Immediate versus staged complete revascularisation in patients presenting with acute coronary syndrome and multivessel coronary disease (BIOVASC): a prospective, open-label, non-inferiority, randomised trial.

BACKGROUND: In patients with acute coronary syndrome and multivessel coronary disease, complete revascularisation by percutaneous coronary intervention (PCI) is associated with improved clinical outcomes. We aimed to investigate whether PCI for non-culprit lesions should be attempted during the index procedure or staged. METHODS: This prospective, open-label, non-inferiority, randomised trial was done at 29 hospitals across Belgium, Italy, the Netherlands, and Spain. We included patients aged 18-85 years presenting with ST-segment elevation myocardial infarction or non-ST-segment elevation acute coronary syndrome and multivessel (ie, two or more coronary arteries with a diameter of 2·5 mm or more and ≥70% stenosis based on visual estimation or positive coronary physiology testing) coronary artery disease with a clearly identifiable culprit lesion. A web-based randomisation module was used to randomly assign patients (1:1), with a random block size of four to eight, stratified by study centre, to undergo immediate complete revascularisation (PCI of the culprit lesion first, followed by other non-culprit lesions deemed to be clinically significant by the operator during the index procedure) or staged complete revascularisation (PCI of only the culprit lesion during the index procedure and PCI of all non-culprit lesions deemed to be clinically significant by the operator within 6 weeks after the index procedure). The primary outcome was the composite of all-cause mortality, myocardial infarction, any unplanned ischaemia-driven revascularisation, or cerebrovascular events at 1 year after the index procedure. Secondary outcomes included all-cause mortality, myocardial infarction, and unplanned ischaemia-driven revascularisation at 1 year after the index procedure. Primary and secondary outcomes were assessed in all randomly assigned patients by intention to treat. Non-inferiority of immediate to staged complete revascularisation was considered to be met if the upper boundary of the 95% CI of the hazard ratio (HR) for the primary outcome did not exceed 1·39. This trial is registered with ClinicalTrials.gov, NCT03621501. FINDINGS: Between June 26, 2018, and Oct 21, 2021, 764 patients (median age 65·7 years [IQR 57·2-72·9] and 598 [78·3%] males) were randomly assigned to the immediate complete revascularisation group and 761 patients (median age 65·3 years [58·6-72·9] and 589 [77·4%] males) were randomly assigned to the staged complete revascularisation group, and were included in the intention-to-treat population. The primary outcome at 1 year occurred in 57 (7·6%) of 764 patients in the immediate complete revascularisation group and in 71 (9·4%) of 761 patients in the staged complete revascularisation group (HR 0·78, 95% CI 0·55-1·11, pnon-inferiority=0·0011). There was no difference in all-cause death between the immediate and staged complete revascularisation groups (14 [1·9%] vs nine [1·2%]; HR 1·56, 95% CI 0·68-3·61, p=0·30). Myocardial infarction occurred in 14 (1·9%) patients in the immediate complete revascularisation group and in 34 (4·5%) patients in the staged complete revascularisation group (HR 0·41, 95% CI 0·22-0·76, p=0·0045). More unplanned ischaemia-driven revascularisations were performed in the staged complete revascularisation group than in the immediate complete revascularisation group (50 [6·7%] patients vs 31 [4·2%] patients; HR 0·61, 95% CI 0·39-0·95, p=0·030). INTERPRETATION: In patients presenting with acute coronary syndrome and multivessel disease, immediate complete revascularisation was non-inferior to staged complete revascularisation for the primary composite outcome and was associated with a reduction in myocardial infarction and unplanned ischaemia-driven revascularisation. FUNDING: Erasmus University Medical Center and Biotronik.

One-year clinical and computed tomography follow-up after implantation of bioresorbable vascular scaffolds in patients with coronary chronic total occlusions.

OBJECTIVES: To assess the safety and efficacy of everolimus-eluting bioresorbable scaffolds (BRS) in the treatment of chronic total occlusions (CTO) using noninvasive multislice computed tomography (MSCT) angiography at one-year follow-up. BACKGROUND: Current evidence regarding the safety and efficacy of BRS for the percutaneous treatment of CTO is limited. METHODS: Between September 2013 and January 2016, patients who received one or more ABSORB BRSs were included at three centers. MSCT (including quantitative analysis) and clinical follow-up were performed at one year. RESULTS: Forty-one CTO patients were included. Mean age was 60 ± 11 years and the majority was male (83%). Average Japanese CTO (J-CTO) score was 0.9 ± 0.9. Seventy-one BRS were implanted in total with, on average, 1.7 ± 0.8 scaffolds/patient, and a total length of 43 ± 20 mm and diameter of 3.1 ± 0.4 mm. One noncardiac death took place. MSCT angiography was performed in 34 (83%) patients: all scaffolds were patent, except in one patient, in whom a patent target vessel was present on subsequent diagnostic angiography. MSCT quality was sufficient for quantitative analyses in 27 patients (46 scaffolds): median reference versus scaffold minimal lumen diameter and minimal lumen area were measured, and showed a small difference of 0.1 mm (-0.2-0.4) (lumen diameter stenosis = 3.0%) and 0.5 mm2 (-1.0-2.0) (lumen area stenosis = 4.2%). CONCLUSIONS: The low number of events and high patency rate at 1 year are encouraging the further use of the ABSORB scaffold for CTOs with low J-CTO score. Noninvasive MSCT angiography is a valid tool to assess scaffold patency, although its image resolution limits the use for quantitative measurements.

First prospective multicenter experience with the 7 French Glidesheath slender for complex transradial coronary interventions.

PURPOSE: To assess the feasibility and safety of the 7 French (Fr) Glidesheath Slender for complex transradial (TR) percutaneous coronary interventions (PCI). BACKGROUND: The TR approach is increasingly used worldwide for coronary and peripheral vascular interventions. However, the small size of the radial artery remains an important limitation for the use of large-bore guiding catheters (>6 Fr), restricting thereby the treatment of highly complex lesions through the TR approach. The 7 Fr Glidesheath slender (Terumo, Tokyo, Japan) is a new dedicated radial sheath with a thinner wall and hydrophilic coating. It combines an inner diameter compatible with any 7 Fr guiding catheter and an outer diameter smaller than current 7 Fr sheaths. METHODS: Prospective multicenter registry of complex TR PCI cases using the 7 Fr Glidesheath Slender to determine the procedural success, rates of vascular complications, radial spasm, and radial artery occlusion (RAO). RESULTS: A total of 60 patients were included. Procedural success was 97% with only one access-site crossover. The use of a 7 Fr guiding catheter was indicated for the treatment of highly complex coronary lesions including distal left main (LM) disease (n = 20), complex non-LM bifurcation lesions (n = 16), chronic total occlusion (n = 15), and severely calcified vessels requiring rotational atherectomy (n = 10). There were three vascular access-site complications (4.7%) including two moderate (type II) local hematoma and one uncomplicated guiding catheter-induced brachial artery dissection. None of the patients experienced major bleeding. The occurrence of radial spasm was reported in seven patients (11%). Doppler ultrasound imaging of the radial artery at 1 month was available in 62 of 64 radial access with three cases of RAO (4.8%). CONCLUSIONS: Use of the 7 Fr Glidesheath slender for complex coronary interventions is feasible and associated with a high rate of procedural success and a low rate of vascular complications. These favorable results need be confirmed in larger multicenter studies. © 2016 Wiley Periodicals, Inc.

Evolving concepts of angiogram: fractional flow reserve discordances in 4000 coronary stenoses.

AIMS: The present analysis addresses the potential clinical and physiologic significance of discordance in severity of coronary artery disease between the angiogram and fractional flow reserve (FFR) in a large and unselected patient population. METHODS AND RESULTS: Between September 1999 and December 2011, FFR and percent diameter stenosis (DS) as assessed by quantitative coronary angiography were obtained in 2986 patients (n = 4086 coronary stenoses), in whom at least one stenosis was of intermediate angiographic severity. Fractional flow reserve correlated slightly but significantly with DS [-0.38 (95% CI: -0.41; -0.36); P < 0.001]. The sensitivity, specificity, and diagnostic accuracy of a ≥ 50% DS for predicting FFR ≤ 0.80 were 61% (95% CI: 59; 63), 67% (95% CI: 65; 69), and 0.64 (95% CI: 0.56; 0.72), respectively. In different anatomical settings, sensitivity and specificity showed marked variations between 35 to 74% and 58 to 76%, respectively, resulting in a discordance in 35% of all cases for these thresholds. For an angiographic threshold of 70% DS, the diagnostic performance by the Youden's index decreased from 0.28 to 0.11 for the overall population. CONCLUSION: The data confirm that one-third of a large patient population shows discordance between angiogram ≥ 50%DS and FFR ≤ 0.8 thresholds of stenosis severity. Left main stenoses are often underestimated by the classical 50% DS cut-off compared with FFR. This discordance offers physiologic insights for future trials. It is hypothesized that the discordance between angiography and FFR is related to technical limitations, such as imprecise luminal border detection by angiography, as well as to physiologic factors, such as variable minimal microvascular resistance.

Fractional flow reserve-guided versus angiography-guided coronary artery bypass graft surgery.

BACKGROUND: Fractional flow reserve (FFR) is well established for patients undergoing percutaneous coronary intervention, yet little is known about candidates for coronary artery bypass graft surgery. METHODS AND RESULTS: From 2006 to 2010, we retrospectively included in this registry 627 consecutive patients treated by coronary artery bypass graft surgery having at least 1 angiographically intermediate stenosis. In 429 patients, coronary artery bypass graft surgery was based solely on angiography (angiography-guided group). In 198 patients, at least 1 intermediate stenosis was grafted with an FFR ≤0.80 or deferred with an FFR >0.80 (FFR-guided group). The end point was major adverse cardiovascular events at 3 years, defined as the composite of overall death, myocardial infarction, and target vessel revascularization. The rate of angiographic multivessel disease was similar in the angiography-guided and FFR-guided groups (404 [94.2%] versus 186 [93.9%]; P=0.722). In the FFR-guided group, this was significantly downgraded after FFR measurements to 86.4% (P<0.001 versus before FFR) and was associated with a smaller number of anastomoses (3 [2-3] versus 3 [2-4]; P<0.001) and rate of on-pump surgery (49% versus 69%; P<0.001). At 3 years, major adverse cardiovascular events were not different between the angiography-guided and FFR-guided groups (12% versus 11%; hazard ratio, 1.030; 95% confidence interval, 0.627-1.692; P=0.908). However, the FFR-guided group compared with the angiography-guided group presented a significantly lower rate of angina (Canadian Cardiovascular Society class II-IV, 31% versus 47%; P<0.001). CONCLUSIONS: FFR-guided coronary artery bypass graft surgery was associated with a lower number of graft anastomoses and a lower rate of on-pump surgery compared with angiography-guided coronary artery bypass graft surgery. This did not result in a higher event rate during up to 36 months of follow-up and was associated with a lower rate of angina.

The Belgian Registry on Coronary Function Testing (BELmicro Registry): Study Population, Prevalence of Coronary Vascular Dysfunction, and Procedural Safety.

Coronary function testing (CFT) plays a pivotal role in the diagnosis of coronary vascular dysfunction and providing patients with tailored therapy. The Belgian registry on CFT (BELmicro registry) is a prospective, observational, multicenter registry including 14 centers in Belgium. All patients who underwent clinically indicated CFT were included in the registry. Baseline characteristics, CFT data, and clinical outcomes were collected. This analysis aimed to describe the baseline characteristics of a real-world population of patients who underwent CFT, evaluate the prevalence of coronary vascular dysfunction, and assess the safety of CFT in daily clinical practice. Between October 2021 and September 2023, 449 patients were enrolled. The mean age was 65 ± 10 years, and 47.4% of patients were men. A total of 59% of patients had hypertension, 18.7% had diabetes, 69.5% had hypercholesterolemia, and 40.1% had a smoking habit. Angina and nonobstructive coronary arteries (ANOCAs) were identified in 85.1% of the patients. Microvascular physiology assessment was performed in 95.5% of patients, vasoreactivity test in 28.5%, and both in 24.0%. coronary microvascular dysfunction was diagnosed in 23.4% of patients with ANOCA, epicardial vasospasm in 26.3%, and microvascular spasm in 14.9%. Rates of major complications were 0.7% for microvascular physiology assessment and 0% for vasoreactivity test. In conclusion, participants in the BELmicro registry represented a real-world population of patients, characterized by a high burden of cardiovascular risk factors. Coronary microvascular dysfunction and coronary vasospasm were frequent in patients with ANOCA. Performing CFT in daily clinical practice was feasible, with a low rate of complications.

Temporary omission of oral anticoagulation in atrial fibrillation patients undergoing percutaneous coronary intervention: rationale and design of the WOEST-3 randomised trial.

The optimal antithrombotic management of atrial fibrillation (AF) patients who require oral anticoagulation (OAC) undergoing percutaneous coronary intervention (PCI) remains unclear. Current guidelines recommend dual antithrombotic therapy (DAT; OAC plus P2Y12 inhibitor - preferably clopidogrel) after a short course of triple antithrombotic therapy (TAT; DAT plus aspirin). Although DAT reduces bleeding risk compared to TAT, this is counterbalanced by an increase in ischaemic events. Aspirin provides early ischaemic benefit, but TAT is associated with an increased haemorrhagic burden; therefore, we propose a 30-day dual antiplatelet therapy (DAPT; aspirin plus P2Y12 inhibitor) strategy post-PCI, temporarily omitting OAC. The study aims to compare bleeding and ischaemic risk between a 30-day DAPT strategy following PCI and a guideline-directed therapy in AF patients requiring OAC. WOEST-3 (ClinicalTrials.gov: NCT04436978) is an investigator-initiated, international, open-label, randomised controlled trial (RCT). AF patients requiring OAC who have undergone successful PCI will be randomised within 72 hours after PCI to guideline-directed therapy (edoxaban plus P2Y12 inhibitor plus limited duration of aspirin) or a 30-day DAPT strategy (P2Y12 inhibitor plus aspirin, immediately discontinuing OAC) followed by DAT (edoxaban plus P2Y12 inhibitor). With a sample size of 2,000 patients, this trial is powered to assess both superiority for major or clinically relevant non-major bleeding and non-inferiority for a composite of all-cause death, myocardial infarction, stroke, systemic embolism or stent thrombosis. In summary, the WOEST-3 trial is the first RCT temporarily omitting OAC in AF patients, comparing a 30-day DAPT strategy with guideline-directed therapy post-PCI to reduce bleeding events without hampering efficacy.

Timing of Complete Multivessel Revascularization in Patients Presenting With Non-ST-Segment Elevation Acute Coronary Syndrome.

BACKGROUND: Complete revascularization of the culprit and all significant nonculprit lesions in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and multivessel disease (MVD) reduces major adverse cardiac events, but optimal timing of revascularization remains unclear. OBJECTIVES: This study aims to compare immediate complete revascularization (ICR) and staged complete revascularization (SCR) in patients presenting with NSTE-ACS and MVD. METHODS: This prespecified substudy of the BIOVASC (Percutaneous Complete Revascularization Strategies Using Sirolimus Eluting Biodegradable Polymer Coated Stents in Patients Presenting With Acute Coronary Syndrome and Multivessel Disease) trial included patients with NSTE-ACS and MVD. Risk differences of the primary composite outcome of all-cause mortality, myocardial infarction (MI), unplanned ischemia-driven revascularization (UIDR), or cerebrovascular events and its individual components were compared between ICR and SCR at 1 year. RESULTS: The BIOVASC trial enrolled 1,525 patients; 917 patients presented with NSTE-ACS, of whom 459 were allocated to ICR and 458 to SCR. Incidences of the primary composite outcome were similar in the 2 groups (7.9% vs 10.1%; risk difference 2.2%; 95% CI: -1.5 to 6.0; P = 0.15). ICR was associated with a significant reduction of MIs (2.0% vs 5.3%; risk difference 3.3%; 95% CI: 0.9 to 5.7; P = 0.006), which was maintained after exclusion of procedure-related MIs occurring during the index or staged procedure (2.0% vs 4.4%; risk difference 2.4%; 95% CI: 0.1 to 4.7; P = 0.032). UIDRs were also reduced in the ICR group (4.2% vs 7.8%; risk difference 3.5%; 95% CI: 0.4 to 6.6; P = 0.018). CONCLUSIONS: ICR is safe in patients with NSTE-ACS and MVD and was associated with a reduction in MIs and UIDRs at 1 year.

A clinical prediction rule for the diagnosis of coronary artery disease: validation, updating, and extension.

AIMS: The aim was to validate, update, and extend the Diamond-Forrester model for estimating the probability of obstructive coronary artery disease (CAD) in a contemporary cohort. METHODS AND RESULTS: Prospectively collected data from 14 hospitals on patients with chest pain without a history of CAD and referred for conventional coronary angiography (CCA) were used. Primary outcome was obstructive CAD, defined as ≥ 50% stenosis in one or more vessels on CCA. The validity of the Diamond-Forrester model was assessed using calibration plots, calibration-in-the-large, and recalibration in logistic regression. The model was subsequently updated and extended by revising the predictive value of age, sex, and type of chest pain. Diagnostic performance was assessed by calculating the area under the receiver operating characteristic curve (c-statistic) and reclassification was determined. We included 2260 patients, of whom 1319 had obstructive CAD on CCA. Validation demonstrated an overestimation of the CAD probability, especially in women. The updated and extended models demonstrated a c-statistic of 0.79 (95% CI 0.77-0.81) and 0.82 (95% CI 0.80-0.84), respectively. Sixteen per cent of men and 64% of women were correctly reclassified. The predicted probability of obstructive CAD ranged from 10% for 50-year-old females with non-specific chest pain to 91% for 80-year-old males with typical chest pain. Predictions varied across hospitals due to differences in disease prevalence. CONCLUSION: Our results suggest that the Diamond-Forrester model overestimates the probability of CAD especially in women. We updated the predictive effects of age, sex, type of chest pain, and hospital setting which improved model performance and we extended it to include patients of 70 years and older.

Diagnostic accuracy of fractional flow reserve from anatomic CT angiography.

CONTEXT: Coronary computed tomographic (CT) angiography is a noninvasive anatomic test for diagnosis of coronary stenosis that does not determine whether a stenosis causes ischemia. In contrast, fractional flow reserve (FFR) is a physiologic measure of coronary stenosis expressing the amount of coronary flow still attainable despite the presence of a stenosis, but it requires an invasive procedure. Noninvasive FFR computed from CT (FFR(CT)) is a novel method for determining the physiologic significance of coronary artery disease (CAD), but its ability to identify ischemia has not been adequately examined to date. OBJECTIVE: To assess the diagnostic performance of FFR(CT) plus CT for diagnosis of hemodynamically significant coronary stenosis. DESIGN, SETTING, AND PATIENTS: Multicenter diagnostic performance study involving 252 stable patients with suspected or known CAD from 17 centers in 5 countries who underwent CT, invasive coronary angiography (ICA), FFR, and FFR(CT) between October 2010 and October 2011. Computed tomography, ICA, FFR, and FFR(CT) were interpreted in blinded fashion by independent core laboratories. Accuracy of FFR(CT) plus CT for diagnosis of ischemia was compared with an invasive FFR reference standard. Ischemia was defined by an FFR or FFR(CT) of 0.80 or less, while anatomically obstructive CAD was defined by a stenosis of 50% or larger on CT and ICA. MAIN OUTCOME MEASURES: The primary study outcome assessed whether FFR(CT) plus CT could improve the per-patient diagnostic accuracy such that the lower boundary of the 1-sided 95% confidence interval of this estimate exceeded 70%. RESULTS: Among study participants, 137 (54.4%) had an abnormal FFR determined by ICA. On a per-patient basis, diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of FFR(CT) plus CT were 73% (95% CI, 67%-78%), 90% (95% CI, 84%-95%), 54% (95% CI, 46%-83%), 67% (95% CI, 60%-74%), and 84% (95% CI, 74%-90%), respectively. Compared with obstructive CAD diagnosed by CT alone (area under the receiver operating characteristic curve [AUC], 0.68; 95% CI, 0.62-0.74), FFR(CT) was associated with improved discrimination (AUC, 0.81; 95% CI, 0.75-0.86; P < .001). CONCLUSION: Although the study did not achieve its prespecified primary outcome goal for the level of per-patient diagnostic accuracy, use of noninvasive FFR(CT) plus CT among stable patients with suspected or known CAD was associated with improved diagnostic accuracy and discrimination vs CT alone for the diagnosis of hemodynamically significant CAD when FFR determined at the time of ICA was the reference standard.

Dual versus triple antithrombotic therapy after percutaneous coronary intervention: the prospective multicentre WOEST 2 Study.

BACKGROUND: For patients on oral anticoagulants (OAC) undergoing percutaneous coronary intervention (PCI), European guidelines have recently changed their recommendations to dual antithrombotic therapy (DAT; P2Y12 inhibitor and OAC) without aspirin. AIMS: The prospective WOEST 2 registry was designed to obtain contemporary real-world data on antithrombotic regimens and related outcomes after PCI in patients with an indication for OAC. METHODS: In this analysis, we compare DAT (P2Y12 inhibitor and OAC) to triple antithrombotic therapy (TAT; aspirin, P2Y12 inhibitor, and OAC) on thrombotic and bleeding outcomes after one year. Clinically relevant bleeding was defined as Bleeding Academic Research Consortium classification (BARC) grade 2, 3, or 5; major bleeding as BARC grade 3 or 5. Major adverse cardiac and cerebrovascular events (MACCE) was defined as a composite of all-cause mortality, myocardial infarction, stent thrombosis, ischaemic stroke, and transient ischaemic attack. RESULTS: A total of 1,075 patients were included between 2014 and 2021. Patients used OAC for atrial fibrillation (93.6%) or mechanical heart valve prosthesis (4.7%). Non-vitamin K oral anticoagulants (NOAC) were prescribed in 53.1% and vitamin K antagonists in 46.9% of patients. At discharge, 60.9% received DAT, and 39.1% TAT. DAT was associated with less clinically relevant and similar major bleeding (16.8% vs 23.4%; p<0.01 and 7.6% vs 7.7%, not significant), compared to TAT. The difference in MACCE between the two groups was not statistically significant (12.4% vs 9.7%; p=0.17). Multivariable adjustment and propensity score matching confirmed these results. CONCLUSIONS: Dual antithrombotic therapy is associated with a substantially lower risk of clinically relevant bleeding without a statistically significant penalty in ischaemic events.

Second-generation everolimus-eluting and paclitaxel-eluting stents in real-life practice (COMPARE): a randomised trial.

BACKGROUND: Everolimus-eluting and paclitaxel-eluting stents, compared with bare metal stents, reduced the risk of restenosis in clinical trials with strict inclusion and exclusion criteria. We compared the safety and efficacy of the second-generation everolimus-eluting and paclitaxel-eluting stents in real-life practice. METHODS: We randomly assigned 1800 consecutive patients (aged 18-85 years) undergoing percutaneous coronary intervention at one centre to treatment with everolimus-eluting or paclitaxel-eluting stents. The primary endpoint was a composite of safety and efficacy (all-cause mortality, myocardial infarction, and target vessel revascularisation) within 12 months. Patients were not told which stent they had been allocated. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT01016041. FINDINGS: Follow-up was completed in 1797 patients. The primary endpoint occurred in 56 (6%) of 897 patients in the everolimus-eluting stent group versus 82 (9%) of 903 in the paclitaxel-eluting stent group (relative risk 0.69 [95% CI 0.50-0.95], p value for superiority=0.02). The difference was attributable to a lower rate of stent thrombosis (6 [<1%] vs 23 [3%], 0.26 [0.11-0-64], p=0.002), myocardial infarction (25 [3%] vs 48 [5%], 0.52 [0.33-0.84], p=0.007), and target vessel revascularisation (21 [2%] vs 54 [6%], 0.39 [0.24-0.64], p=0.0001). Cardiac death, non-fatal myocardial infarction, or target lesion revascularisation occurred in 44 [5%] patients in the everolimus-eluting stent group versus 74 [8%] patients in the paclitaxel-eluting stent group, p value for superiority was 0.005. INTERPRETATION: The everolimus-eluting stent is better than the second generation paclitaxel-eluting stent in unselected patients in terms of safety and efficacy. On the basis of our results, we suggest that paclitaxel-eluting stents should no longer be used in everyday clinical practice. FUNDING: Unrestricted grants from Abbott Vascular and Boston Scientific.

Diagnostic accuracy and clinical utility of noninvasive testing for coronary artery disease.

BACKGROUND: Computed tomography coronary angiography (CTCA) has become a popular noninvasive test for diagnosing coronary artery disease. OBJECTIVE: To compare the accuracy and clinical utility of stress testing and CTCA for identifying patients who require invasive coronary angiography (ICA). DESIGN: Observational study. SETTING: University medical center in Rotterdam, the Netherlands. PATIENTS: 517 patients referred by their treating physicians for evaluation of chest symptoms by using stress testing or ICA. INTERVENTION: Stress testing and CTCA in all patients. MEASUREMENTS: Diagnostic accuracy of stress testing and CTCA compared with ICA; pretest probabilities of disease by Duke clinical score; and clinical utility of noninvasive testing, defined as a pretest or posttest probability that suggests how to proceed with testing (no further testing if < or =5%, proceed with ICA if between 5% and 90%, and refer directly for ICA if > or =90%). RESULTS: Stress testing was not as accurate as CTCA; CTCA sensitivity approached 100%. In patients with a low (<20%) pretest probability of disease, negative stress test or CTCA results suggested no need for ICA. In patients with an intermediate (20% to 80%) pretest probability, a positive CTCA result suggested need to proceed with ICA (posttest probability, 93% [95% CI, 92% to 93%]) and a negative result suggested no need for further testing (posttest probability, 1% [CI, 1% to 1%]). Physicians could proceed directly with ICA in patients with a high (>80%) pretest probability (91% [CI, 90% to 92%]). LIMITATIONS: Referral and verification bias might have influenced findings. Stress testing provides functional information that may add value to that from anatomical (CTCA or ICA) imaging. CONCLUSION: Computed tomography coronary angiography seems most valuable in patients with intermediate pretest probability of disease, because the test can distinguish which of these patients need invasive angiography. These findings need to be confirmed before CTCA can be routinely recommended for these patients.

Incremental value of the CT coronary calcium score for the prediction of coronary artery disease.

OBJECTIVES: To validate published prediction models for the presence of obstructive coronary artery disease (CAD) in patients with new onset stable typical or atypical angina pectoris and to assess the incremental value of the CT coronary calcium score (CTCS). METHODS: We searched the literature for clinical prediction rules for the diagnosis of obstructive CAD, defined as ≥50% stenosis in at least one vessel on conventional coronary angiography. Significant variables were re-analysed in our dataset of 254 patients with logistic regression. CTCS was subsequently included in the models. The area under the receiver operating characteristic curve (AUC) was calculated to assess diagnostic performance. RESULTS: Re-analysing the variables used by Diamond & Forrester yielded an AUC of 0.798, which increased to 0.890 by adding CTCS. For Pryor, Morise 1994, Morise 1997 and Shaw the AUC increased from 0.838 to 0.901, 0.831 to 0.899, 0.840 to 0.898 and 0.833 to 0.899. CTCS significantly improved model performance in each model. CONCLUSIONS: Validation demonstrated good diagnostic performance across all models. CTCS improves the prediction of the presence of obstructive CAD, independent of clinical predictors, and should be considered in its diagnostic work-up.

Clinical impact of CT coronary angiography without exclusion of small coronary artery segments: a real-world and long-term study.

OBJECTIVES: CT coronary angiography (CTCA) has become a valuable diagnostic test in the workup of patients with possible coronary artery disease (CAD). Because of inherent limitations in spatial resolution, epicardial vessels with a small diameter, in general less than 1.5-2 mm, have so far been excluded in studies assessing clinical utility of CTCA. This study sought to assess the clinical impact of CTCA taking into account pathology in small coronary arteries. METHODS: We conducted a retrospective cohort study of all patients with possible CAD who underwent dual-source CTCA and subsequent invasive coronary angiography (ICA) between January 2010 and July 2017. Patients with an Agatston calcium score ≥1000 were reported separately. Diagnostic accuracy of CTCA on a patient, vessel and segment level was calculated. The physician's therapeutic decision was defined as conservative, medical antianginal treatment or revascularisation. Using ICA as the reference, we calculated the precision of CTCA to replicate these therapeutic recommendations. RESULTS: In total, 1209 patients underwent both CTCA and ICA. Overall diagnostic performance of CTCA showed a sensitivity of 90% (95% CI 86% to 93%) and specificity of 40% (95% CI 36% to 45%). With regard to clinical decision making, CTCA showed good performance: 91% of patients who were treated medically or by revascularisation were correctly identified. Prevalence of disease in small vessel segments was low: 16% showed significant CAD on ICA. Prevalence of significant disease was 70% in patients with an Agatston score ≥1000: the majority underwent revascularisation. CONCLUSIONS: From a true patient perspective, without exclusion of smaller coronary artery segments, CTCA allows safe patient management.

Preserved diagnostic performance of dual-source CT coronary angiography with reduced radiation exposure and cancer risk.

PURPOSE: To evaluate the effects of standard and optimal electrocardiographic (ECG) pulsing on diagnostic performance, radiation dose, and cancer risk in symptomatic patients in a "real-world" clinical setting. MATERIALS AND METHODS: The institutional review board approved the study, and all patients gave informed consent. Dual-source computed tomographic (CT) coronary angiography was performed in 436 symptomatic patients (301 men, 135 women; mean age, 61.6 years +/- 10.6 [standard deviation]; age range, 23-89 years) referred for conventional coronary angiography. Standard and optimal ECG pulsing was performed in 327 and 109 patients, respectively. The diagnostic performance of dual-source CT coronary angiography for detection of significant stenosis (>or=50 luminal diameter reduction), with quantitative coronary angiography as the reference standard, was reported as sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios. The mean effective radiation dose, additional fatal cancer risk, and age- and sex-specific cancer risks related to one CT coronary angiographic examination were determined from data averaged over the study population. RESULTS: Mean effective doses with standard and optimal ECG pulsing were 14.2 mSv +/- 3.2 and 10.7 mSv +/- 3.6, respectively. Optimal ECG pulsing resulted in a 43% overall reduction in mean effective radiation dose and cancer risk compared with a nonpulsing protocol (18.8 mSv +/- 3.5) and a 25% overall reduction in mean effective dose compared with the standard pulsing protocol. At patient-by-patient analysis, CT coronary angiography with standard ECG pulsing yielded sensitivity, specificity, and positive and negative predictive values of 100% (95% confidence interval [CI]: 99%, 100%), 85% (95% CI: 81%, 88%), 94% (95% CI: 91%, 96%), and 99% (95% CI: 98%, 100%), respectively, for detection of significant stenosis. Optimal ECG pulsing yielded similar results: Sensitivity, specificity, and positive and negative predictive values were 100% (95% CI: 100%, 100%), 88% (95% CI: 82%, 94%), 97% (95% CI: 93%, 100%), and 100%, respectively. CONCLUSION: Compared with a nonpulsing protocol, optimal ECG pulsing resulted in significant (P < .001) reductions in patient radiation dose and cancer risk (up to 55% reduction in patients with high heart rates) while preserving the diagnostic performance of dual-source CT coronary angiography.

Impact of heart rate frequency and variability on radiation exposure, image quality, and diagnostic performance in dual-source spiral CT coronary angiography.

PURPOSE: To investigate the effect of heart rate frequency (HRF) and heart rate variability (HRV) on radiation exposure, image quality, and diagnostic performance to help detect significant stenosis (> or =50% lumen diameter reduction) by using adaptive electrocardiographic (ECG) pulsing at dual-source (DS) spiral computed tomographic (CT) coronary angiography. MATERIALS AND METHODS: Institutional review committee approval and informed consent were obtained. No prescan beta-blockers were applied. Unenhanced CT and CT coronary angiography with adaptive ECG pulsing were performed in 927 consecutive patients (600 men, 327 women; mean age, 60.3 years +/- 11.0 [standard deviation]) divided in three HRF groups: low, intermediate, and high (< or =65, 66-79, and > or =80 beats/min, respectively), and four HRV groups given mean interbeat difference (IBD) during CT coronary angiography: normal, minor, moderate, and severe (IBDs of 0-1, 2-3, 4-10, and >10, respectively). Radiation exposure and image quality were also evaluated. In 444 of these, diagnostic performance was presented as sensitivity, specificity, positive predictive values (PPVs), and negative predictive values and likelihood ratios with corresponding 95% confidence intervals by using quantitative coronary angiography as the reference standard. RESULTS: CT coronary angiography yielded good image quality in 98% of patients and no significant differences in image quality were found among HRF and HRV groups. Radiation exposure was significantly higher in patients with low versus high HRF and in patients with severe versus normal HRV. No significant differences among HRF and HRV groups in image quality and diagnostic performance were found. A nonsignificant trend was found toward a lower specificity and PPV in patients with a high HRF or severe HRV when compared with low HRF or normal HRV in patients with a low calcium score (Agatston score <100). CONCLUSION: DS spiral CT coronary angiography performed with adaptive ECG pulsing results in preserved diagnostic image quality and performance independent of HRF or HRV at the cost of limited dose reduction in arrhythmic patients.

Graft patency after FFR-guided versus angiography-guided coronary artery bypass grafting: the GRAFFITI trial.

AIMS: The aim of this study was to assess prospectively the clinical benefits of fractional flow reserve (FFR) in guiding coronary artery bypass grafting (CABG). METHODS AND RESULTS: GRAFFITI is a single-blinded, prospective, multicentre, randomised controlled trial of FFR-guided versus angiography-guided CABG. We enrolled patients undergoing coronary angiography, having a significantly diseased left anterior descending artery or left main stem and at least one more major coronary artery with intermediate stenosis, assessed by FFR. Surgical strategy was defined based on angiography, blinded to FFR values prior to randomisation. After randomisation, patients were operated on either following the angiography-based strategy (angiography-guided group) or according to FFR, i.e., with an FFR ≤0.80 as cut-off for grafting (FFR-guided group). The primary endpoint was graft patency at 12 months. Between March 2012 and December 2016, 172 patients were randomised either to the angiography-guided group (84 patients) or to the FFR-guided group (88 patients). The patients had a median of three [3; 4] lesions; diameter stenosis was 65% (50%; 80%), FFR was 0.72 (0.50; 0.82). Compared to the angiography-guided group, the FFR-guided group received fewer anastomoses (3 [3; 3] vs 2 [2; 3], respectively; p=0.004). One-year angiographic follow-up showed no difference in overall graft patency (126 [80%] vs 113 [81%], respectively; p=0.885). One-year clinical follow-up, available in 98% of patients, showed no difference in the composite of death, myocardial infarction, target vessel revascularisation and stroke. CONCLUSIONS: FFR guidance of CABG has no impact on one-year graft patency, but it is associated with a simplified surgical procedure. ClinicalTrials.gov Identifier: NCT01810224.

Diagnostic performance of coronary CT angiography by using different generations of multisection scanners: single-center experience.

PURPOSE: To retrospectively compare sensitivity and specificity of four generations of multidetector computed tomographic (CT) scanners for diagnosing significant (>or=50%) coronary artery stenosis, with quantitative conventional coronary angiography as reference standard. MATERIALS AND METHODS: The institutional review board approved this study. All patients consented to undergo CT studies prior to conventional coronary angiography, after they were informed of the additional radiation dose, and to the use of their data for future retrospective research. Two hundred four patients (157 men, 47 women; mean age, 58 years +/- 11 [standard deviation]), classified in four groups of 51 patients each, underwent coronary CT angiography with four-section, first- and second-generation 16-section, and 64-section CT scanners. Patients in sinus rhythm scheduled for conventional coronary angiography (stable angina, atypical chest pain) were included. Patients with bypass grafts and stents were excluded. Two readers unaware of results of conventional coronary angiography evaluated CT scans. Coronary artery segments of 2 mm or larger in diameter were included for comparative evaluation with quantitative coronary angiography. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for detection of significant stenoses (>or=50% luminal diameter reduction) were calculated. RESULTS: Image quality was rated poor for the following percentages of coronary artery segments: 33.1% at four-section CT, 14.4% at first-generation 16-section CT, 6.3% at second-generation 16-section CT, and 2.6% at 64-section CT. Sensitivity, specificity, PPV, and NPV, respectively, were as follows: 57%, 91%, 60%, and 90% at four-section CT; 90%, 93%, 65%, and 99% at first-generation 16-section CT; 97%, 98%, 87%, and 100% at second-generation 16-section CT; and 99%, 96%, 80%, and 100% at 64-section CT. Diagnostic performance of four-section CT was significantly poorer than that of second-generation 16-section CT (odds ratio = 4.57) and 64-section CT (odds ratio = 2.89). CONCLUSION: Diagnostic performance of coronary CT angiography varies among scanners of different generations. Earlier-generation scanners (four sections) had significantly poorer performance; performance of 16- compared with 64-section CT scanners showed progressive, although not significant, improvement.

Study Design of the Graft Patency After FFR-Guided Versus Angiography-Guided CABG Trial (GRAFFITI).

Clinical benefit of invasive functionally guided revascularization has been mostly investigated and proven for percutaneous coronary intervention. It has never been prospectively evaluated whether a systematic fractional flow reserve (FFR) assessment is also beneficial in guiding coronary artery bypass graft surgery (CABG). The objective of the GRAft patency after FFR-guided versus angiography-guIded CABG (GRAFFITI) trial was to compare an FFR-guided revascularization strategy to the traditional angiography-guided revascularization strategy for patients undergoing CABG. Patients were enrolled with significantly diseased left anterior descending or left main stem and at least one major coronary artery with angiographically intermediate stenosis (30-90% diameter stenosis) that was assessed by FFR. Thereafter, while the FFR values were kept concealed, cardiac surgeons decided their intended procedural strategy based on the coronary angiography alone. At this point, patients underwent 1:1 randomization to either an FFR-guided or an angiography-guided CABG strategy. In case the patient was randomized to angiography-guided arm, cardiac surgeons kept their intended procedural strategy, i.e., CABG was guided solely on the basis of the coronary angiography. In case the patient was randomized to the FFR-guided arm, FFR values were disclosed to the surgeons who revised the surgical protocol according to the functional significance of each coronary stenosis. The primary endpoint of the trial was the rate of graft occlusion at 12 months, assessed by coronary computed tomography or coronary angiography. The secondary endpoints were (1) length of postoperative hospital stay; (2) changes in surgical strategy depending upon FFR results (in FFR-guided group only); and (3) rate of major adverse cardiac and cerebrovascular events, i.e., composite of death, myocardial infarction, stroke, and any revascularization during the follow-up period. This study is the first prospective randomized trial investigating potential clinical benefits, associated with FFR-guided surgical revascularization. TRIAL REGISTRATION: NCT01810224.