Intracoronary (IC) imaging-guided percutaneous coronary intervention (PCI) improves clinical outcomes in patients with high clinical and anatomical risk when compared to interventions guided by angiography alone. Recent Class I recommendations for the use of IC imaging guidance when performing PCI in left main stem or complex lesions may result in a significant uptake as the technology is embraced as standard of care. Routine application of IC imaging will provide interventional cardiologists with a wealth of high-fidelity intracoronary data on plaque composition and distribution. When paired with emerging data regarding the importance of plaque anatomical characteristics, developments in artificial intelligence and computational fluid dynamics, lesion stratification with IC imaging may herald the next paradigm shift in this field. In this review, we will explore this important emerging application of IC imaging to inform morphology-guided PCI, identify high-risk lesions for targeted therapies, and consider the prospects of harnessing automated image interpretation with artificial intelligence technologies to achieve an integrated physiological and morphological assessment. Lesion stratification with IC imaging has the potential to shape the future of interventional cardiology practice to guide therapies within and beyond the confines of the cardiac catheterisation laboratory.

BACKGROUND:The purpose of this study was to prospectively validate the MIRACLE2 score in the GLOBAL-MIRACLE registry, a multicenter, international, prospective registry of patients admitted with resuscitated out-of-hospital cardiac arrest of presumed cardiac cause. METHODS:From January 1, 2022 to May 31, 2023, 770 patients were recruited from 11 centers across 5 countries. The primary end point was poor neurological outcome (Cerebral Performance Category 3-5) at hospital discharge. Model discrimination was assessed by the area under the receiver operating characteristic curve. We compared the discriminatory performance of the MIRACLE2 score against Cardiac Arrest Hospital Prognosis, out-of-hospital cardiac arrest, Target Temperature Management, NULL-PLEASE, C-GRAPH, and rCAST. RESULTS:The primary end point occurred in 395 (51.2%) patients. The MIRACLE2 score had an area under the curve of 0.861 (95% CI, 0.835-0.887). A MIRACLE2 score ≤2 had a negative predictive value of 87.8%, while a score of ≥7 had a positive predictive value of 98.3%. The MIRACLE2 score had equal performance to the TTM risk tool (P=0.12) but better discriminatory performance than other risk tools (P<0.0001). The MIRACLE2 score showed good performance in those with ST-segment-elevation myocardial infarction (0.851 [95% CI, 0.816-0.886]) and without ST-segment-elevation myocardial infarction (0.873 [95% CI, 0.834-0.912]) and in those with cardiogenic shock (0.832 [95% CI, 0.789-0.875]) and without cardiogenic shock (0.853 [95% CI, 0.810-0.895]). CONCLUSIONS:The MIRACLE2 score is a practical risk tool that shows excellent discrimination performance for poor neurological outcome after presumed cardiac cause out-of-hospital cardiac arrest, including based on hemodynamic status and admission 12-lead ECG. Early stratification of out-of-hospital cardiac arrest patients using the MIRACLE2 score should be evaluated in future randomized controlled trials.

BACKGROUND:Cardiogenic shock (CS) is a common complication of patients with resuscitated out-of-hospital cardiac arrest (OHCA). AIMS:This study investigates whether the change in SCAI Shock Grade, measured between hospital and intensive care admission (ICU), is associated with outcome after OHCA. METHODS:Patients with OHCA of suspected cardiac etiology were included from the King's Out-of-Hospital Cardiac Arrest Registry between 2012 and 2021. SCAI Shock Grade was determined on hospital and ICU admission. Patients were categorized into worsening, static, or improving SCAI Grade. The primary endpoint was in-hospital mortality at 30 days. Predictors of SCAI change and circulatory mortality were assessed using univariable and multivariable regression. RESULTS:Of 493 patients (median age 63 years, 77% male), 68% had a shockable rhythm, 80% were witnessed, and 94% had bystander CPR. SCAI Grade between hospital and ICU admission improved in 32% of patients, was static in 43% and deteriorated in 25%. Amongst the overall cohort, circulatory death occurred in 19% of patients and neurological death occurred in 28% of patients. Mortality did not differ between groups based on the change in SCAI grade (p = 0.2). However, circulatory death was more common in patients with deteriorating SCAI Grade (28%), compared to static (19%) and improving (13%) SCAI (p = 0.010). Multivariable regression modeling showed that SCAI change was independently associated with circulatory death, along with age, lactate, and MIRACLE2 score. CONCLUSION:In patients with OHCA complicated by CS, deterioration in SCAI Grade between cardiac center arrival and ICU admission is independently associated with circulatory death.

Background: Out-of-hospital cardiac arrest (OHCA) remains a global health burden where neurological injury sustained is a key predictor of mortality but there are challenges in early risk stratification. This study aims to derive the Pre-MIRACLE2 score, which excludes pH as a component from the MIRACLE2 score, as a means of stratifying neurological risk in a pre-hospital setting. Methods: To validate the Pre-MIRACLE2 score, we used (i) the EUCAR Registry retrospectively analysed from 1 May 2012 to 31 December 2021, and (ii) the GLOBAL-MIRACLE Registry, a prospective cohort analysed from 1 January 2022 to 31 May 2023. The primary outcome was poor neurological outcome (defined as Cerebral Performance Category 3-5) at hospital discharge. Results: From 1 May 2012 until 31 May 2023, 2149 patients were resuscitated from OHCA with sustained return of spontaneous circulation. After excluding patients who remained non-comatose following return of spontaneous circulation and those with incomplete scores, 1402 patients from EUCAR and 747 from GLOBAL-MIRACLE were included in the final analysis. The primary endpoint occurred in 54.4% of the study cohort. The performance of the Pre-MIRACLE2 score for the primary endpoint was excellent, with an area under the receiver operating curve (AUROC) of 0.85 (95% CI 0.83, 0.87). From the prospective validation cohort (GLOBAL-MIRACLE), the AUROC was 0.85 (95% CI 0.82-0.88) with a calibration slope of 1.11 (95% CI 0.95-1.29). Conclusion: The Pre-MIRACLE2 score has the potential to be an effective and pragmatic risk stratification tool for prediction of poor neurological outcome in a pre-hospital environment or where the pH cannot be measured. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was performed according to the principles of the Declaration of Helsinki and was approved by local research ethics or governance committees at each centre for both EUCAR (REC Name: South Central - Hampshire A Research Ethics Committee; REC Reference: 18/SC/0008, IRAS ID: 233062) and GLOBAL-MIRACLE (REC Name: Wales REC 5; REC Reference: 21/WA/0361; IRAS ID: 289784) registries. Both studies were affiliated with King's College Hospital NHS Foundation Trust. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.

Background: Near-infrared spectroscopy combined with intravascular ultrasound (NIRS–IVUS) allows simultaneous assessment of plaque composition and vessel structure. The lipid core burden index (LCBI) and the maximum lipid core burden index over 4 mm (maxLCBI4mm) are established markers of lipid-rich and potentially vulnerable plaques. However real-world reproducibility data for these indices using the contemporary Dualpro™ NIRS–IVUS catheter is unknown. This study aimed to evaluate the reproducibility of LCBI and maxLCBI4mm across repeated NIRS–IVUS pullbacks performed within the same coronary segment using the current-generation catheter system. Methods: This single-center study included consecutive patients who underwent percutaneous coronary intervention (PCI) with adjunctive NIRS–IVUS imaging and had repeated pullbacks of the same coronary segment during the procedure. LCBI and maxLCBI4mm were recorded for each pullback. Reproducibility was assessed using Spearman correlation and intraclass correlation coefficients (ICC), and consistency for the clinically relevant thresholds of maxLCBI4mm was evaluated. Results: A total of 87 paired pullbacks were analyzed (37 pre-PCI, 15 post-lesion preparation, and 35 post-stenting). LCBI demonstrated excellent reproducibility (ρ = 0.95; ICC = 0.95) and maxLCBI4mm also showed strong reproducibility (ρ = 0.90; ICC = 0.91). The threshold of maxLCBI4mm > 400 was concordant between runs in 90% of cases, and the post-stent threshold of >200 showed concordance in 89% of cases. Conclusion: The contemporary Dualpro™ NIRS–IVUS catheter provides highly reproducible measurements of both LCBI and maxLCBI4mm. These findings support the reliability of NIRS–IVUS for identifying lipid-rich plaques and strengthen its suitability for research and clinical applications focused on plaque vulnerability.

AIMS:Out-of-hospital cardiac arrest (OHCA) has high mortality, and outcomes remain heterogeneous despite guidelines recommending universal conveyance to cardiac arrest centres. Early pre-hospital risk stratification may identify patients most likely to benefit. The pre-hospital utility of MIRACLE2 is unknown, so we evaluated the feasibility of rapid point-of-care testing to enable calculation of the MIRACLE2 score after return of spontaneous circulation (ROSC). METHODS AND RESULTS:RAPID-MIRACLE was a prospective, multi-centre observational study conducted across London with the London Ambulance Service. Adult patients with suspected cardiac aetiology OHCA achieving sustained ROSC were enrolled. Pre-hospital point-of-care venous blood-gas sampling was performed with results blinded to receiving hospitals. We evaluated ROSC-MIRACLE2 incorporating post-ROSC pH, compared with a modified MIRACLE2 excluding pH (pre-MIRACLE2) and standard MIRACLE2 calculated on hospital admission. The primary outcome was poor neurological outcome at 30 days, defined as cerebral performance category (CPC) 3-5. Among 292 patients, 48% had poor neurological outcome. ROSC-MIRACLE2 demonstrated excellent discrimination [area under the receiver operating characteristic curve (AUC) 0.89 (95% CI 0.85-0.92)], comparable to pre-MIRACLE2 [AUC 0.88 (95% CI 0.84-0.92)], and admission MIRACLE2 [AUC 0.89 (95% CI 0.85-0.92)]. For ROSC-MIRACLE2, a threshold 0-2, the negative predictive value for good outcome was 0.89 (0.82-0.94). At a threshold ≥5, the positive predictive value was 0.88 (0.82-0.94). In a multi-variable regression model, post-ROSC pH was independently associated with poor neurological outcome and less than 3% of patients with a ROSC pH <7.00 had good neurological outcome. CONCLUSION:In this study, pre-hospital application of ROSC-MIRACLE2 enables early neurological risk stratification following resuscitated OHCA. Point-of-care pH improves prognostic precision, but is constrained by feasibility, whilst the simplified pre-MIRACLE2 score is more practical with comparable performance. Integration into OHCA care pathways may improve patient stratification and resource utilization but requires further study.

BACKGROUND:Out-of-hospital cardiac arrest (OHCA) remains a global health burden where neurological injury sustained is a key predictor of mortality but there are challenges in early risk stratification. This study aims to derive the Pre-MIRACLE2 score, which excludes pH as a component from the MIRACLE2 score, as a means of stratifying neurological risk in a pre-hospital setting. METHODS:To validate the Pre-MIRACLE2 score, we used (i) the EUCAR Registry retrospectively analysed from 1 May 2012 to 31 December 2021, and (ii) the GLOBAL-MIRACLE Registry, a prospective cohort analysed from 1 January 2022 to 31 May 2023. The primary outcome was poor neurological outcome (defined as Cerebral Performance Category 3-5) at hospital discharge. RESULTS:From 1 May 2012 until 31 May 2023, 2149 patients were resuscitated from OHCA with sustained return of spontaneous circulation. After excluding patients who remained non-comatose following return of spontaneous circulation and those with incomplete scores, 1402 patients from EUCAR and 747 from GLOBAL-MIRACLE were included in the final analysis. The primary endpoint occurred in 54.4% of the study cohort. The performance of the Pre-MIRACLE2 score for the primary endpoint was excellent, with an area under the receiver operating curve (AUROC) of 0.85 (95% CI 0.83, 0.87). From the prospective validation cohort (GLOBAL-MIRACLE), the AUROC was 0.85 (95% CI 0.82-0.88) with a calibration slope of 1.11 (95% CI 0.95-1.29). CONCLUSION:The Pre-MIRACLE2 score has the potential to be an effective and pragmatic risk stratification tool for prediction of poor neurological outcome in patients with resuscitated OHCA of suspected cardiac aetiology in a pre-hospital environment or where pH cannot be measured.

Background ST-segment elevation myocardial infarction (STEMI) is treated with immediate primary percutaneous coronary intervention (pPCI) to restore coronary blood flow in the acutely ischaemic territory, but is associated with reperfusion injury limiting the benefit of the therapy. No treatment has proven effective in reducing reperfusion injury. Transcoronary hypothermia has been tested in clinical studies and is well tolerated, but is generally established after crossing the occlusion with a guidewire therefore after initial reperfusion, which might have contributed to the neutral outcomes. Transcatheter strategies may also offer additional benefit through haemodilution and the resultant controlled reperfusion, but this has not been fully investigated for pPCI. Design STEMI-Cool is a pragmatic, registry-based randomised clinical pilot trial to test the recruitment rate, feasibility, and safety of a simple transcoronary cooling and dilution protocol. Sixty STEMI patients undergoing pPCI will be randomised 1:1 to standard of care or continuous infusion of room temperature saline through the guiding catheter to achieve intracoronary temperature reductions of 6 to 8 degrees C, commencing before crossing the coronary occlusion with a guidewire. Mechanistic outcome measures will include microvascular resistance, biomarkers of inflammation before infusion and at 24 hour, and magnetic resonance imaging of myocardial salvage and infarct size. Conclusions STEMI-Cool will investigate the recruitment rate, feasibility and safety of an innovative and simple cooling and diluting strategy for cardioprotection before and during reperfusion with pPCI, aiming to address limitations faced in other studies. Mechanistic outcome measures will allow insight into inflammatory, microvascular and structural changes induced by transcoronary cooling and dilution. (Am Heart J 2025;282:40-50.)

Aims We validated the CREST model, a 5 variable score for stratifying the risk of circulatory aetiology death (CED) following out-of-hospital cardiac arrest (OHCA) and compared its discrimination with the SCAI shock classification. Circulatory aetiology death occurs in approximately a third of patients admitted after resuscitated OHCA. There is an urgent need for improved stratification of the patient with OHCA on arrival to a cardiac arrest centre to improve patient selection for invasive interventions. Methods and results The CREST model and SCAI shock classification were applied to a dual-centre registry of 723 patients with cardiac aetiology OHCA, both with and without ST-elevation myocardial infarction (STEMI), between May 2012 and December 2020. The primary endpoint was a 30-day CED. Of 509 patients included (62.3 years, 75.4% male), 125 patients had CREST = 0 (24.5%), 162 had CREST = 1 (31.8%), 140 had CREST = 2 (27.5%), 75 had CREST = 3 (14.7%), 7 had a CREST of 4 (1.4%), and no patients had CREST = 5. Circulatory aetiology death was observed in 91 (17.9%) patients at 30 days [STEMI: 51/289 (17.6%); non-STEMI (NSTEMI): 40/220 (18.2%)]. For the total population, and both NSTEMI and STEMI subpopulations, an increasing CREST score was associated with increasing CED (all P < 0.001). The CREST score and SCAI classification had similar discrimination for the total population [area under the receiver operating curve (AUC) = 0.72/calibration slope = 0.95], NSTEMI cohort (AUC = 0.75/calibration slope = 0.940), and STEMI cohort (AUC = 0.69 and calibration slope = 0.925). Area under the receiver operating curve meta-analyses demonstrated no significant differences between the two classifications. Conclusion The CREST model and SCAI shock classification show similar prediction results for the development of CED after OHCA.