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.
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.
Jaeger
Beate R
BR
Institut für Klinische Chemie, Klinikum der Universität München, München, Germany.
Bengel
Frank M
FM
Odaka
Kenichi
K
Uberfuhr
Peter
P
Labarrere
Carlos A
CA
Bengsch
Stefan
S
Engelschalk
Clemens
C
Kreuzer
Eckart
E
Reichart
Bruno
B
Schwaiger
Markus
M
Seidel
Dietrich
D
D000925:Anticoagulants / Q000627:therapeutic use; D001781:Blood Component Removal; D001809:Blood Viscosity; D011232:Chemical Precipitation; D008078:Cholesterol, LDL / Q000097:blood* / Q000302:isolation & purification; D003326:Coronary Circulation; D005260:Female; D005340:Fibrinogen / Q000032:analysis* / Q000302:isolation & purification; D016027:Heart Transplantation; D006439:Hemodynamics; D006493:Heparin / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation; D049268:Positron-Emission Tomography; D012039:Regional Blood Flow; D012307:Risk Factors
D000925:Anticoagulants; D008078:Cholesterol, LDL; D005340:Fibrinogen; D006493:Heparin