Regression of transplant coronary artery disease during chronic low-density lipoprotein-apheresis.

BACKGROUND

The pathogenesis of transplant coronary artery disease (TxCAD) is probably multifactorial. Immune mechanisms may be the primary and triggering stimuli, whereas risk factors such as hyperlipoproteinemia or lipoprotein(a) elevation may accelerate the progression of the disease. With the heparin-induced-low-density lipoprotein-precipitation (HELP), low-density lipoprotein (LDL), fibrinogen, and lipoprotein(a) can be reduced about 55%, 50%, and 60%, respectively.

METHODS

We treated eight heart transplant recipients (52.6 +/- 8.1 years old; all men) with weekly LDL-apheresis (HELP-system). At the beginning of the HELP treatment, all patients had survived at least 2 years after surgery, had LDL levels higher than 150 mg/dl in spite of 10 mg pravastatin per day and diet, and had development of significant coronary artery disease as shown by annual coronary angiography. We analyzed three angiograms in each patient taken 16.2 +/- 6.5 months before, at the beginning of (-0.5 +/- 6 months), and after 21.8 +/- 7.4 months of HELP therapy. Two hundred seventy-three coronary artery segments (34 +/- 6 per patient; 6 to 65 single measurements per segment) were analyzed by quantitative coronary angiography. Statistical significances of differences between the angiograms taken at the three time points were evaluated by the paired t test.

RESULTS

Measurements of all coronary artery segments showed a significant decrease of mean luminal diameter during the last 1 to 2.5 years before the HELP treatment from 3.61 +/- 1.1 mm to 3.15 +/- 1 mm (p < 0.0001). During the following 1 to 2.5 years of HELP therapy, the mean luminal diameter increased to 3.4 +/- 1.15 mm (p < 0.0001).

CONCLUSIONS

In long-term heart transplantation survivors with hyperlipidemia, who have development of a rapid progressive coronary artery disease, LDL-apheresis can lead to disease regression. Further studies will be needed to determine whether immunologic factors and growth factors involved in the TxCAD pathogenesis are also eliminated by the HELP therapy and whether HELP is also effective in patients with TxCAD without severe hypercholesterolemia.