Clinical Heart Transplantations
Functional and morphological findings in heart transplant recipients with a normal coronary angiogram: an analysis by dobutamine stress echocardiography, intracoronary Doppler and intravascular ultrasound

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Abstract

Background: Coronary angiography is still the routine screening method for cardiac allograft vasculopathy in most transplant centers. This study was designed to analyze functional and morphologic changes in heart transplant recipients with normal angiographic findings.

Methods

Dobutamine stress echocardiography and intracoronary ultrasound were obtained in 56 patients with a normal coronary angiogram 41 ± 31 months after heart transplantation. Intracoronary Doppler flow velocity measurements before and after intracoronary adenosine administration were performed in 34 of 56 patients. Any regional wall motion abnormalities detected by stress echocardiography were regarded as abnormal. By quantitative intracoronary ultrasound analysis using a 6-grade scale, a mean grade of all coronary segments >3.0 was defined as significant intimal hyperplasia.

Results

Only 17 patients (30%) showed both a normal dobutamine stress echocardiogram and absence of significant intimal hyperplasia by intravascular ultrasound. Abnormal findings were observed in 39 patients (70%): both by dobutamine stress echocardiography and intravascular ultrasound in 22 patients, by intravascular ultrasound alone in 11 patients, and by dobutamine stress echocardiography alone in 6 patients. Coronary flow velocity reserve did not discriminate between patients with normal or abnormal intravascular ultrasound or dobutamine stress echocardiographic findings.

Conclusions

Only a minority of heart transplant patients with a normal coronary angiogram is free of pathological changes, when assessed by intravascular ultrasound and dobutamine stress echocardiography. Coronary flow velocity reserve does not seem useful to further characterize these patients. J Heart Lung Transplant 1999; 18:391–398.

Section snippets

Patient population

From 100 consecutive orthotopic heart transplant recipients undergoing scheduled routine coronary angiography in the chronic postoperative phase (≥10 months after transplantation), 56 patients were selected fulfilling the criteria of A) a normal coronary angiogram by visual analysis and B) an adequate echocardiographic image quality. The mean age was 49 ± 11 years, the postoperative interval was 41 ± 31 (10–144) months. Immunosuppressive therapy consisted of cyclosporine (n = 46), tacrolimus (n

Statistics

Data are given as mean ± standard deviation, unless stated otherwise. Unpaired Student′s t-test, Mann-Whitney U-test, or Fisher′s exact test were used, as appropriate, to assess differences between groups. Differences between stress stages were analyzed with a Wilcoxon rank sum test. A p value of <0.05 was considered significant.

Clinical characteristics

Arterial hypertension requiring medical therapy was present in 51 of 56 patients (91%). The mean systolic / diastolic blood pressure at rest before stress echocardiography was 125 ± 17/76 ± 13 mmHg. There were no differences in blood pressure in subgroups of patients with and without abnormal either echocardiographic or IVUS findings. All patients in this study were non-smokers. Fifteen patients (27%) had diabetes mellitus after transplantation; the prevalence of diabetes was not different in

Discussion

Coronary angiography has remained the most commonly used screening method for CAV.2, 3, 5 Several reports exist, however, on rapid progression from a normal angiogram to severe vasculopathy, that in some cases of sudden death after heart transplantation was diagnosed only at necropsy.4, 20 IVUS has been demonstrated to be the most sensitive invasive tool for diagnosis of CAV in vivo.6, 7, 8, 9, 10 IVUS, however, does not allow to investigate the complete coronary artery system as it is

Conclusion

A normal angiogram alone does not exclude relevant CAV in heart transplant recipients. Despite of a normal coronary angiogram, the majority of patients in this study had functional alterations as regional wall motion abnormalities and impaired systolic wall thickening by dobutamine stress echocardiography and morphologic evidence of CAV in the epicardial arteries by IVUS. Measurement of coronary flow velocity reserve, however, does not seem useful to identify patients with abnormal findings by

References (33)

  • J.D Hosenpud et al.

    The registry of the international society for heart and lung transplantation. Fourteenth official report-1997

    J Heart Lung Transplant

    (1997)
  • S.W Jamieson

    Investigation of heart transplant coronary atherosclerosis

    Circulation

    (1992)
  • M Weis et al.

    Cardiac allograft vasculopathy. A review

    Circulation

    (1997)
  • F.G St. Goar et al.

    Intracoronary ultrasound in cardiac transplant recipientsin vivo evidence of angiographically silent intimal thickening

    Circulation

    (1992)
  • T.J Anderson et al.

    Functional significance of intimal thickening as detected by intravascular ultrasound early and late after cardiac transplantation

    Circulation

    (1993)
  • E.A Caracciolo et al.

    Influence of intimal thickening on coronary blood flow responses in orthotopic heart transplant recipientsa combined intravascular Doppler and imaging study

    Circulation

    (1995)
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    Reprint requests: Christoph H. Spes, MD, Dept. of Cardiology, Medizinische Klinik, Klinikum Innenstadt, University of Munich, Ziemssenstr. 1, D-80336 München, Germany.

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