Timing of invasive strategy in non-ST-elevation acute coronary syndrome: a meta-analysis of randomized controlled trials.

AIMS: The optimal timing of an invasive strategy (IS) in non-ST-elevation acute coronary syndrome (NSTE-ACS) is controversial. Recent randomized controlled trials (RCTs) and long-term follow-up data have yet to be included in a contemporary meta-analysis. METHODS AND RESULTS: A systematic review of RCTs that compared an early IS vs. delayed IS for NSTE-ACS was conducted by searching MEDLINE, Embase, and Cochrane Central Register of Controlled Trials. A meta-analysis was performed by pooling relative risks (RRs) using a random-effects model. The primary outcome was all-cause mortality. Secondary outcomes included myocardial infarction (MI), recurrent ischaemia, admission for heart failure (HF), repeat re-vascularization, major bleeding, stroke, and length of hospital stay. This study was registered with PROSPERO (CRD42021246131). Seventeen RCTs with outcome data from 10 209 patients were included. No significant differences in risk for all-cause mortality [RR: 0.90, 95% confidence interval (CI): 0.78-1.04], MI (RR: 0.86, 95% CI: 0.63-1.16), admission for HF (RR: 0.66, 95% CI: 0.43-1.03), repeat re-vascularization (RR: 1.04, 95% CI: 0.88-1.23), major bleeding (RR: 0.86, 95% CI: 0.68-1.09), or stroke (RR: 0.95, 95% CI: 0.59-1.54) were observed. Recurrent ischaemia (RR: 0.57, 95% CI: 0.40-0.81) and length of stay (median difference: -22 h, 95% CI: -36.7 to -7.5 h) were reduced with an early IS. CONCLUSION: In all-comers with NSTE-ACS, an early IS does not reduce all-cause mortality, MI, admission for HF, repeat re-vascularization, or increase major bleeding or stroke when compared with a delayed IS. Risk of recurrent ischaemia and length of stay are significantly reduced with an early IS.

Comparison of the release of microRNAs and extracellular vesicles from platelets in response to different agonists.

On activation platelets release microRNAs and extracellular vesicles (EV) into circulation. The release of EV from platelets has been shown to be dependent on the agonist; in this study, we investigated whether the microRNA profile or EV released from platelets was also agonist specific. Washed platelets from healthy subjects were maximally stimulated with agonists specific for the receptors for collagen (Glycoprotein VI (GPVI)), thrombin (PAR1/PAR4), or ADP (P2Y1/P2Y12) with/without inhibiting secondary mediators, using aspirin to block cyclooxygenase-1 and apyrase to remove ADP. The released microRNAs were profiled using TaqMan microRNA microarray cards. Platelet-derived EV (pdEV) were characterized by size (Nanoparticle Tracking Analysis, NTA), for procoagulant activity (Annexin-V binding and support of thrombin generation), and for the EV markers CD63 and HSP70. Platelet activation triggered the release of 57-79 different microRNAs, dependent upon agonist, with a core of 46 microRNAs observed with all agonists. There was a high level of correlation between agonists (r2 > 0.98; p < 0.0001 for all), and with the microRNA content of the parent platelets (r2 > 0.98; p < 0.0001). The 46 microRNAs seen in all samples are predicted to have significant effects on the translation of proteins involved in endocytosis, cell cycle control, and differentiation. MiR-223-3p was the most abundant in all samples and has previously been implicated in myeloid lineage development and demonstrated to have anti-inflammatory effects. Stimulation through GPVI produced a pdEV population with significantly more procoagulant activity than the other agonists. Apyrase significantly reduced microRNA and pdEV release, while aspirin had little effect. These data suggest that all tested agonists trigger the release of a similar microRNA profile while the procoagulant activity of the pdEV was agonist dependent. ADP was shown to play an important role in the release of both microRNAs and pdEV.

Acute Heart Failure: Definition, Classification and Epidemiology.

PURPOSE OF REVIEW: The purpose of this review is to describe the extent and scope of acute heart failure (AHF), place it within its clinical context and highlight some of the difficulties in defining it as a pathophysiological entity. RECENT FINDINGS: A diagnosis of AHF is made when patients present acutely with signs and symptoms of heart failure, often with decompensation of pre-existing cardiomyopathy. The most current guidelines classify based on clinical features at initial presentation and are used to both risk stratify and guide the management of haemodynamic compromise. Despite this, AHF remains a diagnosis with a poor prognosis and there is no therapy proven to have long-term mortality benefits. We provide an introduction to AHF and discuss its definition, causes and precipitants. We also present epidemiological and demographic data to suggest that there is significant patient heterogeneity and that AHF is not a single pathology, but rather a range of pathophysiological entities. This poses a challenge when designing clinical trials and may, at least in part, explain why the results in this area have been largely disappointing.

Coronary artery disease and outcomes following transcatheter aortic valve implantation.

BACKGROUND: Aortic stenosis is a life-limiting condition for which transcatheter aortic valve implantation (TAVI) is an established therapy. Coronary artery disease (CAD) is frequently found in this patient group and optimal management in these patients remains uncertain. OBJECTIVES: We sought to examine the association of coexistent CAD on mortality and hospital readmission in patients undergoing TAVI. METHODS: In this observational cohort study, we examined patients who underwent TAVI and segregated them by the presence of obstructive epicardial CAD. The primary outcome was 3-year mortality with secondary outcomes being readmission for (1) all-causes, (2) a MACE (Major Adverse Cardiovascular Event) composite endpoint and (3) acute coronary syndrome. Subsidiary outcomes included patient angina and breathlessness scores. RESULTS: 898 patients underwent TAVI, of which 488 (54.3%) had unobstructed coronary arteries and 410 (45.7%) had obstructive CAD. Overall, n=298 (33.2%) patients experienced the primary mortality endpoint with no significant difference when stratified according to CAD (n=160 (32.9%) vs n=136 (33.2%), HR 0.98, CI 0.78 to 1.24). After multivariate analysis, the presence of CAD had no effect on the primary outcome (HR 0.98, CI 0.68 to 1.40). There was no significant difference in readmission for any cause (n=181, 37.1% (CAD) vs n=169, 41.2% (no CAD), p=0.23), including no significant difference on readmission for MACE (n=48, 9.8% (CAD) vs n=45, 11.0% (no CAD), p=0.11). CAD at the time of TAVI also did not alter breathlessness or angina scores before/after TAVI (p>0.05). CONCLUSION: Coexistent CAD had no significant association with mortality, any-cause readmission or symptoms for patients undergoing TAVI in our cohort.

Diagnosing and phenotyping visual synaesthesia: a preliminary evaluation of the revised test of genuineness (TOG-R).

Synaesthesia, a neurological condition affecting approximately .05% of the population, is characterised by anomalous sensory perception: a stimulus in one sensory modality triggers an automatic, instantaneous, consistent response in another modality (e.g., sound evokes colour) or in a different aspect of the same modality (e.g., black text evokes colour). As evidence was limited to case studies based on self-report, the existence of synaesthesia was regarded with scepticism until the development of the Test of Genuineness (TOG) in 1987, which measures the consistency of stimulus-response linkage: synaesthetes typically score between 70-90% range, whereas controls typically score between 20-38%. However, the TOG had only limited ability to quantify the characteristics of visual synaesthesia. In this study, the revised Test of Genuineness (TOG-R), utilising the Pantone-based Cambridge Synaesthesia Charts, was given to 26 synaesthetes and 23 controls. Results confirmed that the TOG-R is equally accurate in the diagnosis of synaesthesia; synaesthetes scored significantly (t47 = 16.01, p < .001) higher (mean = 71.3%, SEM = 1.4%) than controls (mean = 33%, SEM = 2.0%). The TOG-R provides greater precision in quantifying the closeness of colour matches and enables a more detailed analysis of visual synaesthesia. Synaesthetes were phenotyped into broad- and narrowband based on their overall responsiveness to auditory stimuli, with bandwidth determined primarily by responsiveness to non-word stimuli. They were further sub-phenotyped based on responses to sub-groups of stimuli into word-colour (WC) and music-colour (MC). Development of this instrument has important implications for the diagnosis and phenotyping of visual synaesthesia.