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.

Age and Computed Tomography and Invasive Coronary Angiography in Stable Chest Pain: A Prespecified Secondary Analysis of the DISCHARGE Randomized Clinical Trial.

Importance: The effectiveness and safety of computed tomography (CT) and invasive coronary angiography (ICA) in different age groups is unknown. Objective: To determine the association of age with outcomes of CT and ICA in patients with stable chest pain. Design, Setting, and Participants: The assessor-blinded Diagnostic Imaging Strategies for Patients With Stable Chest Pain and Intermediate Risk of Coronary Artery Disease (DISCHARGE) randomized clinical trial was conducted between October 2015 and April 2019 in 26 European centers. Patients referred for ICA with stable chest pain and an intermediate probability of obstructive coronary artery disease were analyzed in an intention-to-treat analysis. Data were analyzed from July 2022 to January 2023. Interventions: Patients were randomly assigned to a CT-first strategy or a direct-to-ICA strategy. Main Outcomes and Measures: MACE (ie, cardiovascular death, nonfatal myocardial infarction, or stroke) and major procedure-related complications. The primary prespecified outcome of this secondary analysis of age was major adverse cardiovascular events (MACE) at a median follow-up of 3.5 years. Results: Among 3561 patients (mean [SD] age, 60.1 [10.1] years; 2002 female [56.2%]), 2360 (66.3%) were younger than 65 years, 982 (27.6%) were between ages 65 to 75 years, and 219 (6.1%) were older than 75 years. The primary outcome was MACE at a median (IQR) follow-up of 3.5 (2.9-4.2) years for 3523 patients (99%). Modeling age as a continuous variable, age, and randomization group were not associated with MACE (hazard ratio, 1.02; 95% CI, 0.98-1.07; P for interaction = .31). Age and randomization group were associated with major procedure-related complications (odds ratio, 1.15; 95% CI, 1.05-1.27; P for interaction = .005), which were lower in younger patients. Conclusions and Relevance: Age did not modify the effect of randomization group on the primary outcome of MACE but did modify the effect on major procedure-related complications. Results suggest that CT was associated with a lower risk of major procedure-related complications in younger patients. Trial Registration: ClinicalTrials.gov Identifier: NCT02400229.

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.

The Impact of Pulmonary Vein Anatomy on P-Wave Appearance during Sinus Rhythm: Cardiac Computed Tomography Study.

Electrocardigraphy remains a first-line evaluation method for cardiac electrical activity, recorded from the body surface. Since atrial activation is seen on the ECG as a P-wave, several factors are known to impact the appearance of the P-wave, such as the direction of electric impulse, conduction abnormalities, and anatomical characteristics of the atria. This retrospective study aimed to find statistically significant associations between the anatomy of pulmonary veins (PVs) observed in cardiac computed tomography (CT) and P-wave appearance during sinus rhythm on resting ECG. For each patient, a resting 12-lead ECG was recorded, and the field of analysis was P-wave-its duration, morphology, and axis. The evaluation of the CT scan recordings was performed by creating 3D models of the left atrium and analyzing the anatomy of the PVs and left atrial appendages (LAA). Noteworthy correlations were found: anatomy of the left PVs showed an association with LAA volume, LAA morphology, and P-wave notching in lead II. The right PVs demonstrated a relation with the P-wave axis and amplitude. Although these correlations cannot be classified as strong, the results not only expand understanding about discussed variables but also suggest the presence of a subtle and complex relationship, that warrants further exploration.

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.

Coronary revascularization of patients with silent coronary ischemia may reduce the risk of myocardial infarction and cardiovascular death after carotid endarterectomy.

BACKGROUND: Major adverse cardiac events (MACEs) are the primary cause of death after carotid endarterectomy (CEA). We sought to determine whether selective coronary revascularization of CEA patients with asymptomatic coronary ischemia can reduce the risk of MACEs, myocardial infarction (MI), and cardiac death after endarterectomy compared with CEA patients receiving standard cardiac evaluation and care. METHODS: Two groups of patients with no cardiac history or symptoms undergoing elective CEA were compared. Group I: patients enrolled in a prospective study of noninvasive preoperative cardiac evaluation using coronary computed tomography (CT)-derived fractional flow reserve (FFRCT) to detect asymptomatic (silent) coronary ischemia with selective postoperative coronary revascularization. Group II: matched Control patients with standard preoperative cardiac evaluation and no postoperative coronary revascularization. Lesion-specific coronary ischemia in group I was defined as FFRCT ≤ 0.80 distal to coronary stenosis with severe ischemia defined as FFRCT ≤ 0.75. End points included MACEs, cardiac death, MI, cardiovascular (CV) death, stroke, and all-cause death through 3-year follow-up. RESULTS: Group I (n = 100) and group II (n = 100) patients were similar in age (68 vs 67 years), gender (65% vs 62% male), comorbidities, and indications for CEA (53% vs 48% symptomatic carotid stenosis). In group I, FFRCT analysis revealed lesion-specific coronary ischemia in 57% of patients, severe coronary ischemia in 44%, left main ischemia in 7%, and multivessel ischemia in 28%. The status of coronary ischemia in group II was unknown. CEA was performed without complications in both groups, and all patients received optimal postoperative medical therapy. In group I, elective coronary revascularization was performed in 33 patients (27 percutaneous coronary intervention; 6 coronary artery bypass grafting) 1 to 3 months after CEA. Group II patients had no elective coronary revascularization. During 3-year follow-up, compared with group II, group I patients had fewer MACEs (4% vs 17%, hazard ratio [HR]: 0.21 [95% confidence interval (CI): 0.07-0.63], P = .004), fewer cardiac deaths (2% vs 9%, HR: 0.20 [95% CI: 0.04-0.95], P = .030), fewer MIs (3% vs 17%, HR: 0.16 [95% CI: 0.05-0.54], P = .001), and fewer CV deaths (2% vs 12%, HR: 0.16 [95% CI: 0.004-0.07], P = .009). There were no significant differences in the rates of stroke or all-cause death. CONCLUSIONS: Preoperative diagnosis of silent coronary ischemia with selective coronary revascularization after CEA may reduce the risk of MACEs, cardiac death, MI, and CV death during 3-year follow-up compared with CEA patients receiving standard cardiac evaluation and care.

CT or Invasive Coronary Angiography in Stable Chest Pain.

BACKGROUND: In the diagnosis of obstructive coronary artery disease (CAD), computed tomography (CT) is an accurate, noninvasive alternative to invasive coronary angiography (ICA). However, the comparative effectiveness of CT and ICA in the management of CAD to reduce the frequency of major adverse cardiovascular events is uncertain. METHODS: We conducted a pragmatic, randomized trial comparing CT with ICA as initial diagnostic imaging strategies for guiding the treatment of patients with stable chest pain who had an intermediate pretest probability of obstructive CAD and were referred for ICA at one of 26 European centers. The primary outcome was major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) over 3.5 years. Key secondary outcomes were procedure-related complications and angina pectoris. RESULTS: Among 3561 patients (56.2% of whom were women), follow-up was complete for 3523 (98.9%). Major adverse cardiovascular events occurred in 38 of 1808 patients (2.1%) in the CT group and in 52 of 1753 (3.0%) in the ICA group (hazard ratio, 0.70; 95% confidence interval [CI], 0.46 to 1.07; P = 0.10). Major procedure-related complications occurred in 9 patients (0.5%) in the CT group and in 33 (1.9%) in the ICA group (hazard ratio, 0.26; 95% CI, 0.13 to 0.55). Angina during the final 4 weeks of follow-up was reported in 8.8% of the patients in the CT group and in 7.5% of those in the ICA group (odds ratio, 1.17; 95% CI, 0.92 to 1.48). CONCLUSIONS: Among patients referred for ICA because of stable chest pain and intermediate pretest probability of CAD, the risk of major adverse cardiovascular events was similar in the CT group and the ICA group. The frequency of major procedure-related complications was lower with an initial CT strategy. (Funded by the European Union Seventh Framework Program and others; DISCHARGE ClinicalTrials.gov number, NCT02400229.).

Pre-operative Diagnosis of Silent Coronary Ischaemia May Reduce Post-operative Death and Myocardial Infarction and Improve Survival of Patients Undergoing Lower Extremity Surgical Revascularisation.

OBJECTIVE: Patients undergoing peripheral vascular surgery have increased risk of death and myocardial infarction (MI), which may be due to unsuspected (silent) coronary ischaemia. The aim was to determine whether pre-operative diagnosis of silent ischaemia using coronary computed tomography (CT) derived fractional flow reserve (FFRCT) can facilitate multidisciplinary care to reduce post-operative death and MI, and improve survival. METHODS: This was a single centre prospective study with historic controls. Patients with no cardiac symptoms undergoing lower extremity surgical revascularisation with pre-operative coronary CTA-FFRCT testing were compared with historic controls with standard pre-operative testing. Silent coronary ischaemia was defined as FFRCT ≤ 0.80 distal to coronary stenosis with FFRCT ≤ 0.75 indicating severe ischaemia. End points included cardiovascular (CV) death, MI, and all cause death through one year follow up. RESULTS: There were no statistically significant differences between CT angiography (CTA-FFRCT) (n = 135) and control (n = 135) patients with regard to age (66 ± 8 years), sex, comorbidities, or surgery performed. Coronary CTA showed ≥ 50% stenosis in 70% of patients with left main stenosis in 7%. FFRCT revealed silent coronary ischaemia in 68% of patients with severe ischaemia in 53%. The status of coronary ischaemia was unknown in the controls. At 30 days, CV death and MI in the CTA-FFRCT group were not statistically significantly different from controls (0% vs. 3.7% [p = .060] and 0.7% vs. 5.2% [p = .066], respectively). Post-operative coronary revascularisation was performed in 54 patients to relieve silent ischaemia (percutaneous coronary intervention in 47, coronary artery bypass graft in seven). At one year, CTA-FFRCT patients had fewer CV deaths (0.7% vs. 5.9%; p = .036) and MIs (2.2% vs. 8.1%; p = .028) and improved survival (p = .018) compared with controls. CONCLUSION: Pre-operative diagnosis of silent coronary ischaemia in patients undergoing lower extremity revascularisation surgery can facilitate multidisciplinary patient care with selective post-operative coronary revascularisation. This strategy reduced post-operative death and MI and improved one year survival compared with standard care.

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.

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.

Computed tomography versus invasive coronary angiography: design and methods of the pragmatic randomised multicentre DISCHARGE trial.

OBJECTIVES: More than 3.5 million invasive coronary angiographies (ICA) are performed in Europe annually. Approximately 2 million of these invasive procedures might be reduced by noninvasive tests because no coronary intervention is performed. Computed tomography (CT) is the most accurate noninvasive test for detection and exclusion of coronary artery disease (CAD). To investigate the comparative effectiveness of CT and ICA, we designed the European pragmatic multicentre DISCHARGE trial funded by the 7th Framework Programme of the European Union (EC-GA 603266). METHODS: In this trial, patients with a low-to-intermediate pretest probability (10-60 %) of suspected CAD and a clinical indication for ICA because of stable chest pain will be randomised in a 1-to-1 ratio to CT or ICA. CT and ICA findings guide subsequent management decisions by the local heart teams according to current evidence and European guidelines. RESULTS: Major adverse cardiovascular events (MACE) defined as cardiovascular death, myocardial infarction and stroke as a composite endpoint will be the primary outcome measure. Secondary and other outcomes include cost-effectiveness, radiation exposure, health-related quality of life (HRQoL), socioeconomic status, lifestyle, adverse events related to CT/ICA, and gender differences. CONCLUSIONS: The DISCHARGE trial will assess the comparative effectiveness of CT and ICA. KEY POINTS: • Coronary artery disease (CAD) is a major cause of morbidity and mortality. • Invasive coronary angiography (ICA) is the reference standard for detection of CAD. • Noninvasive computed tomography angiography excludes CAD with high sensitivity. • CT may effectively reduce the approximately 2 million negative ICAs in Europe. • DISCHARGE addresses this hypothesis in patients with low-to-intermediate pretest probability for CAD.

Influence of Coronary Calcification on the Diagnostic Performance of CT Angiography Derived FFR in Coronary Artery Disease: A Substudy of the NXT Trial.

OBJECTIVES: The goal of this study was to examine the diagnostic performance of noninvasive fractional flow reserve (FFR) derived from coronary computed tomography angiography (CTA) (FFRCT) in relation to coronary calcification severity. BACKGROUND: FFRCT has shown promising results in identifying lesion-specific ischemia. The extent to which the severity of coronary calcification affects the diagnostic performance of FFRCT is not known. METHODS: Coronary calcification was assessed by using the Agatston score (AS) in 214 patients suspected of having coronary artery disease who underwent coronary CTA, FFRCT, and FFR (FFR examination was performed in 333 vessels). The diagnostic performance of FFRCT (≤0.80) in identifying vessel-specific ischemia (FFR ≤0.80) was investigated across AS quartiles (Q1 to Q4) and for discrimination of ischemia in patients and vessels with a low-mid AS (Q1 to Q3) versus a high AS (Q4). Coronary CTA stenosis was defined as lumen reduction >50%. RESULTS: Mean ± SD per-patient and per-vessel AS were 302 ± 468 (range 0 to 3,599) and 95 ± 172 (range 0 to 1,703), respectively. There was no statistical difference in diagnostic accuracy, sensitivity, or specificity of FFRCT across AS quartiles. Discrimination of ischemia by FFRCT was high in patients with a high AS (416 to 3,599) and a low-mid AS (0 to 415), with no difference in area under the receiver-operating characteristic curve (AUC) (0.86 [95% confidence interval (CI): 0.76 to 0.96] vs. 0.92 [95% CI: 0.88 to 0.96]) (p = 0.45). Similarly, discrimination of ischemia by FFRCT was high in vessels with a high AS (121 to 1,703) and a low-mid AS (0 to 120) (AUC: 0.91 [95% CI: 0.85 to 0.97] vs. 0.95 [95% CI: 0.91 to 0.98]; p = 0.65). Diagnostic accuracy and specificity of FFRCT were significantly higher than for stenosis assessment in each AS quartile at the per-patient (p < 0.001) and per-vessel (p < 0.05) level with similar sensitivity. In vessels with a high AS, FFRCT exhibited improved discrimination of ischemia compared with coronary CTA alone (AUC: 0.91 vs. 0.71; p = 0.004), whereas on a per-patient level, the difference did not reach statistical significance (AUC: 0.86 vs. 0.72; p = 0.09). CONCLUSIONS: FFRCT provided high and superior diagnostic performance compared with coronary CTA interpretation alone in patients and vessels with a high AS.

Treatment of Heart Failure With Associated Functional Mitral Regurgitation Using the ARTO System: Initial Results of the First-in-Human MAVERIC Trial (Mitral Valve Repair Clinical Trial).

OBJECTIVES: MAVERIC (Mitral Valve Repair Clinical Trial) reports the safety and efficacy of the ARTO system in patients with symptomatic heart failure and functional mitral regurgitation (FMR). BACKGROUND: The ARTO system percutaneously modifies the mitral annulus to improve leaflet coaptation in FMR. METHODS: The MAVERIC trial is a prospective, nonrandomized first-in-human study. Key inclusion criteria were systolic heart failure New York Heart Association functional classes II to IV, FMR grade ≥2+, left ventricular (LV) ejection fraction ≤40%, LV end-diastolic diameter >50 mm and ≤75 mm. Exclusion criteria were clinical variables that precluded feasibility of the ARTO procedure. Primary outcomes were safety (30-day major adverse events) and efficacy (MR reduction, LV volumes, and functional status). RESULTS: Eleven patients received the ARTO system, and there were no procedural adverse events. From baseline to 30 days, there were meaningful improvements. Effective regurgitant orifice area decreased from 30.3 ± 11.1 mm(2) to 13.5 ± 7.1 mm(2) and regurgitant volumes from 45.4 ± 15.0 ml to 19.5 ± 10.2 ml. LV end-systolic volume index improved from 77.5 ± 24.3 ml/m(2) to 68.5 ± 21.4 ml/m(2), and LV end-diastolic volume index 118.7 ± 28.6 ml/m(2) to 103.9 ± 21.2 ml/m(2). Mitral annular anteroposterior diameter decreased from 45.0 ± 3.3 mm to 38.7 ± 3.0 mm. Functional status was 81.8% New York Heart Association functional class III/IV improving to 54.6% functional class I/II. At 30 days, there were 2 adverse events: 1 pericardial effusion requiring surgical drainage; and 1 asymptomatic device dislodgement. CONCLUSIONS: The ARTO system is a novel transcatheter device that can be used safely with meaningful efficacy in the treatment of FMR. (Mitral Valve Repair Clinical Trial [MAVERIC]; NCT02302872).