- Email: [email protected]
Postoperative tricuspid regurgitation after adult congenital heart surgery is associated with adverse clinical outcomes
Accepted Manuscript Post-operative Tricuspid Regurgitation following Adult Congenital Heart Surgery is Associated with Adverse Clinical Outcomes Matthew J. Lewis, MD MPH, Jonathan N. Ginns, MD, Siqin Ye, MD, Paul Chai, MD, Jan M. Quaegebeur, MD, Emile Bacha, MD, Marlon S. Rosenbaum, MD PII:
S0022-5223(15)01720-1
DOI:
10.1016/j.jtcvs.2015.09.028
Reference:
YMTC 9939
To appear in:
The Journal of Thoracic and Cardiovascular Surgery
Received Date: 27 April 2015 Revised Date:
28 August 2015
Accepted Date: 3 September 2015
Please cite this article as: Lewis MJ, Ginns JN, Ye S, Chai P, Quaegebeur JM, Bacha E, Rosenbaum MS, Post-operative Tricuspid Regurgitation following Adult Congenital Heart Surgery is Associated with Adverse Clinical Outcomes, The Journal of Thoracic and Cardiovascular Surgery (2015), doi: 10.1016/ j.jtcvs.2015.09.028. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Post-operative Tricuspid Regurgitation following Adult Congenital Heart Surgery is Associated with Adverse Clinical Outcomes
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Matthew J. Lewis* MD MPH, Jonathan N. Ginns#* MD, Siqin Ye† MD, Paul Chai** MD, Jan M. Quaegebeur** MD, Emile Bacha**, MD, Marlon S. Rosenbaum* MD
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*Division of Cardiology, Department of Medicine, Schneeweiss Adult Congenital Heat Center, Columbia University Medical Center, New York, New York
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†Center for Behavioral Cardiovascular Health, Department of Medicine, Columbia University Medical Center, New York, New York
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**Division of Cardiac, Thoracic and Vascular Surgery, Columbia University Medical Center, New York, New York
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All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.
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None of the authors have any conflicts of interest to report and there are no potential conflicts of interest for this manuscript.
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This work is unfunded.
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Division of Thoracic Imaging, Department of Radiology, Columbia University Medical Center, New York, New York.
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Address for Correspondence:
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Matthew Lewis, MD MPH
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Herbert Irving Pavilion
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161 Fort Washington Ave Suite 627
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New York, NY 10032
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Phone: 212-305-6936
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Fax: 212-305-0490
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Email: [email protected]
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List of Abbreviations:
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ACHD = Adult Congenital Heart Disease
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TR = Tricuspid Regurgitation
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TV = Tricuspid Valve
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CHD = Congenital Heart Disease
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PVR = Pulmonary Valve Replacement
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ABSTRACT:
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Background:
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Many patients with adult congenital heart disease (ACHD) will require cardiac surgery during their
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lifetime and some will have concomitant tricuspid regurgitation (TR). However, the optimal
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management of significant TR at the time of cardiac surgery remains unclear. We assessed the
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determinants of adverse outcomes in ACHD patients and ≥moderate TR undergoing cardiac surgery for
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non-TR related indications.
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Methods:
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All adult patients with CHD and ≥moderate TR who underwent cardiac surgery for non-TR related
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indications were included in a retrospective study at our ACHD center. Cohorts were defined by type of
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tricuspid valve (TV) intervention at the time of surgery. The primary endpoint of interest was a
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composite of death, heart transplantation and re-operation on the TV.
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Results:
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107 patients met inclusion criteria and 17 patients (17%) reached the primary endpoint. 68 patients
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(64%) underwent TV repair, 8 (7%) underwent TV replacement, and 31 (29%) did not have a TV
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intervention. By multivariate analysis, ≥moderate post-operative TR was associated with a hazard ratio
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of 6.12 (1.84-20.3) for the primary endpoint (p=0.003). In addition, failure to perform a TV intervention
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at the time of surgery was associated with an odds ratio of 4.17 (1.26-14.3) for ≥moderate post-
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operative TR (p=0.02).
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Conclusions:
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≥Moderate post-operative TR was associated with an increased risk of death, transplant or re-operation
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in ACHD patients undergoing cardiac surgery for non-TR related indications. Concomitant TV
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intervention at the time of cardiac surgery should be considered in ACHD patients with ≥moderate pre-
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operative TR.
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Ultra-mini Abstract:
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Failure to perform a tricuspid valve (TV) intervention at the time of surgery in ACHD patients with
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≥moderate pre-operative tricuspid regurgitation (TR) patients was associated with a >4 fold increase in
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the odds of ≥moderate post-operative TR, while ≥moderate post-operative TR was associated with 6.1
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times the risk of death/TV re-operation.
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INTRODUCTION:
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Approximately one in five adults with congenital heart disease (CHD) will require cardiac surgery during
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their lifetime, with re-operations accounting for nearly 40% of these surgeries.1 Many of these patients
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will have concomitant tricuspid regurgitation (TR) prior to surgery.2 The frequent need for cardiac
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surgery and presence of concomitant tricuspid valve (TV) disease in this population underscore the
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importance of establishing guidelines addressing management of TR at the time of cardiac surgery.
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The etiology of TV disease in adult patients with CHD is variable and includes annular dilation, congenital
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abnormalities of the TV, iatrogenic leaflet damage from prior surgical procedures, or pacemaker lead
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placement.3-5 Because TR in adults with CHD is often felt to be secondary to other cardiac pathology,
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intervention on the TV is often deferred when cardiac surgery is performed for other indications, with
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the belief that improved ventricular remodeling will lead to a reduction in TR over time.6 However,
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given that TR is associated with increased mortality in the general population7 and that TV surgery can
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be performed with low mortality,8,9 it is unclear whether this less aggressive approach to TV repair at the
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time of cardiac surgery represents an optimal strategy. Furthermore, the risk associated with persistent
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TR may be even greater in adult patients with CHD, where right ventricular dysfunction is more
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common.10 Because of the inherent risk of residual TR and the morbidity conferred by multiple
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sternotomies,11,12 defining a strategy to manage TR at the time of cardiac surgery is crucial in this
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population. To address this question, we sought to describe the determinants of mortality, heart
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transplantation, and repeat TV intervention in adult patients with CHD and ≥moderate TR undergoing
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cardiac surgery for non-TR related indications.
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METHODS:
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Study Design:
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We performed a retrospective cohort study of all patients at the Schneeweiss Adult Congenital Heart
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Center at Columbia University with ≥moderate TR who underwent cardiac surgery for non-TV related
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indications between 1/1994 and 1/2015. The main exposure variable of interest was the type of TV
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intervention at the time of surgery, defined as: A) no TV intervention, B) concurrent TV repair, and C)
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concurrent TV replacement. The primary endpoint of interest was a pre-specified composite of death,
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orthotropic heart transplant and re-operation of the TV. The secondary endpoint of interest was degree
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of post-operative TR up to three years following surgery. Because we were interested in non-Ebsteinoid
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TR of the subpulmonic ventricle, patients with congenitally corrected transposition of the great arteries,
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D-transposition of the great arteries with Mustard or Senning repair, Ebstein’s anomaly, and single
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ventricles were excluded from the study. The Columbia University Medical Center institutional review
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board approved this study prior to the onset of study procedures.
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105 Clinical Variables of Interest:
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Demographic and clinical data including patient diagnoses and prior surgical procedures were
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determined through review of electronic and written medical records. Two-dimensional transthoracic
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echocardiograms performed closest to the time of cardiac surgery were utilized to define the degree of
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pre-operative TR. Degree of pre-operative TR was classified as mild, moderate, moderate-severe, or
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severe from echocardiographic assessment based on visual assessment performed by two cardiologists
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(MR/JG) with years of expertise in congenital echocardiography. Only patients with ≥moderate TR were
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included in the study. Degree of post-operative TR was classified as ≤mild or ≥moderate using the same
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methodology and utilizing the last echocardiogram available within a three-year window from each
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patient’s surgery. Similarly, pre-operative echocardiographic right ventricular function was classified as
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normal or abnormal based on visual echocardiographic assessment by the same readers. Patient
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specific data including pre-operative heart failure and functional status were ascertained from the
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patient’s clinical visit closest to the time of surgery.
119 Primary Endpoint:
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The primary endpoint of interest was pre-specified as a composite of death, heart transplant or re-
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operation on the TV. Death was determined via review of the medical record and through the Social
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Security Death Index. Re-operation on the TV was determined via review of the medical records and
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included any surgeries that were performed for TR. Patients were contacted to assess their current
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clinical status and to confirm whether cardiac surgery had occurred since time of last follow-up. In the
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event that cardiac surgery had been performed, medical records were obtained to adjudicate the
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primary end-point. In the case where a patient was unable to be contacted, follow-up was censored at
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the time when status of the patient was last known.
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Data were expressed as frequency (%), median (interquartile range), or mean +/- SD as appropriate.
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Univariate and multivariate testing was performed for the primary endpoint using a Cox proportional
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hazard model. Multivariate models for the primary endpoint were pre-specified to contain ≥moderate
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post-op TR, age, and concomitant TV intervention based on prior literature. Additional variables
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reaching p<0.20 in the univariate analysis were subsequently added. Assumption of proportional
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hazards was verified using a formal significance test based on scaled and unscaled Schoenfeld residuals.
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Univariate and multivariate testing was performed for the predictors of post-op TR using logistic
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regression. Multivariate models for post-op TR were pre-specified to contain age, concomitant TV
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intervention, and degree of pre-operative TR, and any additional variables reaching p<0.20 in the
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univariate analysis were subsequently added. A Kaplan-Meier survivor function was performed for the
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primary end-point by degree of post-operative TR. Statistical analysis was performed using STATA
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statistical software (Version 13.1, Stata Corp, College Station, TX, USA).
143 RESULTS:
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Patient characteristics:
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Of the 1,457 adult patients with CHD who underwent surgery at our institution from 1/1991-1/2015,
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107 (7%) met inclusion criteria. Median time to the primary end point was 2.96 years (interquartile
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range: 6.5 years). Patient characteristics are delineated in Table 1. Forty-five (42%) of 107 patients
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were male and the median age at the time of surgery was 41 years (IQR=14 years). Prior to cardiac
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surgery, 55 patients (51%) had moderate TR, 21 patients had moderate-severe TR (19%), and 31 (30%)
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had severe TR. Primary surgeries included 44 pulmonary valve replacements (41%), 26 atrial septal
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defect repairs (24%), 7 ventricular septal defect repairs (7%), 6 mitral valve replacements (6%), 6 Rastelli
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procedures or conduit replacements (6%), and 18 patients with other procedures (17%).
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At the time of surgery, 68 patients (64%) underwent TV repair, 8 patients (7%) underwent TV
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replacement, and 31 patients (29%) did not have a TV intervention. Of the 68 patients who underwent
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TV repair, 13 patients (19%) underwent an annuloplasty with a tricuspid ring, and 55 patients (81%)
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underwent a De Vega annuloplasty. One patient who underwent TV repair and a concomitant right
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atrial maze procedure had post-operative complete heart block requiring placement of a permanent
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pacemaker. None of the other patients developed post-operative AV block. In each of the eight
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patients who had a TV replacement, a Carpenter-Edwards pericardial xenograft valve was used.
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Primary Endpoint:
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Of the 17 patients (12%) who met the primary endpoint, 10 died, 1 underwent heart transplant and 6
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had repeat operations on the TV. There was no significant difference in the number of patients who
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underwent TV repair or TV replacement who met the primary endpoint. Specific data for each patient
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who met the primary endpoint, including patient diagnosis, age at surgery, type of surgery, type of
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tricuspid intervention, and patient outcome, is listed in Table 2. By univariate analysis, moderate or
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greater post-operative TR and age at the time of surgery were significantly associated with the primary
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endpoint (Table 3). In a multivariate model containing ≥moderate post-operative TR, age at the time of
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surgery, pre-operative congestive heart failure, degree of pre-operative TR and performance of a TV
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intervention, the presence of ≥moderate post-operative TR remained a significant predictor of the
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primary endpoint (Hazard ratio 6.1, 95% CI 1.84-20.3, p=0.004). Figure 1 displays the survivor function
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of patients reaching the primary end-point by degree of post-operative TR.
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175 Post-operative TR:
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Thirty-one patients (32%) had ≥moderate TR post-operatively. There was significant difference in the
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number of patients with ≥moderate TR by year of echocardiogram from time of surgery. By univariate
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analysis, failure to perform a TV intervention at the time of surgery was associated with three times the
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odds of ≥moderate TR post-operatively (p=0.02). In the multivariate analysis, both lack of concomitant
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TV intervention and severe pre-operative TR were significantly associated with the degree of post-
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operative TR. Specifically, the odds ratio (OR) for developing ≥moderate post-operative TV was 4.16
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(95% CI 1.26-14.28, p=0.04) for patients who did not have a TV intervention at the time of surgery (Table
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4).
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Thirty-one patients had severe TR and 27 (87%) had a concurrent tricuspid valve intervention. In
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patients with severe TR, TV intervention was associated with a lower risk of ≥moderate post-operative
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TR (p=0.026). For patients with severe TR, there was no significant difference in the number of patients
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with ≥moderate post-operative TR by replacement or repair (p=0.071). However, pre-operative severe
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TR was associated with 3.6 times the odds of >moderate post-operative TR in the multivariate analysis
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(95% CI 1.09-11.9, p=0.02).
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The optimal management strategy for TR during adult congenital heart surgery has not been
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established. In many cases, TR is not surgically addressed in anticipation of improvement in RV
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dilatation and TV function by correcting an atrial level shunt or pulmonary regurgitation.13-15 However,
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TR has other etiologies and is seen in patients with structural abnormalities of the TV, chronic right
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ventricular hypertension, iatrogenic injury from prior surgeries, pacemaker lead placement or closure of
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a ventricular septal defect.16 Because of the diverse etiologies responsible for TR in adults with CHD, it
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can be difficult to determine if surgical correction of the primary lesions will also improve a patient’s TR.
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While recent studies have shown that TV repair can be performed with low mortality in this population,8
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there is little data comparing outcomes of patients who did and did not undergo concomitant TV
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intervention when surgery is performed primarily for another indication. In order to answer this
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question, we excluded patients with Ebstein’s anomaly, systemic right ventricles, and single ventricles.
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In so doing, we found that patients who were left with moderate or greater TR after cardiac surgery
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were at significantly increased risk of death, heart transplant, or re-operation on the TV. In addition, we
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found that patients who did not have an intervention on the TV at the time of surgery were at an
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increased risk of having moderate or more post-operative TR.
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Although worsening TR may also be associated with poor outcomes in CHD, the management of
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TR in patients undergoing procedures for other indications remains variable. Kogon et al. showed that
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in patients with tetralogy of Fallot and pulmonary stenosis undergoing pulmonary valve replacement
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(PVR) for PR, the degree of TR was not significantly different between patients who did and did not have
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a tricuspid valve annuloplasty at the time of surgery.6 However, this study was limited to a small group
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of 35 patients that included both pediatric and adult patients. Similarly, Cramer et. al. found no
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significant difference in the degree of post-operative TR in patients who did and did not undergo TV
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repair at that time of PVR.17 In contrast, in our cohort of 107 adult patients with congenital heart disease
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undergoing cardiac surgery for non-TR related indications, we found that patients who did not have a TV
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intervention had higher odds of having post-operative TR, particularly in patients with severe TR at the
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time of surgery. Several factors may explain the difference in findings. The median age of our cohort
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was 12 years greater, possibly allowing for worsening TV annular dilation necessitating repair. Our
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larger sample size and greater follow-up time may have also provided the power necessary to detect a
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significant difference. Although under-powering is a possibility, we did not find that any one diagnosis
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was significantly associated with a greater risk of post-operative TR. Furthermore, we found that
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≥moderate postoperative TR was the only significant predictor of death, transplant or repeat operation
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on the tricuspid valve. We believe this finding underscores the need to intervene on the tricuspid valve
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at the time of cardiac surgery in this population.
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These findings may have important clinical implications for the subset of patients who might otherwise undergo percutaneous PVR in the presence of significant TR. In this population, it is unclear
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whether to pursue a percutaneous strategy or to subject patients to repeat surgery to address both the
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pulmonary and tricuspid valve abnormalities. Larger, multicenter studies looking exclusively at this
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group would be necessary to elucidate the best management strategy; however, our findings suggest
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that these patients may be at increased risk if left with ≥moderate TR.
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Tricuspid valve repair can be performed with low mortality in this population, and several
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studies have shown improved outcomes when TV surgery is performed before the onset of heart failure
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in a general cohort. 18-20 Late repair and re-operation carry substantial increased risks over repair at the
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time of concomitant cardiac surgery.21 This may be especially true in our population of adults with
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congenital heart disease, many of whom have had multiple prior sternotomies. In these patients,
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chronic moderate or greater TR is likely to result in significant right ventricular remodeling leading to
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progressive right ventricular dilation and dysfunction. In addition, protracted TR can also result in
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significant right atrial enlargement and predispose patients to atrial tachyarrhythmias. Adult patients
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with congenital heart disease are at increased risk for these complications because many forms of
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congenital heart disease involve right-sided cardiac abnormalities. In our study, all adjudicated deaths
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were secondary to cardiac failure. Thus, while we are unable to show a direct correlation between
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death or heart transplant with degree of TR, our findings suggest that such an association may exist.
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Furthermore, we found that patients with the highest degrees of pre-operative TR and those who did
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not have a TV intervention were at higher risk of having significant post-operative TR. These findings
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suggest that even in patients who are not symptomatic at the time of surgery, significant TR should be
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addressed at the time of surgical repair for other lesions.
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Our study has several limitations. As a retrospective study, patients were not randomized to different
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treatment groups and patients undergoing valve replacement and valve repair were aggregated into a
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single cohort. In addition, a disproportionate number of critically ill patients may have undergone a TV
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replacement, limiting our ability to show a relationship between TV intervention and the primary
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outcome. Furthermore, as a retrospective study, we were unable to show direct causation between TR
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and the primary endpoint or TV intervention and the primary end-point. As a heterogeneous group of
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patients, our sample may also have been too small to detect differences between different anatomic
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lesions examined. Nonetheless, to our knowledge, this is the largest study of adult patients with
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congenital heart disease seeking to address this question. Because we limited the follow-up of our
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patients to three years for this study, our ability to draw conclusions on the durability of outcomes over
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the medium to long-term may also be limited. Finally, as a single center study performed at an
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institution with expertise in adult congenital heart disease, our results may not be generalizable to all
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centers.
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Moderate or greater post-operative TR was associated with a significantly increased risk of death, heart
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transplant or tricuspid valve re-operation in adult CHD patients undergoing cardiac surgery for a non-TR
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related indication. In addition, adult CHD patients with moderate or greater preoperative TR who did
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not undergo a TV intervention at the time of cardiac surgery had increased odds of having moderate or
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greater post-operative TR. While confirmatory prospective studies are required, these findings suggest
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that, in this population, concomitant tricuspid valve intervention at the time of cardiac surgery should
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be considered in patients with moderate or greater pre-operative TR.
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Table 1: Patient Characteristics All (n=107) 45 (42%) 41 (26)
Event (n=17) 8 (47%) 43 (20)
No Event (n= 90) 37 (41%) 40 (22)
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Gender, male (%) Age, median, years (IQR) Diagnosis Secundum ASD 14 (13%) 1 (6%) 13 (14%) Sinus venous ASD 9 (8%) 1 (6%) 8 (9%) Partial AV canal/Primum ASD 12 (11%) 1 (6%) 11 (12%) VSD 9 (8%) 0 (0) 9 (10%) Repaired TOF 30 (28%) 7 (42%) 23 (25%) Unrepaired TOF 2 (2%) 2 (12%) 0 (0) PS 17 (16%) 4 (24%) 13 (14%) DTGA 4 (4%) 0 (0) 4 (4%) Other 10 (9%) 1 (6%) 9 (10%) RVSP, median (IQR) 47 (31) 51 (18) 47 (34) Pre-operative TR Moderate 55 (51%) 8 (47%) 47 (52%) Moderate-Severe 21 (19%) 2 (12%) 19 (21%) Severe 31 (30%) 7 (41%) 24 (27%) Tricuspid Intervention None 31 (29%) 6 (35%) 24 (27%) Repair 68 (64%) 8 (47%) 61 (68%) Replacement 8 (7%) 3 (17%) 5 (5%) Surgical Era 1994-2004 32 (30%) 9 (53%) 23 (25%) 2005-2014 75 (70%) 8 (47%) 67 (75%) ASD = atrial septal defect, VSD= ventricular septal defect, TOF = tetralogy of Fallot, PS = pulmonary stenosis, DTGA= D-transposition of the great arteries following a Rastelli procedure, RVSP = right ventricular systolic pressure
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Table 2: Description of patients meeting the primary endpoint:
TOF TOF rTOF
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rTOF rTOF
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rTOF rTOF rTOF rTOF PS PS PS PS PAPVR Sec ASD, Hypo RV Sec ASD
33 34 28 56 40 41 48 36 64 41 69
Year (Surgery) 1994 1997 2000
Replaced Repaired
2000 2003
Repaired None None Repaired Repaired None Repaired Replaced None Replaced
2004 2005 2010 2010 1995 2000 2005 2008 2004 2005
Outcome Death Death Death
Cause of death Unk Failure Failure
Death Death
Failure Failure
Re-op Re-op Re-op Death Re-op Death OHT Death Re-op Death
Unk Failure Failure Failure
ASD repair, Repaired 2006 Death Unk CABG 17 AVC 43 MV Repair Repaired 2008 Re-op TOF= unrepaired tetralogy of Fallot, rTOF = repaired tetralogy of Fallot, PS = pulmonary stenosis, PAPVR= partial anomalous pulmonary venous return, Sec ASD= secundum type atrial septal defect, hypo RV = hypoplastic right ventricle, AVC= AV canal defect, RVOT = right ventricular outflow tract , MVR = mitral valve replacement, PVR =pulmonary valve replacement, AVR= aortic valve replacement, BDG = bidirectional Glenn, CABG = coronary artery bypass graft, Intraop= intraoperative, Unk = unknown
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TOF repair TOF repair RVOT recon, MVR, maze PVR PVR, MVR, maze PVR PVR AVR, PVR PVR, maze PVR PS resection PVR PVR Repair, maze BDG, maze
TV Intervention None None Repaired
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Age (Surgery) 58 64 57
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Table 3: Univariate and multivariate predictors of the primary endpoint Variable/Increment of Hazard Ratio
Univariate Hazard Ratio (95% CI) 5.3 (1.8-15) 1.03 (0.99-1.07) 2.47 (0.91-6.69) 1.21 (0.41-3.57)
p
Multivariate Hazard Ratio (95% CI) 6.12 (1.84-20.3) 1.02 (0.99-1.06) 2.60 (0.79-8.62) 1.7 (0.44-6.31)
p
≥Moderate Post Op TR 0.002 0.003 Age at Surgery/year 0.05 0.22 Pre-operative CHF 0.08 0.12 Tricuspid Valve Intervention 0.72 0.44 Degree of Pre-Operative TR Moderate Ref Ref Ref Ref Moderate-Severe 0.87 (0.18-4.1) 0.85 0.45 (0.071-2.94) 0.41 Severe 2.4 (0.84-7.1) 0.10 1.05 (0.29-3.95) 0.94 Pre-Operative RV dysfunction 1.48 (0.5-4.43) 0.47 Male Gender 1.1 (0.42-2.82) 0.86 RVSP/mm HG 0.99 (0.96-1.01) 0.46 Tetralogy of Fallot 1.53 (0.56-4.16) 0.40 Pulmonary Stenosis 1.31 (0.42-4.04) 0.63 Atrial Septal Defect 0.58 (0.19-1.79) 0.35 Other Diagnosis 1.19 (0.34-4.16) 0.78 Procedure ASD repair 0.40 (0.09-1.77) 0.23 PVR 1.62 (0.63-4.22) 0.32 Surgical Era 2005-2014 0.70 (0.25-1.96) 0.50 TR= tricuspid regurgitation, CHF = congestive heart failure, RV= right ventricle, RVSP = right ventricular systolic pressure, ASD = atrial septal defect, PVR= pulmonary valve replacement
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Table 4: Univariate and Multivariate predictors of Post-operative TR: Univariate OR (95% CI) 1.01 (0.98-1.04) 3.03 (1.25-7.69)
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Multivariate OR (95% CI) 1.01 (0.98-1.04) 4.17 (1.26-14.3)
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Age at Surgery/year 0.70 0.40 No TV Intervention 0.02 0.02 Degree of Pre-Operative TR Moderate Ref Ref Ref Ref Moderate-Severe 0.89 (0.27-2.89) 0.85 1.94 (0.45-8.22) 0.37 Severe 2.06 (0.80-5.27) 0.13 3.60 (1.09-11.9) 0.04 Pre-Operative RV dysfunction 1.96 (0.82-4.66) 0.13 1.95 (0.76-5.04) 0.16 Pre-op CHF 0.96 (0.41-2.22) 0.94 Male Gender 1.29 (0.56-2.98) 0.54 RVSP/mm HG 1.01 (0.99-1.03) 0.25 Tetralogy of Fallot 0.44 (0.15-1.28) 0.13 0.59 (0.17-2.01) 0.40 Pulmonary Stenosis 0.87 (0.28-2.68) 0.81 Atrial Septal Defect 1.33(0.55-3.17) 0.52 Other Diagnosis 1.47 (0.48-4.48) 0.49 Procedure ASD repair (any) 1.5 (0.56-3.9) 0.43 PVR 0.72 (0.30-1.7) 0.45 TR= tricuspid regurgitation, CHF = congestive heart failure, RV= right ventricle, RVSP = right ventricular systolic pressure, ASD = atrial septal defect, PVR= pulmonary valve replacement
Figure Captions:
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Central Figure: Figure 1: Survivor Function for the Primary Endpoint by Degree of Post-Operative Tricuspid Regurgitation
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1. Zomer AC, Verheugt CL, Vaartjes I, Uiterwaal CS, Langemeijer MM, Koolbergen DR, et al. Surgery in adults with congenital heart disease. Circulation. 2011;124:2195-2201. 2. Said SM, Burkhart HM, Dearani JA. Surgical management of congenital (non-Ebstein) tricuspid valve regurgitation. Seminars in thoracic and cardiovascular surgery. Pediatric cardiac surgery annual 2012;15:46-60. 3. Giamberti A, Chessa M, Ballotta A, Varrica A, Agnetti A, Frigiola A, et al. Functional tricuspid valve regurgitation in adults with congenital heart disease: An emerging problem. The Journal of heart valve disease. 2011;20:565-570. 4. van Slooten YJ, Freling HG, van Melle JP, Mulder BJ, Jongbloed MR, Ebels T, et al. Long-term tricuspid valve prosthesis-related complications in patients with congenital heart disease. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. 2014;45:83-89. 5. Ginns J, Ammash N, Bernier PL. The tricuspid valve in adult congenital heart disease. Heart failure clinics. 2014;10:131-53. 6. Kogon B, Patel M, Leong T, McConnell M, Book W. Management of moderate functional tricuspid valve regurgitation at the time of pulmonary valve replacement: is concomitant tricuspid valve repair necessary? Pediatric cardiology. 2010;31:843-8. 7. Nath J, Foster E, Heidenreich PA. Impact of tricuspid regurgitation on long-term survival. Journal of the American College of Cardiology. 2004;43:405-9. 8. Said SM, Dearani JA, Burkhart HM, Connolly HM, Eidem B, Stensrud PE, et al. Management of tricuspid regurgitation in congenital heart disease: Is survival better with valve repair? The Journal of thoracic and cardiovascular surgery. 2014;147:412-419. 9. Holst KA, Dearani JA, Burkhart HM, Connolly HM, Warnes CA, Li Z, Schaff HV. Reoperative multivalve surgery in adult congenital heart disease. The Annals of thoracic surgery. 2013;95:1383-1389. 10. Warnes CA. Adult congenital heart disease importance of the right ventricle. Journal of the American College of Cardiology. 2009;54:1903-10. 11. Kavarana MN, Savage A, O'Connell R, Rubinstein CS, Flynn-Reeves J, Joshi K, et al. Composite risk factors predict survival after transplantation for congenital heart disease. The Journal of thoracic and cardiovascular surgery. 2013;146:888-893 12. Holst KA, Dearani JA, Burkhart HM, Connolly HM, Warnes CA, Li Z, Schaff HV. Risk factors and early outcomes of multiple reoperations in adults with congenital heart disease. The Annals of thoracic surgery. 2011;92:122-128; discussion 129-130. 13. Szymanski P, Lipczynska M, Klisiewicz A, Hoffman P. Clinical Settings Leading to Presystolic Tricuspid Regurgitation. Echocardiography. 2014. 14. Toyono M, Krasuski RA, Pettersson GB, Matsumura Y, Yamano T, Shiota T. Persistent tricuspid regurgitation and its predictor in adults after percutaneous and isolated surgical closure of secundum atrial septal defect. The American journal of cardiology. 2009;104:856-861. 15. Toyono M, Fukuda S, Gillinov AM, Pettersson GB, Matsumura Y, Wada N, et al. Different determinants of residual tricuspid regurgitation after tricuspid annuloplasty: Comparison of atrial septal defect and mitral valve prolapse. Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography. 2009;22:899-903. 16. Matyal R, Wang A, Mahmood F. Percutaneous ventricular septal defect closure with amplatzer devices resulting in severe tricuspid regurgitation. Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions. 2013;82:E817-20.
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17. Cramer JW, Ginde S, Hill GD, Cohen SB, Bartz PJ, Tweddell JS, et al. Tricuspid repair at pulmonary valve replacement does not alter outcomes in tetralogy of fallot. The Annals of thoracic surgery. 2015;99:899-904. 18. Raikhelkar J, Lin HM, Neckman D, Afonso A, Scurlock C. Isolated tricuspid valve surgery: predictors of adverse outcome and survival. Heart, lung & circulation. 2013;22:211-20. 19. Guenther T, Noebauer C, Mazzitelli D, Busch R, Tassani-Prell P, Lange R. Tricuspid valve surgery: a thirty-year assessment of early and late outcome. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. 2008;34:402-9; discussion 9. 20. Chen SW, Tsai FC, Tsai FC, Chao YK, Huang YK, Chu JJ, et al. Surgical risk and outcome of repair versus replacement for late tricuspid regurgitation in redo operation. The Annals of thoracic surgery. 2012;93:770-775. 21. Pfannmuller B, Moz M, Misfeld M, Borger MA, Funkat AK, Garbade J, et al. Isolated tricuspid valve surgery in patients with previous cardiac surgery. The Journal of thoracic and cardiovascular surgery. 2013;146:841-847.
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S0022-5223(15)01720-1
DOI:
10.1016/j.jtcvs.2015.09.028
Reference:
YMTC 9939
To appear in:
The Journal of Thoracic and Cardiovascular Surgery
Received Date: 27 April 2015 Revised Date:
28 August 2015
Accepted Date: 3 September 2015
Please cite this article as: Lewis MJ, Ginns JN, Ye S, Chai P, Quaegebeur JM, Bacha E, Rosenbaum MS, Post-operative Tricuspid Regurgitation following Adult Congenital Heart Surgery is Associated with Adverse Clinical Outcomes, The Journal of Thoracic and Cardiovascular Surgery (2015), doi: 10.1016/ j.jtcvs.2015.09.028. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Post-operative Tricuspid Regurgitation following Adult Congenital Heart Surgery is Associated with Adverse Clinical Outcomes
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Matthew J. Lewis* MD MPH, Jonathan N. Ginns#* MD, Siqin Ye† MD, Paul Chai** MD, Jan M. Quaegebeur** MD, Emile Bacha**, MD, Marlon S. Rosenbaum* MD
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*Division of Cardiology, Department of Medicine, Schneeweiss Adult Congenital Heat Center, Columbia University Medical Center, New York, New York
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#
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†Center for Behavioral Cardiovascular Health, Department of Medicine, Columbia University Medical Center, New York, New York
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**Division of Cardiac, Thoracic and Vascular Surgery, Columbia University Medical Center, New York, New York
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All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.
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None of the authors have any conflicts of interest to report and there are no potential conflicts of interest for this manuscript.
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This work is unfunded.
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Word Count: 2610
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Division of Thoracic Imaging, Department of Radiology, Columbia University Medical Center, New York, New York.
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Address for Correspondence:
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Matthew Lewis, MD MPH
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Herbert Irving Pavilion
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161 Fort Washington Ave Suite 627
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New York, NY 10032
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Phone: 212-305-6936
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Fax: 212-305-0490
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Email: [email protected]
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List of Abbreviations:
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ACHD = Adult Congenital Heart Disease
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TR = Tricuspid Regurgitation
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TV = Tricuspid Valve
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CHD = Congenital Heart Disease
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PVR = Pulmonary Valve Replacement
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ABSTRACT:
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Background:
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Many patients with adult congenital heart disease (ACHD) will require cardiac surgery during their
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lifetime and some will have concomitant tricuspid regurgitation (TR). However, the optimal
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management of significant TR at the time of cardiac surgery remains unclear. We assessed the
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determinants of adverse outcomes in ACHD patients and ≥moderate TR undergoing cardiac surgery for
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non-TR related indications.
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Methods:
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All adult patients with CHD and ≥moderate TR who underwent cardiac surgery for non-TR related
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indications were included in a retrospective study at our ACHD center. Cohorts were defined by type of
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tricuspid valve (TV) intervention at the time of surgery. The primary endpoint of interest was a
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composite of death, heart transplantation and re-operation on the TV.
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Results:
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107 patients met inclusion criteria and 17 patients (17%) reached the primary endpoint. 68 patients
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(64%) underwent TV repair, 8 (7%) underwent TV replacement, and 31 (29%) did not have a TV
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intervention. By multivariate analysis, ≥moderate post-operative TR was associated with a hazard ratio
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of 6.12 (1.84-20.3) for the primary endpoint (p=0.003). In addition, failure to perform a TV intervention
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at the time of surgery was associated with an odds ratio of 4.17 (1.26-14.3) for ≥moderate post-
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operative TR (p=0.02).
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Conclusions:
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≥Moderate post-operative TR was associated with an increased risk of death, transplant or re-operation
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in ACHD patients undergoing cardiac surgery for non-TR related indications. Concomitant TV
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intervention at the time of cardiac surgery should be considered in ACHD patients with ≥moderate pre-
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operative TR.
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Ultra-mini Abstract:
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Failure to perform a tricuspid valve (TV) intervention at the time of surgery in ACHD patients with
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≥moderate pre-operative tricuspid regurgitation (TR) patients was associated with a >4 fold increase in
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the odds of ≥moderate post-operative TR, while ≥moderate post-operative TR was associated with 6.1
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times the risk of death/TV re-operation.
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INTRODUCTION:
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Approximately one in five adults with congenital heart disease (CHD) will require cardiac surgery during
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their lifetime, with re-operations accounting for nearly 40% of these surgeries.1 Many of these patients
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will have concomitant tricuspid regurgitation (TR) prior to surgery.2 The frequent need for cardiac
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surgery and presence of concomitant tricuspid valve (TV) disease in this population underscore the
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importance of establishing guidelines addressing management of TR at the time of cardiac surgery.
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The etiology of TV disease in adult patients with CHD is variable and includes annular dilation, congenital
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abnormalities of the TV, iatrogenic leaflet damage from prior surgical procedures, or pacemaker lead
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placement.3-5 Because TR in adults with CHD is often felt to be secondary to other cardiac pathology,
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intervention on the TV is often deferred when cardiac surgery is performed for other indications, with
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the belief that improved ventricular remodeling will lead to a reduction in TR over time.6 However,
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given that TR is associated with increased mortality in the general population7 and that TV surgery can
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be performed with low mortality,8,9 it is unclear whether this less aggressive approach to TV repair at the
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time of cardiac surgery represents an optimal strategy. Furthermore, the risk associated with persistent
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TR may be even greater in adult patients with CHD, where right ventricular dysfunction is more
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common.10 Because of the inherent risk of residual TR and the morbidity conferred by multiple
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sternotomies,11,12 defining a strategy to manage TR at the time of cardiac surgery is crucial in this
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population. To address this question, we sought to describe the determinants of mortality, heart
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transplantation, and repeat TV intervention in adult patients with CHD and ≥moderate TR undergoing
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cardiac surgery for non-TR related indications.
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METHODS:
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Study Design:
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We performed a retrospective cohort study of all patients at the Schneeweiss Adult Congenital Heart
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Center at Columbia University with ≥moderate TR who underwent cardiac surgery for non-TV related
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indications between 1/1994 and 1/2015. The main exposure variable of interest was the type of TV
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intervention at the time of surgery, defined as: A) no TV intervention, B) concurrent TV repair, and C)
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concurrent TV replacement. The primary endpoint of interest was a pre-specified composite of death,
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orthotropic heart transplant and re-operation of the TV. The secondary endpoint of interest was degree
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of post-operative TR up to three years following surgery. Because we were interested in non-Ebsteinoid
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TR of the subpulmonic ventricle, patients with congenitally corrected transposition of the great arteries,
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D-transposition of the great arteries with Mustard or Senning repair, Ebstein’s anomaly, and single
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ventricles were excluded from the study. The Columbia University Medical Center institutional review
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board approved this study prior to the onset of study procedures.
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105 Clinical Variables of Interest:
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Demographic and clinical data including patient diagnoses and prior surgical procedures were
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determined through review of electronic and written medical records. Two-dimensional transthoracic
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echocardiograms performed closest to the time of cardiac surgery were utilized to define the degree of
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pre-operative TR. Degree of pre-operative TR was classified as mild, moderate, moderate-severe, or
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severe from echocardiographic assessment based on visual assessment performed by two cardiologists
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(MR/JG) with years of expertise in congenital echocardiography. Only patients with ≥moderate TR were
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included in the study. Degree of post-operative TR was classified as ≤mild or ≥moderate using the same
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methodology and utilizing the last echocardiogram available within a three-year window from each
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patient’s surgery. Similarly, pre-operative echocardiographic right ventricular function was classified as
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normal or abnormal based on visual echocardiographic assessment by the same readers. Patient
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specific data including pre-operative heart failure and functional status were ascertained from the
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patient’s clinical visit closest to the time of surgery.
119 Primary Endpoint:
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The primary endpoint of interest was pre-specified as a composite of death, heart transplant or re-
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operation on the TV. Death was determined via review of the medical record and through the Social
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Security Death Index. Re-operation on the TV was determined via review of the medical records and
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included any surgeries that were performed for TR. Patients were contacted to assess their current
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clinical status and to confirm whether cardiac surgery had occurred since time of last follow-up. In the
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event that cardiac surgery had been performed, medical records were obtained to adjudicate the
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primary end-point. In the case where a patient was unable to be contacted, follow-up was censored at
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the time when status of the patient was last known.
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Data were expressed as frequency (%), median (interquartile range), or mean +/- SD as appropriate.
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Univariate and multivariate testing was performed for the primary endpoint using a Cox proportional
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hazard model. Multivariate models for the primary endpoint were pre-specified to contain ≥moderate
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post-op TR, age, and concomitant TV intervention based on prior literature. Additional variables
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reaching p<0.20 in the univariate analysis were subsequently added. Assumption of proportional
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hazards was verified using a formal significance test based on scaled and unscaled Schoenfeld residuals.
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Univariate and multivariate testing was performed for the predictors of post-op TR using logistic
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regression. Multivariate models for post-op TR were pre-specified to contain age, concomitant TV
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intervention, and degree of pre-operative TR, and any additional variables reaching p<0.20 in the
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univariate analysis were subsequently added. A Kaplan-Meier survivor function was performed for the
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primary end-point by degree of post-operative TR. Statistical analysis was performed using STATA
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statistical software (Version 13.1, Stata Corp, College Station, TX, USA).
143 RESULTS:
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Patient characteristics:
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Of the 1,457 adult patients with CHD who underwent surgery at our institution from 1/1991-1/2015,
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107 (7%) met inclusion criteria. Median time to the primary end point was 2.96 years (interquartile
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range: 6.5 years). Patient characteristics are delineated in Table 1. Forty-five (42%) of 107 patients
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were male and the median age at the time of surgery was 41 years (IQR=14 years). Prior to cardiac
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surgery, 55 patients (51%) had moderate TR, 21 patients had moderate-severe TR (19%), and 31 (30%)
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had severe TR. Primary surgeries included 44 pulmonary valve replacements (41%), 26 atrial septal
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defect repairs (24%), 7 ventricular septal defect repairs (7%), 6 mitral valve replacements (6%), 6 Rastelli
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procedures or conduit replacements (6%), and 18 patients with other procedures (17%).
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At the time of surgery, 68 patients (64%) underwent TV repair, 8 patients (7%) underwent TV
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replacement, and 31 patients (29%) did not have a TV intervention. Of the 68 patients who underwent
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TV repair, 13 patients (19%) underwent an annuloplasty with a tricuspid ring, and 55 patients (81%)
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underwent a De Vega annuloplasty. One patient who underwent TV repair and a concomitant right
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atrial maze procedure had post-operative complete heart block requiring placement of a permanent
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pacemaker. None of the other patients developed post-operative AV block. In each of the eight
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patients who had a TV replacement, a Carpenter-Edwards pericardial xenograft valve was used.
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Primary Endpoint:
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Of the 17 patients (12%) who met the primary endpoint, 10 died, 1 underwent heart transplant and 6
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had repeat operations on the TV. There was no significant difference in the number of patients who
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underwent TV repair or TV replacement who met the primary endpoint. Specific data for each patient
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who met the primary endpoint, including patient diagnosis, age at surgery, type of surgery, type of
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tricuspid intervention, and patient outcome, is listed in Table 2. By univariate analysis, moderate or
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greater post-operative TR and age at the time of surgery were significantly associated with the primary
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endpoint (Table 3). In a multivariate model containing ≥moderate post-operative TR, age at the time of
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surgery, pre-operative congestive heart failure, degree of pre-operative TR and performance of a TV
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intervention, the presence of ≥moderate post-operative TR remained a significant predictor of the
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primary endpoint (Hazard ratio 6.1, 95% CI 1.84-20.3, p=0.004). Figure 1 displays the survivor function
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of patients reaching the primary end-point by degree of post-operative TR.
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175 Post-operative TR:
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Thirty-one patients (32%) had ≥moderate TR post-operatively. There was significant difference in the
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number of patients with ≥moderate TR by year of echocardiogram from time of surgery. By univariate
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analysis, failure to perform a TV intervention at the time of surgery was associated with three times the
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odds of ≥moderate TR post-operatively (p=0.02). In the multivariate analysis, both lack of concomitant
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TV intervention and severe pre-operative TR were significantly associated with the degree of post-
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operative TR. Specifically, the odds ratio (OR) for developing ≥moderate post-operative TV was 4.16
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(95% CI 1.26-14.28, p=0.04) for patients who did not have a TV intervention at the time of surgery (Table
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4).
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Thirty-one patients had severe TR and 27 (87%) had a concurrent tricuspid valve intervention. In
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patients with severe TR, TV intervention was associated with a lower risk of ≥moderate post-operative
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TR (p=0.026). For patients with severe TR, there was no significant difference in the number of patients
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with ≥moderate post-operative TR by replacement or repair (p=0.071). However, pre-operative severe
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TR was associated with 3.6 times the odds of >moderate post-operative TR in the multivariate analysis
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(95% CI 1.09-11.9, p=0.02).
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The optimal management strategy for TR during adult congenital heart surgery has not been
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established. In many cases, TR is not surgically addressed in anticipation of improvement in RV
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dilatation and TV function by correcting an atrial level shunt or pulmonary regurgitation.13-15 However,
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TR has other etiologies and is seen in patients with structural abnormalities of the TV, chronic right
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ventricular hypertension, iatrogenic injury from prior surgeries, pacemaker lead placement or closure of
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a ventricular septal defect.16 Because of the diverse etiologies responsible for TR in adults with CHD, it
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can be difficult to determine if surgical correction of the primary lesions will also improve a patient’s TR.
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While recent studies have shown that TV repair can be performed with low mortality in this population,8
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there is little data comparing outcomes of patients who did and did not undergo concomitant TV
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intervention when surgery is performed primarily for another indication. In order to answer this
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question, we excluded patients with Ebstein’s anomaly, systemic right ventricles, and single ventricles.
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In so doing, we found that patients who were left with moderate or greater TR after cardiac surgery
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were at significantly increased risk of death, heart transplant, or re-operation on the TV. In addition, we
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found that patients who did not have an intervention on the TV at the time of surgery were at an
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increased risk of having moderate or more post-operative TR.
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Although worsening TR may also be associated with poor outcomes in CHD, the management of
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TR in patients undergoing procedures for other indications remains variable. Kogon et al. showed that
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in patients with tetralogy of Fallot and pulmonary stenosis undergoing pulmonary valve replacement
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(PVR) for PR, the degree of TR was not significantly different between patients who did and did not have
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a tricuspid valve annuloplasty at the time of surgery.6 However, this study was limited to a small group
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of 35 patients that included both pediatric and adult patients. Similarly, Cramer et. al. found no
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significant difference in the degree of post-operative TR in patients who did and did not undergo TV
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repair at that time of PVR.17 In contrast, in our cohort of 107 adult patients with congenital heart disease
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undergoing cardiac surgery for non-TR related indications, we found that patients who did not have a TV
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intervention had higher odds of having post-operative TR, particularly in patients with severe TR at the
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time of surgery. Several factors may explain the difference in findings. The median age of our cohort
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was 12 years greater, possibly allowing for worsening TV annular dilation necessitating repair. Our
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larger sample size and greater follow-up time may have also provided the power necessary to detect a
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significant difference. Although under-powering is a possibility, we did not find that any one diagnosis
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was significantly associated with a greater risk of post-operative TR. Furthermore, we found that
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≥moderate postoperative TR was the only significant predictor of death, transplant or repeat operation
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on the tricuspid valve. We believe this finding underscores the need to intervene on the tricuspid valve
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at the time of cardiac surgery in this population.
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These findings may have important clinical implications for the subset of patients who might otherwise undergo percutaneous PVR in the presence of significant TR. In this population, it is unclear
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whether to pursue a percutaneous strategy or to subject patients to repeat surgery to address both the
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pulmonary and tricuspid valve abnormalities. Larger, multicenter studies looking exclusively at this
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group would be necessary to elucidate the best management strategy; however, our findings suggest
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that these patients may be at increased risk if left with ≥moderate TR.
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Tricuspid valve repair can be performed with low mortality in this population, and several
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studies have shown improved outcomes when TV surgery is performed before the onset of heart failure
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in a general cohort. 18-20 Late repair and re-operation carry substantial increased risks over repair at the
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time of concomitant cardiac surgery.21 This may be especially true in our population of adults with
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congenital heart disease, many of whom have had multiple prior sternotomies. In these patients,
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chronic moderate or greater TR is likely to result in significant right ventricular remodeling leading to
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progressive right ventricular dilation and dysfunction. In addition, protracted TR can also result in
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significant right atrial enlargement and predispose patients to atrial tachyarrhythmias. Adult patients
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with congenital heart disease are at increased risk for these complications because many forms of
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congenital heart disease involve right-sided cardiac abnormalities. In our study, all adjudicated deaths
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were secondary to cardiac failure. Thus, while we are unable to show a direct correlation between
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death or heart transplant with degree of TR, our findings suggest that such an association may exist.
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Furthermore, we found that patients with the highest degrees of pre-operative TR and those who did
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not have a TV intervention were at higher risk of having significant post-operative TR. These findings
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suggest that even in patients who are not symptomatic at the time of surgery, significant TR should be
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addressed at the time of surgical repair for other lesions.
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Our study has several limitations. As a retrospective study, patients were not randomized to different
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treatment groups and patients undergoing valve replacement and valve repair were aggregated into a
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single cohort. In addition, a disproportionate number of critically ill patients may have undergone a TV
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replacement, limiting our ability to show a relationship between TV intervention and the primary
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outcome. Furthermore, as a retrospective study, we were unable to show direct causation between TR
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and the primary endpoint or TV intervention and the primary end-point. As a heterogeneous group of
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patients, our sample may also have been too small to detect differences between different anatomic
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lesions examined. Nonetheless, to our knowledge, this is the largest study of adult patients with
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congenital heart disease seeking to address this question. Because we limited the follow-up of our
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patients to three years for this study, our ability to draw conclusions on the durability of outcomes over
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the medium to long-term may also be limited. Finally, as a single center study performed at an
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institution with expertise in adult congenital heart disease, our results may not be generalizable to all
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centers.
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Moderate or greater post-operative TR was associated with a significantly increased risk of death, heart
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transplant or tricuspid valve re-operation in adult CHD patients undergoing cardiac surgery for a non-TR
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related indication. In addition, adult CHD patients with moderate or greater preoperative TR who did
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not undergo a TV intervention at the time of cardiac surgery had increased odds of having moderate or
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greater post-operative TR. While confirmatory prospective studies are required, these findings suggest
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that, in this population, concomitant tricuspid valve intervention at the time of cardiac surgery should
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be considered in patients with moderate or greater pre-operative TR.
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Table 1: Patient Characteristics All (n=107) 45 (42%) 41 (26)
Event (n=17) 8 (47%) 43 (20)
No Event (n= 90) 37 (41%) 40 (22)
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Gender, male (%) Age, median, years (IQR) Diagnosis Secundum ASD 14 (13%) 1 (6%) 13 (14%) Sinus venous ASD 9 (8%) 1 (6%) 8 (9%) Partial AV canal/Primum ASD 12 (11%) 1 (6%) 11 (12%) VSD 9 (8%) 0 (0) 9 (10%) Repaired TOF 30 (28%) 7 (42%) 23 (25%) Unrepaired TOF 2 (2%) 2 (12%) 0 (0) PS 17 (16%) 4 (24%) 13 (14%) DTGA 4 (4%) 0 (0) 4 (4%) Other 10 (9%) 1 (6%) 9 (10%) RVSP, median (IQR) 47 (31) 51 (18) 47 (34) Pre-operative TR Moderate 55 (51%) 8 (47%) 47 (52%) Moderate-Severe 21 (19%) 2 (12%) 19 (21%) Severe 31 (30%) 7 (41%) 24 (27%) Tricuspid Intervention None 31 (29%) 6 (35%) 24 (27%) Repair 68 (64%) 8 (47%) 61 (68%) Replacement 8 (7%) 3 (17%) 5 (5%) Surgical Era 1994-2004 32 (30%) 9 (53%) 23 (25%) 2005-2014 75 (70%) 8 (47%) 67 (75%) ASD = atrial septal defect, VSD= ventricular septal defect, TOF = tetralogy of Fallot, PS = pulmonary stenosis, DTGA= D-transposition of the great arteries following a Rastelli procedure, RVSP = right ventricular systolic pressure
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Table 2: Description of patients meeting the primary endpoint:
TOF TOF rTOF
4 5
rTOF rTOF
38 63
6 7 8 9 10 11 12 13 14 15
rTOF rTOF rTOF rTOF PS PS PS PS PAPVR Sec ASD, Hypo RV Sec ASD
33 34 28 56 40 41 48 36 64 41 69
Year (Surgery) 1994 1997 2000
Replaced Repaired
2000 2003
Repaired None None Repaired Repaired None Repaired Replaced None Replaced
2004 2005 2010 2010 1995 2000 2005 2008 2004 2005
Outcome Death Death Death
Cause of death Unk Failure Failure
Death Death
Failure Failure
Re-op Re-op Re-op Death Re-op Death OHT Death Re-op Death
Unk Failure Failure Failure
ASD repair, Repaired 2006 Death Unk CABG 17 AVC 43 MV Repair Repaired 2008 Re-op TOF= unrepaired tetralogy of Fallot, rTOF = repaired tetralogy of Fallot, PS = pulmonary stenosis, PAPVR= partial anomalous pulmonary venous return, Sec ASD= secundum type atrial septal defect, hypo RV = hypoplastic right ventricle, AVC= AV canal defect, RVOT = right ventricular outflow tract , MVR = mitral valve replacement, PVR =pulmonary valve replacement, AVR= aortic valve replacement, BDG = bidirectional Glenn, CABG = coronary artery bypass graft, Intraop= intraoperative, Unk = unknown
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TOF repair TOF repair RVOT recon, MVR, maze PVR PVR, MVR, maze PVR PVR AVR, PVR PVR, maze PVR PS resection PVR PVR Repair, maze BDG, maze
TV Intervention None None Repaired
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Age (Surgery) 58 64 57
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Table 3: Univariate and multivariate predictors of the primary endpoint Variable/Increment of Hazard Ratio
Univariate Hazard Ratio (95% CI) 5.3 (1.8-15) 1.03 (0.99-1.07) 2.47 (0.91-6.69) 1.21 (0.41-3.57)
p
Multivariate Hazard Ratio (95% CI) 6.12 (1.84-20.3) 1.02 (0.99-1.06) 2.60 (0.79-8.62) 1.7 (0.44-6.31)
p
≥Moderate Post Op TR 0.002 0.003 Age at Surgery/year 0.05 0.22 Pre-operative CHF 0.08 0.12 Tricuspid Valve Intervention 0.72 0.44 Degree of Pre-Operative TR Moderate Ref Ref Ref Ref Moderate-Severe 0.87 (0.18-4.1) 0.85 0.45 (0.071-2.94) 0.41 Severe 2.4 (0.84-7.1) 0.10 1.05 (0.29-3.95) 0.94 Pre-Operative RV dysfunction 1.48 (0.5-4.43) 0.47 Male Gender 1.1 (0.42-2.82) 0.86 RVSP/mm HG 0.99 (0.96-1.01) 0.46 Tetralogy of Fallot 1.53 (0.56-4.16) 0.40 Pulmonary Stenosis 1.31 (0.42-4.04) 0.63 Atrial Septal Defect 0.58 (0.19-1.79) 0.35 Other Diagnosis 1.19 (0.34-4.16) 0.78 Procedure ASD repair 0.40 (0.09-1.77) 0.23 PVR 1.62 (0.63-4.22) 0.32 Surgical Era 2005-2014 0.70 (0.25-1.96) 0.50 TR= tricuspid regurgitation, CHF = congestive heart failure, RV= right ventricle, RVSP = right ventricular systolic pressure, ASD = atrial septal defect, PVR= pulmonary valve replacement
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Table 4: Univariate and Multivariate predictors of Post-operative TR: Univariate OR (95% CI) 1.01 (0.98-1.04) 3.03 (1.25-7.69)
P
Multivariate OR (95% CI) 1.01 (0.98-1.04) 4.17 (1.26-14.3)
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Age at Surgery/year 0.70 0.40 No TV Intervention 0.02 0.02 Degree of Pre-Operative TR Moderate Ref Ref Ref Ref Moderate-Severe 0.89 (0.27-2.89) 0.85 1.94 (0.45-8.22) 0.37 Severe 2.06 (0.80-5.27) 0.13 3.60 (1.09-11.9) 0.04 Pre-Operative RV dysfunction 1.96 (0.82-4.66) 0.13 1.95 (0.76-5.04) 0.16 Pre-op CHF 0.96 (0.41-2.22) 0.94 Male Gender 1.29 (0.56-2.98) 0.54 RVSP/mm HG 1.01 (0.99-1.03) 0.25 Tetralogy of Fallot 0.44 (0.15-1.28) 0.13 0.59 (0.17-2.01) 0.40 Pulmonary Stenosis 0.87 (0.28-2.68) 0.81 Atrial Septal Defect 1.33(0.55-3.17) 0.52 Other Diagnosis 1.47 (0.48-4.48) 0.49 Procedure ASD repair (any) 1.5 (0.56-3.9) 0.43 PVR 0.72 (0.30-1.7) 0.45 TR= tricuspid regurgitation, CHF = congestive heart failure, RV= right ventricle, RVSP = right ventricular systolic pressure, ASD = atrial septal defect, PVR= pulmonary valve replacement
Figure Captions:
290 291
Central Figure: Figure 1: Survivor Function for the Primary Endpoint by Degree of Post-Operative Tricuspid Regurgitation
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References
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