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.

Computed tomography derived anatomical predictors of vascular access complications following transfemoral transcatheter aortic valve implantation: A systematic review.

BACKGROUND: Vascular complications after percutaneous transfemoral transcatheter aortic valve implantation (TAVI) are associated with adverse clinical outcomes and remain a significant challenge. AIMS: The purpose of this review is to synthesize the existing evidence regarding the iliofemoral artery features predictive of vascular complications after TAVI on pre-procedural contrast-enhanced multidetector computed tomography (MDCT). METHODS: A systematic search was performed in Embase and Medline (Pubmed) databases. Studies of patients undergoing transfemoral TAVI with MDCT were included. Studies with only valve-in-valve TAVI, planned surgical intervention and those using fluoroscopic assessment were excluded. Data on study cohort, procedural characteristics and significant predictors of vascular complications were extracted. RESULTS: We identified 23 original studies involving 8697 patients who underwent TAVI between 2006 and 2020. Of all patients, 8514 (97.9%) underwent percutaneous transfemoral-TAVI, of which 8068 (94.8%) had contrast-enhanced MDCT. The incidence of major vascular complications was 6.7 ± 4.1% and minor vascular complications 26.1 ± 7.8%. Significant independent predictors of major and minor complications related to vessel dimensions were common femoral artery depth (>54 mm), sheath-to-iliofemoral artery diameter ratio (>0.91-1.19), sheath-to-femoral artery diameter ratio (>1.03-1.45) and sheath-to-femoral artery area ratio (>1.35). Substantial iliofemoral vessel tortuosity predicted 2-5-fold higher vascular risk. Significant iliofemoral calcification predicted 2-5-fold higher risk. The iliac morphology score was the only hybrid scoring system with predictive value. CONCLUSIONS: Independent iliofemoral predictors of access-site complications in TAVI were related to vessel size, depth, calcification and tortuosity. These should be considered when planning transfemoral TAVI and in the design of future risk prediction models.

Clinical outcomes following single access transfemoral transcatheter aortic valve implantation.

OBJECTIVES: We describe the first experience using calcification of anatomical landmarks to obviate the need for transcatheter aortic valve implantation (TAVI) alignment aortography and secondary TAVI access. BACKGROUND: TAVI alignment conventionally involves secondary femoral access for contrast aortography using a second catheter. Secondary femoral access accounts for up to 25% of all vascular complications. Heavily calcified aortic leaflets are often visible fluoroscopically and can act as markers for TAVI alignment. METHODS: We considered 100 consecutive patients for transfemoral TAVI. The first group was considered for a conventional dual access technique and the subsequent group was considered for a single access technique. Relevant baseline, and procedural and outcome measures were recorded. RESULTS: Baseline characteristics were comparable between groups. Balloon-expandable transcatheter heart valves (THV) were used in all cases. THV implantation was successful in 100% of cases with no procedural or in-hospital mortality. Procedural time and contrast use were lower in the single access group. There were no Valve Academic Research Consortium (VARC)-2 major vascular complications with the single access technique. CONCLUSIONS: This is the first study describing the use of calcification of anatomical landmarks to obviate the need for secondary TAVI access. Notable observations included successful device implantation in all cases, no VARC-2 major vascular complications, comparable rates of paravalvular leak and permanent pacemaker requirement, shorter procedural times, and lower contrast use. Single access TAVI is a viable alternative technique to minimize vascular access, contrast use, and procedural duration in experienced centers and with selected patients, allowing successful device implantation and low complication rates while further streamlining TAVI workflow.

Biological variation of cardiac myosin-binding protein C in healthy individuals.

OBJECTIVES: Cardiac myosin-binding protein C (cMyC) is a novel biomarker of myocardial injury, with a promising role in the triage and risk stratification of patients presenting with acute cardiac disease. In this study, we assess the weekly biological variation of cMyC, to examine its potential in monitoring chronic myocardial injury, and to suggest analytical quality specification for routine use of the test in clinical practice. METHODS: Thirty healthy volunteers were included. Non-fasting samples were obtained once a week for ten consecutive weeks. Samples were tested in duplicate on the Erenna® platform by EMD Millipore Corporation. Outlying measurements and subjects were identified and excluded systematically, and homogeneity of analytical and within-subject variances was achieved before calculating the biological variability (CVI and CVG), reference change values (RCV) and index of individuality (II). RESULTS: Mean age was 38 (range, 21-64) years, and 16 participants were women (53%). The biological variation, RCV and II with 95% confidence interval (CI) were: CVA (%) 19.5 (17.8-21.6), CVI (%) 17.8 (14.8-21.0), CVG (%) 66.9 (50.4-109.9), RCV (%) 106.7 (96.6-120.1)/-51.6 (-54.6 to -49.1) and II 0.42 (0.29-0.56). There was a trend for women to have lower CVG. The calculated RCVs were comparable between genders. CONCLUSIONS: cMyC exhibits acceptable RCV and low II suggesting that it could be suitable for disease monitoring, risk stratification and prognostication if measured serially. Analytical quality specifications based on biological variation are similar to those for cardiac troponin and should be achievable at clinically relevant concentrations.

In-hospital stroke after transcatheter aortic valve implantation: A UK observational cohort analysis.

OBJECTIVES: We sought to identify baseline demographics and procedural factors that might independently predict in-hospital stroke following transcatheter aortic valve implantation (TAVI). BACKGROUND: Stroke is a recognized, albeit infrequent, complication of TAVI. Established predictors of procedure-related in-hospital stroke; however, remain poorly defined. METHODS: We conducted an observational cohort analysis of the multicenter UK TAVI registry. The primary outcome measure was the incidence of in-hospital stroke. RESULTS: A total of 8,652 TAVI procedures were performed from 2007 to 2015. There were 205 in-hospital strokes reported by participating centers equivalent to an overall stroke incidence of 2.4%. Univariate analysis showed that the implantation of balloon-expandable valves caused significantly fewer strokes (balloon-expandable 96/4,613 [2.08%] vs. self-expandable 95/3,272 [2.90%]; p = .020). After multivariable analysis, prior cerebrovascular disease (CVD) (odds ratio [OR] 1.51, 95% confidence interval [CI 1.05-2.17]; p = .03), advanced age at time of operation (OR 1.02 [0.10-1.04]; p = .05), bailout coronary stenting (OR 5.94 [2.03-17.39]; p = .008), and earlier year of procedure (OR 0.93 [0.87-1.00]; p = .04) were associated with an increased in-hospital stroke risk. There was a reduced stroke risk in those who had prior cardiac surgery (OR 0.62 [0.41-0.93]; p = .01) and a first-generation balloon-expandable valve implanted (OR 0.72 [0.53-0.97]; p = .03). In-hospital stroke significantly increased 30-day (OR 5.22 [3.49-7.81]; p < .001) and 1-year mortality (OR 3.21 [2.15-4.78]; p < .001). CONCLUSIONS: In-hospital stroke after TAVI is associated with substantially increased early and late mortality. Factors independently associated with in-hospital stroke were previous CVD, advanced age, no prior cardiac surgery, and deployment of a predominantly first-generation self-expandable transcatheter heart valve.

Survival relative to pacemaker status after transcatheter aortic valve implantation.

OBJECTIVES: To determine whether a permanent pacemaker (PPM) in situ can enhance survival after transcatheter aortic valve implantation (TAVI), in a predominantly inoperable or high risk cohort. BACKGROUND: New conduction disturbances are the most frequent complication of TAVI, often necessitating PPM implantation before hospital discharge. METHODS: We performed an observational cohort analysis of the UK TAVI registry (2007-2015). Primary and secondary endpoints were 30-day post-discharge all-cause mortality and long-term survival, respectively. RESULTS: Of 8,651 procedures, 6,815 complete datasets were analyzed. A PPM at hospital discharge, irrespective of when implantation occurred (PPM 1.68% [22/1309] vs. no PPM 1.47% [81/5506], odds ratio [OR] 1.14, 95% confidence interval [CI] 0.71-1.84; p = .58), or a PPM implanted peri- or post-TAVI only (PPM 1.44% [11/763] vs. no PPM 1.47% [81/5506], OR 0.98 [0.51-1.85]; p = .95) did not significantly reduce the primary endpoint. Patients with a PPM at discharge were older, male, had right bundle branch block at baseline, were more likely to have received a first-generation self-expandable prosthesis and had experienced more peri- and post-procedural complications including bailout valve-in-valve rescue, bleeding and acute kidney injury. A Cox proportional hazards model demonstrated significantly reduced long-term survival in all those with a PPM, irrespective of implantation timing (hazard ratio [HR] 1.14 [1.02-1.26]; p = .019) and those receiving a PPM only at the time of TAVI (HR 1.15 [1.02-1.31]; p = .032). The reasons underlying this observation warrant further investigation. CONCLUSIONS: A PPM did not confer a survival advantage in the first 30 days after hospital discharge following TAVI.

Safety and efficacy of a self-expanding versus a balloon-expandable bioprosthesis for transcatheter aortic valve replacement in patients with symptomatic severe aortic stenosis: a randomised non-inferiority trial.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is the preferred treatment option for older patients with symptomatic severe aortic stenosis. Differences in the properties of available TAVR systems can affect clinical outcomes. Among patients undergoing TAVR, we compared the self-expanding ACURATE neo TAVR system with the balloon-expandable SAPIEN 3 TAVR system with regard to early safety and efficacy. METHODS: In this randomised non-inferiority trial, patients (aged ≥75 years) undergoing transfemoral TAVR for treatment of symptomatic severe aortic stenosis, and who were deemed to be at increased surgical risk, were recruited at 20 tertiary heart valve centres in Germany, the Netherlands, Switzerland, and the UK. Participants were randomly assigned (1:1) to receive treatment with the ACURATE neo or the SAPIEN 3 with a computer-based randomly permuted block scheme, stratified by study centre and Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) category. The primary composite safety and efficacy endpoint comprised all-cause death, any stroke, life-threatening or disabling bleeding, major vascular complications, coronary artery obstruction requiring intervention, acute kidney injury (stage 2 or 3), rehospitalisation for valve-related symptoms or congestive heart failure, valve-related dysfunction requiring repeat procedure, moderate or severe prosthetic valve regurgitation, or prosthetic valve stenosis within 30 days of the procedure. Endpoint assessors were masked to treatment allocation. Non-inferiority of ACURATE neo compared with SAPIEN 3 was assessed in the intention-to-treat population on the basis of a risk-difference margin of 7·7% for the primary composite endpoint, with a one-sided α of 0·05. This trial is registered with ClinicalTrials.gov (number NCT03011346) and is ongoing but not recruiting. FINDINGS: Between Feb 8, 2017, and Feb 2, 2019, up to 5132 patients were screened and 739 (mean age 82·8 years [SD 4·1]; median STS-PROM score 3·5% [IQR 2·6-5·0]) were enrolled. 30-day follow-up was available for 367 (99%) of 372 patients allocated to the ACURATE neo group, and 364 (99%) of 367 allocated to the SAPIEN 3 group. Within 30 days, the primary endpoint occurred in 87 (24%) patients in the ACURATE neo and in 60 (16%) in the SAPIEN 3 group; thus, non-inferiority of the ACURATE neo was not met (absolute risk difference 7·1% [upper 95% confidence limit 12·0%], p=0·42). Secondary analysis of the primary endpoint suggested superiority of the SAPIEN 3 device over the ACURATE neo device (95% CI for risk difference -1·3 to -12·9, p=0·0156). The ACURATE neo and SAPIEN 3 groups did not differ in incidence of all-cause death (nine patients [2%] vs three [1%]) and stroke (seven [2%] vs 11 [3%]); whereas acute kidney injury (11 [3%] vs three [1%]) and moderate or severe prosthetic aortic regurgitation (34 [9%] vs ten [3%]) were more common in the ACURATE neo group. INTERPRETATION: TAVR with the self-expanding ACURATE neo did not meet non-inferiority compared to the balloon-expandable SAPIEN 3 device in terms of early safety and clinical efficacy outcomes. An early composite safety and efficacy endpoint was useful in discriminating the performance of different TAVR systems. FUNDING: Boston Scientific (USA).

"Between a rock and the mitral valve space": Transcatheter mitral valve-in-valve implantation for paravalvular leak and refractory hemolysis complicated by circumflex coronary occlusion.

Transcatheter mitral valve implantation (TMVI) is an emerging field in structural cardiology. A particularly difficult group to treat is high-risk patients requiring valve in mitral annular calcification (ViMAC) intervention, with overall poor procedural success and outcomes in recent registries. This case highlights an unusual complication of paravalvular regurgitation (PVL) through the uncovered stent frame of a balloon expandable transcatheter heart valve (THV) on the left ventricular side of the prosthesis, leading to mechanical hemolysis and subsequent anuric renal failure post a ViMAC procedure. Attempts to treat the PVL with an occlusion plug device were unsuccessful and led to left circumflex coronary occlusion secondary to mechanical compression of the vessel in the posterior mitral valve annulus, a previously unreported phenomenon. A repeat valve-in-valve procedure was performed to treat the PVL, and immediate angioplasty resolved the left circumflex occlusion. High-risk patients requiring TMVI pose multiple challenges to Heart Teams in the treatment of valve pathology. Optimal procedural planning, multimodality imaging, improved THVs, and the awareness of potential complications are fundamental in overcoming the learning curve of TMVI and improved outcome for patients requiring ViMAC.

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.

Transcatheter heart valve interventions: where are we? Where are we going?

Transcatheter heart valve interventions have transformed the outcomes of patients with valvular heart disease (VHD) who are unfavourable candidates for surgery. Technological advances have allowed extension of these interventions to younger or lower risk patients and those with other forms of VHD and may in the future permit earlier treatment of VHD in less symptomatic patients or those with moderate disease. The balance of risks and benefits is likely to differ between lower and higher risk patients, and more evidence is needed to evaluate the net benefit of transcatheter technology in these groups. As academic researchers, clinicians, industry, and patient stakeholders collaborate to research these broader indications for transcatheter valve interventions, it is essential to address (i) device durability and deliverability, (ii) specific anatomical needs (e.g. bicuspid aortic valves, aortic regurgitation, mitral and tricuspid valve disease), (iii) operator training, and (iv) the reinforced importance of the multidisciplinary Heart Team.

Outcomes of transcatheter mitral valve replacement for degenerated bioprostheses, failed annuloplasty rings, and mitral annular calcification.

Aims: We sought to evaluate the outcomes of transcatheter mitral valve replacement (TMVR) for patients with degenerated bioprostheses [valve-in-valve (ViV)], failed annuloplasty rings [valve-in-ring (ViR)], and severe mitral annular calcification [valve-in-mitral annular calcification (ViMAC)]. Methods and results: From the TMVR multicentre registry, procedural and clinical outcomes of ViV, ViR, and ViMAC were compared according to Mitral Valve Academic Research Consortium (MVARC) criteria. A total of 521 patients with mean Society of Thoracic Surgeons score of 9.0 ± 7.0% underwent TMVR (322 patients with ViV, 141 with ViR, and 58 with ViMAC). Trans-septal access and the Sapien valves were used in 39.5% and 90.0%, respectively. Overall technical success was excellent at 87.1%. However, left ventricular outflow tract obstruction occurred more frequently after ViMAC compared with ViR and ViV (39.7% vs. 5.0% vs. 2.2%; P < 0.001), whereas second valve implantation was more frequent in ViR compared with ViMAC and ViV (12.1% vs. 5.2% vs. 2.5%; P < 0.001). Accordingly, technical success rate was higher after ViV compared with ViR and ViMAC (94.4% vs. 80.9% vs. 62.1%; P < 0.001). Compared with ViMAC and ViV groups, ViR group had more frequent post-procedural mitral regurgitation ≥moderate (18.4% vs. 13.8% vs. 5.6%; P < 0.001) and subsequent paravalvular leak closure (7.8% vs. 0.0% vs. 2.2%; P = 0.006). All-cause mortality was higher after ViMAC compared with ViR and ViV at 30 days (34.5% vs. 9.9% vs. 6.2%; log-rank P < 0.001) and 1 year (62.8% vs. 30.6% vs. 14.0%; log-rank P < 0.001). On multivariable analysis, patients with failed annuloplasty rings and severe MAC were at increased risk of mortality after TMVR [ViR vs. ViV, hazard ratio (HR) 1.99, 95% confidence interval (CI) 1.27-3.12; P = 0.003; ViMAC vs. ViV, HR 5.29, 95% CI 3.29-8.51; P < 0.001]. Conclusion: The TMVR provided excellent outcomes for patients with degenerated bioprostheses despite high surgical risk. However, ViR and ViMAC were associated with higher rates of adverse events and mid-term mortality compared with ViV.

General Anesthesia or Conscious Sedation for Transfemoral Aortic Valve Replacement with the SAPIEN 3 Transcatheter Heart Valve.

Differences in the benefits of conscious sedation (CS) and general anesthesia (GA) during transfemoral aortic valve implantation (TAVI) are unclear.We aimed to assess differences in procedural and clinical outcomes based on the type of anesthesia received during TAVI.We analyzed SOURCE 3 Registry data for patients who received the SAPIEN 3 valve by type of anesthesia used during TAVI.Of the 1694 TAVI patients, 1027 received CS and 667 received GA. Patients were similar at baseline (81.5 years; Society of Thoracic Surgeons risk score 7.0). Compared with the GA group, the CS group had fewer intra-procedural transesophageal echocardiography (TEE) and post implantation dilatations performed, and less contrast medium was used. The CS group had significantly less kidney injury at 7 days post-procedure than the GA group (0.4% versus 1.5%, P = 0.014). Moderate paravalvular leaks (PVL) occurred more frequently in the CS group versus the GA group (2.2% versus 0.8%; P = 0.041). No severe PVL were reported. Median total hospital length of stay (LOS) after TAVI was 10 days in the CS group and 11 days in the GS group. At 30 days, all-cause death was 2.1% in CS and 1.7% in GS (P = 0.47), and myocardial infarction was 0.2% in CS and 0.1% in GS (P = 0.83).Our analyses found no significant major outcome differences between CS and GA during TAVI.

Clinical outcomes in unselected patients treated with the PROMUS Element platinum-chromium, everolimus-eluting stent: Final five-year results from the PE PROVE Study.

OBJECTIVES: The goal of this analysis was to evaluate the final 5-year safety and effectiveness of the PROMUS Element platinum-chromium everolimus-eluting stent in unselected patients treated in routine clinical practice. BACKGROUND: The prospective, open-label PROMUS Element™ European Post-Approval Surveillance Study (PE-PROVE) enrolled 1,010 "real-world" patients who received the PROMUS Element stent. Adverse event rates were low at 1-year, and the incidence of stent thrombosis was 0.6%. METHODS: The primary endpoint was target vessel failure (TVF; overall and PE stent-related), a composite of cardiac death, myocardial infarction (MI) related to the target vessel, or target vessel revascularization (TVR) at 1-year post-implantation. Five-year clinical outcomes were evaluated in overall as well as high-risk patient subgroups. RESULTS: The overall 5-year TVF rate was 14.9%, with 7.0% being related to the study stent. Cardiac death, MI and TVR related to the study stent occurred in 0.5%, 3.2%, and 5.7%, respectively. Stent thrombosis through 5-year follow-up was 1.0%. The rates of overall and study stent related TVF were numerically higher in patients with medically treated diabetes, long lesions (≥28 mm), and small diameter vessels (≤2.5 mm) compared to the overall study population. Additionally, favorable stent thrombosis rates through 5 years were reported for the PROMUS Element stent in these high-risk subgroups. CONCLUSIONS: The final 5-year data from the PE-PROVE study demonstrate favorable outcomes and low rates of adverse events with the PE stent when used in "real-world" patients with coronary artery disease.

Physiology of Angina and Its Alleviation With Nitroglycerin: Insights From Invasive Catheter Laboratory Measurements During Exercise.

BACKGROUND: The mechanisms governing exercise-induced angina and its alleviation by the most commonly used antianginal drug, nitroglycerin, are incompletely understood. The purpose of this study was to develop a method by which the effects of antianginal drugs could be evaluated invasively during physiological exercise to gain further understanding of the clinical impact of angina and nitroglycerin. METHODS: Forty patients (mean age, 65.2±7.6 years) with exertional angina and coronary artery disease underwent cardiac catheterization via radial access and performed incremental exercise using a supine cycle ergometer. As they developed limiting angina, sublingual nitroglycerin was administered to half the patients, and all patients continued to exercise for 2 minutes at the same workload. Throughout exercise, distal coronary pressure and flow velocity and central aortic pressure were recorded with sensor wires. RESULTS: Patients continued to exercise after nitroglycerin administration with less ST-segment depression (P=0.003) and therefore myocardial ischemia. Significant reductions in afterload (aortic pressure, P=0.030) and myocardial oxygen demand were seen (tension-time index, P=0.024; rate-pressure product, P=0.046), as well as an increase in myocardial oxygen supply (Buckberg index, P=0.017). Exercise reduced peripheral arterial wave reflection (P<0.05), which was not further augmented by the administration of nitroglycerin (P=0.648). The observed increases in coronary pressure gradient, stenosis resistance, and flow velocity did not reach statistical significance; however, the diastolic velocity-pressure gradient relation was consistent with a significant increase in relative stenosis severity (k coefficient, P<0.0001), in keeping with exercise-induced vasoconstriction of stenosed epicardial segments and dilatation of normal segments, with trends toward reversal with nitroglycerin. CONCLUSIONS: The catheterization laboratory protocol provides a model to study myocardial ischemia and the actions of novel and established antianginal drugs. Administration of nitroglycerin causes changes in the systemic and coronary circulation that combine to reduce myocardial oxygen demand and to increase supply, thereby attenuating exercise-induced ischemia. Designing antianginal therapies that exploit these mechanisms may provide new therapeutic strategies.

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.

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.

A mathematical model of coronary blood flow control: simulation of patient-specific three-dimensional hemodynamics during exercise.

This work presents a mathematical model of the metabolic feedback and adrenergic feedforward control of coronary blood flow that occur during variations in the cardiac workload. It is based on the physiological observations that coronary blood flow closely follows myocardial oxygen demand, that myocardial oxygen debts are repaid, and that control oscillations occur when the system is perturbed and so are phenomenological in nature. Using clinical data, we demonstrate that the model can provide patient-specific estimates of coronary blood flow changes between rest and exercise, requiring only the patient's heart rate and peak aortic pressure as input. The model can be used in zero-dimensional lumped parameter network studies or as a boundary condition for three-dimensional multidomain Navier-Stokes blood flow simulations. For the first time, this model provides feedback control of the coronary vascular resistance, which can be used to enhance the physiological accuracy of any hemodynamic simulation, which includes both a heart model and coronary arteries. This has particular relevance to patient-specific simulation for which heart rate and aortic pressure recordings are available. In addition to providing a simulation tool, under our assumptions, the derivation of our model shows that ß-feedforward control of the coronary microvascular resistance is a mathematical necessity and that the metabolic feedback control must be dependent on two error signals: the historical myocardial oxygen debt, and the instantaneous myocardial oxygen deficit.