Permanent Pacemaker for Rejection Episodes After Heart ...

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Heart Transplantation: A Poor Prognostic Sign ... late after heart transplantation has been associated with ..... Heart Lung Transplant 1993;12:956-64. 3. Blanche ...
Permanent Pacemaker for Rejection Episodes After Heart Transplantation: A Poor Prognostic Sign Carlos Blanche, MD, Lawrence S. C. Czer, MD, Michael C. Fishbein, MD, Johanna J. M. Takkenberg, MD, and Alfredo Trento, MD Department of Cardiothoracic Surgery, Cedars-Sinai Medical Center, Los Angeles, California

Background. The development of arrhythmias early or late after heart transplantation has been associated with acute and chronic rejection. This study aims to document the importance of this relationship and its value as a prognostic sign in those patients who required a permanent pacemaker for rejection episodes. Methods. A retrospective analysis of 158 orthotopic heart transplantations performed in 157 patients between December 1988 and April 1995 was done. The clinical course and the outcome of 6 patients who underwent insertion of a permanent pacemaker for bradyarrhythmias caused by acute or chronic allograft rejection were compared with the course and outcome of 9 patients who had pacemaker placement as a result of sinus node dysfunction not associated with rejection. Results. The mortality rate was 100% for patients

he occurrence of severe bradyarrhythmias early or T late in the posttransplantation period has previously been considered a marker of acute or chronic rejection [1-4]. Although the predictors of permanent pacing after heart transplantation are multiple, the presence of a rejection episode has been implicated as a major factor [5]. However, the prognostic importance of this relationship is uncertain. To explore the association between acute or chronic rejection and the need of permanent pacing after transplantation, we retrospectively reviewed our experience with heart transplant patients who required a permanent pacemaker. In particular, we analyzed the cases of patients whose indication for permanent pacing was an episode of acute cellular or humoral rejection or accelerated allograft atherosclerosis (chronic rejection). This analysis focused on the importance of this relationship and its value as a prognostic sign.

Material and Methods Between December 1988 and April 1995, 158 orthotopic heart transplantations were performed in 157 patients at Cedars-Sinai Medical Center. The first 64 consecutive patients underwent transplantation with the standard operative technique as originally described by S h u m w a y Accepted for publication June 12, 1995. Address reprint requests to Dr Blanche, Heart Transplantation Program, Cedars-Sinai Medical Center, 8700BeverlyBlvd, Suite 6215,Los Angeles, CA 90048. © 1995 by The Society of Thoracic Surgeons

whose indication for permanent pacing was severe acute or chronic rejection. Conversely, 8 of the 9 patients who underwent pacemaker placement for sinus node dysfunction not associated with rejection are long-term survivors; the one late death was due to a noncardiac cause. Conclusions. We observed a strong relationship between bradyarrhythmias requiring a permanent pacemaker and severe acute or chronic allograft rejection. This association suggests a poor prognosis and indicates that these patients should be managed aggressively. Such management includes close immunologic surveillance for cellular and humoral rejection, increased frequency of endomyocardial biopsies and coronary angiography, and early consideration for retransplantation.

(Ann Thorac Surg 1995;60:1263-6)

and colleagues [6]. The subsequent patients had transplantation with an alternative technique previously described [7]. I m m u n o s u p p r e s s i o n consisted of OKT3 induction therapy (5 m g / d for 14 days in the first 112 patients and for 7 days in the last 45 patients) with concomitant administration of cyclosporine (5 m g • kg 1 . d ~ for a level of 120 to 200 ng/mL by fluorescence polarization immunoassay started postoperatively once the serum creatinine level was < 2.0 mg/dL), azathioprine (4 mg/kg preoperatively and 2 m g . k g 1. d 1 postoperatively), and steroids (methylprednisolone sodium succinate [Solu-Medrol], 1 g intraoperatively at removal of the aortic cross-clamp and then 125/xg intravenously every 8 hours for three doses postoperatively, followed by prednisone, 0.25 m g - k g 1. d 1 during OKT3 therapy, increased to 0.5 m g ' k g 1 . d ~, and then tapered in the subsequent 3 to 8 months). Permanent pacemakers were implanted in 15 patients, all of w h o m had transplantation by the standard technique [6]. The indications for permanent pacing were symptomatic bradyarrhythmias (rate 8 seconds) with slow junctional escape rhythm, which necessitated insertion of a permanent DDD pacemaker. The endomyocardial biopsy specimen showed severe acute cellular rejection, and pulsed steroid therapy was instituted. Soon thereafter, the patient experienced multiple intractable ventricular arrhythmias and died. Postmortem examination confirmed severe acute rejection with marked involvement of the conduction system (Fig 1).

A 42-year-old woman underwent heart transplantation for end-stage ischemic heart disease. The postoperative course was complicated by recurrent episodes of cytomegalovirus infection as well as multiple episodes of severe cellular and humoral rejection. Sudden symptomatic bradycardia (