Changes in myocardial vasoreactivity after drastic reduction of plasma fibrinogen and cholesterol: a clinical study in long-term heart transplant survivors using positron emission tomography

J Heart Lung Transplant. 2005 Dec;24(12):2022-30. doi: 10.1016/j.healun.2005.05.009. Epub 2005 Sep 15.

Abstract

Background: Given the central importance of the microvasculature in heart transplant recipients, we investigated the possibility of increasing cardiac perfusion after reduction of low-density lipoprotein (LDL)-cholesterol, lipoprotein (a), C-reactive protein (CRP) and fibrinogen plasma levels after apheresis treatment in transplanted patients.

Methods: Ten long-term heart transplant recipients were examined with positron emission tomography (PET) to measure myocardial perfusion before and after a single heparin-mediated extracorporeal LDL/fibrinogen precipitation (HELP)-apheresis treatment. PET studies were performed the mornings before and after the apheresis treatment. Myocardial blood flow at rest and during adenosine-induced hyperemia was measured using (13)N-ammonia.

Results: HELP-apheresis reduced the plasma levels of LDL-cholesterol, lipoprotein (a) and C-reactive protein by 48% (p < 0.001), fibrinogen by 42% (p = 0.02), plasma viscosity by 14% (p = 0.004) and erythrocyte aggregation by 28% (p < 0.02). Osmolality (<1%) and hematocrit (<2%) remained stable. A single apheresis treatment increased median corrected rest flow by 17.5% (p = 0.007) and median hyperemic flow by 27% (p = 0.02). Median coronary flow reserve increased by 8.1% (p = 0.09). Hyperemic flow after adenosine infusion increased plasma vascular endothelial growth factor levels only before HELP-apheresis (+60%), indicating better ischemic tolerance after apheresis (p = 0.01).

Conclusions: Myocardial perfusion in transplanted hearts increases significantly after single HELP-apheresis treatment. The present study is only a proof of concept, providing complementary evidence to clinical long-term studies showing that cholesterol reduction either with statins and/or apheresis improves heart transplant outcome.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticoagulants / therapeutic use
  • Blood Component Removal*
  • Blood Viscosity
  • Chemical Precipitation
  • Cholesterol, LDL / blood*
  • Cholesterol, LDL / isolation & purification
  • Coronary Circulation*
  • Female
  • Fibrinogen / analysis*
  • Fibrinogen / isolation & purification
  • Heart Transplantation*
  • Hemodynamics
  • Heparin / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Platelet Aggregation
  • Positron-Emission Tomography
  • Regional Blood Flow
  • Risk Factors

Substances

  • Anticoagulants
  • Cholesterol, LDL
  • Fibrinogen
  • Heparin