Aortic Stenosis: Multimorbidity and Myocardial Impact on Patients undergoing Transcatheter Aortic Valve Implantation

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)

Repairing of exit-hole in dissimilar Al-Mg friction stir welding : process and microstructural pattern

The exit-hole is one major discontinuities in the friction based processes, where all the volume of the tool's probe is missing with a depth that corresponds to the full thickness of the processed component. This letter presents a new technique to repair the exit-hole of an Al-Mg friction stir welding, without any third body material with inexpensive probeless tooling, inducing forging, stirring, and thermomechanical consolidation of the local spot joint. Intercalated banned type structures with interpenetrating features were achieved. Composite type mixed structure was obtained at repaired zone with a local tensile strength of 159 MPa

Cardiac Computed Tomography: Application in Valvular Heart Disease

The incidence and prevalence of valvular heart disease (VHD) is increasing and has been described as the next cardiac epidemic. Advances in imaging and therapeutics have revolutionized how we assess and treat patients with VHD. Although echocardiography continues to be the first-line imaging modality to assess the severity and the effects of VHD, advances in cardiac computed tomography (CT) now provide novel insights into VHD. Transcatheter valvular interventions rely heavily on CT guidance for procedural planning, predicting and detecting complications, and monitoring prosthesis. This review focuses on the current role and future prospects of CT in the assessment of aortic and mitral valves for transcatheter interventions, prosthetic valve complications such as thrombosis and endocarditis, and assessment of the myocardium

Invasive or non-invasive imaging for detecting high-risk coronary lesions?

INTRODUCTION: Advances in our understanding about atherosclerotic evolution have enabled us to identify specific plaque characteristics that are associated with coronary plaque vulnerability and cardiovascular events. With constant improvements in signal and image processing an arsenal of invasive and non-invasive imaging modalities have been developed that are capable of identifying these features allowing in vivo assessment of plaque vulnerability. Areas covered: This review article presents the available and emerging imaging modalities introduced to assess plaque morphology and biology, describes the evidence from the first large scale studies that evaluated the efficacy of invasive and non-invasive imaging in detecting lesions that are likely to progress and cause cardiovascular events and discusses the potential implications of the in vivo assessment of coronary artery pathology in the clinical setting. Expert commentary: Invasive imaging, with its high resolution, and in particular hybrid intravascular imaging appears as the ideal approach to study the mechanisms regulating atherosclerotic disease progression; whereas non-invasive imaging is expected to enable complete assessment of coronary tree pathology, detection of high-risk lesions, more accurate risk stratification and thus to allow a personalized treatment of vulnerable patients

Futility in Transcatheter Aortic Valve Implantation: A Search for Clarity

Although transcatheter aortic valve implantation (TAVI) has revolutionised the landscape of treatment for aortic stenosis, there exists a cohort of patients where TAVI is deemed futile. Among the pivotal high-risk trials, one-third to half of patients either died or received no symptomatic benefit from the procedure at 1 year. Futility of TAVI results in the unnecessary exposure of risk for patients and inefficient resource utilisation for healthcare services. Several cardiac and extra-cardiac conditions and frailty increase the risk of mortality despite TAVI. Among the survivors, these comorbidities can inhibit improvements in symptoms and quality of life. However, certain conditions are reversible with TAVI (e.g. functional mitral regurgitation), attenuating the risk and improving outcomes. Quantification of disease severity, identification of reversible factors and a systematic evaluation of frailty can substantially improve risk stratification and outcomes. This review examines the contribution of pre-existing comorbidities towards futility in TAVI and suggests a systematic approach to guide patient evaluation

Identifying Cardiac Amyloid in Aortic Stenosis: ECV Quantification by CT in TAVR Patients.

OBJECTIVES: The purpose of this study was to validate computed tomography measured ECV (ECVCT) as part of routine evaluation for the detection of cardiac amyloid in patients with aortic stenosis (AS)-amyloid. BACKGROUND: AS-amyloid affects 1 in 7 elderly patients referred for transcatheter aortic valve replacement (TAVR). Bone scintigraphy with exclusion of a plasma cell dyscrasia can diagnose transthyretin-related cardiac amyloid noninvasively, for which novel treatments are emerging. Amyloid interstitial expansion increases the myocardial extracellular volume (ECV). METHODS: Patients with severe AS underwent bone scintigraphy (Perugini grade 0, negative; Perugini grades 1 to 3, increasingly positive) and routine TAVR evaluation CT imaging with ECVCT using 3- and 5-min post-contrast acquisitions. Twenty non-AS control patients also had ECVCT performed using the 5-min post-contrast acquisition. RESULTS: A total of 109 patients (43% male; mean age 86 ± 5 years) with severe AS and 20 control subjects were recruited. Sixteen (15%) had AS-amyloid on bone scintigraphy (grade 1, n = 5; grade 2, n = 11). ECVCT was 32 ± 3%, 34 ± 4%, and 43 ± 6% in Perugini grades 0, 1, and 2, respectively (p < 0.001 for trend) with control subjects lower than lone AS (28 ± 2%; p < 0.001). ECVCT accuracy for AS-amyloid detection versus lone AS was 0.87 (0.95 for 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid Perugini grade 2 only), outperforming conventional electrocardiogram and echocardiography parameters. One composite parameter, the voltage/mass ratio, had utility (similar AUC of 0.87 for any cardiac amyloid detection), although in one-third of patients, this could not be calculated due to bundle branch block or ventricular paced rhythm. CONCLUSIONS: ECVCT during routine CT TAVR evaluation can reliably detect AS-amyloid, and the measured ECVCT tracks the degree of infiltration. Another measure of interstitial expansion, the voltage/mass ratio, also performed well

Immune boosting by B.1.1.529 (Omicron) depends on previous SARS-CoV-2 exposure

The Omicron, or Pango lineage B.1.1.529, variant of SARS-CoV-2 carries multiple spike mutations with high transmissibility and partial neutralizing antibody (nAb) escape. Vaccinated individuals show protection from severe disease, often attributed to primed cellular immunity. We investigated T and B cell immunity against B.1.1.529 in triple mRNA vaccinated healthcare workers (HCW) with different SARS-CoV-2 infection histories. B and T cell immunity against previous variants of concern was enhanced in triple vaccinated individuals, but magnitude of T and B cell responses against B.1.1.529 spike protein was reduced. Immune imprinting by infection with the earlier B.1.1.7 (Alpha) variant resulted in less durable binding antibody against B.1.1.529. Previously infection-naïve HCW who became infected during the B.1.1.529 wave showed enhanced immunity against earlier variants, but reduced nAb potency and T cell responses against B.1.1.529 itself. Previous Wuhan Hu-1 infection abrogated T cell recognition and any enhanced cross-reactive neutralizing immunity on infection with B.1.1.529