Microaxial Flow Pump or Standard Care in Infarct-Related Cardiogenic Shock.

BACKGROUND: The effects of temporary mechanical circulatory support with a microaxial flow pump on mortality among patients with ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock remains unclear. METHODS: In an international, multicenter, randomized trial, we assigned patients with STEMI and cardiogenic shock to receive a microaxial flow pump (Impella CP) plus standard care or standard care alone. The primary end point was death from any cause at 180 days. A composite safety end point was severe bleeding, limb ischemia, hemolysis, device failure, or worsening aortic regurgitation. RESULTS: A total of 360 patients underwent randomization, of whom 355 were included in the final analysis (179 in the microaxial-flow-pump group and 176 in the standard-care group). The median age of the patients was 67 years, and 79.2% were men. Death from any cause occurred in 82 of 179 patients (45.8%) in the microaxial-flow-pump group and in 103 of 176 patients (58.5%) in the standard-care group (hazard ratio, 0.74; 95% confidence interval [CI], 0.55 to 0.99; P = 0.04). A composite safety end-point event occurred in 43 patients (24.0%) in the microaxial-flow-pump group and in 11 (6.2%) in the standard-care group (relative risk, 4.74; 95% CI, 2.36 to 9.55). Renal-replacement therapy was administered to 75 patients (41.9%) in the microaxial-flow-pump group and to 47 patients (26.7%) in the standard-care group (relative risk, 1.98; 95% CI, 1.27 to 3.09). CONCLUSIONS: The routine use of a microaxial flow pump with standard care in the treatment of patients with STEMI-related cardiogenic shock led to a lower risk of death from any cause at 180 days than standard care alone. The incidence of a composite of adverse events was higher with the use of the microaxial flow pump. (Funded by the Danish Heart Foundation and Abiomed; DanGer Shock ClinicalTrials.gov number, NCT01633502.).

Randomized comparison of TAVI valves: The Compare-TAVI trial.

INTRODUCTION: Based on technical advancements and clinical evidence, transcatheter aortic valve implantation (TAVI) has been widely adopted. New generation TAVI valve platforms are continually being developed. Ideally, new valves should be superior or at least non-inferior regarding efficacy and safety, when compared to best-in-practice contemporary TAVI valves. METHODS AND ANALYSIS: The Compare-TAVI trial (ClinicalTrials.gov NCT04443023) was launched in 2020, to perform a 1:1 randomized comparison of new vs contemporary TAVI valves, preferably in all comers. Consecutive cohorts will be launched with sample sizes depending on the choice of interim analyses, expected event rates, and chosen superiority or non-inferiority margins. Enrollment has just been finalized in cohort B, comparing the Sapien 3/Sapien 3 Ultra Transcatheter Heart Valve (THV) series (Edwards Lifesciences, Irvine, California, USA) and the Myval/Myval Octacor THV series (Meril Life Sciences Pvt. Ltd., Vapi, Gujarat, India) balloon expandable valves. This non-inferiority study was aimed to include 1062 patients. The 1-year composite safety and efficacy endpoint comprises death, stroke, moderate-severe aortic regurgitation, and moderate-severe valve deterioration. Patients will be followed until withdrawal of consent, death, or completion of 10-year follow-up, whichever comes first. Secondary endpoints will be monitored at 30 days, 1, 3, 5, and 10 years. SUMMARY: The Compare-TAVI organization will launch consecutive cohorts wherein patients scheduled for TAVI are randomized to one of two valves. The aim is to ensure that the short- and long-term performance and safety of new valves being introduced is benchmarked against what achieved by best-in-practice contemporary valves.

Long-term outcomes after coronary intervention with biodegradable polymer stents in patients with acute coronary syndromes.

BACKGROUND: Patients with acute coronary syndromes (ACS) may have worse outcomes after percutaneous coronary intervention compared to patients without ACS. AIMS: To compare 5-year efficacy and safety outcomes in patients with and without ACS treated with biodegradable polymers, the ultrathin strut sirolimus-eluting Orsiro stent (O-SES) or the biolimus-eluting Nobori stent (N-BES). METHODS: The Scandinavian Organisation for Randomized Trials with Clinical Outcome VII is a randomized trial comparing O-SES and N-BES in an all-comer setting. Of 2525 patients, 1329 (53%) patients had ACS and 1196 (47%) patients were without ACS. Endpoints were target lesion failure (TLF) (a composite of cardiac death, target lesion myocardial infarction, or target lesion revascularization) and definite stent thrombosis within 5 years. RESULTS: At 5-year follow-up, TLF did not differ significantly between patients with and without ACS (12.3% vs. 13.2%; rate ratio (RR) 1.00; 95% confidence interval (CI): 0.70-1.44), whereas the risk of definite stent thrombosis was increased in patients with ACS (2.3% vs. 1.3; RR: 2.01 [95% CI: 1.01-3.98]). In patients with ACS, the rate of TLF was similar between O-SES and N-BES (12.4% vs. 12.3%; RR: 1.02; 95% CI: 0.74-1.40). The reduced risk of definite stent thrombosis in O-SES treated ACS patients within the first year (0.2% vs. 1.6%; RR: 0.12; 95% CI: 0.02-0.93) was not maintained after 5 years (1.8% vs. 2.7%; RR: 0.77; 95% CI: 0.37-1.63). CONCLUSION: Patients with ACS had an increased risk of stent thrombosis regardless of the stent type used. Long-term outcomes were similar for ACS patients treated with O-SES or N-BES at 5 years.

Accelerated -Rule-Out of acute Myocardial Infarction using prehospital copeptin and in-hospital troponin: The AROMI study.

AIMS: The present acute myocardial infarction (AMI) rule-out strategies are challenged by the late temporal release of cardiac troponin. Copeptin is a non-specific biomarker of endogenous stress and rises early in AMI, covering the early period where troponin is still normal. An accelerated dual-marker rule-out strategy combining prehospital copeptin and in-hospital high-sensitivity troponin T could reduce length of hospital stay and thus the burden on the health care systems worldwide. The AROMI trial aimed to evaluate if the accelerated dual-marker rule-out strategy could safely reduce length of stay in patients discharged after early rule-out of AMI. METHODS AND RESULTS: Patients with suspected AMI transported to hospital by ambulance were randomized 1:1 to either accelerated rule-out using copeptin measured in a prehospital blood sample and high-sensitivity troponin T measured at arrival to hospital or to standard rule-out using a 0 h/3 h rule-out strategy. The AROMI study included 4351 patients with suspected AMI. The accelerated dual-marker rule-out strategy reduced mean length of stay by 0.9 h (95% confidence interval 0.7-1.1 h) in patients discharged after rule-out of AMI and was non-inferior regarding 30-day major adverse cardiac events when compared to standard rule-out (absolute risk difference -0.4%, 95% confidence interval -2.5 to 1.7; P-value for non-inferiority = 0.013). CONCLUSION: Accelerated dual marker rule-out of AMI, using a combination of prehospital copeptin and first in-hospital high-sensitivity troponin T, reduces length of hospital stay without increasing the rate of 30-day major adverse cardiac events as compared to using a 0 h/3 h rule-out strategy.

Reduced Leaflet Motion after Transcatheter Aortic-Valve Replacement.

BACKGROUND: Subclinical leaflet thickening and reduced leaflet motion of bioprosthetic aortic valves have been documented by four-dimensional computed tomography (CT). Whether anticoagulation can reduce these phenomena after transcatheter aortic-valve replacement (TAVR) is not known. METHODS: In a substudy of a large randomized trial, we randomly assigned patients who had undergone successful TAVR and who did not have an indication for long-term anticoagulation to a rivaroxaban-based antithrombotic strategy (rivaroxaban [10 mg] plus aspirin [75 to 100 mg] once daily) or an antiplatelet-based strategy (clopidogrel [75 mg] plus aspirin [75 to 100 mg] once daily). Patients underwent evaluation by four-dimensional CT at a mean (±SD) of 90±15 days after randomization. The primary end point was the percentage of patients with at least one prosthetic valve leaflet with grade 3 or higher motion reduction (i.e., involving >50% of the leaflet). Leaflet thickening was also assessed. RESULTS: A total of 231 patients were enrolled. At least one prosthetic valve leaflet with grade 3 or higher motion reduction was found in 2 of 97 patients (2.1%) who had scans that could be evaluated in the rivaroxaban group, as compared with 11 of 101 (10.9%) in the antiplatelet group (difference, -8.8 percentage points; 95% confidence interval [CI], -16.5 to -1.9; P = 0.01). Thickening of at least one leaflet was observed in 12 of 97 patients (12.4%) in the rivaroxaban group and in 33 of 102 (32.4%) in the antiplatelet group (difference, -20.0 percentage points; 95% CI, -30.9 to -8.5). In the main trial, the risk of death or thromboembolic events and the risk of life-threatening, disabling, or major bleeding were higher with rivaroxaban (hazard ratios of 1.35 and 1.50, respectively). CONCLUSIONS: In a substudy of a trial involving patients without an indication for long-term anticoagulation who had undergone successful TAVR, a rivaroxaban-based antithrombotic strategy was more effective than an antiplatelet-based strategy in preventing subclinical leaflet-motion abnormalities. However, in the main trial, the rivaroxaban-based strategy was associated with a higher risk of death or thromboembolic complications and a higher risk of bleeding than the antiplatelet-based strategy. (Funded by Bayer; GALILEO-4D ClinicalTrials.gov number, NCT02833948.).

International randomized trial on the effect of revascularization or optimal medical therapy of chronic total coronary occlusions with myocardial ischemia - ISCHEMIA-CTO trial - rationale and design.

BACKGROUND: Chronic total occlusions (CTO) are frequent among patients with coronary artery disease. Revascularization with percutaneous coronary intervention (PCI) is safe and feasible in experienced hands. However, randomized data are needed to demonstrate symptomatic as well as prognostic effect of CTO-PCI compared to optimal medical therapy alone. METHODS: This trial aims to evaluate the effect of CTO PCI in patients with a CTO lesion and target vessel diameter ≥ 2.5 mm, and myocardial ischemia in the relevant territory. First, all patients are subjected to optimal medical therapy (OMT) for at least for 3 months and non-CTO lesions are managed according to guidelines. Subsequently, prior to randomization myocardial ischemia and quality of life (Seattle Questionnaire (SAQ)) is assessed. Patients are divided into two cohorts based on their SAQ score and randomized to either OMT alone or OMT and CTO-PCI. Cohort A is defined as Low- or asymptomatic patients with a quality-of-life score > 60 and/or CCS class < 2, and more than 10 % ischemia in the left ventricle (LV). Cohort B is symptomatic patients with a quality-of-life score < 60 or CCS class angina > 1 and at least ischemia in 5% of the LV. The primary end-point in cohort A is a composite of major adverse cardiac and cerebral events, hospitalization for heart failure and malignant ventricular arrhythmias. The primary endpoint in cohort B is difference in quality of life 6 months after randomization. IMPLICATIONS: This trial is designed to investigate if CTO-PCI improves QoL and MACCE. Both positive and negative outcome of the trial will affect future guidelines and recommendations on how to treat patients with CTO.

Routine revascularization with percutaneous coronary intervention in patients with coronary artery disease undergoing transcatheter aortic valve implantation - the third nordic aortic valve intervention trial - NOTION-3.

BACKGROUND: Coronary artery disease (CAD) frequently coexists with severe aortic valve stenosis (AS) in patients planned for transcatheter aortic valve implantation (TAVI). How to manage CAD in this patient population is still an unresolved question. In particular, it is still not known whether fractional flow reserve (FFR) guided revascularization with percutaneous coronary intervention (PCI) is superior to medical treatment for CAD in terms of clinical outcomes. STUDY DESIGN: The third Nordic Aortic Valve Intervention (NOTION-3) Trial is an open-label investigator-initiated, multicenter multinational trial planned to randomize 452 patients with severe AS and significant CAD to either FFR-guided PCI or medical treatment, in addition to TAVI. Patients are eligible for the study in the presence of at least 1 significant PCI-eligible coronary stenosis. A significant stenosis is defined as either FFR ≤0.80 and/or diameter stenosis >90%. The primary end point is a composite of first occurring all-cause mortality, myocardial infarction, or urgent revascularization (PCI or coronary artery bypass graft performed during unplanned hospital admission) until the last included patient have been followed for 1 year after the TAVI. SUMMARY: NOTION-3 is a multicenter, multinational randomized trial aiming at comparing FFR-guided revascularization vs medical treatment of CAD in patients with severe AS planned for TAVI.

Early healing after treatment of coronary lesions by thin strut everolimus, or thicker strut biolimus eluting bioabsorbable polymer stents: The SORT-OUT VIII OCT study.

AIMS: Early healing after drug-eluting stent (DES) implantation may reduce the risk of stent thrombosis. The aim of this study was to compare patterns of early healing after implantation of the thin strut everolimus-eluting Synergy DES (Boston Scientific) or the biolimus-eluting Biomatix Neoflex DES (Biosensors). METHODS AND RESULTS: A total of 160 patients with the chronic or acute coronary syndrome were randomized 1:1 to Synergy or Biomatrix DES. Optical coherence tomography (OCT) was performed at baseline and at either 1- or 3-month follow-up. The primary endpoint was a coronary stent healing index (CSHI), a weighted index of strut coverage, neointimal hyperplasia, malapposition, and extrastent lumen. A total of 133 cases had OCT follow-up and 119 qualified for matched OCT analysis. The median CSHI score did neither differ significantly between the groups at 1 month: Synergy 8.0 (interquartile range [IQR]: 3.0; 14.0) versus Biomatrix 8.5 (IQR: 4.0; 15.0) (p = 0.47) nor at 3 months: Synergy 6.5 (IQR: 2.0; 13.0) versus Biomatrix 6.0 (IQR: 4.0; 11.0) (p = 0.83). Strut coverage was 84.6% (IQR: 72.0; 97.9) for Synergy versus 77.6% (IQR: 70.1; 90.3) for Biomatrix (p = 0.15) at 1 month and 90.3% (IQR 79.0; 98.8) (Synergy) versus 83.9% (IQR: 77.5; 92.6) (Biomatrix) (p = 0.068) at 3 months. Pooled 1- and 3-month coverage was 88.6% (IQR: 74.4; 98.4) for Synergy compared with 80.7% (IQR: 73.2; 90.8) for Biomatrix (p = 0.02). CONCLUSIONS: The early healing response after treatment with the Synergy or Biomatrix DES did not differ significantly as determined by a healing index. The Synergy DES showed overall better early stent strut coverage.

Impact of acute coronary syndrome on clinical outcomes after revascularization with the dual-therapy CD34 antibody-covered sirolimus-eluting Combo stent and the sirolimus-eluting Orsiro stent.

OBJECTIVES: To compare the efficacy and safety of the dual-therapy CD34 antibody-covered sirolimus-eluting Combo stent (DTS) and the sirolimus-eluting Orsiro stent (O-SES) in patients with and without acute coronary syndrome (ACS) included in the SORT OUT X study. BACKGROUND: The incidence of target lesion failure (TLF) after treatment with modern drug-eluting stents has been reported to be significantly higher in patients with ACS when compared to patients without ACS. Whether the results from the SORT OUT X study apply to patients with and without ACS remains unknown. METHODS: In total, 3146 patients were randomized to stent implantation with DTS (n = 1578; ACS: n = 856) or O-SES (n = 1568; ACS: n = 854). The primary end point, TLF, was a composite of cardiac death, target-lesion myocardial infarction (MI), or target lesion revascularization (TLR) within 1 year. RESULTS: At 1 year, the rate of TLF was higher in the DTS group compared to the O-SES group, both among patients with ACS (6.7% vs. 4.1%; incidence rate ratio: 1.65 [95% confidence interval, CI: 1.08-2.52]) and without ACS (6.0% vs. 3.2%; incidence rate ratio: 1.88 [95% CI: 1.13-3.14]). The differences were mainly explained by higher rates of TLR, whereas rates of cardiac death and target lesion MI did not differ significantly between the two stent groups in patients with or without ACS CONCLUSION: Compared to the O-SES, the DTS was associated with a higher risk of TLF at 12 months in patients with and without ACS. The differences were mainly explained by higher rates of TLR.

Randomized Clinical Comparison of the Dual-Therapy CD34 Antibody-Covered Sirolimus-Eluting Combo Stent With the Sirolimus-Eluting Orsiro Stent in Patients Treated With Percutaneous Coronary Intervention: The SORT OUT X Trial.

BACKGROUND: Target lesion failure remains an issue with contemporary drug-eluting stents. Thus, the dual-therapy sirolimus-eluting and CD34+ antibody-coated Combo stent (DTS) was designed to further improve early healing. This study aimed to investigate whether the DTS is noninferior to the sirolimus-eluting Orsiro stent (SES) in an all-comers patient population. METHODS: The SORT OUT X (Combo Stent Versus Orsiro Stent) trial, was a large-scale, randomized, multicenter, single-blind, 2-arm, noninferiority trial with registry-based follow-up. The primary end point target lesion failure was a composite of cardiac death, myocardial infarction, or target lesion revascularization within 12 months, analyzed using intention-to-treat. The trial was powered for assessing target lesion failure noninferiority of the DTS compared with the SES with a predetermined noninferiority margin of 0.021. RESULTS: A total of 3146 patients were randomized to treatment with the DTS (1578 patients; 2008 lesions) or SES (1568 patients; 1982 lesions). At 12 months, intention-to-treat analysis showed that 100 patients (6.3%) assigned the DTS and 58 patients (3.7%) assigned the SES met the primary end point (absolute risk difference, 2.6% [upper limit of 1-sided 95% CI, 4.1%]; P (noninferiority)=0.76). The SES was superior to the DTS (incidence rate ratios for target lesion failure, 1.74 [95% CI, 1.26-2.41]; P=0.00086). The difference was explained mainly by a higher incidence of target lesion revascularization in the DTS group compared with the SES group (53 [3.4%] vs. 24 [1.5%]; incidence rate ratio, 2.22 [95% CI, 1.37-3.61]; P=0.0012). CONCLUSIONS: The DTS did not confirm noninferiority to the SES for target lesion failure at 12 months in an all-comer population. The SES was superior to the DTS mainly because the DTS was associated with an increased risk of target lesion revascularization. However, rates of death, cardiac death, and myocardial infarction at 12 months did not differ significantly between the 2 stent groups. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03216733.

Performance of quantitative flow ratio in patients with aortic stenosis undergoing transcatheter aortic valve implantation.

OBJECTIVES: This study aims to evaluate the diagnostic performance of quantitative flow ratio (QFR) pre transcatheter aortic valve implantation (TAVI) in patients with aortic valve stenosis (AS) and coronary artery disease (CAD). Post-TAVI fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) was used as reference. BACKGROUND: CAD is prevalent in patients with AS, but the hemodynamics of AS confounds evaluation using pressure wire-based assessments. QFR might be less sensitive to the presence of AS thereby allowing for CAD evaluation before aortic valve replacement. Further, QFR does not require the use of pressure wire and therefore has the potential for reducing costs and complications related to insertion of a coronary pressure wire. METHODS: The diagnostic performance of QFR in coronary angiograms from 28 patients undergoing TAVI was evaluated. In all patients, both FFR and iFR were measured pre- and immediately post-TAVI while QFR was measured pre-TAVI. RESULTS: Using post-TAVI FFR and iFR as reference the diagnostic accuracy of pre-TAVI QFR were 83% (95%CI; 68-97) and 52% (95%CI; 30-74) p = .008, respectively. CONCLUSIONS: Pre-TAVI QFR showed a good diagnostic performance using post-TAVI FFR as reference. QFR could become a wire-free, safe, and quick way of evaluating CAD in patients with severe AS undergoing TAVI.

Impact of diabetes on clinical outcomes after revascularization with the dual therapy CD34 antibody-covered sirolimus-eluting Combo stent and the sirolimus-eluting Orsiro stent.

OBJECTIVES: To compare the efficacy and safety of the dual therapy CD34 antibody-covered sirolimus-eluting Combo stent (DTS) and the sirolimus-eluting Orsiro stent (SES) in patients with and without diabetes mellitus (DM) included in the Scandinavian Organization for Randomized Trials with Clinical Outcome (SORT OUT) X study. BACKGROUND: The incidence of target lesion failure (TLF) after treatment with modern drug-eluting stents has been reported to be significantly higher in patients with DM when compared to patients without DM. Thus, whether the results from the SORT OUT X study apply to patients with and without DM remains unknown. METHODS: In total 3146 patients were randomized to stent implantation with DTS (n = 1578; DM: n = 279) or SES (n = 1568; DM: n = 271). The primary end point, TLF, was a composite of cardiac death, target-lesion myocardial infarction (MI), or target lesion revascularization (TLR) within 1 year. RESULTS: At 1 year, the rate of TLF was increased in the DTS group compared to the SES group, both among patients with DM (9.3% vs. 4.8%; risk difference: 4.5%; incidence rate ratio: 1.99, 95% confidence interval [CI]: 1.02-3.90) and without DM (5.7% vs. 3.5%; incidence rate ratio: 1.67, 95% CI: 1.15-2.42). The differences were mainly explained by higher rates of TLR. CONCLUSION: Compared to the SES, the DTS was associated with an increased risk of TLF at 12 months in patients with and without DM. The differences were mainly explained by higher rates of TLR, whereas rates of cardiac death and target lesion MI did not differ significantly between the two stent groups in patients with or without DM.

Randomized Comparison of the Polymer-Free Biolimus-Coated BioFreedom Stent With the Ultrathin Strut Biodegradable Polymer Sirolimus-Eluting Orsiro Stent in an All-Comers Population Treated With Percutaneous Coronary Intervention: The SORT OUT IX Trial.

BACKGROUND: In patients with increased bleeding risk, the biolimus A9-coated BioFreedom stent, a stainless steel drug-coated stent free from polymer, has shown superiority compared with a bare-metal stent. The aim of this study was to investigate whether the BioFreedom stent is noninferior to a modern ultrathin strut biodegradable polymer cobalt-chromium sirolimus-eluting Orsiro stent in an all-comers patient population treated with percutaneous coronary intervention. METHODS: The SORT OUT IX trial (Scandinavian Organization for Randomized Trials With Clinical Outcome IX), was a large-scale, registry-based, randomized, multicenter, single-blind, 2-arm, noninferiority trial. The primary end point, major adverse cardiovascular events, was defined as the composite of cardiac death, myocardial infarction not related to any segment other than the target lesion, or target lesion revascularization within 1 year, analyzed by intention-to-treat. The trial was powered to assess noninferiority for major adverse cardiovascular events of the BioFreedom stent compared with the Orsiro stent with a predetermined noninferiority margin of 0.021. RESULTS: Between December 14, 2015 and April 21, 2017, 3151 patients were assigned to treatment with the BioFreedom stent (1572 patients, 1966 lesions) or to the Orsiro stent (1579 patients, 1985 lesions). Five patients were lost to follow-up because of emigration (99.9% follow-up rate). Mean age was 66.3±10.9, diabetes mellitus was seen in 19.3% of patients, and 53% of the patients had acute coronary syndromes. At 1 year, intention-to-treat analysis showed that 79 (5.0%) patients, who were assigned the BioFreedom stent, and 59 (3.7%), who were assigned the Orsiro stent, met the primary end point (absolute risk difference 1.29% [upper limit of one-sided 95% CI 2.50%]; Pnoninferiority=0.14). Significantly more patients in the BioFreedom stent group had target lesion revascularization than those in the Orsiro stent group (55 [3.5%] vs 20 [1.3%], rate ratio 2.77 [95% CI, 1.66-4.62]; P<0.0001). CONCLUSIONS: The biolimus A9-coated BioFreedom polymer-free stent did not meet criteria for noninferiority for major adverse cardiovascular events at 12 months when compared with the ultrathin strut biodegradable polymer sirolimus-eluting Orsiro stent in an all-comers population Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02623140.

Dedicated plug based closure for large bore access -The MARVEL prospective registry.

OBJECTIVES: To study safety and performance of the MANTA Vascular closure device (VCD) under real world conditions in 10 centers. BACKGROUND: The MANTA is a novel plug-based device for large bore arteriotomy closure. METHODS: We included all eligible patients who underwent transfemoral large bore percutaneous procedures. Exclusion criteria were per operator's discretion and included severe calcification or marked tortuosity of the access vessel, presence of marked obesity/cachexia or a systolic blood pressure above 180 mmHg. The primary performance endpoint was time to hemostasis. Primary and secondary safety endpoints were major and minor access site related vascular complications up to 30 days, respectively. Vascular complications were adjudicated by an independent clinical event committee according to VARC-2 criteria. We performed multivariable logistic regression to estimate the effect of baseline and procedural characteristics on any and major vascular complications. RESULTS: Between February 2018 and July 2019 500 patients were enrolled undergoing Transcatheter aortic valve replacement (TAVR, N = 496), Balloon aortic valvuloplasty (BAV, N = 2), Mechanical circulatory support (MCS, N = 1) or Endovascular aneurysm repair (EVAR, N = 1). Mean age was 80.8 ± 6.6 years with a median STS-score of 2.7 [IQR 2.0-4.3] %. MANTA access site complications were major in 20 (4%) and minor in 28 patients (5.6%). Median time to hemostasis was 50 [IQR 20-120] sec. Severe femoral artery calcification, scar presence in groin, longer procedure duration, female gender and history of hypertension were independent predictors for vascular complications. CONCLUSION: In this study, MANTA appeared to be a safe and effective device for large bore access closure under real-world conditions.

Mechanical circulatory support for refractory out-of-hospital cardiac arrest: a Danish nationwide multicenter study.

BACKGROUND: Mechanical circulatory support (MCS) with either extracorporeal membrane oxygenation or Impella has shown potential as a salvage therapy for patients with refractory out-of-hospital cardiac arrest (OHCA). The objective of this study was to describe the gradual implementation, survival and adherence to the national consensus with respect to use of MCS for OHCA in Denmark, and to identify factors associated with outcome. METHODS: This retrospective, observational cohort study included patients receiving MCS for OHCA at all tertiary cardiac arrest centers (n = 4) in Denmark between July 2011 and December 2020. Logistic regression and Kaplan-Meier survival analysis were used to determine association with outcome. Outcome was presented as survival to hospital discharge with good neurological outcome, 30-day survival and predictors of 30-day mortality. RESULTS: A total of 259 patients were included in the study. Thirty-day survival was 26%. Sixty-five (25%) survived to hospital discharge and a good neurological outcome (Glasgow-Pittsburgh Cerebral Performance Categories 1-2) was observed in 94% of these patients. Strict adherence to the national consensus showed a 30-day survival rate of 30% compared with 22% in patients violating one or more criteria. Adding criteria to the national consensus such as signs of life during cardiopulmonary resuscitation (CPR), pre-hospital low-flow < 100 min, pH > 6.8 and lactate < 15 mmol/L increased the survival rate to 48%, but would exclude 58% of the survivors from the current cohort. Logistic regression identified asystole (RR 1.36, 95% CI 1.18-1.57), pulseless electrical activity (RR 1.20, 95% CI 1.03-1.41), initial pH < 6.8 (RR 1.28, 95% CI 1.12-1.46) and lactate levels > 15 mmol/L (RR 1.16, 95% CI 1.16-1.53) as factors associated with increased risk of 30-day mortality. Patients presenting signs of life during CPR had reduced risk of 30-day mortality (RR 0.63, 95% CI 0.52-0.76). CONCLUSIONS: A high survival rate with a good neurological outcome was observed in this Danish population of patients treated with MCS for OHCA. Stringent patient selection for MCS may produce higher survival rates but potentially withholds life-saving treatment in a significant proportion of survivors.

A systematic approach to weaning from extracorporeal membrane oxygenation in patients with refractory cardiac failure.

BACKGROUND: Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is commonly used to provide haemodynamic support for patients with severe cardiac failure. However, timing ECMO weaning remains challenging. We aimed to examine if an integrative weaning approach based on predefined haemodynamic, respiratory and echocardiographic criteria is associated with successful weaning. METHODS: All patients weaned from ECMO between April 2017 and April 2019 at Aarhus University Hospital, Denmark, were consecutively enrolled. Predefined haemodynamic, respiratory and echocardiographic criteria were assessed before and during ECMO flow reduction. A weaning attempt was commenced in haemodynamic stable patients and patients remaining stable at minimal flow were weaned from ECMO. Comparisons were made between patients who met the criteria for weaning at first attempt and patients who did not meet these criteria. Patients completing a full weaning attempt with no further need for mechanical support within 24 h were defined as successfully weaned. RESULTS: A total of 38 patients were included in the study, of whom 26 (68%) patients met the criteria for weaning. Among these patients, 25 (96%) could be successfully weaned. Successfully weaned patients were younger and had less need for inotropic support and ECMO duration was shorter. Fulfilling the weaning criteria was associated with successful weaning and both favourable 30-d survival and survival to discharge. CONCLUSION: An integrative weaning approach based on haemodynamic, respiratory and echocardiographic criteria may strengthen the clinical decision process in predicting successful weaning in patients receiving ECMO for refractory cardiac failure.

Effect of Intravenous or Intraosseous Calcium vs Saline on Return of Spontaneous Circulation in Adults With Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial.

Importance: It is unclear whether administration of calcium has a beneficial effect in patients with cardiac arrest. Objective: To determine whether administration of calcium during out-of-hospital cardiac arrest improves return of spontaneous circulation in adults. Design, Setting, and Participants: This double-blind, placebo-controlled randomized clinical trial included 397 adult patients with out-of-hospital cardiac arrest and was conducted in the Central Denmark Region between January 20, 2020, and April 15, 2021. The last 90-day follow-up was on July 15, 2021. Interventions: The intervention consisted of up to 2 intravenous or intraosseous doses with 5 mmol of calcium chloride (n = 197) or saline (n = 200). The first dose was administered immediately after the first dose of epinephrine. Main Outcomes and Measures: The primary outcome was sustained return of spontaneous circulation. The secondary outcomes included survival and a favorable neurological outcome (modified Rankin Scale score of 0-3) at 30 days and 90 days. Results: Based on a planned interim analysis of 383 patients, the steering committee stopped the trial early due to concerns about harm in the calcium group. Of 397 adult patients randomized, 391 were included in the analyses (193 in the calcium group and 198 in the saline group; mean age, 68 [SD, 14] years; 114 [29%] were female). There was no loss to follow-up. There were 37 patients (19%) in the calcium group who had sustained return of spontaneous circulation compared with 53 patients (27%) in the saline group (risk ratio, 0.72 [95% CI, 0.49 to 1.03]; risk difference, -7.6% [95% CI, -16% to 0.8%]; P = .09). At 30 days, 10 patients (5.2%) in the calcium group and 18 patients (9.1%) in the saline group were alive (risk ratio, 0.57 [95% CI, 0.27 to 1.18]; risk difference, -3.9% [95% CI, -9.4% to 1.3%]; P = .17). A favorable neurological outcome at 30 days was observed in 7 patients (3.6%) in the calcium group and in 15 patients (7.6%) in the saline group (risk ratio, 0.48 [95% CI, 0.20 to 1.12]; risk difference, -4.0% [95% CI, -8.9% to 0.7%]; P = .12). Among the patients with calcium values measured who had return of spontaneous circulation, 26 (74%) in the calcium group and 1 (2%) in the saline group had hypercalcemia. Conclusions and Relevance: Among adults with out-of-hospital cardiac arrest, treatment with intravenous or intraosseous calcium compared with saline did not significantly improve sustained return of spontaneous circulation. These results do not support the administration of calcium during out-of-hospital cardiac arrest in adults. Trial Registration: ClinicalTrials.gov Identifier: NCT04153435.

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden.

Distribution and prognostic value of left ventricular global longitudinal strain in elderly patients with symptomatic severe aortic stenosis undergoing transcatheter aortic valve replacement.

AIMS: The aim of present study was to examine the preoperative prevalence and distribution of impaired left ventricular global longitudinal strain (LVGLS) in elderly patients with symptomatic aortic stenosis (AS) undergoing transcutaneous aortic valve replacement (TAVR) and to determine the predictive value of LVGLS on survival. METHODS: We included 411 patients with symptomatic severe AS treated with TAVR during a 5-year period, where a baseline echocardiography including LVGLS assessment was available. RESULTS: Mean age was 80.1 ± 7.1 years and aortic valve area (AVA) index 0.4 ± 0.1 cm2. 78 patients died during a median follow-up of 762 days. Mean left ventricular ejection fraction (LVEF) was 50 ± 13% and mean LVGLS was - 14.0%. LVEF was preserved in 60% of patients, while impaired LVGLS > - 18% was seen in 75% of the patients. Previous myocardial infarction, LVEF < 50%, LVGLS > - 14%, low gradient AS (< 4.0 m/s), tricuspid regurgitant gradient > 30 mmHg were identified as significant univariate predictors of all-cause mortality. On multivariate analysis LVGLS > - 14% (HR 1.79 [1.02-3.14], p = 0.04) was identified as the only independent variable associated with all-cause mortality. Reduced survival was observed with an impaired LVGLS > - 14% in the total population (p < 0.002) but also in patients with high AS gradient with preserved LVEF. LVGLS provided incremental prognostic value with respect to clinical characteristics, AVA and LVEF (χ2 19.9, p = 0.006). CONCLUSIONS: In patients with symptomatic AS undergoing TAVR, impaired LVGLS was highly prevalent despite preserved LVEF. LVGLS > - 14% was an independent predictor of all-cause mortality, and survival was reduced if LVGLS > - 14%.

Rationale and design of DanGer shock: Danish-German cardiogenic shock trial.

OBJECTIVE: The DanGer Shock trial test the hypothesis that left ventricular (LV) mechanical circulatory support with Impella CP transvalvular microaxial flow pump improves survival in patients with ST segment elevation acute myocardial infarction complicated by cardiogenic shock (AMICS) compared to conventional guideline-driven treatment. This paper describes the rationale and design of the randomized trial, in addition to the baseline characteristics of the population screened and enrolled so far. METHODS: The DanGer Shock study is a prospective, multicenter, open-label trial in patients with AMICS randomized 1:1 to Impella CP or current guideline-driven therapy with planned enrollment of 360 patients. Patients comatose after out of hospital cardiac arrest are excluded. Eligible patients are randomized immediately following shock diagnosis. Among patients randomized to receive Impella CP, the device is placed prior to angioplasty. The primary endpoint is all-cause mortality at 180 days. Baseline characteristics of patients screened and randomized in the DanGer Shock as of June 2018 are compared with 2 contemporary AMICS studies. RESULTS: As of end of June 2018, 314 patients were screened and 100 patients were randomized. Patients had median arterial lactate of 5.5 mmol/L (interquartile range 3.7-8.8 mmol/L), median systolic blood pressure of 76 mmHg (interquartile range 70-88 mmHg), and median LV ejection fraction of 20% (interquartile range 10%-30%). CONCLUSION: The DanGer Shock trial will be the first adequately powered randomized trial to address whether mechanical circulatory LV support with Impella CP can improve survival in AMICS. Baseline characteristics of the first 100 randomized patients indicate a population in profound cardiogenic shock.