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.

DANSPOT: A Multicenter Stepped-Wedge Cluster-Randomized Trial of the Reclassification of Acute Myocardial Infarction: Rationale and Study Design.

BACKGROUND: Cardiac troponins are the preferred biomarkers for the diagnosis of acute myocardial infarction. Although sex-specific 99th percentile thresholds of troponins are recommended in international guidelines, the clinical effect of their use is poorly investigated. The DANSPOT Study (The Danish Study of Sex- and Population-Specific 99th percentile upper reference limits of Troponin) aims to evaluate the clinical effect of a prospective implementation of population- and sex-specific diagnostic thresholds of troponins into clinical practice. METHODS: This study is a nationwide, multicenter, stepped-wedge cluster-randomized trial of the implementation of population- and sex-specific thresholds of troponins in 22 of 23 clinical centers in Denmark. We established sex-specific thresholds for 5 different troponin assays based on troponin levels in a healthy Danish reference population. Centers will sequentially cross over from current uniform manufacturer-derived thresholds to the new population- and sex-specific thresholds. The primary cohort is defined as patients with symptoms suggestive of acute coronary syndrome having at least 1 troponin measurement performed within 24 hours of arrival with a peak troponin value between the current uniform threshold and the new sex-specific female and male thresholds. The study will compare the occurrence of the primary outcome, defined as a composite of nonfatal myocardial infarction, unplanned revascularization, and all-cause mortality within 1 year, separately for men and women before and after the implementation of the new sex-specific thresholds. CONCLUSIONS: The DANSPOT Study is expected to show the clinical effects on diagnostics, treatment, and clinical outcomes in patients with myocardial infarction of implementing sex-specific diagnostic thresholds for troponin based on a national Danish reference population. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05336435.

Return to Work After Refractory Out-of-Hospital Cardiac Arrest in Patients Managed With or Without Extracorporeal Cardiopulmonary Resuscitation: A Nationwide Register-Based Study.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) is increasingly used for refractory out-of-hospital cardiac arrest (OHCA). However, survivors managed with ECPR are at risk of poor functional status. The purpose of this study was to investigate return to work (RTW) after refractory OHCA. METHODS AND RESULTS: Of 44 360 patients with OHCA in the period of 2011 to 2020, this nationwide registry-based study included 805 patients with refractory OHCA in the working age (18-65 years) who were employed before OHCA (2% of the total OHCA cohort). Demographics, prehospital characteristics, status at hospital arrival, employment status, and survival were retrieved through the Danish national registries. Sustainable RTW was defined as RTW for ≥6 months without any long sick leave relapses. Median follow-up time was 4.1 years. ECPR and standard advanced cardiovascular life support were applied in 136 and 669 patients, respectively. RTW 1 year after OHCA was similar (39% versus 54%; P=0.2) and sustainable RTW was high in both survivors managed with ECPR and survivors managed with standard advanced cardiovascular life support (83% versus 85%; P>0.9). Younger age and shorter length of hospitalization were associated with RTW in multivariable Cox analysis, whereas ECPR was not. CONCLUSIONS: In refractory OHCA-patients employed prior to OHCA, approximately 1 out of 2 patients were employed after 1 year with no difference between patients treated with ECPR or standard advanced cardiovascular life support. Younger age and shorter length of hospitalization were associated with RTW while ECPR was not.

Impact of mandatory preoperative dental screening on post-procedural risk of infective endocarditis in patients undergoing transcatheter aortic valve implantation: a nationwide retrospective observational study.

Background: Guidelines recommend preoperative dental screening (PDS) prior to cardiac valve surgery, to reduce the incidence of prosthetic valve infective endocarditis (IE). However, limited data support these recommendations, particular in patients undergoing transcatheter aortic valve implantation (TAVI). We aimed to investigate the effect of mandatory PDS on risk of IE in patients undergoing TAVI. Methods: In this observational study, a total of 1133 patients undergoing TAVI in Western-Denmark from 2020 to 2022 were included. Patients were categorized based on two implemented PDS practices: mandatory PDS (MPDS group), and no referral for PDS (NPDS group). Outcome data were retrieved from Danish registries and confirmed using medical records. The primary outcome was incidence of IE. Secondary outcomes were all-cause mortality and composite outcome of all-cause mortality and IE. Findings: Of 568 patients in the MPDS group 126 (22.2%) underwent subsequent oral dental surgery, compared to 8 (1.4%) among 565 patients in the NPDS group. During a median follow-up of 1.9 years (interquartile range 1.4-2.5 years), 31 (2.7%) developed IE. The yearly incidence IE rate was 1.4% (0.8-2.3) and 1.5% (0.8-2.4) in MPDS and NPDS, respectively, p = 0.86. All-cause mortality rates were similar between groups (estimated 2-year overall mortality of 6.7% (4.8-9.2) vs. 4.7% (3.2-6.9), MPDS and NPDS, respectively, p = 0.15). Consistent findings were found in 712 propensity score-matched patients. Interpretation: Mandatory PDS did not demonstrate reduced risk of IE or all-cause mortality compared to targeted PDS in patients undergoing TAVI. Funding: The funder had no role in the study design, data management, or writing.

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.

Outcomes and performance of the ACURATE neo2 transcatheter heart valve in clinical practice: one-yearresults of the ACURATE neo2 PMCF Study.

BACKGROUND: Transcatheter aortic valve implantation is an effective treatment for patients with aortic stenosis; however, complications related to paravalvular leakage (PVL) persist, including increased risk of mortality, cardiovascular mortality, and rehospitalisation. AIMS: We sought to evaluate the clinical outcomes and valve performance at 1 year in patients with severe aortic stenosis treated with the ACURATE neo2 valve in a post-market clinical setting. METHODS: Valve Academic Research Consortium-2 safety events were assessed up to 1 year. Independent core laboratories evaluated echocardiographic measures of valve performance and hypoattenuated leaflet thickening (HALT; as measured by four-dimensional computed tomography). RESULTS: The study enrolled 250 patients (64% female; mean age: 81 years; baseline Society of Thoracic Surgeons risk score: 2.9±2.0%); 246 patients were implanted with ACURATE neo2. All-cause mortality was 0.8% at 30 days and 5.1% at 1 year. The 1-year rates for stroke and disabling stroke were 3.0% and 1.3%, respectively. Overall, HALT of >50% leaflet involvement of at least one leaflet was present in 9% of patients at 30 days and in 12% of patients at 1 year. No association was observed between the presence of HALT and 1-year clinical or haemodynamic outcomes. Early haemodynamic improvements were maintained up to 1 year (mean aortic valve gradient: 47.6±14.5 mmHg at baseline, 7.6±3.2 mmHg at 1 year; mean aortic valve area: 0.7±0.2 cm2 at baseline, 1.7±0.4 cm2 at 1 year). At 1 year, 99% of patients had mild or no/trace PVL (<1% had moderate PVL; no patient had severe PVL). CONCLUSIONS: The study outcomes confirm favourable performance and safety up to 1 year in patients treated with ACURATE neo2 in routine clinical practice. (ClinicalTrials.gov: NCT04655248).

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.

Real-World Experience with Cangrelor as Adjuvant to Percutaneous Coronary Intervention: A Single-Centre Observational Study.

Background: Reversible P2Y12 inhibition can be obtained with cangrelor administered intravenously. More experience with cangrelor use in acute PCI with unknown bleeding risk is needed. Objectives: To describe real-world use of cangrelor including patient and procedure characteristics and patient outcomes. Methods: We performed a single-centre, retrospective, and observational study including all patients treated with cangrelor in relation to percutaneous coronary intervention at Aarhus University Hospital during the years 2016, 2017, and 2018. We recorded procedure indication and priority, the indications for cangrelor use, and patient outcomes within the first 48 hours after initiation of cangrelor treatment. Results: We treated 991 patients with cangrelor in the study period. Of these, 869 (87.7%) had an acute procedure priority. Among acute procedures, patients were mainly treated for STEMI (n = 723) and the remaining were treated for cardiac arrest and acute heart failure. Use of oral P2Y12 inhibitors prior to percutaneous coronary intervention was rare. Fatal bleeding events (n = 6) were only observed among patients undergoing acute procedures. Stent thrombosis was observed in two patients receiving acute treatment for STEMI. Thus, cangrelor can be used in relation to PCI under acute circumstances with advantages in terms of clinical management. The benefits and risks, in terms of patient outcomes, should ideally be assessed in randomized trials.

One-Year Outcomes after Myval Implantation in Patients with Bicuspid Aortic Valve Stenosis-A Multicentre Real-World Experience.

BACKGROUND: Bicuspid aortic valve (BAV) affects approximately 1.5% of the general population and is seen in nearly 50% of candidates for aortic valve replacement (AVR). Despite increasingly utilised transcatheter aortic valve implantation (TAVI) in aortic stenosis (AS) patients, its use among patients with severe bicuspid AS is limited as BAV is a heterogeneous disease associated with multiple and complex anatomical challenges. AIM: To investigate the one-year outcomes of TAVI using the balloon-expandable Myval transcatheter heart valve (THV) (Meril Life Sciences Pvt. Ltd., Vapi, India) in patients with severe bicuspid AS. METHODS AND RESULTS: We collected data from consecutive patients with bicuspid AS who underwent TAVI with the Myval THV and had at least one-year follow-up. Baseline characteristics, procedural, and 30-day echocardiographic and clinical outcomes were collected. Sixty-two patients were included in the study. The median age was 72 [66.3, 77.0] years, 45 (72.6%) were males, and the mean STS PROM score was 3.2 ± 2.2%. All TAVI procedures were performed via the transfemoral route. The median follow-up duration was 13.5 [12.2, 18.3] months; all-cause mortality was reported in 7 (11.3%) patients and cardiovascular hospitalisation in 6 (10.6%) patients. All-stroke was reported in 2 (3.2%), permanent pacemaker implantation 5 (8.3%), and myocardial infarction 1 (1.6%) patients. The echocardiographic assessment revealed a mean pressure gradient of 10 [8, 16.5] mmHg, effective orifice area 1.7 [1.4, 1.9] cm2, moderate AR in 1 (2%), mild AR in 14 (27%), and none/trace AR in 37 (71%). In total, 1 patient was diagnosed with valve thrombosis (2.1%), Stage II (moderate) haemodynamic deterioration was seen in 3 (6.4%), and stage III (severe) haemodynamic deterioration in 1 (2.1%) patient. CONCLUSIONS: TAVI with the Myval THV in selected BAV anatomy is associated with favourable one-year hemodynamic and clinical outcomes.

Differences in diagnostication, and revascularisation of ischaemic heart disease in Western Denmark.

INTRODUCTION: In Denmark, the incidence of and mortality from ischaemic heart disease (IHD) has been declining. In this context, it is of interest to assess any regional differences in diagnostication and invasive treatment of IHD. METHODS: We intended to describe the diagnostication and invasive treatment of IHD in Western Denmark at the regional/municipal level using the Western Denmark Heart Registry. Coronary angiography (CAG), percutaneous coronary intervention (PCI) and coronary arterial bypass grafting were registered from 2000 through 2019; cardiac multislice computed tomography (CMCT), from 2015 through 2019. RESULTS: Concerning the use of revascularisation for acute coronary syndrome (ACS), we found comparable regional activity levels but significant differences between individual municipalities. Furthermore, the use of CAG for chronic coronary syndrome (CCS) was significantly higher and the use of CMCT significantly lower in the North Denmark Region than in the Central and South Denmark Regions. CONCLUSION: We found differences in the rates of PCI for ACS at the municipal level but not between the Western Denmark regions. Furthermore, at the regional level, evaluation of chronic IHD differed regarding use of elective CAG and CMCT, and use of CMCT was not paralleled by a reduction in the number of CAG procedures. This may possibly prompt discussions on the strategy for invasive and non-invasive diagnosis of CCS and on targeted preventive measures. FUNDING: none TRIAL REGISTRATION. not relevant.

Five-Year Clinical Outcome of the Biodegradable Polymer Ultrathin Strut Sirolimus-Eluting Stent Compared to the Biodegradable Polymer Biolimus-Eluting Stent in Patients Treated With Percutaneous Coronary Intervention: From the SORT OUT VII Trial.

BACKGROUND: Biodegradable polymer drug-eluting stents were developed to improve safety and efficacy outcomes for patients undergoing percutaneous coronary intervention. However, few long-term follow-up efficacy studies are available. The study sought to investigate 5-year results from the SORT OUT VII trial (Scandinavian Organization for Randomized Trials With Clinical Outcome) comparing the biodegradable polymer ultrathin-strut sirolimus-eluting Orsiro stent (O-SES) versus the biodegradable polymer biolimus-eluting Nobori stent (N-BES). METHODS: This registry-based, randomized, multicenter, single-blinded, noninferiority trial compared O-SES and N-BES in an all-comer population. The composite primary end point, target lesion failure, consisted of cardiac death, myocardial infarction related to the target lesion, or target lesion revascularization within 1 year. Follow-up was extended to 5 years. RESULTS: Five-year follow-up was completed for 2521 patients (99.8%). Five-year target lesion failure did not differ between O-SES (12.4%) and N-BES (13.1%; rate ratio [RR], 0.94 [95% CI, 0.75-1.18]). Cardiac death (RR, 0.95 [95% CI, 0.67-1.34]), target myocardial infarction (RR, 1.14 [95% CI, 0.76-1.71]), target lesion revascularization (RR, 0.90 [95% CI, 0.67-1.21]), and definite stent thrombosis rates (RR, 0.73 [95% CI, 0.41-1.33]) did not differ significantly between the 2 stents. Within the first year, definite ST was significantly lower for O-SES (0.4%) compared to N-BES (1.2%; RR, 0.33 [95% CI, 0.12-0.92]), but no difference was from 1 through 5 years: O-SES 1.2% and N-BES 0.9% (RR, 1.28 [95% CI, 0.58-2.82]). CONCLUSIONS: Five years after treatment with biodegradable polymer stents, target lesion failure did not differ among O-SES and N-BES. Definite stent thrombosis was less often seen within the first year in the O-SES but the difference was not maintained after 5 years. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT01879358.

Prognostic implications of residual left ventricular hypertrophy and systolic dysfunction in aortic stenosis following transcatheter aortic valve replacement.

The impact of left ventricle (LV) hypertrophy (LVH) regression on contractility-associated measures, the extent of residual cardiac dysfunction and prognostic implications after the initial remodeling process after transcatheter aortic valve replacement (TAVR) has not been investigated. We aimed to assess whether greater LV mass regression from pre-TAVR to 12-months after TAVR was associated with increased systolic function; and assess the prognostic value of residual LVH, systolic function and contractility-associated measures 12-months after TAVR. A total of 439 symptomatic patients were included and examined by echocardiography. LVH regression was assessed as percentage change in LV mass index (LVMi) from baseline to 12-months after TAVR. Midwall fractional shortening (mFS) and stress-corrected (SC-mFS) were used as contractility-associated measures. Primary outcome was all-cause mortality. SC-mFS increased from 0.94 (0.7) at baseline (BS) to 1.22 (0.7) (p < 0.05) 12-months after TAVR for patients with the most LVH regression, compared to patients with no LV regression (BS 1.06 (0.7) to 1.04 (0.5), NS). At 12-months after TAVR, multivariate analysis showed independent prognostic value of LVEF < 50% or GLS < 15% (HR 1.59, p = 0.049) and mFS < 14% (HR 1.99, p = 0.002) for future all cause death. LVH regression in AS after TAVR is associated with significant improvements of LV systolic function in contrast to patients without LV regression. Residual LVH and subsequent LV systolic dysfunction is substantial 12 months after TAVR and are associated with reduced survival. Impaired mFS and the combination of abnormal LVEF or GLS independently predicted all-cause mortality beyond 12 months after TAVR.

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.

Selection of patients for mechanical circulatory support for refractory out-of-hospital cardiac arrest.

OBJECTIVE: To describe characteristics of patients admitted with refractory cardiac arrest for possible extracorporeal cardiopulmonary resuscitation (ECPR) and gain insight into the reasons for refraining from treatment in some. METHODS: Nationwide retrospective cohort study involving all tertiary centres providing ECPR in Denmark. Consecutive patients admitted with ongoing chest compression for evaluation for ECPR treatment were enrolled. Presenting characteristics, duration of no-flow and low-flow time, end-tidal carbon dioxide (ETCO2), lactate and pH, and recording of reasons for refraining from ECPR documented by the treating team were recorded. Outcomes were survival to intensive care unit admission and survival to hospital discharge. RESULTS: Of 579 patients admitted with refractory cardiac arrest for possible ECPR, 221 patients (38%) proceeded to ECPR and 358 patients (62%) were not considered candidates. Median prehospital low-flow time was 70 min (IQR 56 to 85) in ECPR patients and 62 min (48 to 81) in no-ECPR patients, p<0.001. Intra-arrest transport was more than 50 km in 92 (42%) ECPR patients and 135 in no-ECPR patients (38%), p=0.25. The leading causes for not initiating ECPR stated by the treating team were duration of low-flow time in 39%, severe metabolic derangement in 35%, and in 31% low ETCO2. The prevailing combination of contributing factors were non-shockable rhythm, low ETCO2, and metabolic derangement or prehospital low-flow time combined with low ETCO2. Survival to discharge was only achieved in six patients (1.7%) in the no-ECPR group. CONCLUSIONS: In this large nationwide study of patients admitted for possible ECPR, two-thirds of patients were not treated with ECPR. The most frequent reasons to abstain from ECPR were long duration of prehospital low-flow time, metabolic derangement and low ETCO2.

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.

Clinical outcomes of the ACURATE neo2 transcatheter heart valve: a prospective, multicenter, observational, post-market surveillance study.

BACKGROUND: The next-generation ACURATE neo2 transcatheter aortic valve was designed for simplified implantation and to mitigate the risk of paravalvular leak (PVL) compared to the earlier device. AIMS: To collect clinical outcomes and device performance data, including echocardiography and 4-dimensional computed tomography (4D-CT) data, with the ACURATE neo2 transcatheter heart valve in patients with severe aortic stenosis (AS). METHODS: ACURATE neo2 PMCF is a single-arm, multicentre study of patients with severe AS treated in routine clinical practice. The primary safety endpoint was all-cause mortality at 30-days. The primary imaging endpoint was hypo-attenuated leaflet thickening (HALT), measured by core laboratory-adjudicated 4D-CT at 30 days. Secondary endpoints included VARC safety endpoints, procedural success, and evaluation of valve performance via core laboratory-adjudicated echocardiography. RESULTS: The study enrolled 250 patients at 18 European centres (mean age: 80.8 years; 63.6% female; mean STS score: 2.9±2.0%); 246 (98.4%) were successfully treated with ACURATE neo2. The 30-day rates for mortality and disabling stroke were 0.8% and 0%, respectively. The new permanent pacemaker implantation rate was 6.5%. HALT >50% was present in 9.3% of patients at 30 days. Valve haemodynamics improved from baseline to 30 days (mean aortic valve gradient: from 47.6±14.5 mmHg to 8.6±3.9 mmHg; mean aortic valve area: from 0.7±0.2 cm2 to 1.6±0.4 cm2). At 30 days, PVL was evaluated as none/trace in 79.2% of patients, mild in 18.9%, moderate in 1.9%, and severe in 0%. CONCLUSIONS: The study results support the safety and efficacy of TAVI with ACURATE neo2 in patients in routine clinical practice.

Effect of calcium in patients with pulseless electrical activity and electrocardiographic characteristics potentially associated with hyperkalemia and ischemia-sub-study of the Calcium for Out-of-hospital Cardiac Arrest (COCA) trial.

OBJECTIVE: The Calcium for Out-of-hospital Cardiac Arrest (COCA) trial was recently conducted and published. This pre-planned sub-study evaluated the effect of calcium in patients with pulseless electrical activity (PEA) including subgroup analyses based on electrocardiographic characteristics potentially associated with hyperkalemia and ischemia. METHODS: Patients aged ≥ 18 years were included if they had a non-traumatic out-of-hospital cardiac arrest and received adrenaline. The trial drug consisted of calcium chloride (5 mmol) or saline placebo given after the first, and again after the second, dose of adrenaline for a maximum of two doses. This sub-study analyzed patients with PEA as their last known rhythm prior to receiving the trial drug. Outcomes were return of spontaneous circulation and survival at 30 days. RESULTS: 104 patients were analyzed. In the calcium group, 9 patients (20 %) achieved return of spontaneous circulation vs 23 patients (39 %) in the placebo group (risk ratio 0.51; 95 %CI 0.26, 1.00). Subgroup analyses based on electrocardiographic characteristics potentially associated with hyperkalemia and ischemia showed similar results. At 30 days, 1 patient (2.2 %) was alive in the calcium group while 8 patients (13.6 %) were alive in the placebo group (risk ratio 0.16; 95 %CI 0.02, 1.26). CONCLUSION: In adults with out-of-hospital cardiac arrest presenting with PEA, effect estimates suggested harm of calcium administration as compared to placebo but with wide confidence intervals. Results were consistent for patients with electrocardiographic characteristics potentially associated with hyperkalemia and ischemia. The results do not support calcium administration based strictly on electrocardiographic findings seen during out-of-hospital cardiac arrest.

Extracorporeal cardiopulmonary resuscitation: a national study on the association between favourable neurological status and biomarkers of hypoperfusion, inflammation, and organ injury.

AIMS: In refractory out-of-hospital cardiac arrest (OHCA) with prolonged whole-body ischaemia, global tissue injury proceeds even after establishment of circulation with extracorporeal cardiopulmonary resuscitation (ECPR). We aimed to investigate the role of biomarkers reflecting hypoperfusion, inflammation, and organ injury in prognostication of patients with refractory OHCA managed with ECPR. METHODS AND RESULTS: This nationwide retrospective study included 226 adults with refractory OHCA managed with ECPR in Denmark (2011-2020). Biomarkers the first days after ECPR-initiation were assessed. Odds ratio of favourable neurological status (Cerebral Performance Category 1-2) at hospital discharge was estimated by logistic regression analyses. Cut-off values were calculated using the Youden's index. Fifty-six patients (25%) survived to hospital discharge, 51 (91%) with a favourable neurological status. Factors independently associated with favourable neurological status were low flow time <81 min, admission leukocytes ≥12.8 × 109/L, admission lactate <13.2 mmol/L, alkaline phosphatase (ALP) < 56 (day1) or <55 U/L (day2), and day 1 creatine kinase MB (CK-MB) < 500 ng/mL. Selected biomarkers (leukocytes, C-reactive protein, and lactate) were significantly better predictors of favourable neurological status than classic OHCA-variables (sex, age, low-flow time, witnessed arrest, shockable rhythm) alone (P = 0.001) after hospital admission. CONCLUSION: Biomarkers of hypoperfusion (lactate), inflammation (leucocytes), and organ injury (ALP and CK-MB) were independently associated with neurological status at hospital discharge. Biomarkers of hypoperfusion and inflammation (at hospital admission) and organ injury (days 1 and 2 after ECPR) may aid in the clinical decision of when to prolong or terminate ECPR in cases of refractory OHCA.

Effect of calcium vs. placebo on long-term outcomes in patients with out-of-hospital cardiac arrest.

OBJECTIVE: The Calcium for Out-of-hospital Cardiac Arrest (COCA) trial was a randomized, placebo-controlled, double-blind trial of calcium for out-of-hospital cardiac arrest. The primary and secondary outcomes have been reported previously. This article describes the long-term outcomes of the trial. METHODS: Patients aged ≥18 years were included if they had a non-traumatic out-of-hospital cardiac arrest during which they received adrenaline. The trial drug consisted of calcium chloride (5 mmol) or saline placebo given after the first dose of adrenaline and again after the second dose of adrenaline for a maximum of two doses. This article presents pre-specified analyses of 6-month and 1-year outcomes for survival, survival with a favorable neurological outcome (modified Rankin Scale of 3 or less), and health-related quality of life. RESULTS: A total of 391 patients were analyzed. At 1 year, 9 patients (4.7%) were alive in the calcium group while 18 (9.1%) were alive in the placebo group (risk ratio 0.51; 95% confidence interval 0.24, 1.09). At 1 year, 7 patients (3.6%) were alive with a favorable neurological outcome in the calcium group while 17 (8.6%) were alive with a favorable neurological outcome in the placebo group (risk ratio 0.42; 95% confidence interval 0.18, 0.97). Outcomes for health-related quality of life likewise suggested harm of calcium but results were imprecise with wide confidence intervals. CONCLUSIONS: Effect estimates remained constant over time suggesting harm of calcium but with wide confidence intervals. The results do not support calcium administration during out-of-hospital cardiac arrest. TRIAL REGISTRATION: ClinicalTrials.gov-number, NCT04153435.

[Treated prolonged cardiac arrest without severe cognitive impairment].

The cognitive function and quality of life after extracorporeal cardiopulmonary resuscitation (ECPR) remain uncertain. In this case report, a 61-year-old male underwent ECPR for refractory out-of-hospital cardiac arrest after 102 minutes of resuscitation. The cause of cardiac arrest was acute myocardial infarction, and occlusion of the left anterior descending artery was treated with balloon angioplasty. Five years later, the patient had preserved psychical and mental health, cognitive function, and good quality of life despite prolonged cardiopulmonary resuscitation.