Catheter ablation vs. antiarrhythmic drug therapy in patients with symptomatic atrioventricular nodal re-entrant tachycardia: a randomized, controlled trial.

Aims: To conduct a randomized trial in order to guide the optimum therapy of symptomatic atrioventricular nodal re-entrant tachycardia (AVNRT). Methods and Results: Patients with at least one symptomatic episode of tachycardia per month and an electrophysiologic diagnosis of AVNRT were randomly assigned to catheter ablation or chronic antiarrhythmic drug (AAD) therapy with bisoprolol (5 mg od) and/or diltiazem (120-300 mg od). All patients were properly educated to treat subsequent tachycardia episodes with autonomic manoeuvres or a 'pill in the pocket' approach. The primary endpoint of the study was hospital admission for persistent tachycardia cardioversion, during a follow-up period of 5 years. Sixty-one patients were included in the study. In the ablation group, 1 patient was lost to follow-up, and 29 were free of arrhythmia or conduction disturbances at a 5-year follow-up. In the AAD group, three patients were lost to follow-up. Of the remainder, 10 patients (35.7%) continued with initial therapy, 11 patients (39.2%) remained on diltiazem alone, and 7 patients (25%) interrupted their therapy within the first 3 months following randomization, and subsequently developed an episode requiring cardioversion. During a follow-up of 5 years, 21 patients in the AAD group required hospital admission for cardioversion. Survival free from the study endpoint was significantly higher in the ablation group compared with the AAD group (log-rank test, P < 0.001). Conclusions: Catheter ablation is the therapy of choice for symptomatic AVNRT. Antiarrhythmic drug therapy is ineffective and not well tolerated

Vortex formation and recirculation zones in left anterior descending artery stenoses: computational fluid dynamics analysis

Flow patterns may affect the potential of thrombus formation following plaque rupture. Computational fluid dynamics (CFD) were employed to assess hemodynamic conditions, and particularly flow recirculation and vortex formation in reconstructed arterial models associated with ST-elevation myocardial infraction (STEMI) or stable coronary stenosis (SCS) in the left anterior descending coronary artery (LAD). Results indicate that in the arterial models associated with STEMI, a 50% diameter stenosis immediately before or after a bifurcation creates a recirculation zone and vortex formation at the orifice of the bifurcation branch, for most of the cardiac cycle, thus allowing the creation of stagnating flow. These flow patterns are not seen in the SCS model with an identical stenosis. Post-stenotic recirculation in the presence of a 90% stenosis was evident at both the STEMI and SCS models. The presence of 90% diameter stenosis resulted in flow reduction in the LAD of 51.5% and 35.9% in the STEMI models and 37.6% in the SCS model, for a 10 mmHg pressure drop. CFD simulations in a reconstructed model of stenotic LAD segments indicate that specific anatomic characteristics create zones of vortices and flow recirculation that promote thrombus formation and potentially myocardial infarction

Piezo1 channels sense whole body physical activity to reset cardiovascular homeostasis and enhance performance

Mammalian biology adapts to physical activity but the molecular mechanisms sensing the activity remain enigmatic. Recent studies have revealed how Piezo1 protein senses mechanical force to enable vascular development. Here, we address Piezo1 in adult endothelium, the major control site in physical activity. Mice without endothelial Piezo1 lack obvious phenotype but close inspection reveals a specific effect on endothelium-dependent relaxation in mesenteric resistance artery. Strikingly, the Piezo1 is required for elevated blood pressure during whole body physical activity but not blood pressure during inactivity. Piezo1 is responsible for flow-sensitive non-inactivating non-selective cationic channels which depolarize the membrane potential. As fluid flow increases, depolarization increases to activate voltage-gated Ca2+ channels in the adjacent vascular smooth muscle cells, causing vasoconstriction. Physical performance is compromised in mice which lack endothelial Piezo1 and there is weight loss after sustained activity. The data suggest that Piezo1 channels sense physical activity to advantageously reset vascular control

How achievable are COVID-19 clinical trial recruitment targets? A UK observational cohort study and trials registry analysis

OBJECTIVES: To analyse enrolment to interventional trials during the first wave of the COVID-19 pandemic in England and describe the barriers to successful recruitment in the circumstance of a further wave or future pandemics. DESIGN: We analysed registered interventional COVID-19 trial data and concurrently did a prospective observational study of hospitalised patients with COVID-19 who were being assessed for eligibility to one of the RECOVERY, C19-ACS or SIMPLE trials. SETTING: Interventional COVID-19 trial data were analysed from the clinicaltrials.gov and International Standard Randomized Controlled Trial Number databases on 12 July 2020. The patient cohort was taken from five centres in a respiratory National Institute for Health Research network. Population and modelling data were taken from published reports from the UK government and Medical Research Council Biostatistics Unit. PARTICIPANTS: 2082 consecutive admitted patients with laboratory-confirmed SARS-CoV-2 infection from 27 March 2020 were included. MAIN OUTCOME MEASURES: Proportions enrolled, and reasons for exclusion from the aforementioned trials. Comparisons of trial recruitment targets with estimated feasible recruitment numbers. RESULTS: Analysis of trial registration data for COVID-19 treatment studies enrolling in England showed that by 12 July 2020, 29 142 participants were needed. In the observational study, 430 (20.7%) proceeded to randomisation. 82 (3.9%) declined participation, 699 (33.6%) were excluded on clinical grounds, 363 (17.4%) were medically fit for discharge and 153 (7.3%) were receiving palliative care. With 111 037 people hospitalised with COVID-19 in England by 12 July 2020, we determine that 22 985 people were potentially suitable for trial enrolment. We estimate a UK hospitalisation rate of 2.38%, and that another 1.25 million infections would be required to meet recruitment targets of ongoing trials. CONCLUSIONS: Feasible recruitment rates, study design and proliferation of trials can limit the number, and size, that will successfully complete recruitment. We consider that fewer, more appropriately designed trials, prioritising cooperation between centres would maximise productivity in a further wave

Intracardiac echocardiography to guide transseptal catheterization for radiofrequency catheter ablation of left-sided accessory pathways: two case reports

Intracardiac echocardiography (ICE) is a useful tool for guiding transseptal puncture during electrophysiological mapping and ablation procedures. Left-sided accessory pathways (LSAP) can be ablated by using two different modalities: retrograde approach through the aortic valve and transseptal approach with puncture of the fossa ovalis. We shall report two cases of LSAP where transcatheter radiofrequency ablation (TCRFA) was firstly attempted via transaortic approach with ineffective results. Subsequently, a transseptal approach under ICE guidance has been performed. During atrial septal puncture ICE was able to locate the needle tip position precisely and provided a clear visualization of the "tenting effect" on the fossa ovalis. ICE allowed a better mapping of the mitral ring and a more effective catheter ablation manipulation and tip contact which resulted in a persistent and complete ablation of the accessory pathway with a shorter time of fluoroscopic exposure. ICE-guided transseptal approach might be a promising modality for TCRFA of LSAP

Prognostic value of fractional flow reserve: Linking physiologic severity to clinical outcomes

BACKGROUND: Fractional flow reserve (FFR) has become an established tool for guiding treatment, but its graded relationship to clinical outcomes as modulated by medical therapy versus revascularization remains unclear.OBJECTIVES: The study hypothesized that FFR displays a continuous relationship between its numeric value and prognosis, such that lower FFR values confer a higher risk and therefore receive larger absolute benefits from revascularization.METHODS: Meta-analysis of study- and patient-level data investigated prognosis after FFR measurement. An interaction term between FFR and revascularization status allowed for an outcomes-based threshold.RESULTS: A total of 9,173 (study-level) and 6,961 (patient-level) lesions were included with a median follow-up of 16 and 14 months, respectively. Clinical events increased as FFR decreased, and revascularization showed larger net benefit for lower baseline FFR values. Outcomes-derived FFR thresholds generally occurred around the range 0.75 to 0.80, although limited due to confounding by indication. FFR measured immediately after stenting also showed an inverse relationship with prognosis (hazard ratio: 0.86, 95% confidence interval: 0.80 to 0.93; p < 0.001). An FFR-assisted strategy led to revascularization roughly half as often as an anatomy-based strategy, but with 20% fewer adverse events and 10% better angina relief.CONCLUSIONS: FFR demonstrates a continuous and independent relationship with subsequent outcomes, modulated by medical therapy versus revascularization. Lesions with lower FFR values receive larger absolute benefits from revascularization. Measurement of FFR immediately after stenting also shows an inverse gradient of risk, likely from residual diffuse disease. An FFR-guided revascularization strategy significantly reduces events and increases freedom from angina with fewer procedures than an anatomy-based strategy

MicroRNAs as Biomarkers for Myocardial Infarction

MicroRNAs (miRs) are short non-coding RNA molecules involved in post-transcriptional gene regulation by binding to the 3′ untranslated region of a messenger RNA (mRNA), thereby inhibiting the translation or inducing mRNA destabilization. MiRs are generally considered to act as intracellular mediators essential for normal cardiac function, and their deregulated expression profiles have been associated with cardiovascular diseases. Recent studies have revealed the existence of freely circulating miRs in human peripheral blood, which are present in a stable nature. This has raised the possibility that miRs may be released in the circulation and can serve as novel diagnostic markers for acute or chronic human disorders, including myocardial infarction (MI). This review summarizes the recent findings of miRs that fulfill the criteria of candidate biomarkers for MI

Direct detection and measurement of wall shear stress using a filamentous bio-nanoparticle

The wall shear stress (WSS) that a moving fluid exerts on a surface affects many processes including those relating to vascular function. WSS plays an important role in normal physiology (e.g. angiogenesis) and affects the microvasculature's primary function of molecular transport. Points of fluctuating WSS show abnormalities in a number of diseases; however, there is no established technique for measuring WSS directly in physiological systems. All current methods rely on estimates obtained from measured velocity gradients in bulk flow data. In this work, we report a nanosensor that can directly measure WSS in microfluidic chambers with sub-micron spatial resolution by using a specific type of virus, the bacteriophage M13, which has been fluorescently labeled and anchored to a surface. It is demonstrated that the nanosensor can be calibrated and adapted for biological tissue, revealing WSS in micro-domains of cells that cannot be calculated accurately from bulk flow measurements. This method lends itself to a platform applicable to many applications in biology and microfluidics