Clinical heart transplantation
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

https://doi.org/10.1016/j.healun.2005.05.009Get rights and content

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 13N-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.

Section snippets

Objective and Study Design

The primary objective of this study was the comparison of myocardial blood flow before and shortly after apheresis treatment. Secondary objectives were the analysis of the hemorheologic consequences and the possible role of mediators such as nitric oxide or vascular endothelial growth factor (VEGF) in this setting. The study protocol is outlined in Figure 1. First, a baseline PET examination was performed under rest conditions and after adenosine infusion. At that time, patients had elevated

Comparison of Laboratory Variables

Plasma concentrations of LDL-cholesterol (LDL-C), lipoprotein (a), fibrinogen and CRP before and after apheresis are outlined in Table 2. The baseline concentration of LDL-cholesterol was elevated considerably (191 ± 44 mg/dl), as were the concentrations of lipoprotein (a) (63 ± 29 mg/dl), CRP (0.95 ± 1.31 mg/dl) and fibrinogen (4.65 ± 0.95 g/liter). HELP-apheresis significantly reduced the concentrations to almost normal levels. On the following day before the second PET study the

Discussion

Long-term transplant survival involves a number of adaptation processes in the hemodynamic environment to accommodate the allograft for daily physiologic needs, despite advanced graft arteriosclerosis. The present study has demonstrated that a 50% reduction of most of the relevant atherogenic blood compounds after a single HELP-apheresis treatment has significant hemodynamic implications for cardiac allograft macro- and microcirculation. Remarkably, these findings suggest that the

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    Supported by B. Braun AG, Melsungen, Germany.

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