One-year vasculopathy, as defined by an increase in Maximal Intimal Thickness (MIT) of > 0.5mm by intravascular ultrasound was shown to be predictive of 5-year clinical events. This data was presented by Jon Kobashigawa, MD, UCLA Medical School, during the session entitled "Multi-Center Intravascular Ultrasound Validation Study Among Heart Transplant Recipients: Outcomes after 5 years."
Patients with first-year change in MIT ³ 0.5 mm compared to those patients with MIT < 0.5mm had higher incidence of death or graft loss (20.8% vs. 5.9%, p=0.007), more Non-Fatal cardiac events, or more newly occurring angiographic luminal irregularities (65.2% vs. 32.6%, p=0.004).
In a second presentation, Randall Starling, MD, of the Cleveland Clinic Foundation, described the favorable effect of the proliferation signal inhibitor everolimus on cardiac allograft vasculopathy, and its concomitant reduction in acute rejection rates, is maintained through 24 months.
In this 634-patient study conducted in 54 centers worldwide, prospective analysis of the IVUS-population (matched analysis, n=149) was performed. This study, using rigorous IVUS techniques, revealed that the early findings of attenuation of development of intimal thickening by using everolimus remained even on analysis of 2 year end-points.
Dr. Javier Segovia, Clinic Puerta de Hierro, Madrid, reported in a third study that sirolimus, another proliferation signal inhibitor, reduced coronary lesions of patients with established cardiac allograft vasculopathy. In this small trial, there was suggestion of a plaque regression in those treated as compared with conventional immunosuppressive regimens.
During the panel discussion, following the presentations, chaired by Mandeep Mehra, MD, Ochsner Clinic Foundation, New Orleans, Dr. Mehra discussed the importance of the choice of using a threshold of intimal thickness of > 0.5mm versus > 0.3mm (as used in the MMF versus AZA study presented earlier in the congress). The panel responded that an increase of at least 0.5mm has been more robustly validated as a clinically relevant measurement and represents an "unequivocal" threshold of abnormality.
Panelist Javier Segovia, MD, added that "a cut-off of 0.3mm MIT may be too close to the limit of precision of this technique (0.2mm). Furthermore, 0.3mm MIT is sometimes observed in the donor heart early after transplantation."
The value of IVUS end-points as a valid surrogate in the context of a therapeutic intervention was also debated. While most panel members agreed that discrepancies exist in the data to date, clinical decisions cannot be delayed for several years until the long term evidence is available.
Dr. Starling, co-moderator for the session, stated in conclusion, "What is striking in the results presented today is that the direction and magnitude of all intravascular ultrasound measurements were concordant in favor of everolimus as a preventative strategy and sirolimus in the regression of cardiac allograft vasculopathy."
About IVUS and Cardiac Allograft Vasculopathy
Cardiac allograft vasculopathy, or transplant vessel damage, is a thickening of artery walls in a transplanted heart, which can result in restricted blood flow and sometimes clots, causing heart attacks and other life threatening events. Ultrasound can be used to measure thickening in arterial walls.
The International Society for Heart and Lung Transplantation (ISHLT) is a not-for-profit organization dedicated to the advancement of the science and treatment of end-stage heart and lung diseases. Created in 1981 at a gathering of about 15 cardiologists and cardiac surgeons, the Society now includes more than 2,200 members from 45-plus countries, representing a variety of disciplines involved in the management and treatment of end-stage heart and lung disease.
ISHLT maintains two databases. The International Heart and Lung Transplant Registry is a one-of-a-kind registry that has been collecting data since 1983 from 223 hospitals from 18 countries. The ISHLT Mechanical Circulatory Device (MCSD) database has been collecting data since 2002 with the aim of identifying patient populations who may benefit from MCSD implantation; generating predictive models for outcomes; and assessing the mechanical and biological reliability of current and future devices.