International Progress In Heart Transplantation and The “Vienna Factor” Mandeep R. Mehra, MD President , International Society For Heart and Lung Transplantation Editor-in-Chief, Journal of Heart and Lung Transplantation Herbert Berger Chair in Medicine, Professor and Head of Cardiology Assistant Dean for Clinical Services, University of Maryland School of Medicine Baltimore, MD Disclosures: consultant to Roche, Astellas, XDX, Novartis
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International Progress In Heart Transplantation and The “Vienna Factor” Mandeep R. Mehra, MD President, International Society For Heart and Lung Transplantation.
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International Progress In Heart Transplantation
and The “Vienna Factor”
Mandeep R. Mehra, MDPresident , International Society For Heart and Lung Transplantation
Editor-in-Chief, Journal of Heart and Lung TransplantationHerbert Berger Chair in Medicine, Professor and Head of CardiologyAssistant Dean for Clinical Services, University of Maryland School of
MedicineBaltimore, MD
Disclosures: consultant to Roche, Astellas, XDX, Novartis
The Fascination With Transplantation Has Existed For Centuries
• Scientific Exchange
• Financial pressures
1982: The Launch of the Society Journal
Medium of Progress
•The International Registry
•Guidelines and position Statements
Vienna HeroesWOLNER
WIESELTHALER
LAUFER
ZUCKERMANN
KLEPETKO
GRIMM
Vienna Contributions• Pharmacokinetics And Dynamics Of Novel
Immunosuppression
• Genomic And Proteomic Biomarkers For Cardiac Rejection And Cardiac Allograft Vasculopathy
• Novel Aspects Of Mechanical Circulatory Support
• International Advocacy
Specific Causes of Death One Year After Cardiac Transplantation
Kirklin JK, et al. J Thorac Cardiovasc Surg 2003; 125:881-90.
Intimal thickening (mm) Kobashigawa JA et al. J Am Coll Cardiol 2005; 45:1532-7.Mehra M et al. J Heart Lung Transplant 1995; 14:S207-11.
Tuzcu EM et al. J Am Coll Cardiol 2005; 45:1538-42.
0.35 0.50 1.000
Early
Mid
Late
Normal
SevereAbnormal
LowHighModerate
Risk of cardiac event
Post-transplantation
time
“Prognostically relevant”- High plaque burden- Link with cardiac events
IVUS Findings Versus Survival in Heart Transplantation
Therapy Attenuation of Intimal
Thickening
Rejection Non – Immune Effects
Survival (Duration Studied)
Statins Modest Rejection with HDC
Lipids
CRP
Improved
(10 years)
Mycophenolate mofetil
Modest Rejection
with HDC
Neutral Improved
(3 years)
Everolimus / sirolimus
Marked Acute cellular rejection only
Less CMV
Worse triglycerides
and renal function
No improveme
nt
(4 years)
Mehra MR. Am J Transplant 2006Mehra MR. Am J Transplant 2006
Multi-Detector Coronary CTA• Sigurdsson G JACC
2006;48:772-8.– 16 slice, n=54 >1.5 mm
vessel, NPV 99%, PPV 81%
• Gregory SA AJC 2006;98:877-884.– 64 slice, n=20, IVUS and
QCA, IVUS NPV 77%, PPV 89%
• Limitations contrast, radiation
• Prognosis??
Adapted after: Medzhitov R, Janeway CA Jr: Science, 2002
Danger SignalsDrive subsequent
immune activation and Inflammation
Infection/Injury
Pathogen-associated molecular patterns (PAMPs)
Toll
APC
MHC/peptide Co-stimulator
TCR CD28
Activation of the adaptive immune response
IMMUNOLOGICAL FACTORS
CLINICAL OUTCOME
Engraftment
“Danger Signals”IMMUNE ACTIVATION
RELATED INFLAMMATION
NON-IMMUNOLOGICAL FACTORS
VASCULOPATHY
“DANGER SIGNALS”
To cease smoking is the easiest thing I ever did…..
I ought to know because I've done it a thousand times
Mark Twain, 1905
Tobacco Exposure After Heart Transplantation: How Frequent?
Mehra M et al. American Journal of Transplantation 2005
• In 86 consecutive heart transplant recipients, 28 had evidence of significant tobacco exposure
• 32.5% rate of recrudescence– 14 with urine positivity (denied exposure)– 12 admitted exposure and had urine positivity– 2 admitted to smoking but were not urine
positive
Smoking Kills The Cardiac Allograft
Botha et al. American Journal of Transplantation 2008
The Cardiac Allograft Is Going Up In Smoke: A Call to Action
Mehra M et al. American Journal of Transplantation 2005Mehra M. American Journal of Transplantation 2008
• A Third of patients resume smoking after a heart transplant!
• Although advances in prevention of rejection allow median survival of 15 years, smokers reduce their average life span by 4.5 years
• Most deaths occur due to development of accelerated coronary artery disease and new cancers
A B
C D
A: Normal proximal tubular epithelial cells from a rat without cigarette smoke exposure; B: Swollen tubular epithelial cells, vacuoles, damaged glomerulus and fibrosis in a rat exposed to cigarette smoke for 30 days; C: normal glomerulus and D: completely damaged glomerulus in a rat exposed to cigarette smoke
Science is nothing but developed perception, interpreted intent,