Coronary Artery Calcium Score Predicts Major Adverse Cardiovascular Events in Stable Chest Pain.

Background Coronary artery calcium (CAC) has prognostic value for major adverse cardiovascular events (MACE) in asymptomatic individuals, whereas its role in symptomatic patients is less clear. Purpose To assess the prognostic value of CAC scoring for MACE in participants with stable chest pain initially referred for invasive coronary angiography (ICA). Materials and Methods This prespecified subgroup analysis from the Diagnostic Imaging Strategies for Patients With Stable Chest Pain and Intermediate Risk of Coronary Artery Disease (DISCHARGE) trial, conducted between October 2015 and April 2019 across 26 centers in 16 countries, focused on adult patients with stable chest pain referred for ICA. Participants were randomly assigned to undergo either ICA or coronary CT. CAC scores from noncontrast CT scans were categorized into low, intermediate, and high groups based on scores of 0, 1-399, and 400 or higher, respectively. The end point of the study was the occurrence of MACE (myocardial infarction, stroke, and cardiovascular death) over a median 3.5-year follow-up, analyzed using Cox proportional hazard regression tests. Results The study involved 1749 participants (mean age, 60 years ± 10 [SD]; 992 female). The prevalence of obstructive coronary artery disease (CAD) at CT angiography rose from 4.1% (95% CI: 2.8, 5.8) in the CAC score 0 group to 76.1% (95% CI: 70.3, 81.2) in the CAC score 400 or higher group. Revascularization rates increased from 1.7% to 46.2% across the same groups (P < .001). The CAC score 0 group had a lower MACE risk (0.5%; HR, 0.08 [95% CI: 0.02, 0.30]; P < .001), as did the 1-399 CAC score group (1.9%; HR, 0.27 [95% CI: 0.13, 0.59]; P = .001), compared with the 400 or higher CAC score group (6.8%). No significant difference in MACE between sexes was observed (P = .68). Conclusion In participants with stable chest pain initially referred for ICA, a CAC score of 0 showed very low risk of MACE, and higher CAC scores showed increasing risk of obstructive CAD, revascularization, and MACE at follow-up. Clinical trial registration no. NCT02400229 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Hanneman and Gulsin in this issue.

Effect of Body Mass Index on Effectiveness of CT versus Invasive Coronary Angiography in Stable Chest Pain: The DISCHARGE Trial.

Background Recent trials support the role of cardiac CT in the evaluation of symptomatic patients suspected of having coronary artery disease (CAD); however, body mass index (BMI) has been reported to negatively impact CT image quality. Purpose To compare initial use of CT versus invasive coronary angiography (ICA) on clinical outcomes in patients with stable chest pain stratified by BMI category. Materials and Methods This prospective study represents a prespecified BMI subgroup analysis of the multicenter Diagnostic Imaging Strategies for Patients with Stable Chest Pain and Intermediate Risk of Coronary Artery Disease (DISCHARGE) trial conducted between October 2015 and April 2019. Adult patients with stable chest pain and a CAD pretest probability of 10%-60% were randomly assigned to undergo initial CT or ICA. The primary end point was major adverse cardiovascular events (MACE), including cardiovascular death, nonfatal myocardial infarction, or stroke. The secondary end point was an expanded MACE composite, including transient ischemic attack, and major procedure-related complications. Competing risk analyses were performed using the Fine and Gray subdistribution Cox proportional hazard model to assess the impact of the relationship between BMI and initial management with CT or ICA on the study outcomes, whereas noncardiovascular death and unknown causes of death were considered competing risk events. Results Among the 3457 participants included, 831 (24.0%), 1358 (39.3%), and 1268 (36.7%) had a BMI of less than 25, between 25 and 30, and greater than 30 kg/m2, respectively. No interaction was found between CT or ICA and BMI for MACE (P = .29), the expanded MACE composite (P = .38), or major procedure-related complications (P = .49). Across all BMI subgroups, expanded MACE composite events (CT, 10 of 409 [2.4%] to 23 of 697 [3.3%]; ICA, 26 of 661 [3.9%] to 21 of 422 [5.1%]) and major procedure-related complications during initial management (CT, one of 638 [0.2%] to five of 697 [0.7%]; ICA, nine of 630 [1.4%] to 12 of 422 [2.9%]) were less frequent in the CT versus ICA group. Participants with a BMI exceeding 30 kg/m² exhibited a higher nondiagnostic CT rate (7.1%, P = .044) compared to participants with lower BMI. Conclusion There was no evidence of a difference in outcomes between CT and ICA across the three BMI subgroups. Clinical trial registration no. NCT02400229 © RSNA, 2024 Supplemental material is available for this article.

Impact of smoking in patients with suspected coronary artery disease in the randomised DISCHARGE trial.

OBJECTIVES: To investigate if the effect of cardiac computed tomography (CT) vs. invasive coronary angiography (ICA) on cardiovascular events differs based on smoking status. MATERIALS AND METHODS: This pre-specified subgroup analysis of the pragmatic, prospective, multicentre, randomised DISCHARGE trial (NCT02400229) involved 3561 patients with suspected coronary artery disease (CAD). The primary endpoint was major adverse cardiovascular events (MACE: cardiovascular death, non-fatal myocardial infarction, or stroke). Secondary endpoints included an expanded MACE composite (MACE, transient ischaemic attack, or major procedure-related complications). RESULTS: Of 3445 randomised patients with smoking data (mean age 59.1 years + / - 9.7, 1151 men), at 3.5-year follow-up, the effect of CT vs. ICA on MACE was consistent across smoking groups (p for interaction = 0.98). The percutaneous coronary intervention rate was significantly lower with a CT-first strategy in smokers and former smokers (p = 0.01 for both). A CT-first strategy reduced the hazard of major procedure-related complications (HR: 0.21, 95% CI: 0.03, 0.81; p = 0.045) across smoking groups. In current smokers, the expanded MACE composite was lower in the CT- compared to the ICA-first strategy (2.3% (8) vs 6.0% (18), HR: 0.38; 95% CI: 0.17, 0.88). The rate of non-obstructive CAD was significantly higher in all three smoking groups in the CT-first strategy. CONCLUSION: For patients with stable chest pain referred for ICA, the clinical outcomes of CT were consistent across smoking status. The CT-first approach led to a higher detection rate of non-obstructive CAD and fewer major procedure-related complications in smokers. CLINICAL RELEVANCE STATEMENT: This pre-specified sub-analysis of the DISCHARGE trial confirms that a CT-first strategy in patients with stable chest pain referred for invasive coronary angiography with an intermediate pre-test probability of coronary artery disease is as effective as and safer than invasive coronary angiography, irrespective of smoking status. TRIAL REGISTRATION: ClinicalTrials.gov NCT02400229. KEY POINTS: • No randomised studies have assessed smoking status on CT effectiveness in symptomatic patients referred for invasive coronary angiography. • A CT-first strategy results in comparable adverse events, fewer complications, and increased coronary artery disease detection, irrespective of smoking status. • A CT-first strategy is safe and effective for stable chest pain patients with intermediate pre-test probability for CAD, including never smokers.

Chronic kidney disease stage is associated with the number of risk factors in type 2 diabetes patients (STages Of NEphropathy in type 2 diabetes and Heart Failure - STONE HF).

AIMS: To study the association between risk factors and chronic kidney disease (CKD), and characterize medication use in Finnish primary care type 2 diabetes (T2D) patients. METHODS: Data on clinical characteristics, laboratory measurements, and medications were collected from medical records. The primary outcome measure was notable CKD (stage 3-5, eGFR <60 ml/min/1.73 m2) and/or increased albuminuria. The explanatory variables were individual risk factors and risk factor groups based on their number (0-2, 3-4, 5-6, >7). Spearman's rank correlation coefficient and risk ratio analysis were used to analyze the association between the number of risk factors and CKD stage, and between the number of risk factors and notable CKD, respectively. RESULTS: Altogether, 1335 patients with T2D in 60 Finnish primary care centers were recruited for this cross-sectional study. Three-quarters of T2D patients had 3 risk factors and 36% had ≥ 5 risk factors. Compared to patients with 0-2 risk factors, patients with 3-4, 5-6, and ≥ 7 risk factors had a 5.5-fold, 9.9-fold, and 15.9-fold risk of notable CKD (p < 0.001), respectively. Heart failure was most strongly associated with notable CKD (risk ratio, 3.7; p < 0.001). CONCLUSIONS: Number of risk factors was strongly associated with advanced-stage CKD.

Computed Tomography Versus Invasive Coronary Angiography in Patients With Diabetes and Suspected Coronary Artery Disease.

OBJECTIVE: To compare cardiac computed tomography (CT) with invasive coronary angiography (ICA) as the initial strategy in patients with diabetes and stable chest pain. RESEARCH DESIGN AND METHODS: This prespecified analysis of the multicenter DISCHARGE trial in 16 European countries was performed in patients with stable chest pain and intermediate pretest probability of coronary artery disease. The primary end point was a major adverse cardiac event (MACE) (cardiovascular death, nonfatal myocardial infarction, or stroke), and the secondary end point was expanded MACE (including transient ischemic attacks and major procedure-related complications). RESULTS: Follow-up at a median of 3.5 years was available in 3,541 patients of whom 557 (CT group n = 263 vs. ICA group n = 294) had diabetes and 2,984 (CT group n = 1,536 vs. ICA group n = 1,448) did not. No statistically significant diabetes interaction was found for MACE (P = 0.45), expanded MACE (P = 0.35), or major procedure-related complications (P = 0.49). In both patients with and without diabetes, the rate of MACE did not differ between CT and ICA groups. In patients with diabetes, the expanded MACE end point occurred less frequently in the CT group than in the ICA group (3.8% [10 of 263] vs. 8.2% [24 of 294], hazard ratio [HR] 0.45 [95% CI 0.22-0.95]), as did the major procedure-related complication rate (0.4% [1 of 263] vs. 2.7% [8 of 294], HR 0.30 [95% CI 0.13 - 0.63]). CONCLUSIONS: In patients with diabetes referred for ICA for the investigation of stable chest pain, a CT-first strategy compared with an ICA-first strategy showed no difference in MACE and may potentially be associated with a lower rate of expanded MACE and major procedure-related complications.

Comparative effectiveness of initial computed tomography and invasive coronary angiography in women and men with stable chest pain and suspected coronary artery disease: multicentre randomised trial.

OBJECTIVE: To assess the comparative effectiveness of computed tomography and invasive coronary angiography in women and men with stable chest pain suspected to be caused by coronary artery disease. DESIGN: Prospective, multicentre, randomised pragmatic trial. SETTING: Hospitals at 26 sites in 16 European countries. PARTICIPANTS: 2002 (56.2%) women and 1559 (43.8%) men (total of 3561 patients) with suspected coronary artery disease referred for invasive coronary angiography on the basis of stable chest pain and a pre-test probability of obstructive coronary artery disease of 10-60%. INTERVENTION: Both women and men were randomised 1:1 (with stratification by gender and centre) to a strategy of either computed tomography or invasive coronary angiography as the initial diagnostic test (1019 and 983 women, and 789 and 770 men, respectively), and an intention-to-treat analysis was performed. Randomised allocation could not be blinded, but outcomes were assessed by investigators blinded to randomisation group. MAIN OUTCOME MEASURES: The primary endpoint was major adverse cardiovascular events (MACE; cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke). Key secondary endpoints were an expanded MACE composite (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, transient ischaemic attack, or major procedure related complication) and major procedure related complications. RESULTS: Follow-up at a median of 3.5 years was available in 98.9% (1979/2002) of women and in 99.0% (1544/1559) of men. No statistically significant gender interaction was found for MACE (P=0.29), the expanded MACE composite (P=0.45), or major procedure related complications (P=0.11). In both genders, the rate of MACE did not differ between the computed tomography and invasive coronary angiography groups. In men, the expanded MACE composite endpoint occurred less frequently in the computed tomography group than in the invasive coronary angiography group (22 (2.8%) v 41 (5.3%); hazard ratio 0.52, 95% confidence interval 0.31 to 0.87). In women, the risk of having a major procedure related complication was lower in the computed tomography group than in the invasive coronary angiography group (3 (0.3%) v 21 (2.1%); hazard ratio 0.14, 0.04 to 0.46). CONCLUSION: This study found no evidence for a difference between women and men in the benefit of using computed tomography rather than invasive coronary angiography as the initial diagnostic test for the management of stable chest pain in patients with an intermediate pre-test probability of coronary artery disease. An initial computed tomography scan was associated with fewer major procedure related complications in women and a lower frequency of the expanded MACE composite in men. TRIAL REGISTRATION: NCT02400229ClinicalTrials.gov NCT02400229.

The majority of type 2 diabetic patients in Finnish primary care are at very high risk of cardiovascular events: A cross-sectional chart review study (STONE HF).

AIMS: To characterize clinical profiles, prevalence of chronic kidney disease (CKD), and treatment patterns in type 2 diabetes (T2D) and heart failure (HF) patients in Finnish primary care. METHODS: A total of 1385 patients (1196 with T2D, 50 with HF, and 139 with T2D and HF) in 60 Finnish primary care centers were recruited to this cross-sectional study. Data on demographic and clinical characteristics, laboratory measurements, and medications were collected retrospectively from medical records. T2D patients were classified according to their risk of cardiovascular (CV) events as very high-risk (62%) and other patients (38%). RESULTS: Of the T2D patients, 10% (139/1335) had a diagnosis of HF and 42% (457/1090) had stage 3-5 CKD and/or albuminuria based on laboratory measurement. Of the HF patients, 74% (139/189) had T2D and 78% (114/146) had stage 3-5 CKD and/or albuminuria. Metformin was the most frequently used medication in both very high-risk patients (74%) and other patients (86%). SGLT2 inhibitors and/or GLP-1 analogues were used by 37% of very high-risk patients compared to 42% in other patients. CONCLUSIONS: The majority of T2D patients in Finnish primary care are at very high risk of cardiovascular events. However, the implementation of treatments with proven cardioprotective effects in very high-risk patients is currently suboptimal.

Effect of Inhaled Xenon on Cardiac Function in Comatose Survivors of Out-of-Hospital Cardiac Arrest-A Substudy of the Xenon in Combination With Hypothermia After Cardiac Arrest Trial.

This explorative substudy aimed at determining the effect of inhaled xenon on left ventricular function by echocardiography in comatose survivors of out-of-hospital cardiac arrest. DESIGN: A randomized two-group single-blinded phase 2 clinical drug trial. SETTING: A multipurpose ICU in two university hospitals. PATIENTS: Of the 110 randomized comatose survivors after out-of-hospital cardiac arrest with a shockable rhythm in the xenon in combination with hypothermia after cardiac arrest trial, 38 patients (24-76 yr old) with complete echocardiography were included in this study. INTERVENTIONS: Patients were randomized to receive either inhaled xenon combined with hypothermia (33°C) for 24 hours or hypothermia treatment alone. Echocardiography was performed at hospital admission and 24 ± 4 hours after hypothermia. MEASUREMENTS AND MAIN RESULTS: Left ventricular ejection fraction, myocardial longitudinal systolic strain, and diastolic function were analyzed blinded to treatment. There were 17 xenon and 21 control patients in whom echocardiography was completed. Clinical characteristics did not differ significantly between the groups. At admission, ejection fraction was similar in xenon and control patients (39% ± 10% vs 38% ± 11%; p = 0.711) but higher in xenon than control patients after hypothermia (50% ± 10% vs 42% ± 10%; p = 0.014). Global longitudinal systolic strain was similar in xenon and control patients at admission (-9.0% ± 3.8% vs -8.1% ± 3.6%; p = 0.555) but better in xenon than control patients after hypothermia (-14.4.0% ± 4.0% vs -10.5% ± 4.0%; p = 0.006). In patients with coronary artery disease, longitudinal strain improved in the nonischemic myocardial segments in xenon patients. There were no changes in diastolic function between the groups. CONCLUSIONS: Among comatose survivors of a cardiac cause out-of-hospital cardiac arrest, inhaled xenon combined with hypothermia was associated with greater recovery of left ventricular systolic function in comparison with hypothermia alone.

Clinical pre-test probability for obstructive coronary artery disease: insights from the European DISCHARGE pilot study.

OBJECTIVES: To test the accuracy of clinical pre-test probability (PTP) for prediction of obstructive coronary artery disease (CAD) in a pan-European setting. METHODS: Patients with suspected CAD and stable chest pain who were clinically referred for invasive coronary angiography (ICA) or computed tomography (CT) were included by clinical sites participating in the pilot study of the European multi-centre DISCHARGE trial. PTP of CAD was determined using the Diamond-Forrester (D+F) prediction model initially introduced in 1979 and the updated D+F model from 2011. Obstructive coronary artery disease (CAD) was defined by one at least 50% diameter coronary stenosis by both CT and ICA. RESULTS: In total, 1440 patients (654 female, 786 male) were included at 25 clinical sites from May 2014 until July 2017. Of these patients, 725 underwent CT, while 715 underwent ICA. Both prediction models overestimated the prevalence of obstructive CAD (31.7%, 456 of 1440 patients, PTP: initial D+F 58.9% (28.1-90.6%), updated D+F 47.3% (34.2-59.9%), both p < 0.001), but overestimation of disease prevalence was higher for the initial D+F (p < 0.001). The discriminative ability was higher for the updated D+F 2011 (AUC of 0.73 95% confidence interval [CI] 0.70-0.76 versus AUC of 0.70 CI 0.67-0.73 for the initial D+F; p < 0.001; odds ratio (or) 1.55 CI 1.29-1.86, net reclassification index 0.11 CI 0.05-0.16, p < 0.001). CONCLUSIONS: Clinical PTP calculation using the initial and updated D+F prediction models relevantly overestimates the actual prevalence of obstructive CAD in patients with stable chest pain clinically referred for ICA and CT suggesting that further refinements to improve clinical decision-making are needed. TRIAL REGISTRATION: https://www.clinicaltrials.gov/ct2/show/NCT02400229 KEY POINTS: • Clinical pre-test probability calculation using the initial and updated D+F model overestimates the prevalence of obstructive CAD identified by ICA and CT. • Overestimation of disease prevalence is higher for the initial D+F compared with the updated D+F. • Diagnostic accuracy of PTP assessment varies strongly between different clinical sites throughout Europe.

Cardiovascular event rates increase after each recurrence and associate with poor statin adherence.

AIMS: The study evaluated the quality of cardiovascular prevention in real-world clinical practice. The recurrence of up to five cardiovascular events was assessed, as data on recurrence beyond the first event and interindividual variations in event rates past the second event have been sparse. Low-density lipoprotein cholesterol concentrations and lipid-lowering therapy use were investigated. METHODS: This retrospective register-based study included adult patients with an incident cardiovascular event between 2004 and 2016 treated in the hospital district of southwest Finland. Patients were followed for consecutive cardiovascular events or cardiovascular death, low-density lipoprotein cholesterol and statin purchases. The timing of event recurrence was evaluated, and predictive factors were assessed. RESULTS: A wide interindividual variation in cardiovascular event recurrence was observed, each additional event caused an increased risk, the median time of recurrence decreased from 7 to one year for the second and fifth event. Event rates increased correspondingly from 12 to 43/100 patient-years and were most pronounced in the first years following the previous event. The low-density lipoprotein cholesterol goal (<1.8 mmol/l) was reached by 18% in the year after the event and statin underuse was associated with an increased risk of recurrence. Six months after the index event high intensity statins were used by only 22% of the cohort. CONCLUSION: The study provides new perspectives on individual risk assessment showing that event rates are not stable for all patients but increase 1.2-1.9-fold per consecutive event. The underuse of statins and poor adherence support the identification of these patients for intensified multifactorial preventive measures.

Assessment of myocardial viability with [15O]water PET: A validation study in experimental myocardial infarction.

BACKGROUND: Assessment of myocardial viability is often needed in patients with chest pain and reduced ejection fraction. We evaluated the performance of reduced resting MBF, perfusable tissue fraction (PTF), and perfusable tissue index (PTI) in the assessment of myocardial viability in a pig model of myocardial infarction (MI). METHODS AND RESULTS: Pigs underwent resting [15O]water PET perfusion study 12 weeks after surgical (n = 16) or 2 weeks after catheter-based (n = 4) occlusion of the proximal left anterior descending coronary artery. MBF, PTF, and PTI were compared with volume fraction of MI in matched segments as assessed by triphenyl tetrazolium chloride staining of LV slices. MBF and PTF were lower in infarcted than non-infarcted segments. Segmental analysis of MBF showed similar area under the curve (AUC) of 0.85, 0.86, and 0.90 with relative MBF, PTF, and PTI for the detection of viable myocardium defined as infarct volume fraction of < 75%. Cut-off values of relative MBF of ≥ 67% and PTF of ≥ 66% resulted in accuracies of 90% and 81%, respectively. CONCLUSIONS: Our results indicate that resting MBF, PTF, and PTI based on [15O]water PET perfusion imaging are useful for the assessment of myocardial viability.

Full feature selection for estimating KAP radiation dose in coronary angiographies and percutaneous coronary interventions.

In interventional cardiology (IC) the radiation dose variation is very significant, and its estimation has been difficult due to the complexity of the treatments. In order to tackle this problem, the aim of this study was to identify the most important demographic and clinical features to estimate Kerma-Area Product (KAP) radiation dose in coronary angiographies (CA) and percutaneous coronary interventions (PCI). The study was retrospective using clinical patient data from 838 CA and PCI procedures. A total of 59 features were extracted from the patient data and 9 different filter-based feature selection methods were used to select the most informative features in terms of the KAP radiation dose from the treatments. The selected features were then used in a support vector regression (SVR) model to evaluate their performance in estimating the radiation dose. The ten highest-ranking features were: (1) FN1AC (CA), (2) FN2BA (PCI), (3) weight, (4) post-stenosis 0%, (5) multi-vessel disease, (6) number of procedures 3, (7) pre-stenosis 100%, (8) American Heart Association (AHA) score C, (9) pre-stenosis 85% and (10) gender. The performance of the SVR model increased (mean squared error ≈ 450) with the number of features approximately up to 30 features. The identification of the most informative features for CA and PCI KAP is an important step in determining suitable complexity models for clinical practice. The highest-ranking features can be used as individual predictors of IC procedure KAP or can be incorporated into combined complexity score or different estimation models in the future.

Correction to: Pilot study of the multicentre DISCHARGE trial: image quality and protocol adherence results of computed tomography and invasive coronary angiography.

The original version of this article, published on 16 December 2019, unfortunately contained two mistakes.

Randomised comparison of provisional side branch stenting versus a two-stent strategy for treatment of true coronary bifurcation lesions involving a large side branch: the Nordic-Baltic Bifurcation Study IV.

Background: It is still uncertain whether coronary bifurcations with lesions involving a large side branch (SB) should be treated by stenting the main vessel and provisional stenting of the SB (simple) or by routine two-stent techniques (complex). We aimed to compare clinical outcome after treatment of lesions in large bifurcations by simple or complex stent implantation. Methods: The study was a randomised, superiority trial. Enrolment required a SB≥2.75 mm, ≥50% diameter stenosis in both vessels, and allowed SB lesion length up to 15 mm. The primary endpoint was a composite of cardiac death, non-procedural myocardial infarction and target lesion revascularisation at 6 months. Two-year clinical follow-up was included in this primary reporting due to lower than expected event rates. Results: A total of 450 patients were assigned to simple stenting (n=221) or complex stenting (n=229) in 14 Nordic and Baltic centres. Two-year follow-up was available in 218 (98.6%) and 228 (99.5%) patients, respectively. The primary endpoint of major adverse cardiac events (MACE) at 6 months was 5.5% vs 2.2% (risk differences 3.2%, 95% CI -0.2 to 6.8, p=0.07) and at 2 years 12.9% vs 8.4% (HR 0.63, 95% CI 0.35 to 1.13, p=0.12) after simple versus complex treatment. In the subgroup treated by newer generation drug-eluting stents, MACE was 12.0% vs 5.6% (HR 0.45, 95% CI 0.17 to 1.17, p=0.10) after simple versus complex treatment. Conclusion: In the treatment of bifurcation lesions involving a large SB with ostial stenosis, routine two-stent techniques did not improve outcome significantly compared with treatment by the simpler main vessel stenting technique after 2 years. Trial registration number: NCT01496638.

Pilot study of the multicentre DISCHARGE Trial: image quality and protocol adherence results of computed tomography and invasive coronary angiography.

OBJECTIVE: To implement detailed EU cardiac computed tomography angiography (CCTA) quality criteria in the multicentre DISCHARGE trial (FP72007-2013, EC-GA 603266), we reviewed image quality and adherence to CCTA protocol and to the recommendations of invasive coronary angiography (ICA) in a pilot study. MATERIALS AND METHODS: From every clinical centre, imaging datasets of three patients per arm were assessed for adherence to the inclusion/exclusion criteria of the pilot study, predefined standards for the CCTA protocol and ICA recommendations, image quality and non-diagnostic (NDX) rate. These parameters were compared via multinomial regression and ANOVA. If a site did not reach the minimum quality level, additional datasets had to be sent before entering into the final accepted database (FADB). RESULTS: We analysed 226 cases (150 CCTA/76 ICA). The inclusion/exclusion criteria were not met by 6 of the 226 (2.7%) datasets. The predefined standard was not met by 13 of 76 ICA datasets (17.1%). This percentage decreased between the initial CCTA database and the FADB (multinomial regression, 53 of 70 vs 17 of 75 [76%] vs [23%]). The signal-to-noise ratio and contrast-to-noise ratio of the FADB did not improve significantly (ANOVA, p = 0.20; p = 0.09). The CTA NDX rate was reduced, but not significantly (initial CCTA database 15 of 70 [21.4%]) and FADB 9 of 75 [12%]; p = 0.13). CONCLUSION: We were able to increase conformity to the inclusion/exclusion criteria and CCTA protocol, improve image quality and decrease the CCTA NDX rate by implementing EU CCTA quality criteria and ICA recommendations. KEY POINTS: • Failure to meet protocol adherence in cardiac CTA was high in the pilot study (77.6%). • Image quality varies between sites and can be improved by feedback given by the core lab. • Conformance with new EU cardiac CT quality criteria might render cardiac CTA findings more consistent and comparable.

Drug-coated balloon for treatment of de-novo coronary artery lesions in patients with high bleeding risk (DEBUT): a single-blind, randomised, non-inferiority trial.

BACKGROUND: The optimal technique of percutaneous coronary intervention in patients at high bleeding risk is not known. The hypothesis of the DEBUT trial was that percutaneous coronary intervention with drug-coated balloons is non-inferior to percutaneous coronary intervention with bare-metal stents for this population. METHODS: The DEBUT trial is a randomised, single-blind non-inferiority trial done at five sites in Finland. Patients were eligible if they had an ischaemic de-novo lesion in a coronary artery or bypass graft that could be treated with drug-coated balloons, at least one risk factor for bleeding, and a reference vessel diameter of 2·5-4·0 mm. Those with myocardial infarction with ST-elevation, bifurcation lesions needing a two-stent technique, in-stent restenosis, and flow-limiting dissection or substantial recoil (>30%) of the target lesion after predilation were excluded. After successful predilation of the target lesion, patients were randomly assigned (1:1), by use of a computer-generated random sequence, to percutaneous coronary intervention with a balloon coated with paclitaxel and iopromide or a bare-metal stent. The primary outcome was major adverse cardiac events at 9 months. Non-inferiority was shown if the absolute risk difference was no more than 3%. All prespecified analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01781546. FINDINGS: Between May 22, 2013, and Jan 16, 2017, 220 patients were recruited for the study and 208 patients were assigned to percutaneous coronary intervention with drug-coated balloon (n=102) or bare metal stent (n=106). At 9 months, major adverse cardiac events had occurred in one patient (1%) in the drug-coated balloon group and in 15 patients (14%) in the bare-metal stent group (absolute risk difference -13·2 percentage points [95% CI -6·2 to -21·1], risk ratio 0·07 [95% CI 0·01 to 0·52]; p<0·00001 for non-inferiority and p=0·00034 for superiority). Two definitive stent thrombosis events occurred in the bare metal stent group but no acute vessel closures in the drug-coated balloon group. INTERPRETATIONS: Percutaneous coronary intervention with drug-coated balloon was superior to bare-metal stents in patients at bleeding risk. The drug-coated balloon-only coronary intervention is a novel strategy to treat this difficult patient population. Comparison of this approach to the new generation drug-eluting stents is warranted in the future. FUNDING: B Braun Medical AG, AstraZeneca, and Competitive State Research Funding of the Kuopio University Hospital Catchment Area.

Inhaled Xenon Attenuates Myocardial Damage in Comatose Survivors of Out-of-Hospital Cardiac Arrest: The Xe-Hypotheca Trial.

BACKGROUND: The authors previously reported that inhaled xenon combined with hypothermia attenuates brain white matter injury in comatose survivors of out-of-hospital cardiac arrest (OHCA). OBJECTIVES: A pre-defined secondary objective was to assess the effect of inhaled xenon on myocardial ischemic damage in the same study population. METHODS: A total of 110 comatose patients who had experienced OHCA from a cardiac cause were randomized to receive either inhaled xenon (40% end-tidal concentration) combined with hypothermia (33°C) for 24 h (n = 55; xenon group) or hypothermia treatment alone (n = 55; control group). Troponin-T levels were measured at hospital admission, and at 24 h, 48 h, and 72 h post-cardiac arrest. All available cases were analyzed for troponin-T release. RESULTS: Troponin-T measurements were available from 54 xenon patients and 54 control patients. The baseline characteristics did not differ significantly between the groups. After adjustments for age, sex, study site, primary coronary percutaneous intervention (PCI), and norepinephrine dose, the mean ± SD post-arrival incremental change of the ln-transformed troponin-T at 72 h was 0.79 ± 1.54 in the xenon group and 1.56 ± 1.38 in the control group (adjusted mean difference -0.66; 95% confidence interval: -1.16 to -0.16; p = 0.01). The effect of xenon on the change in the troponin-T values did not differ in patients with or without PCI or in those with a diagnosis of ST-segment elevation myocardial infarction (group by PCI or ST-segment elevation myocardial infarction interaction effect; p = 0.86 and p = 0.71, respectively). CONCLUSIONS: Among comatose survivors of OHCA, in comparison with hypothermia alone, inhaled xenon combined with hypothermia suggested a less severe myocardial injury as demonstrated by the significantly reduced release of troponin-T.

Frequency and angiographic characteristics of coronary microvascular dysfunction in stable angina: a hybrid imaging study.

AIMS: Coronary microvascular dysfunction (CMD) can cause angina in the absence of obstructive coronary artery disease (CAD). We studied the frequency and angiographic characteristics of CMD in symptomatic patients with suspected stable CAD and identified CMD as diffusely abnormal coronary vasodilator capacity by positron emission tomography (PET) perfusion imaging. METHODS AND RESULTS: We recruited prospectively 189 patients with intermediate pre-test probability of CAD who underwent coronary computed tomography angiography and quantitative 15O-water PET perfusion imaging followed by invasive coronary angiography, and assessment of fractional flow reserve when feasible. Prevalence of obstructive epicardial CAD was 37%. Absolute myocardial blood flow was diffusely reduced (<2.4 mL/g/min) within the left ventricle during adenosine stress in 32 (17%) patients. In 15 (8%) patients, this was explained by three-vessel obstructive CAD, whereas the remaining 17 (9%) were diagnosed with CMD. Of these, 2 (1% of all patients) had no coronary atherosclerosis, 5 (3% of all patients) had non-obstructive atherosclerosis, and in 10 (5% of all patients) CMD co-existed with obstructive CAD. Atypical angina or non-anginal chest pain (53%) was the most common presentation. Older age and male sex were associated with CMD, but other risk factors of CAD were equally common in patients with or without CMD. CONCLUSION: Coronary microvascular dysfunction exists in 9% of symptomatic stable patients with suspected CAD. However, the prevalence of microvascular dysfunction without any coronary atherosclerosis is low (1%) in this population.

Outcome of poor initial TIMI flow in patients presenting with acute coronary syndrome.

OBJECTIVES: We explored the predictors and outcome of poor, versus good, initial TIMI flow in patients with acute coronary syndrome (ACS). DESIGN: We performed post-hoc analysis of a randomized trial of patients presenting with ACS who received 2 comparative stents. Poor initial TIMI flow was defined as baseline TIMI flow grade 0/1 at the initial coronary angiography. The primary endpoint was major adverse cardiac events (MACE): a composite of cardiac death, non-fatal myocardial infarction or ischemia-driven target lesion revascularization. Stent thrombosis (ST) was adjudicated according to the criteria of definite ST described by the Academic Research Consortium. Propensity score-matched analysis was performed. We report data after 5-year follow-up. RESULTS: Of 827 patients enrolled, 279 (33.7%) had initial TIMI 0/1 flow. Median follow-up duration was 5.0 years. Presentation by ST-elevation myocardial infarction and target vessel other than left anterior descending artery predicted initial TIMI 0/1 flow. MACE rate was comparable between the 2 subgroups (14% versus 15.9%, in patients with poor versus good initial TIMI flow, respectively, p = .46). Individual endpoints were comparable (p > .05 for all). Definite ST was more frequent in patients with initial TIMI 0/1 flow (3.6% versus 1.5%, respectively, p = .048). This was driven by more frequent early events (30 days) (p = .036); late/very late events were comparable (p = 1.0). CONCLUSIONS: Predictors of poor initial TIMI flow included presentation by ST-elevation myocardial infarction, and target vessel other than left anterior descending artery. Definite ST occurred more in patients with poor, versus good, initial TIMI flow, mainly driven by difference in early events.