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      Intravascular Ultrasound Correlates with Coronary Flow Reserve and Predicts the Survival in Angiographically Normal Cardiac Transplant Recipients

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          Abstract

          Objectives: We aimed to determine whether epicardial and intramyocardial arteries were involved concordantly in early cardiac allograft vasculopathy. Methods: Thirty consecutive recipients who had received cardiac transplantation more than 1 year before and had a normal coronary angiogram were enrolled for intravascular ultrasound (IVUS), fractional flow reserve, coronary flow reserve and dipyridamole thallium-201 single photon emission computed tomography. Graft failure including cardiac death and retransplantation served as the primary outcome. Results: Plaque volume index and maximum area stenosis calculated from IVUS measurements correlated with coronary flow reserve deterioration in a subgroup of patients with normal fractional flow reserve (n = 13; r = –0.80, p = 0.001 and r = –0.91, p <0.0001, respectively). After follow-up for 18.4 ± 7.6 months, maximum area stenosis was found to be an independent predictor of graft failure (hazard ratio 1.43, 95% confidence interval 1.08–1.89, p = 0.012). Conclusion: In patients with physiologically normal epicardial coronary arteries, impairment of microvascular integrity correlates with the plaque burden measured by IVUS, suggesting the concordant involvement of both epicardial and resistant vessels in early cardiac allograft vasculopathy. Evident epicardial coronary narrowing on IVUS may predict graft failure in spite of normal coronary angiograms.

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          Most cited references 19

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          Intravascular ultrasound evidence of angiographically silent progression in coronary atherosclerosis predicts long-term morbidity and mortality after cardiac transplantation.

          The aim of this study was to determine whether angiographically silent early coronary intimal thickening could predict long-term morbidity and mortality. Although intravascular ultrasound (IVUS) is widely used to detect early transplant coronary disease, its prognostic significance has not been well defined. The study cohort consisted of 143 patients who underwent early multivessel (2.1 +/- 0.7 arteries/patient) IVUS examination 1.0 +/- 0.5 month and 12.0 +/- 1.0 month after transplantation. The change in intimal thickness was evaluated using paired analysis of 1,069 matched sites. Rapidly progressive vasculopathy was defined as the change in intimal thickness >/=0.5 mm. Patients were followed for a primary end point of all-cause mortality and a secondary composite end point of mortality and nonfatal myocardial infarction (MI). Angiographic disease, defined as any >/=50% diameter stenosis, was assessed in 126 patients. Intravascular ultrasound at one year demonstrated rapid progression in 54 (37%) of 143 patients and new lesions in 67 (47%) of 143 of patients. At a mean clinical follow-up of 5.9 years, more patients with rapidly progressive vasculopathy died, as compared with those without (26% vs. 11%, p = 0.03). Death and MI also occurred more frequently among those with rapid progression than in those without it (51% vs. 16%, p /=0.5 mm in intimal thickness within the first year after transplantation, is a powerful predictor of all-cause mortality, MI, and angiographic abnormalities. Accordingly, such patients may be candidates for more aggressive anti-atherosclerotic and/or immunosuppressive therapy.
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            Coronary endothelial dysfunction after heart transplantation predicts allograft vasculopathy and cardiac death.

            Coronary endothelial dysfunction may be an early marker for cardiac allograft vasculopathy (CAV) in orthotopic heart transplant recipients. Using serial studies with intravascular ultrasound and Doppler flow-wire measurements, we have previously demonstrated that annual decrements in coronary endothelial function are associated with progressive intimal thickening. The present study tested whether endothelial dysfunction predicts subsequent clinical events, including cardiac death and CAV development. Seventy-three patients were studied yearly beginning at transplantation until a prespecified end point was reached. End points were angiographic evidence of CAV (>50% stenosis) or cardiac death (graft failure or sudden death). At each study, coronary endothelial function was measured with intracoronary infusions of adenosine (32-microgram bolus), acetylcholine (54 microgram over 2 minutes), and nitroglycerin (200 microgram) into the left anterior descending coronary artery; intravascular ultrasound images and Doppler velocities were recorded simultaneously. Of the 73 patients studied, 14 reached an end point during the study (6 CAV and 8 deaths, including 4 with known CAV, 1 graft failure, and 3 sudden). On the last study performed, the group with an end point had decreased epicardial (constriction of 11.1+/-2.9% versus dilation of 1.7+/-2.2%, P=0.01) and microvascular (flow increase of 75+/-20% versus 149+/-16%, P=0.03) endothelium-dependent responses to acetylcholine compared with the patients who did not reach an end point. Responses to adenosine and nitroglycerin did not differ significantly. Endothelial dysfunction, as detected by abnormal responses to acetylcholine, preceded the development of clinical end points. These data implicate endothelial dysfunction in the development of clinically significant vasculopathy and suggest that serial studies of endothelial function have clinical utility.
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              Simultaneous assessment of fractional and coronary flow reserves in cardiac transplant recipients: Physiologic Investigation for Transplant Arteriopathy (PITA Study).

              The utility of measuring fractional flow reserve (FFR) to assess cardiac transplant arteriopathy has not been evaluated. Measuring coronary flow reserve (CFR) as well as FFR could add information about the microcirculation, but until recently, this has required two coronary wires. We evaluated a new method for simultaneously measuring FFR and CFR with a single wire to investigate transplant arteriopathy. In 53 cases of asymptomatic cardiac transplant recipients without angiographically significant coronary disease, FFR and thermodilution-derived CFR (CFRthermo) were measured simultaneously with the same coronary pressure wire in the left anterior descending artery and compared with volumetric intravascular ultrasound (IVUS) imaging. The average FFR was 0.88+/-0.07; in 75% of cases, the FFR was less than the normal threshold of 0.94; and in 15% of cases, the FFR was or =0.94) and the CFR was abnormal (<2.0), suggesting predominant microcirculatory dysfunction. FFR correlates with IVUS findings and is abnormal in a significant proportion of asymptomatic cardiac transplant patients with normal angiograms. Simultaneous measurement of CFR with the same pressure wire, with the use of a novel coronary thermodilution technique, is feasible and adds information to the physiological evaluation of these patients.
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                Author and article information

                Journal
                CRD
                Cardiology
                10.1159/issn.0008-6312
                Cardiology
                S. Karger AG
                0008-6312
                1421-9751
                2008
                January 2008
                03 August 2007
                : 109
                : 2
                : 93-98
                Affiliations
                Departments of aInternal Medicine, bNuclear Medicine and cSurgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
                Article
                105548 Cardiology 2008;109:93–98
                10.1159/000105548
                17664873
                © 2007 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 1, Tables: 3, References: 28, Pages: 6
                Categories
                Original Research

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