In patients with ST-segment elevation myocardial infarction (STEMI), the use of percutaneous coronary intervention (PCI) to restore blood flow in an infarct-related coronary artery improves outcomes. ...The use of PCI in non-infarct-related coronary arteries remains controversial.
We randomly assigned 885 patients with STEMI and multivessel disease who had undergone primary PCI of an infarct-related coronary artery in a 1:2 ratio to undergo complete revascularization of non-infarct-related coronary arteries guided by fractional flow reserve (FFR) (295 patients) or to undergo no revascularization of non-infarct-related coronary arteries (590 patients). The FFR procedure was performed in both groups, but in the latter group, both the patients and their cardiologist were unaware of the findings on FFR. The primary end point was a composite of death from any cause, nonfatal myocardial infarction, revascularization, and cerebrovascular events at 12 months. Clinically indicated elective revascularizations performed within 45 days after primary PCI were not counted as events in the group receiving PCI for an infarct-related coronary artery only.
The primary outcome occurred in 23 patients in the complete-revascularization group and in 121 patients in the infarct-artery-only group that did not receive complete revascularization, a finding that translates to 8 and 21 events per 100 patients, respectively (hazard ratio, 0.35; 95% confidence interval CI, 0.22 to 0.55; P<0.001). Death occurred in 4 patients in the complete-revascularization group and in 10 patients in the infarct-artery-only group (1.4% vs. 1.7%) (hazard ratio, 0.80; 95% CI, 0.25 to 2.56), myocardial infarction in 7 and 28 patients, respectively (2.4% vs. 4.7%) (hazard ratio, 0.50; 95% CI, 0.22 to 1.13), revascularization in 18 and 103 patients (6.1% vs. 17.5%) (hazard ratio, 0.32; 95% CI, 0.20 to 0.54), and cerebrovascular events in 0 and 4 patients (0 vs. 0.7%). An FFR-related serious adverse event occurred in 2 patients (both in the group receiving infarct-related treatment only).
In patients with STEMI and multivessel disease who underwent primary PCI of an infarct-related artery, the addition of FFR-guided complete revascularization of non-infarct-related arteries in the acute setting resulted in a risk of a composite cardiovascular outcome that was lower than the risk among those who were treated for the infarct-related artery only. This finding was mainly supported by a reduction in subsequent revascularizations. (Funded by Maasstad Cardiovascular Research and others; Compare-Acute ClinicalTrials.gov number, NCT01399736 .).
Summary Background The relation between platelet reactivity and stent thrombosis, major bleeding, and other adverse events after coronary artery implantation of drug-eluting stents has been ...incompletely characterised. We aimed to determine the relation between platelet reactivity during dual therapy with aspirin and clopidogrel and clinical outcomes after successful coronary drug-eluting stent implantation. Methods ADAPT-DES was a prospective, multicentre registry of patients successfully treated with one or more drug-eluting stents and given aspirin and clopidogrel at 10–15 US and European hospitals. We assessed platelet reactivity in those patients after successful percutaneous coronary intervention using VerifyNow point-of-care assays, and assigned different cutoffs to define high platelet reactivity. The primary endpoint was definite or probable stent thrombosis; other endpoints were all-cause mortality, myocardial infarction, and clinically relevant bleeding. We did a propensity-adjusted multivariable analysis to determine the relation between platelet reactivity and subsequent adverse events. This study is registered with ClinicalTrials.gov , number NCT00638794. Findings Between Jan 7, 2008, and Sept 16, 2010, 8665 patients were prospectively enrolled at 11 sites, of which 8582 were eligible. At 1-year follow-up, stent thrombosis had occurred in 70 (0·8%) patients, myocardial infarction in 269 (3·1%), clinically relevant bleeding in 531 (6·2%), and death in 161 (1·9%) patients. High platelet reactivity on clopidogrel was strongly related to stent thrombosis (adjusted HR 2·49 95% CI 1·43–4·31, p=0·001) and myocardial infarction (adjusted HR 1·42 1·09–1·86, p=0·01), was inversely related to bleeding (adjusted HR 0·73 0·61–0·89, p=0·002), but was not related to mortality (adjusted HR 1·20 0·85–1·70, p=0·30). High platelet reactivity on aspirin was not significantly associated with stent thrombosis (adjusted HR 1·46 0·58–3·64, p=0·42), myocardial infarction, or death, but was inversely related to bleeding (adjusted HR 0·65 0·43–0·99, p=0·04). Interpretation The findings from this study emphasise the counter-balancing effects of haemorrhagic and ischaemic complications after stent implantation, and suggest that safer drugs or tailored strategies for the use of more potent agents must be developed if the benefits of greater platelet inhibition in patients with cardiovascular disease are to be realised. Funding Boston Scientific, Abbott Vascular, Medtronic, Cordis, Biosensors, The Medicines Company, Daiichi-Sankyo, Eli Lilly, Volcano, and Accumetrics
We sought to evaluate the frequency of early hypo-attenuated leaflet thickening (HALT) of the SAPIEN 3 transcatheter aortic valve (S3).
Of 249 patients who had undergone S3 implantation, we studied ...156 consecutive patients (85 women, median age 82.2 ± 5.5 years) by electrocardiogram (ECG)-triggered dual-source computed tomography angiography (CTA) after a median of 5 days post-transcatheter aortic valve implantation. The prosthesis was assessed for HALT. Apart from heparin, peri-interventional antithrombotic therapy consisted of single- (aspirin 29%) or dual- (aspirin plus clopidogrel 71%) antiplatelet therapy. Hypo-attenuated leaflet thickening was found in 16 patients 10.3% (95% confidence interval (CI) 5.5-15.0%) of the patients. None of the baseline and procedural variables were significantly associated with HALT, nor did we find a significant association with the antithrombotic regimen, either peri-interventionally or at the time of CTA. Hypo-attenuated leaflet thickening was found in 6 of 45 patients with peri-interventional single-antiplatelet therapy and in 10 of 111 patients with dual-antiplatelet therapy at the time of intervention 13.3% (95% CI 3.4-23.3%) vs. 9% (95% CI 3.7-14.3%), P = 0.42. Hypo-attenuated leaflet thickening was not associated with clinical symptoms, but a small, albeit significant difference in mean pressure gradient at the time of CTA (11.6 ± 3.4 vs. 14.9 ± 5.3 mmHg, P = 0.026). Full anticoagulation led to almost complete resolution of HALT in 13 patients with follow-up CTA.
Irrespective of the antiplatelet regimen, early HALT occurred in 10% of our patients undergoing transcatheter aortic S3 implantation. Early HALT is clinically inapparent and reversible by full anticoagulation.
Background
Reticulated platelets (RP) are the youngest circulating platelets in blood. An increased amount of this subpopulation is associated with higher cardiovascular risk and mortality.
...Objectives
It is unknown to what extent intrinsic properties of RP contribute to their hyperreactive features. This study is the first providing a multifactorial approach based on ultrastructural, transcriptional, and functional analysis of RP compared to non‐RP sorted by flow cytometry.
Methods
Reticulated platelets and non‐RP were sorted after platelet staining with SYTO 13. Employing transmission electron microscopy, 1089 micrographs were analyzed for platelet size, amounts of intracellular structures, and anatomical surrogates indicating activation. Long and small RNA‐sequencing (RNA‐seq) were performed for analyzing differential gene expression. Functional analysis of P‐selectin—an upregulated mRNA in RP—was performed in healthy subjects and patients on P2Y12‐inhibitors.
Results
Electron micrographs uncovered distinct ultrastructural differences in RP versus non‐RP. Cross sections were 1.9‐fold larger in RP (P < .0001). Amounts of α‐granules, dense granules, open canalicular system‐openings, and mitochondria were increased in RP, which persisted after adjustment for platelet size. Long RNA‐seq showed 1212 upregulated transcripts that are predominantly associated to platelet shape change, aggregation, and activation; 1264 mRNAs were downregulated in RP. Small RNA‐seq did not reveal any differentially expressed transcripts. Functional analysis displayed higher P‐selectin expression as compared to non‐RP upon ADP‐ or TRAP‐stimulation.
Conclusions
Our results demonstrate that altered intrinsic structural and molecular properties contribute to the hyperreactivity of RP. These properties and an increased amount of RP may account for the association with cardiovascular risk.
In current international guidelines, intraaortic balloon counterpulsation is considered to be a class I treatment for cardiogenic shock complicating acute myocardial infarction. However, evidence is ...based mainly on registry data, and there is a paucity of randomized clinical trials.
In this randomized, prospective, open-label, multicenter trial, we randomly assigned 600 patients with cardiogenic shock complicating acute myocardial infarction to intraaortic balloon counterpulsation (IABP group, 301 patients) or no intraaortic balloon counterpulsation (control group, 299 patients). All patients were expected to undergo early revascularization (by means of percutaneous coronary intervention or bypass surgery) and to receive the best available medical therapy. The primary efficacy end point was 30-day all-cause mortality. Safety assessments included major bleeding, peripheral ischemic complications, sepsis, and stroke.
A total of 300 patients in the IABP group and 298 in the control group were included in the analysis of the primary end point. At 30 days, 119 patients in the IABP group (39.7%) and 123 patients in the control group (41.3%) had died (relative risk with IABP, 0.96; 95% confidence interval, 0.79 to 1.17; P=0.69). There were no significant differences in secondary end points or in process-of-care measures, including the time to hemodynamic stabilization, the length of stay in the intensive care unit, serum lactate levels, the dose and duration of catecholamine therapy, and renal function. The IABP group and the control group did not differ significantly with respect to the rates of major bleeding (3.3% and 4.4%, respectively; P=0.51), peripheral ischemic complications (4.3% and 3.4%, P=0.53), sepsis (15.7% and 20.5%, P=0.15), and stroke (0.7% and 1.7%, P=0.28).
The use of intraaortic balloon counterpulsation did not significantly reduce 30-day mortality in patients with cardiogenic shock complicating acute myocardial infarction for whom an early revascularization strategy was planned. (Funded by the German Research Foundation and others; IABP-SHOCK II ClinicalTrials.gov number, NCT00491036.).
Background
Constant elevations of the serum concentration of cardiac troponin T (TnT) indicate a myocardial injury that may affect the long‐term outcome of transcatheter aortic valve replacement ...(TAVR).
Objectives
We sought to investigate the impact of pre‐TAVR TnT on outcomes after TAVR during long‐term follow‐up.
Methods
In a retrospective, observational study we compared long term outcomes after TAVR between tertiles of preinterventional high‐sensitivity TnT. Systematic follow‐up was performed annually for 5 years. The primary endpoint was a composite of all‐cause death and any rehospitalization.
Results
Between 2010 and 2018, 2,129 patients with severe aortic valve stenosis underwent TAVR at our institution (mean age 82.6 years, 57.2% female, logistic EuroSCORE 20.5 ± 15.8). Boundaries for TnT tertiles were <21 ng/L and >42 ng/L. The median follow‐up was 895 days. Three‐year incidences for the primary endpoint were 70.9%, 76.6%, and 81.7% in the low, middle, and high tertile (log rank p < .001). Compared with the first tertile, the corresponding adjusted hazard ratios were 1.23 (95%‐CI 1.08–1.40, p < .001) and 1.50 (95%‐CI 1.32–1.70, p < .001) for the second and third tertile. We found consistent differences between TnT strata for all‐cause death (3‐year incidences 23.3%, 33.3%, and 47.1%; adjusted p < .001) and rehospitalization (3‐year incidences 64.7%, 68.7% and 72.0%; adjusted p < .001), including significant differences in deaths (p < .001). The association between TnT and outcome was independent of coronary artery disease or low aortic valve gradient.
Conclusions
TnT before TAVR is strongly associated with all‐cause death and rehospitalization during 3‐year follow‐up.
The SOURCE 3 Registry (SAPIEN Aortic Bioprosthesis European Outcome) is a European multicenter, observational registry of the latest generation of transcatheter heart valve, the SAPIEN 3 (Edwards ...Lifesciences, Irvine, CA). Its purpose is to document outcomes of clinical safety and performance after European approval was given.
Here, we present the 30-day outcome of the SOURCE 3 Registry. All data are self-reported, and all participating centers have committed to support their consecutive experience with the SAPIEN 3 transcatheter heart valve, dependent on patient consent, before the start of the study. Adverse events are defined with Valve Academic Research Consortium 2 criteria and adjudicated by an independent clinical events committee.
A total of 1950 patients from 80 centers in 10 countries were enrolled between July 2014 and October 2015. Of those, 1947 patients underwent transcatheter aortic valve implantation (TAVI) with the SAPIEN 3 (mean age, 81.6±6.6 years; 48.1% female). Main comorbidities included coronary artery disease (51.5%), renal insufficiency (27.4%), diabetes mellitus (29.5%), chronic obstructive pulmonary disease (16.0%), and a mean logistic EuroSCORE of 18.3±13.2. Transfemoral access was used in 87.1% (n=1695); nontransfemoral, in 252 patients. Conscious sedation was used in 59.9% of transfemoral procedures, and in 50% of patients, TAVI was performed without aortic balloon valvuloplasty. Implantation success (1 valve in the intended location) was 98.3%. Conversion to conventional surgery (0.6%) and use of cardiopulmonary bypass (0.7%) were rare. Adverse events were low, with site-reported 30-day all-cause mortality of 2.2%, cardiovascular mortality of 1.1%, stroke of 1.4%, major vascular complications of 4.1%, life-threatening bleeding of 5%, and post-TAVI pacemaker implantation of 12%. Moderate or greater paravalvular regurgitation was observed in 3.1% of reporting patients.
Results from the SOURCE 3 Registry demonstrate contemporary European trends and good outcomes of TAVI in daily practice when this third-generation TAVI device is used.
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