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Objectives: The aim of this study was to assess clinical outcomes after combined pressure and flow assessment of coronary lesions. Background: Although fractional flow reserve (FFR) remains the invasive reference standard for revascularization, approximately 40% of stenoses have discordant coronary flow reserve (CFR). Optimal treatment for these disagreements remains unclear. Methods: A total of 455 subjects with 668 lesions were enrolled from 12 sites in 6 countries. Only lesions with reduced FFR and CFR underwent revascularization; all other combinations received initial medical therapy. Results: Fourteen percent of lesions had FFR ≤0.8 but CFR ≥2.0 while 23% of lesions had FFR >0.8 but CFR 0.8 and CFR ≥2.0 (6.2% event rate) exceeded the prespecified +10% noninferiority margin (P = 0.090). Target vessel failure models using both continuous FFR and continuous CFR found that only higher FFR was associated with reduced target vessel failure (Cox P = 0.007) after initial medical treatment. Central core laboratory review accepted 69.8% of all tracings with mean differences of 0.8 and CFR ≥2.0. These results do not support using invasive CFR ≥2.0 to defer revascularization for lesions with reduced FFR if the patient would otherwise be a candidate on the basis of the entire clinical scenario and treatment preference.

Introduction: The predictors of stent treatment failure and their importance 10 years after treatment with drug-eluting stents (DESs) have not been reported in detail. Methods: Data were retrieved from the SORT-OUT II database encompassing 2,849 non-left main coronary lesions in 2,073 unselected all-comer patients treated with first-generation DES and followed clinically for 10 years. Stent treatment failure (STF) was defined as definite or probable stent thrombosis, target lesion revascularization (TLR), or >70% restenosis left untreated. Target lesion failure (TLF) was defined as cardiac death, target vessel myocardial infarction, or TLR. Characteristics predicting higher hazard ratios (HRs) were identified by the multivariate Cox regression analysis. Results: A stent diameter ≤2.5 versus ≥3.5 mm had STF 23.3 versus 11.8% and TLF 27.9 versus 18.8%. Stent length 40 mm had STF 13.0 versus 29.0% and TLF 18.7 versus 34.6%. In multivariate analysis, decreasing stent diameter (HR: 1.24 [3.0 mm] to 2.12 [2.25 mm], reference ≥3.5 mm) and increasing stent length (HR: 1.15 [20–30 mm] to 2.07 [>40 mm], reference Conclusions: Ten-year outcomes show large variations depending on the stent size and a few patient and lesion characteristics. The calculation of a PS from these unambiguous variables may be used to improve the risk estimate in individual lesions and patients.

Objectives This study was designed to compare head-to-head fractional flow reserve (FFR) derived from coronary computed tomography angiography (CTA) (FFRCT) and cardiac magnetic resonance (CMR) stress perfusion imaging for prediction of standard-of-care–guided coronary revascularization in patients with stable chest pain and obstructive coronary artery disease by coronary CTA. Background FFRCT is a novel modality for noninvasive functional testing. The clinical utility of FFRCT compared to CMR stress perfusion imaging in symptomatic patients with coronary artery disease is unknown. Methods Prospective study of patients (n=110) with stable angina pectoris and 1 or more coronary stenosis ≥50% by coronary CTA. All patients underwent invasive coronary angiography. Revascularization was FFR-guided in stenoses ranging from 30% to 90%. FFRCT ≤0.80 in 1 or more coronary artery or a reversible perfusion defect (≥2 segments) by CMR categorized patients with ischemia. FFRCT and CMR were analyzed by core laboratories blinded for patient management. Results A total of 38 patients (35%) underwent revascularization. Per-patient diagnostic performance for identifying standard-of-care–guided revascularization, (95% confidence interval) yielded a sensitivity of 97% (86 to 100) for FFRCT versus 47% (31 to 64) for CMR, p 0.05, respectively. Conclusions In patients with stable chest pain referred to invasive coronary angiography based on coronary CTA, FFRCT and CMR yielded similar overall diagnostic accuracy. Sensitivity for prediction of revascularization was highest for FFRCT, whereas specificity was highest for CMR.

BACKGROUND: Patients with three-vessel coronary artery disease have been found to have better outcomes with coronary-artery bypass grafting (CABG) than with percutaneous coronary intervention (PCI), but studies in which PCI is guided by measurement of fractional flow reserve (FFR) have been lacking.METHODS: In this multicenter, international, noninferiority trial, patients with three-vessel coronary artery disease were randomly assigned to undergo CABG or FFR-guided PCI with current-generation zotarolimus-eluting stents. The primary end point was the occurrence within 1 year of a major adverse cardiac or cerebrovascular event, defined as death from any cause, myocardial infarction, stroke, or repeat revascularization. Noninferiority of FFR-guided PCI to CABG was prespecified as an upper boundary of less than 1.65 for the 95% confidence interval of the hazard ratio. Secondary end points included a composite of death, myocardial infarction, or stroke; safety was also assessed.RESULTS: A total of 1500 patients underwent randomization at 48 centers. Patients assigned to undergo PCI received a mean (±SD) of 3.7±1.9 stents, and those assigned to undergo CABG received 3.4±1.0 distal anastomoses. The 1-year incidence of the composite primary end point was 10.6% among patients randomly assigned to undergo FFR-guided PCI and 6.9% among those assigned to undergo CABG (hazard ratio, 1.5; 95% confidence interval [CI], 1.1 to 2.2), findings that were not consistent with noninferiority of FFR-guided PCI (P = 0.35 for noninferiority). The incidence of death, myocardial infarction, or stroke was 7.3% in the FFR-guided PCI group and 5.2% in the CABG group (hazard ratio, 1.4; 95% CI, 0.9 to 2.1). The incidences of major bleeding, arrhythmia, and acute kidney injury were higher in the CABG group than in the FFR-guided PCI group.CONCLUSIONS: In patients with three-vessel coronary artery disease, FFR-guided PCI was not found to be noninferior to CABG with respect to the incidence of a composite of death, myocardial infarction, stroke, or repeat revascularization at 1 year. (Funded by Medtronic and Abbott Vascular; FAME 3 ClinicalTrials.gov number, NCT02100722.).

BACKGROUND: There are limited data on the association of membranous septum (MS) morphology and transcatheter heart valve (THV) implantation depth, and the development of new conduction abnormalities (CA) after transcatheter aortic valve implantation (TAVI). AIMS: The aim of this study was to describe the morphology of the MS and predict the risk of new CA after TAVI based on the MS morphology and THV implantation depth. METHODS: Based on preprocedural CT scans, the MS depth was measured for every 25% of the entire MS width in 272 TAVI patients without preprocedural bundle branch block (BBB) or pacemaker. Post-procedural CT scans for THV implantation depth assessment were available in 130 of these patients. RESULTS: The MS depth was a median of 2.5 mm (IQR 1.4-3.8) deeper at the posterior edge when compared to the anterior edge of the MS. New CA developed in 7.1% of patients in whom the THV did not cross the lower MS border at its anterior edge (3.6% with new BBB and high degree CA, respectively), in 18.8% of patients (15.6% with new BBB and 3.1% with new high-degree CA) where the THV overlapped the lower MS border by

BACKGROUND:Investigating the effect of newly approved oncological drugs in the real-world is warranted. With emerging novel treatments rapidly being approved for urothelial tract cancers, we aimed to assess real-world data, regarding effect and safety, during the first year after approval of pembrolizumab in Denmark for patients with locally advanced and unresectable or metastatic urothelial tract cancer (mUTC) in the first- and second-line setting.MATERIALS AND METHOD:At the six oncological departments treating mUTC in Denmark, we identified all mUTC patients receiving pembrolizumab during the first year after approval, between March 1, 2018 and February 28, 2019. A retrospective data collection was conducted from January to June 2020. Patient characteristics matching that of the relevant clinical trials for pembrolizumab in first- and second-line treatment-setting, overall survival (OS), progression-free survival (PFS), toxicity and tumor response were assessed.RESULTS:139 patients were identified, 53 in first-line treatment, 77 in second-line, and 9 receiving third or later lines of treatment. The population was characterized by a majority of males (70%), most patients had ECOG PS 0–1 (60.4%) and primary tumor in the bladder was predominant (90.6%). The overall response rate (ORR) in first-line was 30.2%, PFS was 3,5 months (95%CI 2,3–7,9 months) and OS 9,2 months (95%CI 7,0–20.9 months). For second-line treatment the ORR was 27,3%, PFS 2,9 months (95%CI 2,5–5,3) and OS 9.1 months (95%CI 5,4–12,8 months). Toxicity was comparable to clinical trials without any new toxicities registered.CONCLUSION:Real-world data on response rates, OS, PFS and toxicity for patients with mUTC receiving pembrolizumab in first- and second-line, shows comparable results to clinical trials. This study further establishes immunotherapy as an effective and tolerable treatment for mUTC. BACKGROUND: Investigating the effect of newly approved oncological drugs in the real-world is warranted. With emerging novel treatments rapidly being approved for urothelial tract cancers, we aimed to assess real-world data, regarding effect and safety, during the first year after approval of pembrolizumab in Denmark for patients with locally advanced and unresectable or metastatic urothelial tract cancer (mUTC) in the first- and second-line setting. MATERIALS AND METHOD: At the six oncological departments treating mUTC in Denmark, we identified all mUTC patients receiving pembrolizumab during the first year after approval, between March 1, 2018 and February 28, 2019. A retrospective data collection was conducted from January to June 2020. Patient characteristics matching that of the relevant clinical trials for pembrolizumab in first- and second-line treatment-setting, overall survival (OS), progression-free survival (PFS), toxicity and tumor response were assessed. RESULTS: 139 patients were identified, 53 in first-line treatment, 77 in second-line, and 9 receiving third or later lines of treatment. The population was characterized by a majority of males (70%), most patients had ECOG PS 0-1 (60.4%) and primary tumor in the bladder was predominant (90.6%). The overall response rate (ORR) in first-line was 30.2%, PFS was 3,5 months (95%CI 2,3-7,9 months) and OS 9,2 months (95%CI 7,0-20.9 months). For second-line treatment the ORR was 27,3%, PFS 2,9 months (95%CI 2,5-5,3) and OS 9.1 months (95%CI 5,4-12,8 months). Toxicity was comparable to clinical trials without any new toxicities registered. CONCLUSION: Real-world data on response rates, OS, PFS and toxicity for patients with mUTC receiving pembrolizumab in first- and second-line, shows comparable results to clinical trials. This study further establishes immunotherapy as an effective and tolerable treatment for mUTC.

BACKGROUND: The optimal revascularisation strategy for patients with left main coronary artery disease is uncertain. We therefore aimed to evaluate long-term outcomes for patients treated with percutaneous coronary intervention (PCI) with drug-eluting stents versus coronary artery bypass grafting (CABG).METHODS: In this individual patient data meta-analysis, we searched MEDLINE, Embase, and the Cochrane database using the search terms "left main", "percutaneous coronary intervention" or "stent", and "coronary artery bypass graft*" to identify randomised controlled trials (RCTs) published in English between database inception and Aug 31, 2021, comparing PCI with drug-eluting stents with CABG in patients with left main coronary artery disease that had at least 5 years of patient follow-up for all-cause mortality. Two authors (MSS and BAB) identified studies meeting the criteria. The primary endpoint was 5-year all-cause mortality. Secondary endpoints were cardiovascular death, spontaneous myocardial infarction, procedural myocardial infarction, stroke, and repeat revascularisation. We used a one-stage approach; event rates were calculated by use of the Kaplan-Meier method and treatment group comparisons were made by use of a Cox frailty model, with trial as a random effect. In Bayesian analyses, the probabilities of absolute risk differences in the primary endpoint between PCI and CABG being more than 0·0%, and at least 1·0%, 2·5%, or 5·0%, were calculated.FINDINGS: Our literature search yielded 1599 results, of which four RCTs-SYNTAX, PRECOMBAT, NOBLE, and EXCEL-meeting our inclusion criteria were included in our meta-analysis. 4394 patients, with a median SYNTAX score of 25·0 (IQR 18·0-31·0), were randomly assigned to PCI (n=2197) or CABG (n=2197). The Kaplan-Meier estimate of 5-year all-cause death was 11·2% (95% CI 9·9-12·6) with PCI and 10·2% (9·0-11·6) with CABG (hazard ratio 1·10, 95% CI 0·91-1·32; p=0·33), resulting in a non-statistically significant absolute risk difference of 0·9% (95% CI -0·9 to 2·8). In Bayesian analyses, there was an 85·7% probability that death at 5 years was greater with PCI than with CABG; this difference was more likely than not less than 1·0% (INTERPRETATION: Among patients with left main coronary artery disease and, largely, low or intermediate coronary anatomical complexity, there was no statistically significant difference in 5-year all-cause death between PCI and CABG, although a Bayesian approach suggested a difference probably exists (more likely than not FUNDING: No external funding.

Objective: We explored the comparability of anxiety measures from register- and survey-based data including analyses of prevalence and associations with selected psychiatric and somatic diseases. Methods: We measured anxiety using Danish registers (hospital diagnosis and anxiolytic drug prescriptions), self-reports, symptom checklist (SCL) scores, and a clinical interview in 7493 adults with mean age 52 (SD 13.3) years who participated in a health survey between 2012 and 2015. We estimated the prevalence of anxiety, agreement between different measures and performed quantitative bias analysis. Results: The lifetime prevalence of hospital diagnosed anxiety, anxiolytic drug prescriptions, and self-reported anxiety were 4.4%, 6.2%, and 5.1%, respectively, after adjusting for selective participation. The agreement between the different anxiety measures was low. Thus, 25% with an anxiety diagnosis and 20% with anxiolytic drug prescriptions also had a high SCL score. Anxiolytic drugs were the only measure significantly associated with higher odds of heart disease. Hospital diagnosis and self-reported anxiety were associated with depression with odds ratio (OR) above 15, whereas anxiolytic drug prescriptions were less strongly associated (OR = 2.2(95% confidence interval: 1.26–3.91)). The risk estimates attenuated considerably when correcting for measurement error, whereas the ORs became slightly higher when the selective participation in the survey was accounted for. Conclusion: Anxiety diagnosed in hospitals and self-reported anxiety showed low level of agreement but provide comparable results regarding frequency measures and associations with disease outcomes.

We compared 10-year clinical outcomes in diabetes and nondiabetes patients treated with Endeavor zotarolimus-eluting (ZES) or Cypher sirolimus-eluting coronary stents (SES). A total of 1,162 patients were randomized to ZES (169 with diabetes) and 1,170 patients were randomized to SES (168 with diabetes). Patients were further stratified by diabetes status at the time of inclusion. A subgroup of patients with diabetes (n = 88) underwent angiographic re-evaluation 10 months after stent implantation. End points included a combined end point of death or myocardial infarction, and the individual end points of death, myocardial infarction, and revascularization. In patients with diabetes, we found no difference in the combined end point (odds ratio [OR] 0.81, 95% confidence interval [CI] 0.53 to 1.24), death (OR 0.80, 95% CI 0.51 to 1.25), or in MI (OR 1.07, 95% CI 0.60 to 1.91). However, diabetics with ZES more frequently underwent coronary revascularization compared with SES patients (OR 1.93, 95% CI 1.05 to 3.66). In patients without diabetes, ZES and SES had similar 10-year rates of all end points (death: OR 1.13, 95% CI 0.93 to 1.39; MI: OR 0.80, 95% CI 0.61 to 1.05; revascularization: OR 0.81, 95% CI 0.61 to 1.09). Landmark analysis from 5 to 10 years showed no difference in outcomes between SES and ZES in either subgroup. In conclusion, at 10 years, SES and ZES performed similarly in patients with and without diabetes. Although coronary revascularization was more prevalent in diabetes patients with ZES, this may, in part, have been related to the angiographic follow-up that was offered to a subgroup of diabetes patients.

A patient with chest pain and inferoseptal ischemia at Rubidium-82 Positron Emission Tomography (82RbPET) was revascularized in a stenosis in the LAD/D1 bifurcation, while a CTO RCA was left untreated. One-year follow-up with Seattle Angina Questionnaire and repeat 82RbPET revealed symptom relief and improved inferoseptal perfusion likely through LAD collateralization.

BACKGROUND: The aim of this study was to compare the 12-month clinical outcomes of patients treated with Magmaris or Orsiro. Second generation drug-eluting absorbable metal scaffold Magmaris (Dreams 2G) has proved to be safe and effective in the BIOSOLVE-II study. Similarly, biodegradable polymer sirolimus-eluting stent, Orsiro has shown notable clinical results even in all-comer populations.METHODS: Magmaris group patients were taken from the BIOSOLVE-II and BIOSOLVE-III trials, while the patients from Orsiro group were enrolled in BIOFLOW-II trial. The primary outcome was explored using a time-to-event assessment of the unadjusted clinical outcomes for target lesion failure (TLF) at 12 months, followed by a multivariate analysis adjusting for all the significantly different covariates between the groups.RESULTS: The study population consisted of 482 patients (521 lesions), 184 patients (189 lesions) in Magmaris group and 298 patients (332 lesions) in Orsiro group. The mean age was 65.5 ± 10.8 and 62.7 ± 10.4 years in Magmaris and Orsiro groups, respectively (p = 0.005). Magmaris and Orsiro unadjusted TLF rates were 6.0 and 6.4% with no significant difference between the groups (p = 0.869). In the multivariate analysis, there were no meaningful differences between Magmaris and Orsiro groups. Finally, none of the groups presented device thrombosis cases at 12 months.CONCLUSION: At 12 months there were no significant differences between Magmaris and Orsiro groups neither in the unadjusted assessment nor in the multivariate analysis for target lesion failure. These results should be taken as hypothesis generating and may warrant a head to head comparison on a randomized fashion.

Background Multiple barriers for accessing hepatitis C virus (HCV) treatment were identified during the interferon-based (IFN) treatment era for people who inject drugs (PWID). Whether these barriers persist since the introduction of IFN-free direct-acting antiviral (DAA) agents in Canada remains to be documented. This study examined temporal trends in HCV treatment initiation and associated factors during the transition from INF-based to all-oral DAA regimens. Methods The study population was drawn from a prospective cohort of PWID in Montreal, Canada. At three-month/one-year intervals between 2011 and 2017, participants with chronic HCV infection completed an interviewer-administered questionnaire on socio-demographic characteristics, drug use and health service utilisation, including HCV treatment. Time-updated Cox multivariate regression models, stratified by DAA + INF (2011-2013) and all-oral DAA (2014–2017) availability periods, were conducted to examine associations between time to HCV treatment initiation and associated barriers and facilitators. Results Of 308 participants (85% male, median age 42 [IQR: 33, 50]), 80 (26%) initiated HCV treatment during 915 person-years (PY). Incidence rates increased from 1.6 /100 PY (95%CI:0.9–2.6) in 2011 to 12.7 (10.6–15.1) in 2017 (p-trend = 0.0012). In multivariate analyses, visiting a primary care physician (2011–2013: aHR = 3.63[1.21–10.9]; 2014–2017: 2.52[1.10–5.77]) and frequent injection (0.23[0.05–0.99] and 0.49[0.24–0.99]) were consistently associated with treatment initiation. Participants aged >40 (2.27[1.24–4.13]), receiving opioid agonist therapy (OAT) (2.17[1.19–3.94]), and reporting prior HCV treatment (3.00[1.75–5.15]) were more likely to initiate treatment in the all-oral DAA period. Conclusion Treatment initiation increased between 2011 and 2017, but still remains low among PWID. Primary care visiting was a key facilitator regardless of the period, while engagement in OAT and health services, indicated by prior HCV treatment, increased the likelihood of treatment initiation in the DAA era. These findings suggest that access to health services is essential but not enough to scale up treatment in this population.

We aimed to identify factors influencing the sensitivity of perfusion imaging after an initial positive coronary computed tomography angiography (CCTA) using invasive coronary angiography (ICA) with conditional fractional flow reserve (FFR) as reference. Secondly we aimed to identify factors associated with revascularisation and to evaluate treatment outcome after ICA. We analysed 292 consecutive patients with suspected significant coronary artery disease (CAD) at CCTA, who underwent perfusion imaging with either cardiac magnetic resonance (CMR) or myocardial perfusion scintigraphy (MPS) followed by ICA with conditional FFR. Stratified analysis and uni- and multiple logistic regression analyses were performed to identify predictors of diagnostic agreement between perfusion scans and ICA and predictors of revascularisation. Myocardial ischemia evaluated with perfusion scans was present in 65/292 (22%) while 117/292 (40%) had obstructive CAD evaluated by ICA. Revascularisation rate was 90/292 (31%). The overall sensitivity for perfusion scans was 39% (30–48), specificity 89% (83–93), PPV 69% (57–80) and NPV 68% (62–74). Stratified analysis showed higher sensitivities in patients with multi-vessel disease at CCTA 49% (37–60) and typical chest pain 50% (37–60). Predictors of revascularisation were multi-vessel disease by CCTA (OR 3.51 [1.91–6.48]) and a positive perfusion scan (OR 4.69 [2.49–8.83]). The sensitivity for perfusion scans after CCTA was highest in patients with typical angina and multiple lesions at CCTA and predicted diagnostic agreement between perfusion scans and ICA. Abnormal perfusion and multi vessel disease at CCTA predicted revascularisation.

AIMS: CT-QFR is a novel coronary computed tomography angiography (CTA) based method for on-site evaluation of patients with suspected obstructive coronary artery disease (CAD). We compared the diagnostic performance of CT-QFR with myocardial perfusion scintigraphy (MPS) and cardiovascular magnetic resonance (CMR) as second-line tests in patients with suspected obstructive CAD after coronary CTA.METHODS AND RESULTS: Paired analysis of CT-QFR and MPS or CMR, with an invasive FFR-based classification as reference standard. Symptomatic patients with >50% diameter stenosis on coronary CTA were randomized to MPS or CMR and referred for invasive coronary angiography. The rate of coronary CTA not feasible for CT-QFR analysis was 17%. Paired patient-level data were available for 118 patients in the MPS group and 113 in the CMR group, respectively. Patient-level diagnostic accuracy was better for CT-QFR than for both MPS ((82.2% (95%CI 75.2-89.2) vs. 70.3% (95%CI 62.0-78.7), p=0.029) and CMR ((77.0% (95%CI 69.1-84.9) vs. 65.5% (95%CI 56.6-74.4), p=0.047). Following a positive coronary CTA and with the intention-to diagnose, CT-QFR, CMR and MPS were equally suitable as rule-in and rule-out modalities.CONCLUSIONS: The diagnostic performance of CT-QFR as second-line test was at least similar to MPS and CMR for the evaluation of obstructive coronary artery disease in symptomatic patients presenting with ≥50% diameter stenosis on coronary CTA.

Objectives To compare the early vascular healing of ruptured plaques (RP) and non-ruptured plaques (NRP) one month after primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI), using optical coherence tomography (OCT). Background Vascular healing and strut coverage are important factors in reducing the risk of stent thrombosis after PCI. Influence of underlying lesion characteristics and differences in healing response between RP and NRP are unknown. Methods Twenty-six STEMI-patients underwent PCI and implantation of a polymer-free drug-coated Biofreedom stent (BF-BES). OCT was performed pre-PCI, post-PCI and at 1-month follow-up. The patients were divided into two groups: RP=15 and NRP=11. OCT analyses of culprit lesion, post stent implantation at baseline and follow-up were performed to determine the difference in vascular healing based on presence of uncovered and/or malapposed stent struts and intraluminal filling defects. Results The stent coverage did not differ significantly between the two groups at 1-month follow-up with percentage of uncovered struts: RP 26.5% [IQR 15.0-49.0] and NRP 28.1% [IQR 15.5-38.8] for NRP (p=0.78). At 1-month, RP showed an increased percentage of late acquired malapposed struts (1.4% [IQR 0.8-2.4] vs. 0.0% [IQR 0.0-1.4], p=0.03) and a larger total malapposition area (1.3 mm2 [IQR 0.4-2.5] vs. 0.0 mm2 [IQR 0.0-0.9], p=0.01), compared to NRP. Conclusion Three out of four struts were covered within one month after stenting. The vascular healing was comparable in RP and NRP on stent coverage. However, RP had more and larger late acquired malapposition areas. Condensed abstract In 26 patients with ST-segment elevation myocardial infarction optical coherence tomography was performed before and after implantation of a Biofreedom (BF-BES) polymer-free drug-coated stent, and after one month. Lesion morphology was determined and divided into two groups: ruptured plaques (RP) or non-ruptured plaques (NRP). The stent coverage did not differ significantly between the two groups at 1-month follow-up with percentage of uncovered struts: RP 26.5% [IQR 15.0-49.0] and NRP 28.1% [IQR 15.5-38.8] for NRP (p=0.78). Culprit lesions with RP had more and larger areas of late acquired malapposed struts compared to lesions with NRP.

Aims Recent technological advances enable diagnosing of obstructive coronary artery disease (CAD) from heart sound analysis with a high negative predictive value. However, the prognostic impact of this approach remains unknown. To investigate the prognostic value of heart sound analysis as two scores, the Acoustic-score and the CAD-score, in patients with suspected CAD which is treated according to standard of care. Methods and results Consecutive patients with angina symptoms referred for coronary computed tomography angiography (CTA) were enrolled. The Acoustic-score was developed from eight acoustic CAD-related features. This score was combined with risk factors to generate the CAD-score. A cut-off score >20 was pre-specified for both scores to indicate disease. If coronary CTA raised suspicion of obstructive CAD, patients were referred to invasive angiography and revascularized when indicated. Of 1675 enrolled patients, 1464 (87.4%) were included in this substudy. The combined primary endpoint was all-cause mortality and myocardial infarction (n = 26). Follow-up was 3.1 (2.7–3.4) years. Of patients with primary endpoints, the Acoustic-score was >20 in 25 (96%); the CAD-score was >20 in 22 (85%). In an unadjusted Cox analysis of the primary endpoints, the hazard ratio for scores >20 under current standard clinical care was 12.6 (1.7–93.2) for the Acoustic-score and 5.4 (1.9–15.7) for the CAD-score. The CAD-score contained prognostic information even after adjusting for lipid-lowering therapy initiation, stenosis at CTA, and early revascularization. Conclusion Heart sound analysis seems to carry prognostic information and may improve initial risk stratification of patients with suspected CAD. Clinicaltrials.org ID NCT02264717.

Background: In coronary artery bypass grafting (CABG), the use of fractional flow reserve (FFR) is insufficiently investigated. Stenosis assessment usually relies on visual estimates of lesion severity. This study evaluated health-related quality of life (HRQoL) and angina after FFR- versus angiography-guided CABG. Methods: One hundred patients referred for CABG were randomized to FFR- or angiography-guided CABG. In the FFR group, lesions with FFR>0.80 were deferred, while the surgeon was blinded to the FFR values in the angiography group. Before and 6 months after CABG, HRQoL was assessed by the health state classifier EQ-5D of the EuroQoL 5-level instrument and angina status based on the Canadian Cardiovascular Society classification system were registered. Results: Six-month angiography included FFR evaluations of deferred lesions. In total, completed EQ-5D of the EuroQoL 5-level instrument questionnaires were available in 86 patients (43 in the FFR versus 43 in the angiography-guided group). HRQoL was significantly improved and angina significantly decreased from baseline to 6 months after CABG with no difference between the randomization groups. Graft failure rates and clinical outcomes were similar in both groups. Patients with graft failure or FFRP =0.004) and more angina compared with patients without graft failure or FFR≥0.80 at 6-month follow-up. Conclusions: FFR- versus angiography-guided CABG demonstrated similar improvements in HRQoL and angina 6 months after CABG. Graft failure or low FFR in deferred lesions were associated with low HRQoL and angina. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02477371

Background: Polygenic risk scores (PRSs) are associated with coronary artery disease (CAD), but the clinical potential of using PRSs at the single-patient level for risk stratification has yet to be established. We investigated whether adding a PRS to clinical risk factors (CRFs) improves risk stratification in patients referred to coronary computed tomography angiography on a suspicion of obstructive CAD. Methods: In this prespecified diagnostic substudy of the Dan-NICAD trial (Danish study of Non-Invasive testing in Coronary Artery Disease), we included 1617 consecutive patients with stable chest symptoms and no history of CAD referred for coronary computed tomography angiography. CRFs used for risk stratification were age, sex, symptoms, prior or active smoking, antihypertensive treatment, lipid-lowering treatment, and diabetes. In addition, patients were genotyped, and their PRSs were calculated. All patients underwent coronary computed tomography angiography. Patients with a suspected ≥50% stenosis also underwent invasive coronary angiography with fractional flow reserve. A combined end point of obstructive CAD was defined as a visual invasive coronary angiography stenosis >90%, fractional flow reserve 50% if fractional flow reserve measurements were not feasible. Results: The PRS was associated with obstructive CAD independent of CRFs (adjusted odds ratio, 1.8 [95% CI, 1.5–2.2] per SD). The PRS had an area under the curve of 0.63 (0.59–0.68), which was similar to that for age and sex. Combining the PRS with CRFs led to a CRF+PRS model with area under the curve of 0.75 (0.71–0.79), which was 0.04 more than the CRF model ( P =0.0029). By using pretest probability (pretest probability) cutoffs at 5% and 15%, a net reclassification improvement of 15.8% ( P =3.1×10 −4 ) was obtained, with a down-classification of risk in 24% of patients (211 of 862) in whom the pretest probability was 5% to 15% based on CRFs alone. Conclusions: Adding a PRS improved risk stratification of obstructive CAD beyond CRFs, suggesting a modest clinical potential of using PRSs to guide diagnostic testing in the contemporary clinical setting. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02264717.

OBJECTIVE: To evaluate the diagnostic performance of quantitative flow ratio (QFR) related to fractional flow reserve (FFR) and resting distal-to-aortic pressure ratio (resting Pd/Pa) concordance.BACKGROUND: QFR is a method for computation of FFR based on standard coronary angiography. It is unclear how QFR is performed in patients with discordance between FFR and resting pressure ratios (distal-to-aortic pressure ratio [Pd/Pa]).MATERIALS AND METHODS: The main comparison was the diagnostic performance of QFR with FFR as reference stratified by correspondence between FFR and resting Pd/Pa. Secondary outcome measures included distribution of clinical or procedural characteristics stratified by FFR and resting Pd/Pa correspondence.RESULTS: Four prospective studies matched the inclusion criteria. Analysis was performed on patient level data reaching a total of 759 patients and 887 vessels with paired FFR, QFR, and resting Pd/Pa. Median FFR was 0.85 (IQR: 0.77-0.90). Diagnostic accuracy of QFR with FFR as reference was higher if FFR corresponded to resting Pd/Pa: accuracy 90% (95% CI: 88-92) versus 72% (95% CI: 64-80), p CONCLUSION: Diagnostic performance of QFR with FFR as reference is reduced for lesions with discordant FFR (≤0.80) and resting Pd/Pa (≤0.92) measurements.

Background Near-infrared spectroscopy (NIRS) and intravascular ultrasound are promising imaging modalities to identify non-obstructive plaques likely to cause coronary-related events. We aimed to assess whether combined NIRS and intravascular ultrasound can identify high-risk plaques and patients that are at risk for future major adverse cardiac events (MACEs). Methods PROSPECT II is an investigator-sponsored, multicentre, prospective natural history study done at 14 university hospitals and two community hospitals in Denmark, Norway, and Sweden. We recruited patients of any age with recent (within past 4 weeks) myocardial infarction. After treatment of all flow-limiting coronary lesions, three-vessel imaging was done with a combined NIRS and intravascular ultrasound catheter. Untreated lesions (also known as non-culprit lesions) were identified by intravascular ultrasound and their lipid content was assessed by NIRS. The primary outcome was the covariate-adjusted rate of MACEs (the composite of cardiac death, myocardial infarction, unstable angina, or progressive angina) arising from untreated non-culprit lesions during follow-up. The relations between plaques with high lipid content, large plaque burden, and small lumen areas and patient-level and lesion-level events were determined. This trial is registered with ClinicalTrials.gov, NCT02171065. Findings Between June 10, 2014, and Dec 20, 2017, 3629 non-culprit lesions were characterised in 898 patients (153 [17 women, 745 [83 men; median age 63 [IQR 55-70] years). Median follow-up was 3.7 (IQR 3.0-4.4) years. Adverse events within 4 years occurred in 112 (13.2 951.0-15.6) of 898 patients, with 66 (8.0 95.2-10.0) arising from 78 untreated non-culprit lesions (mean baseline angiographic diameter stenosis 46.9[SD 15.9]). Highly lipidic lesions (851 [24 of 3500 lesions, present in 520 [59 of 884 patients) were an independent predictor of patient-level non-culprit lesion-related MACEs (adjusted odds ratio 2.27, 95.25-4.13) and nonculprit lesion-specific MACEs (7.83, 4.12-14.89). Large plaque burden (787 [22 of 3629 lesions, present in 530 [59 of 898 patients) was also an independent predictor of non-culprit lesion-related MACEs. Lesions with both large plaque burden by intravascular ultrasound and large lipid-rich cores by NIRS had a 4-year non-culprit lesion-related MACE rate of 7.095.0-10.0). Patients in whom one or more such lesions were identified had a 4-year non-culprit lesion-related MACE rate of 13.295.4-17.6). Interpretation Combined NIRS and intravascular ultrasound detects angiographically non-obstructive lesions with a high lipid content and large plaque burden that are at increased risk for future adverse cardiac outcomes. Copyright (C) 2021 Elsevier Ltd. All rights reserved. BackgroundNear-infrared spectroscopy (NIRS) and intravascular ultrasound are promising imaging modalities to identify non-obstructive plaques likely to cause coronary-related events. We aimed to assess whether combined NIRS and intravascular ultrasound can identify high-risk plaques and patients that are at risk for future major adverse cardiac events (MACEs).MethodsPROSPECT II is an investigator-sponsored, multicentre, prospective natural history study done at 14 university hospitals and two community hospitals in Denmark, Norway, and Sweden. We recruited patients of any age with recent (within past 4 weeks) myocardial infarction. After treatment of all flow-limiting coronary lesions, three-vessel imaging was done with a combined NIRS and intravascular ultrasound catheter. Untreated lesions (also known as non-culprit lesions) were identified by intravascular ultrasound and their lipid content was assessed by NIRS. The primary outcome was the covariate-adjusted rate of MACEs (the composite of cardiac death, myocardial infarction, unstable angina, or progressive angina) arising from untreated non-culprit lesions during follow-up. The relations between plaques with high lipid content, large plaque burden, and small lumen areas and patient-level and lesion-level events were determined. This trial is registered with ClinicalTrials.gov, NCT02171065.FindingsBetween June 10, 2014, and Dec 20, 2017, 3629 non-culprit lesions were characterised in 898 patients (153 [17%] women, 745 [83%] men; median age 63 [IQR 55–70] years). Median follow-up was 3·7 (IQR 3·0–4·4) years. Adverse events within 4 years occurred in 112 (13·2%, 95% CI 11·0–15·6) of 898 patients, with 66 (8·0%, 95% CI 6·2–10·0) arising from 78 untreated non-culprit lesions (mean baseline angiographic diameter stenosis 46·9% [SD 15·9]). Highly lipidic lesions (851 [24%] of 3500 lesions, present in 520 [59%] of 884 patients) were an independent predictor of patient-level non-culprit lesion-related MACEs (adjusted odds ratio 2·27, 95% CI 1·25–4·13) and non-culprit lesion-specific MACEs (7·83, 4·12–14·89). Large plaque burden (787 [22%] of 3629 lesions, present in 530 [59%] of 898 patients) was also an independent predictor of non-culprit lesion-related MACEs. Lesions with both large plaque burden by intravascular ultrasound and large lipid-rich cores by NIRS had a 4-year non-culprit lesion-related MACE rate of 7·0% (95% CI 4·0–10·0). Patients in whom one or more such lesions were identified had a 4-year non-culprit lesion-related MACE rate of 13·2% (95% CI 9·4–17·6).InterpretationCombined NIRS and intravascular ultrasound detects angiographically non-obstructive lesions with a high lipid content and large plaque burden that are at increased risk for future adverse cardiac outcomes.FundingAbbott Vascular, Infraredx, and The Medicines Company.

Children with congenital heart defects (CHDs) have increased risk of cognitive disabilities for reasons not fully understood. Previous studies have indicated signs of disrupted fetal brain growth from mid-gestation measured with ultrasound and magnetic resonance imaging (MRI) and infants with CHDs have decreased brain volumes at birth. We measured the total and regional brain volumes of infants with and without CHDs using MRI to investigate, if certain areas of the brain are at particular risk of disrupted growth. MRI brain volumetry analyses were performed on 20 infants; 10 with- (postmenstrual age 39–54 weeks, mean 44 weeks + 5 days) and 10 without CHDs (postmenstrual age 39–52 weeks, mean 43 weeks + 5 days). In six infants with- and eight infants without CHDs grey and white matter were also differentiated. Infants with CHDs had smaller brains (48 ml smaller; 95% CI, 6.1–90; p = 0.03), cerebrums (37.8 ml smaller; 95% CI, 0.8–74.8; p = 0.04), and cerebral grey matter (25.8 ml smaller; 95% CI, 3.5–48; p = 0.03) than infants without CHD. Brain volume differences observed within weeks after birth in children with CHDs confirm that the brain impact, which increase the risk of cognitive disabilities, may begin during pregnancy.

Background Real-world treatment patterns and survival outcomes of locally advanced, unresectable, and metastatic urinary tract cancer (mUTC) patients have not previously been studied in a nationwide, population-based cohort. Objective To describe treatment patterns and survival outcomes in mUTC patients treated in the real-world clinical setting. Design, setting, and participants This nationwide, population-based study included all mUTC patients initiating first-line chemotherapy at Danish oncology departments from January 2010 to March 2016. Data were retrospectively obtained from electronic medical records. Outcome measurements and statistical analysis Outcome measurements were descriptive. Kaplan-Meier was used for survival analysis. Results and limitations Of 952 patients included in the study, 46.2% initiated standard gemcitabine/cisplatin (GC) and 21.1% gemcitabine/carboplatin (CaG); the remaining patients initiated other treatment regimens. Median follow-up was 11.6 mo. The overall response rate and disease control rate were 43.0% and 61.7% in all patients, 51.4% and 69.1% in GC-treated patients, and 34.4% and 58.8% in CaG-treated patients, respectively. Median overall survival (OS) was 11.7 (95% confidence interval [CI]: 10.8–12.5) mo in all patients, 14.0 (95% CI: 12.5–15.5) mo in GC-treated patients, and 9.8 (95% CI: 8.7–10.9) mo in CaG-treated patients. Limitations include the retrospective study design. Conclusions Real-world mUTC patients are older and less fit than patients enrolled in clinical trials; despite this, tumor responses and survival are comparable. Survival in our patient cohort is also comparable with that reported from other real-world studies in this patient group. Patient summary We studied treatment patterns and survival in urinary tract cancer patients receiving chemotherapy in the real-world clinical practice. Survival in our patient cohort was comparable with that reported from clinical trials and other real-world studies in this patient group., Take Home Message Most metastatic urothelial tract cancer patients receiving chemotherapy in the real-world clinical setting at Danish oncology departments receive cisplatin-based treatment. Survival in our patient cohort was comparable with the survival reported in clinical trials and in other real-world studies in this patient group.

BACKGROUND: Patients with affective disorder seem to experience higher risks of several somatic diseases, but no studies have provided estimates of both absolute and relative risks for these diseases in the same population.METHODS: A prospective cohort of all patients age ≥18 years old with a hospital contact with affective disorder between 1997-2014 (n=246,282) and a random sample from the background population (n=167,562) was followed for hospitalizations with cardiovascular disease, diabetes, cancers, chronic obstructive pulmonary disease (COPD), asthma, inflammatory bowel disease, hip fracture, psoriasis, migraine, or dementia. Adjusted absolute and relative risk estimates were calculated using multivariable adjusted Aalen's additive and Cox proportional hazard regression models.RESULTS: After adjustments, the absolute risk difference was 130.6 (95% confidence interval [CI] 125.5-135.7) additional cases per 10,000 person-years among affective disorder patients compared to the reference population. The corresponding hazard ratio for any somatic disease was 1.50 (95% CI 1.48-1.52). The strongest associations were found for dementia, hip fracture, COPD, and stroke on both the relative and absolute scale. The patients did not have higher risk of cancers except for lung cancer and brain tumors. Risk estimates tended to be slightly higher for individuals with depression or other affective disorder compared to bipolar disorder.LIMITATIONS: Limitations include use of register-based data, risk of reverse causation and Berkson's bias.CONCLUSIONS: Patients with affective disorder have both higher absolute and relative risk of most somatic diseases except for cancers. Further identification of the shared mechanisms will facilitate the development of targeted interventions.

Objective Sarcopenia is known to influence cancer-related complications and overall survival. However, the effect of cancer treatment on the development or progression of sarcopenia is relatively unknown. The primary aim of this systematic review was to determine the prevalence and development of sarcopenia among people with bladder cancer. Data Sources A systematic search was performed in PubMed, Web of Science, and EMBASE. Studies with ≥2 assessments of sarcopenia were eligible for inclusion. Five retrospective cohorts were included with a total of 438 participants. The baseline prevalence of sarcopenia across studies varied from 25% to 69% and post-treatment prevalence from 50% to 81%. The average loss of muscle mass was 2.2% to 10% during a time course of 3 to 12 months. Conclusion The prevalence of sarcopenia markedly increased during cancer treatment in patients with bladder cancer. Further research into the effect of different treatment regimens on the development of sarcopenia, and how these changes might affect functional capacity and survival is needed. Implications for Nursing Practice The development of sarcopenia is important to understand because of its negative affect on quality of life, complications, and mortality. Further, understanding how sarcopenia develops during treatment could potentially strengthen nurses’ future care plans for patients with bladder cancer.

Background: Observational and small, randomized studies suggest that influenza vaccine may reduce future cardiovascular events in patients with cardiovascular disease. Methods: We conducted an investigator-initiated, randomized, double-blind trial to compare inactivated influenza vaccine with saline placebo administered shortly after myocardial infarction (MI; 99.7% of patients) or high-risk stable coronary heart disease (0.3%). The primary end point was the composite of all-cause death, MI, or stent thrombosis at 12 months. A hierarchical testing strategy was used for the key secondary end points: all-cause death, cardiovascular death, MI, and stent thrombosis. Results: Because of the COVID-19 pandemic, the data safety and monitoring board recommended to halt the trial before attaining the prespecified sample size. Between October 1, 2016, and March 1, 2020, 2571 participants were randomized at 30 centers across 8 countries. Participants assigned to influenza vaccine totaled 1290 and individuals assigned to placebo equaled 1281; of these, 2532 received the study treatment (1272 influenza vaccine and 1260 placebo) and were included in the modified intention to treat analysis. Over the 12-month follow-up, the primary outcome occurred in 67 participants (5.3%) assigned influenza vaccine and 91 participants (7.2%) assigned placebo (hazard ratio, 0.72 [95% CI, 0.52–0.99]; P =0.040). Rates of all-cause death were 2.9% and 4.9% (hazard ratio, 0.59 [95% CI, 0.39–0.89]; P =0.010), rates of cardiovascular death were 2.7% and 4.5%, (hazard ratio, 0.59 [95% CI, 0.39–0.90]; P =0.014), and rates of MI were 2.0% and 2.4% (hazard ratio, 0.86 [95% CI, 0.50–1.46]; P =0.57) in the influenza vaccine and placebo groups, respectively. Conclusions: Influenza vaccination early after an MI or in high-risk coronary heart disease resulted in a lower risk of a composite of all-cause death, MI, or stent thrombosis, and a lower risk of all-cause death and cardiovascular death, as well, at 12 months compared with placebo. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02831608.

Background: In the treatment of left main coronary artery (LMCA) disease, patients’ age may affect the clinical outcome after percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). This study stratified the clinical outcome according to the age of patients treated for LMCA stenosis with PCI or CABG in the Nordic-Baltic-British Left Main Revascularization (NOBLE) study. Methods: Patients with LMCA disease were enrolled in 36 centers in northern Europe and randomized 1:1 to treatment by PCI or CABG. Eligible patients had stable angina pectoris, unstable angina pectoris, or non-ST elevation myocardial infarction. The primary endpoint was major adverse cardiac or cerebrovascular events (MACCEs), a composite of all-cause mortality, nonprocedural myocardial infarction, any repeat coronary revascularization, and stroke. Age-stratified analysis was performed for the groups younger and older than 67 years and for patients older than 80 years. Results: For patients ≥67 years, the 5-year MACCEs were 35.7 versus 22.3% (hazard ratio [HR] 1.72 [95% confidence interval [CI] 1.27–2.33], p = 0.0004) for PCI versus CABG. The difference in MACCEs was driven by more myocardial infarctions (10.8 vs. 3.8% HR 3.01 [95% CI 1.52–5.96], p = 0.0009) and more repeat revascularizations (19.5 vs. 10.0% HR 2.01 [95% CI 1.29–3.12], p = 0.002). In patients younger than 67 years, MACCE was 20.5 versus 15.3% (HR 1.38 [95% CI 0.93–2.06], p = 0.11 for PCI versus CABG. All-cause mortality was similar after PCI and CABG in both age-groups. On multivariate analysis, age was a predictor of MACCE, along with PCI, diabetes, and SYNTAX score. Conclusions: As the overall NOBLE results show revascularization of LMCA disease, age of 67 years or older was associated with lower 5-year MACCE after CABG compared to PCI. Clinical outcomes were not significantly different in the subgroup younger than 67 years, although no significant interaction was present between age and treatment. Mortality was similar for all subgroups (ClinicalTrials.gov identifier: NCT01496651).

Aims The aim of present study was to examine the preoperative prevalence and distribution of impaired left ventricular global longitudinal strain (LVGLS) in elderly patients with symptomatic aortic stenosis (AS) undergoing transcutaneous aortic valve replacement (TAVR) and to determine the predictive value of LVGLS on survival. Methods We included 411 patients with symptomatic severe AS treated with TAVR during a 5-year period, where a baseline echocardiography including LVGLS assessment was available. Results Mean age was 80.1 ± 7.1 years and aortic valve area (AVA) index 0.4 ± 0.1 cm2. 78 patients died during a median follow-up of 762 days. Mean left ventricular ejection fraction (LVEF) was 50 ± 13% and mean LVGLS was − 14.0%. LVEF was preserved in 60% of patients, while impaired LVGLS > − 18% was seen in 75% of the patients. Previous myocardial infarction, LVEF − 14%, low gradient AS ( 30 mmHg were identified as significant univariate predictors of all-cause mortality. On multivariate analysis LVGLS > − 14% (HR 1.79 [1.02–3.14], p = 0.04) was identified as the only independent variable associated with all-cause mortality. Reduced survival was observed with an impaired LVGLS > − 14% in the total population (p 2 19.9, p = 0.006). Conclusions In patients with symptomatic AS undergoing TAVR, impaired LVGLS was highly prevalent despite preserved LVEF. LVGLS > − 14% was an independent predictor of all-cause mortality, and survival was reduced if LVGLS > − 14%.

OBJECTIVES: This study aims to evaluate the diagnostic performance of quantitative flow ratio (QFR) pre transcatheter aortic valve implantation (TAVI) in patients with aortic valve stenosis (AS) and coronary artery disease (CAD). Post-TAVI fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) was used as reference.BACKGROUND: CAD is prevalent in patients with AS, but the hemodynamics of AS confounds evaluation using pressure wire-based assessments. QFR might be less sensitive to the presence of AS thereby allowing for CAD evaluation before aortic valve replacement. Further, QFR does not require the use of pressure wire and therefore has the potential for reducing costs and complications related to insertion of a coronary pressure wire.METHODS: The diagnostic performance of QFR in coronary angiograms from 28 patients undergoing TAVI was evaluated. In all patients, both FFR and iFR were measured pre- and immediately post-TAVI while QFR was measured pre-TAVI.RESULTS: Using post-TAVI FFR and iFR as reference the diagnostic accuracy of pre-TAVI QFR were 83% (95%CI; 68-97) and 52% (95%CI; 30-74) p = .008, respectively.CONCLUSIONS: Pre-TAVI QFR showed a good diagnostic performance using post-TAVI FFR as reference. QFR could become a wire-free, safe, and quick way of evaluating CAD in patients with severe AS undergoing TAVI.

Background The recently updated pre-test probability (PTP) model for diagnosing chronic coronary syndrome suggested by the European Society of Cardiology (ESC) was designed to predict the presence of obstructive coronary artery disease (CAD). In addition to this model, identification of non-obstructive CAD and utilization of preventive interventions may also lower rates of death and non-fatal myocardial infarction. Opposite to the ESC PTP, the minimal risk tool (MRT) is a new model developed to identify individuals without CAD but symptoms suggestive of CAD. We explored a combined use of the 2 models to predict the absence or presence of obstructive CAD. Methods This was a sub-study of the Danish study of Non-Invasive testing in Coronary Artery Disease (Dan-NICAD) which included patients with low-intermediate PTP of CAD. Minimal risk was defined as having a coronary calcium score of 0, no evidence of coronary atherosclerosis at coronary computed tomography angiography, and no cardiovascular (CV) events defined as myocardial infarction, death or revascularization in the mean observation period of 3.1 [2.7–3.4] years. Obstructive CAD was defined as a fractional flow reserve 90% lumen reduction). The risk factors included in the MRT were age, sex, smoking history, diabetes mellitus, dyslipidaemia, family history of premature CAD, hypertension, symptoms related to stress, and high-density lipoprotein concentration. Based on a point-system ranging from 0–5, the MRT and the ESC PTP were combined (dual-PTP) (figure 1). A dual-PTP ≤1 indicated very low risk. Using both minimal risk and obstructive CAD as references, the dual PTP was compared to the MRT and the ESC PTP through tests of model discrimination. Results Of the 1544 eligible patients, 710 (46%) had normal coronary arteries and no CV events. Obstructive CAD was diagnosed in 152 (10%). Equivalent to a dual-PTP 50% or ESC PTP 5–15% and MRT >75% were classified as very low risk. Of these patients, 84% were at true minimal risk (red area figure 1). Furthermore, only 6 patients would have been diagnosed with obstructive CAD at ICA, and 0 events would be missed. The dual-PTP was non-inferior to the MRT and the ESC PTP in identifying patients having minimal risk and obstructive CAD, respectively (minimal risk: c-statistics 0.74 (0.72–0.77) vs. 0.76 (0.73–0.78); obstructive CAD: c-statistics 0.66 (0.62–0.70) vs. (0.67 (0.63–0.72)). The dual-PTP was superior to the ESC PTP in discriminating patients at minimal risk (c-statistics 0.74 (0.72–0.77) vs. 0.69 (0.67–0.71). Conclusions Combining the ESC PTP and the MRT, the dual-PTP seems to enable accurate prediction of both patients with minimal risk and patients with obstructive CAD. Based on the dual-PTP, patients can safely be deferred from or referred for diagnostic testing Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Aarhus University, Health Research Fund of Central Denmark Region

AIMS: This study sought to evaluate the incidence of ruptured plaques and nonruptured plaques (NRP) and to compare patient characteristics and detailed plaque morphology features between the two culprit types in ST-segment elevation myocardial infarction (STEMI) patients, using optical coherence tomography (OCT).METHODS AND RESULTS: Using OCT, the culprit lesions in patients with STEMI were assessed prior to stent implantation. The culprit lesion was categorized as ruptured plaques or NRP, and the plaque components were evaluated. Fifty-two patients (69.3%) presented with ruptured plaques and 23 (30.7%) with NRP. Patients with NRP were younger (58.0 ± 10.4 vs 64.7 ± 9.9 years, P = 0.01) and more often smokers (72.7% vs 37.1%, P = 0.001), compared to ruptured plaques. NRP contained significantly more fibrotic plaque (20.0% [interquartile range (IQR) 13.7-29.8] vs 11.3% [IQR 6.9-18.1], P = 0.005), but less lipidic plaque (44.0% ± 13.7 vs 59.3% ± 13.6, P CONCLUSIONS: One-third of STEMI patients had culprit lesions without an OCT-detectable ruptured plaque. Culprit lesions with NRP contained less vulnerable plaque components, such as lipid plaque, TCFAs and macrophages compared to ruptured plaques.

AIMS: We aimed to investigate the association between the use and findings of IVUS with clinical outcomes in the PCI arm of a randomised trial of LMS PCI.METHODS AND RESULTS: The NOBLE trial randomised patients with LMS disease to treatment by PCI or CABG. Of 603 patients treated by PCI, 435 (72%) underwent post-PCI IVUS assessment, 224 of which were analysed in a core laboratory. At five years, the composite of MACCE was 18.9% if post-PCI IVUS was performed versus 25.0% if it was not performed (p=0.45, after adjustment). Overall repeat revascularisation was not reduced (10.6% vs 16.5%, p=0.11); however, LMS TLR was (5.1% vs 11.6%, p=0.01) if IVUS was used. For comparison of stent expansion, LMS MSA was split into tertiles. We found no significant difference in MACCE, death, myocardial infarction or stent thrombosis between tertiles. There was a significant difference between the lower and upper tertiles for repeat revascularisation (17.6% vs 5.2%, p=0.02) and LMS TLR (12.2% vs 0%, p=0.002).CONCLUSIONS: Post-PCI IVUS assessment and adequate stent expansion are not associated with reduced MACCE; however, there is an association with reduced LMS TLR. The use of intracoronary imaging to prevent stent underexpansion in LMS PCI is likely to improve outcomes.

Risk stratification in patients with suspected coronary artery disease (CAD) is important. Recently, the minimal-risk-tool (MRT) was developed to identify individuals with low CAD risk despite symptoms in order to avoid unnecessary testing. We aimed to validate and update the MRT-model in a contemporary cohort. The Dan-NICAD trial cohort, consisting of 1675 consecutive patients referred for coronary computed tomography angiography (CTA), was used to calculate the MRT-score based on the published fitted variable coefficients from the PROMISE and SCOT-HEART trials. Minimal risk was defined as zero calcium score, no coronary atherosclerosis at coronary CTA, and no cardiovascular events in the follow-up period. We tested an updated MRT-model by pooling the fitted variable coefficients from all three trials. A total of 1544 patients fulfilling the inclusion criteria were followed for 3.1 [2.7-3.4] years. In 710 (46%) patients, the criteria for minimal risk were fulfilled. Despite substantial coefficient variation, the MRTs based on the PROMISE, the SCOT-HEART and the updated MRT variables showed similar moderate to high discriminative performance for minimal risk estimation. Although all three models tended to underestimate minimal risk, the updated MRT had the best performance. Using a 75% minimal risk cut-off, the updated MRT showed a sensitivity of 11.6% (95% CI 9.3-14.2%) and specificity of 99.3% (95% CI 98.6-99.8%). An updated MRT model based on three large studies increased calibration compared to the existing MRT models, whereas discrimination was similar despite substantial coefficient variation. The updated MRT might supplement currently recommended pre-test probability models.

Item does not contain fulltext BACKGROUND: The Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) trial was a non-inferiority trial that compared percutaneous coronary intervention (PCI) using first-generation paclitaxel-eluting stents with coronary artery bypass grafting (CABG) in patients with de-novo three-vessel and left main coronary artery disease, and reported results up to 5 years. We now report 10-year all-cause death results. METHODS: The SYNTAX Extended Survival (SYNTAXES) study is an investigator-driven extension of follow-up of a multicentre, randomised controlled trial done in 85 hospitals across 18 North American and European countries. Patients with de-novo three-vessel and left main coronary artery disease were randomly assigned (1:1) to the PCI group or CABG group. Patients with a history of PCI or CABG, acute myocardial infarction, or an indication for concomitant cardiac surgery were excluded. The primary endpoint of the SYNTAXES study was 10-year all-cause death, which was assessed according to the intention-to-treat principle. Prespecified subgroup analyses were performed according to the presence or absence of left main coronary artery disease and diabetes, and according to coronary complexity defined by core laboratory SYNTAX score tertiles. This study is registered with ClinicalTrials.gov, NCT03417050. FINDINGS: From March, 2005, to April, 2007, 1800 patients were randomly assigned to the PCI (n=903) or CABG (n=897) group. Vital status information at 10 years was complete for 841 (93%) patients in the PCI group and 848 (95%) patients in the CABG group. At 10 years, 244 (27%) patients had died after PCI and 211 (24%) after CABG (hazard ratio 1.17 [95% CI 0.97-1.41], p=0.092). Among patients with three-vessel disease, 151 (28%) of 546 had died after PCI versus 113 (21%) of 549 after CABG (hazard ratio 1.41 [95% CI 1.10-1.80]), and among patients with left main coronary artery disease, 93 (26%) of 357 had died after PCI versus 98 (28%) of 348 after CABG (0.90 [0.68-1.20], pinteraction=0.019). There was no treatment-by-subgroup interaction with diabetes (pinteraction=0.66) and no linear trend across SYNTAX score tertiles (ptrend=0.30). INTERPRETATION: At 10 years, no significant difference existed in all-cause death between PCI using first-generation paclitaxel-eluting stents and CABG. However, CABG provided a significant survival benefit in patients with three-vessel disease, but not in patients with left main coronary artery disease. FUNDING: German Foundation of Heart Research (SYNTAXES study, 5-10-year follow-up) and Boston Scientific Corporation (SYNTAX study, 0-5-year follow-up).

OBJECTIVES: We evaluated the diagnostic performance of quantitative flow ratio (QFR) assessment of nonculprit lesions (NCLs) based on acute setting angiograms obtained in patients with ST-segment elevation myocardial infarction (STEMI) with QFR, fractional flow reserve (FFR), and instantaneous wave-free ratio (iFR) in the staged setting as reference.BACKGROUND: QFR is an angiography-based approach for the functional evaluation of coronary artery lesions.METHODS: This was a post-hoc analysis of the iSTEMI study. NCLs were assessed with iFR in the acute setting and with iFR and FFR at staged (median 13 days) follow-up. Acute and staged QFR values were computed in a core laboratory based on the coronary angiography recordings. Diagnostic cut-off values were ≤0.80 for QFR and FFR, and ≤0.89 for iFR.RESULTS: Staged iFR and FFR data were available for 146 NCLs in 112 patients in the iSTEMI study. Among these, QFR analysis was feasible in 103 (71%) lesions assessed in the acute setting with a mean QFR value of 0.82 (IQR: 0.73-0.91). Staged QFR, FFR, and iFR were 0.80 (IQR: 0.70-0.90), 0.81 (IQR: 0.71-0.88), and 0.91 (IQR: 0.87-0.96), respectively. Classification agreement of acute and staged QFR was 93% (95%Cl: 87-99). The classification agreement of acute QFR was 84% (95%CI: 76-90) using staged FFR as reference and 74% (95%CI: 65-83) using staged iFR as reference.CONCLUSIONS: Acute QFR showed a very good diagnostic performance with staged QFR as reference, a good diagnostic performance with staged FFR as reference, and a moderate diagnostic performance with staged iFR as reference.

BACKGROUND: Impaired fetal growth may increase vulnerability towards metabolic disturbances associated with some medications. We examined whether birth weight and ponderal index modify the association between psychotropic medication and type 2 diabetes among young adults with severe psychiatric diagnosis.METHODS: A total of 36,957 individuals born in Denmark between 1973 and 1983 with a diagnosis of schizophrenia, bipolar disorder, or depression were followed from first diagnosis until 2018. Cox proportional hazard models were applied to analyse risk of type 2 diabetes with use of psychotropic medications and interactions between psychotropic medication and birth weight and ponderal index, respectively.RESULTS: During follow-up, 1575 (4.2%) individuals received a diagnosis of type 2 diabetes. Use of antipsychotic, mood stabilizing and antidepressant medications were associated with higher hazard ratios (HRs) of type 2 diabetes (HRantipsychotics 1.68 [95%CI 1.49-1.90]; HRmood stabilizing medication 1.41 [95%CI 1.25-1.59]; HRantidepressants 2.00 [95%CI 1.68-2.37]), as were a birth weight below 2500 g (HR 1.13 [95%CI 1.01-1.28]), and high ponderal index (HR 1.26 [95%CI 1.11-1.43]). The highest rates of type 2 diabetes for each psychotropic medication category were found in medication users with low birth weight or high ponderal index. However, neither birth weight nor ponderal index significantly modified the association between psychotropic medication and diabetes risk.CONCLUSION: Psychotropic medication use, birth weight, and ponderal index were risk factors for type 2 diabetes in patients with severe mental illness, but neither birth weight nor ponderal index modified the association between psychotropic medication and type 2 diabetes.

Background: Clinical outcomes following coronary computed tomography–derived fractional flow reserve (FFR CT) testing in clinical practice are unknown. Objectives: This study sought to assess real-world clinical outcomes following a diagnostic strategy including first-line coronary computed tomography angiography (CTA) with selective FFR CT testing. Methods: The study reviewed the results of 3,674 consecutive patients with stable chest pain evaluated with CTA and FFR CT testing to guide downstream management in patients with intermediate stenosis (30% to 70%). The composite endpoint (all-cause death, myocardial infarction, hospitalization for unstable angina, and unplanned revascularization) was determined in 4 patient groups: 1) CTA stenosis CT >0.80, OMT, no additional testing; 3) FFR CT ≤0.80, OMT, no additional testing; and 4) FFR CT ≤0.80, OMT, and referral to invasive coronary angiography. Patients were followed for a median of 24 (range 8 to 41) months. Results: FFR CT was available in 677 patients, and the test result was negative (>0.80) in 410 (61%) patients. In 75% of the patients with FFR CT >0.80, maximum coronary stenosis was ≥50%. The cumulative incidence proportion (95% confidence interval [CI]) of the composite endpoint at the end of follow-up was comparable in groups 1 (2.8%; 95% CI: 1.4% to 4.9%) and 2 (3.9%; 95% CI: 2.0% to 6.9%) (p = 0.58) but was higher (when compared with group 1) in groups 3 (9.4%; p = 0.04) and 4 (6.6%; p = 0.08). Risk of myocardial infarction was lower in group 4 (1.3%) than in group 3 (8%; p < 0.001). Conclusions: In patients with intermediate-range coronary stenosis, FFR CT is effective in differentiating patients who do not require further diagnostic testing or intervention (FFR CT >0.80) from higher-risk patients (FFR CT ≤0.80) in whom further testing with invasive coronary angiography and possibly intervention may be needed. Further studies assessing the risk and optimal management strategy in patients undergoing first-line CTA with selective FFR CT testing are needed.

AIMS: The aim of the study was to evaluate the incidence and causes of rehospitalisation within one year after percutaneous coronary intervention (PCI) in a country where the National Health Service provides universal tax-supported healthcare, guaranteeing residents free hospital access.METHODS AND RESULTS: Between January 2010 and September 2014, 17,111 patients were treated with PCI in two University Hospitals in Western Denmark. Patients who were readmitted within one year after PCI were identified. The overall one-year readmission rate was 50.4%. The cause was angina/myocardial infarction (MI) in 4,282 patients (49.7%), and other reasons in 4,334 (50.3%). Predictors of angina/MI-related readmissions were female gender (odds ratio [OR] 1.15, 95% confidence interval [CI]: 1.07-1.25), diabetes (OR 1.14, 95% CI: 1.04-1.26), age (per 10-year increase) (OR 0.86, 95% CI: 0.83-0.88), and indication for index PCI (stable angina pectoris as reference): ST-segment elevation myocardial infarction (OR 1.34, 95% CI: 1.23-1.47) and non-ST-segment elevation myocardial infarction (OR 1.18, 95% CI: 1.08-1.29). Predictors for other readmissions were female gender (OR 1.09, 95% CI: 1.01-1.18), diabetes (OR 1.29, 95% CI: 1.18-1.42), age (OR 1.30, 95% CI: 1.26-1.34) and Charlson comorbidity index ≥3 (OR 3.03, 95% CI: 2.71-3.27).CONCLUSIONS: In an unselected patient cohort treated with PCI, half of the patients were rehospitalised within one year, highlighting the impact of comorbidity in patients with ischaemic heart disease.

Objectives The authors sought to compare reclassification of treatment strategy following instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR). Background iFR was noninferior to FFR in 2 large randomized controlled trials in guiding coronary revascularization. Reclassification of treatment strategy by FFR is well-studied, but similar reports on iFR are lacking. Methods The iFR-SWEDEHEART (Instantaneous Wave-Free Ratio Versus Fractional Flow Reserve in Patients With Stable Angina Pectoris or Acute Coronary Syndrome Trial) study randomized 2,037 participants with stable angina or acute coronary syndrome to treatment guided by iFR or FFR. Interventionalists entered the preferred treatment (optimal medical therapy [OMT], percutaneous coronary intervention [PCI], or coronary artery bypass grafting [CABG]) on the basis of coronary angiograms, and the final treatment decision was mandated by the iFR/FFR measurements. Results In the iFR/FFR (n = 1,009/n = 1,004) populations, angiogram-based treatment approaches were similar (p = 0.50) with respect to OMT (38%/35%), PCI of 1 (37%/39%), 2 (15%/16%), and 3 vessels (2%/2%) and CABG (8%/8%). iFR and FFR reclassified 40% and 41% of patients, respectively (p = 0.78). The majority of reclassifications were conversion of PCI to OMT in both the iFR/FFR groups (31.4%/29.0%). Reclassification increased with increasing number of lesions evaluated (odds ratio per evaluated lesion for FFR: 1.46 [95% confidence interval: 1.22 to 1.76] vs. iFR 1.37 [95% confidence interval: 1.18 to 1.59]). Reclassification rates for patients with 1, 2, and 3 assessed vessels were 36%, 52%, and 53% (p Conclusions Reclassification of treatment strategy of intermediate lesions was common and occurred in 40% of patients with iFR or FFR. The most frequent reclassification was conversion from PCI to OMT regardless of physiology modality. Irrespective of the physiological index reclassification of angiogram-based treatment strategy increased with the number of lesions evaluated.

BACKGROUND: Coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) are used for coronary revascularization in patients with multivessel and left main coronary artery disease. Stroke is among the most feared complications of revascularization. Due to its infrequency, studies with large numbers of patients are required to detect differences in stroke rates between CABG and PCI.OBJECTIVES: This study sought to compare rates of stroke after CABG and PCI and the impact of procedural stroke on long-term mortality.METHODS: We performed a collaborative individual patient-data pooled analysis of 11 randomized clinical trials comparing CABG with PCI using stents; ERACI II (Argentine Randomized Study: Coronary Angioplasty With Stenting Versus Coronary Bypass Surgery in Patients With Multiple Vessel Disease) (n = 450), ARTS (Arterial Revascularization Therapy Study) (n = 1,205), MASS II (Medicine, Angioplasty, or Surgery Study) (n = 408), SoS (Stent or Surgery) trial (n = 988), SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) trial (n = 1,800), PRECOMBAT (Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease) trial (n = 600), FREEDOM (Comparison of Two Treatments for Multivessel Coronary Artery Disease in Individuals With Diabetes) trial (n = 1,900), VA CARDS (Coronary Artery Revascularization in Diabetes) (n = 198), BEST (Bypass Surgery Versus Everolimus-Eluting Stent Implantation for Multivessel Coronary Artery Disease) (n = 880), NOBLE (Percutaneous Coronary Angioplasty Versus Coronary Artery Bypass Grafting in Treatment of Unprotected Left Main Stenosis) trial (n = 1,184), and EXCEL (Evaluation of Xience Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial (n = 1,905). The 30-day and 5-year stroke rates were compared between CABG and PCI using a random effects Cox proportional hazards model, stratified by trial. The impact of stroke on 5-year mortality was explored.RESULTS: The analysis included 11,518 patients randomly assigned to PCI (n = 5,753) or CABG (n = 5,765) with a mean follow-up of 3.8 ± 1.4 years during which a total of 293 strokes occurred. At 30 days, the rate of stroke was 0.4% after PCI and 1.1% after CABG (hazard ratio [HR]: 0.33; 95% confidence interval [CI]: 0.20 to 0.53; p < 0.001). At 5-year follow-up, stroke remained significantly lower after PCI than after CABG (2.6% vs. 3.2%; HR: 0.77; 95% CI: 0.61 to 0.97; p = 0.027). Rates of stroke between 31 days and 5 years were comparable: 2.2% after PCI versus 2.1% after CABG (HR: 1.05; 95% CI: 0.80 to 1.38; p = 0.72). No significant interactions between treatment and baseline clinical or angiographic variables for the 5-year rate of stroke were present, except for diabetic patients (PCI: 2.6% vs. CABG: 4.9%) and nondiabetic patients (PCI: 2.6% vs. CABG: 2.4%) (p for interaction = 0.004). Patients who experienced a stroke within 30 days of the procedure had significantly higher 5-year mortality versus those without a stroke, both after PCI (45.7% vs. 11.1%, p < 0.001) and CABG (41.5% vs. 8.9%, p < 0.001).CONCLUSIONS: This individual patient-data pooled analysis demonstrates that 5-year stroke rates are significantly lower after PCI compared with CABG, driven by a reduced risk of stroke in the 30-day post-procedural period but a similar risk of stroke between 31 days and 5 years. The greater risk of stroke after CABG compared with PCI was confined to patients with multivessel disease and diabetes. Five-year mortality was markedly higher for patients experiencing a stroke within 30 days after revascularization.

BACKGROUND: Numerous randomised trials have compared coronary artery bypass grafting (CABG) with percutaneous coronary intervention (PCI) for patients with coronary artery disease. However, no studies have been powered to detect a difference in mortality between the revascularisation strategies.METHODS: We did a systematic review up to July 19, 2017, to identify randomised clinical trials comparing CABG with PCI using stents. Eligible studies included patients with multivessel or left main coronary artery disease who did not present with acute myocardial infarction, did PCI with stents (bare-metal or drug-eluting), and had more than 1 year of follow-up for all-cause mortality. In a collaborative, pooled analysis of individual patient data from the identified trials, we estimated all-cause mortality up to 5 years using Kaplan-Meier analyses and compared PCI with CABG using a random-effects Cox proportional-hazards model stratified by trial. Consistency of treatment effect was explored in subgroup analyses, with subgroups defined according to baseline clinical and anatomical characteristics.FINDINGS: We included 11 randomised trials involving 11 518 patients selected by heart teams who were assigned to PCI (n=5753) or to CABG (n=5765). 976 patients died over a mean follow-up of 3·8 years (SD 1·4). Mean Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) score was 26·0 (SD 9·5), with 1798 (22·1%) of 8138 patients having a SYNTAX score of 33 or higher. 5 year all-cause mortality was 11·2% after PCI and 9·2% after CABG (hazard ratio [HR] 1·20, 95% CI 1·06-1·37; p=0·0038). 5 year all-cause mortality was significantly different between the interventions in patients with multivessel disease (11·5% after PCI vs 8·9% after CABG; HR 1·28, 95% CI 1·09-1·49; p=0·0019), including in those with diabetes (15·5% vs 10·0%; 1·48, 1·19-1·84; p=0·0004), but not in those without diabetes (8·7% vs 8·0%; 1·08, 0·86-1·36; p=0·49). SYNTAX score had a significant effect on the difference between the interventions in multivessel disease. 5 year all-cause mortality was similar between the interventions in patients with left main disease (10·7% after PCI vs 10·5% after CABG; 1·07, 0·87-1·33; p=0·52), regardless of diabetes status and SYNTAX score.INTERPRETATION: CABG had a mortality benefit over PCI in patients with multivessel disease, particularly those with diabetes and higher coronary complexity. No benefit for CABG over PCI was seen in patients with left main disease. Longer follow-up is needed to better define mortality differences between the revascularisation strategies.FUNDING: None.

Background Frequent injecting increases hepatitis C (HCV) acquisition risk among people who inject drugs (PWID). However, few studies have examined how temporal fluctuations in injecting frequency may effect HCV infection risk. Thus, this study examined HCV incidence according to injecting frequency trajectories followed by PWID over one year in Montreal, Canada. Methods At three-month intervals from March 2011 to June 2016, HCV-uninfected PWID (never infected or cleared infection) enrolled in the Hepatitis Cohort (HEPCO) completed interviewer-administered questionnaires and HCV testing. At each visit, participants reported the number of injecting days (0–30 days) for each of the past three months. In previous work, using group-based trajectory modeling, we identified five injecting frequency trajectories followed by participants over one year (months 1–12 of follow-up), including sporadic, infrequent, increasing, decreasing, and frequent injecting. In this study, we estimated group-specific HCV incidence (months 1–63 of follow-up) using posterior probabilities to assign participants to their most likely trajectory group. Results Of 386 participants (mean age=40, 82% male, 48% never HCV-infected), 72 acquired HCV during 893 person-years of follow-up. HCV incidence for the whole study sample was 8.1 per 100 person-years (95%CI=6.4–10.1). Trajectory group-specific HCV incidences were highest for those injecting drugs with decreasing (23.9, 14.4–37.5) or increasing frequency (16.0, 10.1–24.3), intermediate for those injecting at consistently high frequency (10.2, 5.4–17.8), and lowest for those injecting infrequently (3.9, 2.2–6.5) or sporadically (4.3, 2.2–7.6). Conclusion Results suggest that PWID at highest HCV risk are those injecting at high frequency, either transitorily (increasing, decreasing injecting) or consistently (frequent injecting). This study highlights changes in injecting frequency as a potentially important dimension to consider among the factors leading to HCV acquisition. Clinical and public health interventions tailored to PWID with different injecting frequency profiles may contribute to HCV prevention.

INTRODUCTION: Variation of muscle strength and function have not been studied in patients with chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy whose treatment regimen has been changed from intravenous to subcutaneous immunoglobulin (IVIG to SCIG).METHODS: In a prospective open label study, patients were changed from monthly IVIG to weekly SCIG. The primary endpoint was the variation of isokinetic muscle strength (cIKS). Secondary endpoints were variation of Medical Research Council (MRC) score, grip strength (GS), 9-hole-peg test (9-HPT), 40-meter-walk test (40-MWT).RESULTS: The coefficient of variance of cIKS during the IVIG and SCIG treatment periods was unchanged (6.97±4.83% vs. 5.50±3.13%, mean± SD, p=0.21). The variation of the 9-HPT and the 40 MWT were significantly lower in the SCIG group(p=0.01 and p=0.005, respectively).DISCUSSION: When therapy was changed from IVIG to SCIG, fluctuation of muscle strength was unchanged, whereas performance fluctuations were diminished This article is protected by copyright. All rights reserved.

ObjectiveDiagnosing coronary artery disease (CAD) continues to require substantial healthcare resources. Acoustic analysis of transcutaneous heart sounds of cardiac movement and intracoronary turbulence due to obstructive coronary disease could potentially change this. The aim of this study was thus to test the diagnostic accuracy of a new portable acoustic device for detection of CAD.MethodsWe included 1675 patients consecutively with low to intermediate likelihood of CAD who had been referred for cardiac CT angiography. If significant obstruction was suspected in any coronary segment, patients were referred to invasive angiography and fractional flow reserve (FFR) assessment. Heart sound analysis was performed in all patients. A predefined acoustic CAD-score algorithm was evaluated; subsequently, we developed and validated an updated CAD-score algorithm that included both acoustic features and clinical risk factors. Low risk is indicated by a CAD-score value ≤20.ResultsHaemodynamically significant CAD assessed from FFR was present in 145 (10.0%) patients. In the entire cohort, the predefined CAD-score had a sensitivity of 63% and a specificity of 44%. In total, 50% had an updated CAD-score value ≤20. At this cut-off, sensitivity was 81% (95% CI 73% to 87%), specificity 53% (95% CI 50% to 56%), positive predictive value 16% (95% CI 13% to 18%) and negative predictive value 96% (95% CI 95% to 98%) for diagnosing haemodynamically significant CAD.ConclusionSound-based detection of CAD enables risk stratification superior to clinical risk scores. With a negative predictive value of 96%, this new acoustic rule-out system could potentially supplement clinical assessment to guide decisions on the need for further diagnostic investigation.Trial registration numberClinicalTrials.gov identifier NCT02264717; Results.

Objectives This study sought to investigate the effect of post-dilatation on angiographic and intracoronary imaging parameters in the setting of primary percutaneous coronary intervention comparing the everolimus-eluting bioresorbable scaffold (BRS) with the everolimus-eluting metallic stent (EES). Background Routine post-dilatation of BRS has been suggested to improve post-procedural angiographic and subsequent device-related clinical outcomes. Methods In the ABSORB STEMI TROFI II trial, 191 patients with ST-segment elevation myocardial infarction were randomly assigned to treatment with BRS (n = 95) or EES (n = 96). Minimal lumen area and healing score as assessed by optical coherence tomography at 6 months were compared between BRS- and EES-treated patients stratified according to post-dilatation status. Results Primary percutaneous coronary intervention with post-dilatation was performed in 48 (50.5%) BRS- and 25 (25.5%) EES-treated lesions. There were no differences in baseline characteristics and post-procedural minimal lumen diameter between groups. In the BRS group, lesions with post-dilatation were associated with a trend toward a smaller minimal lumen area at 6 months (5.07 ± 1.68 mm2 vs. 5.72 ± 1.77 mm2; p = 0.09) and significantly larger angiographic late lumen loss (0.28 ± 0.34 mm vs. 0.12 ± 0.25 mm; p = 0.02), whereas no difference was observed in the EES arm (5.46 ± 2.18 mm2 vs. 5.55 ± 1.77 mm2; p = 0.85). The neointimal healing score was low and comparable between groups with and without post-dilation (BRS: 1.55 ± 2.61 vs. 1.92 ± 2.17; p = 0.48; EES: 2.50 ± 3.33 vs. 2.90 ± 4.80; p = 0.72). Conclusions In the setting of selected patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention with BRS or EES, post-dilatation did not translate into larger lumen area or improved arterial healing at follow-up. (ABSORB STEMI: The TROFI II; NCT01986803)

Uncontrolled activation of transforming growth factor beta (TGF-β) family members is hypothesized to participate in type 2 diabetes (T2D) dependent diabetic nephropathy (DN). We evaluated and compared downstream activation of the Smad2-signaling pathway in kidney samples from T2D patients to kidneys from the T2D model of leptin receptor deficient db/db mouse. Furthermore, expression of TGF-β family members was evaluated to elucidate molecular mechanisms in the mouse model. Kidney samples from patients with advanced stages of DN showed elevated pSmad2 staining whereas db/db mouse kidneys surprisingly showed a decrease in pSmad2 in the tubular compartment. Structurally, kidney tissue showed dilated tubules and expanded glomeruli, but no clear fibrotic pattern was found in the diabetic mice. Selective TGF-β family members were up-regulated at the mRNA level. Antagonists of bone morphogenetic protein (BMP) ligands, such as Gremlin1, USAG1 and Sclerostin, were strongly up-regulated suggesting a dampening effect on BMP pathways. Together, these results indicate a lack of translation from T2D patient kidneys to the db/db model with regards to Smad signaling pathway. It is plausible that a strong up-regulation of BMP antagonizing factors account for the lack of Smad1/5/8 activation, in spite of increased expression of several BMP members.

Background Poor cardiorespiratory fitness (CRF) increases morbidity and mortality risks. Routine CRF assessment in clinical practice has thus been advocated, but little is known about the effect. In this study, we investigated the effect of CRF assessment on CRF in a preventive health check programme. Methods We used a randomised design, in which we invited 4153 middle-aged adults and included 2201 participants who received a preventive health check with CRF assessment (intervention) or without CRF assessment (control). After 1 year, participants were examined. The primary outcomes were adjusted absolute (l/min), relative (ml/kg/min), and poor (%) CRF assessed by the Astrand-Ryhming test. We adjusted for baseline physical activity and intra-cluster correlation within general practices. Results A total of 901 attended the 1-year follow-up. In the intervention group, absolute CRF, relative CRF, and poor CRF were 2.7 l/min (95% confidence interval [CI]: 2.6; 2.8), 34.5 ml/kg/min (95% CI: 33.5; 35.4), and 31.0% (95% CI: 26.8; 35.2). In the control group, the corresponding figures were 2.8 l/min (95% CI: 2.7; 2.9), 35.2 ml/kg/min (95% CI: 34.2; 36.1), and 25.9% (95% CI: 21.8; 30.0). Adjusted absolute CRF was lower in the intervention group (-0.1 l/min [95% CI: -0.2; -0.01]). Adjusted relative CRF (-0.7 ml/kg/min [95% CI: -2.0; 0.6]) and poor CRF (5.0% [95% CI: -0.002; 10.1]) did not differ between groups. No differences were found when adjusting for potential confounding factors. Conclusion Preventive health checks with CRF assessment did not provide higher CRF levels at 1-year follow-up than preventive health checks without CRF assessment.

Objectives The aims of this study were to characterize cardiac allograft vasculopathy (CAV) phenotypes using optical coherence tomography (OCT) and to evaluate the prognostic significance of OCT-determined CAV severity. Background Intravascular OCT enables in vivo characterization of CAV microstructure after heart transplantation. Methods Sixty-two patients undergoing heart transplantation were enrolled at routine angiography from September 2013 through October 2015 and prospectively followed until censoring on May 27, 2016. Optical coherence tomographic acquisitions aimed for the longest possible pull-backs, including proximal segments of all 3 major vessels. Plaques and bright spots were analyzed by delineating circumferential borders and measuring the angulation of total circumference. Layers were contoured for absolute and relative estimates. Nonfatal CAV progression (NFCP) during follow-up was registered. NFCP included occluded vessels or severe (≥70%) new angiographic coronary stenosis or percutaneous coronary intervention. Results A total of 172 vessels were categorized as follows: no CAV, n = 111; mild to moderate CAV ( Conclusions OCT enables the detection of CAV-associated plaque compositions and allows early detection and differentiation of vessel wall disease not visible on angiography. LFP was the most prevalent plaque component, was strongly associated with NFCP, and may be associated with stepwise CAV progression caused by organizing mural thrombi. (The GRAFT Study: Evaluation of Graft Function, Rejection and Cardiac Allograft Vasculopathy in First Heart Transplant Recipients; NCT02077764)

OBJECTIVES: The goal of this study was to assess the real-world clinical utility of fractional flow reserve (FFR) derived from coronary computed tomography angiography (FFRCT) for decision-making in patients with stable coronary artery disease (CAD).BACKGROUND: FFRCT has shown promising results in identifying lesion-specific ischemia. The real-world feasibility and influence on the diagnostic work-up of FFRCT testing in patients suspected of having CAD are unknown.METHODS: We reviewed the complete diagnostic work-up of nonemergent patients referred for coronary computed tomography angiography over a 12-month period at Aarhus University Hospital, Denmark, including all patients with new-onset chest pain with no known CAD and with intermediate-range coronary lesions (lumen reduction, 30% to 70%) referred for FFRCT. The study evaluated the consequences on downstream diagnostic testing, the agreement between FFRCT and invasively measured FFR or instantaneous wave-free ratio (iFR), and the short-term clinical outcome after FFRCT testing.RESULTS: Among 1,248 patients referred for computed tomography angiography, 189 patients (mean age 59 years; 59% male) were referred for FFRCT, with a conclusive FFRCT result obtained in 185 (98%). FFRCT was ≤0.80 in 31% of patients and 10% of vessels. After FFRCT testing, invasive angiography was performed in 29%, with FFR measured in 19% and iFR in 1% of patients (with a tendency toward declining FFR-iFR guidance during the study period). FFRCT ≤0.80 correctly classified 73% (27 of 37) of patients and 70% (37 of 53) of vessels using FFR ≤0.80 or iFR ≤0.90 as the reference standard. In patients with FFRCT >0.80 being deferred from invasive coronary angiography, no adverse cardiac events occurred during a median follow-up period of 12 (range 6 to 18 months) months.CONCLUSIONS: FFRCT testing is feasible in real-world symptomatic patients with intermediate-range stenosis determined by coronary computed tomography angiography. Implementation of FFRCT for clinical decision-making may influence the downstream diagnostic workflow of patients. Patients with an FFRCT value >0.80 being deferred from invasive coronary angiography have a favorable short-term prognosis.

Aims To assess the use of downstream coronary angiography (ICA) and short-term safety of frontline coronary CT angiography (CTA) with selective CT-derived fractional flow reserve (FFR CT) testing in stable patients with typical angina pectoris. Methods Between 1 January 2016 and 30 June 2016 all patients (N = 774) referred to non-emergent ICA or coronary CTA and results at Aarhus University Hospital on a suspicion of CAD had frontline CTA performed. Downstream testing and treatment within 3 months and adverse events >_90 days were registered. Patients were divided into two groups according to the presence of typical angina pectoris, which according to local practice would have resulted in referral to ICA, (low-intermediate-risk, n = 593 [76%]; high-risk, n = 181 [24%]) with mean pre-test probability of CAD of 31 ± 16% and 67 ± 16%, respectively. Coronary CTA was performed in 745 (96%) patients in whom FFR CT was prescribed in 212 (28%) patients. In the high- vs. low-intermediate-risk group, ICA was cancelled in 75% vs. 91%. Coronary revascularization was performed more frequently in high-risk than in low-intermediate-risk patients, 76% vs. 52% (P = 0.03). Mean follow-up time was 157 ± 50 days. Serious clinical events occurred in four patients, but not in any patients with cancelled ICA by coronary CTA with selective FFR CT testing. Conclusion Frontline coronary CTA with selective FFR CT testing in stable patients with typical angina pectoris in real-world practice is associated with a high rate of safe cancellation of planned ICAs.