IntroductionStudy aims were to evaluate the elastic properties of vascular substitutes frequently used for pulmonary artery (PA) replacement, and then to compare their compliance and stiffness indexes to those of human PA. MethodsA bench-test pulsatile flow experiment was developed to perfuse human cadaveric vascular substitutes (PA, thoracic aorta, human pericardial conduit), bovine pericardial conduit, and prosthetic vascular substitutes (polytetrafluorethylene and Dacron grafts) at a flow and low pulsed pressure mimicking pulmonary circulation. Intraluminal pressure was measured. An ultrasound system with an echo-tracking function was used to monitor vessel wall movements. The diameter, compliance, and stiffness index were calculated for each vascular substitute and compared to the human PA at mean pressures ranging from 10 to 50 mmHg. ResultsThe compliance of the PA and the thoracic aorta were similar at mean physiological pressures of 10 mmHg and 20 mmHg. The PA was significantly less compliant than the aorta at mean pressures above 30 mmHg (P = 0.017). However, there was no difference in stiffness index between the two substitutes over the entire pressure range. Compared to the PA, human pericardial conduit was less compliant at 10 mmHg (P = 0.033) and stiffer at 10 mmHg (P = 0.00038) and 20 mmHg (P = 0.026). Bovine pericardial conduit and synthetic prostheses were significantly less compliant and stiffer than the PA for mean pressures of 10, 20, and 30 mmHg. There were no differences at 40 and 50 mmHg. ConclusionsAllogenic arterial grafts appear to be the most suitable vascular substitutes in terms of compliance and stiffness for PA replacement.

Shortages of drugs and medical devices have tended to increase in France and worldwide, with consequences for patients and healthcare professionals. Preventing shortages of health products has become a priority for regulatory authorities, including the French National Agency for Medicines and Health Products Safety (ANSM). To highlight perspectives for a better prevention, we described and analyzed the management of shortages in the availability of health products in France over the last 10 years. The supply chain was mapped to identify the main causes of shortages and stakeholders involved in managing shortages throughout the supply chain. National and European initiatives and regulatory measures were reviewed. A retrospective nationwide data analysis from the French reporting system of health product shortage reports was conducted over 10 years for drugs (2013-2022) and over an 18-month period for medical devices, from 1st March 2022 to 31st August 2023. An increase in drug shortage reports was observed, rising from 404 in 2013 to 3,761 in 2022 for drugs, with a relatively constant distribution of affected therapeutic classes. In 2022, the main reported causes of drug shortage risk were insufficient production capacity (27.1%), increased sales volume (21.5%), or lack of supply (13.6%). Over half of the reports on medical devices (55.4%) were objectified as indispensable, and their causes were mainly due to a lack of supply (48.2%), discontinuation of marketing (14.9%), increased sales volume (13.2%), and regulatory reasons (9.6%). ANSM and French authorities have engaged a public health policy for prevention and management of health product shortages including financial penalties, minimum safety stocks for Major Therapeutic Interest drugs, and a shortage management plan. Based on 10 years of experience, four priority measures have been identified to anticipate the risk of heath products shortages based: the importance of a national coordination from raw materials to local market, the implementation of new prevention and management actions in the supply chain, strengthening European cooperation and regulation including the establishment of a list of critical drugs, and promoting transparency and information.

Abstract Background PCI-related myocardial infarction (MI) or injury are frequent events that have been shown to be associated with long-term ischemic outcomes and mortality. Determinants of these events with the validated definition of PCI-related myocardial infarction (MI) or injury are not well documented in contemporary elective PCI. Methods The ALPHEUS-MI study is a prespecified analysis of the ALPHEUS randomized trial conducted in 49 centers of two European countries which recruited 1910 patients with chronic coronary syndrome undergoing elective PCI. We analyzed the rate and predictors of periprocedural myocardial necrosis using the primary and secondary endpoint of the ALPHEUS trial (3rd and 4th universal definition of MI) and the ARC2/SCAI definitions. Multivariable model including patient’s demographic, angiographic and procedural characteristics were performed for each definition to determine predictors of periprocedural events. Findings : The primary endpoint of the ALPHEUS trial (type 4a MI or major myocardial injury) occurred in 35.85% of the patients (3rd universal definition of MI); the secondary endpoint of the ALPHEUS trial (type 4a MI and any myocardial injury) occurred in 77.21% of the patients (4th universal definition of MI); significant periprocedural myocardial injury occurred in 3.24% of the patients (ARC2/SCAI definition) and periprocedural MI (ARC2/SCAI definition) in 2.02% of the patients. The rate of events followed a stepwise increase according to the number of high-risk features with all definitions (figure). High risk features were characterized by patients’ characteristics, the complexity of the coronary lesion (anatomy and atheroma burden) and the complexity of the PCI procedure itself. The only common predictor of MI or myocardial injury present with the 4 definitions was the total length of stent implanted (>60mm) ; adjOR 3.23 (2.49-4.18) p<0,001 (type 4a MI/major injury 3rd UDMI ) , adjOR 3.82 (2.51-5.8) p<0,001 (type 4a MI/any injury 4th UDMI) , adjOR 2.2 (1.24-3.91) p=0,007 (myocardial injury ARC2/SCAI) and adjOR 6.0 (3.04-11.9) p<0,001 (MI ARC2/SCAI). Conclusion Whatever definition of type 4aMI and myocardial injury, the strongest predictor of myocardial necrosis seems to be the length of stent implanted which reflects both the severity of atheroma burden and the complexity of PCI.

Severe coronary artery calcification, too often underestimated, increases the complexity of percutaneous coronary interventions. Atherectomy is one of preferred approach for the preparation of calcified lesions before stent placement. Orbital atherectomy is a new method that has proven to be safe and effective in the preparation of calcium plaques (ORBIT I and ORBIT II studies). The recent introduction in France allows to perform a prospective registry named REFORCE. Its main objective is to include 300 patients in order to evaluate security and safety of the device in France during routine use.

Vasospastic angina, also described as Prinzmetal angina, was first described as a variant form of angina at rest with transient ST-segment elevation; it is common and present in many clinical scenarios, including chronic and acute coronary syndromes, sudden cardiac death, arrhythmia and syncope. However, vasospastic angina remains underdiagnosed, and provocative tests are rarely performed. The gold-standard diagnostic approach uses invasive coronary angiography to induce coronary spasm using ergonovine, methylergonovine or acetylcholine as provocative stimuli. The lack of uniform protocol decreases the use and performance of these tests, accounting for vasospastic angina underestimation. This position paper from the French Coronary Atheroma and Interventional Cardiology Group (GACI) aims to review the indications for provocative tests, the testing conditions, drug protocols and positivity criteria.

Duplex ultrasound (DUS) is an essential tool for characterizing and monitoring arteriovenous (AV) access for hemodialysis. The aim of the work described here, requested by the French Society of Vascular Medicine in collaboration with the French-Speaking Vascular Access Society, is to propose a standardized methodology for performing and documenting DUS, taking into account the variety of AV access techniques and the problems routinely encountered. A steering committee reviewed the literature and selected the relevant references. A draft was prepared, and all items with missing or conflicting data were submitted to a Delphi consensus. The final document was discussed and approved by all participants. The principles of DUS evaluation of AV access consist of examination of the afferent artery, the anastomosis and the entire venous drainage system. DUS uses B-mode ultrasound, color flow, pulsed wave and power Doppler analysis. DUS can be used in a variety of clinical situations, which can directly influence the methodology of the examination and the interpretation of the results. Blood flow should be assessed as it correlates with the risk of thrombosis. The measurement should be adapted to the different anatomical and hemodynamic conditions encountered. Characterization of stenosis should take into account the residual diameter of the drainage vein and its hemodynamic consequences. Other complications can be assessed with a standardized DUS examination. When performed according to a rigorous methodology, DUS of the AV access allows a comprehensive assessment of its functionality and eliminates the need for further invasive diagnostic procedures.

Obstructive coronary artery disease is the main cause of death worldwide. By tracking events and gaining feedback on patient management, the most relevant information is provided to public health services to further improve prognosis. To create an inclusive and accurate registry of all percutaneous coronary intervention (PCI) procedures performed in France, to assess and improve the quality of care and create research incentives. Also, to describe the methodology of this French national registry of interventional cardiology, and present early key findings. The France PCI registry is a multicentre observational registry that includes consecutive patients undergoing coronary angiography and/or PCI. The registry was set up to provide online data analysis and structured reports of PCI activity, including process of care measures and assessment of risk-adjusted outcomes in all French PCI centres that are willing to participate. More than 150 baseline data items, describing demographic status, PCI indications and techniques, and in-hospital and 1-year outcomes, are captured into local reporting software by medical doctors and local research technicians, with subsequent encryption and internet transfer to central data servers. Annual activity reports and scoring tools available on the France PCI website enable users to benchmark and improve clinical practices. External validation and consistency assessments are performed, with feedback of data completeness to centres. Between 01 January 2014 and 31 December 2022, participating centres increased from six to 47, and collected 364,770 invasive coronary angiograms and 176,030 PCIs, including 54,049 non-ST-segment elevation myocardial infarction cases and 31,631 ST-segment elevation myocardial infarction cases. Fifteen studies stemming from the France PCI registry have already been published. This fully electronic, daily updated, high-quality, low-cost, national registry is sustainable, and is now expanding. Merging with medicoeconomic databases and nested randomized scientific studies are ongoing steps to expand its scientific potential.

Tumor genomic profiling and PD-L1 testing mean lung cancer management can be tackled through a personalized approach. Targeted therapies and immunotherapy are necessary to improve survival and preserve the patients' quality of life. Early access to innovation before marketing authorization (MA) is possible in France through clinical trials and an early-access program called a Temporary Authorization for Use (ATU), which is a unique regulatory system in Europe. This study aims to assess the impact of early access to innovation through clinical trials and ATUs in thoracic oncology. Data from clinical trials between 2018 and 2021 and ATUs between 2005 and 2019 were collected internally and assessed for drugs in thoracic oncology, with specific focus on 2 ATUs, respectively, atezolizumab and durvalumab. From 2018 to 2021, the National Agency for the Safety of Medicines and Health Products authorized 145 clinical trials in lung cancer. Between 2005 and 2019, 19 drugs obtained an EU MA or an MA extension for a therapeutic indication in lung cancer. During this period, 11 of these drugs were granted an ATU, corresponding to 6851 patients treated. Of this total number of patients, data were collected for 33.1% and 71.2%, who received durvalumab and atezolizumab, respectively. Real-life efficacy data were consistent with the clinical trial data. Over the past 15years, clinical trials and the French early access program have allowed considerable early access to therapeutic innovation in real life for patients, especially in thoracic oncology.

5521 Background: Niraparib (NI) maintenance is a standard of care in platinum-sensitive ROC. Based on pivotal randomized trials, toxicity profile appears manageable through adapted drug dosing. However, data on tolerance and feasibility for unselected patients (pts) are missing, especially regarding pts’ reported adverse events (AE). Methods: NIQOLE study is a real-life longitudinal multicenter, phase IV study in ROC pts treated with NI maintenance. NI starting dose was adapted to pts’ weight and platelet count. The primary endpoint was to describe physicians’ reported AE (NCI-CTC-AE, grading from 0 to 5) leading to treatment modifications (TM), defined by dose reduction or treatment interruption/discontinuation from baseline to month 3 and delay of first TM. Secondary endpoints included duration of treatment and pts’ reported AE. Progression rates were exploratory endpoints. Owing to a digital device, pts provided remoted weekly AE (NCI PRO-CTC-AE, grading from 0 to 3) which were accessible to investigators. Concordance between the main symptomatic AEs reported by pts and those reported by physicians was analyzed. Results: 139 pts were treated: median age 70 [44-88], high-grade serous histology 91%, BRCA mutation 5%, first relapse 72%, prior bevacizumab 71%. The median delay from platinum-based regimen and NI was 49 days [15-109]. NI starting dose was 200 mg in 80% of pts and the median treatment duration was 5.6 months [0.2-21]. Progression rates at 3 and 6 months were 19 and 45%, respectively. At 3 months, 60% (n=84%) of pts had at least one TM, of whom 47% (n=66) were treatment-related AEs: dose reduction in 17/66 (26%), interruption in 53/66 (80%) and discontinuation in 11/66 (17%). The first AE inducing TM occurred at 22 days (median) [2 -91]. Thrombocytopenia was the main AE leading to TM (70% of cases). 24% of AEs were grade 3-4. Remoted PRO-CTC-AEs were acknowledged by physicians in 59% of cases of whom 31% led to adaptation of pts’ care. During the 3 months, 98% of pts reported symptomatic AEs (including nausea, constipation, fatigue, dry mouth and insomnia), of which 66% were grade 3. There was a very poor correlation (<0.20) between symptomatic AEs reported by the pts vs by the physicians (table). Conclusions: In real life, despite initial individual dosing, NI maintenance requires frequent TM during the first 3 months of treatment. There is a strong discrepancy between symptomatic AEs regularly captured by pts and those reported by physicians during clinics. Next generation of clinical trials should integrate pts' perspective to better assess toxicity and manage treatment course. Clinical trial information: NCT03752216 . [Table: see text]

TPS615 Background: Adjuvant Endocrine Therapy (ET) is the cornerstone treatment of localized hormone-receptor positive (HR+) breast cancer, with demonstrated benefits on overall survival (30-40% relative decrease in mortality) but also on the risk of local and contralateral relapse (43-50% relative decrease). While the relative benefit of 5 years of ET is identical for small tumors as compared to larger ones, the absolute benefit is much lower, and the risk-benefit ratio becomes questionable given the frequent and impactful side effects of ET which are associated with non-adherence. If recent trials tested longer durations as compared to 5 years for high-risk cancers, older trials have tested shorter durations. Five years appeared at that time as the gold standard because of optimal benefit-risk ratios of tamoxifen among rather high-risk patients. However, shorter treatments of 2-3 years were already associated with substantial benefits and may be enough for very low risk patients. The purpose of this study is to demonstrate that adjuvant ET limited to 2 years of aromatase inhibitor (AI) in postmenopausal women at very low risk of recurrence as determined with a MammaPrint and BluePrint Ultra Low Risk Luminal test result can ensure very high survival without metastatic relapse and allows a reduction of side effects and a better quality of life. Methods: LESS (NCT05297617) is a prospective, national, multicenter, single-arm, interventional, non-threshold crossing phase II study evaluating a therapeutic de-escalation that limits adjuvant ET to 2 years of AI. Approximately 696 post-menopausal patients with an invasive unilateral, HR+, HER2-negative, without indication of adjuvant chemoT and genomically-assessed MammaPrint/BluePrint UltraLow risk Luminal A breast cancer tumors, will be enrolled. LESS will include two sub cohorts: the majority of patients with Grade 2, pT1c-2, pN0/N1mic tumors, and up to 80 patients ≥65 years with Grade 1, pT1, pN0 and Ki67<10% tumors. The primary endpoint is distant metastasis free survival (DMFS) defined as the time from date of registration to date of first event of distant recurrence, death, or second primary non-breast invasive cancer. Secondary endpoints include the assessment of quality of life parameters and psychological aspects related to this de-escalation. The null hypothesis (H0) that, in the study population after 2 years of adjuvant AI, DMFS at 5 years is lower or equal to 94.5% will be tested against the alternative - that it is above 94.5%. For an expected DMFS of 96.7% under the alternative hypothesis, a total of 37 DMFS events are required in order to provide approximately 85% power at a one-sided significance level of 0.05 to reject H0 using a logrank test. The 1st patient was included in October 2022, initiating the 2-year inclusion period and 10 years FU per patient. Clinical trial information: NCT05297617 .