Explore the vast range of titles available.

Background Targeted temperature management (TTM) is recommended following cardiac arrest; however, time to target temperature varies in clinical practice. We hypothesised the effects of a target temperature of 33 °C when compared to normothermia would differ based on average time to hypothermia and those patients achieving hypothermia fastest would have more favorable outcomes. Methods In this post-hoc analysis of the TTM-2 trial, patients after out of hospital cardiac arrest were randomized to targeted hypothermia (33 °C), followed by controlled re-warming, or normothermia with early treatment of fever (body temperature, ≥ 37.8 °C). The average temperature at 4 h (240 min) after return of spontaneous circulation (ROSC) was calculated for participating sites. Primary outcome was death from any cause at 6 months. Secondary outcome was poor functional outcome at 6 months (score of 4–6 on modified Rankin scale). Results A total of 1592 participants were evaluated for the primary outcome. We found no evidence of heterogeneity of intervention effect based on the average time to target temperature on mortality ( p  = 0.17). Of patients allocated to hypothermia at the fastest sites, 71 of 145 (49%) had died compared to 68 of 148 (46%) of the normothermia group (relative risk with hypothermia, 1.07; 95% confidence interval 0.84–1.36). Poor functional outcome was reported in 74/144 (51%) patients in the hypothermia group, and 75/147 (51%) patients in the normothermia group (relative risk with hypothermia 1.01 (95% CI 0.80–1.26). Conclusions Using a hospital’s average time to hypothermia did not significantly alter the effect of TTM of 33 °C compared to normothermia and early treatment of fever.

Percutaneous coronary intervention (PCI) for coronary chronic total occlusion (CTO) has been performed for the improvement of symptoms and quality of life in patients with stable angina. The ORBITA study demonstrated the role of the placebo effect in contemporary PCI in non-CTO chronic coronary syndromes. However, the benefit of CTO PCI beyond that of a placebo has not been demonstrated. The ORBITA-CTO pilot study will be a double-blind, placebo-controlled study of CTO PCI randomising patients who have: (1) been accepted by a CTO operator for PCI; (2) experienced symptoms due to a CTO; (3) evidence of ischaemia; (4) evidence of viability within the CTO territory; and (5) a J-CTO score ≤3. Patients will undergo medication optimisation that will ensure they are on at least a minimum amount of anti-anginals and complete questionnaires. Patients will record their symptoms on an app daily throughout the study. Patients will undergo randomisation procedures, including an overnight stay, and be discharged the following day. All anti-anginals will be stopped after randomisation and re-initiated on a patient-led basis during the 6-month follow-up period. At follow-up, patients will undergo repeat questionnaires and unblinding, with a further 2-week unblinded follow-up. The co-primary outcomes are feasibility (blinding) in this cohort and angina symptom score using an ordinal clinical outcome scale for angina. Secondary outcomes include changes in quality-of-life measures, Seattle Angina Questionnaire (SAQ), peak VO2, and anaerobic threshold on the cardiopulmonary exercise test. The feasibility of a placebo-controlled CTO PCI study will lead to future studies assessing efficacy. The impact of CTO PCI on angina measured using a novel daily symptom app may provide improved fidelity in assessing symptoms in patients with CTO's.

The coronary sinus reducer (CSR) is proposed to reduce angina in patients with stable coronary artery disease by improving myocardial perfusion. We aimed to measure its efficacy, compared with placebo, on myocardial ischaemia reduction and symptom improvement. ORBITA-COSMIC was a double-blind, randomised, placebo-controlled trial conducted at six UK hospitals. Patients aged 18 years or older with angina, stable coronary artery disease, ischaemia, and no further options for treatment were eligible. All patients completed a quantitative adenosine-stress perfusion cardiac magnetic resonance scan, symptom and quality-of-life questionnaires, and a treadmill exercise test before entering a 2-week symptom assessment phase, in which patients reported their angina symptoms using a smartphone application (ORBITA-app). Patients were randomly assigned (1:1) to receive either CSR or placebo. Both participants and investigators were masked to study assignment. After the CSR implantation or placebo procedure, patients entered a 6-month blinded follow-up phase in which they reported their daily symptoms in the ORBITA-app. At 6 months, all assessments were repeated. The primary outcome was myocardial blood flow in segments designated ischaemic at enrolment during the adenosine-stress perfusion cardiac magnetic resonance scan. The primary symptom outcome was the number of daily angina episodes. Analysis was done by intention-to-treat and followed Bayesian methodology. The study is registered with ClinicalTrials.gov, NCT04892537, and completed. Between May 26, 2021, and June 28, 2023, 61 patients were enrolled, of whom 51 (44 [86%] male; seven [14%] female) were randomly assigned to either the CSR group (n=25) or the placebo group (n=26). Of these, 50 patients were included in the intention-to-treat analysis (24 in the CSR group and 26 in the placebo group). 454 (57%) of 800 imaged cardiac segments were ischaemic at enrolment, with a median stress myocardial blood flow of 1·08 mL/min per g (IQR 0·77–1·41). Myocardial blood flow in ischaemic segments did not improve with CSR compared with placebo (difference 0·06 mL/min per g [95% CrI –0·09 to 0·20]; Pr(Benefit)=78·8%). The number of daily angina episodes was reduced with CSR compared with placebo (OR 1·40 [95% CrI 1·08 to 1·83]; Pr(Benefit)=99·4%). There were two CSR embolisation events in the CSR group, and no acute coronary syndrome events or deaths in either group. ORBITA-COSMIC found no evidence that the CSR improved transmural myocardial perfusion, but the CSR did improve angina compared with placebo. These findings provide evidence for the use of CSR as a further antianginal option for patients with stable coronary artery disease. Medical Research Council, Imperial College Healthcare Charity, National Institute for Health and Care Research Imperial Biomedical Research Centre, St Mary's Coronary Flow Trust, British Heart Foundation.

Fractional flow reserve (FFR) uses pressure-based measurements to assess the severity of a coronary stenosis. Distal pressure (Pd) is often at a different vertical height to that of the proximal aortic pressure (Pa). The difference in pressure between Pd and Pa due to hydrostatic pressure, may impact FFR calculation. One hundred computed tomography coronary angiographies were used to measure height differences between the coronary ostia and points in the coronary tree. Mean heights were used to calculate the hydrostatic pressure effect in each artery, using a correction factor of 0.8 mmHg/cm. This was tested in a simulation of intermediate coronary stenosis to give the \"corrected FFR\" (cFFR) and percentage of values, which crossed a threshold of 0.8. The mean height from coronary ostium to distal left anterior descending (LAD) was +5.26 cm, distal circumflex (Cx) -3.35 cm, distal right coronary artery-posterior left ventricular artery (RCA-PLV) -5.74 cm and distal RCA-posterior descending artery (PDA) +1.83 cm. For LAD, correction resulted in a mean change in FFR of +0.042, -0.027 in the Cx, -0.046 in the PLV and +0.015 in the PDA. Using 200 random FFR values between 0.75 and 0.85, the resulting cFFR crossed the clinical treatment threshold of 0.8 in 43% of LAD, 27% of Cx, 47% of PLV and 15% of PDA cases. There are significant vertical height differences between the distal artery (Pd) and its point of normalization (Pa). This is likely to have a modest effect on FFR, and correcting for this results in a proportion of values crossing treatment thresholds. Operators should be mindful of this phenomenon when interpreting FFR values.

Fractional flow reserve (FFR) assessment of remote arteries, in the context of a bystander chronic total occlusion (CTO), can lead to false positive results. Adenosine stress cardiovascular magnetic resonance (CMR) evaluates perfusion defects across the entire myocardium and may therefore be a reliable tool in the work-up of remote lesions in CTO patients. The IMPACT-CTO study investigated donor artery invasive physiology before, immediately post, and at 4 months following right coronary artery (RCA) CTO percutaneous coronary intervention (PCI). The aim of this subanalysis was to assess the concordance between baseline perfusion CMR and serial FFR evaluation of left anterior descending artery (LAD) ischemia in patients from the IMPACT-CTO study. Baseline adenosine stress CMR examinations from 26 patients were analyzed for qualitative evidence of LAD ischemia. The results were correlated with the serial LAD FFR measurements. The present findings demonstrated that before RCA CTO PCI, there was 62% agreement between perfusion CMR and FFR (ischemic threshold £ 0.8) in the assessment of LAD ischemia (k = 0.29; fair concordance). At 4 months after revascularization, there was 77% agreement (k = 0.52; moderate concordance) between the index CMR assessment of LAD ischemia and the follow-up LAD FFR. Concordance was improved at a LAD FFR ischemic threshold of £ 0.75. In this hypothesis generating study, baseline CMR assessment of LAD ischemia correlated better with the 4 months LAD FFR data (threshold £ 0.8) as compared to the FFR measurements taken prior to RCA CTO revascularization.

Continuous Thermodilution is a novel method of quantifying coronary flow (Q) in mL/min. To account for variability of Q within the cardiac cycle, the trace is smoothened with a 2 s moving average filter. This can sometimes be ineffective due to significant heart rate variability, ventricular extrasystoles, and deep inspiration, resulting in a fluctuating temperature trace and ambiguity in the location of the “steady state”. This study aims to assess whether a longer moving average filter would smoothen any fluctuations within the continuous thermodilution traces resulting in improved interpretability and reproducibility on a test–retest basis. Patients with ANOCA underwent repeat continuous thermodilution measurements. Analysis of traces were performed at averages of 10, 15, and 20 s to determine the maximum acceptable average. The maximum acceptable average was subsequently applied as a moving average filter and the traces were re-analysed to assess the practical consequences of a longer moving average. Reproducibility was then assessed and compared to a 2 s moving average. Of the averages tested, only 10 s met the criteria for acceptance. When the data was reanalysed with a 10 s moving average filter, there was no significant improvement in reproducibility, however, it resulted in a 12% diagnostic mismatch. Applying a longer moving average filter to continuous thermodilution data does not improve reproducibility. Furthermore, it results in a loss of fidelity on the traces, and a 12% diagnostic mismatch. Overall, current practice should be maintained.

Background Individuals receiving a standardised daily dose of 2000 mg of the n -3 highly unsaturated fatty acid (HUFA) eicosapentaenoic acid (EPA) for 12 months in the seAFOod polyp prevention trial demonstrated wide inter-individual variability in red blood cell (RBC) EPA levels (expressed as % of total measured fatty acids). Eicosapentaenoic acid can be converted to n -3 docosapentaenoic acid ( n -3DPA) by the elongase elongation of very long-chain fatty acids (ELOVL) 2 . We tested whether single nucleotide polymorphisms (SNPs) in ELOVL2 (rs3734398, rs2236212, rs953413, rs3798713, rs9393903) are associated with differential RBC EPA and n -3DPA levels in seAFOod trial participants at baseline and while receiving EPA supplementation. Results Six hundred and three seAFOod trial participants had ELOVL2 genotype and RBC n -3 HUFA data. All five ELOVL2 SNPs were in strong linkage disequilibrium (R 2 > 0.95). Therefore, we focussed on rs953413 (genotype frequency: GG 30.8%, GA 50.1% and AA 19.1%), as the best characterised SNP, which is believed to be functional in human liver cells. Prior to trial intervention, minor (A) homozygotes displayed higher levels of n -3DPA ( P  < 0.01), but not EPA ( P  > 0.05), in RBCs than major (G) allele carriers. The trend towards a greater increase in n -3DPA values in AA homozygotes during EPA treatment compared with GA heterozygotes or GG homozygotes did not reach statistical significance. There was also no significant difference in the change in RBC EPA or DHA levels during EPA treatment according to rs953413 genotype. Conclusions A secondary analysis of the seAFOod trial found that minor (A allele) homozygotes for the ELOVL2 SNP rs953413 have a higher baseline RBC n -3DPA level than G allele carriers. However, rs953413 genotype did not significantly influence ΔEPA, Δ n -3DPA, or ΔDHA levels during 6 or 12 months of high-dose EPA supplementation. Therefore, we do not provide evidence that genetic variation in ELOVL2 contributes to the inter-individual variability in the circulating EPA level associated with high-dose EPA supplementation.

Intracoronary continuous thermodilution has been recently proposed as an invasive method to quantify absolute coronary flow (Qabs) and resistance (Rabs) in vivo. The aim of the present study is to develop and validate of a novel pressure-wire- and microcatheter-free surrogate of coronary flow and resistance derived from a standard coronary angiogram. Angiography derived coronary flow (Qangio) and resistance (Rangio) was prospectively validated in a two-center cohort of patients from Oxford Heart Centre and the Essex Cardiothoracic Centre. Qabs and Rabs were measured during resting and hyperemic conditions with continuous thermodilution using the Rayflow microcatheter. Qangio and Rangio were computed from the diagnostic coronary angiogram in a blinded fashion in resting and hyperemic conditions. A total of 62 patients and 115 vessels were included in the present analysis. The median Qabs at rest was 75 ml/min (53–95) and 151 ml/min (105–203) during hyperemia; Qangio at rest was 84 ml/min (66–108) and 154 ml/min (115–195) during hyperemia. There was a strong correlation between Qabs and Qangio (R = 0,72; p < 0.001, R = 0,86; p < 0.001 respectively) with satisfactory interclass correlation (0.841, 95% CI 0.509–0.957; p = 0.0003). The median Rabs was 1111 mmHg/(L/min) (830-1581.4) at rest and 454 mmHg/(L/min) (348–610) during hyperemia; angiographic resistance (Rangio) was 937.4 mmHg/(L/min) (695.4–1261.9) at rest and 492.4 mmHg/(L/min) (406–697) during hyperemia. There was a strong correlation between Rabs and Rangio in both conditions (R = 0,81; p < 0.001 and R = 0,78; p < 0.001 respectively). The was a good correlation between absolute coronary flow reserve (CFR) and angiography-derived CFR (R = 0,61; p < 0.001) and between absolute microvascular resistance reserve (MRR) and angiography-derived MRR (R = 0,49; p < 0.001).Condensed abstractWe developed and validated a novel non-invasive, fully angiographic, pressure-wire- and microcatheter-free method to quantify coronary flow and resistance in resting and hyperemic conditions. Angiography-derived coronary flow and resistance was prospectively validated in a two-center cohort of 62 patients and 115 vessels against absolute coronary flow and resistance measured with Rayflow microcatheter. We found a strong correlation between angiography-derived flow and resistance and absolute coronary flow and resistance, with satisfactory interclass correlation. There was a good correlation between absolute coronary flow reserve (CFR) and angiography-derived CFR and between absolute microvascular resistance reserve (MRR) and angiography-derived MRR.

The presence of activated macrophages is an important predictor of atherosclerotic plaque rupture. In this study, our aim was to determine the accuracy of 18 F- fluorodeoxyglucose (FDG) microPET imaging for quantifying aortic wall macrophage content in a rabbit model of atherosclerosis. Rabbits were divided into a control group and two groups post aortic balloon injury: 6 months high-cholesterol diet (HC); and 3 months HC followed by 3 months low-cholesterol diet plus statin (LCS). In vivo and ex vivo microPET, ex vivo well counting and histological quantification of the atherosclerotic aortas were performed for all groups. Macrophage density was greater in the HC group than the LCS group (5.1 ± 1.4% vs. 0.6 ± 0.7%, P  < 0.001) with a trend towards greater macrophage density in LCS compared to controls ( P  = 0.08). There was a strong correlation across all groups between macrophage density and standardized uptake value (SUV) derived from ex vivo microPET ( r  = 0.95, P  < 0.001) and well counting ( r  = 0.96, P  < 0.001). Ex vivo FDG SUV was significantly different between the three groups ( P  < 0.001). However, the correlation between in vivo microPET FDG SUV and macrophage density was insignificant ( r  = 0.16, P  = 0.57) with no statistical differences in FDG SUV seen between the three groups. This study confirms that in an animal model of inflamed and non-inflamed atherosclerosis, significant differences in FDG SUV allow differentiation of highly inflamed atherosclerotic aortas from those stabilized by statin therapy and low cholesterol diet and controls.

Background/Objectives: Neuroprognostication after out-of-hospital cardiac arrest (OHCA) remains clinically challenging, particularly when withdrawal of life-sustaining treatment (WLST) is considered. International guidelines recommend delayed, multimodal assessment, but real-world descriptions of how this is operationalised within multidisciplinary pathways remain limited. Methods: We conducted a single-centre retrospective observational cohort study of adults admitted to a tertiary cardiac arrest centre intensive care unit following OHCA between June 2022 and December 2025. Patients were conveyed according to the British Cardiovascular Intervention Society OHCA pathway; therefore, this was a selected cardiac arrest centre cohort enriched for shockable rhythms and suspected reversible cardiac causes, rather than an unselected OHCA population. Patients who remained unconscious at ≥72 h following a sedation hold entered a structured multidisciplinary team (MDT) neuroprognostication pathway. Outcomes included survival to hospital discharge, Cerebral Performance Category (CPC) at discharge, neuroprognostication investigation use, and timing of WLST. Results: Of 406 patients admitted following OHCA, 310 were admitted to ICU and included in the analysis. The cohort was predominantly male (82.3%), with a mean age of 63.8 years; 82.9% had ventricular fibrillation as the initial rhythm. Overall, 182 patients (58.7%) survived to hospital discharge, of whom 160 (87.9%) had a favourable neurological outcome (CPC 1–2). A total of 119 patients entered the neuroprognostication pathway. Of these, 72 underwent WLST after completed MDT review, 10 died before MDT decision-making, and 37 survived to hospital discharge. Among patients undergoing WLST, investigation use was high: CT brain 100%, NSE 91.7%, EEG 90.3%, SSEP 88.9%, and MRI brain 27.8%. Median time to WLST was 5.5 days. Conclusions: In this selected tertiary CAC cohort, enriched for shockable rhythms through BCIS pathway-based conveyance, survival to hospital discharge was high and neurological outcomes among survivors were predominantly favourable. Within this setting, delayed, multimodal neuroprognostication and WLST decision-making were operationalised through a structured MDT pathway aligned with contemporary guideline recommendations. These findings provide contemporary real-world benchmark data on pathway implementation for comparable centres seeking to evaluate or develop structured neuroprognostication services.