Patel, Kush P; (2023) Aortic Stenosis: Multimorbidity and Myocardial Impact on Patients undergoing Transcatheter Aortic Valve Implantation. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Introduction: In aortic stenosis (AS), the myocardium remodels to compensate for the obstruction to forward flow before eventually decompensating, often acutely- termed acute decompensated AS (ADAS). Patients with AS often have other comorbidities, including coronary artery disease (CAD), cardiac amyloidosis (ATTR) and frailty which may also influence the myocardium and outcomes. This thesis examines the impact of multimorbidity on the myocardium and outcomes, diagnostic markers and decompensation in three patient populations: ATTR, CAD and ADAS. / Methods: To evaluate the impact of AS and ATTR on the combined phenotype AS-ATTR, I compared 4 prospective cohorts (n=583): elderly controls, severe AS, AS-ATTR and ATTR. Using a single-centre, registry I retrospectively evaluated the impact o mong 1902 transcatheter aortic valve implantation (TAVI) patients, I assessed the impact of CAD stratified by location (left main stem (LMS) vs non-LMS) and territory (single-vessel vs multi-vessel) on mortality. I examined the diagnostic ability of 3 commonly used metrics: Troponin T, ischaemic ECG and angina, to diagnose a type 1 NSTEMI in 273 AS patients with acute presentations. I compared outcomes with TAVI in patients with ADAS vs non-ADAS. Within the ADAS cohort, I evaluated the prognostic role of a new echo based staging classification. / Results: Dual pathology with AS-ATTR is more closely related to ATTR than it is to AS, despite a similar burden of amyloid. Only LMS CAD was independently associated with mortality (HR: 1.57) after the first year post-TAVI. All 3 metrics have a low sensitivity and diagnostic ability (AUC 0.625, 0.559 and 0.692 respectively). TAVI procedural complications and mortality were similar between ADAS and non-ADAS cohorts. However, ADAS independently predicted mortality at 30 days (HR 1.02). Among ADAS patients, advanced cardiac damage/dysfunction predicts mortality at 1 year (HR 1.853) whilst frailty predicts mortality at 2.4 years (HR 1.667). / Conclusions: This thesis has demonstrated the effect of dual pathology (AS-ATTR) on altering the resultant AS phenotype, the prognostic impact of multimorbidity (frailty and LMS CAD) in TAVI, the impact of AS on confounding common diagnostic pathways (NSTEMI) and identified a novel prognostic marker (ADAS).

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