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Positron Emission Tomography Is Associated with the Presence of Cardiac Allograft Vasculopathy on Coronary Angiography
S154
The Journal of Heart and Lung Transplantation, Vol 36, No 4S, April 2017
Conclusion: Those with end-stage heart failure and renal failure represent a critically ill cohort of OHT candidates. In those requiring dialysis after listing for OHT, a SHK strategy confers superior survival compared to HTA or KAH. Future revisions to organ allocation should take into account both the appropriateness of SHK, as well as superiority of SHK over sequential transplant strategies.
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3( 92) Attenuation of Cardiac Allograft Vasculopathy in Dual Organ Transplantation K.J. Clerkin ,1 S.W. Restaino,1 F. Latif,1 M.A. Farr,1 E. Zorn,2 D.M. Mancini,3 K. Takeda,4 H. Takayama,4 Y. Naka,4 P.C. Colombo,1 V.K. Topkara.1 1Cardiology, Columbia University Medical Center, New York, NY; 2Immunology, Columbia University Medical Center, New York, NY; 3Cardiology, Icahn School of Medicine at Mount Sinai, New York, NY; 4Cardiac Surgery, Columbia University Medical Center, New York, NY. Purpose: Combined organ transplants represented 4.2% of all heart transplants (HT) in 2014. Small single center studies have suggested a decreased risk of cardiac allograft vasculopathy (CAV) in dual organ transplantation compared with HT alone. This study sought to determine if combined solid organ transplantation is protective against CAV among patients propensity score matched for CAV risk factors. Methods: Patients who underwent HT, heart-kidney (HK), heart-lung (HLu), and heart-liver (HLi) transplant between Jan 1st, 1995 and Aug 31st, 2014 were identified in the UNOS registry. A propensity score was calculated using a non-parsimonious multivariable logistic regression model, including recipient CAV risk factors (age, sex, dyslipidemia, DM, HTN, BMI, ischemic etiology of heart failure, CMV status), donor CAV risk factors (# of HLA mismatches, age, sex, DM, HTN, tobacco use, BMI, CMV status, and intracerebral hemorrhage), and other clinical characteristics of interest (race, PRA> 10%, MCS use, former tobacco use). Kaplan-Meier survival analysis and adjusted Cox proportionalhazards regression adjusting for post-transplant MMF and PSI use were performed. Results: There were 38,862 HT patients and 1,524 dual organ transplant patients identified. Adjusted analysis of the cohort demonstrated a 38% decrease in the risk of developing CAV for those who underwent a dual organ transplant compared with those undergoing only HT (95% CI 0.63-0.82, p< 0 .0001). Propensity score matching produced 765 HK pairs, 117 HLi pairs, and 419 HLu pairs. There was a non-significant trend towards a decreased risk of CAV among HK (HR 0.84, 95% CI 0.63-1.11) and HLi (HR 0.71, 95% CI 0.32-1.58) recipients. HLu recipients had a 50% decreased risk of CAV (95% CI 0.31-0.79, p= 0 .003) on adjusted analysis. Conclusion: Dual organ recipients had a decreased risk of CAV, which was attributable to a 50% decreased risk with HLu transplant. The immunologic mechanism by which HLu transplant confers this benefit merits further investigation.
Impact of Cardiac Allograft Vasculopathy and Treated Rejection on Sudden Cardiac Death in Patients Receiving a Cardiac Transplant. An Analysis of the ISHLT Registry Data A.C. Alba ,1 C.S. Fan,2 C. Manlhiot,2 A.I. Dipchand,3 J. Stehlik,4 H.J. Ross.1 1Toronto General Hospital - University Health Network, Toronto, ON, Canada; 2The Hospital for Sick Children - University of Toronto, Toronto, ON, Canada; 3Heart Transplant Program, The Hospital for Sick Children - University of Toronto, Toronto, ON, Canada; 4University of Utah School of Medicine, Salt Lake City, UT. Purpose: Sudden cardiac death (SCD) is responsible for approximately 10% of post-heart transplant (HTx) deaths. Evidence from case series and cohort studies has shown controversial results about the effect of rejection and cardiac allograft vasculopathy (CAV) on the risk of SCD. We hypothesized that patients developing CAV and/or rejection will have different SCD risk. We tested this hypothesis in a retrospective cohort study. Methods: Adult HTx recipients from the ISHLT registry were included in this analysis. We excluded patients who died within 3 months of HTx. We used multivariable competing risk survival analysis to evaluate the association between any degree CAV or rejection and SCD risk accounting for other modes of death. CAV was entered as time-dependent covariate. Rejection was defined as any episode of treated rejection within the first 3 months after HTx. Other covariates in the model were recipient age and sex, type of cardiomyopathy, BMI at transplant, smoking history, pre-HTx diabetes, hypertension, renal function and pulmonary hypertension, prior use of mechanical circulatory support or intravenous inotropes and panel reactive antibodies. Results: In this cohort of 28,451 patients, the median (inter-quartile range) age was 54 (44-61) years, 24% patients were female. The incidence of CAV was 30% at 10 years and 7% had an episode of treated rejection in the first 3 months post-HTx. During a median follow up of 4 (2 - 6.8) years, 721 patients died suddenly. The incidence of SCD was 1.1%, 3% and 4.5% at 1, 6 and 10 years, respectively. Patients with CAV had a 22% increased risk of SCD (HR 1.22, 95%CI 1.11-1.35, p< 0.001). Treated rejection was not associated with a significantly higher SCD risk of SCD (HR 1.1, 95%CI 0.99-1.22, p= 0.089). However, patients with both CAV and history of treated rejection had a 66% significantly higher risk of SCD (HR 1.66, 95% CI 1.3-2.1, p< 0.001). Conclusion: The risk of SCD after HTx was significantly increased in patients with CAV. This risk was more pronounced if patients additionally had treated rejection early post-HTx. These results provide important information about the risk of SCD and the potential to identify patients who would benefit from implantable cardioverter defibrillator. 3( 94) Positron Emission Tomography Is Associated with the Presence of Cardiac Allograft Vasculopathy on Coronary Angiography M.C. Konerman ,1 J.J. Lazarus,1 R.L. Weinberg,1 M. Ghannam,1 A. Saleh,1 H. Yun,1 V.M. Moles,1 S.L. Hummel,1 R.V. Shah,2 J.R. Corbett,1 K.D. Aaronson,1 M.M. Colvin,1 T.M. Koelling,1 V.L. Murthy.1 1University of Michigan, Ann Arbor, MI; 2Beth Israel Deaconess Medical Center, Boston, MA.
Abstracts S155 Purpose: Cardiac allograft vasculopathy (CAV) is associated with significant morbidity and mortality following orthotopic heart transplantation (OHT). Coronary angiography is the gold standard for detecting CAV. Positron emission tomography (PET) enables non-invasive quantitative assessment of coronary flow reserve (CFR). We evaluated whether PET imaging is associated with the presence of CAV on angiography. Methods: We retrospectively identified patients with prior OHT who underwent rest/stress rubidium-82 cardiac PET imaging within one year of coronary angiography. We quantified global CFR for the left ventricle using dynamic PET data. CAV was characterized using ISHLT nomenclature. Pearson correlation, logistic regression, and ROC curves were used to assess the relationships between CFR, stress myocardial blood flow (MBF), summed stress score (SSS), and angiographic CAV. Results: A total of 42 patients (age 57 ± 13 years, 64% male) underwent cardiac rubidium-82 PET imaging within 12 months of coronary angiography. The mean time from OHT to first PET imaging was 7.2 ± 5.5 years. Comorbidities were common [48% diabetes, 81% hypertension, 67% chronic kidney disease (GFR < 60 mL/min), 50% obesity]. The mean global CFR was 2.24 ± 0.76. 22 patients (52%) had CAV by ISHLT criteria with 11 patients having moderate-severe CAV (ISHLT grade 2-3). CFR was significantly correlated with the presence of CAV (r = -0.447; p = 0.0029). CFR was associated with the presence of moderate-severe CAV when adjusted for SSS [OR = 0.18 (95% CI 0.06-0.48; p = 0.04)]. Stress MBF similarly was associated with the presence of moderate-severe CAV when adjusted for SSS [OR = 0.24 (95% CI 0.06-0.70; p= 0.03)]. SSS was not associated with moderate-severe CAV (p= 0.07). Conclusion: CFR and stress MBF are associated with the presence of CAV by ISHLT criteria. Future studies should investigate whether PET imaging could replace coronary angiography as the preferred means for screening and monitoring progression of CAV.
computer analysis is reported using signed errors of intimal and medial thickness and compared with inter-observer variability. Results: Computer analysis required ~96 secs of computer time and 2 to 15 minutes of JEI interactions per pullback depending on vessel structural complexity. Comparable manual analysis requires over 12 hours of expert time per pullback. Errors of intimal and medial layer thickness of computer analysis were 7.7±14.0µm and -11.5±18.3µm, respectively. Thicknesses correlated well with the independent standard (R= 0.97, 0.66). Inter-observer variabilities of the same measures were -3.6±9.7µm and -3.2±12.6µm. Conclusion: Our new highly automated method offers performance statistically indistinguishable (p= NS) from that of expert tracing. The reported approach is fast, efficient, and facilitates accurate layer-specific quantification of coronary wall thickness changes after HTx.
3( 95) Highly Automated Analysis of Intimal and Medial Thickness in HeartTransplant Coronary OCT Facilitates Longitudinal Studies of CAV Progression Z. Chen ,1 A. Wahle,1 Z. Guo,1 H. Zhang,1 V. Karmazin,2 A. Tomasek,3 H. Bedanova,3 J.J. Lopez,4 T. Kovarnik,5 M. Pazdernik,2 M. Sonka.1 1University of Iowa, Iowa City, IA; 2IKEM, Prague, Czech Republic; 3Cardiovascular and Transplantation Surgery, Brno, Czech Republic; 4Loyola University, Chicago, IL; 5Charles University, Prague, Czech Republic. Purpose: Coronary Autograft Vasculopathy (CAV) is a frequent complication of heart transplantation (HTx). To help identify patients destined for cardiac graft failure, early determination of layer-specific coronary wall thickening is of major importance. We developed and validated quantitative analysis of coronary OCT (Optical Coherence Tomography) to highly automatically determine intimal and medial thickness in all images of OCT pullback. Methods: Lumen surface, intimal and media layers are identified by automated multi-surface graph-based optimization, approved by expert observer, and adjusted if needed using our Just-Enough-Interaction (JEI) approach. Intimal and medial layer thicknesses are determined for each image frame of the 3D pullback. Performance was assessed in 38 OCT pullbacks from 20 HTx patients (538±1 image frames each, 10,760 frames total). Two experts manually traced independent standard in a subset of 394 image frames (~10 frames/pullback), inter-observer variability was determined. Correctness of
3( 96) Strategies to Reduce Tricuspid Regurgitation After Heart Transplant K. Karl ,1 A.M. Borkon,1 S. Aggarwal,1 K. Allen,1 R. Davis,1 A. Pak,1 E. Thompson,1 J. Wang,2 A. Kao,3 A. Magalski,3 S. Lawhorn,3 T. Khumari,3 B. Austin.3 1Cardiovascular Surgery, Mid America Heart Institute of Saint Luke's Hospital, Kansas City, MO; 2Biostatistics, Mid America Heart Institute of Saint Luke's Hospital, Kansas City, MO; 3Cardiology, Mid America Heart Institute of Saint Luke's Hospital, Kansas City, MO. Purpose: Tricuspid regurgitation (TR) following heart transplant (HT) is common and often leads to reduced quality of life, need for valve replacement or even re-transplant. TR appearing 30-days or more after HT (late TR) is most often arises from heart biopsy surveillance of rejection and injury to the tricuspid valve apparatus. Strategies to reduce TR are greatly needed. Methods: Between January 1, 2000 and July 1, 2015, 464 HT performed at our institution were retrospectively studied. Excluded were 2 patients with intraoperative deaths and 7 patients without available post-HT echocardiographic data. All post HT echocardiograms, RV biopsy and gene expression profiling (GEP) tests were analyzed for 455 HT. Severity of TR was graded on a scale of 0 (none) to 4 ( severe). Biopsies were performed according to ISHLT-based protocols; between 1 week and 36 months post HT, decreasing in frequency over time, unless otherwise indicated. GEP testing between 4
The Journal of Heart and Lung Transplantation, Vol 36, No 4S, April 2017
Conclusion: Those with end-stage heart failure and renal failure represent a critically ill cohort of OHT candidates. In those requiring dialysis after listing for OHT, a SHK strategy confers superior survival compared to HTA or KAH. Future revisions to organ allocation should take into account both the appropriateness of SHK, as well as superiority of SHK over sequential transplant strategies.
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3( 92) Attenuation of Cardiac Allograft Vasculopathy in Dual Organ Transplantation K.J. Clerkin ,1 S.W. Restaino,1 F. Latif,1 M.A. Farr,1 E. Zorn,2 D.M. Mancini,3 K. Takeda,4 H. Takayama,4 Y. Naka,4 P.C. Colombo,1 V.K. Topkara.1 1Cardiology, Columbia University Medical Center, New York, NY; 2Immunology, Columbia University Medical Center, New York, NY; 3Cardiology, Icahn School of Medicine at Mount Sinai, New York, NY; 4Cardiac Surgery, Columbia University Medical Center, New York, NY. Purpose: Combined organ transplants represented 4.2% of all heart transplants (HT) in 2014. Small single center studies have suggested a decreased risk of cardiac allograft vasculopathy (CAV) in dual organ transplantation compared with HT alone. This study sought to determine if combined solid organ transplantation is protective against CAV among patients propensity score matched for CAV risk factors. Methods: Patients who underwent HT, heart-kidney (HK), heart-lung (HLu), and heart-liver (HLi) transplant between Jan 1st, 1995 and Aug 31st, 2014 were identified in the UNOS registry. A propensity score was calculated using a non-parsimonious multivariable logistic regression model, including recipient CAV risk factors (age, sex, dyslipidemia, DM, HTN, BMI, ischemic etiology of heart failure, CMV status), donor CAV risk factors (# of HLA mismatches, age, sex, DM, HTN, tobacco use, BMI, CMV status, and intracerebral hemorrhage), and other clinical characteristics of interest (race, PRA> 10%, MCS use, former tobacco use). Kaplan-Meier survival analysis and adjusted Cox proportionalhazards regression adjusting for post-transplant MMF and PSI use were performed. Results: There were 38,862 HT patients and 1,524 dual organ transplant patients identified. Adjusted analysis of the cohort demonstrated a 38% decrease in the risk of developing CAV for those who underwent a dual organ transplant compared with those undergoing only HT (95% CI 0.63-0.82, p< 0 .0001). Propensity score matching produced 765 HK pairs, 117 HLi pairs, and 419 HLu pairs. There was a non-significant trend towards a decreased risk of CAV among HK (HR 0.84, 95% CI 0.63-1.11) and HLi (HR 0.71, 95% CI 0.32-1.58) recipients. HLu recipients had a 50% decreased risk of CAV (95% CI 0.31-0.79, p= 0 .003) on adjusted analysis. Conclusion: Dual organ recipients had a decreased risk of CAV, which was attributable to a 50% decreased risk with HLu transplant. The immunologic mechanism by which HLu transplant confers this benefit merits further investigation.
Impact of Cardiac Allograft Vasculopathy and Treated Rejection on Sudden Cardiac Death in Patients Receiving a Cardiac Transplant. An Analysis of the ISHLT Registry Data A.C. Alba ,1 C.S. Fan,2 C. Manlhiot,2 A.I. Dipchand,3 J. Stehlik,4 H.J. Ross.1 1Toronto General Hospital - University Health Network, Toronto, ON, Canada; 2The Hospital for Sick Children - University of Toronto, Toronto, ON, Canada; 3Heart Transplant Program, The Hospital for Sick Children - University of Toronto, Toronto, ON, Canada; 4University of Utah School of Medicine, Salt Lake City, UT. Purpose: Sudden cardiac death (SCD) is responsible for approximately 10% of post-heart transplant (HTx) deaths. Evidence from case series and cohort studies has shown controversial results about the effect of rejection and cardiac allograft vasculopathy (CAV) on the risk of SCD. We hypothesized that patients developing CAV and/or rejection will have different SCD risk. We tested this hypothesis in a retrospective cohort study. Methods: Adult HTx recipients from the ISHLT registry were included in this analysis. We excluded patients who died within 3 months of HTx. We used multivariable competing risk survival analysis to evaluate the association between any degree CAV or rejection and SCD risk accounting for other modes of death. CAV was entered as time-dependent covariate. Rejection was defined as any episode of treated rejection within the first 3 months after HTx. Other covariates in the model were recipient age and sex, type of cardiomyopathy, BMI at transplant, smoking history, pre-HTx diabetes, hypertension, renal function and pulmonary hypertension, prior use of mechanical circulatory support or intravenous inotropes and panel reactive antibodies. Results: In this cohort of 28,451 patients, the median (inter-quartile range) age was 54 (44-61) years, 24% patients were female. The incidence of CAV was 30% at 10 years and 7% had an episode of treated rejection in the first 3 months post-HTx. During a median follow up of 4 (2 - 6.8) years, 721 patients died suddenly. The incidence of SCD was 1.1%, 3% and 4.5% at 1, 6 and 10 years, respectively. Patients with CAV had a 22% increased risk of SCD (HR 1.22, 95%CI 1.11-1.35, p< 0.001). Treated rejection was not associated with a significantly higher SCD risk of SCD (HR 1.1, 95%CI 0.99-1.22, p= 0.089). However, patients with both CAV and history of treated rejection had a 66% significantly higher risk of SCD (HR 1.66, 95% CI 1.3-2.1, p< 0.001). Conclusion: The risk of SCD after HTx was significantly increased in patients with CAV. This risk was more pronounced if patients additionally had treated rejection early post-HTx. These results provide important information about the risk of SCD and the potential to identify patients who would benefit from implantable cardioverter defibrillator. 3( 94) Positron Emission Tomography Is Associated with the Presence of Cardiac Allograft Vasculopathy on Coronary Angiography M.C. Konerman ,1 J.J. Lazarus,1 R.L. Weinberg,1 M. Ghannam,1 A. Saleh,1 H. Yun,1 V.M. Moles,1 S.L. Hummel,1 R.V. Shah,2 J.R. Corbett,1 K.D. Aaronson,1 M.M. Colvin,1 T.M. Koelling,1 V.L. Murthy.1 1University of Michigan, Ann Arbor, MI; 2Beth Israel Deaconess Medical Center, Boston, MA.
Abstracts S155 Purpose: Cardiac allograft vasculopathy (CAV) is associated with significant morbidity and mortality following orthotopic heart transplantation (OHT). Coronary angiography is the gold standard for detecting CAV. Positron emission tomography (PET) enables non-invasive quantitative assessment of coronary flow reserve (CFR). We evaluated whether PET imaging is associated with the presence of CAV on angiography. Methods: We retrospectively identified patients with prior OHT who underwent rest/stress rubidium-82 cardiac PET imaging within one year of coronary angiography. We quantified global CFR for the left ventricle using dynamic PET data. CAV was characterized using ISHLT nomenclature. Pearson correlation, logistic regression, and ROC curves were used to assess the relationships between CFR, stress myocardial blood flow (MBF), summed stress score (SSS), and angiographic CAV. Results: A total of 42 patients (age 57 ± 13 years, 64% male) underwent cardiac rubidium-82 PET imaging within 12 months of coronary angiography. The mean time from OHT to first PET imaging was 7.2 ± 5.5 years. Comorbidities were common [48% diabetes, 81% hypertension, 67% chronic kidney disease (GFR < 60 mL/min), 50% obesity]. The mean global CFR was 2.24 ± 0.76. 22 patients (52%) had CAV by ISHLT criteria with 11 patients having moderate-severe CAV (ISHLT grade 2-3). CFR was significantly correlated with the presence of CAV (r = -0.447; p = 0.0029). CFR was associated with the presence of moderate-severe CAV when adjusted for SSS [OR = 0.18 (95% CI 0.06-0.48; p = 0.04)]. Stress MBF similarly was associated with the presence of moderate-severe CAV when adjusted for SSS [OR = 0.24 (95% CI 0.06-0.70; p= 0.03)]. SSS was not associated with moderate-severe CAV (p= 0.07). Conclusion: CFR and stress MBF are associated with the presence of CAV by ISHLT criteria. Future studies should investigate whether PET imaging could replace coronary angiography as the preferred means for screening and monitoring progression of CAV.
computer analysis is reported using signed errors of intimal and medial thickness and compared with inter-observer variability. Results: Computer analysis required ~96 secs of computer time and 2 to 15 minutes of JEI interactions per pullback depending on vessel structural complexity. Comparable manual analysis requires over 12 hours of expert time per pullback. Errors of intimal and medial layer thickness of computer analysis were 7.7±14.0µm and -11.5±18.3µm, respectively. Thicknesses correlated well with the independent standard (R= 0.97, 0.66). Inter-observer variabilities of the same measures were -3.6±9.7µm and -3.2±12.6µm. Conclusion: Our new highly automated method offers performance statistically indistinguishable (p= NS) from that of expert tracing. The reported approach is fast, efficient, and facilitates accurate layer-specific quantification of coronary wall thickness changes after HTx.
3( 95) Highly Automated Analysis of Intimal and Medial Thickness in HeartTransplant Coronary OCT Facilitates Longitudinal Studies of CAV Progression Z. Chen ,1 A. Wahle,1 Z. Guo,1 H. Zhang,1 V. Karmazin,2 A. Tomasek,3 H. Bedanova,3 J.J. Lopez,4 T. Kovarnik,5 M. Pazdernik,2 M. Sonka.1 1University of Iowa, Iowa City, IA; 2IKEM, Prague, Czech Republic; 3Cardiovascular and Transplantation Surgery, Brno, Czech Republic; 4Loyola University, Chicago, IL; 5Charles University, Prague, Czech Republic. Purpose: Coronary Autograft Vasculopathy (CAV) is a frequent complication of heart transplantation (HTx). To help identify patients destined for cardiac graft failure, early determination of layer-specific coronary wall thickening is of major importance. We developed and validated quantitative analysis of coronary OCT (Optical Coherence Tomography) to highly automatically determine intimal and medial thickness in all images of OCT pullback. Methods: Lumen surface, intimal and media layers are identified by automated multi-surface graph-based optimization, approved by expert observer, and adjusted if needed using our Just-Enough-Interaction (JEI) approach. Intimal and medial layer thicknesses are determined for each image frame of the 3D pullback. Performance was assessed in 38 OCT pullbacks from 20 HTx patients (538±1 image frames each, 10,760 frames total). Two experts manually traced independent standard in a subset of 394 image frames (~10 frames/pullback), inter-observer variability was determined. Correctness of
3( 96) Strategies to Reduce Tricuspid Regurgitation After Heart Transplant K. Karl ,1 A.M. Borkon,1 S. Aggarwal,1 K. Allen,1 R. Davis,1 A. Pak,1 E. Thompson,1 J. Wang,2 A. Kao,3 A. Magalski,3 S. Lawhorn,3 T. Khumari,3 B. Austin.3 1Cardiovascular Surgery, Mid America Heart Institute of Saint Luke's Hospital, Kansas City, MO; 2Biostatistics, Mid America Heart Institute of Saint Luke's Hospital, Kansas City, MO; 3Cardiology, Mid America Heart Institute of Saint Luke's Hospital, Kansas City, MO. Purpose: Tricuspid regurgitation (TR) following heart transplant (HT) is common and often leads to reduced quality of life, need for valve replacement or even re-transplant. TR appearing 30-days or more after HT (late TR) is most often arises from heart biopsy surveillance of rejection and injury to the tricuspid valve apparatus. Strategies to reduce TR are greatly needed. Methods: Between January 1, 2000 and July 1, 2015, 464 HT performed at our institution were retrospectively studied. Excluded were 2 patients with intraoperative deaths and 7 patients without available post-HT echocardiographic data. All post HT echocardiograms, RV biopsy and gene expression profiling (GEP) tests were analyzed for 455 HT. Severity of TR was graded on a scale of 0 (none) to 4 ( severe). Biopsies were performed according to ISHLT-based protocols; between 1 week and 36 months post HT, decreasing in frequency over time, unless otherwise indicated. GEP testing between 4