Donor-Transmitted Atherosclerosis Associated With Worsening Cardiac Allograft Vasculopathy After Heart Transplantation: Serial Volumetric Intravascular Ultrasound Analysis

Background The influence of preexisting donor-transmitted atherosclerosis (DA) on cardiac allograft vasculopathy (CAV) development remains unclear. Methods We performed 3-dimensional intravascular ultrasound (3D-IVUS) analysis in 42 heart transplantation (HTx) recipients at 2.1 ± 0.9 months (baseline) and 12.2 ± 0.4 months post-HTx, as well as consecutive 3D-IVUS analyses up to 3 years post-HTx in 35 of the 42 recipients. Donor-transmitted atherosclerosis was defined as a maximal intimal thickness of 0.5 mm or greater at baseline. Changes in volumetric IVUS parameters were compared in recipients with (DA group) and without DA (DA-free group) at baseline, 1 year, and 3 years post-HTx. Results Donor-transmitted atherosclerosis was observed in 57.1% of 42 recipients. The DA group exhibited a significantly greater increase in plaque volume at 1 year post-HTx (P < 0.001), leading to increased percent plaque volume (plaque volume/vessel volume, [%]) (P < 0.001) and decreased luminal volume (P = 0.021). Donor-transmitted atherosclerosis was independently associated with a greater increase in percent plaque volume during the first post-HTx year (P = 0.011). From 1 to 3 years post-HTx, the DA group underwent continuous reduction in luminal volume (P = 0.022). These changes resulted in a higher incidence of angiographic CAV at 3 years post-HTx in the DA group (58.8% vs 5.6%, P = 0.002). Conclusions This volumetric IVUS study suggests that DA correlates with the worsening change in CAV several years post-HTx. Donor-transmitted atherosclerosis recipients may require more aggressive treatment to prevent subsequent CAV progression.

[1]  H. Ishibashi-Ueda,et al.  Risk Stratification for Cardiac Allograft Vasculopathy in Heart Transplant Recipients - Annual Intravascular Ultrasound Evaluation. , 2016, Circulation journal : official journal of the Japanese Circulation Society.

[2]  Takamasa Sato,et al.  Suppressive effects of conversion from mycophenolate mofetil to everolimus for the development of cardiac allograft vasculopathy in maintenance of heart transplant recipients. , 2016, International journal of cardiology.

[3]  H. Ishibashi-Ueda,et al.  Incidence, etiology, and outcome of primary graft dysfunction in adult heart transplant recipients: a single-center experience in Japan , 2016, Heart and Vessels.

[4]  A. Yeung,et al.  Paradoxical Vessel Remodeling of the Proximal Segment of the Left Anterior Descending Artery Predicts Long-Term Mortality After Heart Transplantation. , 2015, JACC. Heart failure.

[5]  L. Lund,et al.  The Registry of the International Society for Heart and Lung Transplantation: Thirty-second Official Adult Heart Transplantation Report--2015; Focus Theme: Early Graft Failure. , 2015, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[6]  G. Ewald,et al.  Everolimus Versus Mycophenolate Mofetil in Heart Transplantation: A Randomized, Multicenter Trial , 2013, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[7]  F. Fallani,et al.  Differential Effect of Everolimus on Progression of Early and Late Cardiac Allograft Vasculopathy in Current Clinical Practice , 2013, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[8]  H. Lehmkuhl,et al.  Impact of De Novo Everolimus-Based Immunosuppression on Incisional Complications in Heart Transplantation , 2011, Transplantation.

[9]  A. Yeung,et al.  Impact of Donor-Transmitted Atherosclerosis on Early Cardiac Allograft Vasculopathy: New Findings by Three-Dimensional Intravascular Ultrasound Analysis , 2011, Transplantation.

[10]  R. Starling,et al.  International Society for Heart and Lung Transplantation working formulation of a standardized nomenclature for cardiac allograft vasculopathy-2010. , 2010, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[11]  D. Thijssen,et al.  Impact of age, sex, and exercise on brachial artery flow-mediated dilatation. , 2009, American journal of physiology. Heart and circulatory physiology.

[12]  W. Kremers,et al.  Acute cellular rejection and the subsequent development of allograft vasculopathy after cardiac transplantation. , 2009, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[13]  M. Weis,et al.  Cardiac allograft vasculopathy: recent developments. , 2008, Circulation.

[14]  P. Libby,et al.  Vascular remodeling in transplant vasculopathy. , 2007, Circulation research.

[15]  B. McManus,et al.  Allograft Vasculopathy Versus Atherosclerosis , 2006, Circulation research.

[16]  J. Tobis,et al.  Influence of pre-existing donor atherosclerosis on the development of cardiac allograft vasculopathy and outcomes in heart transplant recipients. , 2006, Journal of the American College of Cardiology.

[17]  G. Ewald,et al.  Tacrolimus with Mycophenolate Mofetil (MMF) or Sirolimus vs. Cyclosporine with MMF in Cardiac Transplant Patients: 1‐Year Report , 2006, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[18]  E. Tuzcu,et al.  Intravascular ultrasound evidence of angiographically silent progression in coronary atherosclerosis predicts long-term morbidity and mortality after cardiac transplantation. , 2005, Journal of the American College of Cardiology.

[19]  A. Yeung,et al.  Multicenter intravascular ultrasound validation study among heart transplant recipients: outcomes after five years. , 2005, Journal of the American College of Cardiology.

[20]  Silviu Itescu,et al.  Revision of the 1990 working formulation for the standardization of nomenclature in the diagnosis of heart rejection. , 2005, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[21]  E. Tuzcu,et al.  Lumen Loss in Transplant Coronary Artery Disease Is a Biphasic Process Involving Early Intimal Thickening and Late Constrictive Remodeling: Results From a 5-Year Serial Intravascular Ultrasound Study , 2001, Circulation.

[22]  Steven E. Nissen,et al.  High Prevalence of Coronary Atherosclerosis in Asymptomatic Teenagers and Young Adults: Evidence From Intravascular Ultrasound , 2001, Circulation.

[23]  A. Yeung,et al.  Role of vascular remodeling in the pathogenesis of early transplant coronary artery disease: a multicenter prospective intravascular ultrasound study. , 2001, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[24]  C. Tracy,et al.  American College of Cardiology Clinical Expert Consensus Document on Standards for Acquisition, Measurement and Reporting of Intravascular Ultrasound Studies (IVUS). A report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. , 2001, Journal of the American College of Cardiology.

[25]  J. Tobis,et al.  Longitudinal study of vascular remodeling in coronary arteries after heart transplantation. , 2000, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[26]  A. Haverich,et al.  Volumetric remodeling of the proximal left coronary artery: early versus late after heart transplantation. , 1999, Journal of the American College of Cardiology.

[27]  E. Tuzcu,et al.  Development of transplantation vasculopathy and progression of donor-transmitted atherosclerosis: comparison by serial intravascular ultrasound imaging. , 1998, Circulation.

[28]  D. Renlund,et al.  A randomized active-controlled trial of mycophenolate mofetil in heart transplant recipients. Mycophenolate Mofetil Investigators. , 1998, Transplantation.

[29]  A. Haverich,et al.  Mechanism of luminal narrowing in cardiac allograft vasculopathy: inadequate vascular remodeling rather than intimal hyperplasia is the major predictor of coronary artery stenosis. Working Group on Cardiac Allograft Vasculopathy. , 1998, American heart journal.

[30]  A. Yeung,et al.  Relation of donor age and preexisting coronary artery disease on angiography and intracoronary ultrasound to later development of accelerated allograft coronary artery disease. , 1997, Journal of the American College of Cardiology.

[31]  A. Yeung,et al.  Incidence and progression of transplant coronary artery disease over 1 year: results of a multicenter trial with use of intravascular ultrasound. Multicenter Intravascular Ultrasound Transplant Study Group. , 1995, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[32]  L. Yeatman,et al.  Effect of pravastatin on outcomes after cardiac transplantation. , 1995, The New England journal of medicine.

[33]  A. Yeung,et al.  Influence of preexistent donor coronary artery disease on the progression of transplant vasculopathy. An intravascular ultrasound study. , 1995, Circulation.

[34]  A. Wechsler,et al.  Heart transplantation. , 1985, Investigative radiology.

[35]  Antonio Paes De Carvalho,et al.  Spread of activity through the atrioventricular node. , 1960 .