Cardiac allograft vasculopathy prevention

Jump to navigation Jump to search

Cardiac allograft vasculopathy Microchapters

Home

Patient Information

Overview

Historical Perspective

Pathophysiology

Differentiating Cardiac allograft vasculopathy from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

Chest X Ray

Coronary Angiography

Intravascular Ultrasound

Optical Coherence Tomography

CT

MRI

Echocardiography

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Cardiac allograft vasculopathy prevention On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Cardiac allograft vasculopathy prevention

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Cardiac allograft vasculopathy prevention

CDC on Cardiac allograft vasculopathy prevention

Cardiac allograft vasculopathy prevention in the news

Blogs on Cardiac allograft vasculopathy prevention

Directions to Hospitals Treating Cardiac allograft vasculopathy

Risk calculators and risk factors for Cardiac allograft vasculopathy prevention

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aarti Narayan, M.B.B.S [2] Raviteja Guddeti, M.B.B.S. [3]

Overview

Prevention

As the pathogenesis of CAV consists of both immunological and non-immunological insults, it has been suggested that preventative strategies should consist of control of risk factors for CAV and optimal immunosuppressive therapy. However, the best preventative strategy to delay development of CAV is yet to be determined.

Optimization of Immunosuppressive Therapy

The rapamycin derivatives, sirolimus and everolimus, have been proven to have significant benefit in the prevention of CAV in addition to statins. Other options for immunosuppressive therapy include [1]:

Everolimus and Sirolimus

  • Act by inhibiting mTOR (mammalian target), thereby having anti-proliferative effects in response to allo-antigens.
  • Everolimus is currently not FDA approved for clinical use in the United States.
  • Associated with significantly reduced incidence of graft rejection.
  • Serial IVUS studies to evaluate intimal proliferation demonstrated smaller increase in maximal intimal thickness and intimal index in patients taking everolimus [2]. Similar results were found in trials that studied sirolimus [3].
  • Side effect profile:

Mycophenolate mofetil

Calcineurin inhibitors

Non-Immunosuppressive therapy

Non-immunosuppressive therapy includes:

Statins

  • Obesity, elevated levels of cyclosporine, use of steroids and insulin resistance all contribute to the development of hyperlipidemia in cardiac transplant patients. Use of statins have proven to reduce mortality in multiple randomized controlled trials.
  • Immunomodulatory effects of statins include:
    • Inhibition of smooth muscle proliferation
      • By inhibiting lipid production, statins halt the intra-cellular signal transduction and consequently protein synthesis
      • By inhibiting expression of genes for growth factors essential for proliferation of smooth muscles
    • Direct influence on gene expression of endothelin-1, leading to improved endothelial function thereby protecting against atherogenesis.
    • Prevents attachment of monocytes to endothelium, which is the first step in atherogenesis [5]
    • In the presence of immunosuppressants like cyclosporin A, statins reduce natural killer cell activity, T cell proliferation and activity in vitro. Moreover, statin induced LDL receptor activation leads to increase in intracellularly available LDL-bound cyclosporin A [6].
  • The effects of simvastatin over a period of 8 years was studied in a randomized controlled trial by Wenke and colleagues [5] in which the study group received simvastatin on the fourth post-operative day, whereas the control group was managed with dietary therapy alone. At the end of 8 years, the Kaplan-Meier survival rate was 88.6% in the simvastatin group versus 59.5% in the control group (P< 0.006 by log rank, HR 0.24,95% CI, 0.08-0.71). The incidence of transplant vasculopathy was also found to be lower in the simvastatin group compared to the control group.

References

  1. Mehra MR (2006). "Contemporary concepts in prevention and treatment of cardiac allograft vasculopathy". Am J Transplant. 6 (6): 1248–56. doi:10.1111/j.1600-6143.2006.01314.x. PMID 16686747.
  2. Eisen HJ, Tuzcu EM, Dorent R, Kobashigawa J, Mancini D, Valantine-von Kaeppler HA; et al. (2003). "Everolimus for the prevention of allograft rejection and vasculopathy in cardiac-transplant recipients". N Engl J Med. 349 (9): 847–58. doi:10.1056/NEJMoa022171. PMID 12944570.
  3. Matsuo Y, Cassar A, Yoshino S, Flammer AJ, Li J, Gulati R; et al. (2013). "Attenuation of cardiac allograft vasculopathy by sirolimus: Relationship to time interval after heart transplantation". J Heart Lung Transplant. 32 (8): 784–91. doi:10.1016/j.healun.2013.05.015. PMC 3727915. PMID 23856215.
  4. Eisen HJ, Kobashigawa J, Keogh A, Bourge R, Renlund D, Mentzer R; et al. (2005). "Three-year results of a randomized, double-blind, controlled trial of mycophenolate mofetil versus azathioprine in cardiac transplant recipients". J Heart Lung Transplant. 24 (5): 517–25. doi:10.1016/j.healun.2005.02.002. PMID 15896747.
  5. 5.0 5.1 Wenke K, Meiser B, Thiery J, Nagel D, von Scheidt W, Krobot K; et al. (2003). "Simvastatin initiated early after heart transplantation: 8-year prospective experience". Circulation. 107 (1): 93–7. PMID 12515749.
  6. Kurakata S, Kada M, Shimada Y, Komai T, Nomoto K (1996). "Effects of different inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, pravastatin sodium and simvastatin, on sterol synthesis and immunological functions in human lymphocytes in vitro". Immunopharmacology. 34 (1): 51–61. PMID 8880225.

Template:WH Template:WS