Determinants of myocardial injury following transcatheter aortic valve implantation: a pre-specified substudy from the POPular TAVI trial
Authors: Van Ginkel D J , Brouwer J , Nijenhuis V J , Delewi R , Swaans M J , Timmers L , Rensing B J W M , Baan J , Ten Berg J M 
Published: October 2022

Abstract

Background
Myocardial injury is frequently observed in patients undergoing transcatheter aortic valve implantation (TAVI) and has been linked to worse prognosis [1,2]. Yet, knowledge concerning the underlying mechanisms and preventive strategies is scarce.

Purpose
To identify clinical determinants and the effect of periprocedural antithrombotic strategies on markers of myocardial injury after TAVI.

Methods
The POPular TAVI trial was a prospective, open label, multicentre randomized controlled trial, investigating the addition of clopidogrel to aspirin (cohort A) or oral anticoagulation (OAC) (cohort B) in patients undergoing TAVI [3] Patients randomised to clopidogrel received a 300mg loading dose before TAVI, followed by a 75mg maintenance dose once daily. In patients using OAC, this was continued during TAVI with an international normalized ratio aimed at 2.0. All OAC patients used a vitamin-K antagonist. Blood samples were taken at baseline, 6, 24, 48, and 72 hours following TAVI to determine myocardial injury using Creatine Kinase-MB (CK-MB) and high-sensitive cardiac troponin T (hs-cTnT) according to the VARC-2 criteria. Also, baseline and procedural variables were collected in detail. A linear mixed effects model was used for pair-wise analysis of the changes in enzyme levels at different time points between groups. Regression analysis was performed using the logistic regression model. Statistical analyses were performed using R (version 3.4.1).

Results
In total, 131 patients undergoing transfemoral TAVI were included at two study sites, of whom 63 (48%) received clopidogrel and 68 (52%) did not. Almost half of the patients (45%) were on OAC. The rise in CK-MB (mean peak 23.4±13.3 U/l) and hs-cTnT (mean peak of 0.23±0.33 ug/) was maximal at 6 and 24 hours, respectively. The CK-MB and hs-cTnT levels did not differ between the clopidogrel and no clopidogrel group at any time point (figure 1). Myocardial injury occurred in 18 (30.1%) patients receiving OAC versus 39 (54.2%) patients not receiving OAC (p=0.007). The course of hs-cTnT reached higher levels in patients with chronic kidney disease (p&lt;0.001) and in patients with a preserved left ventricular ejection fraction (LVEF) (p=0.008). Also, the use of a controlled mechanical expanding prosthesis was associated with a higher rise of hs-cTnT (p=0.007). (Figure 2) In multivariable analysis, predictors of a maximal increase in hs-cTnT were a preserved LVEF (OR 1.15, 95% CI 1.02–1.30) and chronic kidney disease (OR 1.13, 95% CI 1.01–1.28). Other procedural factors, like balloon dilation and rapid ventricular pacing, were not associated with myocardial injury.

Conclusions
The addition of clopidogrel to aspirin or OAC during TAVI was not associated with a reduction in myocardial injury. Instead, OAC therapy, as compared to aspirin, was associated with a reduction in rise and fall of hs-cTnT. Also, patients with a preserved LVEF or chronic kidney disease observed higher levels of hs-cTnT.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): ZonMWSt. Antonius Research Fund