Critical Care Cardiology Trials Network (CCCTN): a cohort profile.

AIMS: The aims of the Critical Care Cardiology Trials Network (CCCTN) are to develop a registry to investigate the epidemiology of cardiac critical illness and to establish a multicentre research network to conduct randomised clinical trials (RCTs) in patients with cardiac critical illness. METHODS AND RESULTS: The CCCTN was founded in 2017 with 16 centres and has grown to a research network of over 40 academic and clinical centres in the United States and Canada. Each centre enters data for consecutive cardiac intensive care unit (CICU) admissions for at least 2 months of each calendar year. More than 20 000 unique CICU admissions are now included in the CCCTN Registry. To date, scientific observations from the CCCTN Registry include description of variations in care, the epidemiology and outcomes of all CICU patients, as well as subsets of patients with specific disease states, such as shock, heart failure, renal dysfunction, and respiratory failure. The CCCTN has also characterised utilization patterns, including use of mechanical circulatory support in response to changes in the heart transplantation allocation system, and the use and impact of multidisciplinary shock teams. Over years of multicentre collaboration, the CCCTN has established a robust research network to facilitate multicentre registry-based randomised trials in patients with cardiac critical illness. CONCLUSION: The CCCTN is a large, prospective registry dedicated to describing processes-of-care and expanding clinical knowledge in cardiac critical illness. The CCCTN will serve as an investigational platform from which to conduct randomised controlled trials in this important patient population.

Predictors of Survival and Favorable Neurologic Outcome in Patients Treated with eCPR: a Systematic Review and Meta-analysis.

Extracorporeal cardiopulmonary resuscitation (eCPR) can improve survival in selected patients with cardiac arrest (CA). In this meta-analysis, we evaluated factors associated with short-term survival and favorable neurologic outcome (FNO) post-eCPR. In June 2019, we systematically searched electronic databases for studies reporting on survival and predictors associated with short-term survival or FNO post-eCPR using multivariable analysis. We meta-analyzed outcomes and predictors using the inverse variance method with a random-effects model. We identified 92 studies with 13 factors amenable to meta-analysis. Pooled short-term survival and FNO were 25% and 16% respectively. Lower lactate, return of spontaneous circulation, shockable rhythm, shorter CPR duration, baseline pH, shorter low-flow time, and history of hypertension were significantly associated with short-term survival. In addition, shockable rhythm, lower lactate, and use of targeted temperature management were associated with FNO. The identified factors associated with short-term survival and FNO post-eCPR could guide prognosis prediction at the time of CA.

Association of left anterior descending artery involvement on clinical outcomes among patients with STEMI presenting with and without out-of-hospital cardiac arrest.

Background: ST-segment elevation myocardial infarction (STEMI) outcomes are influenced by the location of the culprit vessel with worse outcomes portended with a left anterior descending (LAD) culprit lesion. However, relatively little is known about the independent association of LAD involvement with clinical outcomes of patients with STEMI with and without out-of-hospital cardiac arrest (OHCA). Methods: We identified 91 patients with and 929 without a preceding OHCA within the Vancouver Coastal Health Authority who presented with an acute STEMI and underwent primary percutaneous coronary intervention between 26 June 2007 and 31 March 2016. Results: Patients with STEMI with OHCA had higher rates of in-hospital cardiac arrest (43.3% vs 8.3%, p<0.001), heart failure (50.5% vs 11.3%, p<0.001), cardiogenic shock (49.5% vs 5.7%, p<0.001), mortality (35.2% vs 3.3%, p<0.001) and reduced left ventricular ejection fraction (LVEF; 42.9% vs 47.3%, p<0.001) compared with those without OHCA. Among patients without OHCA, LAD involvement was associated with increased heart failure (18.1% vs 5.2%, p<0.001), in-hospital cardiac arrest (10.7% vs 6.2%, p<0.014), cardiogenic shock (8.4% vs 3.3%, p<0.001), reduced LVEF (43.0% vs 51.2%, p<0.001) and mortality (5.2% vs 1.3%, p=0.003) compared with patients without LAD involvement. With the exception of LVEF, these associations were not seen among patients with STEMI with OHCA and an LAD culprit. The presence of an LAD culprit was not independently associated with increased hospital mortality among patients with OHCA after adjusting for potential confounding factors. Conclusion: Our study has demonstrated a differential impact of LAD involvement on clinical outcomes among patients with STEMI who present with and without OHCA. Our data highlight the complexity surrounding the prognostication following OHCA complicating STEMI and demonstrate that other mechanisms other than LAD involvement contribute to the high mortality associated with OHCA as a result of STEMI.

Coronary Vasospasm Following Heart Transplantation: Rapid Progression to Aggressive Cardiac Allograft Vasculopathy.

Coronary artery vasospasm (CVS) has been described in orthotopic heart transplant patients but is rare in the post-transplanted, denervated heart. Severe CVS has been associated with accelerated cardiac allograft vasculopathy (CAV) and allograft rejection. Allograft vasculopathy is the leading cause of decreased long-term survival in orthotopic heart transplant. The prognostic significance and relationship of the presence and severity of CVS with CAV are not well understood. We present a case of severe symptomatic CVS with rapid development of severe CAV. Our case emphasizes the need for close angiographic surveillance and intracoronary imaging for early detection of CAV in the presence of vasospasm.

[Congenital coronary artery fistulas: clinical and therapeutic consideration]. / Kongenitalne koronarne arterijske fistule: klinicko i terapijsko razmatranje.

A coronary artery fistula is a link between one or more coronary arteries with another heart cavity or a segment of systemic or pulmonary circulation. Arterial blood from a coronary vessel enters another segment via myocardial capillary bed. These are very rare anomalies which constitute approximately 0.2 - 0.4% of all congenital heart defects. Still, they are clinically significant if they are of medium or large size and are manifested with a series of clinical symptoms such as angina pectoris, arrhythmias, myocardial infarction, endocarditis, progressive dilatation, heart failure and cardiomyopathy, pulmonary hypertension, thrombosis of the fistula and formation of aneurysms with possible ruptures. We present six patients with a coronary arterial fistula, their history, diagnostic procedures and outcomes. Therapeutic closure of coronary artery fistulas is recommended in all symptomatic, but also in asymptomatic patients, if there are significant roentgenographic, electrocardiographic and other abnormalities. In recent times transcatheter closure of coronary fistulas has become a possible alternative to surgery and is becoming increasingly used thanks to improved diagnostic possibilities and technology. If possible, interventional closure of fistulas is precisely the method preferred in pediatric patients. The choice of method depends on the anatomy of the fistula, presence or absence of additional defects, and on the experience of an interventional cardiologist or a heart surgeon. If performed well, the effects of both methods are good. This paper presents two children with a fistula between the right coronary artery and the right ventricle (RV), one child with a fistula between LAD and RV, one child with a fistula between the main tree of the left coronary artery (LCA) and RV, one child with a fistula between LCA and the right ventricular outflow tract (RVOT), and one child with a fistula between LCA and the right atrium (RA). The last one (LCA-RA) is not described in the latest classification of anomalies of coronary blood vessels in children based on MSCT coronarography, so we consider our presentation to be a contribution to the new classification. Along with the descriptions of fistulas and presentations of interventional and cardiosurgical interventions, we are also presenting a rare case of spontaneous closing of the fistula within the first six months and of a reopening of the fistula between the right coronary artery and the right ventricle after six years.

Monitoring protein-protein interactions between the mammalian integral membrane transporters and PDZ-interacting partners using a modified split-ubiquitin membrane yeast two-hybrid system.

PDZ-binding motifs are found in the C-terminal tails of numerous integral membrane proteins where they mediate specific protein-protein interactions by binding to PDZ-containing proteins. Conventional yeast two-hybrid screens have been used to probe protein-protein interactions of these soluble C termini. However, to date no in vivo technology has been available to study interactions between the full-length integral membrane proteins and their cognate PDZ-interacting partners. We previously developed a split-ubiquitin membrane yeast two-hybrid (MYTH) system to test interactions between such integral membrane proteins by using a transcriptional output based on cleavage of a transcription factor from the C terminus of membrane-inserted baits. Here we modified MYTH to permit detection of C-terminal PDZ domain interactions by redirecting the transcription factor moiety from the C to the N terminus of a given integral membrane protein thus liberating their native C termini. We successfully applied this "MYTH 2.0" system to five different mammalian full-length renal transporters and identified novel PDZ domain-containing partners of the phosphate (NaPi-IIa) and sulfate (NaS1) transporters that would have otherwise not been detectable. Furthermore this assay was applied to locate the PDZ-binding domain on the NaS1 protein. We showed that the PDZ-binding domain for PDZK1 on NaS1 is upstream of its C terminus, whereas the two interacting proteins, NHERF-1 and NHERF-2, bind at a location closer to the N terminus of NaS1. Moreover NHERF-1 and NHERF-2 increased functional sulfate uptake in Xenopus oocytes when co-expressed with NaS1. Finally we used MYTH 2.0 to demonstrate that the NaPi-IIa transporter homodimerizes via protein-protein interactions within the lipid bilayer. In summary, our study establishes the MYTH 2.0 system as a novel tool for interactive proteomics studies of membrane protein complexes.