Multivessel PCI Guided by FFR or Angiography for Myocardial Infarction.

BACKGROUND: In patients with ST-elevation myocardial infarction (STEMI) who have multivessel disease, percutaneous coronary intervention (PCI) for nonculprit lesions (complete revascularization) is superior to treatment of the culprit lesion alone. However, whether complete revascularization that is guided by fractional flow reserve (FFR) is superior to an angiography-guided procedure is unclear. METHODS: In this multicenter trial, we randomly assigned patients with STEMI and multivessel disease who had undergone successful PCI of the infarct-related artery to receive complete revascularization guided by either FFR or angiography. The primary outcome was a composite of death from any cause, nonfatal myocardial infarction, or unplanned hospitalization leading to urgent revascularization at 1 year. RESULTS: The mean (±SD) number of stents that were placed per patient for nonculprit lesions was 1.01±0.99 in the FFR-guided group and 1.50±0.86 in the angiography-guided group. During follow-up, a primary outcome event occurred in 32 of 586 patients (5.5%) in the FFR-guided group and in 24 of 577 patients (4.2%) in the angiography-guided group (hazard ratio, 1.32; 95% confidence interval, 0.78 to 2.23; P = 0.31). Death occurred in 9 patients (1.5%) in the FFR-guided group and in 10 (1.7%) in the angiography-guided group; nonfatal myocardial infarction in 18 (3.1%) and 10 (1.7%), respectively; and unplanned hospitalization leading to urgent revascularization in 15 (2.6%) and 11 (1.9%), respectively. CONCLUSIONS: In patients with STEMI undergoing complete revascularization, an FFR-guided strategy did not have a significant benefit over an angiography-guided strategy with respect to the risk of death, myocardial infarction, or urgent revascularization at 1 year. However, given the wide confidence intervals for the estimate of effect, the findings do not allow for a conclusive interpretation. (Funded by the French Ministry of Health and Abbott; FLOWER-MI ClinicalTrials.gov number, NCT02943954.).

Impact of the Sars-Cov-2 outbreak on the initial clinical presentation of new solid cancer diagnoses: a systematic review and meta-analysis.

BACKGROUND: The COVID-19 pandemic might have delayed cancer diagnosis and management. The aim of this systematic review was to compare the initial tumor stage of new cancer diagnoses before and after the pandemic. METHODS: We systematically reviewed articles that compared the tumor stage of new solid cancer diagnoses before and after the initial pandemic waves. We conducted a random-effects meta-analysis to compare the rate of metastatic tumors and the distribution of stages at diagnosis. Subgroup analyses were performed by primary tumor site and by country. RESULTS: From 2,013 studies published between January 2020 and April 2022, we included 58 studies with 109,996 patients. The rate of metastatic tumors was higher after the COVID-19 outbreak than before (pooled OR: 1.29 (95% CI, 1.06-1.57), I2: 89% (95% CI, 86-91)). For specific cancers, common ORs reached statistical significance for breast (OR: 1.51 (95% CI 1.07-2.12)) and gynecologic (OR: 1.51 (95% CI 1.04-2.18)) cancers, but not for other cancer types. According to countries, common OR (95% CI) reached statistical significance only for Italy: 1.55 (1.01-2.39) and Spain:1.14 (1.02-1.29). Rates were comparable for stage I-II versus III-IV in studies for which that information was available, and for stages I-II versus stage III in studies that did not include metastatic patients. CONCLUSIONS: Despite inter-study heterogeneity, our meta-analysis showed a higher rate of metastatic tumors at diagnosis after the pandemic. The burden of social distancing policies might explain those results, as patients may have delayed seeking care.

No changes in clinical presentation, treatment strategies and survival of pancreatic cancer cases during the SARS-COV-2 outbreak: A retrospective multicenter cohort study on real-world data.

The SARS-COV-2 pandemic disrupted healthcare systems. We assessed its impact on the presentation, care trajectories and outcomes of new pancreatic cancers (PCs) in the Paris area. We performed a retrospective multicenter cohort study on the data warehouse of Greater Paris University Hospitals (AP-HP). We identified all patients newly referred with a PC between January 1, 2019, and June 30, 2021, and excluded endocrine tumors. Using claims data and health records, we analyzed the timeline of care trajectories, the initial tumor stage, the treatment categories: pancreatectomy, exclusive systemic therapy or exclusive best supportive care (BSC). We calculated patients' 1-year overall survival (OS) and compared indicators in 2019 and 2020 to 2021. We included 2335 patients. Referral fell by 29% during the first lockdown. The median time from biopsy and from first MDM to treatment were 25 days (16-50) and 21 days (11-40), respectively. Between 2019 and 2020 to 2021, the rate of metastatic tumors (36% vs 33%, P = .39), the pTNM distribution of the 464 cases with upfront tumor resection (P = .80), and the proportion of treatment categories did not vary: tumor resection (32% vs 33%), exclusive systemic therapy (49% vs 49%), exclusive BSC (19% vs 19%). The 1-year OS rates in 2019 vs 2020 to 2021 were 92% vs 89% (aHR = 1.42; 95% CI, 0.82-2.48), 52% vs 56% (aHR = 0.88; 95% CI, 0.73-1.08), 13% vs 10% (aHR = 1.00; 95% CI, 0.78-1.25), in the treatment categories, respectively. Despite an initial decrease in the number of new PCs, we did not observe any stage shift. OS did not vary significantly.

Systematic Review and Meta-analysis of Clinical Outcomes After Endovascular Treatment in Patients With Femoropopliteal Lesions Greater Than 150 mm.

OBJECTIVE: Indications for endovascular treatment of femoropopliteal (FP) lesions have steadily increased over the past decade. Accordingly, the number of devices has also increased but the choice of the best endovascular treatment remains to be defined. The aim of this meta-analysis was to summarize all studies investigating endovascular treatment of FP lesions greater than 150 mm from 2010 to 2021. METHODS: Articles were searched using PubMed, Scopus, and Cochrane. Included studies were randomized controlled trials (RCTs), cohort studies, and case series (prospective and retrospective) that evaluated any endovascular procedure in patients with long FP lesions classified TASC (Trans-Atlantic Inter-Society Consensus document II on management of peripheral arterial disease) C and/or D, and a mean length >150 mm, primary outcome had to be the 1-year primary patency. Overall estimate of primary patency, secondary patency, and freedom from target lesion revascularization (TLR) at 1 year depending on the different devices were investigated. The meta-analysis was conducted following the requirements of the MOOSE (Meta-analysis of Observational Studies in Epidemiology) checklist. RESULTS: Forty-four papers comprising 4847 patients and 5282 treated limbs were included. Mean lesions length ranged from 150.5 to 330 mm. The pooled 1-year primary and secondary patencies, and freedom from TLR rates were 0.71 (95% CI: 0.67-0.74), 0.87 (95% CI: 0.83-0.91), and 0.79 (95% CI: 0.74-0.84), respectively. Primary permeability at 1 year were 0.68 (95% CI: 0.62-0.73), 0.67 (95% CI: 0.60-0.74), 0.74 (95% CI: 0.64-0.84), and 0.83 (95% CI: 0.78-0.88) for bare metal stents, covered stents (CSs), drug-eluting stents, and drug-coated balloons (DCBs), respectively. Lesions treated with DCB had the highest 1-year primary patency rate. CONCLUSIONS: At 1-year, endovascular procedures for FP lesions greater than 150 mm obtain satisfactory results. High primary patency rates were obtained with drug-coated devices, while CSs obtained less favorable results. Randomized studies comparing different devices in the treatment of long FP lesions remain necessary to determine the most optimal approach for the management of these patients. CLINICAL IMPACT: This paper highlights on the one hand the satisfactory results of endovascular treatment on complex femoropopliteal lesions formerly reserved for conventional surgery. On the other hand, among the available devices, paclitaxel-eluting devices seem to show superior results which should make them recommended as first-line treatment.

Development of a natural language processing model for deriving breast cancer quality indicators : A cross-sectional, multicenter study.

OBJECTIVES: Medico-administrative data are promising to automate the calculation of Healthcare Quality and Safety Indicators. Nevertheless, not all relevant indicators can be calculated with this data alone. Our feasibility study objective is to analyze 1) the availability of data sources; 2) the availability of each indicator elementary variables, and 3) to apply natural language processing to automatically retrieve such information. METHOD: We performed a multicenter cross-sectional observational feasibility study on the clinical data warehouse of Assistance Publique - Hôpitaux de Paris (AP-HP). We studied the management of breast cancer patients treated at AP-HP between January 2019 and June 2021, and the quality indicators published by the European Society of Breast Cancer Specialist, using claims data from the Programme de Médicalisation du Système d'Information (PMSI) and pathology reports. For each indicator, we calculated the number (%) of patients for whom all necessary data sources were available, and the number (%) of patients for whom all elementary variables were available in the sources, and for whom the related HQSI was computable. To extract useful data from the free text reports, we developed and validated dedicated rule-based algorithms, whose performance metrics were assessed with recall, precision, and f1-score. RESULTS: Out of 5785 female patients diagnosed with a breast cancer (60.9 years, IQR [50.0-71.9]), 5,147 (89.0%) had procedures related to breast cancer recorded in the PMSI, and 3732 (72.5%) had at least one surgery. Out of the 34 key indicators, 9 could be calculated with the PMSI alone, and 6 others became so using the data from pathology reports. Ten elementary variables were needed to calculate the 6 indicators combining the PMSI and pathology reports. The necessary sources were available for 58.8% to 94.6% of patients, depending on the indicators. The extraction algorithms developed had an average accuracy of 76.5% (min-max [32.7%-93.3%]), an average precision of 77.7% [10.0%-97.4%] and an average sensitivity of 71.6% [2.8% to 100.0%]. Once these algorithms applied, the variables needed to calculate the indicators were extracted for 2% to 88% of patients, depending on the indicators. DISCUSSION: The availability of medical reports in the electronic health records, of the elementary variables within the reports, and the performance of the extraction algorithms limit the population for which the indicators can be calculated. CONCLUSIONS: The automated calculation of quality indicators from electronic health records is a prospect that comes up against many practical obstacles.

Impact of two waves of Sars-Cov2 outbreak on the number, clinical presentation, care trajectories and survival of patients newly referred for a colorectal cancer: A French multicentric cohort study from a large group of university hospitals.

The SARS-Cov2 may have impaired care trajectories, patient overall survival (OS), tumor stage at initial presentation for new colorectal cancer (CRC) cases. This study aimed at assessing those indicators before and after the beginning of the pandemic in France. In this retrospective cohort study, we collected prospectively the clinical data of the 11.4 million of patients referred to the Greater Paris University Hospitals (AP-HP). We identified new CRC cases between 1 January 2018 and 31 December 2020, and compared indicators for 2018-2019 to 2020. pTNM tumor stage was extracted from postoperative pathology reports for localized colon cancer, and metastatic status was extracted from CT-scan baseline text reports. Between 2018 and 2020, 3602 and 1083 new colon and rectal cancers were referred to the AP-HP, respectively. The 1-year OS rates reached 94%, 93% and 76% for new CRC patients undergoing a resection of the primary tumor, in 2018-2019, in 2020 without any Sars-Cov2 infection and in 2020 with a Sars-Cov2 infection, respectively (HR 3.78, 95% CI 2.1-7.1). For patients undergoing other kind of anticancer treatment, the percentages are 64%, 66% and 27% (HR 2.1, 95% CI 1.4-3.3). Tumor stage at initial presentation, emergency level of primary tumor resection, delays between the first multidisciplinary meeting and the first anticancer treatment did not differ over time. The SARS-Cov2 pandemic has been associated with less newly diagnosed CRC patients and worse 1-year OS rates attributable to the infection itself rather than to its impact on hospital care delivery or tumor stage at initial presentation.

Geographical Ambulatory Endovascular Revascularisation Disparities in France From 2015 to 2019.

OBJECTIVE: Despite efficiency and safety evidence, ambulatory endovascular revascularisation for lower extremity arterial disease (LEAD) accounted for only 5% of interventions in France in 2016. Such a low rate suggests temporal and geographical space disparities. The aim of this study was to describe the space-time development of ambulatory endovascular revascularisation for LEAD in France and to investigate the contributions of healthcare services and population characteristics as potential determinants. METHODS: A retrospective study of discharge data from French hospitals that performed endovascular procedures for LEAD between 2015 and 2019 was conducted. Space-time analyses with Moran's Index, zero inflated Poisson regression, and clustering approaches were applied. Spatial clusters were compared on the basis of healthcare services and population characteristics (including poverty and single man household as proxies of social isolation). RESULTS: Between 2015 and 2019, the number of ambulatory interventions tripled (1 104 vs.3 130). Of the 86 French departments, the proportion with >5% of ambulatory interventions increased from 10.7% to 28.7% over the study period. In 2019, ambulatory activity in French departments ranged from 0% to 39%. This change was accompanied by a northwest to northeast spatial trend. The clusters of 27 departments with substantial ambulatory activity differed from the others notably by the mortality rate of lower limb arterial thromboembolic diseases in males (OR 3.15, 95% CI 1.2-8.1), the proportion of single man households of age ≥75 (OR 0.37, 95% CI 0.2-0.8), and the poverty rate of people aged 50-59 years (OR 0.69, 95% CI 0.5-0.9). CONCLUSIONS: The development of ambulatory interventions for LEAD in France is encouraging but heterogeneous. Some determinants of this evolution are clearly population based, with a positive impact of needs to take care of the burden of LEAD but negative effects of social isolation and poverty. Research should be conducted to overcome some patient constraints such as isolation.

Triaging acute pulmonary embolism for home treatment by Hestia or simplified PESI criteria: the HOME-PE randomized trial.

AIMS: The aim of this study is to compare the Hestia rule vs. the simplified Pulmonary Embolism Severity Index (sPESI) for triaging patients with acute pulmonary embolism (PE) for home treatment. METHODS AND RESULTS: Normotensive patients with PE of 26 hospitals from France, Belgium, the Netherlands, and Switzerland were randomized to either triaging with Hestia or sPESI. They were designated for home treatment if the triaging tool was negative and if the physician-in-charge, taking into account the patient's opinion, did not consider that hospitalization was required. The main outcomes were the 30-day composite of recurrent venous thrombo-embolism, major bleeding or all-cause death (non-inferiority analysis with 2.5% absolute risk difference as margin), and the rate of patients discharged home within 24 h after randomization (NCT02811237). From January 2017 through July 2019, 1975 patients were included. In the per-protocol population, the primary outcome occurred in 3.82% (34/891) in the Hestia arm and 3.57% (32/896) in the sPESI arm (P = 0.004 for non-inferiority). In the intention-to-treat population, 38.4% of the Hestia patients (378/984) were treated at home vs. 36.6% (361/986) of the sPESI patients (P = 0.41 for superiority), with a 30-day composite outcome rate of 1.33% (5/375) and 1.11% (4/359), respectively. No recurrent or fatal PE occurred in either home treatment arm. CONCLUSIONS: For triaging PE patients, the strategy based on the Hestia rule and the strategy based on sPESI had similar safety and effectiveness. With either tool complemented by the overruling of the physician-in-charge, more than a third of patients were treated at home with a low incidence of complications.

Association between the timing of consultation-liaison psychiatry interventions and the length of stay in general hospital.

BACKGROUND: Psychiatric comorbidities are frequent in patients admitted in general hospital and are associated with greater lengths of stay (LOS). Early consultation-liaison psychiatry (CLP) interventions may reduce the LOS but previous studies were underpowered to allow subgroup analyses and have generally not considered the severity of the condition for which patients were admitted ('disease severity'). AIMS: To investigate the association between the timing of CLP interventions and LOS in a general hospital. METHOD: We retrospectively included 4500 consecutive patients admitted in non-psychiatric wards of a university hospital between 2008 and 2016 who had a first CLP intervention. We used general linear models to examine the association between the referral time, defined as log(days before the consultation)/log(LOS), and log(LOS), adjusting for age, gender, year of admission, place of residence, main psychiatric diagnosis, admission to the intensive care unit (ICU), main physical condition and disease severity. RESULTS: Referral time was associated with log(LOS) (ß = 0.31; P <0.001), notably for older patients (ß = 0.43; P <0.001) and those admitted to the ICU (ß = 0.50; P <0.001), but not for those with psychotic disorders (ß = -0.20; P = 0.10). The association was confirmed when considering the expected LOS for each patient. For instance, for an expected LOS of 10 days, a CLP intervention on day 3 compared with day 6 was associated with a reduction of the actual LOS of 2.4 days. CONCLUSIONS: Earlier CLP interventions were associated with a clinically significant shorter LOS in a large population even after adjusting for disease severity. Early CLP interventions may have benefits for both patients and health-related costs.

Electrochemical skin conductance by Sudoscan®: a new tool to predict intradialytic hypotension.

BACKGROUND: Intradialytic hypotension (IDH), a common complication in haemodialysis (HD) patients, is associated with multiple risk factors including cardiac dysfunction and alterations of the peripheral autonomic nervous system. To what extent dysautonomia may contribute to the occurrence of IDH remains elusive. We sought to investigate the clinical utility of Sudocan®, a device that quantifies dysautonomia, in the prediction of IDH. METHODS: We conducted a prospective monocentric study in adult HD patients from July 2019 to February 2020. Dysautonomia was assessed by the measurements of hand and foot electrochemical skin conductance (ESC) using Sudocan®, before HD. The primary endpoint was the incidence of IDH (The National Kidney Foundation/Kidney-Dialysis Outcome Quality Initiative definition), according to the presence of a pathological hand and/or foot ESC value, during the 3-month study period. RESULTS: A total of 176 HD patients (64 ± 14 years old) were enrolled. Mean pre-dialysis HD hand and foot ESC was 45 ± 20 and 54 ± 22 µS, respectively. About 35% and 40% of patients had a pathological ESC at the hand and foot, respectively. IDH occurred in 46 patients. Logistic regression showed that pathologic pre-dialysis HD hand ESC was associated with an increased risk of IDH [odds ratio = 2.56, 95% CI (1.04-6.67), P = 0.04]. The cumulative risk incidence of IHD during the study was 5.65 [95% CI (2.04-15.71), P = 0.001] and 3.71 [95% CI (1.41-9.76), P = 0.008], with a pathological hand and foot ESC, respectively. CONCLUSIONS: A pathological hand ESC, as assessed by a non-invasive Sudoscan® test, is associated with an increased risk of IDH.

Asymptomatic left ventricular dysfunction in patients with type 2 diabetes free of cardiovascular disease and its relationship with clinical characteristics: The DIACAR cohort study.

AIMS: To assess the prevalence, type and clinical factors associated with left ventricular (LV) dysfunction in patients with type 2 diabetes mellitus (T2DM) by performing a comprehensive echocardiographic Doppler assessment including speckle tracking. METHODS: Two hundred T2DM patients without overt cardiovascular disease were prospectively enrolled in a single-centre cohort study between 2018 and 2019. RESULTS: Left ventricular mass was increased in 24 patients (12%) and relative wall thickness (h/r) was increased in 46 patients (23%). Left atrial (LA) enlargement was observed in 27 patients (13.6%) and global longitudinal strain (GLS) was reduced in 38 patients (20.3%). In univariate analysis, LV hypertrophy (LVH) or increased h/r were associated with age, renal function, hypertension and B-type natriuretic peptide (BNP) plasma level. LA dilation was associated with age, history of hypertension, diabetes duration and complications, insulin treatment, BNP level and renal function. GLS was associated with body mass index (BMI) and, in a borderline manner, with diabetes duration. In multivariate analysis, hypertension was associated with LVH and with h/r and a borderline relationship was observed for female gender (LVH), age and insulin treatment (h/r). Age, hypertension and, in a borderline manner, insulin treatment were associated with LA dilation. BMI and shorter diabetes duration were associated with reduced GLS. CONCLUSION: A high prevalence of asymptomatic cardiac dysfunction/structural abnormalities was observed in patients with T2DM without overt cardiac disease and was associated with either age, diabetes duration or treatment and with comorbidities including hypertension and obesity. Whether these preclinical abnormalities are associated with poor outcomes warrants further study.

Patent foramen ovale closure in stroke patients with migraine in the CLOSE trial. The CLOSE-MIG study.

BACKGROUND AND PURPOSE: The efficacy of patent foramen ovale (PFO) closure to reduce the frequency of migraine attacks remains controversial. METHODS: This was a planned sub-study in migraine patients enrolled in a randomized, clinical trial designed to assess the superiority of PFO closure plus antiplatelet therapy over antiplatelet therapy alone to prevent stroke recurrence in patients younger than 60 years with a PFO-associated cryptogenic ischaemic stroke. The main outcome was the mean annual number of migraine attacks in migraine patients with aura and in those without aura, as recorded at each follow-up visit by study neurologists. RESULTS: Of 473 patients randomized to PFO closure or antiplatelet therapy, 145 (mean age 41.9 years; women 58.6%) had migraine (75 with aura and 70 without aura). Sixty-seven patients were randomized to PFO closure and 78 to antiplatelet therapy. During a mean follow-up of about 5 years, there were no differences between antiplatelet-only and PFO closure groups in the mean annual number of migraine attacks, both in migraine patients with aura (9.2 [11.9] vs. 12.0 [19.1], p = 0.81) and in those without aura (12.1 [16.1] vs. 11.8 [18.4], p > 0.999). There were no differences between treatment groups regarding cessation of migraine attacks, migraine-related disability at 2 years and use of migraine-preventive drugs during follow-up. CONCLUSIONS: In young and middle-aged adults with PFO-associated cryptogenic stroke and migraine, PFO closure plus antiplatelet therapy did not reduce the mean annual number of migraine attacks compared to antiplatelet therapy alone, in migraine patients both with and without aura.

The Epidemiology of Patients' Email Addresses in a French University Hospital: Case-Control Study.

BACKGROUND: Health care professionals are caught between the wish of patients to speed up health-related communication via emails and the need for protecting health information. OBJECTIVE: We aimed to analyze the demographic characteristics of patients providing an email, and study the distribution of emails' domain names. METHODS: We used the information system of the European Hospital Georges Pompidou (HEGP) to identify patients who provided an email address. We used a 1:1 matching strategy to study the demographic characteristics of the patients associated with the presence of an email, and described the characteristics of the emails used (in terms of types of emails-free, business, and personal). RESULTS: Overall, 4.22% (41,004/971,822) of the total population of patients provided an email address. The year of last contact with the patient is the strongest driver of the presence of an email address (odds ratio [OR] 20.8, 95% CI 18.9-22.9). Patients more likely to provide an email address were treated for chronic conditions and were more likely born between 1950 and 1969 (taking patients born before 1950 as reference [OR 1.60, 95% CI 1.54-1.67], and compared to those born after 1990 [OR 0.56, 95% CI 0.53-0.59]). Of the 41,004 email addresses collected, 37,779 were associated with known email providers, 31,005 email addresses were associated with Google, Microsoft, Orange, and Yahoo!, 2878 with business emails addresses, and 347 email addresses with personalized domain names. CONCLUSIONS: Emails have been collected only recently in our institution. The importance of the year of last contact probably reflects this recent change in contact information collection policy. The demographic characteristics and especially the age distribution are likely the result of a population bias in the hospital: patients providing email are more likely to be treated for chronic diseases. A risk analysis of the use of email revealed several situations that could constitute a breach of privacy that is both likely and with major consequences. Patients treated for chronic diseases are more likely to provide an email address, and are also more at risk in case of privacy breach. Several common situations could expose their private information. We recommend a very restrictive use of the emails for health communication.

Heterogeneity of Treatment Effects in an Analysis of Pooled Individual Patient Data From Randomized Trials of Device Closure of Patent Foramen Ovale After Stroke.

Importance: Patent foramen ovale (PFO)-associated strokes comprise approximately 10% of ischemic strokes in adults aged 18 to 60 years. While device closure decreases stroke recurrence risk overall, the best treatment for any individual is often unclear. Objective: To evaluate heterogeneity of treatment effect of PFO closure on stroke recurrence based on previously developed scoring systems. Design, Setting, and Participants: Investigators for the Systematic, Collaborative, PFO Closure Evaluation (SCOPE) Consortium pooled individual patient data from all 6 randomized clinical trials that compared PFO closure plus medical therapy vs medical therapy alone in patients with PFO-associated stroke, and included a total of 3740 participants. The trials were conducted worldwide from 2000 to 2017. Exposures: PFO closure plus medical therapy vs medical therapy alone. Subgroup analyses used the Risk of Paradoxical Embolism (RoPE) Score (a 10-point scoring system in which higher scores reflect younger age and the absence of vascular risk factors) and the PFO-Associated Stroke Causal Likelihood (PASCAL) Classification System, which combines the RoPE Score with high-risk PFO features (either an atrial septal aneurysm or a large-sized shunt) to classify patients into 3 categories of causal relatedness: unlikely, possible, and probable. Main Outcomes and Measures: Ischemic stroke. Results: Over a median follow-up of 57 months (IQR, 24-64), 121 outcomes occurred in 3740 patients. The annualized incidence of stroke with medical therapy was 1.09% (95% CI, 0.88%-1.36%) and with device closure was 0.47% (95% CI, 0.35%-0.65%) (adjusted hazard ratio [HR], 0.41 [95% CI, 0.28-0.60]). The subgroup analyses showed statistically significant interaction effects. Patients with low vs high RoPE Score had HRs of 0.61 (95% CI, 0.37-1.00) and 0.21 (95% CI, 0.11-0.42), respectively (P for interaction = .02). Patients classified as unlikely, possible, and probable using the PASCAL Classification System had HRs of 1.14 (95% CI, 0.53-2.46), 0.38 (95% CI, 0.22-0.65), and 0.10 (95% CI, 0.03-0.35), respectively (P for interaction = .003). The 2-year absolute risk reduction was -0.7% (95% CI, -4.0% to 2.6%), 2.1% (95% CI, 0.6%-3.6%), and 2.1% (95% CI, 0.9%-3.4%) in the unlikely, possible, and probable PASCAL categories, respectively. Device-associated adverse events were generally higher among patients classified as unlikely; the absolute risk increases in atrial fibrillation beyond day 45 after randomization with a device were 4.41% (95% CI, 1.02% to 7.80%), 1.53% (95% CI, 0.33% to 2.72%), and 0.65% (95% CI, -0.41% to 1.71%) in the unlikely, possible, and probable PASCAL categories, respectively. Conclusions and Relevance: Among patients aged 18 to 60 years with PFO-associated stroke, risk reduction for recurrent stroke with device closure varied across groups classified by their probabilities that the stroke was causally related to the PFO. Application of this classification system has the potential to guide individualized decision-making.

Patent Foramen Ovale Closure or Anticoagulation vs. Antiplatelets after Stroke.

BACKGROUND: Trials of patent foramen ovale (PFO) closure to prevent recurrent stroke have been inconclusive. We investigated whether patients with cryptogenic stroke and echocardiographic features representing risk of stroke would benefit from PFO closure or anticoagulation, as compared with antiplatelet therapy. METHODS: In a multicenter, randomized, open-label trial, we assigned, in a 1:1:1 ratio, patients 16 to 60 years of age who had had a recent stroke attributed to PFO, with an associated atrial septal aneurysm or large interatrial shunt, to transcatheter PFO closure plus long-term antiplatelet therapy (PFO closure group), antiplatelet therapy alone (antiplatelet-only group), or oral anticoagulation (anticoagulation group) (randomization group 1). Patients with contraindications to anticoagulants or to PFO closure were randomly assigned to the alternative noncontraindicated treatment or to antiplatelet therapy (randomization groups 2 and 3). The primary outcome was occurrence of stroke. The comparison of PFO closure plus antiplatelet therapy with antiplatelet therapy alone was performed with combined data from randomization groups 1 and 2, and the comparison of oral anticoagulation with antiplatelet therapy alone was performed with combined data from randomization groups 1 and 3. RESULTS: A total of 663 patients underwent randomization and were followed for a mean (±SD) of 5.3±2.0 years. In the analysis of randomization groups 1 and 2, no stroke occurred among the 238 patients in the PFO closure group, whereas stroke occurred in 14 of the 235 patients in the antiplatelet-only group (hazard ratio, 0.03; 95% confidence interval, 0 to 0.26; P<0.001). Procedural complications from PFO closure occurred in 14 patients (5.9%). The rate of atrial fibrillation was higher in the PFO closure group than in the antiplatelet-only group (4.6% vs. 0.9%, P=0.02). The number of serious adverse events did not differ significantly between the treatment groups (P=0.56). In the analysis of randomization groups 1 and 3, stroke occurred in 3 of 187 patients assigned to oral anticoagulants and in 7 of 174 patients assigned to antiplatelet therapy alone. CONCLUSIONS: Among patients who had had a recent cryptogenic stroke attributed to PFO with an associated atrial septal aneurysm or large interatrial shunt, the rate of stroke recurrence was lower among those assigned to PFO closure combined with antiplatelet therapy than among those assigned to antiplatelet therapy alone. PFO closure was associated with an increased risk of atrial fibrillation. (Funded by the French Ministry of Health; CLOSE ClinicalTrials.gov number, NCT00562289 .).

Relationship of Tumor Radiation-absorbed Dose to Survival and Response in Hepatocellular Carcinoma Treated with Transarterial Radioembolization with 90Y in the SARAH Study.

Background Little is known about factors that influence the efficacy of transarterial radioembolization (TARE). Purpose To determine the relationship between tumor radiation-absorbed dose and survival and tumor response in locally advanced inoperable hepatocellular carcinoma treated with TARE. Materials and Methods This was a secondary analysis of prospectively acquired data (between December 2011 and March 2015) from participants who received TARE in the Sorafenib versus Radioembolization in Advanced Hepatocellular Carcinoma (SARAH) trial (ClinicalTrials.gov identifier: NCT01482442). Tumor-absorbed dose was computed using technetium 99m (99mTc) macroaggregated human albumin (MAA) SPECT/CT. Visual agreement among CT, 99mTc-MAA SPECT/CT, and yttrium 90 (90Y) SPECT/CT or PET/CT was scored as optimal, suboptimal, or not optimal. Overall survival (OS) and tumor response at 6-month follow-up CT (Response Evaluation Criteria in Solid Tumors, version 1.1) were assessed. OS was evaluated using Kaplan-Meier tests. A propensity score comparing participants receiving a tumor dose greater than or equal to 100 Gy (best cut-off according to the receiver operating characteristic curve and median tumor radiation-absorbed dose values in the study groups) with those receiving sorafenib was calculated. Results One hundred twenty-one participants (median age, 67 years; interquartile range [IQR]: 61-73 years; 110 men) were evaluated in the dose-survival group, and 109 (median age, 66 years; IQR: 61-71 years; 100 men) were evaluated in the dose-tumor response group. In the dose-survival group, median OS was 9.3 months (95% confidence interval [CI]: 6.7 months, 10.7 months), and median tumor radiation-absorbed dose was 112 Gy (IQR: 68-220 Gy). Participants who received at least 100 Gy (n = 67) had longer survival than those who received less than 100 Gy (median, 14.1 months [95% CI: 9.6 months, 18.6 months] vs 6.1 months [95% CI: 4.9 months, 6.8 months], respectively; P < .001), and those with optimal agreement (n = 24) had the longest median OS (24.9 months; 95% CI: 9.6 months, 33.9 months). In the dose-tumor response group, tumor radiation-absorbed dose was higher in participants with disease control versus those with progressive disease (median, 121 Gy [IQR: 86-190 Gy] vs 85 Gy [IQR: 58-164 Gy]; P = .02). The highest disease control rate was observed in 31 of 40 participants (78%) with a tumor radiation-absorbed dose greater than or equal to 100 Gy and optimal agreement. Conclusion Higher tumor radiation-absorbed dose computed at technetium 99m macroaggregated human albumin SPECT/CT was associated with better overall survival and disease control in hepatocellular carcinoma treated with transarterial radioembolization with yttrium 90 in the Sorafenib versus Radioembolization in Advanced Hepatocellular Carcinoma trial. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Sofocleous and Kamarinos in this issue.

Rationale and design of the Flow Evaluation to Guide Revascularization in Multivessel ST-Elevation Myocardial Infarction (FLOWER-MI) trial.

BACKGROUND: In ST-elevation myocardial infarction (STEMI) patients presenting with multivessel disease (MVD), recent studies have demonstrated the superiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) for non-culprit lesions compared to culprit lesion treatment-only therapy. FFR- and angio-guided PCI have however never been compared in STEMI patients. TRIAL DESIGN: FLOWER-MI is an open-label multicenter national randomized clinical trial. The aim is to investigate FFR-guided complete revascularization in comparison to angio-guided complete revascularization in STEMI patients with successful PCI of the culprit lesion and ≥50% stenosis in at least one additional non-culprit lesion requiring PCI. Eligible patients will be randomized after successful primary PCI in a 1:1 fashion to either FFR-guided or angio-guided complete revascularization during the index procedure or a staged procedure before discharge (≤5 days). Patients assigned to FFR guidance first have FFR measured in each non-culprit vessel and only undergo PCI if FFR is ≤0.80. The primary end point of the study is a composite of major adverse cardiac events, including all-cause death, non-fatal MI, and unplanned hospitalization leading to urgent revascularization at 1 year. Secondary end points will include the individual adverse events, cost-effectiveness, quality of life, and 30-day, 6-month, and 3-year outcomes. Based on estimated event rates, a sample size of 1170 patients is needed to show superiority of the FFR-guided revascularization with 80% power. CONCLUSION: The aim of FLOWER-MI trial is to assess whether FFR-guided complete revascularization in the acute setting is superior angio-guided complete revascularization.

EMERGEncy versus delayed coronary angiogram in survivors of out-of-hospital cardiac arrest with no obvious non-cardiac cause of arrest: Design of the EMERGE trial.

BACKGROUND: In adults, the most common cause of out-of-hospital cardiac arrests (OHCA) is acute coronary artery occlusion. If an immediate coronary angiogram (CAG) is recommended for survivors presenting a ST segment elevation on the electrocardiogram (ECG) performed after resuscitation, there is still a debate regarding the best strategy in patients without ST segment elevation. HYPOTHESIS: Performing an immediate CAG after an OHCA without ST segment elevation on the post-resuscitation ECG and no obvious non-cardiac cause of arrest could lead to a better 180-day survival rate with no or minimal neurological sequel as compared with a delayed CAG performed 48 to 96 hours after the arrest. DESIGN: The EMERGE trial is a prospective national, randomized, open and parallel group trial, in which 970 survivors of OHCA will be randomized (1:1) to either immediate (as soon as possible after return of spontaneous circulation) or delayed (48 to 96 h) CAG. Participants will be OHCA patients with no ST segment elevation on the post resuscitation ECG and no obvious non-cardiac cause of arrest. The primary endpoint of the study is the 180-day survival rate with no or minimal neurological sequel corresponding to Cerebral Performance Category (CPC) 1 or 2. The secondary endpoints are: occurrence of shock during the first 48 hours, ventricular tachycardia and/or fibrillation during the first 48 hours, change in left ventricular ejection fraction between baseline and 180 days assessed by echocardiogram, neurological status evaluated by the CPC score at intensive care unit (ICU) discharge and day 90 neurological status assessed by the Glasgow Outcome Scale Extended score (GOSE) at 90 and 180 days, overall survival rate, and hospital length of stay. SUMMARY: The EMERGE trial is a prospective, multicenter, randomized, controlled trial that will assess the 180-day survival rate with no or minimal neurologic sequel in patients resuscitated from an OHCA without ST segment elevation and who will be managed with either immediate or delayed CAG.

Tumor burden and liver function in HCC patient selection for selective internal radiation therapy: SARAH post-hoc study.

Aim: To determine whether a liver tumor burden ≤25% and well-preserved liver function (albumin-bilirubin grade 1) are appropriate criteria for identifying patients with unresectable hepatocellular carcinoma who may benefit from selective internal radiation therapy (SIRT) using 90yttrium resin microspheres versus sorafenib. Patients & methods: Post-hoc analysis of patients in the intention-to-treat population of the SARAH trial (SIRT vs sorafenib) with ≤25% tumor burden and albumin-bilirubin grade 1. Primary end point: overall survival. Results: Median overall survival was 21.9 months (95% CI: 15.2-32.5, n = 37) with SIRT and 17.0 months (11.6-20.8, n = 48) with sorafenib (hazard ratios: 0.73; 95% CI: 0.44-1.21; p = 0.22). Conclusion: A combination of good liver function and low tumor burden may be relevant for selection of hepatocellular carcinoma patients for SIRT.

Cardiovascular outcome trials in patients with chronic kidney disease: challenges associated with selection of patients and endpoints.

Although cardiovascular disease is a major health burden for patients with chronic kidney disease, most cardiovascular outcome trials have excluded patients with advanced chronic kidney disease. Moreover, the major cardiovascular outcome trials that have been conducted in patients with end-stage renal disease have not demonstrated a treatment benefit. Thus, clinicians have limited evidence to guide the management of cardiovascular disease in patients with chronic kidney disease, particularly those on dialysis. Several factors contribute to both the paucity of trials and the apparent lack of observed treatment effect in completed studies. Challenges associated with conducting trials in this population include patient heterogeneity, complexity of renal pathophysiology and its interaction with cardiovascular disease, and competing risks for death. The Investigator Network Initiative Cardiovascular and Renal Clinical Trialists (INI-CRCT), an international organization of academic cardiovascular and renal clinical trialists, held a meeting of regulators and experts in nephrology, cardiology, and clinical trial methodology. The group identified several research priorities, summarized in this paper, that should be pursued to advance the field towards achieving improved cardiovascular outcomes for these patients. Cardiovascular and renal clinical trialists must partner to address the uncertainties in the field through collaborative research and design clinical trials that reflect the specific needs of the chronic and end-stage kidney disease populations, with the shared goal of generating robust evidence to guide the management of cardiovascular disease in patients with kidney disease.