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Increased Platelet Aggregation in Heart Transplant Recipients with Cardiac Allograft Vasculopathy
Abstracts Results: Mean s-Mg was 2.0§0.3mg/dL vs 1.6§0.1 mg/dL for the high and low s-Mg groups, respectively (p<0.001). Baseline patient and donor clinical and demographic characteristics were similar for the two groups. Kaplan-Meier survival analysis showed that at 15 years after HT survival was higher in the high s-Mg group than in the low s-Mg group (82 vs 38%, log-rank p=0.013, Figure). Similarly, 15-year freedom from CAV was significantly higher in the high vs low s-Mg group (82 vs 42%, log-rank p<0.001, Figure). There were no significant differences in freedom from NF-MACE or ATR between the two groups. Multivariate analyses consistently demonstrated that low s-Mg was independently associated with a significant >3-fold increased risk of mortality and >4-fold increased risk of CAV (95% CI 1.3-11.8, p=0.02; 95% CI 1.6-15.1, p=0.01 respectively). Conclusion: Low post-HT s-Mg is independently associated with increased mortality and CAV in HT patients. Larger prospective studies are needed to confirm these findings and to examine the effect of Mg supplementation.
S99 and arachidonic acid (AA). Results were reported as area under the curve (aggregation units (AU)*min). If patients received aspirin therapy and it was considered safe to interrupt treatment for 7 days, patients were included in the study. Healthy individuals (n=116) served as controls. CAV burden was determined by echocardiography and coronary angiography based on ISHLT classification. HTx-patients were divided into two groups; no CAV (CAV 0, n=39) and CAV (CAV 1-3, n=20). Results: We found a significant increase in ADP-induced platelet aggregation in HTx-patients with CAV vs. no CAV (902 (95% CI 807-998) vs. 790 (95% CI 733-847) AU*min, P=0.03) and also when comparing with healthy individuals (810 (95 % CI 779-841) AU*min, P=0.03). AAinduced aggregation was higher in HTx-patients with CAV vs. no CAV, though non-significant (998 (95 % CI 908-1089) vs. 905 (95 % CI 840970) AU*min, P=0.09). Conclusion: HTx-patients with CAV have significantly increased ADPinduced platelet aggregation compared with HTx-patients without CAV and healthy individuals, suggesting that patients with CAV could potentially benefit from treatment with ADP receptor inhibitors. Overall, our results indicate that increased platelet aggregation may contribute to CAV development and progression.
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221 Increased Platelet Aggregation in Heart Transplant Recipients with Cardiac Allograft Vasculopathy K.P. Bjerre,1 K. Berg,1 T.S. Clemmensen,2 S.H. Poulsen,1 S.D. Kristensen,1 A. Hvas,1 E.L. Grove,1 and H. Eiskjñr.1 1Aarhus University Hospital, Aarhus N, Denmark; and the 2Horsens Regional Hospital, Horsens, Denmark. Purpose: Cardiac allograft vasculopathy (CAV) remains a leading challenge to long-term survival after heart transplantation (HTx). Imaging of the coronary artery wall with optical coherence tomography has revealed layered fibrotic plaques resembling organized clots. Thus, thrombosis is suggested as a potential mechanism contributing to development and progression of CAV. We aimed to clarify whether HTx-patients with CAV have increased platelet aggregation compared with HTx-patients without CAV and healthy individuals. Methods: In a cross sectional study, platelet aggregation was measured in whole blood from 59 HTx-patients (median 8.6 years from HTx) employing MultiplateÒ Analyzer using adenosine diphosphate (ADP)
Mild Acute Cellular Rejection is Not Associated with Development of Cardiac Allograft Vasculopathy Assessed by Intravascular Ultrasound and Coronary Angiography in Heart Transplant Recipients - A Substudy of the SCHEDULE Trial L.M. Nelson,1 A.K. Andreassen,2 S. Arora,2 B. Andersson,3 E. Gude,2 H. Eiskjñr,4 G. Radegran,5 G. Dellgren,6 L. Gullestad,7 and 1 1 F. Gustafsson. Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; 2Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway; 3 Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden; 4Department of Cardiology, Aarhus University Hospital, Skejby, Aarhus, Denmark; 5The Clinic for Heart Failure and Valvular Disease, Skane University Hospital and Lund University, Lund, Sweden; 6Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden; and the 7 Department of Cardiology, Oslo University Hospital, Rikshospitalet, and University of Oslo, Oslo, Norway. Purpose: The impact of mild (1R) acute cellular rejection (ACR) on the development of cardiac allograft vasculopathy (CAV) after heart transplantation (HTx) remains unclear. We aimed to investigate the association between mild ACR within 1 year of HTx and development of CAV at 3 years post HTx. Methods: This is a substudy of the SCHEDULE trial (n=115) in which de novo HTx recipients were randomized to either (i) everolimus or (ii) conventional CNI-based immunosuppression. 76 patients (66%) were eligible for inclusion based on matched intravascular ultrasound (IVUS) examinations at baseline (BL) and 3 years post HTx. Biopsy proven ACR within year 1 was recorded and graded according to ISHLT criteria (1R, 2R, 3R). Development of CAV was assessed by IVUS and coronary angiography at year 3 post HTx. Results: Median age was 53 years (45-61) and 71% were male. In 67% of patients ACR was recorded during year 1 (1R in 63%, 2R in 24%, and 3R in 3% of patients, respectively). Patients were grouped by rejection profile: no ACR (33%), only 1R (42%), at least one 2R/3R (25%). At 3 years post HTx 49% of patients had CAV on IVUS (maximal intimal thickness, MIT ≥ 0.5 mm) with no difference in the incidence of IVUS-CAV between groups (p=0.43). Median ΔMITBL-3Y was 0.09 mm (0.05-0.15) with no significant difference among groups (p=0.84) (figure 1). At 3 years post HTx angiographic CAV was present in 26% of patients with no significant between group difference (no ACR: 40%, only 1R: 24%, at least one 2R/3R: 7%; p=0.06). No correlation was found between number of 1R and ΔMITBL-3Y (r=-0.03, p=0.83). Number of 1R did not predict ΔMITBL3Y in an adjusted linear regression model (p=0.69). No significant interaction with treatment regimen (everolimus/CNI) was found (p=0.84).
S99 and arachidonic acid (AA). Results were reported as area under the curve (aggregation units (AU)*min). If patients received aspirin therapy and it was considered safe to interrupt treatment for 7 days, patients were included in the study. Healthy individuals (n=116) served as controls. CAV burden was determined by echocardiography and coronary angiography based on ISHLT classification. HTx-patients were divided into two groups; no CAV (CAV 0, n=39) and CAV (CAV 1-3, n=20). Results: We found a significant increase in ADP-induced platelet aggregation in HTx-patients with CAV vs. no CAV (902 (95% CI 807-998) vs. 790 (95% CI 733-847) AU*min, P=0.03) and also when comparing with healthy individuals (810 (95 % CI 779-841) AU*min, P=0.03). AAinduced aggregation was higher in HTx-patients with CAV vs. no CAV, though non-significant (998 (95 % CI 908-1089) vs. 905 (95 % CI 840970) AU*min, P=0.09). Conclusion: HTx-patients with CAV have significantly increased ADPinduced platelet aggregation compared with HTx-patients without CAV and healthy individuals, suggesting that patients with CAV could potentially benefit from treatment with ADP receptor inhibitors. Overall, our results indicate that increased platelet aggregation may contribute to CAV development and progression.
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221 Increased Platelet Aggregation in Heart Transplant Recipients with Cardiac Allograft Vasculopathy K.P. Bjerre,1 K. Berg,1 T.S. Clemmensen,2 S.H. Poulsen,1 S.D. Kristensen,1 A. Hvas,1 E.L. Grove,1 and H. Eiskjñr.1 1Aarhus University Hospital, Aarhus N, Denmark; and the 2Horsens Regional Hospital, Horsens, Denmark. Purpose: Cardiac allograft vasculopathy (CAV) remains a leading challenge to long-term survival after heart transplantation (HTx). Imaging of the coronary artery wall with optical coherence tomography has revealed layered fibrotic plaques resembling organized clots. Thus, thrombosis is suggested as a potential mechanism contributing to development and progression of CAV. We aimed to clarify whether HTx-patients with CAV have increased platelet aggregation compared with HTx-patients without CAV and healthy individuals. Methods: In a cross sectional study, platelet aggregation was measured in whole blood from 59 HTx-patients (median 8.6 years from HTx) employing MultiplateÒ Analyzer using adenosine diphosphate (ADP)
Mild Acute Cellular Rejection is Not Associated with Development of Cardiac Allograft Vasculopathy Assessed by Intravascular Ultrasound and Coronary Angiography in Heart Transplant Recipients - A Substudy of the SCHEDULE Trial L.M. Nelson,1 A.K. Andreassen,2 S. Arora,2 B. Andersson,3 E. Gude,2 H. Eiskjñr,4 G. Radegran,5 G. Dellgren,6 L. Gullestad,7 and 1 1 F. Gustafsson. Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; 2Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway; 3 Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden; 4Department of Cardiology, Aarhus University Hospital, Skejby, Aarhus, Denmark; 5The Clinic for Heart Failure and Valvular Disease, Skane University Hospital and Lund University, Lund, Sweden; 6Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden; and the 7 Department of Cardiology, Oslo University Hospital, Rikshospitalet, and University of Oslo, Oslo, Norway. Purpose: The impact of mild (1R) acute cellular rejection (ACR) on the development of cardiac allograft vasculopathy (CAV) after heart transplantation (HTx) remains unclear. We aimed to investigate the association between mild ACR within 1 year of HTx and development of CAV at 3 years post HTx. Methods: This is a substudy of the SCHEDULE trial (n=115) in which de novo HTx recipients were randomized to either (i) everolimus or (ii) conventional CNI-based immunosuppression. 76 patients (66%) were eligible for inclusion based on matched intravascular ultrasound (IVUS) examinations at baseline (BL) and 3 years post HTx. Biopsy proven ACR within year 1 was recorded and graded according to ISHLT criteria (1R, 2R, 3R). Development of CAV was assessed by IVUS and coronary angiography at year 3 post HTx. Results: Median age was 53 years (45-61) and 71% were male. In 67% of patients ACR was recorded during year 1 (1R in 63%, 2R in 24%, and 3R in 3% of patients, respectively). Patients were grouped by rejection profile: no ACR (33%), only 1R (42%), at least one 2R/3R (25%). At 3 years post HTx 49% of patients had CAV on IVUS (maximal intimal thickness, MIT ≥ 0.5 mm) with no difference in the incidence of IVUS-CAV between groups (p=0.43). Median ΔMITBL-3Y was 0.09 mm (0.05-0.15) with no significant difference among groups (p=0.84) (figure 1). At 3 years post HTx angiographic CAV was present in 26% of patients with no significant between group difference (no ACR: 40%, only 1R: 24%, at least one 2R/3R: 7%; p=0.06). No correlation was found between number of 1R and ΔMITBL-3Y (r=-0.03, p=0.83). Number of 1R did not predict ΔMITBL3Y in an adjusted linear regression model (p=0.69). No significant interaction with treatment regimen (everolimus/CNI) was found (p=0.84).