Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Five-year outcomes following timely primary percutaneous intervention, late primary percutaneous intervention, or a pharmaco-invasive strategy in ST-segment elevation myocardial infarction: the FAST-MI programme

International audienceAIMS : ST-segment elevation myocardial infarction (STEMI) guidelines recommend primary percutaneous coronary intervention (pPCI) as the default reperfusion strategy when feasible ≤120 min of diagnostic ECG, and a pharmaco-invasive strategy otherwise. There is, however, a lack of direct evidence to support the guidelines, and in real-world situations, pPCI is often performed beyond recommended timelines. To assess 5-year outcomes according to timing of pPCI (timely vs. late) compared with a pharmaco-invasive strategy (fibrinolysis with referral to PCI centre).METHODS AND RESULTS : The French registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction (FAST-MI) programme consists of nationwide observational surveys consecutively recruiting patients admitted for acute myocardial infarction every 5 years. Among the 4250 STEMI patients in the 2005 and 2010 cohorts, those with reperfusion therapy and onset-to-first call time 120 min), and 824 (28%) intravenous fibrinolysis. Five-year survival was higher with a pharmaco-invasive strategy (89.8%) compared with late pPCI [79.5%; adjusted hazard ratio (HR) 1.51; 1.13-2.02] and similar to timely pPCI (88.2%, adjusted HR 1.02; 0.75-1.38). Concordant results were observed in propensity score-matched cohorts and for event-free survival.CONCLUSION : A substantial proportion of patients have pPCI beyond recommended timelines. As foreseen by the guidelines, these patients have poorer 5-year outcomes, compared with a pharmaco-invasive strategy

Rationale and design of the ULYSS trial: A randomized multicenter evaluation of the efficacy of early Impella CP implantation in acute coronary syndrome complicated by cardiogenic shock

Context: Despite 20 years of improvement in acute coronary syndromes care, patients with acute myocardial infarction complicated by cardiogenic shock (AMICS) remains a major clinical challenge with a stable incidence and mortality. While intra-aortic balloon pump (IABP) did not meet its expectations, percutaneous mechanical circulatory supports (pMCS) with higher hemodynamic support, large availability and quick implementation may improve AMICS prognosis by enabling early hemodynamic stabilization and unloading. Both interventional and observational studies suggested a clinical benefit in selected patients of the IMPELLAⓇ CP device within in a well-defined therapeutic strategy. While promising, these preliminary results are challenged by others suggesting a higher rate of complications and possible poorer outcome. Given these conflicting data and its high cost, a randomized clinical trial is warranted to delineate the benefits and risks of this new therapeutic strategy.Design: The ULYSS trial is a prospective randomized open label, 2 parallel multicenter clinical trial that plans to enroll patients with AMICS for whom an emergent percutaneous coronary intervention (PCI) is intended. Patients will be randomized to an experimental therapeutic strategy with pre-PCI implantation of an IMPELLAⓇ CP device on top of standard medical therapy or to a control group undergoing PCI and standard medical therapy. The primary objective of this study is to compare the efficacy of this experimental strategy by a composite end point of death, need to escalate to ECMO, long-term left ventricular assist device or heart transplantation at 1 month. Among secondary objectives 1-year efficacy, safety and cost effectiveness will be assessed.Clinical trial registration: NCT05366452

Prior balloon valvuloplasty versus DIRECT transcatheter Aortic Valve Implantation (DIRECTAVI): study protocol for a randomized controlled trial

Abstract Background Balloon predilatation of the aortic valve has been regarded as an essential step during the transcatheter aortic valve implantation (TAVI) procedure. However, recent evidence has suggested that aortic valvuloplasty may cause complications and that high success rates may be obtained without prior dilatation of the valve. We hypothesize that TAVI performed without predilatation of the aortic valve and using new-generation balloon-expandable transcatheter heart valves is associated with a better net clinical benefit than TAVI performed with predilatation. Methods/design The transcatheter aortic valve implantation without prior balloon dilatation (DIRECTAVI) trial is a randomized controlled open label trial that includes 240 patients randomized to TAVI performed with prior balloon valvuloplasty (control arm) or direct implantation of the valve (test arm). All patients with an indication for TAVI will be included excepting those requiring transapical access. The trial tests the hypothesis that the strategy of direct implantation of the new-generation balloon-expandable SAPIEN 3 valve is noninferior to current medical practice using predilatation of the valve. The primary endpoint assessing efficacy and safety of the procedure consists of immediate procedural success and secondary endpoints include complications at 30-day follow-up (VARC-2 criteria). A subgroup analysis evaluates neurological ischemic events with cerebral MRI imaging (25 patients in each strategy group) performed before and between 1 and 3 days after the procedure. Discussion This prospective randomized study is designed to assess the efficacy and safety of TAVI performed without prior dilatation of the aortic valve using new-generation balloon-expandable transcatheter heart valves. We aim to provide robust evidence of the advantages of this strategy to allow the interventional cardiologist to use it in everyday practice. Trial registration ClinicalTrials.gov identifier: NCT02729519 . Registered on 15 July 2016

083: Medical hypothesis: heart rate on admission and CRP are correlated, in acute pericarditis: a link between heart rate and pericardial inflammation?

IntroductionRest is usually recommended in acute pericarditis, as it could help to lower heart rate (HR) and contribute to limit “mechanical inflammation”. Whether HR on admission could be correlated and perhaps participate to inflammation has not been reported.MethodsBetween March 2007 and February 2010, we conducted a retrospective study on all patients admitted in our center for acute pericarditis. Diagnosis criteria included 2 among the following: typical chest pain, friction rub, pericardial effusion on cardiac echography, or typical ECG findings. Primary endpoint was biology: CRP on admission, on days 1, 2, 3, and especially peak. We evaluated also recurrences and clinical events during hospitalization and at one month.ResultsWe included 73 patients. Median age was 38.0 y (CI 25-75% 28.0-51.0) and median hospitalization duration was 2.0 d (1.5-3.0). 27% of the patients presented pericardial effusion. Heart rate on admission was 88.0 bpm (CI 25-75%: 76.0-100.0) and on discharge 72.0 (65.0-80.0)). Heart rate on admission was significantly correlated with CRP on admission (r=0.34, n=69; p=0.004), CRP peak (r=0.54; n=61; p<0.0001), CRP on discharge (r=0.32; p=0.021) and temperature on admission (r=0.40; n=39; p=0.01). Multivariate analysis showed that HR on admission is associated with an elevated CRP peak, independently of temperature on admission. Fever was scarcely observed (19.5%), and was neither correlated to HR nor CRP, after multivariate analysis.ConclusionIn acute pericarditis, HR on admission is independently correlated with CRP levels. These observations could suggest a link between HR and pericardial inflammation

Feasibility and Safety of Transcatheter Aortic Valve Implantation Performed Without Intensive Care Unit Admission

International audienceAdmission to the intensive care unit (ICU) is a standard of care after transcatheter aortic valve implantation (TAVI); however, the improvement of the procedure and the need to minimize the unnecessary use of medical resources call into question this strategy. We evaluated prospectively 177 consecutive patients who underwent TAVI. Low-risk patients, admitted to conventional cardiology units, had stable clinical state, transfemoral access, no right bundle branch block, permanent pacing with a self-expandable valve, and no complication occurring during the procedure. High-risk patients included all the others transferred to ICU. In-hospital events were the primary end point (Valve Academic Research Consortium 2 criteria). The mean age of patients was 83.5 ± 6.5 years, and the mean logistic EuroSCORE was 14.6 ± 9.7%. The balloon-expandable SAPIEN 3 valve was mainly used (n = 148; 83.6%), mostly with transfemoral access (n = 167; 94.4%). Among the 61 patients (34.5%) included in the low-risk group, only 1 (1.6%) had a minor complication (negative predictive value 98.4%, 95% confidence interval [CI] 0.91 to 0.99). Conversely, 31 patients (26.7%) from the high-risk group had clinical events (positive predictive value 26.7%, 95% CI 0.19 to 0.35), mainly conductive disorders requiring pacemaker (n = 26; 14.7%). In multivariate analysis, right bundle branch block (odds ratio [OR] 14.1, 95% CI 3.5 to 56.3), use of the self-expandable valve without a pacemaker (OR 5.5, 95% CI 2 to 16.3), vitamin K antagonist treatment (OR 3.8, 95% CI 1.1 to 12.6), and female gender (OR 2.6, 95% CI 1.003 to 6.9) were preprocedural predictive factors of adverse events. In conclusion, our results suggested that TAVI can be performed safely without ICU admission in selected patients. This strategy may optimize efficiency and cost-effectiveness of procedures

Immediate vs Delayed Stenting in ST-Elevation Myocardial Infarction: Rationale and Design of the International PRIMACY Bayesian Randomized Controlled Trial

International audienc