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Open in new tab Download slide OBJECTIVES The aim of this study was to describe the epidemiology of patients undergoing diagnostic and/or curative surgical pulmonary resections for lung opacities suspected of being localized primary lung cancers without preoperative tissue confirmation. METHODS We performed a single-centre retrospective study of a prospectively implemented institutional database of all patients who underwent pulmonary resection between January 2010 and December 2020. Patients were selected when surgery complied with the Fleischner society guidelines. We performed a multivariable logistic regression to determine the preoperative variables associated with malignancy. RESULTS Among 1392 patients, 213 (15.3%) had a final diagnosis of benignancy. We quantified futile parenchymal resections in 29 (2.1%) patients defined by an anatomical resection of >2 lung segments for benign lesions that did not modified the clinical management. Compared with patients with malignancies, patients with benignancies were younger (57.5 vs 63.9 years, P  < 0.001), had lower preoperative risk profile (thoracoscore 0.4 vs 2.1, P  < 0.001), had a higher proportion of wedge resection (50.7% vs 12.2%, P  < 0.01) and experienced a lower burden of postoperative complication (Clavien–Dindo IV or V, 0.4% vs 5.6%, P  < 0.001). Preoperative independent variables associated with malignancy were (adjusted odd ratio [95% confident interval]) age 1.02 [1.00; 1.04], smoking (year-pack) 1.005 (1.00; 1.01), history of cardiovascular disease 2.06 [1.30; 3.30], history of controlled cancer 2.74 [1.30; 6.88] and clinical N involvement 4.20 [1.11; 37.44]. CONCLUSIONS Futile parenchymal lung resection for suspicious opacities without preoperative tissue diagnosis is rare (2.1%) while surgery for benign lesions represented 15.3% and has a satisfactory safety profile with very low postoperative morbi-mortality. [ABSTRACT FROM AUTHOR]

A striking feature of the human pulmonary circulation is that mean (mPAP) and systolic (sPAP) pulmonary artery pressures (PAPs) are strongly related and, thus, are essentially redundant. According to the empirical formula documented under normotensive and hypertensive conditions (mPAP = 0.61 sPAP + 2 mmHg), sPAP matches ~160%mPAP on average. This attests to the high pulsatility of PAP, as also witnessed by the near equality of PA pulse pressure and mPAP. Our prospective study tested if pressure redundancy and high pulsatility also apply in a piglet model of chronic thromboembolic pulmonary hypertension (CTEPH). At baseline (Week‐0, W0), Sham (n = 8) and CTEPH (n = 27) had similar mPAP and stroke volume. At W6, mPAP increased in CTEPH only, with a two‐ to three‐fold increase in PA stiffness and total pulmonary resistance. Seven CTEPH piglets were also studied at W16 at baseline, after volume loading, and after acute pulmonary embolism associated with dobutamine infusion. There was a strong linear relationship between sPAP and mPAP (1) at W0 and W6 (n = 70 data points, r² = 0.95); (2) in the subgroup studied at W16 (n = 21, r² = 0.97); and (3) when all data were pooled (n = 91, r² = 0.97, sPAP range 9–112 mmHg). The PA pulsatility was lower than that expected based on observations in humans: sPAP matched ~120%mPAP only and PA pulse pressure was markedly lower than mPAP. In conclusion, the redundancy between mPAP and sPAP seems a characteristic of the pulmonary circulation independent of the species. However, it is suggested that the sPAP thresholds used to define PH in animals are species‐ and/or model‐dependent and thus must be validated. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide Open in new tab Download slide OBJECTIVES Direct involvement of the superior vena cava (SVC) by non-small cell lung cancer (NSCLC) requires en-bloc tumour resection with complete vascular clamping and prosthetic replacement. We report the outcomes of this highly demanding procedure in the largest patient cohort to date. METHODS We searched our institution's database for patients who underwent complete en-bloc resection of NSCLC invading the SVC followed by prosthetic SVC replacement, between 1980 and 2018. Patients with cN2, cN3 or distant metastases were not eligible. RESULTS We identified 48 patients (38 males, 10 females; mean age of 57 years; tumour size, 1.9–17 cm). Neoadjuvant therapy was administered to 17 and adjuvant therapy to 31 patients. R0 resection was achieved in 41 (85%) patients; lymph node involvement was pN0 in 8, pN1 in 23, pN2 in 14 and pN3 in 3 patients. Five patients died within 30 days of surgery. Right pneumonectomy was significantly associated with postoperative death (P  =   0.02). Postoperative complications developed in 13 other patients. No neurologic events related to SVC clamping occurred. Graft thrombosis developed in 2 patients. Median survival was 24 months; 3-, 5- and 10-year survival rates were 45%, 40% and 35%, respectively; and corresponding disease-free survival rates were 37%, 37% and 30%, respectively. By univariable analysis, only margin-free (R0) resection was associated with better survival (P  =   0.02). CONCLUSIONS In highly selected patients with NSCLC involving the SVC, mortality is acceptable after complete en-bloc resection and prosthetic replacement done in an expert centre. SVC involvement should not preclude consideration of curative resection in selected patients. [ABSTRACT FROM AUTHOR]

Background: In en bloc vertebrectomy, the posterior approach is associated with limited access to anterior structures (vertebral body, esophagus, aorta, azygos vein). Video-assisted thoracoscopic surgery (VATS) might prove to be advantageous during thoracic en bloc vertebrectomy by allowing a combined anterior-posterior access in the prone position. We describe the technique and review the outcomes of 33 cases of video-assisted thoracoscopic en bloc vertebrectomy.Methods: A retrospective, single-center cohort study included all cases of VATS with a minimum follow-up of 1 year. A team of thoracic and orthopaedic surgeons performed the surgical procedure with the patient in a single, prone position. Anterior release was carried out thoracoscopically, followed by posterior en bloc tumor removal.Results: From 2003 to 2019, 33 patients were included. Nine patients underwent total vertebrectomy (8 had single-level and 1 had 3-level), and 24 patients underwent partial vertebrectomy (1 had single-level, 8 had 2-level, 13 had 3-level, and 2 had 4-level). Ten patients had pulmonary resection. Histology revealed 18 cases (55%) of primary bone tumors, 6 cases (18%) of lung cancer invading the spine, 6 cases (18%) of solitary metastasis, and 3 other cases (9%). The margins were tumor-free in 28 cases (85%). The median operative time was 240 minutes (range, 150 to 510 minutes), with a median blood loss of 1,200 mL (range, 400 to 6,700 mL), and there were 2 cases of conversion to thoracotomy. A total of 33 complications occurred in 18 patients (55%), and these were predominantly pulmonary. One death was surgery-related (infection). One patient had a persistent monoplegia. At a median follow-up of 63 months (range, 12 to 156 months), there were 21 surviving patients (64%) with 2 local recurrences and 1 distant recurrence, and 2 patients (6%) were lost to follow-up. The survival rates were 94% at 1 year, 71% at 2 years, and 68% at 5 years.Conclusions: VATS en bloc vertebrectomy may be indicated for T2-to-T11 spine tumors with the exception of massive tumors, substantial chest wall and/or mediastinal invasion, and lung cancer exceeding 7 cm. The technique yielded satisfactory surgical and oncologic outcomes.Level Of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Aims Risk stratification in heart failure (HF) relies on several established clinical risk scores, however, myocardial deformation, right heart metrics, and exercise performance have not usually been considered. This study sought to assess the incremental value of advanced echocardiographic and cardiopulmonary exercise testing (CPX) parameters to validated risk scores in HF. Methods and results The Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) and Metabolic Exercise Test Data Combined with Cardiac and Kidney Indexes (MECKI) scores were applied to 208 ambulatory patients with dilated cardiomyopathy (DCM) who completed echocardiography in conjunction with CPX as part of the Stanford Exercise Testing registry. Patients were followed for the composite end point of death, heart transplant, left ventricular device implantation, and hospitalization for acute HF. Mean age, left ventricular ejection fraction (LVEF), and left ventricular global longitudinal strain (LVGLS) were 47 ± 13 years, 33 ± 13%, and −10.6 ± 4.4%, respectively, while right ventricular free-wall longitudinal strain was −18.8 ± 5.5%. Partial correlation mapping identified strong correlations between LVEF, LVGLS, and LV systolic strain rate, with a moderate correlation between these metrics and peak VO2. Over a median follow up of 5.3 years, the composite end point occurred in 60 patients. Cox proportional hazards identified MAGGIC score [hazard ratio (HR) (2.04 [1.39–3.01], P  < 0.01], peak VO2 HR (0.52 [0.28–0.97], P  = 0.04), and right atrial volume indexed (RAVI) HR (1.31 [1.07–1.61], P  < 0.01) as independent correlates of outcome. RAVI remained an independent correlate when combined with the MECKI score (2.21 [1.59–3.07]), P  < 0.01, RAVI, 1.33 [1.06–1.67], P  = 0.01). Conclusion Our study demonstrates that RAVI is complementary to well-validated HF risk scores and highlights the importance of exercise performance in DCM. [ABSTRACT FROM AUTHOR]

Background Extracorporeal life support (ECLS) can be used to sustain patients having cardiorespiratory failure after pulmonary endarterectomy (PEA). We aimed to assess outcomes and to identify factors associated with short-term survival among patients who required ECLS after PEA. Methods We reviewed the charts of consecutive patients who required ECLS after PEA between 2005 and 2013 at our institution. Patients with failed PEA were scheduled for heart-lung transplantation, and patients with potentially reversible hemodynamic or respiratory failure were given appropriate supportive care until recovery. Results Of the 829 patients who underwent PEA, 31 (3.7%) required postoperative ECLS. Of these, 23 continued to receive support, and 8 were listed for heart-lung transplantation during ECLS. Overall inhospital survival was 48.4% (15 of 31). Of patients listed for transplantation, 2 died while on support; 4 of the 6 patients undergoing transplantation lived to hospital discharge. Of the 23 supportive care patients, 11 (47.8%) were alive at hospital discharge. The factors associated with survival were younger age ( p = 0.02), larger post-PEA decrease in mean pulmonary artery pressure ( p = 0.020), lower post-PEA total pulmonary resistance ( p = 0.008), and pure respiratory failure related to reperfusion edema or airway bleeding ( p = 0.003). Conclusions Extracorporeal life support may be useful to support patients with complications after PEA either to recovery or to salvage transplantation. [ABSTRACT FROM AUTHOR]

OBJECTIVES We observed early acute lung injury (ALI) after a switch from veno-arterial extracorporeal life support (VA-ECLS) to long-term mechanical circulatory support (MCS). The aim of our study was to analyse the frequency, impact on mortality and characteristics of patients presenting ALI after MCS implantation in the bridge-to-bridge (BTB) strategy. METHODS We retrospectively analysed data from 55 consecutive cardiogenic shock patients who underwent a BTB strategy between January 2004 and March 2012 in our centre. ALI was defined as severe acute respiratory failure (PaO2/FiO2 <200) with or without need for iterative VA-ECLS or veno-venous (VV)-exracorporeal membrane oxygenation (ECMO) occurring within 48 h of MCS implantation. RESULTS ALI was observed in 15 of 55 (27%) patients. Eleven patients required VV-ECMO or VA-ECLS and 4 were treated medically. The median (interquartile range) duration of support under a long-term device was 47.5 (168.8) days. Mortality while on long-term support was significantly higher in patients who developed ALI (13 of 15, 87%) than in those who did not (21 of 40, 53%; P = 0.03). Hazard ratio for death while on support in patients who developed ALI when compared with those who did not was 3.390 (95% confidence interval, 1.636–7.026, P = 0.001). Univariate risk factors for postimplant ALI included: signs of pulmonary oedema while under extracorporeal life support (ECLS) during the week preceding long-term device implantation; mechanical ventilation, the incomplete recovery of renal and hepatic functions and the number of red blood cell units transfused at the time of long-term device implantation, and use of pulsatile, biventricular support. CONCLUSIONS Implantation of a long-term MCS device in patients on ECLS can result in severe ALI, which is associated with ominous outcomes. Various preimplant risk factors for ALI have been identified and might allow devising strategies to prevent this complication. [ABSTRACT FROM AUTHOR]

Angiophagy has been described as a non-fibrinolytic mechanism of pulmonary artery (PA) patency restoration after distal (<50 µm in diameter) pulmonary embolism in mice. We hypothesized that angiophagy could achieve muscularized PA patency restoration after pulmonary embolism in piglets and humans. Angiophagy was defined by pathological assessment as the moving of an embolic specimen from the lumen to the interstitium according to three stages in a pig model of chronic thromboembolic pulmonary hypertension (CTEPH) 6 to 10 weeks after embolization with enbucrilate: the embolic specimen is (I) covered by endothelial cells, (II) covered by endothelial cells and smooth muscle cells, and (III) located in the adventitia. In animals, we observed the three stages of the pulmonary angiophagy of enbucrilate emboli in <300 µm PA. Stages II and III were observed in 300 to 1000 μm PA, and only Stage I was observed in larger-diameter PA (>1000 μm). In lung samples from patients with histories of pulmonary embolisms, we observed PA angiophagy stigma for embolic specimens derived from blood clots and from bone marrow emboli. This study provides an original pathological description and staging of PA angiophagy in a large animal model of CTEPH and in humans after pulmonary embolism. [ABSTRACT FROM AUTHOR]

Background: Tricuspid annular systolic excursion (TAPSE) or velocities (s′) and right ventricular (RV) end‐systolic dimensions are predictors of outcome in patients with pulmonary hypertension (PH). We explored the value of combining peak s′ and RV end‐systolic area index (RVESAi) as a surrogate of RV‐pulmonary artery (RV–PA) coupling in a large animal of precapillary PH as well as clinically. Method: The first experimental group included four control and four piglets with thromboembolic disease. RV–PA coupling was assessed by ventricular to arterial elastance ratio (Ees/Ea) at baseline, after esmolol and dobutamine administration. Echocardiographic metrics included s′, TAPSE, fractional area change (RVFAC), and RVESAi. The findings were validated in six piglets with severe PH. Clinical cohorts were stable outpatients (n = 141) and acutely decompensated pulmonary arterial hypertension (n = 48). Results: In the first experimental group, the best linear correlates of Ees/Ea were s′ (R2 =.51, p <.001) and RVESAi (R2 =.50, p <.001), while RVFAC (R2 =.17, p =.01) and TAPSE showed weaker association (R2 =.21, p =.39). The ratio s′/RVESAi showed nominally but not significantly (higher) association with Ees/Ea (R2 =.58, p <.01). The association between changes in s′/RVESAi and Ees/Ea was strong (R2 =.56, p <.001). In more severe PH, Ees/Ea and changes in Ees/Ea correlated significantly with s′/RVESAi and changes in s′/RVESAi (R2 =.69; p <.001 and R2 =.64, p <.001, respectively). In the two clinical cohorts, the s′/RVESAi did not emerge as a stronger predictor of outcome than RVESAi. Conclusion: RV s′/RVESAi index represents a reasonable bedside‐usable surrogate of RV–PA coupling and of its acute variations in PH. Its incremental prognostic value over end‐systolic dimension alone remains to be proven. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary arterial hypertension (IPAH) is a complex disease associated with vascular remodeling and a proliferative disorder in pulmonary artery smooth muscle cells (PASMCs) that has been variably described as having neoplastic features. To decode the phenotype of PASMCs in IPAH, PASMCs from explanted lungs of patients with IPAH (IPAH-PASMCs) and from controls (C-PASMCs) were cultured. The IPAH-PASMCs grew faster than the controls; however, both growth curves plateaued, suggesting contact inhibition in IPAH cells. No proliferation was seen without stimulation with exogenous growth factors, suggesting that IPAH cells are incapable of self-sufficient growth. IPAH-PASMCs were more resistant to apoptosis than C-PASMCs, consistent with the increase in the Bcl2/Bax ratio. As cell replication is governed by telomere length, these parameters were assessed jointly. Compared to C-PASMCs, IPAH-PASMCs had longer telomeres, but a limited replicative capacity. Additionally, it was noted that IPAH-PASMCs had a shift in energy production from mitochondrial oxidative phosphorylation to aerobic glycolysis. As DNA damage and genomic instability are strongly implicated in IPAH development a comparative genomic hybridization was performed on genomic DNA from PASMCs which showed multiple break-points unaffected by IPAH severity. Activation of DNA damage/repair factors (γH2AX, p53, and GADD45) in response to cisplatin was measured. All proteins showed lower phosphorylation in IPAH samples than in controls, suggesting that the cells were resistant to DNA damage. Despite the cancer-like processes that are associated with end-stage IPAH-PASMCs, we identified no evidence of self-sufficient proliferation in these cells—the defining feature of neoplasia. [ABSTRACT FROM AUTHOR]

• The number of octogenarians with an early-stage NSCLC almost doubled each 5-year interval of the study period. • The implementation of a dedicated geriatric pathway and the use of minimally invasive approaches were both associated with improved outcomes. • Overall survival was influenced by lower co-morbidity index, highest predicted postoperative DLCO values, and absence of diabetes mellitus. We investigated on the benefit/risk ratio of surgery in octogenarians with early-stage non-small cell lung cancer (NSCLC). From 2005–2020, 100 octogenarians were operated on for a clinical stage IA to IIA NSCLC. All patients had undergone whole body PET -scan and brain imaging. Operability was assessed according to current guidelines regarding the cardiopulmonary function. Since 2015, patients followed a dedicated geriatric evaluation pathway. Minimally invasive approaches were used in 66 patients, and a thoracotomy in 34. Clavien-Dindo grade ≥ 4 complications occurred in 15 patients within 90 days, including 7 fatalities. At multivariable analysis, the number of co-morbidities was their single independent prognosticator. Following resection, 24 patients met pathological criteria for adjuvant therapy among whom 3 (12.5 %) received platinum-based chemotherapy. Five-year survival rates were overall (OS) 47 ± 6.3 %, disease-free (DFS) 77.6 ± 5.1 %, and lung cancer-specific (CSS) 74.7 ± 6.3 %. Diabetes mellitus impaired significantly long-term outcomes in these 3 dimensions. OS was improved since the introduction of a dedicated geriatric assessment pathway (72.3 % vs. 6.4 %, P = 0.00002), and when minimally invasive techniques were used (42.3 % vs. 11.3 %; P = 0.02). CSS was improved by the performance of systematic lymphadenectomy (55.3 % vs. 26.9 %; P = 0.04). Multivariable and recursive partitioning analyses showed that a decision tree could be built to predict overall survival on the basis of diabetes mellitus, high co-morbidity index and low ppoDLCO values. The introduction of a dedicated geriatric assessment pathway to select octogenarians for lung cancer surgery was associated with OS values that are similar to outcomes in younger patients. The use of minimally invasive surgery and the performance of systematic lymphadenectomy were also associated with improved long-term survival. Octogenarians with multiple co-morbid conditions, diabetes mellitus, or low ppo DLCO values may be more appropriately treated with SBRT. [ABSTRACT FROM AUTHOR]

Introduction: Lung transplantation (LTx) aims at improving survival and quality of life for patients with end-stage lung diseases. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is used as intraoperative support for LTx, despite no precise guidelines for its initiation. We aim to evaluate two strategies of VA-ECMO initiation in the perioperative period in patients with obstructive or restrictive lung disease requiring bilateral LTx. In the control 'on-demand' arm, high haemodynamic and respiratory needs will dictate VA-ECMO initiation; in the experimental 'systematic' arm, VA-ECMO will be pre-emptively initiated. We hypothesise a 'systematic' strategy will increase the number of ventilatory-free days at day 28., Methods and Analysis: We designed a multicentre randomised controlled trial in parallel groups. Adult patients with obstructive or restrictive lung disease requiring bilateral LTx, without a formal indication for pre-emptive VA-ECMO before LTx, will be included. Patients with preoperative pulmonary hypertension with haemodynamic collapse, ECMO as a bridge to transplantation, severe hypoxaemia or hypercarbia will be secondarily excluded. In the systematic group, VA-ECMO will be systematically implanted before the first pulmonary artery cross-clamp. In the on-demand group, VA-ECMO will be implanted intraoperatively if haemodynamic or respiratory indices meet preplanned criteria. Non-inclusion, secondary exclusion and VA-ECMO initiation criteria were validated by a Delphi process among investigators. Postoperative weaning of ECMO and mechanical ventilation will be managed according to best practice guidelines. The number of ventilator-free days at 28 days (primary endpoint) will be compared between the two groups in the intention-to-treat population. Secondary endpoints encompass organ failure occurrence, day 28, day 90 and year 1 vital status, and adverse events., Ethics and Dissemination: The sponsor is the Assistance Publique-Hôpitaux de Paris. The ECMOToP protocol version 2.1 was approved by Comité de Protection des Personnes Ile de France VIII. Results will be published in international peer-reviewed medical journals., Trial Registration Number: NCT05664204., Competing Interests: Competing interests: JM declares congress reimbursement fees from Biotest. PMor declares consulting fees from iPerf. PMon declares lecture honoraria and board fees from Pfizer, MSD and Menarini. PE, DB, AC, JF, JJ, PL, OM, PP, HR, ES, JT, FT, MV, YC and HM declare no competing interest., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Our goal was to evaluate the association between the distance of the tumour to the visceral pleura and the rate of local recurrence in patients surgically treated for stage pI lung cancer., Methods: We conducted a single-centre retrospective review of 578 consecutive patients with clinical stage IA lung cancer who underwent a lobectomy or segmentectomy from January 2010 to December 2019. We excluded 107 patients with positive margins, previous lung cancer, neoadjuvant treatment and pathological stage II or higher status or for whom preoperative computed tomography (CT) scans were not available at the time of the study. The distance between the tumour and the closest visceral pleura area (fissure/mediastinum/lateral) was assessed by 2 independent investigators who used preoperative CT scans and multiplanar 3-dimensional reconstructions. An area under the receiver operating characteristic curve analysis was performed to determine the best threshold for the tumour/pleura distance. Then multivariable survival analyses were used to assess the relationship between local recurrence and this threshold in relation to other variables., Results: Local recurrence occurred in 27/471 patients (5.8%). A cut-off value of 5 mm between the tumour and the pleura was determined statistically. In the multivariable analysis, the local recurrence rate was significantly higher in patients with a tumour-to-pleura distance ≤5 mm compared to patients with a tumour-to-pleura distance >5 mm (8.5% vs 2.7%, hazard ratio 3.36, 95% confidence interval: 1.31-8.59, P = 0.012). Subgroup analyses of patients with pIA and tumour size ≤2 cm identified local recurrences in 4/78 patients treated with segmentectomy (5.1%), with a significantly higher occurrence with tumour-to-pleura distances ≤5 mm (11.4% vs 0%, P = 0.037), and in 16/292 patients treated with lobectomy (5.5%) without significant higher occurrence in tumour-to-pleura distances of ≤5 mm (7.7% vs 3.4%, P = 0.13)., Conclusions: The peripheral location of a lung tumour is associated with a higher rate of local recurrence and should be taken into account during preoperative planning when considering segmental versus lobar resection., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Introduction: Eligibility criteria definition for a lung cancer screening (LCS) is an unmet need. We hypothesised that patients with a history of atheromatous cardiovascular disease (ACVD) associated with tobacco consumption are at risk of lung cancer (LC). The main objective is to assess LC prevalence among patients with ACVD and history of tobacco consumption by using low-dose chest CT scan. Secondary objectives include the evaluation LCS in this population and the constitution of a biological biobank to stratify risk of LC., Methods and Analysis: We are performing a monocentric 'single-centre' prospective study among patients followed up in adult cardiovascular programmes of vascular surgery, cardiology and cardiac surgery recruited from 18 November 2019 to 18 May 2021. The inclusion criteria are (1) age 45-75 years old, (2) history of ACVD and (3) history of daily tobacco consumption for 10 years prior to onset of ACVD. Exclusion criteria are symptoms of LC, existing follow-up for pulmonary nodule, fibrosis, pulmonary hypertension, resting dyspnoea and active pulmonary infectious disease. We targeted the inclusion of 500 patients. After inclusion (V0), patients are scheduled for a low-dose chest CT and blood and faeces harvesting within 7 months (V1). Each patient is scheduled for a follow-up by telephonic visits at month 3 (V2), month 6 (V3) and month 12 (V4) after V1. Each patient is followed up until 1 year after V1 (14 February 2023). We measure LC prevalence and quantify the National Lung Screening Trial and Dutch-Belgian Randomized Lung Cancer Screening Trial (NELSON) trial eligibility criteria, radiation, positive screening, false positivity, rate of localised LC diagnosis, quality of life with the Short Form 12 (SF-12) and anxiety with the Spielberger State-Trait Anxiety Inventory A and B (STAI-YA and STAI-YB, respectively), smoking cessation and onset of cardiovascular and oncological events within 1 year of follow-up. A case-control study nested in the cohort is performed to identify clinical or biological candidate biomarkers of LC., Ethics and Dissemination: The study was approved according the French Jardé law; the study is referenced at the French 'Agence Nationale de Sécurité du Médicament et des Produits de Santé' (reference ID RCB: 2019-A00262-55) and registered on clinicaltrial.gov. The results of the study will be presented after the closure of the follow-up scheduled on 14 February 2023 and disseminated through peer-reviewed journals and national and international conferences., Trial Registration Number: NCT03976804., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: The aim of this study was to describe the epidemiology of patients undergoing diagnostic and/or curative surgical pulmonary resections for lung opacities suspected of being localized primary lung cancers without preoperative tissue confirmation., Methods: We performed a single-centre retrospective study of a prospectively implemented institutional database of all patients who underwent pulmonary resection between January 2010 and December 2020. Patients were selected when surgery complied with the Fleischner society guidelines. We performed a multivariable logistic regression to determine the preoperative variables associated with malignancy., Results: Among 1392 patients, 213 (15.3%) had a final diagnosis of benignancy. We quantified futile parenchymal resections in 29 (2.1%) patients defined by an anatomical resection of >2 lung segments for benign lesions that did not modified the clinical management. Compared with patients with malignancies, patients with benignancies were younger (57.5 vs 63.9 years, P < 0.001), had lower preoperative risk profile (thoracoscore 0.4 vs 2.1, P < 0.001), had a higher proportion of wedge resection (50.7% vs 12.2%, P < 0.01) and experienced a lower burden of postoperative complication (Clavien-Dindo IV or V, 0.4% vs 5.6%, P < 0.001). Preoperative independent variables associated with malignancy were (adjusted odd ratio [95% confident interval]) age 1.02 [1.00; 1.04], smoking (year-pack) 1.005 (1.00; 1.01), history of cardiovascular disease 2.06 [1.30; 3.30], history of controlled cancer 2.74 [1.30; 6.88] and clinical N involvement 4.20 [1.11; 37.44]., Conclusions: Futile parenchymal lung resection for suspicious opacities without preoperative tissue diagnosis is rare (2.1%) while surgery for benign lesions represented 15.3% and has a satisfactory safety profile with very low postoperative morbi-mortality., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

The development of acute right heart failure (ARHF) in the context of chronic pulmonary hypertension (PH) is associated with poor short-term outcomes. The morphological and functional phenotyping of the right ventricle is of particular importance in the context of hemodynamic compromise in patients with ARHF. Here, we describe a method to induce ARHF in a previously described large animal model of chronic PH, and to phenotype, dynamically, right ventricular function using the gold standard method (i.e., pressure-volume PV loops) and with a non-invasive clinically available method (i.e., echocardiography). Chronic PH is first induced in pigs by left pulmonary artery ligation and right lower lobe embolism with biological glue once a week for 5 weeks. After 16 weeks, ARHF is induced by successive volume loading using saline followed by iterative pulmonary embolism until the ratio of the systolic pulmonary pressure over systemic pressure reaches 0.9 or until the systolic systemic pressure decreases below 90 mmHg. Hemodynamics are restored with dobutamine infusion (from 2.5 µg/kg/min to 7.5 µg/kg/min). PV-loops and echocardiography are performed during each condition. Each condition requires around 40 minutes for induction, hemodynamic stabilization and data acquisition. Out of 9 animals, 2 died immediately after pulmonary embolism and 7 completed the protocol, which illustrates the learning curve of the model. The model induced a 3-fold increase in mean pulmonary artery pressure. The PV-loop analysis showed that ventriculo-arterial coupling was preserved after volume loading, decreased after acute pulmonary embolism and was restored with dobutamine. Echocardiographic acquisitions allowed to quantify right ventricular parameters of morphology and function with good quality. We identified right ventricular ischemic lesions in the model. The model can be used to compare different treatments or to validate non-invasive parameters of right ventricular morphology and function in the context of ARHF.

Pulmonary hypertension is associated with stiffening of pulmonary arteries which increases right ventricular pulsatile loading. High pulmonary artery wedge pressure (PAWP) in postcapillary pulmonary hypertension (Pc-PH) further decreases pulmonary arterial compliance (PAC) at a given pulmonary vascular resistance (PVR) compared with precapillary pulmonary hypertension, thus responsible for a higher total arterial load. In all other vascular beds, arterial compliance is considered as mainly determined by the distending pressure, due to non-linear stress-strain behaviour of arteries. We tested the applicability, advantages and drawbacks of two comparison methods of PAC depending on the level of mean pulmonary arterial pressure (mPAP; isobaric PAC) or PVR. Right heart catheterisation data including PAC (stroke volume/pulse pressure) were obtained in 112 Pc-PH (of whom 61 had combined postcapillary and precapillary pulmonary hypertension) and 719 idiopathic pulmonary arterial hypertension (iPAH). PAC could be compared over the same mPAP range (25-66 mmHg) in 792 (95.3%) out of 831 patients and over the same PVR range (3-10.7 WU) in only 520 (62.6%) out of 831 patients. The main assumption underlying comparisons at a given PVR was not verified as the PVR×PAC product (RC-time) was not constant but on the contrary more variable than mPAP. In the 788/831 (94.8%) patients studied over the same PAC range (0.62-6.5 mL·mmHg -1 ), PVR and thus total arterial load tended to be higher in iPAH. Our study favours comparing PAC at fixed mPAP level (isobaric PAC) rather than at fixed PVR. A reappraisal of the effects of PAWP on the pulsatile and total arterial load put on the right heart is needed, and this point deserves further studies., Competing Interests: Conflict of interest: D. Chemla has nothing to disclose. Conflict of interest: E. Berthelot has nothing to disclose. Conflict of interest: J. Weatherald reports grants, personal fees and nonfinancial support from Janssen Inc. and Actelion, personal fees and nonfinancial support from Bayer, and personal fees from Novartis, outside the submitted work. Conflict of interest: E.M.T. Lau has nothing to disclose. Conflict of interest: L. Savale reports grants, personal fees and nonfinancial support from Actelion, personal fees and nonfinancial support from MSD and Bayer, and grants, personal fees and nonfinancial support from GSK, outside the submitted work. Conflict of interest: A. Beurnier has nothing to disclose. Conflict of interest: D. Montani reports grants and personal fees from Actelion and Bayer, personal fees from GSK, personal fees from Pfizer, grants, personal fees and nonfinancial support from MSD, personal fees from Chiesi and Boehringer, and nonfinancial support from Acceleron, outside the submitted work. Conflict of interest: O. Sitbon reports grants, personal fees and nonfinancial support from Actelion Pharmaceuticals, personal fees and nonfinancial support from Bayer, grants from GlaxoSmithKline, grants, personal fees and nonfinancial support from Merck, and personal fees from Ferrer, Gossamer Bio and Acceleron, outside the submitted work. Conflict of interest: P. Attal has nothing to disclose. Conflict of interest: D. Boulate has nothing to disclose. Conflict of interest: P. Assayag has nothing to disclose. Conflict of interest: M. Humbert reports personal fees from Acceleron, grants and personal fees from Actelion and Bayer, and personal fees from GSK, Merck, Novartis, AstraZeneca and Sanofi, outside the submitted work. Conflict of interest: P. Hervé has nothing to disclose., (Copyright ©The authors 2021.)

The relative pulmonary to systemic pressure ratio (mean pulmonary arterial pressure/mean arterial pressure) has been proven to be valuable in cardiac surgery. Little is known on the prognostic value of baseline and trajectory of mean pulmonary arterial pressure/mean arterial pressure in pulmonary arterial hypertension. Patients with confirmed idiopathic, familial, drug and toxins, or connective tissue disease-related pulmonary arterial hypertension and at least one complete right heart catheterization were included and prospectively followed-up for 5.9 ± 4.03 years. Correlates of the primary end point (i.e. death or lung transplant need) during follow-up were determined using Cox regression modeling. Results showed that among the 308 patients included, 187 had at least one follow-up catheterization (median time between catheterizations: 2.16 (1.16-3.19) years). In the total cohort (mean age 47.3 ± 14.9 years, 82.8% of female and 58.1% in New York Heart Association class 3 or 4), mean pulmonary arterial pressure/mean arterial pressure (1.38 (1.07-1.77)) was associated with outcome ( p  = 0.01). Mean pulmonary arterial pressure/mean arterial pressure was incremental to a basic model (including right atrial pressure, systolic blood pressure, New York Heart Association class 3 or 4, and connective tissue disease) for outcome prediction, while mean pulmonary arterial pressure was not. In the 187 patients with a follow-up catheterization, both delta mean pulmonary arterial pressure and delta mean pulmonary arterial pressure/mean arterial pressure were associated with outcome (1.32 (1.11-1.58) and 1.31 (1.1-1.57) respectively, p  < 0.01). Mean pulmonary arterial pressure and mean pulmonary arterial pressure/mean arterial pressure were both incremental to the basic model, while worsening in mean pulmonary arterial pressure or mean pulmonary arterial pressure/mean arterial pressure did not reach significance. In conclusion, mean pulmonary arterial pressure/mean arterial pressure at baseline prognosticates long-term outcome with a significant, albeit modest, incremental value to basic variables., (© The Author(s) 2020.)

Aims: Risk stratification in heart failure (HF) relies on several established clinical risk scores, however, myocardial deformation, right heart metrics, and exercise performance have not usually been considered. This study sought to assess the incremental value of advanced echocardiographic and cardiopulmonary exercise testing (CPX) parameters to validated risk scores in HF., Methods and Results: The Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) and Metabolic Exercise Test Data Combined with Cardiac and Kidney Indexes (MECKI) scores were applied to 208 ambulatory patients with dilated cardiomyopathy (DCM) who completed echocardiography in conjunction with CPX as part of the Stanford Exercise Testing registry. Patients were followed for the composite end point of death, heart transplant, left ventricular device implantation, and hospitalization for acute HF. Mean age, left ventricular ejection fraction (LVEF), and left ventricular global longitudinal strain (LVGLS) were 47 ± 13 years, 33 ± 13%, and -10.6 ± 4.4%, respectively, while right ventricular free-wall longitudinal strain was -18.8 ± 5.5%. Partial correlation mapping identified strong correlations between LVEF, LVGLS, and LV systolic strain rate, with a moderate correlation between these metrics and peak VO2. Over a median follow up of 5.3 years, the composite end point occurred in 60 patients. Cox proportional hazards identified MAGGIC score [hazard ratio (HR) (2.04 [1.39-3.01], P < 0.01], peak VO2 HR (0.52 [0.28-0.97], P = 0.04), and right atrial volume indexed (RAVI) HR (1.31 [1.07-1.61], P < 0.01) as independent correlates of outcome. RAVI remained an independent correlate when combined with the MECKI score (2.21 [1.59-3.07]), P < 0.01, RAVI, 1.33 [1.06-1.67], P = 0.01)., Conclusion: Our study demonstrates that RAVI is complementary to well-validated HF risk scores and highlights the importance of exercise performance in DCM.

Right ventricular (RV) response to exercise or pharmacological stress is not well documented in pulmonary hypertension (PH). We investigated the relationship between RV reserve and ventricular-arterial coupling. Surgical ligation of the left pulmonary artery was performed in 13 Large White piglets (PH group), thereafter weekly embolisations of the right lower lobe were performed for 5 weeks. A control group of six piglets underwent sham procedures. Right heart catheterisation and echocardiography were performed at week 6. Pressure-volume loops were recorded before and after dobutamine infusion. Induction of experimental PH resulted in a higher mean ± sd pulmonary artery pressure (34 ± 9 versus 14 ± 2 mmHg; p<0.01) and in a lower ventricular-arterial coupling efficiency (0.66 ± 0.18 versus 1.24 ± 0.17; p<0.01) compared with controls at 6 weeks. Dobutamine-induced relative changes in RV stroke volume index (SVI) and end-systolic elastance were lower in the PH group (mean ± SD 47 ± 5% versus 20 ± 5%, p<0.01, and 81 ± 37% versus 32 ± 14%, p<0.01, respectively). Change in SVI was strongly associated with resting ventricular-arterial coupling (R(2)=0.74; p<0.01). RV reserve was associated with ventricular-arterial coupling in a porcine model of chronic pressure overload., (Copyright ©ERS 2015.)