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HIGHER LEVELS OF ASYMMETRIC DIMETHYLARGININE ARE ASSOCIATED WITH LOWER FRACTIONAL FLOW RESERVE AFTER ORTHOTOPIC HEART TRANSPLANTATION
1355 JACC April 5, 2016 Volume 67, Issue 13
Heart Failure and Cardiomyopathies HIGHER LEVELS OF ASYMMETRIC DIMETHYLARGININE ARE ASSOCIATED WITH LOWER FRACTIONAL FLOW RESERVE AFTER ORTHOTOPIC HEART TRANSPLANTATION Poster Contributions Poster Area, South Hall A1 Saturday, April 02, 2016, 3:45 p.m.-4:30 p.m. Session Title: Heart Transplant and LVADs: New Approaches to Old Issues Abstract Category: 26. Heart Failure and Cardiomyopathies: Clinical Presentation Number: 1136-047 Authors: Rushi Parikh, Kiran Khush, Helen Luikart, Vedant Pargaonkar, Yuhei Kobayashi, Janghoon Lee, Seema Sinha, Garrett Cohen, Hannah Valantine, Alan Yeung, William Fearon, Stanford University School of Medicine, Stanford, CA, USA
Background: Cardiac allograft vasculopathy (CAV) is the leading cause of late mortality after orthotopic heart transplantation (OHT). Endothelial dysfunction is a precursor to the development of both native coronary artery disease (CAD) and CAV. Asymmetric dimethylarginine (ADMA) inhibits endothelial nitric oxide synthase, and higher levels are associated with endothelial dysfunction and development of CAV. In patients with CAD, elevated levels of ADMA correlate with greater degrees of epicardial atherosclerosis and ischemia as assessed by fractional flow reserve (FFR). The relationship between ADMA and FFR and other coronary physiologic indices in the OHT population is unknown. Methods: FFR, coronary flow reserve (CFR), and the index of microcirculatory resistance (IMR) were measured with a coronary pressure wire in the left anterior descending artery within 1 month of OHT (baseline) and again at 1 year. ADMA was assayed at these time points using high performance liquid chromatography. Consistent with prior studies, we used an ADMA threshold of >0.70 µM to identify high-risk patients. Correlation coefficients were derived between ADMA levels and the coronary physiologic indices.
Results: In 47 OHT recipients, higher baseline levels of ADMA were significantly associated with lower baseline FFR values (-8.0% per 0.1 µM, R=0.33, p=0.024). This association remained significant 1 year after OHT (-11.7% per 0.1 µM, R=0.39, p=0.0085). At both baseline and 1 year, those with high-risk ADMA levels had significantly lower FFR values compared to those with low-risk ADMA levels [0.86 vs. 0.91, p=0.031 and 0.84 vs. 0.89, p=0.014, respectively). However, baseline levels of ADMA were not associated with annual FFR values. There was no appreciable correlation between ADMA and measures of microvascular function (CFR or IMR) at baseline or 1 year. Conclusions: Elevated levels of ADMA soon after OHT are significantly associated with lower FFR values but not CFR or IMR. This novel finding suggests that ADMA is a predictor of the epicardial ischemic potential of CAV in OHT recipients. Larger, longitudinal studies are needed to investigate the role ADMA may play in guiding earlier treatment of CAV.
Heart Failure and Cardiomyopathies HIGHER LEVELS OF ASYMMETRIC DIMETHYLARGININE ARE ASSOCIATED WITH LOWER FRACTIONAL FLOW RESERVE AFTER ORTHOTOPIC HEART TRANSPLANTATION Poster Contributions Poster Area, South Hall A1 Saturday, April 02, 2016, 3:45 p.m.-4:30 p.m. Session Title: Heart Transplant and LVADs: New Approaches to Old Issues Abstract Category: 26. Heart Failure and Cardiomyopathies: Clinical Presentation Number: 1136-047 Authors: Rushi Parikh, Kiran Khush, Helen Luikart, Vedant Pargaonkar, Yuhei Kobayashi, Janghoon Lee, Seema Sinha, Garrett Cohen, Hannah Valantine, Alan Yeung, William Fearon, Stanford University School of Medicine, Stanford, CA, USA
Background: Cardiac allograft vasculopathy (CAV) is the leading cause of late mortality after orthotopic heart transplantation (OHT). Endothelial dysfunction is a precursor to the development of both native coronary artery disease (CAD) and CAV. Asymmetric dimethylarginine (ADMA) inhibits endothelial nitric oxide synthase, and higher levels are associated with endothelial dysfunction and development of CAV. In patients with CAD, elevated levels of ADMA correlate with greater degrees of epicardial atherosclerosis and ischemia as assessed by fractional flow reserve (FFR). The relationship between ADMA and FFR and other coronary physiologic indices in the OHT population is unknown. Methods: FFR, coronary flow reserve (CFR), and the index of microcirculatory resistance (IMR) were measured with a coronary pressure wire in the left anterior descending artery within 1 month of OHT (baseline) and again at 1 year. ADMA was assayed at these time points using high performance liquid chromatography. Consistent with prior studies, we used an ADMA threshold of >0.70 µM to identify high-risk patients. Correlation coefficients were derived between ADMA levels and the coronary physiologic indices.
Results: In 47 OHT recipients, higher baseline levels of ADMA were significantly associated with lower baseline FFR values (-8.0% per 0.1 µM, R=0.33, p=0.024). This association remained significant 1 year after OHT (-11.7% per 0.1 µM, R=0.39, p=0.0085). At both baseline and 1 year, those with high-risk ADMA levels had significantly lower FFR values compared to those with low-risk ADMA levels [0.86 vs. 0.91, p=0.031 and 0.84 vs. 0.89, p=0.014, respectively). However, baseline levels of ADMA were not associated with annual FFR values. There was no appreciable correlation between ADMA and measures of microvascular function (CFR or IMR) at baseline or 1 year. Conclusions: Elevated levels of ADMA soon after OHT are significantly associated with lower FFR values but not CFR or IMR. This novel finding suggests that ADMA is a predictor of the epicardial ischemic potential of CAV in OHT recipients. Larger, longitudinal studies are needed to investigate the role ADMA may play in guiding earlier treatment of CAV.