Multiple recurrent episodes of pacemaker-associated postcardiac injury syndrome

Postcardiac injury syndrome (PCIS) is an autoimmune disease that causes damage to the pericardium, myocardium, and pleura after myocardial infarction, cardiac surgery, or trauma. Although most cases are benign, anti-inflammatory agents may be used to treat PCIS. Rarely, PCIS may become refractory or recur after anti-inflammatory treatment. 1Lee Y.J. et al.Pacemaker-Associated Post-cardiac Injury Syndrome Presenting with Tamponade and Recurrent Pleural Effusion.Clin Med Insights Case Rep. 2020; 131179547620965559https://doi.org/10.1177/1179547620965559Crossref Scopus (0) Google Scholar In such cases, long-term oral corticosteroids are usually prescribed2Cevik C. Wilborn T. Corona R. Schanzmeyer E. Nugent K. Post-cardiac injury syndrome following transvenous pacemaker insertion: A case report and review of the literature.Heart Lung Circ. 2009; 18: 379-383https://doi.org/10.1016/j.hlc.2009.04.001Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar; however, the optimal duration of administration remains unclear. We report a patient who experienced multiple recurrent episodes of pacemaker lead-related PCIS that were treated with oral prednisone and pericardial drainage. A 70-year-old woman with complete atrioventricular block underwent dual chamber pacemaker implantation. She had no history of autoimmune disease, systemic inflammatory disease, or metal allergy. Six months after implantation, she presented with dyspnea, edema, and pericardial effusion that improved with administration of ibuprofen and colchicine for one month. A recurrent pericardial effusion appeared on echocardiography 18 months later. A pleural effusion was also noted and serum liver transaminase concentrations were mildly elevated (aspartate aminotransferase, 39 IU/L; alanine aminotransferase, 31 IU/L; B-type natriuretic peptide, 129.5 pg/mL). Diuretics failed to reduce the size of the pericardial effusion; therefore, pericardiocentesis was performed and 200 mL of bloody fluid was drained. Fluid cultures were negative and no malignant cells were detected. Because pacemaker lead perforation of the right ventricle (RV) was suspected, the patient was transferred to our hospital for further management. Device interrogation showed normal pacemaker function. Sensing and pacing thresholds were optimal. Right ventriculography showed no leakage into the pericardial space (Supplemental video). On computed tomography, the tip of the RV screw-in pacing lead was protruding into the pericardial cavity and the pericardial fluid density was 35 to 40 Hounsfield units. Therefore, hemorrhagic pericardial effusion was suspected. Transvenous lead extraction was performed under thoracotomy ready to operative repair in case of cardiac perforation. The opened pericardial space showed a remarkably thick epicardium (Figure 1A). No bleeding around the heart was visualized. The fluid in the pericardial sac was exudative (red blood cells, 76 × 104/μL; pericardial fluid/serum protein ratio, 0.75; lactate dehydrogenase, 230 U/L) and contained clots. These findings suggested that the effusion was caused by hemorrhagic pericarditis, presumably triggered by the lead tip. Microscopic examination of hematoxylin–eosin-stained slides of the resected pericardium showed pericardial fibrous thickening, infiltration of inflammatory cells, hemosiderin deposition, and microvascular growth (Figure 1B). A diagnosis of PCIS was rendered. All leads were completely removed and a pericardial window was created to drain the pericardial effusion into the pleural cavity. Device interrogation showed that the RV pacing percentage was <1% before the operation. Atrioventricular block was not observed on electrocardiography during the patient’s hospitalization. An electrophysiological study showed no conduction system abnormalities (Wenckebach rate, 200 bpm [baseline]; 130 bpm [procainamide administration]; atrial-His bundle interval, 102 ms; His-ventricular interval: 21 ms). Therefore, she was discharged without pacemaker implantation to prevent PCIS recurrence. One month later, she presented to the emergency department because of faintness and shortness of breath with exertion. Electrocardiography showed complete atrioventricular block (heart rate, 35 bpm). Dual chamber pacemaker implantation was then performed. An RV lead was implanted in the RV septum to avoid cardiac perforation in the apex or free wall of the RV. Left bundle branch pacing was achieved (Supplemental figure). Two months after lead extraction, a pleural effusion owing to the pericardial window was diagnosed. Diuretics were ineffective and repeated thoracentesis was required. Recurrent PCIS was suspected. Ibuprofen (900 mg/day for 5 days, tapered over 7 months) and colchicine (0.5 mg/day for 15 months) were initiated; nonetheless, the pleural effusion continued to accumulate. Oral prednisone (0.5 mg/kg/day) was then initiated. Triple therapy with ibuprofen, colchicine, and prednisone was carefully tapered over 20 months and prednisone was eventually discontinued. Although a small pleural effusion has recurred (Figure 2), no relapses have occurred in the 2 years since cessation of prednisone. Post-pacemaker implantation pericarditis is a rare form of PCIS. Reported incidence rates of pericarditis associated with an active fixation lead without frank perforation range from 0.6% to 5% 3Ellenbogen K.A. Wood M.A. Shepard R.K. Delayed complications following pacemaker implantation.Pacing Clin Electrophysiol. 2002; 25: 1155-1158https://doi.org/10.1046/j.1460-9592.2002.01155.xCrossref PubMed Scopus (113) Google Scholar. Although the underlying mechanism is not well understood, an immune-mediated inflammatory response to initial cardiac injury triggered by a pacemaker lead has been hypothesized 2Cevik C. Wilborn T. Corona R. Schanzmeyer E. Nugent K. Post-cardiac injury syndrome following transvenous pacemaker insertion: A case report and review of the literature.Heart Lung Circ. 2009; 18: 379-383https://doi.org/10.1016/j.hlc.2009.04.001Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar. Post-pacemaker implantation pericarditis typically presents with symptoms 1 to 6 weeks after the initial pericardial damage 4Patel Z.K. Shah M.S. Bharucha R. Benz M. Post-cardiac Injury Syndrome Following Permanent Dual-Chamber Pacemaker Implantation.Cureus. 2022; 14e21737https://doi.org/10.7759/cureus.21737Crossref Google Scholar. Advanced age, female sex, and use of active fixation leads are independent risk factors for developing post-pacemaker insertion pericarditis 5Ohlow M.A. Lauer B. Brunelli M. Geller J.C. Incidence and predictors of pericardial effusion after permanent heart rhythm device implantation: prospective evaluation of 968 consecutive patients.Circ J. 2013; 77: 975-981https://doi.org/10.1253/circj.cj-12-0707Crossref PubMed Scopus (0) Google Scholar. In our patient, the initial episode of pericarditis was thought to be triggered by lead tip stimulation of the pericardium before it was extracted. This resulted in sustained inflammation and blood pooling within the pericardial cavity. The pericardial thickening observed on histological examination reinforces the hypothesis that the pericardial inflammation was sustained for a long period after lead extraction. However, PCIS recurrence after lead removal might also have been related to the pericardial window procedure. Regardless, PCIS caused by minimally invasive procedures such as cardiac catheterization and pericardial fenestration generally has a good prognosis; repeated recurrences on steroid therapy are rare. Recurrent pericarditis occurs in up to 50% of cases of acute pericarditis. Moreover, it can occur during the clinical course of PCIS 6Imazio M. Hoit B.D. Post-cardiac injury syndromes. An emerging cause of pericardial diseases.Int J Cardiol. 2013; 168: 648-652https://doi.org/10.1016/j.ijcard.2012.09.052Abstract Full Text Full Text PDF PubMed Scopus (151) Google Scholar. Although the short-term course of PCIS is usually benign, constrictive pericarditis may develop in up to 5% of patients during long-term follow-up 7 8. Post-pericardiotomy syndrome after cardiac surgery is the most common cause of PCIS (20% to 30% of cases). Because microperforation after percutaneous coronary intervention is a less common cause (<1% to 5% of cases), the clinical outcomes and rate of recurrence associated with PCIS caused by microperforation has not been clarified. However, prompt treatment of the initial pericarditis episode and any recurrence might shorten the disease course and reduce the incidence of subsequent recurrences 7Imazio M. Lazaros G. Brucato A. Gaita F. Recurrent pericarditis: new and emerging therapeutic options.Nature Reviews Cardiology. 2016; 13: 99-105https://doi.org/10.1038/nrcardio.2015.115Crossref PubMed Scopus (51) Google Scholar. Early diagnosis of pacemaker-induced PCIS is important because most patients respond well to non-steroidal anti-inflammatory drugs, colchicine, and/or steroids 9Sedaghat-Hamedani F. et al.Post cardiac injury syndrome after initially uncomplicated CRT-D implantation: a case report and a systematic review.Clin Res Cardiol. 2014; 103: 781-789https://doi.org/10.1007/s00392-014-0716-0Crossref PubMed Scopus (16) Google Scholar. Other common etiologies of pericardial effusion including infection, autoimmune disease, and malignancy should be excluded before diagnosing PCIS. Overt or microscopic lead perforation should also be considered. PCIS may be difficult to distinguish, even when appropriate imaging studies and device interrogation have been performed. If pericardial hemorrhage is clear, open surgical extraction of the lead is required, as demonstrated by our case. Patients with pacemaker-related recurrent PCIS may require long-term treatment with high-dose anti-inflammatory medications. However, the optimal management strategy remains unclear. Our patient was treated with non-steroidal anti-inflammatory agents, pericardiocentesis, prednisone, pacemaker lead removal, and a pericardial window. To the best of our knowledge, this is the first report of multiple recurrent episodes of pacemaker-induced PCIS during steroid therapy. Funding sources: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.