Post-Procedure Monocyte Count Levels Predict Major Adverse Cardiovascular Events (MACE) Following Transcatheter Aortic Valve Implantation (TAVI) for Aortic Stenosis.

BACKGROUND: Aortic stenosis has recently been characterised as having an inflammatory aetiology, beyond the traditional degenerative model. Recruitment of monocytes has been associated with inflammation contributing to progression of calcific aortic-valve disease. Prior research has demonstrated that pre-procedure inflammatory biomarkers do not consistently discriminate poorer outcomes in those with aortic stenosis. It remains, however, unclear if postprocedure inflammatory biomarkers, which are influenced by intraprocedural pro-inflammatory insults, can predict major adverse cardiovascular events (MACE) post transcatheter aortic valve implantation (TAVI). METHOD: All patients with postprocedure monocyte levels undergoing transcatheter aortic valve implantation at The Alfred Hospital, Melbourne, Australia (2008-2019) were included. The highest monocyte count from postprocedure days 1 to 3 was used. Patients were divided into "high" or "low" postprocedure monocyte count groups using the Youden Index. The incidence of 30-day MACE a composite of stroke, acute myocardial infarction, and death) was then compared. RESULTS: In total, 472 patients were included (54% men, median age 84 years). Fourteen (14) patients (3%) suffered a 30-day MACE. Those with high postprocedure monocyte count were more likely to: be hypertensive (p=0.049); have a higher Society of Thoracic Surgeons risk score (p=0.032); and, undergo non-transfemoral access (p=0.018). A high (≥0.975) postprocedure monocyte count was significantly associated with 30-day MACE (odds ratio [OR] 1.16 for each 0.1 increase in monocyte, p=0.025). This association remained present on multivariable analysis adjusted for age, sex, Society of Thoracic Surgeons risk score, and self-expanding valve prosthesis type (OR 1.17, p=0.028). CONCLUSIONS: The association between postprocedure monocytosis and 30-day MACE suggests that minimising peri-procedural inflammatory insults may improve outcomes. This inexpensive and readily available biomarker may also aid in tailored risk stratification for patients.

Transcatheter Aortic Valve Therapy for Bicuspid Aortic Valve Stenosis.

Transcatheter aortic valve implantation (TAVI) has become first-line treatment for older adults with severe aortic stenosis (AS), however, patients with bicuspid aortic valve (BAV) have been traditionally excluded from randomised trials and guidelines. As familiarity and proficiency of TAVI operators have improved, case-series and observational data have demonstrated the feasibility of successful TAVI in bicuspid aortic valve aortic stenosis (BAV-AS), however, patients with BAV-AS have several distinct characteristics that influence the likelihood of TAVI success. This review aims to summarise the pathophysiology and classification of BAV, published safety data, anatomical challenges and procedural considerations essential for pre-procedural planning, patient selection and procedural success of TAVI in BAV.

Uncoupling the Vicious Cycle of Mechanical Stress and Inflammation in Calcific Aortic Valve Disease.

Calcific aortic valve disease (CAVD) is a common acquired valvulopathy, which carries a high burden of mortality. Chronic inflammation has been postulated as the predominant pathophysiological process underlying CAVD. So far, no effective medical therapies exist to halt the progression of CAVD. This review aims to outline the known pathways of inflammation and calcification in CAVD, focussing on the critical roles of mechanical stress and mechanosensing in the perpetuation of valvular inflammation. Following initiation of valvular inflammation, dysregulation of proinflammatory and osteoregulatory signalling pathways stimulates endothelial-mesenchymal transition of valvular endothelial cells (VECs) and differentiation of valvular interstitial cells (VICs) into active myofibroblastic and osteoblastic phenotypes, which in turn mediate valvular extracellular matrix remodelling and calcification. Mechanosensitive signalling pathways convert mechanical forces experienced by valve leaflets and circulating cells into biochemical signals and may provide the positive feedback loop that promotes acceleration of disease progression in the advanced stages of CAVD. Mechanosensing is implicated in multiple aspects of CAVD pathophysiology. The mechanosensitive RhoA/ROCK and YAP/TAZ systems are implicated in aortic valve leaflet mineralisation in response to increased substrate stiffness. Exposure of aortic valve leaflets, endothelial cells and platelets to high shear stress results in increased expression of mediators of VIC differentiation. Upregulation of the Piezo1 mechanoreceptor has been demonstrated to promote inflammation in CAVD, which normalises following transcatheter valve replacement. Genetic variants and inhibition of Notch signalling accentuate VIC responses to altered mechanical stresses. The study of mechanosensing pathways has revealed promising insights into the mechanisms that perpetuate inflammation and calcification in CAVD. Mechanotransduction of altered mechanical stresses may provide the sought-after coupling link that drives a vicious cycle of chronic inflammation in CAVD. Mechanosensing pathways may yield promising targets for therapeutic interventions and prognostic biomarkers with the potential to improve the management of CAVD.

Acute Coronary Syndrome in the COVID-19 Pandemic: Reduced Cases and Increased Ischaemic Time.

BACKGROUND: The COVID-19 pandemic has led to unprecedented stress on health care systems, and has affected acute coronary syndrome treatment at every step. This study aimed to examine the impact of COVID-19 on patient presentations with acute coronary syndromes during the first and second pandemic wave in Melbourne, Victoria. METHOD: A retrospective cohort study of adults presenting with cute coronary syndrome during the first pandemic wave from 1 March 2020 to 31 April 2020 and the second pandemic wave from 1 July 2020 to 31 August 2020 was compared to a control period from 1 March to 31 April 2019 at a single sub-tertiary referral centre in Melbourne, Victoria servicing a catchment area with a relatively high incidence of COVID-19 cases. RESULTS: Three-hundred-and-thirty-five (335) patients were hospitalised with acute coronary syndromes across all three time periods. The total number of patients presenting with an acute coronary syndrome was reduced during the pandemic, with a higher proportion of ST elevation myocardial infarctions. Ischaemic times increased with time from symptom onset to first medical contact rising from 191 minutes in the control period to 292 minutes in the first wave (p=0.06) and 271 minutes in the second wave (p=0.06). Coronary angiography with subsequent revascularisation significantly increased from 55% in the control period undergoing revascularisation to 69% in the first wave (p<0.001) and 74% in the second wave (p<0.001). CONCLUSION: A concerning reduction in acute coronary presentations occurred during the COVID-19 pandemic, associated with longer ischaemic times and a higher proportion requiring revascularisation. It is crucial that public awareness campaigns are instituted to address the contributing patient factors in future waves.

Incidence of normal white cell count and C-reactive protein in adults with acute appendicitis.

BACKGROUND: Normal C-reactive protein (CRP) and white cell count (WCC) are often used to exclude a diagnosis of acute appendicitis in the Emergency Department (ED). Retrospective review of 281 adult patients with acute appendicitis was performed to study the incidence of normal CRP and WCC on admission and examine any possible predisposing factors. METHOD: Retrospective analysis of patient clinical records yielded CRP, WCC, operative diagnosis, time of symptom onset, imaging results and history and examination features. Case-control analysis was performed with patients with normal CRP and WCC considered the case group and those with raised CRP or WCC considered controls. Groups were compared using Mann-Whitney U-test and chi-squared analysis. RESULTS: Of 281 consecutive patients with histologically proven appendicitis, 24 (8.54%) had normal CRP and WCC on presentation to ED. There were no significant differences in age, sex or time to blood collection between groups. Three patients had normal WCC and CRP and an Alvarado score of 4 or less on presentation. Three patients had persistently normal CRP and WCC on repeated testing. There was a trend towards earlier presentation in patients with normal CRP and WCC with 75.0% versus 58.4% presenting within 24 h of symptom onset (OR 2.14, P = 0.112). CONCLUSION: Acute appendicitis remains diagnostically challenging and cannot be excluded on the basis of normal CRP and WCC. Serial clinical and biochemical assessment is warranted in patients with acute abdominal pain, particularly in those presenting early after symptom onset.

Role of MIF in myocardial ischaemia and infarction: insight from recent clinical and experimental findings.

First discovered in 1966 as an inflammatory cytokine, MIF (macrophage migration inhibitory factor) has been extensively studied for its pivotal role in a variety of inflammatory diseases, including rheumatoid arthritis and atherosclerosis. Although initial studies over a decade ago reported increases in circulating MIF levels following acute MI (myocardial infarction), the dynamic changes in MIF and its pathophysiological significance following MI have been unknown until recently. In the present review, we summarize recent experimental and clinical studies examining the diverse functions of MIF across the spectrum of acute MI from brief ischaemia to post-infarct healing. Following an acute ischaemic insult, MIF is rapidly released from jeopardized cardiomyocytes, followed by a persistent MIF production and release from activated immune cells, resulting in a sustained increase in circulating levels of MIF. Recent studies have documented two distinct actions of MIF following acute MI. In the supra-acute phase of ischaemia, MIF mediates cardioprotection via several distinct mechanisms, including metabolic activation, apoptosis suppression and antioxidative stress. In prolonged myocardial ischaemia, however, MIF promotes inflammatory responses with largely detrimental effects on cardiac function and remodelling. The pro-inflammatory properties of MIF are complex and involve MIF derived from cardiac and immune cells contributing sequentially to the innate immune response evoked by MI. Emerging evidence on the role of MIF in myocardial ischaemia and infarction highlights a significant potential for the clinical use of MIF agonists or antagonists and as a unique cardiac biomarker.