Expedited transfer to a cardiac arrest centre for non-ST-elevation out-of-hospital cardiac arrest (ARREST): a UK prospective, multicentre, parallel, randomised clinical trial.

BACKGROUND: The International Liaison Committee on Resuscitation has called for a randomised trial of delivery to a cardiac arrest centre. We aimed to assess whether expedited delivery to a cardiac arrest centre compared with current standard of care following resuscitated cardiac arrest reduces deaths. METHODS: ARREST is a prospective, parallel, multicentre, open-label, randomised superiority trial. Patients (aged ≥18 years) with return of spontaneous circulation following out-of-hospital cardiac arrest without ST elevation were randomly assigned (1:1) at the scene of their cardiac arrest by London Ambulance Service staff using a secure online randomisation system to expedited delivery to the cardiac catheter laboratory at one of seven cardiac arrest centres or standard of care with delivery to the geographically closest emergency department at one of 32 hospitals in London, UK. Masking of the ambulance staff who delivered the interventions and those reporting treatment outcomes in hospital was not possible. The primary outcome was all-cause mortality at 30 days, analysed in the intention-to-treat (ITT) population excluding those with unknown mortality status. Safety outcomes were analysed in the ITT population. The trial was prospectively registered with the International Standard Randomised Controlled Trials Registry, 96585404. FINDINGS: Between Jan 15, 2018, and Dec 1, 2022, 862 patients were enrolled, of whom 431 (50%) were randomly assigned to a cardiac arrest centre and 431 (50%) to standard care. 20 participants withdrew from the cardiac arrest centre group and 19 from the standard care group, due to lack of consent or unknown mortality status, leaving 411 participants in the cardiac arrest centre group and 412 in the standard care group for the primary analysis. Of 822 participants for whom data were available, 560 (68%) were male and 262 (32%) were female. The primary endpoint of 30-day mortality occurred in 258 (63%) of 411 participants in the cardiac arrest centre group and in 258 (63%) of 412 in the standard care group (unadjusted risk ratio for survival 1·00, 95% CI 0·90-1·11; p=0·96). Eight (2%) of 414 patients in the cardiac arrest centre group and three (1%) of 413 in the standard care group had serious adverse events, none of which were deemed related to the trial intervention. INTERPRETATION: In adult patients without ST elevation, transfer to a cardiac arrest centre following resuscitated cardiac arrest in the community did not reduce deaths. FUNDING: British Heart Foundation.

Impact of COVID-19 pandemic on the management of nonculprit lesions in patients presenting with ST-elevation myocardial infarction: Outcomes from the pan-London heart attack centers.

BACKGROUND: The impact of COVID-19 on the diagnosis and management of nonculprit lesions remains unclear. OBJECTIVES: This study sought to evaluate the management and outcomes of patients with nonculprit lesions during the COVID-19 pandemic. METHODS: We conducted a retrospective observational analysis of consecutive primary percutaneous coronary intervention (PPCI) pathway activations across the heart attack center network in London, UK. Data from the study period in 2020 were compared with prepandemic data in 2019. The primary outcome was the rate of nonculprit lesion percutaneous coronary intervention (PCI) and secondary outcomes included major adverse cardiovascular events. RESULTS: A total of 788 patients undergoing PPCI were identified, 209 (60%) in 2020 cohort and 263 (60%) in 2019 cohort had nonculprit lesions (p = .89). There was less functional assessment of the significance of nonculprit lesions in the 2020 cohort compared to 2019 cohort; in 8% 2020 cohort versus 15% 2019 cohort (p = .01). There was no difference in rates of PCI for nonculprit disease in the 2019 and 2020 cohorts (31% vs 30%, p = .11). Patients in 2020 cohort underwent nonculprit lesion PCI sooner than the 2019 cohort (p < .001). At 6 months there was higher rates of unplanned revascularization (4% vs. 2%, p = .05) and repeat myocardial infarction (4% vs. 1%, p = .02) in the 2019 cohort compared to 2020 cohort. CONCLUSION: Changes to clinical practice during the COVID-19 pandemic were associated with reduced rates of unplanned revascularization and myocardial infarction at 6-months follow-up, and despite the pandemic, there was no difference in mortality, suggesting that it is not only safe but maybe more efficacious.

Effect of Transcatheter Aortic Valve Implantation vs Surgical Aortic Valve Replacement on All-Cause Mortality in Patients With Aortic Stenosis: A Randomized Clinical Trial.

Importance: Transcatheter aortic valve implantation (TAVI) is a less invasive alternative to surgical aortic valve replacement and is the treatment of choice for patients at high operative risk. The role of TAVI in patients at lower risk is unclear. Objective: To determine whether TAVI is noninferior to surgery in patients at moderately increased operative risk. Design, Setting, and Participants: In this randomized clinical trial conducted at 34 UK centers, 913 patients aged 70 years or older with severe, symptomatic aortic stenosis and moderately increased operative risk due to age or comorbidity were enrolled between April 2014 and April 2018 and followed up through April 2019. Interventions: TAVI using any valve with a CE mark (indicating conformity of the valve with all legal and safety requirements for sale throughout the European Economic Area) and any access route (n = 458) or surgical aortic valve replacement (surgery; n = 455). Main Outcomes and Measures: The primary outcome was all-cause mortality at 1 year. The primary hypothesis was that TAVI was noninferior to surgery, with a noninferiority margin of 5% for the upper limit of the 1-sided 97.5% CI for the absolute between-group difference in mortality. There were 36 secondary outcomes (30 reported herein), including duration of hospital stay, major bleeding events, vascular complications, conduction disturbance requiring pacemaker implantation, and aortic regurgitation. Results: Among 913 patients randomized (median age, 81 years [IQR, 78 to 84 years]; 424 [46%] were female; median Society of Thoracic Surgeons mortality risk score, 2.6% [IQR, 2.0% to 3.4%]), 912 (99.9%) completed follow-up and were included in the noninferiority analysis. At 1 year, there were 21 deaths (4.6%) in the TAVI group and 30 deaths (6.6%) in the surgery group, with an adjusted absolute risk difference of -2.0% (1-sided 97.5% CI, -∞ to 1.2%; P < .001 for noninferiority). Of 30 prespecified secondary outcomes reported herein, 24 showed no significant difference at 1 year. TAVI was associated with significantly shorter postprocedural hospitalization (median of 3 days [IQR, 2 to 5 days] vs 8 days [IQR, 6 to 13 days] in the surgery group). At 1 year, there were significantly fewer major bleeding events after TAVI compared with surgery (7.2% vs 20.2%, respectively; adjusted hazard ratio [HR], 0.33 [95% CI, 0.24 to 0.45]) but significantly more vascular complications (10.3% vs 2.4%; adjusted HR, 4.42 [95% CI, 2.54 to 7.71]), conduction disturbances requiring pacemaker implantation (14.2% vs 7.3%; adjusted HR, 2.05 [95% CI, 1.43 to 2.94]), and mild (38.3% vs 11.7%) or moderate (2.3% vs 0.6%) aortic regurgitation (adjusted odds ratio for mild, moderate, or severe [no instance of severe reported] aortic regurgitation combined vs none, 4.89 [95% CI, 3.08 to 7.75]). Conclusions and Relevance: Among patients aged 70 years or older with severe, symptomatic aortic stenosis and moderately increased operative risk, TAVI was noninferior to surgery with respect to all-cause mortality at 1 year. Trial Registration: isrctn.com Identifier: ISRCTN57819173.

Initial experience of a self-expanding transcatheter aortic valve with an outer pericardial wrap: The United Kingdom and Ireland Implanters' registry.

OBJECTIVES: The United Kingdom and Ireland Implanters' registry is a multicenter registry which reports on real-world experience with new transcatheter heart valves. BACKGROUND: The Evolut PRO (Medtronic, Minneapolis, MN) transcatheter aortic valve is a self-expanding transcatheter aortic valve with an outer pericardial wrap, designed to minimize paravalvular regurgitation. METHODS: Between July 2017 and December 2018, clinical, procedural, and 30-day outcome data were prospectively collected from all patients receiving the Evolut PRO valve across nine participating centers in the United Kingdom and Ireland. The primary efficacy outcome was the Valve Academic Research Consortium-2 (VARC-2)-defined endpoint of device success. The primary safety outcome was the VARC-2-defined composite endpoint of early safety at 30 days. RESULTS: A total of 317 patients underwent implantation. Mean age was 81.8 ± 6.4 years and Society of Thoracic Surgeons Predicted Risk of Mortality Score 5.5 ± 1.8%. Iliofemoral access was used in 99.1% of patients. Device success was 91.2%. Mean gradient was 7.6 ± 4.7 mmHg and effective orifice area 1.9 ± 0.7 cm2 . The incidence of moderate paravalvular regurgitation was 1.7% and there was no severe paravalvular regurgitation. A new permanent pacemaker was implanted in 17.8% of patients without a pacemaker at baseline. Early safety was demonstrated in 92.7%. At 30 days, all-cause mortality was 0.6%, stroke 3.8%, and major vascular complication 2.8%. CONCLUSIONS: Real-world experience of the Evolut PRO transcatheter aortic valve demonstrated favorable procedural success, safety, valve function, and incidence of new permanent pacemaker implantation.

Comparison of warfarin versus DOACs in patients with concomitant indication for oral anticoagulation undergoing TAVI; results from the ATLAS registry.

The optimal antithrombotic therapy for patients undergoing TAVI with concomitant indication for oral anticoagulation remains unclear. In this high-risk population group, there is a paucity of data with regards to the use of DOACs. In the present study we compared long-term clinical outcomes of TAVI patients requiring anticoagulation, treated with warfarin versus DOACs. Consecutive patients, who underwent TAVI with indication for oral anticoagulation from the multicenter ATLAS registry were studied and divided in two groups depending on the chosen anticoagulation regimen, warfarin vs. DOACs. 30-day survival, as well as estimated 1 and 2-year all-cause mortality were compared between groups. The secondary endpoint included in-hospital major or life-threatening bleeding. The study group included 217 patients (102 treated with warfarin; 115 treated with DOACs). Kaplan-Meier estimated survival was found to be statistically similar in the warfarin and DOAC groups (90.6% vs. 93.7% for 1-year and 84.5% vs. 88.5%, for 2-year survival, respectively, Plog-rank = 0.984). Adjusted hazard ratio for all cause mortality was similar between the two groups (HRwarfarin vs. DOAC = 1.15; 95% CI 0.33 to 4.04, p = 0.829). Propensity matching revealed similar results. At 30-days, all-cause mortality was found to be comparable between the two groups. With regards to BARC defined bleeding complications, major and life-threatening complications did not differ between the two anticoagulation groups (6% vs. 8% for warfarin and DOACs respectively, p = 0.857). DOACs seem to demonstrate a similar safety and efficacy profile compared to warfarin in TAVI patients with a concomitant indication for oral anticoagulation.

The association between the public reporting of individual operator outcomes with patient profiles, procedural management, and mortality after percutaneous coronary intervention: an observational study from the Pan-London PCI (BCIS) Registry using an interrupted time series analysis.

AIMS: The public reporting of healthcare outcomes has a number of potential benefits; however, unintended consequences may limit its effectiveness as a quality improvement process. We aimed to assess whether the introduction of individual operator specific outcome reporting after percutaneous coronary intervention (PCI) in the UK was associated with a change in patient risk factor profiles, procedural management, or 30-day mortality outcomes in a large cohort of consecutive patients. METHODS AND RESULTS: This was an observational cohort study of 123 780 consecutive PCI procedures from the Pan-London (UK) PCI registry, from January 2005 to December 2015. Outcomes were compared pre- (2005-11) and post- (2011-15) public reporting including the use of an interrupted time series analysis. Patients treated after public reporting was introduced were older and had more complex medical problems. Despite this, reported in-hospital major adverse cardiovascular and cerebrovascular events rates were significantly lower after the introduction of public reporting (2.3 vs. 2.7%, P < 0.0001). Interrupted time series analysis demonstrated evidence of a reduction in 30-day mortality rates after the introduction of public reporting, which was over and above the existing trend in mortality before the introduction of public outcome reporting (35% decrease relative risk 0.64, 95% confidence interval 0.55-0.77; P < 0.0001). CONCLUSION: The introduction of public reporting has been associated with an improvement in outcomes after PCI in this data set, without evidence of risk-averse behaviour. However, the lower reported complication rates might suggest a change in operator behaviour and decision-making confirming the need for continued surveillance of the impact of public reporting on outcomes and operator behaviour.

Real-world comparison of the new 34 mm self-expandable transcatheter aortic prosthesis Evolut R to its 31 mm core valve predecessor.

OBJECTIVES: The aim of the present study was to compare the incidence of periprocedural complications and short-term outcomes between the second-generation recapturable 34 mm Evolut-R and its first-generation 31 mm predecessor. BACKGROUND: Although already in extensive clinical use in real world patients, the periprocedural complications and clinical outcomes of the new 34 mm device have not been investigated yet. METHODS: Consecutive patients who had undergone transcatheter aortic valve implantation in two centers with either a 31 mm CoreValve or a 34 mm Evolut-R device were retrospectively studied. Periprocedural complications of malpositioning, valve-in-valve implantation, conversion to full sternotomy or percutaneous coronary intervention and vascular complications were compared between the two groups. Short-term outcomes at discharge were compared using Valve Academic Research Consortium (VARC-2) criteria. RESULTS: The study group included 106 patients (35 Evolut-R 34 mm; 71 CoreValve 31 mm). Significantly lower rates of valve-in-valve implantation were demonstrated for the 34 mm group compared to the first-generation device (0% vs. 11.9%, respectively, P = 0.036). All other periprocedural complications were similar between groups. At discharge, the rates of new pacemaker implantation (5.7% vs. 26.8%, P = 0.037) and bleeding complications (2.9% vs. 19.6%, P = 0.025) were statistically significantly lower among the 34 mm group. With regards to VARC-2 defined combined endpoints, rates of early safety were significantly improved among the 34 mm group compared to 31 mm group (0% vs. 27.9%, respectively, P = 0.004). CONCLUSIONS: The recently introduced 34 mm Evolut-R seems to demonstrate an improved safety profile, as evidenced by the reduced bleeding rates, lower rates of valve-in-valve implantation and lower PPM rates compared to its 31 mm predecessor.

Initial experience of a large, self-expanding, and fully recapturable transcatheter aortic valve: The UK & Ireland Implanters' registry.

OBJECTIVES: The UK & Ireland Implanters' registry is a multicenter registry which reports on real-world experience with novel transcatheter heart valves. BACKGROUND: The 34 mm Evolut R transcatheter aortic valve is a self-expanding and fully recapturable transcatheter aortic valve, designed to treat patients with a large aortic annulus. METHODS: Between January 2017 and April 2018, clinical, procedural and 30-day outcome data were prospectively collected from all patients receiving the 34 mm Evolut R valve across 17 participating centers in the United Kingdom and Ireland. The primary efficacy outcome was the Valve Academic Research Consortium-2(VARC-2)-defined endpoint of device success. The primary safety outcome was the VARC-2-defined composite endpoint of early safety at 30 days. RESULTS: A total of 217 patients underwent attempted implant. Mean age was 79.5 ± 8.8 years and Society of Thoracic Surgeons Predicted Risk of Mortality Score 5.2% ± 3.4%. Iliofemoral access was used in 91.2% of patients. Device success was 79.7%. Mean gradient was 7.0 ± 4.6 mmHg and effective orifice area 2.0 ± 0.6 cm2 . Paravalvular regurgitation was more than mild in 7.2%. A new permanent pacemaker was implanted in 15.7%. Early safety was demonstrated in 91.2%. At 30 days, all-cause mortality was 3.2%, stroke 3.7%, and major vascular complication 2.3%. CONCLUSIONS: Real-world experience of the 34 mm Evolut R transcatheter aortic valve demonstrated acceptable procedural success, safety, valve function, and incidence of new permanent pacemaker implantation.

Rationale and design of: A Randomized tRial of Expedited transfer to a cardiac arrest center for non-ST elevation out-of-hospital cardiac arrest: The ARREST randomized controlled trial.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is a global public health issue. There is wide variation in both regional and inter-hospital survival rates from OHCA and overall survival remains poor at 7%. Regionalization of care into cardiac arrest centers (CAC) improves outcomes following cardiac arrest from ST elevation myocardial infarction (STEMI) through concentration of services and greater provider experience. The International Liaison Committee on Resuscitation (ILCOR) recommends delivery of all post-arrest patients to a CAC, but that randomized controlled trials are necessary in patients without ST elevation (STE). METHODS/DESIGN: Following completion of a pilot randomized trial to assess safety and feasibility of conducting a large-scale randomized controlled trial in patients following OHCA of presumed cardiac cause without STE, we present the rationale and design of A Randomized tRial of Expedited transfer to a cardiac arrest center for non-ST elevation OHCA (ARREST). In total 860 patients will be enrolled and randomized (1:1) to expedited transfer to CAC (24/7 access to interventional cardiology facilities, cooling and goal-directed therapies) or to the current standard of care, which comprises delivery to the nearest emergency department. Primary outcome is 30-day all-cause mortality and secondary outcomes are 30-day and 3-month neurological status and 3, 6 and 12-month mortality. Patients will be followed up for one year after enrolment. CONCLUSION: Post-arrest care is time-critical, requires a multi-disciplinary approach and may be more optimally delivered in centers with greater provider experience. This trial would help to demonstrate if regionalization of post-arrest care to CACs reduces mortality in patients without STE, which could dramatically reshape emergency care provision.

The prognostic significance of incomplete revascularization and untreated coronary anatomy following percutaneous coronary intervention: An analysis of 6,755 patients with multivessel disease.

BACKGROUND: More than half of the patients undergoing percutaneous coronary intervention (PCI) have multivessel disease. Whether complete revascularization impacts long-term mortality or whether selected patients or those with specific coronary anatomy benefit from complete revascularization is unclear. METHODS: A total of 14,452 patients underwent PCI between 2004 and 2015 at Harefield Hospital, UK. Of these, 7,076 patients had multivessel disease. We excluded 321 patients with left main-stem stenosis ≥50%, with 6,755 patients included in the analysis (936 patients had complete revascularization). RESULTS: The unadjusted 3-year mortality rates were lower with complete revascularization (10.8% vs 13.1%, P = 0.047). However, multivariable-adjusted analyses indicated that complete revascularization was not independently associated with mortality (HR = 1.01, 95% CI: 0.78-1.31, P = 0.939). These findings were unchanged when addressing measured confounding using propensity-matched analyses (HR = 1.16, 95% CI: 0.81-1.65, P = 0.417) and inverse probability treatment weighted analyses (HR = 1.01, 95% CI: 0.77-1.33, P = 0.950); and unmeasured confounding using instrumental variable analyses (Δ = 0.9%, 95% CI: -2.5%, 4.3%, P = 0.958). There was no association with mortality and untreated LAD disease (HR = 0.92, 95% CI: 0.72-1.17, P = 0.482) and LCx disease (HR = 0.90, 95% CI: 0.74-1.10, P = 0.999). However, untreated proximal LAD disease (HR = 1.23, 95% CI: 1.06-1.51, P = 0.045) and RCA disease (HR = 1.36, 95% CI: 1.08-1.65, P = 0.007) was associated with increased mortality, particularly in patients with ST-elevation acute coronary syndrome (STEACS). CONCLUSIONS: In this study of unselected patients undergoing PCI, complete revascularization did not confer a mortality benefit. However, the presence of untreated proximal LAD and RCA disease was prognostic in patients with STEACS. Thus, complete revascularization may be considered in select patient groups with anatomical subsets of coronary disease.

A feasibility and safety study of intracoronary hemodilution during primary coronary angioplasty in order to reduce reperfusion injury in myocardial infarction.

OBJECTIVES: We designed a pilot study to evaluate safety and feasibility of an inexpensive and simple approach to intracoronary hemodilution during primary angioplasty (PPCI) to reduce reperfusion injury. INTRODUCTION: Early revascularization in acute myocardial infarction decreases infarct size and improves outcomes. However, abrupt restoration of coronary flow results in myocardial reperfusion injury and increased final infarct size. Dilution of coronary blood during revascularization may help reduce this damage. If proved effective, such an approach would need to be simple and suitable for widespread adoption. METHODS: Ten patients presenting with STEMI underwent intracoronary dilution with room temperature Hartmann's solution delivered through the guiding catheter during primary angioplasty (PPCI). Infusion of perfusate began prior to crossing the occluded artery with the guidewire, continuing until 10 min after completion of the balloon and stenting procedure. Infusion was briefly interrupted for contrast injection and pressure monitoring. The outcome measures were safety, including intracoronary temperature reduction and volume of intracoronary perfusate infused, and technical feasibility. RESULTS: There were no significant symptomatic, hemodynamic, ECG ST/T segment or rhythm changes observed during perfusate administration. The median (interquartile range) volume of perfusate administered was 550 mL (350-725 mL) and the median intracoronary temperature reduction observed was 3.4°Celsius. Myocardial salvage was 0.54 (0.43-0.65). CONCLUSIONS: Transcatheter intracoronary hemodilution with room temperature perfusate during PPCI is feasible and appears safe. Such a strategy is simple and inexpensive, with potential to be widely applied. Further mechanistic and subsequent outcome powered studies are required to evaluate whether this strategy can reduce reperfusion injury in STEMI.

Infarct size following complete revascularization in patients presenting with STEMI: a comparison of immediate and staged in-hospital non-infarct related artery PCI subgroups in the CvLPRIT study.

BACKGROUND: The CvLPRIT study showed a trend for improved clinical outcomes in the complete revascularisation (CR) group in those treated with an immediate, as opposed to staged in-hospital approach in patients with multivessel coronary disease undergoing primary percutaneous intervention (PPCI). We aimed to assess infarct size and left ventricular function in patients undergoing immediate compared with staged CR for multivessel disease at PPCI. METHODS: The Cardiovascular Magnetic Resonance (CMR) substudy of CvLPRIT was a multicentre, prospective, randomized, open label, blinded endpoint trial in PPCI patients with multivessel disease. These data refer to a post-hoc analysis in 93 patients randomized to the CR arm (63 immediate, 30 staged) who completed a pre-discharge CMR scan (median 2 and 4 days respectively) after PPCI. The decision to stage non-IRA revascularization was at the discretion of the treating interventional cardiologist. RESULTS: Patients treated with a staged approach had more visible thrombus (26/30 vs. 31/62, p = 0.001), higher SYNTAX score in the IRA (9.5, 8-16 vs. 8.0, 5.5-11, p = 0.04) and a greater incidence of no-reflow (23.3 % vs. 1.6 % p < 0.001) than those treated with immediate CR. After adjustment for confounders, staged patients had larger infarct size (19.7 % [11.7-37.6] vs. 11.6 % [6.8-18.2] of LV Mass, p = 0.012) and lower ejection fraction (42.2 ± 10 % vs. 47.4 ± 9 %, p = 0.019) compared with immediate CR. CONCLUSIONS: Of patients randomized to CR in the CMR substudy of CvLPRIT, those in whom the operator chose to stage revascularization had larger infarct size and lower ejection fraction, which persisted after adjusting for important covariates than those who underwent immediate CR. Prospective randomized trials are needed to assess whether immediate CR results in better clinical outcomes than staged CR. TRIAL REGISTRATION: ISRCTN70913605 , Registered 24th February 2011.

Real-time monitoring of endogenous lipid peroxidation by exhaled ethylene in patients undergoing cardiac surgery.

Pulmonary and systemic organ injury produced by oxidative stress including lipid peroxidation is a fundamental tenet of ischemia-reperfusion injury, inflammatory response to cardiac surgery, and cardiopulmonary bypass (CPB) but is not routinely measured in a surgically relevant time frame. To initiate a paradigm shift toward noninvasive and real-time monitoring of endogenous lipid peroxidation, we have explored pulmonary excretion and dynamism of exhaled breath ethylene during cardiac surgery to test the hypothesis that surgical technique and ischemia-reperfusion triggers lipid peroxidation. We have employed laser photoacoustic spectroscopy to measure real-time trace concentrations of ethylene from the patient breath and from the CPB machine. Patients undergoing aortic or mitral valve surgery-requiring CPB (n = 15) or off-pump coronary artery bypass surgery (OPCAB) (n = 7) were studied. Skin and tissue incision by diathermy caused striking (> 30-fold) increases in exhaled ethylene resulting in elevated levels until CPB. Gaseous ethylene in the CPB circuit was raised upon the establishment of CPB (> 10-fold) and decreased over time. Reperfusion of myocardium and lungs did not appear to enhance ethylene levels significantly. During OPCAB surgery, we have observed increased ethylene in 16 of 30 documented reperfusion events associated with coronary and aortic anastomoses. Therefore, novel real-time monitoring of endogenous lipid peroxidation in the intraoperative setting provides unparalleled detail of endogenous and surgery-triggered production of ethylene. Diathermy and unprotected regional myocardial ischemia and reperfusion are the most significant contributors to increased ethylene.

High incidence of acute coronary occlusion in patients without protocol positive ST segment elevation referred to an open access primary angioplasty programme.

BACKGROUND: Primary percutaneous coronary intervention (PPCI) programmes vary in admission criteria from open referral to acceptance of electrocardiogram (ECG) protocol positive patients only. Rigid criteria may result in some patients with acutely occluded coronary arteries not receiving timely reperfusion therapy. OBJECTIVE: To compare the prevalence of acute coronary occlusion and, in these cases, single time point biomarker estimates of myocardial infarct size between patients presenting with protocol positive ECG changes and those presenting with less diagnostic changes in the primary angioplasty cohort of an open access PPCI programme. METHODS: We retrospectively performed a single centre cross sectional analysis of consecutive patients receiving PPCI between January and August 2008. Cases were categorised according to presenting ECG-group A: protocol positive (ST segment elevation/left bundle branch block/posterior ST elevation myocardial infarction), group B: ST segment depression or T-wave inversion, or group C: minor ECG changes. Clinical characteristics, coronary flow grades and 12 h postprocedure troponin-I levels were reviewed. RESULTS: During the study period there were 513 activations of the PPCI service, of which 390 underwent immediate angiography and 308 underwent PPCI. Of those undergoing PPCI, 221 (72%) were in group A, 41 (13%) in group B and 46 (15%) in group C. Prevalence of coronary occlusion was 75% in group A compared with 73% in group B and 63% in group C. Median 12 h postintervention troponin-I (25th-75th percentile) for those with coronary occlusion was significantly higher in group A patients; 28.9 µg/l (13.2-58.5) versus 18.1 µg/l (6.7-32.4) for group B (p=0.03); and 15.5 µg/l (3.8-22.0) for group C (p<0.001), suggesting greater infarct size in group A. CONCLUSIONS: A number of patients referred to an open access PPCI programme have protocol negative ECGs but myocardial infarction and acute coronary artery occlusion amenable to angioplasty.

Midterm Outcomes in Patients With Aortic Stenosis Treated With Contemporary Balloon-Expandable and Self-Expanding Valves: Does Valve Size Have an Impact on Outcome?

Background No data currently exist comparing the contemporary iterations of balloon-expandable (BE) Edwards SAPIEN 3/Ultra and the self-expanding (SE) Medtronic Evolut PRO/R34 valves. The aim of the study was the comparison of these transcatheter heart valves with emphasis on patients with small aortic annulus. Methods and Results In this retrospective registry, periprocedural outcomes and midterm all-cause mortality were analyzed. A total of 1673 patients (917 SE versus 756 BE) were followed up for a median of 15 months. A total of 194 patients died (11.6%) during follow-up. SE and BE groups showed similar survival at 1 (92.6% versus 90.6%) and 3 (80.3% versus 85.2%) years (Plog-rank=0.136). Compared with the BE group, patients treated with the SE device had lower peak (16.3±8 mm Hg SE versus 21.9±8 mm Hg BE) and mean (8.8±5 mm Hg SE versus 11.5±5 mm Hg BE) gradients at discharge. Conversely, the BE group demonstrated lower rates of at least moderate paravalvular regurgitation postoperatively (5.6% versus 0.7% for SE and BE valves, respectively; P<0.001). In patients treated with small transcatheter heart valves (≤26 mm for SE and ≤23 mm for BE; N=284 for SE and N=260 for BE), survival was higher among patients treated with SE valves at both 1 (96.7% SE versus 92.1% BE) and 3 (91.8% SE versus 82.2% BE) years (Plog-rank=0.042). In propensity-matched patients treated with small transcatheter heart valve, there remained a trend for higher survival among the SE group at both 1 (97% SE versus 92.3% BE) and 3 years (91.8% SE versus 78.7% BE), Plog-rank=0.096). Conclusions Real-world comparison of the latest-generation SE and BE devices demonstrated similar survival up to 3 years' follow-up. In patients with small transcatheter heart valves, there may be a trend for improved survival among those treated with SE valves.

Time to TAVI: streamlining the pathway to treatment.

INTRODUCTION: Severe aortic stenosis is a major cause of morbidity and mortality. The existing treatment pathway for transcatheter aortic valve implantation (TAVI) traditionally relies on tertiary Heart Valve Centre workup. However, this has been associated with delays to treatment, in breach of British Cardiovascular Intervention Society targets. A novel pathway with emphasis on comprehensive patient workup at a local centre, alongside close collaboration with a Heart Valve Centre, may help reduce the time to TAVI. METHODS: The centre performing local workup implemented a novel TAVI referral pathway. Data were collected retrospectively for all outpatients referred for consideration of TAVI to a Heart Valve Centre from November 2020 to November 2021. The main outcome of time to TAVI was calculated as the time from Heart Valve Centre referral to TAVI, or alternative intervention, expressed in days. For the centre performing local workup, referral was defined as the date of multidisciplinary team discussion. For this centre, a total pathway time from echocardiographic diagnosis to TAVI was also evaluated. A secondary outcome of the proportion of referrals proceeding to TAVI at the Heart Valve Centre was analysed. RESULTS: Mean±SD time from referral to TAVI was significantly lower at the centre performing local workup, when compared with centres with traditional referral pathways (32.4±64 to 126±257 days, p<0.00001). The total pathway time from echocardiographic diagnosis to TAVI for the centre performing local workup was 89.9±67.6 days, which was also significantly shorter than referral to TAVI time from all other centres (p<0.003). Centres without local workup had a significantly lower percentage of patients accepted for TAVI (49.5% vs 97.8%, p<0.00001). DISCUSSION: A novel TAVI pathway with emphasis on local workup within a non-surgical centre significantly reduced both the time to TAVI and rejection rates from a Heart Valve Centre. If adopted across the other centres, this approach may help improve access to TAVI.

Brachial artery low-flow-mediated constriction is increased early after coronary intervention and reduces during recovery after acute coronary syndrome: characterization of a recently described index of vascular function.

AIMS: The endothelium plays a role in regulating vascular tone. Acute and dynamic changes in low-flow-mediated constriction (L-FMC) and how it changes with regard to traditional flow-mediated dilatation (FMD) have not been described. We aimed to investigate the changes in brachial artery L-FMC following percutaneous coronary intervention (PCI) and during recovery from non-ST-segment elevation myocardial infarction (NSTEMI). METHODS AND RESULTS: FMD was performed in accordance with a previously described technique in patients before and after PCI and in the recovery phase of NSTEMI, but in addition, L-FMC data were acquired from the last 30 s of cuff inflation. About 135 scans were performed in 96 participants (10 healthy volunteers and 86 patients). Measurement of brachial L-FMC was reproducible over hours. L-FMC was greater among patients with unstable vs. stable coronary atherosclerosis (-1.33 ±1.09% vs. -0.03 ± 1.26%, P < 0.01). Following PCI, FMD reduced (4.43 ± 2.93% vs. 1.66 ± 2.16%, P < 0.01) and L-FMC increased (-0.33 ± 0.76% vs. -1.63 ± 1.15%, P = 0.02). Furthermore, during convalescence from NSTEMI, L-FMC reduced (-1.37 ± 1.19% vs. 0.01 ± 0.82%, P = 0.02) in parallel with improvements in FMD (2.54 ± 2.19% vs. 5.15 ± 3.07%, P < 0.01). CONCLUSION: Brachial L-FMC can be measured reliably. Differences were observed between patients with stable and unstable coronary disease. L-FMC was acutely increased following PCI associated with reduced FMD and, in the recovery from NSTEMI, L-FMC reduced associated with increased FMD. These novel findings characterize acute and subacute variations in brachial L-FMC. The pathophysiological and clinical implications of these observations require further study.

Very early invasive angiography versus standard of care in higher-risk non-ST elevation myocardial infarction: study protocol for the prospective multicentre randomised controlled RAPID N-STEMI trial.

BACKGROUND: There are a paucity of randomised data on the optimal timing of invasive coronary angiography (ICA) in higher-risk patients with non-ST elevation myocardial infarction (N-STEMI). International guideline recommendations for early ICA are primarily based on retrospective subgroup analyses of neutral trials. AIMS: The RAPID N-STEMI trial aims to determine whether very early percutaneous revascularisation improves clinical outcomes as compared with a standard of care strategy in higher-risk N-STEMI patients. METHODS AND ANALYSIS: RAPID N-STEMI is a prospective, multicentre, open-label, randomised-controlled, pragmatic strategy trial. Higher-risk N-STEMI patients, as defined by Global Registry of Acute Coronary Events 2.0 score ≥118, or >90 with at least one additional high-risk feature, were randomised to either: very early ICA±revascularisation or standard of care timing of ICA±revascularisation. The primary outcome is the proportion of participants with at least one of the following events (all-cause mortality, non-fatal myocardial infarction and hospital admission for heart failure) at 12 months. Key secondary outcomes include major bleeding and stroke. A hypothesis generating cardiac magnetic resonance (CMR) substudy will provide mechanistic data on infarct size, myocardial salvage and residual ischaemia post percutaneous coronary intervention. On 7 April 2021, the sponsor discontinued enrolment due to the impact of the COVID-19 pandemic and lower than expected event rates. 425 patients were enrolled, and 61 patients underwent CMR. ETHICS AND DISSEMINATION: The trial has been reviewed and approved by the East of England Cambridge East Research Ethics Committee (18/EE/0222). The study results will be submitted for publication within 6 months of completion. TRIAL REGISTRATION NUMBER: NCT03707314; Pre-results.