Relation of Prolonged Pacemaker Dependency After Cardiac Surgery to Mortality
2020; Elsevier BV; Volume: 138; Linguagem: Inglês
10.1016/j.amjcard.2020.10.010
ISSN1879-1913
AutoresRoberto Lorusso, Justine M. Ravaux, Fabio Barili, Elham Bidar, Kevin Vernooy, Michele Di Mauro, Antonio Miceli, Alessandro Parolari, Andrea Daprati, Veronika A. Myasoedova, Francesco Alamanni, Carlo De Vincentiis, Ezio Aimè, Francesco Nicolini, Gianluca Gonzi, Andrea Colli, Gino Gerosa, Michele De Bonis, Gabriele Paglino, Paolo Della Bella, Guglielmo Mario Actis Dato, Egidio Varone, Sandro Sponga, Mauro Toniolo, Alessandro Proclemer, Ugolino Livi, Giovanni Mariscalco, Marzia Cottini, Cesare Beghi, Roberto Scrofani, Davide Foresti, Francesco Paolo Tritto, Rosario Gregorio, Emmanuel Villa, Giovanni Troise, Domenico Pecora, Giuseppe Filiberto Serraino, Federica Jiritano, Francesco Rosato, Elena Grasso, Domenico Paparella, Lillà Amorese, Enrico Vizzardi, Marco Solinas, Giuseppe Arena, Daniele Maselli, Caterina Simon, Mattia Glauber, Maurizio Merlo,
Tópico(s)Cardiac Valve Diseases and Treatments
Resumo•In a retrospective multicenter study, around 1% of the patients require PPI after cardiac surgery.•More than 30% of these patients recover A/V conduction property within months.•Pacemaker dependency is associated with higher mortality.•SR before surgery seems to have a protective effect on pacemaker dependency. Permanent pacemaker implantation (PPI) represents a rare complication after cardiac surgery, with no uniform agreement on timing and no information on follow-up. A multicenter retrospective study was designed to assess pacemaker dependency (PMD) and long-term mortality after cardiac surgery procedures. Between 2004 and 2016, PPI-patients from 18 centers were followed. Time-to-event data were evaluated with semiparametric regression Cox models and semiparametric Fine and Gray model for competing risk framework. Of 859 (0.90%) PPI-patients, 30% were pacemaker independent (PMI) at 6 months. PMD showed higher mortality compared with PMI (10-year survival 80.1% ± 2.6% and 92.2% +2.4%, respectively, log-rank p-value < 0.001) with an unadjusted hazard ratio for death of 0.36 (95% CI 0.20 to 0.65, p< 0.001 favoring PMI) and an adjusted hazard ratio of 0.19 (95% CI 0.08 to 0.45, p< 0.001 with PMD as reference). Crude cumulative incidence function of restored PMI rhythm at follow-up at 6 months, 1 year and 12 years were 30.5% (95% CI 27.3% to 33.7%), 33.7% (95% CI 30.4% to 36.9%) and 37.2% (95% CI 33.8% to 40.6%) respectively. PMI was favored by preoperative sinus rhythm with normal conduction (SR) (HR 2.37, 95% CI 1.65 to 3.40, p< 0.001), whereas coronary artery bypass grafting and aortic valve replacement were independently associated with PMD (HR 0.63, 95% CI 0.45 to 0.88, p = 0.006 and HR 0.807, 95% CI 0.65 to 0.99, p = 0.047 respectively). Time-to-implantation was not associated with increased rate of PMI. Although 30% of PPI-patients are PMI after 6 months, PMD is associated with higher mortality at long term. Permanent pacemaker implantation (PPI) represents a rare complication after cardiac surgery, with no uniform agreement on timing and no information on follow-up. A multicenter retrospective study was designed to assess pacemaker dependency (PMD) and long-term mortality after cardiac surgery procedures. Between 2004 and 2016, PPI-patients from 18 centers were followed. Time-to-event data were evaluated with semiparametric regression Cox models and semiparametric Fine and Gray model for competing risk framework. Of 859 (0.90%) PPI-patients, 30% were pacemaker independent (PMI) at 6 months. PMD showed higher mortality compared with PMI (10-year survival 80.1% ± 2.6% and 92.2% +2.4%, respectively, log-rank p-value < 0.001) with an unadjusted hazard ratio for death of 0.36 (95% CI 0.20 to 0.65, p< 0.001 favoring PMI) and an adjusted hazard ratio of 0.19 (95% CI 0.08 to 0.45, p< 0.001 with PMD as reference). Crude cumulative incidence function of restored PMI rhythm at follow-up at 6 months, 1 year and 12 years were 30.5% (95% CI 27.3% to 33.7%), 33.7% (95% CI 30.4% to 36.9%) and 37.2% (95% CI 33.8% to 40.6%) respectively. PMI was favored by preoperative sinus rhythm with normal conduction (SR) (HR 2.37, 95% CI 1.65 to 3.40, p< 0.001), whereas coronary artery bypass grafting and aortic valve replacement were independently associated with PMD (HR 0.63, 95% CI 0.45 to 0.88, p = 0.006 and HR 0.807, 95% CI 0.65 to 0.99, p = 0.047 respectively). Time-to-implantation was not associated with increased rate of PMI. Although 30% of PPI-patients are PMI after 6 months, PMD is associated with higher mortality at long term. Permanent pacemaker implantation (PPI) after cardiac surgery for brady-arrhythmia's and/or atrio-ventricular (A/V) conduction defects occurs in up to 1%to 3% of patients after coronary artery bypass graft (CABG), 5% after mitral valve replacement (MVR), and reportedly up to 12% after aortic valve replacement (AVR).1Matthews IG Fazal IA Bates MG Turley AJ In patients undergoing aortic valve replacement, what factors predict the requirement for permanent pacemaker implantation?.Interact Cardiovasc Thorac Surg. 2011; 12: 475-479Crossref PubMed Scopus (61) Google Scholar, 2Onalan O Crystal A Lashevsky I Khalameizer V Lau C Goldman B Fremes S Newman D Lukomsky M Crystal E Determinants of pacemaker dependency after coronary and/or mitral or aortic valve surgery with long-term follow-up.Am J Cardiol. 2008; 101: 203-208Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar, 3Steyers 3rd, CM Khera R Bhave P Pacemaker dependency after cardiac surgery: a systematic review of current evidence.PLoS One. 2015; 10e0140340Crossref PubMed Scopus (28) Google Scholar. Brady-arrhythmia's requiring pacemaker implant include sick sinus syndrome, atrial fibrillation with slow ventricular response, and several degrees of A/V block.3Steyers 3rd, CM Khera R Bhave P Pacemaker dependency after cardiac surgery: a systematic review of current evidence.PLoS One. 2015; 10e0140340Crossref PubMed Scopus (28) Google Scholar Although pacemaker dependency decays with time, depending on the type of indication, new or recurrent conduction disturbances may develop at variable time points after hospital discharge.2Onalan O Crystal A Lashevsky I Khalameizer V Lau C Goldman B Fremes S Newman D Lukomsky M Crystal E Determinants of pacemaker dependency after coronary and/or mitral or aortic valve surgery with long-term follow-up.Am J Cardiol. 2008; 101: 203-208Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar,4Raza SS Li JM John R Chen LY Tholakanahalli VN Mbai M Adabag AS Long-term mortality and pacing outcomes of patients with permanent pacemaker implantation after cardiac surgery.Pacing Clin Electrophysiol. 2011; 34: 331-338Crossref PubMed Scopus (51) Google Scholar,5Rene AG Sastry A Horowitz JM Cheung J Liu CF Thomas G Ip JE Lerman BB Markowitz SM Recovery of atrioventricular conduction after pacemaker placement following cardiac valvular surgery.J Cardiovasc Electrophysiol. 2013; 24: 1383-1387Crossref PubMed Scopus (21) Google Scholar However, data addressing this topic are heterogeneous, dependent on local protocols, and, therefore, poorly informative.3Steyers 3rd, CM Khera R Bhave P Pacemaker dependency after cardiac surgery: a systematic review of current evidence.PLoS One. 2015; 10e0140340Crossref PubMed Scopus (28) Google Scholar Current guidelines consider advanced second or third degree A/V block lasting at least 7 days after cardiac surgery as a class I indication for PPI, but the evidence is based on relatively small studies ranging between 150 and 250 patients, with short-term follow up.6Epstein AE DiMarco JP Ellenbogen KA Estes 3rd, NA Freedman RA Gettes LS Gillinov AM Gregoratos G Hammill SC Hayes DL Hlatky MA Newby LK Page RL Schoenfeld MH Silka MJ Stevenson LW Sweeney MO Tracy CM Epstein AE Darbar D DiMarco JP Dunbar SB Estes 3rd, NAM Ferguson TB Hammill SC Karasik PE Link MS Marine JE Schoenfeld MH Shanker AJ Silka MJ Stevenson LW Stevenson WG Varosy PD American College Cardiology FoundationAmerican Heart Association Task Force on Practice GuidelinesHeart Rhythm Society2012 ACCF/AHA/HRS focused update incorporated into the ACCF/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.J Am Coll Cardiol. 2013; 61: e6-75PubMed Google Scholar,7Kusumoto FM Schoenfeld MH Barrett C Edgerton JR Ellenbogen KA Gold MR Goldschlager NF Hamilton RM Joglar JA Kim RJ Lee R Marine JE McLeod CJ Oken KR Patton KK Pellegrini CN Selzman KA Thompson A Varosy PD 2018 ACC/AHA/HRS guideline on the evaluation and management of patients with bradycardia and cardiac conduction delay: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society.J Am Coll Cardiol. 2019; 74: 932-987Crossref PubMed Scopus (88) Google Scholar Also, the impact of a PPI after cardiac surgery on survival is not known. Based on these premises we developed a multicenter working group to thoroughly investigate the actual incidence of PPI after cardiac surgery procedures in a large population. The purposes of this study were to evaluate the pacemaker dependency after PPI, to describe the influence of pre-operative sinus rhythm with normal conduction (SR) on pacemaker dependency and to assess the long-term mortality after PPI. The study population was retrospectively extracted, analyzing the institutional databases of 18 cardiac surgery units that are part of the G.I.R.O.C. (Italian Group for Research Outcome in Cardiac Surgery) and adhered to the study protocol. The requirement for PPI was determined by the cardiologist, the cardiac surgeon and the electrophysiologist of each center. All datasets analyzed were collected and responded to the requirements of a minimum dataset of predefined variables. Patients who underwent cardiac surgery from January 2004 to December 2016 requiring postoperative PPI during the hospitalization related to cardiac surgery procedures were included in the study. Patients with preoperative indication to PPI, who underwent implantable cardioverter defibrillator or cardiac resynchronization therapy treatment, were excluded. Preoperative and demographic information, operative data, and perioperative mortality and complications for all patients were retrieved from the institutional databases. The primary outcomes included pacemaker dependency at follow-up and long-term mortality. The secondary outcome described the influence of pre-operative SR on pacemaker dependency. Pacemaker dependency was defined as the absence of intrinsic rhythm on a postdischarge assessment performed by reducing the pacemaker frequency below 40 beats per minute (bpm) during 15 seconds. The presence of SR with associated conduction status and the presence of supraventricular arrhythmia were also recorded. Patients were considered pacemaker independent (PMI) if they had SR or atrial fibrillation with an adequate ventricular response at 40 bpm. Follow-up information was obtained by direct patient visit and electrophysiology analysis on simple EKG tracings. Patient data collection was truncated on December 31, 2016; patients who did not experience the events were considered as rightly censored. The study was conducted after approval of the individual Ethical Committees at each institution (Principal Investigator Ethical Committee approval nr.1467, date March 4, 2014). Normally distributed variables (by Kolmogorov-Smirnov test) are reported as mean and standard deviation, non-normally distributed variables are reported as median and quartiles. Pairwise comparison was performed with student's t test or Mann-Whitney U-test in case of continuous variables and chi-square with Fisher's exact test in case of categorical variables. Following discharge, the primary events were managed as time-to-event data and analyzed with nonparametric and semiparametric methods. Discharge from hospital after surgery was defined as beginning of follow-up and all intraoperative deaths and in-hospital were excluded from time-to-event analysis. Time-to-event distributions were separately analyzed according to primary event-type (death, cardiac death and freedom from pacemaker dependency), using Kaplan-Meier estimates and Cox regression for the time-to-death analysis and Fine & Gray models in competing risk framework for time-to-cardiac death (with no-cardiac death as competing risk) and time-to-freedom from pacemaker dependency (with death as competing risk). The variables selection for the Cox models was performed by a forward stepwise regression (probability of stay = 0.10, probability of entry = 0.05). For time-to-cardiac death and time-to-freedom from pacemaker dependency, nonparametric analyses of the outcome variables of interest were computed with the cumulative incidence function (CIF), and subdistribution hazards and comparisons were computed by means of Fine and Gray test. Direct regression modeling of the effect of covariates on CIF was performed through the semi-parametric proportional hazard model for the subdistribution hazards proposed by Fine and Gray, allowing for time-varying effect of the covariates. The variables selection for the Fine & Gray models was performed by a forward stepwise regression with the Bayesian Information Criterion as selection criteria. Hazards proportionality and time-dependent effects were checked with the analysis of Shoenfeld residuals, Kolmogorov-Smirnov test, and Cramer von Mises test. Missing values occurred for variables with a max of 3%. The center effect was evaluated with mixed effect model with center as random effect. Missing values were substituted by means of multiple imputation, as described in order to reduce bias and increase statistical power. For all analyses, we used R 3.3.1 (R Development Core Team (2016), R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. ISBN 3-900051-07-0, URL http://www.R-project.org/) Patient population included 94.693 cardiac surgery procedures from January 2004 to December 2016. During this period, 859 patients (0.90%) underwent PPI within 30 days after surgery. Table 1 shows the baseline characteristics of the study groups. Median time from cardiac surgery to PPI was 8 days (ranging from 2 to 10 days).Table 1Baseline characteristics of patients (n = 859)Pre-operative Data and Co-morbities VariablesStudy Group (n = 859)Age, mean (SD) (years)68,7 (12,4)Women443 (51,6%)Hypertension537 (62,5%)Active endocarditis45 (5,2%)Diabetes mellitus (requiring drug treatment)184 (21,4%)Previous stroke47 (5,5%)Chronic renal failure48 (5,6%)Dialysis9 (1,1%)Chronic pulmonary disease123 (14,3%)Pulmonary hypertension (systolic PA pressure >55 mm Hg172 (20,0%)Extracardiac arteriopathy*any one or more of the following: claudication, carotid occlusion or >50% stenosis, previous or planned intervention on the abdominal aorta, limb arteries or carotids.124 (14,4%)Previous myocardial infarction81 (9,4%)Recent myocardial infarction36 (4,2%)Left ventricular ejection fraction, mean (SD), %54,2 (11,4)NYHA Class III/IV410 (47,7%)Previous cardiac surgery105 (12,2%)Urgent status of operation27 (3,1%)ECG Sinus rhythm640 (74,5%) Left bundle branch block87 (10,1%) Right bundle branch block88 (10,2%) Bi-fascicular block9 (1,0%) Left anterior fascicular block71 (8,3%) Left posterior fascicular block5 (0,6%) First-degree atrioventricular block88 (10,2%) Second-degree atrioventricular block26 (3,0%) Atrial fibrillation186 (21,7%)Surgery Coronary artery bypass grafting239 (27,8%) Aortic valve replacement387 (45,1%) Aortic root surgery44 (5,1%) Mitral valve surgery375 (43,6%) Tricuspid valve surgery178 (20,7%) Myxoma excision4 (0,5%) Atrial septal defect closure16 (1,9%) Ventricular septal defect closure9 (1,0%) Surgery for atrial fibrillation47 (5,5%) any one or more of the following: claudication, carotid occlusion or >50% stenosis, previous or planned intervention on the abdominal aorta, limb arteries or carotids. Open table in a new tab Seven patients who underwent PPI (7/859, 0.81%) died during their primary hospitalization and no death was PPI related. Eighty patients died after discharge (9.4%). Survival rate at 1, 5, and 12 years were 96.8% (95% CI: 95.6% to 98.0%), 90.4% (95% CI: 88.3% to 92.6%), and 85.1% (95% CI: 81.9% to 88.5%) respectively. Cardiac mortality rates at 1, 5, and 12 years were 2.2% (95% CI: 1.2% to 3.2%), 4.4% (95% CI 2.9% to 5.8%), and 6.2% (95% CI 3.9% to 8.4%) respectively. Figure 1, Panel A shows the Kaplan-Meier estimates for the long-term survival curves, of patients with PMD at follow-up and those who restored A/V conduction (PMI) (Log-rank p-value < 0.001), based on 4642.53 patient-years follow-up and a median follow-up of 61.8 months. Figure 1, Panel B shows the CIFs of the cardiac death between PMD and PMI, with noncardiac death as a competing risk and vice-versa (Gray test p-value = 0.057 and 0.008 respectively). The unadjusted hazard ratio for overall mortality was 0.39 (95% CI 0.22 to 0.69, p-value = 0.001), in favor of PMI. The adjusted hazard ratio was 0.22 (95% CI 0.09 to 0.52, p-value < 0.001) with PMD as reference group, thereby confirming association of PMD with increased long-term mortality (Table 2). No center effect was pointed out in the regression modeling. The long-term predicted survival curves with 95% CI, are shown in Figure 1 Panel C. The assumption of hazards proportionality for the Cox model was confirmed by the analysis of Schoenfeld residuals (per-variable Grambsch-Therneau test p-value > 0.05 for all regressors). Hence, PMI qualified as an independent protective factor for long-term mortality after surgery and PPI.Table 2Hazard ratios of the adjusted Cox semiparametric model for predicting long-term mortalityVariableHazard Ratio95% CI of HRp valuePMI0,220,09–0,52<0,001Diabetes mellitus2,461,48–4,08<0,001Active endocarditis1,910,87–4,200,09Chronic renal failure2,751,43–5,270,006 Open table in a new tab Table 3Hazard ratios of the adjusted Fine and Gray model for predicting restored PM-independencyVariableHazard Ratio95% CI of HRp valuePre-operative SR2,171,50–3,12<0,001Coronary artery bypass grafting0,600,42–0,830,006Aortic valve replacement0,870,67–1,110,084 Open table in a new tab Figure 2, Panel A reports the CIFs of restored pacemaker-independent rhythm at follow-up. Crude CIF at 6 months, 1 year, and 12 years were 30.5% (95% CI 27.3% to 33.7%), 33.7% (95% CI 30.4% to 36.9%), and 37.2% (95% CI 33.8% to 40.6%) respectively. As evident in Figure 1, more than 30% of patients with postoperative PPI returned to a prevalent non-PMD rhythm. Direct regression modeling of the effect of covariates on CIF of PMI demonstrated that PMI was favored by preoperative SR (HR 2.17, 95% CI 1.50 to 3.12, p value < .001), whereas AVR (HR 0.87, 95% CI 0.68 to 1.11, p= .084), and CABG (HR 0.60, 95% CI 0.42 to 0.83, p= 0.006) were independently associated to PM dependency (Kolmogorov-Smirnov test and Cramer von Mises test p-values > 0.05), and MVR was not significant (HR 0,848 95% CI 0,659 to 1,090, p = 0.2). No center effect was pointed out in the regression modeling. Preoperative SR qualified as an independent factor favoring PMI after PPI. Figure 2 Panel B shows the adjusted CIF of PMI in patients with preoperative SR and nonpreoperative SR. To our knowledge, this is the largest study on patients who underwent PPI after cardiac surgery with an extended long-term follow up. Our incidence of PPI was 0.90%, in accordance with published reports.4Raza SS Li JM John R Chen LY Tholakanahalli VN Mbai M Adabag AS Long-term mortality and pacing outcomes of patients with permanent pacemaker implantation after cardiac surgery.Pacing Clin Electrophysiol. 2011; 34: 331-338Crossref PubMed Scopus (51) Google Scholar,8Merin O Ilan M Oren A Fink D Deeb M Bitran D Silberman S Permanent pacemaker implantation following cardiac surgery: indications and long-term follow-up.Pacing Clin Electrophysiol. 2009; 32: 7-12Crossref PubMed Scopus (72) Google Scholar,9Del Rizzo DF Nishimura S Lau C Sever J Goldman BS Cardiac pacing following surgery for acquired heart disease.J Card Surg. 1996; 11: 332-340Crossref PubMed Scopus (39) Google Scholar Merin et al8Merin O Ilan M Oren A Fink D Deeb M Bitran D Silberman S Permanent pacemaker implantation following cardiac surgery: indications and long-term follow-up.Pacing Clin Electrophysiol. 2009; 32: 7-12Crossref PubMed Scopus (72) Google Scholar found PPI incidence of 1.4% in almost 5,000 cardiac surgery procedures; whereas Del Rizzo et al9Del Rizzo DF Nishimura S Lau C Sever J Goldman BS Cardiac pacing following surgery for acquired heart disease.J Card Surg. 1996; 11: 332-340Crossref PubMed Scopus (39) Google Scholar observed this event in 1.3% of the patients. Higher rate of PPI (2.2%) is also described in another series of 6,268 patients4Raza SS Li JM John R Chen LY Tholakanahalli VN Mbai M Adabag AS Long-term mortality and pacing outcomes of patients with permanent pacemaker implantation after cardiac surgery.Pacing Clin Electrophysiol. 2011; 34: 331-338Crossref PubMed Scopus (51) Google Scholar. PPI occurs more often after valvular surgery due to the close vicinity of the conduction system to the operated cardiac structures,10Baraki H Al Ahmad A Jeng-Singh S Saito S Schmitto JD Fleischer B Haverich A Kutschka I Pacemaker dependency after isolated aortic valve replacement: do conductance disorders recover over time?.Interact Cardiovasc Thorac Surg. 2013; 16: 476-481Crossref PubMed Scopus (36) Google Scholar and is reported in up to 16% in MVR.11Salhiyyah K Kattach H Ashoub A Patrick D Miskolczi S Tsang G Ohri SK Barlow CW Velissaris T Livesey S Mitral valve replacement in severely calcified mitral valve annulus: a 10-year experience.Eur J Cardiothorac Surg. 2017; 52: 440-444Crossref PubMed Scopus (15) Google Scholar Recently, Leyva and colleagues published the largest cohort of patients who underwent valvular surgery and focused on time to PPI after surgery during a follow-up of 10 years.12Leyva F Qiu T McNulty D Evison F Marshall H Gasparini M Long-term requirement for pacemaker implantation after cardiac valve replacement surgery.Heart Rhythm. 2017; 14: 529-534Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar They found higher chances of PPI in AVR compared with MVR, with higher chances in multiple valve replacements.12Leyva F Qiu T McNulty D Evison F Marshall H Gasparini M Long-term requirement for pacemaker implantation after cardiac valve replacement surgery.Heart Rhythm. 2017; 14: 529-534Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar Nevertheless, they did not look at PMD of the PPI patients at the long-term follow-up. In the current cohort, more than 30% of patients were PMI after 6 months follow-up. Interestingly, at 12-year follow-up, an additional 8% of patients were independent from pacemaker activity, suggesting that the rhythm recovery occurs mostly in the first 6 months rather than during the following years. Cumulative probabilities of PMI in patients with A/V block of 63% at 5 years and 30% at 10 years are described; also emphasizing a regression of PMD at long-term follow-up after surgery.2Onalan O Crystal A Lashevsky I Khalameizer V Lau C Goldman B Fremes S Newman D Lukomsky M Crystal E Determinants of pacemaker dependency after coronary and/or mitral or aortic valve surgery with long-term follow-up.Am J Cardiol. 2008; 101: 203-208Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar In our series, PPI occurred within the first months in almost 50% of patients. These data suggest that it should be possible to reduce rates of PPI by optimizing patient selection and by investigating predictors of PMD. In our study, predictors of PMD in the long run were CABG and AVR. Although MVR may have higher incidence of PPI in the early postoperative phase, SR recovery at the long run is more common in these groups. Indeed, PMI has been demonstrated in up to 40% of PPI patients after cardiac surgery at different time points.5Rene AG Sastry A Horowitz JM Cheung J Liu CF Thomas G Ip JE Lerman BB Markowitz SM Recovery of atrioventricular conduction after pacemaker placement following cardiac valvular surgery.J Cardiovasc Electrophysiol. 2013; 24: 1383-1387Crossref PubMed Scopus (21) Google Scholar,8Merin O Ilan M Oren A Fink D Deeb M Bitran D Silberman S Permanent pacemaker implantation following cardiac surgery: indications and long-term follow-up.Pacing Clin Electrophysiol. 2009; 32: 7-12Crossref PubMed Scopus (72) Google Scholar The pathophysiology of A/V conduction disturbances after cardiac surgery may be multifactorial, with direct injury of the conduction structures as the most frequent.13Caspi J Amar R Elami A Safadi T Merin G Frequency and significance of complete atrioventricular block after coronary artery bypass grafting.Am J Cardiol. 1989; 63: 526-529Abstract Full Text PDF PubMed Scopus (27) Google Scholar Interestingly, pathological examination of the conduction system in patients with A/V block after AVR showed "old" lesions which existed prior to the surgery and recent lesions attributed to mechanical compression of the conduction system.14Fukuda T Hawley RL Edwards JE Lesions of conduction tissue complicating aortic valvular replacement.Chest. 1976; 69: 605-614Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar In line with this, preexisting bundle branch block is an independent predictor of PPI in valvular surgery15Vogt F Pfeiffer S Dell'Aquila AM Fischlein T Santarpino G Sutureless aortic valve replacement with Perceval bioprosthesis: are there predicting factors for postoperative pacemaker implantation?.Interact Cardiovasc Thorac Surg. 2016; 22: 253-258Crossref PubMed Scopus (60) Google Scholar as a result of high degree A/V block, further emphasizing the role of mechanical impact on the A/V conduction system.16Urena M Webb JG Tamburino C Munoz-Garcia AJ Cheema A Dager AE Serra V Amat-Santos IJ Barbanti M Immè S Briales JHA Benitez LM Lawati HA Cucalon AM Del Blanco BG Lopez J Dumont E Delarochellière R Ribeiro HB Nombela-Franco L Philippon F Rodès-Cabau J Permanent pacemaker implantation after transcatheter aortic valve implantation: impact on late clinical outcomes and left ventricular function.Circulation. 2014; 129: 1233-1243Crossref PubMed Scopus (199) Google Scholar Thus, in theory, preexisting lesions make patients prone to conduction disturbances, and the extent of accumulating lesions during surgery may (transiently) surpass the threshold above which A/V block persists postoperatively. This is further illustrated in the protective effect of normal SR prior to surgery in our study and in others8Merin O Ilan M Oren A Fink D Deeb M Bitran D Silberman S Permanent pacemaker implantation following cardiac surgery: indications and long-term follow-up.Pacing Clin Electrophysiol. 2009; 32: 7-12Crossref PubMed Scopus (72) Google Scholar and the recovery of a large number of PPI patients during follow-up. A novel finding in this study is the impact of PMD on survival. Although previous studies failed to show higher mortality in PPI patients, we demonstrate a survival benefit of restored rhythm in patients with PMI at follow-up. As well in general population, PPI patients with structural heart disease show greater mortality during follow-up compared with PPI patients without structural heart disease.17Pyatt JR Somauroo JD Jackson M Grayson AD Osula S Aggarwal RK Charles RG Connelly DT Long-term survival after permanent pacemaker implantation: analysis of predictors for increased mortality.Europace. 2002; 4: 113-119Crossref PubMed Scopus (43) Google Scholar Also, as demonstrated by the DAVID trial, as the right ventricle pacing can increase morbidity and mortality at follow-up, absence of ventricular back-up pacing should be a potential explanation for the protective effect of the restored sinus rhythm in this study.18Wilkoff BL Cook JR Epstein AE Greene HL Hallstrom AP Hsia H Kutalek SP Sharma A Dual Chamber and VVI Implantable Defibrillator trial investigatorsThe Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial.JAMA. 2002; 288: 3115-3125Crossref PubMed Scopus (1614) Google Scholar Furthermore, important predictors of long-term mortality in PPI patients in general population are age, cardiomyopathy and valvular heart disease17Pyatt JR Somauroo JD Jackson M Grayson AD Osula S Aggarwal RK Charles RG Connelly DT Long-term survival after permanent pacemaker implantation: analysis of predictors for increased mortality.Europace. 2002; 4: 113-119Crossref PubMed Scopus (43) Google Scholar In our population, chronic renal failure and diabetes were important predictors of long-term mortality in PPI patients. Leyva et al12Leyva F Qiu T McNulty D Evison F Marshall H Gasparini M Long-term requirement for pacemaker implantation after cardiac valve replacement surgery.Heart Rhythm. 2017; 14: 529-534Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar demonstrated higher chances of late PPI after valve surgery in patients with diabetes, renal impairment and heart failure. Notably, while PPI patients with sick sinus syndrome show better survival than those with high degree A/V block,19Jahangir A Shen WK Neubauer SA Ballard DJ Hammill SC Hodge DO Lohse CM Gersh BJ Hayes DL Relation between mode of pacing and long-term survival in the very elderly.J Am Coll Cardiol. 1999; 33: 1208-1216Crossref PubMed Scopus (51) Google Scholar patients with atrial fibrillation at time of implant seem to have the worse outcomes.20Brunner M Olschewski M Geibel A Bode C Zehender M Long-term survival after pacemaker implantation. Prognostic importance of gender and baseline patient characteristics.Eur Heart J. 2004; 25: 88-95Crossref PubMed Scopus (92) Google Scholar These findings suggest that PMD may be a surrogate characteristic of specific underlying diseases such as cardiomyopathy and renal impairment, all of which may contribute to higher mortality. Our study has several limitations. This is a multicenter retrospective study and, therefore, inherent limitation due to such data collection should be considered for result interpretation. No information was available on pacemaker indication, cardiac pacing or echocardiographics findings. The lack of pacemaker indication may have led to inclusion of some patients with paroxysmal atrial fibrillation and conversion pauses, making therefore the incidence and interpretation postoperative of A/V conduction recovery not fully appropriate. However, to our knowledge, this study represents the largest investigation assessing such a perioperative complication. PMD might also have been largely undetected based on different institutional policies for PPI-patient follow-up: however, all patients have been examined at the pacemaker outpatient clinic including reduced PM rate to disclose undergoing native heart rate. Post-discharge pharmacological therapy was also not completely available in the study population and, therefore, it might have impact on overall recovery and timing of reappearance of A/V conduction. Finally, complications related to PPI either at early or late stage were not completely collected, and, therefore, not available for data assessment and presentation In conclusion, this study represents the largest data collection about PPI immediately after cardiac surgery and indicates that PPI incidence in such a setting is relatively low (around 1%). Our data confirmed that a high proportion of these patients (>40%) recover A/V conduction property, and this event occurs within months after PPI in most patients. PMD, however, was associated with higher mortality during prolonged follow-up. SR prior to surgery seems to have a protective effect on PMD after PPI. The data underlying this article will be shared on reasonable request to the corresponding author. Roberto Lorusso: Conceptualization, Methodology, Investigation, Validation, Writing – original draft, Writing – Review and Editing, Visualization, Supervision. Justine M. Ravaux: Conceptualization, Methodology, Investigation, Validation, Writing – original draft, Writing – Review and Editing, Visualization, Supervision. Elham Bidar: Resources, Formal Analysis. Fabio Barili: Software, Formal Analysis, Data curation. Kevin Vernooy: Validation, Writing – Review and Editing. Michele Di Mauro: Software, Formal Analysis, Data curation. Antonio Miceli: Resources, Investigations. Alessandro Parolari: Resources, Investigations. Andrea Daprati: Resources, Investigations. Veronika Myasoedova: Resources, Investigations. Francesco Alamanni: Resources, Investigations. Carlo De Vincentiis: Resources, Investigations. Ezio Aime': Resources, Investigations. Francesco Nicolini: Resources, Investigations. GianLuca Gonzi: Resources, Investigations. Andrea Colli: Resources, Investigations. Gino Gerosa: Resources, Investigations. Michele De Bonis: Resources, Investigations. Gabriele Paglino: Resources, Investigations. Paolo Della Bella: Resources, Investigations. Guglielmo Actis Dato: Resources, Investigations. Egidio Varone: Resources, Investigations. Sandro Sponga: Resources, Investigations. Mauro Toniolo: Resources, Investigations. Alessandro Proclemer: Resources, Investigations. Ugolino Livi: Resources, Investigations. Giovanni Mariscalco: Resources, Investigations. Marzia Cottini: Resources, Investigations. Cesare Beghi: Resources, Investigations. Roberto Scrofani: Resources, Investigations. Davide Foresti: Resources, Investigations. Francesco Paolo Tritto: Resources, Investigations. Rosario Gregorio: Resources, Investigations.Emmanuel Villa: Resources, Investigations. Giovanni Troise: Resources, Investigations. Domenico Pecora: Resources, Investigations. Filiberto Serraino: Resources, Investigations. Federica Jiritano: Resources, Investigations. Francesco Rosato: Resources, Investigations. Elena Grasso: Resources, Investigations. Domenico Paparella: Resources, Investigations. Lilla Amorese: Resources, Investigations. Enrico Vizzardi: Resources, Investigations. Marco Solinas: Resources, Investigations. Giuseppe Arena: Resources, Investigations. Daniele Maselli: Resources, Investigations. Caterina Simon: Resources, Investigations. Mattia Glauber: Resources, Investigations. Maurizio Merlo: Resources, Investigations. The authors declare that they have no known competing financial interests or personal relations that could have appeared to influence the work reported in this study. The following colleagues are gratefully acknowledged for their contribution: Francesco Alamanni, 5 Lorenzo Menicanti, 6 Tiziano Gherli, 7 Alberto Pozzoli, 10 Francesco Parisi 11 Carlo Antona, 15 Claudio Grossi, 20 Antonio Curnis 21
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