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Coronary Computed Tomography to Screen for Cardiac Allograft Vasculopathy Post Orthotopic Heart Transplant
Abstracts S297 9( 19) Coronary Computed Tomography to Screen for Cardiac Allograft Vasculopathy Post Orthotopic Heart Transplant R. Tanner ,1 J. Buckley,1 D. Murphy,2 L. Lawler,2 N. Mahon,3 J. O'Neill.1 1Heart Transplant, Mater Misericordiae University Hospital, Dublin, Ireland; 2Radiology, Mater Misericordiae University Hospital, Dublin, Ireland; 3Cardiology, Mater Misericordiae University Hospital, Dublin, Ireland. Purpose: Background: Cardiac allograft vasculopathy (CAV) remains one of the most common causes of death beyond the first year post-transplantation. Coronary computed tomography angiography (CCTA) has been suggested as an alternate to conventional coronary angiogram (CCAG)in the surveillance for CAV. Aim: To assess the utility of CCTA in surveillance for CAV in Orthotopic Heart Transplant (OHT) recipients. Methods: A single centre retrospective review of all OHT recipients between 1985 and 2010. All patients undergoing CCTA for CAV surveillance who were at least 5 years post OHT were included. Degree of stenosis on CCTA was compared to established CAV ISHLT classification on CCAG. Stenosis on CCTA was defined as; absent stenosis (< 1%), mild (1-49%), moderate (50-70%) or severe (> 70%). Results: We identified 31 patients who underwent CCTA for CAV surveillance between June 2011 and October 2016. Baseline patient demographics are outlined in table 1. Following CCTA 11 patients (35%) underwent CCAG. Absent, mild, moderate and severe stenosis on CCTA correlated with CAV ISHLT grade 0, 1, 2 and 3 respectively on CCTA in 10 out 11 of patients (91%). One case reported as mid left anterior descending artery bridging on CCTA was subsequently graded as ISHLT 1 on CCAG. All patients (n= 3) with severe stenosis on CCTA subsequently had CAV ISHLT grade 3 and underwent coronary intervention. TABLE 1
N (%) / (IQR)
Male sex Median age (years) Median time since transplant (years) Mean Creatinine clearance (ml/min) Stenosis on CCTA - None (< 1%) - Mild (1-49%) - Moderate (50-69%) - Severe (> 70%)
20 (65) 58 (44-66) 11 (9-15) 67 22 (71) 4 (13) 2 (6) 3 (10)
Conclusion: CCTA may be a reliable less invasive imaging modality compared to CCAG in patients post OHT to assess for CAV. Our analysis correlates with findings of previous studies on surveillance for CAV.
9( 20) Time Dependent Covariate Method for Assessing Impact of CAV Severity on Mortality After Cardiac Transplantation F. Foroutan ,1 A. Alba,1 S. Bhagra,1 J. Duero Posada,1 M. Alhussein,1 A.K. McDiarmid,1 A. Malik,1 G. Guyatt,2 H. Ross.1 1Cardiology, Toronto General Hospital, Toronto, ON, Canada; 2Health Research Methodology, McMaster University, Hamilton, ON, Canada. Purpose: Cardiac allograft vasculopathy (CAV) is a major cause of mortality beyond the first year following heart transplantation (HTx). ISHLT Registry data has shown an absolute 10% increase in 10-year mortality in patients with CAV diagnosed within 3-years post-transplant compared to those without. CAV severity can progress over time. Failure to account for this progression may lead to imprecise risk estimates for mortality. The aim of this study was to assess the prognostic impact of CAV accounting for changes in CAV severity over time. Methods: We conducted a single institution retrospective cohort study of 264 consecutive HTx recipients (transplanted 2000 - 2015). Three reviewers independently categorized CAV according to the 2010 ISHLT criteria (CAV 0, 1, 2 and 3) in duplicates. We performed Cox-proportional hazard regression analysis to assess relationship between CAV and all-cause mortality, with
CAV severity as a time-dependent covariate. We also evaluated the relationship between CAV at first angiogram and mortality. Results: Mean age of HTx recipients was 48 (12) years (68% male), mean donor age 34 (14) years (61% male). Of the 735 angiograms performed, 61.6% showed CAV 0, 32.1% CAV 1, 1.8% CAV 2, and 5.4% CAV 3. We observed 37 deaths during a median follow-up of 5.3 years (IQR 3.3 - 7.7). After adjusting for use of sirolimus, we found a progressive increase in hazard of mortality with increase in severity of CAV (CAV 1 HR 2.86, 95% CI 1.22 - 6.67; CAV 2 HR 5.54, 95% CI 1.38 - 22.29; CAV 3 HR 6.07, 95% CI 1.15 - 17.71; c-statistics 0.71). The mortality risk associated with CAV severity based on first angiography showed poorer discrimination (c-statistics 0.63), though hazard ratios for CAV 1, 2 and 3 were similar (Table). Conclusion: The ISHLT CAV classification has greater discrimination for mortality when analyzed as a time dependent risk factor for mortality. We recommend adding serial measurement of CAV severity over time in patients as part of the assessment of CAV impact on mortality post HTx.
9( 21) Increased Heart Rate After Heart Transplant Is Not Associated with Early Progression of Cardiac Allograft Vasculopathy (CAV) - A Prospective Study Using Highly Automatic Coronary Optical Coherence Tomography Segmentation Software in 3D M. Pazdernik ,1 T. Kovarnik,1 Z. Chen,2 A. Wahle,2 V. Karmazin,1 V. Melenovsky,1 J. Kautzner,1 A. Tomasek,3 H. Bedanova,3 M. Sonka.2 1IKEM, Prague, Czech Republic; 2University if Iowa, Iowa City, IA; 3Centre of Cardiovascular and Transplantation Surgery, Brno, Czech Republic. Purpose: Previous experimental and clinical data suggested that sustained elevation of heart rate may contribute to the pathogenesis of vascular disease. A hypothesis was formed that sinus tachycardia in heart transplant (HTx) patients resulting from cardiac denervation may be one of the contributing factors for development of CAV. However, contradictory data exist in the HTx population. Methods: In a prospective, observational, multi-centre study consisting of 33 consecutive patients who underwent HTx between 2014-2015 in IKEM Prague and St. Anna hospital in Brno, Czech Republic. OCT imaging and 24 hour ECG Holter monitoring was performed in 1st and 12th months after HTx. Highly automated in-house developed segmentation software allowed quantitative analysis of intimal thickening in the entire 3D pullback. To overcome the inherent limitation of OCT imaging that is unable to depict full intimal layer in thick plaques due to insufficient penetration of the imaging beam and utilizing the assumption that CAV is a diffuse process, intimal thickening was measured within a 90° angular sector surrounding the location of minimal intimal thickness in each OCT frame. This measure of intimal thickness around the minimal thickness served as a surrogate intimal thickness (SIT) for progression assessment. Results: A total number of 28448 corresponding frames from paired 1-month and 12-month pullbacks [LAD (n= 25), RCx (5), RCA (3)] were grouped into 501 3-mm segments for progression of SIT. Mean change of the per-segment SIT was 23.7±21.1µm. Mean heart rate was 80.3±8.6 min-1 in the 1st month after HTx, 84.2±10.6 min-1 in the 12th month with the average heart rate in both periods of 82.2±8.0 min-1. No correlation between heart rate and progression of intimal thickness within 12 months after HTx was found in either of the groups (R= 0.14, p= 0.45 in month 1, R= -0.18, p= 0.33 in month 12; R= -0.04, p= 0.81 for averaged heart rate).
N (%) / (IQR)
Male sex Median age (years) Median time since transplant (years) Mean Creatinine clearance (ml/min) Stenosis on CCTA - None (< 1%) - Mild (1-49%) - Moderate (50-69%) - Severe (> 70%)
20 (65) 58 (44-66) 11 (9-15) 67 22 (71) 4 (13) 2 (6) 3 (10)
Conclusion: CCTA may be a reliable less invasive imaging modality compared to CCAG in patients post OHT to assess for CAV. Our analysis correlates with findings of previous studies on surveillance for CAV.
9( 20) Time Dependent Covariate Method for Assessing Impact of CAV Severity on Mortality After Cardiac Transplantation F. Foroutan ,1 A. Alba,1 S. Bhagra,1 J. Duero Posada,1 M. Alhussein,1 A.K. McDiarmid,1 A. Malik,1 G. Guyatt,2 H. Ross.1 1Cardiology, Toronto General Hospital, Toronto, ON, Canada; 2Health Research Methodology, McMaster University, Hamilton, ON, Canada. Purpose: Cardiac allograft vasculopathy (CAV) is a major cause of mortality beyond the first year following heart transplantation (HTx). ISHLT Registry data has shown an absolute 10% increase in 10-year mortality in patients with CAV diagnosed within 3-years post-transplant compared to those without. CAV severity can progress over time. Failure to account for this progression may lead to imprecise risk estimates for mortality. The aim of this study was to assess the prognostic impact of CAV accounting for changes in CAV severity over time. Methods: We conducted a single institution retrospective cohort study of 264 consecutive HTx recipients (transplanted 2000 - 2015). Three reviewers independently categorized CAV according to the 2010 ISHLT criteria (CAV 0, 1, 2 and 3) in duplicates. We performed Cox-proportional hazard regression analysis to assess relationship between CAV and all-cause mortality, with
CAV severity as a time-dependent covariate. We also evaluated the relationship between CAV at first angiogram and mortality. Results: Mean age of HTx recipients was 48 (12) years (68% male), mean donor age 34 (14) years (61% male). Of the 735 angiograms performed, 61.6% showed CAV 0, 32.1% CAV 1, 1.8% CAV 2, and 5.4% CAV 3. We observed 37 deaths during a median follow-up of 5.3 years (IQR 3.3 - 7.7). After adjusting for use of sirolimus, we found a progressive increase in hazard of mortality with increase in severity of CAV (CAV 1 HR 2.86, 95% CI 1.22 - 6.67; CAV 2 HR 5.54, 95% CI 1.38 - 22.29; CAV 3 HR 6.07, 95% CI 1.15 - 17.71; c-statistics 0.71). The mortality risk associated with CAV severity based on first angiography showed poorer discrimination (c-statistics 0.63), though hazard ratios for CAV 1, 2 and 3 were similar (Table). Conclusion: The ISHLT CAV classification has greater discrimination for mortality when analyzed as a time dependent risk factor for mortality. We recommend adding serial measurement of CAV severity over time in patients as part of the assessment of CAV impact on mortality post HTx.
9( 21) Increased Heart Rate After Heart Transplant Is Not Associated with Early Progression of Cardiac Allograft Vasculopathy (CAV) - A Prospective Study Using Highly Automatic Coronary Optical Coherence Tomography Segmentation Software in 3D M. Pazdernik ,1 T. Kovarnik,1 Z. Chen,2 A. Wahle,2 V. Karmazin,1 V. Melenovsky,1 J. Kautzner,1 A. Tomasek,3 H. Bedanova,3 M. Sonka.2 1IKEM, Prague, Czech Republic; 2University if Iowa, Iowa City, IA; 3Centre of Cardiovascular and Transplantation Surgery, Brno, Czech Republic. Purpose: Previous experimental and clinical data suggested that sustained elevation of heart rate may contribute to the pathogenesis of vascular disease. A hypothesis was formed that sinus tachycardia in heart transplant (HTx) patients resulting from cardiac denervation may be one of the contributing factors for development of CAV. However, contradictory data exist in the HTx population. Methods: In a prospective, observational, multi-centre study consisting of 33 consecutive patients who underwent HTx between 2014-2015 in IKEM Prague and St. Anna hospital in Brno, Czech Republic. OCT imaging and 24 hour ECG Holter monitoring was performed in 1st and 12th months after HTx. Highly automated in-house developed segmentation software allowed quantitative analysis of intimal thickening in the entire 3D pullback. To overcome the inherent limitation of OCT imaging that is unable to depict full intimal layer in thick plaques due to insufficient penetration of the imaging beam and utilizing the assumption that CAV is a diffuse process, intimal thickening was measured within a 90° angular sector surrounding the location of minimal intimal thickness in each OCT frame. This measure of intimal thickness around the minimal thickness served as a surrogate intimal thickness (SIT) for progression assessment. Results: A total number of 28448 corresponding frames from paired 1-month and 12-month pullbacks [LAD (n= 25), RCx (5), RCA (3)] were grouped into 501 3-mm segments for progression of SIT. Mean change of the per-segment SIT was 23.7±21.1µm. Mean heart rate was 80.3±8.6 min-1 in the 1st month after HTx, 84.2±10.6 min-1 in the 12th month with the average heart rate in both periods of 82.2±8.0 min-1. No correlation between heart rate and progression of intimal thickness within 12 months after HTx was found in either of the groups (R= 0.14, p= 0.45 in month 1, R= -0.18, p= 0.33 in month 12; R= -0.04, p= 0.81 for averaged heart rate).