Usefulness of speckle tracking echocardiography and biomarkers for detecting acute cellular rejection after heart transplantation

Abstract

Background: Acute cellular rejection (ACR) is a major complication after heart transplantation. Endomyocardial biopsy (EMB) remains the gold standard for its diagnosis, but it has concerning complications. We evaluated the usefulness of speckle tracking echocardiography (STE) and biomarkers for detecting ACR after heart transplantation.

Methods: We prospectively studied 60 transplant patients with normal left and right ventricular systolic function who underwent EMB for surveillance 6 months after transplantation. Sixty age- and sex-matched healthy individuals constituted the control group. Conventional echocardiographic parameters, left ventricular global longitudinal, radial and circumferential strain (LV-GLS, LV-GRS and LV-GCS, respectively), left ventricular systolic twist (LV-twist) and right ventricular free wall longitudinal strain (RV-FWLS) were analyzed just before the procedure. We also measured biomarkers at the same moment.

Results: Among the 60 studied patients, 17 (28%) had severe ACR (grade ≥ 2R), and 43 (72%) had no significant ACR (grade 0 - 1R). The absolute values of LV-GLS, LV-twist and RV-FWLS were lower in transplant patients with ACR degree ≥ 2 R than in those without ACR (12.5% ± 2.9% vs 14.8% ± 2.3%, p=0.002; 13.9° ± 4.8° vs 17.1° ± 3.2°, p=0.048; 16.6% ± 2.9% vs 21.4%± 3.2%, p < 0.001; respectively), while no differences were observed between the LV-GRS or LV-GCS. All of these parameters were lower in the transplant group without ACR than in the nontransplant control group, except for the LV-twist. Cardiac troponin I levels were significantly higher in patients with significant ACR than in patients without significant ACR [0.19 ng/mL (0.09-1.31) vs 0.05 ng/mL (0.01-0.18), p=0.007]. The combination of troponin with LV-GLS, RV-FWLS and LV-Twist had an area under curve for the detection of ACR of 0.80 (0.68-0.92), 0.89 (0.81-0.93) and 0.79 (0.66-0.92), respectively.

Conclusion: Heart transplant patients have altered left ventricular dynamics compared with control individuals. The combination of troponin with strain parameters had higher accuracy for the detection of ACR than the isolated variables and this association might select patients with a higher risk for ACR who will benefit from an EMB procedure in the first year after heart transplantation.

Keywords: Acute cellular rejection; Heart transplantation; Speckle tracking echocardiography.

Fig. 1

Study flow diagram. EMB = endomyocardial biopsy; ACR = acute cellular rejection

Fig. 2

Twist, left ventricular global longitudinal strain and right ventricular free wall longitudinal strain in the control group and in two groups of heart transplant patients, those with and those without significant acute cellular rejection (R ≥2 vs. R ≤1) ANOVA: F-test. *Significative to 5% (Tukey test for all pairwise comparisons); 1: Ctrl = Control (Cardiac untransplanted patients); 2: Heart transplant patients without rejection (R ≤1); 3: Heart transplant patients with rejection (R ≥2). SD: Standard Deviation; LV-GLS: Left Ventricular Global Longitudinal Strain; RV-FWLS, Right Ventricular Free Wall Longitudinal Strain

Fig. 3

a Receiver operating characteristic curve demonstrating troponin, the right ventricular free wall longitudinal strain, left ventricular global longitudinal strain and left ventricular twist values obtained by speckle-tracking echocardiography for the diagnosis of acute cellular rejection in heart transplant patients. b Receiver operating characteristic curve demonstrating troponin combined with right ventricular free wall longitudinal strain, left ventricular global longitudinal strain and with left ventricular twist values obtained by speckle-tracking echocardiography for the diagnosis of acute cellular rejection in heart transplant patients. AUC = area under curve; CI = confidence interval; LV GLS, left ventricular global longitudinal strain; RV FWLS, right ventricular free wall longitudinal strain