Background Non-ST-segment-elevation myocardial infarction (NSTEMI) accounts for the majority of acute coronary syndrome presentations. Invasive coronary angiography (ICA) is recommended but challenging to deliver within guideline-recommended timeframes and unnecessary in patients without obstructive disease. CT coronary angiography (CTCA) offers a non-invasive alternative for lower-risk patients that may reduce procedural-related complications and optimise resource use by avoiding unnecessary ICA.Methods We conducted a systematic review and meta-analysis following Cochrane standards. Four databases were searched from January 2005 to March 2025. Eligible studies included adult patients with NSTEMI undergoing CTCA to guide management, with comparators of standard care (ICA-first strategies). Primary outcomes were ICA utilisation, composite cardiovascular events (myocardial infarction, cardiovascular and all-cause death) and diagnostic accuracy of CTCA versus ICA.Results From 12 058 records, eight studies met inclusion criteria; three randomised controlled trial (RCT) studies and five observational cohorts; total n≈2700. Across two RCTs, a CTCA-first strategy did not significantly reduce ICA use (pooled relative risk (RR)=0.82 (0.55–1.22)). Evidence for composite clinical outcomes was heterogeneous: The Rapid Assessment of Potential Ischaemic Heart Disease with CTCA trial reported no difference in death or MI, whereas the trial, Computed Tomography Cardiac Angiography Before Invasive Coronary Angiography in Patients with Previous Bypass Surgery, observed reduced events at 1 year (RR=0.63 (0.43–0.94)). Pooled diagnostic accuracy for >50% stenosis from observational studies demonstrated high sensitivity (96.3%) and moderate specificity (79.6%), with high heterogeneity. Length of stay and patient satisfaction were similar or improved with CTCA-first strategies, though cost-effectiveness data were limited. Overall evidence quality ranged from moderate (RCTs) to low (observational studies).Conclusions CTCA demonstrates excellent diagnostic accuracy and may reduce complications while maintaining clinical outcomes in patients with NSTEMI. Current evidence does not show consistent reductions in ICA use or major adverse events. Larger trials are needed to clarify its role in NSTEMI management pathways.PROSPERO registration number CRD420251003903

BACKGROUND:Patients with prior coronary artery bypass grafting (CABG) account for around 10% of non-ST-elevation acute coronary syndromes (NSTE-ACS), but the optimal diagnostic and management strategy remains uncertain. Invasive coronary angiography (ICA) in this group is technically challenging, carries increased risk and often does not lead to percutaneous coronary intervention (PCI). CT coronary angiography (CTCA) may help identify which patients benefit from ICA and reduce unnecessary invasive procedures. METHODS:In the BYPASS-CTCA (Randomised Controlled Trial to Assess Whether Computed Tomography Cardiac Angiography Can Improve Invasive Coronary Angiography in Bypass Surgery Patients) study, patients with prior CABG undergoing ICA were randomised to CTCA plus ICA or ICA alone. For this analysis, anonymised case vignettes and CTCA reports from 150 patients with NSTE-ACS were independently reviewed by 50 experienced interventional cardiologists (median 17 years post-qualification; 5103 total case reviews). Agreement on management strategy before and after CTCA was assessed using Fleiss' κ statistic. RESULTS:Based on clinical information alone, respondents chose medical therapy in 13.2% of cases, with poor agreement on management strategy (κ=0.14, 95% CI 0.11 to 0.17). After reviewing CTCA, agreement improved to moderate (κ=0.53, 95% CI 0.48 to 0.58; p<0.001), and medical management was selected in 39.3% (p<0.001). When invasive management was selected post-CTCA, PCI was required in 85% of cases, and a selective angiographic approach was planned in 79%. CONCLUSIONS:Management decisions for post-CABG NSTE-ACS vary widely among experienced cardiologists. Incorporating CTCA into the diagnostic pathway substantially improves consensus, reduces unnecessary invasive angiography and enables targeted, lower-risk procedures. These findings support evaluation of a CTCA-guided strategy in a prospective randomised trial.

AbstractPatients who have previously undergone coronary artery bypass grafting (CABG) may present with non-ST-elevation acute coronary syndromes (NSTE-ACSs). In this setting, guidelines recommend routine invasive angiography. However, patients with CABG were often excluded from key trials that informed contemporary guidelines and invasive angiography is known to be of higher risk in these patients. In this article, the authors review the evidence and propose a trial to address the question, "Should patients with prior CABG who present with NSTE-ACSs routinely undergo invasive angiography?"

Background: In patients with cardiogenic shock (CS), predicting risk of mortality may improve treatment allocation beyond intensive care admission and thereby outcomes. Troponin appears to be a suitable biomarker but has primarily been evaluated in the setting of infarct-related CS, not in heart failure-related CS (HF-CS), which accounts for almost 50% of cases. Objectives: To assess the association of Troponin T with shock severity and mortality in HF-CS patients. Methods: Heart failure-related CS patients treated in 15 tertiary care centres (5 European countries, 2016–2021) were retrospectively enrolled (NCT03313687). Association of baseline high-sensitive Troponin T and its 24-h kinetics with shock severity according to the SCAI classification and with in-hospital mortality was assessed by fitting multivariable adjusted regression models. Results: N = 477 patients (mean age 62 years, 30.2% women). High-sensitive Troponin T at baseline (median 164 ng/l) was significantly associated with in-hospital mortality (HR 1.008, 95%CI 1.002–1.013, p < 0.01). Increasing Troponin within 24 h from baseline indicated a 2.4-fold higher risk of death vs. decreasing Troponin levels (HR 2.439, 95% CI 1.070–5.558, p = 0.03). In addition, higher Troponin T levels correlate with higher SCAI stages (e.g., baseline Troponin T per 250 ng/l increase: OR 5.268, 95%CI: 1.637, 16.953, p < 0.01 for SCAI stage D vs. C). Conclusions: Troponin T, a marker of myocardial injury, associates with shock severity in patients with heart failure-related CS. It predicts mortality both with its baseline value as well as with its 24-h kinetics. Thus, Troponin may be a suitable marker to guide therapy or clinical trial enrolment in these patients. Graphical abstract Central Illustration. Baseline Troponin and its 24-hour kinetics predict all-cause in-hospital mortality in patients with heart failure-related cardiogenic shock. In addition, Troponin associates with shock severity according to the SCAI classification. SCAI: Society for Cardiovascular Angiography and Interventions.

AIMS:Heart failure-related cardiogenic shock (HF-CS) accounts for about half of CS cases, with a paucity of data regarding the role of kidney injury in this subset. This study aims to evaluate patient characteristics and outcome associated with renal function in patients with HF-CS. METHODS AND RESULTS:In this multicentre, international, retrospective study, patients with HF-CS from 16 tertiary care centres in five countries were enrolled between 2010 and 2021. To investigate differences in clinical presentation, complications, and 30-day mortality, based on renal function, adjusted logistic and Cox regression models were fitted. Among 1010 HF-CS patients, the median age was 64 (interquartile range [IQR] 52-75) years, with 71.7% being male. Median baseline creatinine was 1.7 (IQR 1.2-2.5) mg/dl, corresponding to an estimated glomerular filtration rate (eGFR) of 41.0 (IQR 25.2-62.2) ml/min/1.73 m2. In patients with acute kidney injury (AKI), 30-day mortality increased with AKI stages (no AKI 41.7%, AKI stage 1 43.3%, AKI stage 2 50.0%, AKI stage 3 63.7%; adjusted hazard ratio [HR] for AKI stage 3 1.97, 95% confidence interval [CI] 1.56-2.48, p < 0.001). Similarly, severe renal dysfunction (eGFR ≤ median) was associated with a 21% higher 30-day mortality risk (61.0% vs. 40.1%; adjusted HR 1.48, 95% CI 1.20-1.84, p < 0.001). Sepsis and bleeding were associated with both AKI and renal dysfunction, even after adjustment. CONCLUSIONS:In HF-CS, kidney injury is associated with higher 30-day mortality, potentially mediated by bleeding and sepsis. These findings support the consideration of kidney function as a prognostic marker and call for the development and evaluation of kidney-restoring adjunct interventions in HF-CS.

BACKGROUND AND AIMS:Contrast-induced nephropathy (CIN), also known as contrast-associated acute kidney injury (CA-AKI) underlies a significant proportion of the morbidity and mortality following coronary angiographic procedures in high-risk patients and remains a significant unmet need. In pre-clinical studies inorganic nitrate, which is chemically reduced in vivo to nitric oxide, is renoprotective but this observation is yet to be translated clinically. In this study, the efficacy of inorganic nitrate in the prevention of CIN in high-risk patients presenting with acute coronary syndromes (ACS) is reported.METHODS:NITRATE-CIN is a double-blind, randomized, single-centre, placebo-controlled trial assessing efficacy of inorganic nitrate in CIN prevention in at-risk patients presenting with ACS. Patients were randomized 1:1 to once daily potassium nitrate (12 mmol) or placebo (potassium chloride) capsules for 5 days. The primary endpoint was CIN (KDIGO criteria). Secondary outcomes included kidney function [estimated glomerular filtration rate (eGFR)] at 3 months, rates of procedural myocardial infarction, and major adverse cardiac events (MACE) at 12 months. This study is registered with ClinicalTrials.gov: NCT03627130.RESULTS:Over 3 years, 640 patients were randomized with a median follow-up of 1.0 years, 319 received inorganic nitrate with 321 received placebo. The mean age of trial participants was 71.0 years, with 73.3% male and 75.2% Caucasian; 45.9% had diabetes, 56.0% had chronic kidney disease (eGFR <60 mL/min) and the mean Mehran score of the population was 10. Inorganic nitrate treatment significantly reduced CIN rates (9.1%) vs. placebo (30.5%, P < .001). This difference persisted after adjustment for baseline creatinine and diabetes status (odds ratio 0.21, 95% confidence interval 0.13-0.34). Secondary outcomes were improved with inorganic nitrate, with lower rates of procedural myocardial infarction (2.7% vs. 12.5%, P = .003), improved 3-month renal function (between-group change in eGFR 5.17, 95% CI 2.94-7.39) and reduced 1-year MACE (9.1% vs. 18.1%, P = .001) vs. placebo.CONCLUSIONS:In patients at risk of renal injury undergoing coronary angiography for ACS, a short (5 day) course of once-daily inorganic nitrate reduced CIN, improved kidney outcomes at 3 months, and MACE events at 1 year compared to placebo.

BACKGROUND:In patients with previous coronary artery bypass grafting, computed tomography cardiac angiography (CTCA) before invasive coronary angiography (ICA) was demonstrated in the BYPASS-CTCA trial (Randomized Controlled Trial to Assess Whether Computed Tomography Cardiac Angiography Can Improve Invasive Coronary Angiography in Bypass Surgery Patients) to reduce procedure time and incidence of contrast-associated acute kidney injury, with greater levels of patient satisfaction. Patient-related outcomes, utilization of further diagnostic imaging resources, and longer-term incidence of major adverse cardiac events were key secondary end points not yet reported. METHODS:Patients with prior coronary artery bypass grafting referred for ICA were randomized 1:1 to undergo CTCA before ICA or ICA alone and followed up for a median of 3 (2.2-3.4) years. Angina status was assessed using the Seattle Angina Questionnaire and overall quality of life using the EQ-5D-5L. The incidence of noninvasive imaging use and major adverse cardiac events were compared between the 2 groups. RESULTS:In all, 688 patients were randomized, 344 to CTCA+ICA and 344 to ICA only. The mean age of participants was 69.8 years, with 45% undergoing ICA for acute coronary syndromes and the remainder stable angina. At 3 months follow-up, patients in the CTCA+ICA group were more likely to be angina-free (51.7% versus 43.2%; P=0.03) with greater quality of life (EQ-5D-5L index, 81.6 versus 74.4; P=0.001), although these improvements did not persist. At 3 years follow-up, imaging resource use (35.8% versus 45.1%; odds ratio, 0.68 [95% CI, 0.50-0.92]; P=0.013) and incidence of major adverse cardiac events were lower in the CTCA+ICA group (35.8% versus 43.5%; hazard ratio, 0.73 [95% CI, 0.58-0.93]; P=0.010). CONCLUSIONS:In patients with prior coronary artery bypass grafting undergoing ICA, CTCA before ICA leads to reductions in the use of imaging resources and the rate of major cardiac events out to 3 years, but with similar patient-related outcome measures. Together with the initial findings of BYPASS-CTCA, these data are supportive of routinely undertaking a CTCA before ICA in patients with prior coronary artery bypass grafting. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT03736018.

Background Heart failure–related cardiogenic shock (HF-CS) accounts for a significant proportion of all CS cases. Nevertheless, there is a lack of evidence on sex-related differences in HF-CS, especially regarding use of treatment and mortality risk in women vs. men. This study aimed to investigate potential differences in clinical presentation, use of treatments, and mortality between women and men with HF-CS. Methods In this international observational study, patients with HF-CS (without acute myocardial infarction) from 16 tertiary-care centers in five countries were enrolled between 2010 and 2021. Logistic and Cox regression models were used to assess differences in clinical presentation, use of treatments, and 30-day mortality in women vs. men with HF-CS. Results N = 1030 patients with HF-CS were analyzed, of whom 290 (28.2%) were women. Compared to men, women were more likely to be older, less likely to have a known history of heart failure or cardiovascular risk factors, and lower rates of highly depressed left ventricular ejection fraction and renal dysfunction. Nevertheless, CS severity as well as use of treatments were comparable, and female sex was not independently associated with 30-day mortality (53.0% vs. 50.8%; adjusted HR 0.94, 95% CI 0.75–1.19). Conclusions In this large HF-CS registry, sex disparities in risk factors and clinical presentation were observed. Despite these differences, the use of treatments was comparable, and both sexes exhibited similarly high mortality rates. Further research is necessary to evaluate if sex-tailored treatment, accounting for the differences in cardiovascular risk factors and clinical presentation, might improve outcomes in HF-CS. Graphical abstract Sex-related differences in clinical characteristics, shock severity, and mortality in patients with heart failure–related cardiogenic shock. Summary for the main study findings. AMI, acute myocardial infarction; CI, confidence interval; HF-CS, heart failure–related cardiogenic shock; LVEF, left ventricular ejection fraction; MCS, mechanical circulatory support; SCAI, Society for Cardiovascular Angiography & Interventions.

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AimsThe REGENERATE-COBRA trial (NCT05711849) will assess the safety and efficacy of an intracoronary infusion of autologous bone marrow-derived mononuclear cells in refractory angina patients with no revascularization options who are symptomatic despite optimal medical and device therapy.MethodsREGENERATE-COBRA is a single site, blinded, randomized, sham-controlled, Phase II clinical trial enrolling 110 refractory angina patients with no revascularization options who are symptomatic despite optimal medical and device therapy. Patients will be randomized to either autologous bone marrow derived-mononuclear cells or a sham procedure. Patients in the cell-treated arm will undergo a bone marrow aspiration and an intracoronary infusion of autologous bone marrow derived-mononuclear cells. Patients in the control arm will undergo a sham bone marrow aspiration and a sham intracoronary infusion. The trial's primary endpoint is an improvement in Canadian Cardiovascular Society (CCS) angina class by 2 classes between baseline and 6 months. Secondary endpoints include change in: CCS class at 12 months, myocardial ischemic burden (as measured by perfusion imaging) at 6 months, quality of life at 6 and 12 months (as measured by EQ-5D-5L, EQ-5D-VAS and Seattle Angina Questionnaire), angina frequency at 6 and 12 months, total exercise time (as measured by a modified Bruce protocol) and major adverse cardiovascular events at 6 and 12 months.ConclusionsThis is the first trial to assess the safety and efficacy of an intracoronary infusion of autologous bone marrow-derived unfractionated mononuclear cells in symptomatic refractory angina patients who have exhausted conventional therapeutic options.

Aims Heart failure‐related cardiogenic shock (HF‐CS) accounts for a significant proportion of CS cases. Whether patients with de novo HF and those with acute‐on‐chronic HF in CS differ in clinical characteristics and outcome remains unclear. The aim of this study was to evaluate differences in clinical presentation and mortality between patients with de novo and acute‐on‐chronic HF‐CS. Methods and results In this international observational study, patients with HF‐CS from 16 tertiary care centres in five countries were enrolled between 2010 and 2021. To investigate differences in clinical presentation and 30‐day mortality, adjusted logistic/Cox regression models were fitted. Patients ( n = 1030) with HF‐CS were analysed, of whom 486 (47.2%) presented with de novo HF‐CS and 544 (52.8%) with acute‐on‐chronic HF‐CS. Traditional markers of CS severity (e.g. blood pressure, heart rate and lactate) as well as use of treatments were comparable between groups. However, patients with acute‐on‐chronic HF‐CS were more likely to have a higher CS severity and also a higher mortality risk, after adjusting for relevant confounders (de novo HF 45.5%, acute‐on‐chronic HF 55.9%, adjusted hazard ratio 1.38, 95% confidence interval 1.10–1.72, p = 0.005). Conclusion In this large HF‐CS cohort, acute‐on‐chronic HF‐CS was associated with more severe CS and higher mortality risk compared to de novo HF‐CS, although traditional markers of CS severity and use of treatments were comparable. These findings highlight the vast heterogeneity of patients with HF‐CS, emphasize that HF chronicity is a relevant disease modifier in CS, and indicate that future clinical trials should account for this.

BackgroundDespite tremendous therapeutic advancements, a significant proportion of coronary artery disease patients suffer from refractory angina pectoris, that is, quality-of-life-compromising angina that is non-manageable with established pharmacological and interventional treatment options. Adenoviral vascular endothelial growth factor-DΔNΔC(AdVEGF-D)-encoding gene therapy (GT) holds promise for the treatment of refractory angina.MethodsReGenHeart is an investigator-initiated, multicentre, randomised, placebo-controlled and double-blinded phase 2 clinical trial that aims to study the safety and efficacy of intramyocardially administered angiogenic AdVEGF-D GT for refractory angina. Patients will be randomised in a 2:1 ratio and blocks of six to receive either AdVEGF-D or placebo. Primary endpoints are improvements in functional capacity assessed with the 6 min walking test and angina symptoms with Canadian Cardiovascular Society class after 6 month follow-up. Secondary endpoints are improvements in myocardial perfusion assessed with either positron emission tomography or single-photon emission CT after 6 month follow-up and functional capacity and angina symptoms after 12 months. In addition, changes in the quality of life, the use of angina medication and the incidence of major adverse cardiac and cerebrovascular events will be evaluated.ConclusionsThe phase 2 ReGenHeart trial will provide knowledge of the safety and efficacy of AdVEGF-D GT to ameliorate symptoms in refractory angina patients, extending and further testing positive results from the preceding phase 1/2a trial.

Background: Computed tomography cardiac angiography (CTCA) is recommended for the evaluation of patients with prior coronary artery bypass graft (CABG) surgery. The BYPASS-CTCA study demonstrated that CTCA prior to invasive coronary angiography (ICA) in CABG patients leads to signi ficant reductions in procedure time and contrast-induced nephropathy (CIN), alongside improved patient satisfaction. However, whether CTCA information was used to facilitate selective graft cannulation at ICA was not protocol mandated. In this post-hoc analysis we investigated the in fluence of CTCA facilitated selective graft assessment on angiographic parameters and study endpoints. Methods: BYPASS-CTCA was a randomized controlled trial in which patients with previous CABG referred for ICA were randomized to undergo CTCA prior to ICA, or ICA alone. In this post-hoc analysis we assessed the impact of selective ICA (grafts not invasively cannulated based on the CTCA result) following CTCA versus non-selective ICA (imaging all grafts irrespective of CTCA findings). The primary endpoints were ICA procedural duration, incidence of CIN, and patient satisfaction post -ICA. Secondary endpoints included the incidence of procedural complications and 1-year major adverse cardiac events. Results: In the CTCA cohort (n = 343), 214 (62.4%) patients had selective coronary angiography performed, whereas 129 (37.6%) patients had non-selective ICA. Procedure times were signi ficantly reduced in the selective CTCA + ICA group compared to the non-selective CTCA + ICA group (-5.82min, 95% CI -7.99 to -3.65, p < 0.001) along with reduction of CIN (1.5% vs 5.8%, OR 0.26, 95% CI 0.10 to 0.98). No difference was seen in patient satisfaction with the ICA, however procedural complications (0.9% vs 4.7%, OR 0.21, 95% CI 0.09 -0.87) and 1-year major adverse cardiac events (13.1% vs 20.9%, HR 0.55, 95% CI 0.32 -0.96) were signi ficantly lower in the selective group. Conclusions: In patients with prior CABG, CTCA guided selective angiographic assessment of bypass grafts is associated with improved procedural parameters, lower complication rates and better 12-month outcomes. Taken in addition to the main findings of the BYPASS-CTCA trial, these results suggest a synergistic approach between CTCA and ICA should be considered in this patient group. Registration: ClinicalTrials.gov, NCT03736018.

BACKGROUND: Patients with previous coronary artery bypass grafting often require invasive coronary angiography (ICA). However, for these patients, the procedure is technically more challenging and has a higher risk of complications. Observational studies suggest that computed tomography cardiac angiography (CTCA) may facilitate ICA in this group, but this has not been tested in a randomized controlled trial. METHODS: This study was a single-center, open-label randomized controlled trial assessing the benefit of adjunctive CTCA in patients with previous coronary artery bypass grafting referred for ICA. Patients were randomized 1:1 to undergo CTCA before ICA or ICA alone. The co–primary end points were procedural duration of the ICA (defined as the interval between local anesthesia administration for obtaining vascular access and removal of the last catheter), patient satisfaction after ICA using a validated questionnaire, and the incidence of contrast-induced nephropathy. Linear regression was used for procedural duration and patient satisfaction score; contrast-induced nephropathy was analyzed using logistic regression. We applied the Bonferroni correction, with P <0.017 considered significant and 98.33% CIs presented. Secondary end points included incidence of procedural complications and 1-year major adverse cardiac events. RESULTS: Over 3 years, 688 patients were randomized with a median follow-up of 1.0 years. The mean age was 69.8±10.4 years, 108 (15.7%) were women, 402 (58.4%) were White, and there was a high burden of comorbidity (85.3% hypertension and 53.8% diabetes). The median time from coronary artery bypass grafting to angiography was 12.0 years, and there were a median of 3 (interquartile range, 2 to 3) grafts per participant. Procedure duration of the ICA was significantly shorter in the CTCA+ICA group (CTCA+ICA, 18.6±9.5 minutes versus ICA alone, 39.5±16.9 minutes [98.33% CI, −23.5 to −18.4]; P <0.001), alongside improved mean ICA satisfaction scores (1=very good to 5=very poor; −1.1 difference [98.33% CI, −1.2 to −0.9]; P <0.001), and reduced incidence of contrast-induced nephropathy (3.4% versus 27.9%; odds ratio, 0.09 [98.33% CI, 0.04–0.2]; P <0.001). Procedural complications (2.3% versus 10.8%; odds ratio, 0.2 [95% CI, 0.1–0.4]; P <0.001) and 1-year major adverse cardiac events (16.0% versus 29.4%; hazard ratio, 0.4 [95% CI, 0.3–0.6]; P <0.001) were also lower in the CTCA+ICA group. CONCLUSIONS: For patients with previous coronary artery bypass grafting, CTCA before ICA leads to reductions in procedure time and contrast-induced nephropathy, with improved patient satisfaction. CTCA before ICA should be considered in this group of patients. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03736018.