Caracterización del daño neurológico asociado a la TAVI y estrategias terapéuticas para su prevención

Abstract

Transcatheter aortic valve implantation (TAVI) is now the principal therapeutic option in patients with severe aortic stenosis deemed at high surgical risk. Implementing TAVI in a lower risk profile population could be limited by relatively high incidence of neurological damage related with the procedure. Neurological damage has been classified at different levels: clinical (stroke or transient ischemic attack), subclinical (silent embolic infarcts after procedure demonstrated by Diffusion Weighted resonance Imaging [DWI]), and cognitive. DWI studies performed in high risk patients have demonstrated the ubiquitous presence of subclinical damage following TAVI. However its effects on cognition showed inconclusive results. To date, the risk of subclinical damage and cognitive fluctuations following TAVI in a population deemed at lower risk is unknown. There are currently two main strategies to prevent neurological damage related with TAVI: pharmacological (antithrombotic agents) and mechanical (embolic protection devices). Guidelines recommend antiplatelet therapy (APT) post-TAVR to reduce the risk of stroke. However, data on the efficacy and safety of this recommendation in the setting of a concomitant indication for oral anticoagulation (due to atrial fibrillation [AF]) are scare. The first objective (study 1) was to compare the degree of neurological damage using DWI and cognitive testing between TAVI and surgical aortic valve implantation (SAVR) in patients deemed at intermediate surgical risk. The second objective (study 2) was to examine the risk of ischemic events and bleeding episodes associated with differing antithrombotic strategies in patients undergoing TAVI with concomitant AF. The two studies presented were observational. Study #1 was conducted in Vall Hebron Hospital. Forty-six patients undergoing TAVI (78.8±8.3 years, STS score 4.4±1.7) and 37 patients undergoing SAVR (78.9±6.2 years, STS score 4.7±1.7) were compared. DWI was performed within the first 15 days post-procedure. A cognitive assessment was performed at baseline and at 3 months follow-up. TAVI and SAVR groups were comparable in terms of baseline characteristics. There were no differences in incidence of stroke (2.2% in TAVR vs. 5.4% in SAVR, p=0.58), neither in the rate of acute ischemic cerebral lesions detected by DWI (45% vs. 40.7%, adjusted OR 0.95 [0.25-3.65], p=0.94). An older age was a predictor of new lesions (p=0.01), and therapy with vitamin K antagonist (VKA) had a protective effect (p=0.037). Overall no significant changes were observed in global cognitive scores post-intervention. Study #2 was a real world multicenter evaluation comprising 621 patients with AF undergoing TAVI. Two groups were compared: mono-therapy (MT) group (with the use of VKA alone, n=101) vs. multi-antithrombotic (MAT) group (with the use of VKA plus APT, as recommended by guidelines, n=520). During a follow-up of 13 months there were no differences between groups in the rates of stroke (MT 5% vs. MAT 5.2%, HR 1.25 [0.45-3.48], p=0.67), major cardiovascular endpoint (combined of stroke, myocardial infarction or cardiovascular death, p=0.33) or death (p=0.76), however a higher risk of major or life-threatening bleeding was found in the MAT group (HR 1.85 [1.05-3.28], p=0.04). Study #1 found similar rate of cerebral damage following TAVI and SAVR in patients at intermediate risk. Although acute lesions occurred frequently in both strategies, their cognitive impact was not clinically relevant. Study #2 found that in TAVI recipients prescribed VKA therapy for AF, concomitant APT use appears not to reduce the incidence of stroke, major adverse cardiovascular events, or death, while increasing the risk of major or life-threatening bleeding. Though only observational, the important lessons to be drawn from this thesis are that under a neurological perspective implementing TAVI in an intermediate risk populations appears reasonable; and that the currently recommendation of prescribing APT for patients with AF who are already on long-term anticoagulation does not confer any benefit while potentially being harmful.

Date of Award	4 Sept 2017
Original language	Spanish
Awarding Institution	Vall d'Hebron University Hospital (HUVH)
Supervisor	Maria Pilar Tornos Mas (Director) & Ignacio Jose Ferreira Gonzalez (Director)