increased morbidity and mortality. However, triggers and implications in patients with heart transplantation are not clear.

Objectives: The purpose of this research paper is to identify and explain the determinants for the onset of electrical conductivity alterations in patients with a heart transplant, as well as to describe the most common arrhythmias and their pathological implications.

Materials and methods: A literature review was made in the PubMed online database for a total of 411 results. In addition, clinical practice guidelines on cardiac transplantation, cardiovascular electrophysiology and infective endocarditis were searched. Sixty articles related to the objectives of this study were chosen.

Results: Surgical technique, heart denervation, sinus node trauma, graft rejection, endomyocardial biopsies and infections are the main factors that compromise organ viability and the life of transplanted patients. These factors can be observed as sinus rhythm disturbances.

Conclusions: When a cardiac arrhythmia is detected, the medical team must provide a treatment that is not limited to symptomatic and sinus rhythm control. An active search of the etiology must be initiated since it may indicate an underlying pathological process.

Introducción. Las alteraciones del ritmo cardíaco están asociadas con un aumento en la morbimortalidad; sin embargo, en pacientes con trasplante cardíaco no son claros sus desencadenantes ni implicaciones.

Objetivos. Realizar una búsqueda en la literatura para identificar y explicar los determinantes en la generación de alteraciones de la conducción eléctrica en pacientes con trasplante cardíaco, así como describir las principales arritmias que pueden presentarse, explicando sus implicaciones patológicas.

Materiales y métodos. Se realizó una búsqueda en la base de datos PubMed que arrojó un total de 411 resultados. Además, se buscaron las guías de práctica clínica sobre trasplante cardíaco, electrofisiología cardiovascular y endocarditis infecciosa. Se eligieron 60 artículos que lograban responder a los objetivos de este estudio.

Resultados. La técnica quirúrgica, la denervación cardíaca, las lesiones del nodo sinusal, el rechazo del injerto, las biopsias endomiocárdicas y las infecciones son los principales factores que comprometen la viabilidad del órgano y la vida del paciente trasplantado, manifestándose como alteraciones del ritmo sinusal.

Conclusiones. Ante la detección de alguna arritmia cardíaca, el equipo médico debe proporcionar un manejo que no se limite al control sintomático y del ritmo sinusal, sino que se debe iniciar una búsqueda activa de su etiología, ya que esta puede ser la manifestación de un proceso patológico subyacente.


57498

review PAPER

DOI: https://doi.org/10.15446/revfacmed.v65n3.57498

Electrocardiographic alterations associated with heart
transplantation. Triggers, mechanisms and meaning

Alteraciones electrocardiográficas en el paciente con trasplante cardíaco.
Desencadenantes, mecanismos y su significado

Received: 18/05/2016. Accepted: 29/06/2016.

David Mauricio Figueroa-Bohórquez1 Xiomara Benavides1 Luz Garzón1, Daniel Espinel1 Luis Suarez1 María Uribe2 Linda Gómez-Aristizabal1 Eyner Lozano-Márquez1

1 Universidad Nacional de Colombia - Bogotá Campus - Faculty of Medicine - Department of Surgery - Human Organ and Tissue
Transplantation Group - Bogotá D.C. - Colombia.

2 Universidad del Rosario - Faculty of Medicine - Bogotá D.C. - Colombia.

Corresponding author: David Mauricio Figueroa-Bohórquez. Human Organ and Tissue Transplantation Group, Department of Surgery, Faculty of Medicine, Universidad Nacional de Colombia. Carrera 30 No. 45-03, building 471, office: 124. Phone number:
+57 1 3165000, ext.: 15105; mobile number +57 3153741070. Bogotá D.C. Colombia. Email: damfigueroabo@unal.edu.co.

| Abstract |

Introduction: Heart rhythm disorders are associated with increased morbidity and mortality. However, triggers and implications in patients with heart transplantation are not clear.

Objectives: The purpose of this research paper is to identify and explain the determinants for the onset of electrical conductivity alterations in patients with a heart transplant, as well as to describe the most common arrhythmias and their pathological implications.

Materials and methods: A literature review was made in the PubMed online database for a total of 411 results. In addition, clinical practice guidelines on cardiac transplantation, cardiovascular electrophysiology and infective endocarditis were searched. Sixty articles related to the objectives of this study were chosen.

Results: Surgical technique, heart denervation, sinus node trauma, graft rejection, endomyocardial biopsies and infections are the main factors that compromise organ viability and the life of transplanted patients. These factors can be observed as sinus rhythm
disturbances.

Conclusions: When a cardiac arrhythmia is detected, the medical team must provide a treatment that is not limited to symptomatic and sinus rhythm control. An active search of the etiology must be initiated since it may indicate an underlying pathological process.

Keywords: Heart transplantation; Arrhythmias; Cardiac; Bradycardia; Tachycardia (MeSH).

Figueroa-Bohórquez DM, Benavides X, Garzón L, Espinel D, Suarez L, Uribe M, et al. Electrocardiographic alterations associated with heart transplantation. Triggers, mechanisms and meaning. Rev. Fac. Med. 2017;65(3):483-9. English. doi: https://doi.org/10.15446/revfacmed.v65n3.57498.

| Resumen |

Introducción. Las alteraciones del ritmo cardíaco están asociadas con un aumento en la morbimortalidad; sin embargo, en pacientes con trasplante cardíaco no son claros sus desencadenantes ni implicaciones.

Objetivos. Realizar una búsqueda en la literatura para identificar y explicar los determinantes en la generación de alteraciones de la conducción eléctrica en pacientes con trasplante cardíaco, así como describir las principales arritmias que pueden presentarse, explicando sus implicaciones patológicas.

Materiales y métodos. Se realizó una búsqueda en la base de datos PubMed que arrojó un total de 411 resultados. Además, se buscaron las guías de práctica clínica sobre trasplante cardíaco, electrofisiología cardiovascular y endocarditis infecciosa. Se eligieron 60 artículos que lograban responder a los objetivos de este estudio.

Resultados. La técnica quirúrgica, la denervación cardíaca, las lesiones del nodo sinusal, el rechazo del injerto, las biopsias endomiocárdicas y las infecciones son los principales factores que comprometen la viabilidad del órgano y la vida del paciente trasplantado, manifestándose como alteraciones del ritmo sinusal.

Conclusiones. Ante la detección de alguna arritmia cardíaca, el equipo médico debe proporcionar un manejo que no se limite al control sintomático y del ritmo sinusal, sino que se debe iniciar una búsqueda activa de su etiología, ya que esta puede ser la manifestación de un proceso patológico subyacente.

Palabras clave: Trasplante de corazón; Arritmia cardíaca; Bradicardia; Taquicardia (MeSH).

Figueroa-Bohórquez DM, Benavides X, Garzón L, Espinel D, Suarez L, Uribe M, et al. [Alteraciones electrocardiográficas en el paciente con trasplante cardíaco. Desencadenantes, mecanismos y su significado]. Rev. Fac. Med. 2017;65(3):483-9. English. doi: https://doi.org/10.15446/revfacmed.v65n3.57498.

Introduction

Despite the progress in pharmacological treatment, organ transplantation can lead to multiple chronic pathologies that cannot be properly addressed with medical management (1). Cardiac transplantation is reserved for patients with heart disease who evolve to advanced and symptomatic heart failure despite optimal medical management, in other words, functional status D and functional class IV according to the New York Heart Association classification (NYHA) (2).

With the development and improvement of surgical techniques, as well as the improvement of post-transplant management, the patient is expected to restore hemodynamic stability, improve functional class and have a better quality of life, reaching survivor rates at 1 year and 10 years close to 90% and 50%, respectively (2-5).

Often, survival and quality of life are compromised by the onset of arrhythmias at any time after transplantation, and triggers and implications are not clear to date. The purpose of this article is to conduct a literature review to identify and explain the variables associated with cardiac transplantation that influence alterations in sinus rhythm and electrical conduction, during or after surgery. Similarly, a description of the main arrhythmias that patients may suffer after orthotopic cardiac transplantation and its consequences is presented.

Materials and methods

A systematic review was made in the PubMed database based on multiple combinations of MESH terms: “heart transplantation”, “Arrhythmias, Cardiac”, “Tachycardia, Ventricular”, “Tachycardia, Supraventricular”, “Bradycardia”, “Pacemaker, Artificial” and “Catheter Ablation”. The search was limited to studies in human. Articles that addressed heterotopic heart transplantation or that were written in a language other than English or Spanish were excluded. 411 articles were obtained.

The abstracts obtained after the search were analyzed, and those that coincided with the objectives of this study were selected. In addition, the national guidelines for cardiac transplantation and cardiovascular electrophysiology were consulted in the official website of the Colombian Society of Cardiology, while information on clinical practice guidelines for infective endocarditis were obtained from the European Society of Cardiology website. In total, 60 articles were chosen and used as reference for this review.

Factors associated with the development of cardiac arrhythmias

Surgical technique

The biauricular transplantation technique was first described by Lower and Shumway in the 1960s, and is characterized by myocardium anastomosis between both donor atria and a remnant of these structures in the recipient. Later, in the 1990s, the literature described the bicaval technique, in which anastomosis occurs in the large vessels in both portions of the vena cava and around the pulmonary veins, resulting in less manipulation and alteration of the atria (6).

Currently, a strong discussion has taken place around which techniques should be preferred, since long-term results do not show significant differences, although multiple publications demonstrate the benefits of the bicaval technique with respect to the standard technique (3,7-11).

The biauricular technique has demonstrated that suture lines form scars that act as low voltage areas, and that they isolate electrically the donor tissue from the receptor tissue, which is the reason for a higher incidence of flutter-type arrhythmias in patients who undergo this surgical technique.

Furthermore, randomized controlled studies have reported that the use of the bicaval technique needs less pacemakers implantation; however, no association was established between the permanent use of this device and long-term survival (12- 14). Czer et al. (12) developed a study comparing the functional class of transplanted patients with both surgical techniques during physical activity, considering variables such as heart rate, oxygen consumption, carbon dioxide production and duration of exercise, without finding differences between both groups.

Denervation and reinnervation

All surgical techniques involve cardiac denervation, which causes the heart to lose its autonomic regulation and, in consequence, the variability of the heart rate as a way of physiological adaptation to different stimuli of the environment. For this reason, the transplanted organ is guided by the sinus node rhythm and only responds to chronotropic, inotropic and dromotropic stimuli of the circulating catecholamines (15), and to the changes in blood volume caused by the venous return that stimulates a determined contraction force according to Frank-Starling’s law (16).

Similarly, sympathetic reinnervation is considered unpredictable, disordered, often incomplete and variable among patients, leading to aberrant reinnervation, which may cause multiple sinus rhythm disorders (17-20). A study led by Uberfuhr (20) in Germany found that about 60% of patients with orthotopic heart transplantation had some degree of sympathetic reinnervation.

Sinus node dysfunction

Sinus node dysfunction —defined as the absence of sinus rhythm, sinus node recovery time greater than 1.4 ms or secondary electrical pauses during electrophysiological examinations— is the most common cause of early implantation of pacemakers in transplant patients, that is, before 3 months after surgery (21-23). Depending on the series, a prevalence between 10% and 45% of early sinus dysfunction is reported, reaching implantation rates of up to 30% in this group of patients (12,24). Early sinus dysfunction is largely attributed to the surgical procedure, whether caused by trauma, node ischemia due to nodal artery injury, or prolonged ischemia times. Over the years, a decrease in the incidence of sinus node alterations has been reported, which has been attributed to the improvement of the surgical technique (25).

Deleuze et al. (13) compared the results of both surgical techniques in the postoperative period of 81 heart transplants, finding that the biauricular technique showed a higher prevalence of sinus node dysfunction, while patients treated with the bicaval technique did not require implantation of a pacemaker within the first 30 days, although 12.5% of them did (25). AV blocks and sinus dysfunction three months after the procedure are, to the same extent, the main indication of the implantation of a permanent pacemaker.

Recovery of sinus node function is common, particularly, when these changes occur rapidly after transplantation (21,26,27). Late sinus node dysfunction occurs three months after transplantation, and about 5% of patients require implantation of pacemakers for this reason according to a study published by Luebbert et al. (6), who did not find a higher prevalence related to any surgical technique, age, sex or pre-transplant diagnosis.

Rejection of the graft

About 20-30% of patients have experienced graft rejection during the first year after transplantation. This process is defined as the presence of inflammatory infiltrate in the transplanted tissue. Hence, taking endomyocardial biopsies is necessary for diagnosis and classification. Based on the results of the histological examination of the sample, it can be established whether there is any degree of cellular or humoral rejection according to the International Society for Heart and Lung Transplantation in 2004 (28,29). Despite the efforts and good results that relate findings by magnetic resonance to graft rejection cases, the gold standard is still histological study (30). Some series claim that the presence of acute graft rejection is closely related to the onset of cardiac arrhythmias, especially with flutter and atrial fibrillation, but this remains a controversial issue. Ahmari et al. (31) from the Mayo Clinic state that the recurrence of moderate to severe acute rejections results in cardiac fibrosis that compromises diastolic function and predisposes the development of atrial flutter, and that these markers imply poor prognosis in the long term. Thus, the next step should be to rule out acute rejection of the graft to detect de novo alterations (17,32).

Chronic graft rejection in heart transplantation refers to cardiac graft vasculopathy (CGV). Although this process was initially understood as an immune-mediated process, today it is now known as a multifactorial process that includes alloimmune, autoimmune and non-immune mediated responses (24).

The progression of intraluminal changes, which ends in the occlusion of the coronary macrovasculature and microvasculature flow, begins as a lesion and apoptosis process in the endothelial parenchyma that leads to the concentric proliferation of the smooth muscle and to the failure of the cardiac graft, creating a terrain for the onset of both atrial and ventricular arrhythmias (24).

The development of CGV is the most predisposing factor to myocardial tissue ischemia and fibrous tissue formation, and the one that affects survival the most; thus, it is the main cause of death at 3 years after transplantation, together with malignant processes (30). At 5 years, 30% of transplant patients suffer CGV (24,33), and multiple episodes of acute rejection are considered as a risk factor for its development. The gold standard for this pathology is coronary angiography, which is why it is performed routinely in these patients.

Biopsies

Biopsies are routinely performed, and in cases when the medical team deems them necessary to rule out acute rejection of the graft. This procedure is usually performed under local anesthesia, has a mortality rate of 0.4% (29), and is considered the gold standard for detecting rejection (34).

Despite being relatively safe, the main complications of biopsy are ventricular perforation and cardiac tamponade, atrial or ventricular arrhythmias, pneumothorax, tricuspid insufficiency, ventricular coronary fistula, transient cardiac arrest, carotid artery puncture, infection and venous hematoma (29,35).

For this type of procedure, the transjugular route is the first option for access, whereas the femoral vein route is used in case of difficulty with jugular access or if coronary angiography is performed during the procedure.

There is no consensus as to how often routine biopsies should be taken. The Colombian cardiac transplant guidelines of 2009 suggest that 11 biopsies should be taken during the first year (29), while the international guidelines for cardiac transplantation and lung cancer of 2010 propose 18 biopsies during the same period of time (36). Nguyen et al. (37) recommend a maximum of 31 endomyocardial biopsies, since they demonstrated that exceeding this number of repetitions increases the risk of severe tricuspid insufficiency.

Over time, progress in immunosuppressive treatment has decreased rejection rates, which would explain the decrease in the frequency of this diagnostic procedure. However, further studies are needed to establish a global consensus in this regard, since acute rejection is usually a subclinical process with severe long-term repercussions.

During the procedure, ventricular arrhythmias are common, but they are usually temporary and transient. In the long term, third degree atrioventricular (AV) blocks have been associated (27) because of the frequency of this procedure, although this is not widely described in the literature and is considered an uncommon event.

Magnetic resonance imaging is suggested to replace endomyocardial biopsies, obtaining promising results in preliminary studies (38,39).

Infections

Immunosuppressive therapy opens the door to a large number of microorganisms that the immune system could control if it functions properly. According to the type of therapy and the postoperative time, the etiological agents of greater incidence vary (29). About 12% of deaths after transplantation within the first month are associated with infections by nosocomial bacterial microorganisms in different sites. Between the second and sixth month, infectious pathologies are usually caused by opportunistic infections and the reactivation of latent infections. Finally, microorganisms acquired in the community are the most frequent after the sixth month (29,40).

Estimations indicate that about 1.5% of cardiac transplant patients are infected with infectious endocarditis (IE), mostly by Staphylococcus aureus and Aspergillus fumigatus. Risk factors include the use of central catheters in the perioperative period and frequent endomyocardial biopsies (41).

Electrical conduction disorders are observed in 1% to 15% of IE patients, mostly manifested as AV blocks, branch blocks and atrial fibrillation. The presence of these alterations is associated with poor prognosis and higher mortality (42). Infections caused by agents such as cytomegalovirus and Chlamydia pneumoniae favor the development of CGV and, consequently, graft failure and cardiac arrhythmias caused by the mechanisms described above. C. pneumoniae infection is associated with greater severity of CGV (24).

Drugs

The average effect of amiodarone is prolonged, so it is possible to continue to observe its effects for several days in patients who took it before the transplantation. In patients who develop early sinus dysfunction, the effect of amiodarone may further compromise the electrical conduction of the transplanted organ (17).

Arrhythmia in the transplanted patient

Tachyarrhythmias

Supraventricular tachyarrhythmias

Supraventricular tachyarrhythmias have a high incidence in transplanted patients, greatly compromising their quality of life and survival. Dahu et al. (43) proposed five mechanisms involved in the development of atrial arrhythmias: 1) reentrant in the donor’s atrium associated with the scar or the valve; 2) focal tachycardia in the donor’s atrium; 3) atrial fibrillation in the donor’s atrium; 4) re-entry arrhythmias that compromise two or more reconnections between donor and recipient atrium, and 5) arrhythmias originating in the recipient atrium that pass to the donor through one or more focal reconnections.

In turn, Vaseghi et al. (32) reviewed supraventricular tachycardia, and proposed another mechanism related to pre-existing alterations in the electrical conduction of the donor, which are manifested as AV nodal reentrant tachycardia and re-entry tachycardia associated with abnormal beam (32,44).

Supraventricular tachyarrhythmias can be classified as:

Atrial fibrillation, which is common in the early postoperative period and is almost always associated with graft manipulation, inflammatory period and autonomic changes. The incidence of atrial fibrillation decreases progressively, becoming exceptional during the late postoperative period in the absence of vasculopathy, rejection or infection (17,32,43,45). These low numbers are associated with the isolation of pulmonary veins, cava veins and the posterior wall of the atrium, which are the main foci of generation. This occurs because the surgical scar acts as an electrical insulator between recipient and donor atria remnants (46).

When atrial fibrillation is identified, the first step to take should be discarding the clinical cases previously mentioned as possible triggers. The control of these pathologies may be sufficient in most cases to stop their development. Antiarrhythmic drugs of choice are amiodarone and procainamide, which are not usually formulated for a long time because of the high resolution rate of this type of cardiac arrhythmia, which is associated with the management of its triggers. Controlling immunosuppression levels is necessary due to the interaction of amiodarone and warfarin with ciclosporin and tacrolimus (17). In case of persistence, catheter ablation is the treatment of choice for this disorder (17).

Atrial Flutter is the most common type of arrhythmia in patients after a heart transplant. In non-transplanted patients, the isthmus-dependent atrial flutter is formed by a counterclockwise circuit, which compromises the tricuspid valve, the Thebesian valve, the opening of the superior and inferior vena cava, and the crista terminalis. In transplanted patients, a similar circuit is formed, with the difference that the posterior line of the latter conforms the atrial suture line (47). This type of arrhythmia is more common in the biauricular technique (48).

Mitral annular flutter is less common and has no major incidence on a particular type of surgical technique. Just like atrial fibrillation, the development of flutter is also associated with periods of acute rejection, infection or vasculopathy, and their identification should stimulate the active search of these entities in the transplanted patient. When these causes are discarded and treated, as well as ventricular dysfunction and valvular pathology, catheter ablation is recommended to form an electrical block line between the tricuspid ring and the atrial suture for the right atrial-dependent flutter (48), whereas ablation of the anterior line of the circuit is recommended for the left atrium (49).

Focal atrial tachycardia is caused by the formation of depolarization foci near the atrial scar that take control of the heart rhythm. Scars, together with fibrosis, predispose to the formation of areas of slow electrical conduction, and provide the substrate for the production of macroreentrants and the development of focal atrial tachycardia. Elsik et al. (45) reported patients in whom the focus is found in the donor’s atrium, while Vaseghi et al. (32) describe cases in which depolarization begins in the atrial remnant of the recipient and passes into the donor tissue through bridges formed by fibroblasts, which create gap-like junctions that allow electrical transmission. Definitive treatment is focal catheter ablation.

Atrial reentrant and nodal reentrant tachycardia require a preexisting route in the donor that allows a macroreentrant. Although they have been described in the literature, they are uncommon in transplanted patients. Radiofrequency ablation is curative (32).

Ventricular tachyarrhythmias

Ventricular extrasystoles and non-sustained ventricular tachycardia may be common in the early post-transplant period. The subsequent development of sustained and non-sustained ventricular tachycardia suggests an episode of acute rejection or graft vasculopathy (18), while taking into account other rare etiologies that may have similar clinical features and may be reversible, such as idiopathic fascicular ventricular tachycardia (50).

The most common arrest rhythm in cardiac denervation in sudden death events is asystole, followed by pulseless electrical activity; both are non-defibrillating rhythms, so the use of automatic implantable defibrillators remains controversial (17,51).

Bradyarrhythmias

Bradyarrhythmias may appear during the early or late period after a heart transplant, and can be caused by sinus node dysfunction or errors in the electrical conduction, with functional or dysfunctional sinus node.

In the early postoperative period, the transplanted heart usually requires positive chronotropic agents or temporary pacemaker implantation. It has been demonstrated that the donor’s sinus node is hypersensitive to these pharmacological agents, so its use must be cautious (52).

Early sinus node dysfunction puts the patient’s life at risk in the early postoperative days, and its multifactorial etiology is almost always associated with circumstances that depend on the surgical procedure (12,21,53,54). As for late sinus dysfunction, the role of graft rejection in its development is controversial.

Sinus dysfunction may be paroxysmal or persistent, and may be manifested as sinus bradycardia or as a total stop of the sinoatrial node (53,54). To control these entities, a therapeutic test can be performed with isoprenaline, dopamine, dobutamine or theophylline in search of increased heart rate and recovery of sinus rhythm. If this therapy fails, the use of pacemakers should be considered (21,55).

The 2011 Colombian guide to cardiovascular electrophysiology (56) provides the following recommendations for the implantation of a permanent pacemaker:

Class I: it is indicated in symptomatic, inappropriate, persistent or not-expected-to-improve bradycardia.

Class IIA: it is considered in symptomatic, recurrent and prolonged bradycardia that limits rehabilitation or discharge during the post-surgical recovery phase of the transplant (level of evidence C).

Class IIB: it is considered in patients with syncope after cardiac transplantation although bradyarrhythmia has not been documented (level of evidence C).

Early implantation of a permanent pacemaker occurs when the heart rate has not been normalized with other interventions after three weeks (57). Early sinus dysfunction in the early postoperative period is usually not associated with damage to the electrical conduction system, so bicameral pacemakers with AAIR/DDDR function that seek physiological stimulation and preserve AV synchrony have been widely used in the last years. However, after one year of implantation, the frequency of activity of these devices decreases, in most cases due to the recovery of the sinus function (55,57,58).

In the late postoperative period, errors in the conduction of the nerve impulse are predominant, with AV blocks being the leading cause of implantation of cardiac pacemakers in this period. This phenomenon has been attributed to the development of graft rejection, since electrical conduction tissue has been proven as a typical target of humoral response during this process (52,56,59).

Conclusions

The development of arrhythmias is a frequent issue and, in some cases, puts the life of the patient at risk. This complication is related to multiple triggers. There are factors associated with the surgical procedure itself, such as ischemia times, sinus node injury, and excessive manipulation of the atria due to the surgical technique and cardiac denervation, as well as other mechanisms related to the preoperative and post-surgical periods, such as acute rejection episodes, reinnervation, ventricular biopsies, graft vasculopathy, systemic infections, and drug effects.

The most common arrhythmias are bradycardia, which, in a significant percentage, will require implantation of permanent pacemakers. The most frequent tachyarrhythmia is the isthmus-dependent flutter, which can be treated with catheter ablation. The most common rhythm of cardiac arrest in these patients is asystole, unlike the general population, where more defibrillatory rhythms such as tachycardia and ventricular fibrillation occur.

The detection of any cardiac arrhythmia should lead to think of the possibility that this is the manifestation of an underlying pathological process that puts at risk the viability of the organ and the life of the patient. The medical team is obliged manage this condition in a way that is not limited to symptomatic control and sinus rhythm, but to initiate an active search for its etiology to give optimal therapeutic management to each patient.

Conflict of interest

None stated by the authors.

Funding

None stated by the authors.

Acknowledgement

To Dr. Ana María Barón, cardiologist and cardiac transplant specialist, for her support during the development of this article.

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13.Deleuze PH, Benvenuti C, Mazzucotelli JP, Perdrix C, Le Besnerais P, Mourtada A, et al. Orthotopic cardiac transplantation with direct caval anastomosis: Is it the optimal procedure? J Thorac Cardiovasc Surg. 1995;109(4):731-37. http://doi.org/fjm6g4.

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15.Estorch-Cabrera M, Flotats-Giralt A, Campreciós-Crespo M, Marí-Aparici C, Bernà-Roqueta L, Catafau-Alcántara AM, et al. Reinervación simpática del corazón trasplantado. Estudio realizado con metayodobenzilguanidina marcada con yodo-123. Rev Esp Cardiol. 1998;51(5):369-74. http://doi.org/b47g.

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23.Markewitz A, Kemkes BM, Reble B, Osterholzer G, Reichart B, Puricelii C, et al. Particularities of dual chamber pacemaker therapy in patients after orthotopic heart transplantation. Pacing Clin Electrophysiol. 1987;10(2):326-32. http://doi.org/bzhb3m.

24.Costello JP, Mohanakumar T, Nath DS. Mechanisms of chronic cardiac allograft rejection. Tex Heart Inst J. 2013;40(4):395-9.

25.Heinz G, Kratochwill C, Schmid S, Kreiner G, Siostrzonek P, Pacher R, et al. Sinus node dysfunction after orthotopic heart transplantation: the Vienna experience 1987-1993. Pacing Clin Electrophysiol. 1994;17(11 pt 2):2057-63. http://doi.org/fg8r58.

26.Heinz G, Kratochwill C, Koller-Strametz J, Kreiner G, Grimm M, Grabenwöger M, et al. Benign prognosis of early sinus node dysfunction after orthotopic cardiac transplantation. Pacing Clin Electrophysiol. 1998;21(2):422-9. http://doi.org/bhjtzg.

27.Stecker EC, Strelich KR, Chugh SS, Crispell K, McAnulty JH. Arrhythmias After Orthotopic Heart Transplantation. J Card Fail. 2005;11(6):464-72. http://doi.org/fjfnnf.

28.Stewart S, Winters GL, Fishbein MC, Tazelaar HD, Kobashigawa J, Abrams J, et al. Revision of the 1990 Working Formulation for the Standardization of Nomenclature in the Diagnosis of Heart Rejection. J Heart Lung Transplant. 2005;24(11):1710-20. http://doi.org/d2825g.

29.Beltran-Bohórquez JR, Franco-Reyes C, Echeverría LE, Gómez-López EA, Fernández-Vergara D, Gómez-Mesa JE, et al. Guías colombianas de cardiología. Trasplante cardíaco. Revista Colombiana de Cardiología. 2009;16(Supl 2):44-53.

30.Lavine KJ, Sintek M, Novak E, Ewald G, Geltman E, Joseph S, et al. Coronary collaterals predict improved survival and allograft function in patients with coronary allograft vasculopathy. Circ Heart Fail. 2013;6(4):773-84. http://doi.org/f49759.

31.Ahmari SL, Bunch TJ, Chandra A, Chandra V, Ujino K, Daly RC, et al. Prevalence, pathophysiology, and clinical significance of post-heart transplant atrial fibrillation and atrial flutter. J Heart Lung Transplant. 2006;25(1):53-60. http://doi.org/c6n4pq.

32.Vaseghi M, Boyle NG, Kedia R, Patel JK, Cesario DA, Wiener I, et al. Supraventricular Tachycardia After Orthotopic Cardiac Transplantation. J Am Coll Cardiol. 2008;51(23):2241-9. http://doi.org/fq2g6t.

33.Krieghoff C, Barten MJ, Hildebrand L, Grothoff M, Lehmkuhl L, Lücke C, et al. Assessment of sub-clinical acute cellular rejection after heart transplantation: comparison of cardiac magnetic resonance imaging and endomyocardial biopsy. Eur Radiol. 2014;24(10):2360-71. http://doi.org/b47v.

34.From AM, Maleszewski JJ, Rihal CS. Current Status of Endomyocardial Biopsy. Mayo Clin Proc. 2011;86(11):1095-102. http://doi.org/c9cpd4.

35.Vollroth M, Seeburger J, Kiefer P, Garbade J, Mohr FW, Barten MJ. Mitral Valve Regurgitation: A severe complication following left ventricular biopsy 15 years after heart transplantation. Case Rep Transplant. 2013;2013:407875. http://doi.org/b47w.

36.Costanzo MR, Dipchand A, Starling R, Anderson A, Chan M, Desai S, et al. The International Society of Heart and Lung Transplantation Guidelines for the care of heart transplant recipients. J Heart Lung Transplant. 2010;29(8):914-56. http://doi.org/ct8c2k.

37.Nguyen V, Cantarovich M, Cecere R, Giannetti N. Tricuspid regurgitation after cardiac transplantation: how many biopsies are too many? J Heart Lung Transplant. 2005;24(7 Suppl):S227-31. http://doi.org/cq7pmc.

38.Miller CA, Naish JH, Shaw SM, Yonan N, Williams SG, Clark D, et al. Multiparametric cardiovascular magnetic resonance surveillance of acute cardiac allograft rejection and characterisation of transplantation-associated myocardial injury: a pilot study. J Cardiovasc Magn Reson. 2014;16:52-63. http://doi.org/b47x.

39.Korosoglou G, Osman NF, Dengler TJ, Riedle N, Steen H, Lehrke S, et al. Strain-encoded cardiac magnetic resonance for the evaluation of chronic allograft vasculopathy in transplant recipients. Am J Transplant. 2009;9(11):2587-96. http://doi.org/ds2bpp.

40.Mangini S, Alves BR, Silvestre OM, Pires PV, Tachotti-Pires LJ, Cardoso-Curiati MN, et al. Heart transplantation: review. Einstein. 2015;13(2):310-8. http://doi.org/b47z.

41.Sherman-Weber S, Axelrod P, Suh B, Rubin S, Beltramo D, Manacchio J, et al. Infective endocarditis following orthotopic heart transplantation: 10 cases and a review of the literature. Transpl Infect Dis. 2004;6(4):165-70. http://doi.org/dzrxjr.

42.Habib G, Lancellotti P, Antunes MJ, Bongiorni MG, Casalta JP, Del Zotti F, et al. 2015 ESC Guidelines for the management of infective endocarditis: The Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM). Eur Heart J. 2015;36(44):3075-128. http://doi.org/b472.

43.Dahu MI, Hutchinson MD. What Is the Mechanism of the Atrial Arrhythmia in a Patient After Orthotopic Heart Transplantation? J Cardiovasc Electrophysiol. 2012;23(2):225-7. http://doi.org/fgvrx7.

44.Sharma PP, Marcus FI. Radiofrequency ablation of an accessory pathway years after heart transplant: a case report. J Heart Lung Transplant. 1999;18(8):792-5. http://doi.org/dmsrtd.

45.Elsik M, Teh A, Ling LH, Virdee M, Parameshwar J, Fynn SP, et al. Supraventricular arrhythmias late after orthotopic cardiac transplantation: electrocardiographic and electrophysiological characterization and radiofrequency ablation. Europace. 2012;14(10):1498-505. http://doi.org/f4cpsx.

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48.Heist EK, Doshi SK, Singh JP, Di Salvo T, Semigran MJ, Reddy VY, et al. Catheter ablation of atrial flutter after orthotopic heart transplantation. J Cardiovasc Electrophysiol. 2004;15(12):1366-70. http://doi.org/djbqgz.

49.Makanjee B, Klein GJ, Derval N, Skanes AC. An Anterior Ablation Line Is Preferred for Perimitral Flutter After Heart Transplant. J Cardiovasc Electrophysiol. 2010;21(5):574-6. http://doi.org/dwpskf.

50.Clarke N, Mason M, Paul V. Radiofrequency ablation of a fascicular tachycardia after orthotopic cardiac transplantation. Heart. 1998;79(4):414-6. http://doi.org/b473.

51.Vaseghi M, Lellouche N, Ritter H, Fonarow GC, Patel JK, Moriguchi J, et al. Mode and mechanisms of death after orthotopic heart transplantation. Heart Rhythm. 2009;6(4):503-9. http://doi.org/fbnddg.

52.Scott CD, McComb JM, Dark JH, Bexton RS. Permanent pacing after cardiac transplantation. Br Heart J. 1993;69(5):399-403. http://doi.org/bwsp8j.

53.Thompson MA, Patel H. Posttransplant Pacemaker Placement: Case Series and Review. Ochsner J. 2010;10(4):236-40.

54.Lee KJ, Jung YS, Lee CJ, Wi J, Shin S, Kim T, et al. Permanent pacemaker for syncope after heart transplantation with bicaval technique. Yonsei Med J. 50(4):588-90. http://doi.org/bk36rr.

55.Cataldo R, Olsen S, Freedman RA. Atrioventricular block occurring late after heart transplantation: presentation of three cases and literature review. Pacing Clin Electrophysiol. 1996;19(3):325-30. http://doi.org/fdsdzw.

56.Noworolski R, Przybylowski P, Majewski J, Sadowski J, Lelakowski J. Early and Late Indications for Implantation of Cardiac Pacemakers in Patients After Heart Transplantation: A Single-Center Experience. Transplant Proc. 2011;43(8):3074-5. http://doi.org/cwvn4h.

57.Patel VS, Lim M, Massin EK, Jonsyn GP, Ates P, Abou-Awdi NL, et al. Sudden cardiac death in cardiac transplant recipients. Circulation. 1996;94(9 Suppl):273-7.

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59.Negrete-Salcedo A, Vargas-Rugeles C, Orjuela-Guerrero A, Pérez-Molina C, Álvarez-Ortiz A, Rodríguez-Guerrero DA, et al. Guías colombianas de electrofisiología cardiovascular. Recomendaciones clínicas y niveles de evidencia. Actualización 2011. Rev Col Cardiol. 2011;18(Supl 3):214-26.

Iván “Ivanquio” Benavides

“El niño vacío” – 008

Técnica: tinta, color digital

Recibido: 18 de mayo de 2016; Aceptado: 29 de junio de 2016

Abstract

Introduction:

Heart rhythm disorders are associated with increased morbidity and mortality. However, triggers and implications in patients with heart transplantation are not clear.

Objectives:

The purpose of this research paper is to identify and explain the determinants for the onset of electrical conductivity alterations in patients with a heart transplant, as well as to describe the most common arrhythmias and their pathological implications.

Materials and methods:

A literature review was made in the PubMed online database for a total of 411 results. In addition, clinical practice guidelines on cardiac transplantation, cardiovascular electrophysiology and infective endocarditis were searched. Sixty articles related to the objectives of this study were chosen.

Results:

Surgical technique, heart denervation, sinus node trauma, graft rejection, endomyocardial biopsies and infections are the main factors that compromise organ viability and the life of transplanted patients. These factors can be observed as sinus rhythm disturbances.

Conclusions:

When a cardiac arrhythmia is detected, the medical team must provide a treatment that is not limited to symptomatic and sinus rhythm control. An active search of the etiology must be initiated since it may indicate an underlying pathological process.

Keywords:

Heart transplantation, Arrhythmias, Cardiac, Bradycardia, Tachycardia (MeSH).

Resumen

Introducción.

Las alteraciones del ritmo cardíaco están asociadas con un aumento en la morbimortalidad; sin embargo, en pacientes con trasplante cardíaco no son claros sus desencadenantes ni implicaciones.

Objetivos.

Realizar una búsqueda en la literatura para identificar y explicar los determinantes en la generación de alteraciones de la conducción eléctrica en pacientes con trasplante cardíaco, así como describir las principales arritmias que pueden presentarse, explicando sus implicaciones patológicas.

Materiales y métodos.

Se realizó una búsqueda en la base de datos PubMed que arrojó un total de 411 resultados. Además, se buscaron las guías de práctica clínica sobre trasplante cardíaco, electrofisiología cardiovascular y endocarditis infecciosa. Se eligieron 60 artículos que lograban responder a los objetivos de este estudio.

Resultados.

La técnica quirúrgica, la denervación cardíaca, las lesiones del nodo sinusal, el rechazo del injerto, las biopsias endomiocárdicas y las infecciones son los principales factores que comprometen la viabilidad del órgano y la vida del paciente trasplantado, manifestándose como alteraciones del ritmo sinusal.

Conclusiones.

Ante la detección de alguna arritmia cardíaca, el equipo médico debe proporcionar un manejo que no se limite al control sintomático y del ritmo sinusal, sino que se debe iniciar una búsqueda activa de su etiología, ya que esta puede ser la manifestación de un proceso patológico subyacente.

Palabras clave:

Trasplante de corazón, Arritmia cardíaca, Bradicardia, Taquicardia (MeSH).

Introduction

Despite the progress in pharmacological treatment, organ transplantation can lead to multiple chronic pathologies that cannot be properly addressed with medical management 1. Cardiac transplantation is reserved for patients with heart disease who evolve to advanced and symptomatic heart failure despite optimal medical management, in other words, functional status D and functional class IV according to the New York Heart Association classification (NYHA) 2.

With the development and improvement of surgical techniques, as well as the improvement of post-transplant management, the patient is expected to restore hemodynamic stability, improve functional class and have a better quality of life, reaching survivor rates at 1 year and 10 years close to 90% and 50%, respectively 2-5.

Often, survival and quality of life are compromised by the onset of arrhythmias at any time after transplantation, and triggers and implications are not clear to date. The purpose of this article is to conduct a literature review to identify and explain the variables associated with cardiac transplantation that influence alterations in sinus rhythm and electrical conduction, during or after surgery. Similarly, a description of the main arrhythmias that patients may suffer after orthotopic cardiac transplantation and its consequences is presented.

Materials and methods

A systematic review was made in the PubMed database based on multiple combinations of MESH terms: "heart transplantation", "Arrhythmias, Cardiac", "Tachycardia, Ventricular", "Tachycardia, Supraventricular", "Bradycardia", "Pacemaker, Artificial" and "Catheter Ablation". The search was limited to studies in human. Articles that addressed heterotopic heart transplantation or that were written in a language other than English or Spanish were excluded. 411 articles were obtained.

The abstracts obtained after the search were analyzed, and those that coincided with the objectives of this study were selected. In addition, the national guidelines for cardiac transplantation and cardiovascular electrophysiology were consulted in the official website of the Colombian Society of Cardiology, while information on clinical practice guidelines for infective endocarditis were obtained from the European Society of Cardiology website. In total, 60 articles were chosen and used as reference for this review.

Factors associated with the development of cardiac arrhythmias

Surgical technique

The biauricular transplantation technique was first described by Lower and Shumway in the 1960s, and is characterized by myocardium anastomosis between both donor atria and a remnant of these structures in the recipient. Later, in the 1990s, the literature described the bicaval technique, in which anastomosis occurs in the large vessels in both portions of the vena cava and around the pulmonary veins, resulting in less manipulation and alteration of the atria 6.

Currently, a strong discussion has taken place around which techniques should be preferred, since long-term results do not show significant differences, although multiple publications demonstrate the benefits of the bicaval technique with respect to the standard technique 3,7-11.

The biauricular technique has demonstrated that suture lines form scars that act as low voltage areas, and that they isolate electrically the donor tissue from the receptor tissue, which is the reason for a higher incidence of flutter-type arrhythmias in patients who undergo this surgical technique.

Furthermore, randomized controlled studies have reported that the use of the bicaval technique needs less pacemakers implantation; however, no association was established between the permanent use of this device and long-term survival 12-14. Czer et al. 12 developed a study comparing the functional class of transplanted patients with both surgical techniques during physical activity, considering variables such as heart rate, oxygen consumption, carbon dioxide production and duration of exercise, without finding differences between both groups.

Denervation and reinnervation

All surgical techniques involve cardiac denervation, which causes the heart to lose its autonomic regulation and, in consequence, the variability of the heart rate as a way of physiological adaptation to different stimuli of the environment. For this reason, the transplanted organ is guided by the sinus node rhythm and only responds to chronotropic, inotropic and dromotropic stimuli of the circulating catecholamines 15, and to the changes in blood volume caused by the venous return that stimulates a determined contraction force according to Frank-Starling's law 16.

Similarly, sympathetic reinnervation is considered unpredictable, disordered, often incomplete and variable among patients, leading to aberrant reinnervation, which may cause multiple sinus rhythm disorders 17-20. A study led by Uberfuhr 20 in Germany found that about 60% of patients with orthotopic heart transplantation had some degree of sympathetic reinnervation.

Sinus node dysfunction

Sinus node dysfunction -defined as the absence of sinus rhythm, sinus node recovery time greater than 1.4 ms or secondary electrical pauses during electrophysiological examinations- is the most common cause of early implantation of pacemakers in transplant patients, that is, before 3 months after surgery 21-23. Depending on the series, a prevalence between 10% and 45% of early sinus dysfunction is reported, reaching implantation rates of up to 30% in this group of patients 12,24. Early sinus dysfunction is largely attributed to the surgical procedure, whether caused by trauma, node ischemia due to nodal artery injury, or prolonged ischemia times. Over the years, a decrease in the incidence of sinus node alterations has been reported, which has been attributed to the improvement of the surgical technique 25.

Deleuze et al. 13 compared the results of both surgical techniques in the postoperative period of 81 heart transplants, finding that the biauricular technique showed a higher prevalence of sinus node dysfunction, while patients treated with the bicaval technique did not require implantation of a pacemaker within the first 30 days, although 12.5% of them did 25. AV blocks and sinus dysfunction three months after the procedure are, to the same extent, the main indication of the implantation of a permanent pacemaker.

Recovery of sinus node function is common, particularly, when these changes occur rapidly after transplantation 21,26,27. Late sinus node dysfunction occurs three months after transplantation, and about 5% of patients require implantation of pacemakers for this reason according to a study published by Luebbert et al. 6, who did not find a higher prevalence related to any surgical technique, age, sex or pre-transplant diagnosis.

Rejection of the graft

About 20-30% of patients have experienced graft rejection during the first year after transplantation. This process is defined as the presence of inflammatory infiltrate in the transplanted tissue. Hence, taking endomyocardial biopsies is necessary for diagnosis and classification. Based on the results of the histological examination of the sample, it can be established whether there is any degree of cellular or humoral rejection according to the International Society for Heart and Lung Transplantation in 2004 28,29. Despite the efforts and good results that relate findings by magnetic resonance to graft rejection cases, the gold standard is still histological study 30. Some series claim that the presence of acute graft rejection is closely related to the onset of cardiac arrhythmias, especially with flutter and atrial fibrillation, but this remains a controversial issue. Ahmari et al. 31 from the Mayo Clinic state that the recurrence of moderate to severe acute rejections results in cardiac fibrosis that compromises diastolic function and predisposes the development of atrial flutter, and that these markers imply poor prognosis in the long term. Thus, the next step should be to rule out acute rejection of the graft to detect de novo alterations 17,32.

Chronic graft rejection in heart transplantation refers to cardiac graft vasculopathy (CGV). Although this process was initially understood as an immune-mediated process, today it is now known as a multifactorial process that includes alloimmune, autoimmune and non-immune mediated responses 24.

The progression of intraluminal changes, which ends in the occlusion of the coronary macrovasculature and microvasculature flow, begins as a lesion and apoptosis process in the endothelial parenchyma that leads to the concentric proliferation of the smooth muscle and to the failure of the cardiac graft, creating a terrain for the onset of both atrial and ventricular arrhythmias 24.

The development of CGV is the most predisposing factor to myocardial tissue ischemia and fibrous tissue formation, and the one that affects survival the most; thus, it is the main cause of death at 3 years after transplantation, together with malignant processes 30. At 5 years, 30% of transplant patients suffer CGV 24,33, and multiple episodes of acute rejection are considered as a risk factor for its development. The gold standard for this pathology is coronary angiography, which is why it is performed routinely in these patients.

Biopsies

Biopsies are routinely performed, and in cases when the medical team deems them necessary to rule out acute rejection of the graft. This procedure is usually performed under local anesthesia, has a mortality rate of 0.4% 29, and is considered the gold standard for detecting rejection 34.

Despite being relatively safe, the main complications of biopsy are ventricular perforation and cardiac tamponade, atrial or ventricular arrhythmias, pneumothorax, tricuspid insufficiency, ventricular coronary fistula, transient cardiac arrest, carotid artery puncture, infection and venous hematoma 29,35.

For this type of procedure, the transjugular route is the first option for access, whereas the femoral vein route is used in case of difficulty with jugular access or if coronary angiography is performed during the procedure.

There is no consensus as to how often routine biopsies should be taken. The Colombian cardiac transplant guidelines of 2009 suggest that 11 biopsies should be taken during the first year 29, while the international guidelines for cardiac transplantation and lung cancer of 2010 propose 18 biopsies during the same period of time 36. Nguyen et al. 37 recommend a maximum of 31 endomyocardial biopsies, since they demonstrated that exceeding this number of repetitions increases the risk of severe tricuspid insufficiency.

Over time, progress in immunosuppressive treatment has decreased rejection rates, which would explain the decrease in the frequency of this diagnostic procedure. However, further studies are needed to establish a global consensus in this regard, since acute rejection is usually a subclinical process with severe long-term repercussions.

During the procedure, ventricular arrhythmias are common, but they are usually temporary and transient. In the long term, third degree atrioventricular (AV) blocks have been associated 27 because of the frequency of this procedure, although this is not widely described in the literature and is considered an uncommon event.

Magnetic resonance imaging is suggested to replace endomyocardial biopsies, obtaining promising results in preliminary studies 38,39.

Infections

Immunosuppressive therapy opens the door to a large number of microorganisms that the immune system could control if it functions properly. According to the type of therapy and the postoperative time, the etiological agents of greater incidence vary 29. About 12% of deaths after transplantation within the first month are associated with infections by nosocomial bacterial microorganisms in different sites. Between the second and sixth month, infectious pathologies are usually caused by opportunistic infections and the reactivation of latent infections. Finally, microorganisms acquired in the community are the most frequent after the sixth month 29,40.

Estimations indicate that about 1.5% of cardiac transplant patients are infected with infectious endocarditis (IE), mostly by Staphylococcus aureus and Aspergillus fumigatus. Risk factors include the use of central catheters in the perioperative period and frequent endomyocardial biopsies 41.

Electrical conduction disorders are observed in 1% to 15% of IE patients, mostly manifested as AV blocks, branch blocks and atrial fibrillation. The presence of these alterations is associated with poor prognosis and higher mortality 42. Infections caused by agents such as cytomegalovirus and Chlamydia pneumoniae favor the development of CGV and, consequently, graft failure and cardiac arrhythmias caused by the mechanisms described above. C. pneumoniae infection is associated with greater severity of CGV 24.

Drugs

The average effect of amiodarone is prolonged, so it is possible to continue to observe its effects for several days in patients who took it before the transplantation. In patients who develop early sinus dysfunction, the effect of amiodarone may further compromise the electrical conduction of the transplanted organ 17.

Arrhythmia in the transplanted patient

Tachyarrhythmias

Supraventricular tachyarrhythmias

Supraventricular tachyarrhythmias have a high incidence in transplanted patients, greatly compromising their quality of life and survival. Dahu et al. 43 proposed five mechanisms involved in the development of atrial arrhythmias: 1) reentrant in the donor's atrium associated with the scar or the valve; 2) focal tachycardia in the donor's atrium; 3) atrial fibrillation in the donor's atrium; 4) re-entry arrhythmias that compromise two or more reconnections between donor and recipient atrium, and 5) arrhythmias originating in the recipient atrium that pass to the donor through one or more focal reconnections.

In turn, Vaseghi et al. 32 reviewed supraventricular tachycardia, and proposed another mechanism related to pre-existing alterations in the electrical conduction of the donor, which are manifested as AV nodal reentrant tachycardia and re-entry tachycardia associated with abnormal beam 32,44.

Supraventricular tachyarrhythmias can be classified as:

Atrial fibrillation, which is common in the early postoperative period and is almost always associated with graft manipulation, inflammatory period and autonomic changes. The incidence of atrial fibrillation decreases progressively, becoming exceptional during the late postoperative period in the absence of vasculopathy, rejection or infection 17,32,43,45. These low numbers are associated with the isolation of pulmonary veins, cava veins and the posterior wall of the atrium, which are the main foci of generation. This occurs because the surgical scar acts as an electrical insulator between recipient and donor atria remnants 46.

When atrial fibrillation is identified, the first step to take should be discarding the clinical cases previously mentioned as possible triggers. The control of these pathologies may be sufficient in most cases to stop their development. Antiarrhythmic drugs of choice are amiodarone and procainamide, which are not usually formulated for a long time because of the high resolution rate of this type of cardiac arrhythmia, which is associated with the management of its triggers. Controlling immunosuppression levels is necessary due to the interaction of amiodarone and warfarin with ciclosporin and tacrolimus 17. In case of persistence, catheter ablation is the treatment of choice for this disorder 17.

Atrial Flutter is the most common type of arrhythmia in patients after a heart transplant. In non-transplanted patients, the isthmus-dependent atrial flutter is formed by a counterclockwise circuit, which compromises the tricuspid valve, the Thebesian valve, the opening of the superior and inferior vena cava, and the crista terminalis. In transplanted patients, a similar circuit is formed, with the difference that the posterior line of the latter conforms the atrial suture line 47. This type of arrhythmia is more common in the biauricular technique 48.

Mitral annular flutter is less common and has no major incidence on a particular type of surgical technique. Just like atrial fibrillation, the development of flutter is also associated with periods of acute rejection, infection or vasculopathy, and their identification should stimulate the active search of these entities in the transplanted patient. When these causes are discarded and treated, as well as ventricular dysfunction and valvular pathology, catheter ablation is recommended to form an electrical block line between the tricuspid ring and the atrial suture for the right atrial-dependent flutter 48, whereas ablation of the anterior line of the circuit is recommended for the left atrium 49.

Focal atrial tachycardia is caused by the formation of depolarization foci near the atrial scar that take control of the heart rhythm. Scars, together with fibrosis, predispose to the formation of areas of slow electrical conduction, and provide the substrate for the production of macroreentrants and the development of focal atrial tachycardia. Elsik et al. 45 reported patients in whom the focus is found in the donor's atrium, while Vaseghi et al. 32 describe cases in which depolarization begins in the atrial remnant of the recipient and passes into the donor tissue through bridges formed by fibroblasts, which create gap-like junctions that allow electrical transmission. Definitive treatment is focal catheter ablation.

Atrial reentrant and nodal reentrant tachycardia require a preexisting route in the donor that allows a macroreentrant. Although they have been described in the literature, they are uncommon in transplanted patients. Radiofrequency ablation is curative 32.

Ventricular tachyarrhythmias

Ventricular extrasystoles and non-sustained ventricular tachycardia may be common in the early post-transplant period. The subsequent development of sustained and non-sustained ventricular tachycardia suggests an episode of acute rejection or graft vasculopathy 18, while taking into account other rare etiologies that may have similar clinical features and may be reversible, such as idiopathic fascicular ventricular tachycardia 50.

The most common arrest rhythm in cardiac denervation in sudden death events is asystole, followed by pulseless electrical activity; both are non-defibrillating rhythms, so the use of automatic implantable defibrillators remains controversial 17,51.

Bradyarrhythmias

Bradyarrhythmias may appear during the early or late period after a heart transplant, and can be caused by sinus node dysfunction or errors in the electrical conduction, with functional or dysfunctional sinus node.

In the early postoperative period, the transplanted heart usually requires positive chronotropic agents or temporary pacemaker implantation. It has been demonstrated that the donor's sinus node is hypersensitive to these pharmacological agents, so its use must be cautious 52.

Early sinus node dysfunction puts the patient's life at risk in the early postoperative days, and its multifactorial etiology is almost always associated with circumstances that depend on the surgical procedure 12,21,53,54. As for late sinus dysfunction, the role of graft rejection in its development is controversial.

Sinus dysfunction may be paroxysmal or persistent, and may be manifested as sinus bradycardia or as a total stop of the sinoatrial node 53,54. To control these entities, a therapeutic test can be performed with isoprenaline, dopamine, dobutamine or theophylline in search of increased heart rate and recovery of sinus rhythm. If this therapy fails, the use of pacemakers should be considered 21,55.

The 2011 Colombian guide to cardiovascular electrophysiology (56) provides the following recommendations for the implantation of a permanent pacemaker:

Class I: it is indicated in symptomatic, inappropriate, persistent or not-expected-to-improve bradycardia.

Class IIA: it is considered in symptomatic, recurrent and prolonged bradycardia that limits rehabilitation or discharge during the post-surgical recovery phase of the transplant (level of evidence C). Class IIB: it is considered in patients with syncope after cardiac transplantation although bradyarrhythmia has not been documented (level of evidence C).

Early implantation of a permanent pacemaker occurs when the heart rate has not been normalized with other interventions after three weeks 57. Early sinus dysfunction in the early postoperative period is usually not associated with damage to the electrical conduction system, so bicameral pacemakers with AAIR/DDDR function that seek physiological stimulation and preserve AV synchrony have been widely used in the last years. However, after one year of implantation, the frequency of activity of these devices decreases, in most cases due to the recovery of the sinus function 55,57,58.

In the late postoperative period, errors in the conduction of the nerve impulse are predominant, with AV blocks being the leading cause of implantation of cardiac pacemakers in this period. This phenomenon has been attributed to the development of graft rejection, since electrical conduction tissue has been proven as a typical target of humoral response during this process 52,56,59.

Conclusions

The development of arrhythmias is a frequent issue and, in some cases, puts the life of the patient at risk. This complication is related to multiple triggers. There are factors associated with the surgical procedure itself, such as ischemia times, sinus node injury, and excessive manipulation of the atria due to the surgical technique and cardiac denervation, as well as other mechanisms related to the preoperative and post-surgical periods, such as acute rejection episodes, reinnervation, ventricular biopsies, graft vasculopathy, systemic infections, and drug effects.

The most common arrhythmias are bradycardia, which, in a significant percentage, will require implantation of permanent pacemakers. The most frequent tachyarrhythmia is the isthmus-dependent flutter, which can be treated with catheter ablation. The most common rhythm of cardiac arrest in these patients is asystole, unlike the general population, where more defibrillatory rhythms such as tachycardia and ventricular fibrillation occur.

The detection of any cardiac arrhythmia should lead to think of the possibility that this is the manifestation of an underlying pathological process that puts at risk the viability of the organ and the life of the patient. The medical team is obliged manage this condition in a way that is not limited to symptomatic control and sinus rhythm, but to initiate an active search for its etiology to give optimal therapeutic management to each patient.

Acknowledgement

To Dr. Ana María Barón, cardiologist and cardiac transplant specialist, for her support during the development of this article.

References

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Figueroa-Bohórquez DM, Benavides X, Garzón L, Espinel D, Suarez L, Uribe M, et al. Electrocardiographic alterations associated with heart transplantation. Triggers, mechanisms and meaning. Rev. Fac. Med. 2017;65(3):483-9. English. doi: http://dx.doi.org/10.15446/revfacmed.v65n3.57498.
Figueroa-Bohórquez DM, Benavides X, Garzón L, Espinel D, Suarez L, Uribe M, et al. [Alteraciones electrocardiográficas en el paciente con trasplante cardíaco. Desencadenantes, mecanismos y su significado]. Rev. Fac. Med. 2017;65(3):483-9. English. doi: http://dx.doi.org/10.15446/revfacmed.v65n3.57498.
None stated by the authors.

Referencias

Castañeda-Millán D, Alarcón F, Ovalle D, Martínez C, González L, Burbano-Perea L, et al. Actitudes y creencias sobre la donación de órganos en Colombia: ¿Dónde se deben enfocar los esfuerzos para mejorar las tasas nacionales de donación? Rev. Fac. Med. 2014;62(1):17-25.

Ceruti B, Chiesa P, Tambasco J, Anzíbar R, Gutiérrez C, Barboza S, et al. Trasplante cardíaco. Experiencia de 15 años del Instituto de Cardiología Infantil. Rev Urug Cardiol. 2012;27(3):273-85.

Sekar B, Critchley W, Williams SG, Shaw SM. Should we consider heart rate reduction in cardiac transplant recipients? Clin Cardiol. 2013;36(2):68-73. http://doi.org/b47c.

Almenar L, Segovia J, Crespo-Leiro MG, Palomo J, Arizón JM, González-Vílchez F, et al. Registro Español de Trasplante Cardíaco. XXIII Informe Oficial de la Sección de Insuficiencia Cardíaca y Trasplante Cardíaco de la Sociedad Española de Cardiología (1984-2011). Rev Esp Cardiol. 2012;65(11):1030-8. http://doi.org/f2fsfg.

Tonsho M, Michel S, Ahmed Z, Alessandrini A, Madsen JC. Heart transplantation: challenges facing the field. Cold Spring Harb Perspect Med. 2014;4:(5). http://doi.org/b47d.

Luebbert JJ, Lee FA, Rosenfeld LE. Pacemaker Therapy for Early and Late Sinus Node Dysfunction in Orthotopic Heart Transplant Recipients: A Single-Center Experience. Pacing Clin Electrophysiol. 2008;31(9):1108-12. http://doi.org/djbk26.

Jacob S, Sellke F. Is bicaval orthotopic heart transplantation superior to the biatrial technique? Interact Cardiovasc Thorac Surg. 2009;9(2):333-42. http://doi.org/cz9bhf.

Locali RF, Matsuoka PK, Cherbo T, Gabriel EA, Buffolo E. Should biatrial heart transplantation still be performed?: A Meta-analysis. Arq Bras Cardiol. 2010;94(6):829-40. http://doi.org/bsx4p9.

Dell’Aquila AM, Mastrobuoni S, Bastarrika G, Praschker BL, Agüero PA, Castaño S, et al. Bicaval versus standard technique in orthotopic heart transplant: assessment of atrial performance at magnetic resonance and transthoracic echocardiography. Interact Cardiovasc Thorac Surg. 2012;14(4):457-62. http://doi.org/fzmjp7.

Markowicz-Pawlus E, Duszańska A, Przybylski R, Szulik M, Streb W, Zembala M, et al. Does the method of heart transplantation affect left ventricular filling? Kardiol Pol. 2012;70(8):769-73.

Davies RR, Russo MJ, Morgan JA, Sorabella RA, Naka Y, Chen JM. Standard versus bicaval techniques for orthotopic heart transplantation: an analysis of the United Network for Organ Sharing database. J Thorac Cardiovasc Surg. 2010;140(3):700-8. http://doi.org/ddsrpd.

Czer LS, Cohen MH, Gallagher SP, Czer LA, Soukiasian HJ, Rafiei M, et al. Exercise performance comparison of bicaval and biatrial orthotopic heart transplant recipients. Transplant Proc. 2011;43(10):3857-62. http://doi.org/dqd2vk.

Deleuze PH, Benvenuti C, Mazzucotelli JP, Perdrix C, Le Besnerais P, Mourtada A, et al. Orthotopic cardiac transplantation with direct caval anastomosis: Is it the optimal procedure? J Thorac Cardiovasc Surg. 1995;109(4):731-37. http://doi.org/fjm6g4.

Meyer SR, Modry DL, Bainey K, Koshal A, Mullen JC, Rebeyka IM, et al. Declining need for permanent pacemaker insertion with the bicaval technique of orthotopic heart transplantation. Can J Cardiol. 2005;21(2):159-63.

Estorch-Cabrera M, Flotats-Giralt A, Campreciós-Crespo M, Marí-Aparici C, Bernà-Roqueta L, Catafau-Alcántara AM, et al. Reinervación simpática del corazón trasplantado. Estudio realizado con metayodobenzilguanidina marcada con yodo-123. Rev Esp Cardiol. 1998;51(5):369-74. http://doi.org/b47g.

Kobirumaki-Shimozawa F, Inoue T, Shintani SA, Oyama K, Terui T, Minamisawa S, et al. Cardiac thin filament regulation and the Frank-Starling mechanism. J Physiol Sci. 2014;64(4):221-32. http://doi.org/f58ccd.

Thajudeen A, Stecker EC, Shehata M, Patel J, Wang X, McAnulty JH Rr, et al. Arrhythmias After Heart Transplantation: Mechanisms and Management. J Am Heart Assoc. 2012;1(2):e001461. http://doi.org/b47j.

Sanatani S, Chiu C, Nykanen D, Coles J, West L, Hamilton R. Evolution of Heart Rate Control After Transplantation: Conduction Versus Autonomic Innervation. Pediatr Cardiol. 2004;25(2):113-8. http://doi.org/bjz6tf.

Buendía-Fuentes F, Martínez-Dolz L, Almenar Bonet L, Sánchez-Lázaro I, Navarro Manchón J, Sánchez-Gómez JM, et al. Normalization of the heart rate response to exercise 6 months after cardiac transplantation. Transplant Proc. 2010;42(8):3186-88. http://doi.org/ccqz25.

Uberfuhr P, Frey AW, Ziegler S, Reichart B, Schwaiger M. Sympathetic reinnervation of sinus node and left ventricle after heart transplantation in humans: regional differences assessed by heart rate variability and positron emission tomography. J Heart Lung Transplant. 2000;19(4):317-23. http://doi.org/c79mh9.

Bacal F, Bocchi EA, Vieira ML, Lopes N, Moreira LF, Fiorelli A, et al. Permanent and temporary pacemaker implantation after orthotopic heart transplantation. Arq Bras Cardiol. 2000;74(1):5-12. http://doi.org/bbdnhg.

Jacquet L, Ziady G, Stein K, Griffith B, Armitage J, Hardesty R, et al. Cardiac rhythim disturbances early after orthotopic heart transplantation: prevalence and clinical importance of the observed abnormalities. J Am Coll Cardiol. 1990;16(4):832-7. http://doi.org/d2c6f4.

Markewitz A, Kemkes BM, Reble B, Osterholzer G, Reichart B, Puricelii C, et al. Particularities of dual chamber pacemaker therapy in patients after orthotopic heart transplantation. Pacing Clin Electrophysiol. 1987;10(2):326-32. http://doi.org/bzhb3m.

Costello JP, Mohanakumar T, Nath DS. Mechanisms of chronic cardiac allograft rejection. Tex Heart Inst J. 2013;40(4):395-9.

Heinz G, Kratochwill C, Schmid S, Kreiner G, Siostrzonek P, Pacher R, et al. Sinus node dysfunction after orthotopic heart transplantation: the Vienna experience 1987-1993. Pacing Clin Electrophysiol. 1994;17(11 pt 2):2057-63. http://doi.org/fg8r58.

Heinz G, Kratochwill C, Koller-Strametz J, Kreiner G, Grimm M, Grabenwöger M, et al. Benign prognosis of early sinus node dysfunction after orthotopic cardiac transplantation. Pacing Clin Electrophysiol. 1998;21(2):422-9. http://doi.org/bhjtzg.

Stecker EC, Strelich KR, Chugh SS, Crispell K, McAnulty JH. Arrhythmias After Orthotopic Heart Transplantation. J Card Fail. 2005;11(6):464-72. http://doi.org/fjfnnf.

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Cómo citar

APA

Figueroa-Bohórquez, D. M., Benavides, X., Garzón, L., Espinel, D., Suarez, L., Uribe, M., Gómez-Aristizabal, L. y Lozano Márquez, E. (2017). Electrocardiographic alterations associated with heart transplantation. Triggers, mechanisms and meaning. Revista de la Facultad de Medicina, 65(3), 483–489. https://doi.org/10.15446/revfacmed.v65n3.57498

ACM

[1]
Figueroa-Bohórquez, D.M., Benavides, X., Garzón, L., Espinel, D., Suarez, L., Uribe, M., Gómez-Aristizabal, L. y Lozano Márquez, E. 2017. Electrocardiographic alterations associated with heart transplantation. Triggers, mechanisms and meaning. Revista de la Facultad de Medicina. 65, 3 (jul. 2017), 483–489. DOI:https://doi.org/10.15446/revfacmed.v65n3.57498.

ACS

(1)
Figueroa-Bohórquez, D. M.; Benavides, X.; Garzón, L.; Espinel, D.; Suarez, L.; Uribe, M.; Gómez-Aristizabal, L.; Lozano Márquez, E. Electrocardiographic alterations associated with heart transplantation. Triggers, mechanisms and meaning. Rev. Fac. Med. 2017, 65, 483-489.

ABNT

FIGUEROA-BOHÓRQUEZ, D. M.; BENAVIDES, X.; GARZÓN, L.; ESPINEL, D.; SUAREZ, L.; URIBE, M.; GÓMEZ-ARISTIZABAL, L.; LOZANO MÁRQUEZ, E. Electrocardiographic alterations associated with heart transplantation. Triggers, mechanisms and meaning. Revista de la Facultad de Medicina, [S. l.], v. 65, n. 3, p. 483–489, 2017. DOI: 10.15446/revfacmed.v65n3.57498. Disponível em: https://revistas.unal.edu.co/index.php/revfacmed/article/view/57498. Acesso em: 29 mar. 2024.

Chicago

Figueroa-Bohórquez, David Mauricio, Xiomara Benavides, Luz Garzón, Daniel Espinel, Luis Suarez, María Uribe, Linda Gómez-Aristizabal, y Eyner Lozano Márquez. 2017. «Electrocardiographic alterations associated with heart transplantation. Triggers, mechanisms and meaning». Revista De La Facultad De Medicina 65 (3):483-89. https://doi.org/10.15446/revfacmed.v65n3.57498.

Harvard

Figueroa-Bohórquez, D. M., Benavides, X., Garzón, L., Espinel, D., Suarez, L., Uribe, M., Gómez-Aristizabal, L. y Lozano Márquez, E. (2017) «Electrocardiographic alterations associated with heart transplantation. Triggers, mechanisms and meaning», Revista de la Facultad de Medicina, 65(3), pp. 483–489. doi: 10.15446/revfacmed.v65n3.57498.

IEEE

[1]
D. M. Figueroa-Bohórquez, «Electrocardiographic alterations associated with heart transplantation. Triggers, mechanisms and meaning», Rev. Fac. Med., vol. 65, n.º 3, pp. 483–489, jul. 2017.

MLA

Figueroa-Bohórquez, D. M., X. Benavides, L. Garzón, D. Espinel, L. Suarez, M. Uribe, L. Gómez-Aristizabal, y E. Lozano Márquez. «Electrocardiographic alterations associated with heart transplantation. Triggers, mechanisms and meaning». Revista de la Facultad de Medicina, vol. 65, n.º 3, julio de 2017, pp. 483-9, doi:10.15446/revfacmed.v65n3.57498.

Turabian

Figueroa-Bohórquez, David Mauricio, Xiomara Benavides, Luz Garzón, Daniel Espinel, Luis Suarez, María Uribe, Linda Gómez-Aristizabal, y Eyner Lozano Márquez. «Electrocardiographic alterations associated with heart transplantation. Triggers, mechanisms and meaning». Revista de la Facultad de Medicina 65, no. 3 (julio 1, 2017): 483–489. Accedido marzo 29, 2024. https://revistas.unal.edu.co/index.php/revfacmed/article/view/57498.

Vancouver

1.
Figueroa-Bohórquez DM, Benavides X, Garzón L, Espinel D, Suarez L, Uribe M, Gómez-Aristizabal L, Lozano Márquez E. Electrocardiographic alterations associated with heart transplantation. Triggers, mechanisms and meaning. Rev. Fac. Med. [Internet]. 1 de julio de 2017 [citado 29 de marzo de 2024];65(3):483-9. Disponible en: https://revistas.unal.edu.co/index.php/revfacmed/article/view/57498

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1. Juan Felipe Rivillas-Reyes, Erwin Felipe Hernández-Durán, Jessica Liliana Morales-Manrique, Maria Paula Rivillas, Eyner Lozano-Marquez, Harvey Lozano-Marquez. (2020). Inducción de tolerancia por vía oral en trasplante de órganos y tejidos. Revisión de la Literatura. Revista de la Facultad de Medicina, 68(1) https://doi.org/10.15446/revfacmed.v68n1.72108.

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