Original article
Validation of the usefulness of 2-dimensional strain parameters to exclude acute rejection after heart transplantation: a multicenter studyValidación de la utilidad de los parámetros de deformación miocárdica para excluir el rechazo agudo tras el trasplante cardiaco: un estudio multicéntrico

https://doi.org/10.1016/j.rec.2020.01.012Get rights and content

Abstract

Introduction and objectives

Two-dimensional speckle-tracking echocardiography has emerged as a promising alternative to endomyocardial biopsy to rule out acute cellular rejection after orthotopic heart transplantation (OHT) in single center studies. In an original cohort, 15.5% and 17% of cutoff points for left ventricular global longitudinal strain (LVGLS) and free-wall right ventricular longitudinal strain, respectively, achieved 100% negative predictive value to exclude moderate or severe acute cellular rejection (ACR ≥ 2R). Our objective was to demonstrate the usefulness of speckle-tracking and validate these cutoff points in an external cohort.

Methods

A prospective, multicenter study that included patients who were monitored during their first year after OHT was conducted. Echocardiographic studies analyzed by local investigators were compared with simultaneous paired endomyocardial biopsies samples.

Results

A total of 501 endomyocardial biopsy-echocardiographic studies were included in 99 patients. ACR ≥ 2R was present in 7.4% of samples. LVGLS and free-wall right ventricular longitudinal strain were significantly reduced during ACR ≥ 2R on univariate analysis. On multivariate analysis, LVGLS was independently associated with the presence of ACR ≥ 2R. The original cutoff points demonstrated a negative predictive value of 94.3% to exclude ACR ≥ 2R.

Conclusions

This study maintained a strong negative predictive value to exclude ACR ≥ 2R after OHT and LVGLS was independently associated with the presence of ACR ≥ 2R. We propose the use of speckle-tracking, especially LVGLS, as part of the noninvasive diagnosis and management of ACR.

Resumen

Introducción y objetivos

Algunos estudios indican que los parámetros de strain por speckle-tracking pueden ser una alternativa no invasiva a la biopsia endomiocárdica para excluir el rechazo celular agudo (RCA) moderado o grave (≥ 2R) tras el trasplante cardiaco (TxC). En una cohorte inicial, unos puntos de corte del 15,5% para el strain longitudinal global del ventrículo izquierdo (SLGVI) y el 17% para el strain de pared libre del ventrículo derecho mostraron un valor predictivo negativo del 100% para excluir RCA ≥ 2R. Nuestro objetivo es analizar la utilidad del strain y validar estos puntos de corte en una cohorte multicéntrica prospectiva externa.

Métodos

Estudio multicéntrico y prospectivo que incluyó a pacientes con seguimiento el primer año tras el TC. Se compararon los resultados de biopsias electivas con ecocardiogramas realizados el mismo día.

Resultados

Se incluyó a 99 pacientes y 501 pares de biopsias-ecocardiogramas. El RCA ≥ 2R en las biopsias fue del 7,4%. El SLGVI y el strain longitudinal de pared libre del ventrículo derecho fueron menores durante los RCA ≥ 2R en el análisis univariante. En el análisis multivariante, el SLGVI se asoció de manera independiente con el RCA ≥ 2R. Los puntos de corte originales mostraron un valor predictivo negativo del 94,3% el RCA ≥ 2R.

Conclusiones

Este estudio mantiene un alto valor predictivo negativo para excluir RCA ≥ 2R tras el TxC y el SLGVI se asoció de manera independiente con el RCA ≥ 2R. El strain y, principalmente, el SLGVI pueden ser de utilidad en el diagnóstico y el tratamiento no invasivo del RCA.

Section snippets

INTRODUCTION

Advances in immunosuppression have led to a decrease in the incidence of acute cellular rejection (ACR) after orthotopic heart transplant (OHT).1 However, ACR is still a major concern as its presence is related to graft loss and reduced long-term survival.2 Thus, active ACR surveillance after OHT is mandatory. This is especially relevant given that the current “gold standard” technique for ACR detection is endomyocardial biopsy (EMB), which is an invasive method that is not free of

METHODS

This multicenter study was performed by 7 Spanish cardiac transplant centers. Patients admitted for OHT were consecutively and prospectively included in the study from December 2015 to December 2016 and were monitored during their first year after OHT. We evaluated pairs of EMB and echocardiographic studies performed within 24 hours of the EMB and always before ACR treatment in patients requiring this treatment.

EMBs were performed periodically at 15 days, 1 month, 2 months, 3 months, 6 months

RESULTS

From December 2015 to December 2016, 99 patients were included in the study (table 2 of the supplementary data). Five patients were excluded due to a suboptimal echocardiographic window. We initially included 516 EMB and echocardiographic paired studies, although 15 (2.9%) pairs were excluded due to insufficient material in EMB that precluded their comparison with echocardiograms. Finally, 501 EMB and their corresponding echocardiographic evaluations were analyzed. The average number of EMB per

DISCUSSION

In this multicenter study, we sought to validate the value of STE parameters to exclude ACR in asymptomatic patients during the first year after OHT. To the best of our knowledge, this is the first multicenter study to evaluate the usefulness of STE in ACR after OHT. We also assessed the usefulness of RV strain analysis, which has been poorly described to date in this scenario.

Our study confirms the reduction in left ventricular and right ventricular STE parameters during ACR ≥ 2R. Furthermore,

CONCLUSIONS

Our results demonstrate a strong NPV when both LVGLS and free-wall RVLS are combined providing a feasible and helpful tool in the noninvasive management of ACR. Besides, LVGLS was independently associated with the presence of ACR ≥ 2R. We propose the use of STE parameters particularly in clinically stable low-risk patients with higher STE absolute values in order to alleviate the burden of repeated EMB. Further studies with larger sample size are needed to confirm these results.

WHAT IS KNOWN ABOUT THIS TOPIC?

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    STE parameters

FUNDING

This study received a research grant from the Working Group on Heart Failure and Heart Transplantation of the Spanish Society of Cardiology.

CONFLICTS OF INTEREST

C.-H. Li reports speaker fees from Philips, outside the submitted work. The other authors declare no conflicts of interest.

Acknowledgements

The authors are grateful to Fina Casals, Zulaika Grille, Paula Blanco and all the Heart Transplantation and Cardiac Imaging Units that collaborated in this project.

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    © 2020 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.