[Updated indications and contraindications in 2022 for lung transplantation in France]. / Transplantation pulmonaire en France : actualisation des indications et contre-indications en 2022.

Lung transplantation (LTx) is the last-resort treatment for end-stage respiratory insufficiency, whatever its origin, and represents a steadily expanding field of endeavor. Major developments have been impelled over the years by painstaking efforts at LTx centers to improve donor and recipient selection, and multifaceted attempts have been made to meet the challenges raised by surgical management, perioperative care, and long-term medical complications. The number of procedures has increased, leading to improved post-LTx prognosis. One consequence of these multiple developments has been a pruning away of contraindications over time, which has, in some ways, complicated the patient selection process. With these considerations in mind, the Francophone Pulmonology Society (Société de Pneumology de Langue Française [SPLF]) has set up a task force to produce up-to-date working guidelines designed to assist pulmonologists in managing end-stage respiratory insufficiency, determining which patients may be eligible for LTx, and appropriately timing LTx-center referral. The task force has examined the most recent literature and evaluated the risk factors that continue to limit patient survival after LTx. Ideally, the objectives of LTx are to prolong life while improving quality of life. The guidelines developed by the task force apply to a limited resource and are consistent with the ethical principles described below.

[Hepatopulmonary syndrome: Prevalence, pathophysiology and clinical implications]. / Syndrome hépatopulmonaire : prévalence, physiopathologie et implications cliniques.

Hepatopulmonary syndrome (HPS) is a pulmonary vascular disease induced by portal hypertension that is characterized by dilation of the pulmonary capillaries and right-to-left shunting, leading to gas exchange abnormalities. While dysregulation of several endothelial cell (EC)-derived angiocrine factors and the development of HPS have been associated, the field is currently lacking in mechanistic understanding on how they contribute to disease initiation, perpetuation, and worsening. Although substantial progress has been made in the description of clinical characteristics and outcomes, no specific targeting therapy has been shown to have a long-term effect on the evolution of HPS; only liver transplantation can lead full or partial reversibility of the syndrome. This article aims to provide a comprehensive review of the clinical and epidemiological definitions of HPS and to describe its experimental models as well as recent advances in understanding the pathophysiology of the disease, with specific focus on BMP-9 and its signaling pathway.

[Management of right ventricular failure in pulmonary vascular diseases]. / Prise en charge de l'insuffisance ventriculaire droite aiguë compliquant les maladies vasculaires pulmonaires.

Right ventricular failure (RVF) is a common cause of admission to the intensive care unit and its presence is a major prognostic factor in acute pulmonary embolism (PE) and chronic pulmonary hypertension (PH). RVF results from an incapacity of the RV to adapt to an increase in afterload so it can become critical in acute PE and chronic PH. The presence of RVF in cases of acute PE with haemodynamic instability is an indication for thrombolytic therapy. RVF represents the most common cause of death in chronic PH. Factors triggering RV failure in PH, such as infection, PE, arrhythmias, or unplanned withdrawal of pulmonary arterial hypertension (PAH)-targeted therapy, have to be considered and treated if identified. However, RVF may also represent progression to end-stage disease. The management of RVF in patients with PH requires expertise and consists of optimization of fluid balance (with diuretics), cardiac output (with inotropic support such as dobutamine), perfusion pressure (with norepinephrine), and reduction of RV afterload with PAH-targeted therapies. Extracorporeal life support, lung transplantation or heart-lung transplantation should be considered in cases of refractory RVF in eligible patients.

Klippel-Trenaunay syndrome as a rare cause of chronic thromboemboembolic pulmonary hypertension.

Klippel-Trenaunay syndrome (KTS) is a congenital disorder characterized by cutaneous capillary malformations, soft tissue and bone hypertrophy, and multiple capillary, venous or lymphatic malformations. KTS is associated with recurrent thromboembolic events. We reported herein five cases of chronic thromboembolic pulmonary hypertension (CTEPH) associated with KTS (age minimum-maximum 26-50 years old, 3 males/2 females). Hemodynamics showed severe pulmonary hypertension (PH) with pulmonary vascular resistance ranging from 5.6 to 18.3 Wood units (WU), associated with marked clinical impairment (NYHA functional class III or IV in 4 patients). Computed tomography (CT) of the chest and pulmonary angiography confirmed proximal CTEPH accessible to surgical intervention in one patient and distal forms of CTEPH in 4 patients. Evolution after pulmonary endarterectomy showed hemodynamic normalization, while the patients with distal CTEPH had severe outcomes with 2 early deaths after PH diagnosis (44 and 35 months respectively). One patient with distal CTEPH was still alive 16 years after diagnosis on specific PH therapy and one was transplanted after 15 years because of right heart failure (death after 12 months). Histological analysis of the lung explants showed typical chronic thromboembolic material specific for CTEPH. In conclusion, KTS may be complicated by severe CTEPH requiring careful anticoagulation and multidisciplinary follow-up in expert centers to screen for disease potentially accessible to endarterectomy. In the modern management era of CTEPH, balloon pulmonary angioplasty will certainly be an interesting option in patients with inoperable disease.

Identifying chronic thromboembolic pulmonary hypertension through the French national hospital discharge database.

Chronic thromboembolic pulmonary hypertension (CTEPH), a rare pulmonary vascular disease, is often misdiagnosed due to nonspecific symptoms. The objective of the study was to develop, refine and validate a case ascertainment algorithm to identify CTEPH patients within the French exhaustive hospital discharge database (PMSI), and to use it to estimate the annual number of hospitalized patients with CTEPH in France in 2015, as a proxy for disease prevalence. As ICD-10 coding specifically for CTEPH was not available at the time of the study, a case ascertainment algorithm was developed in close collaboration with an expert committee, using a two-step process (refinement and validation), based on matched data from PMSI and hospital medical records from 2 centres. The best-performing algorithm (specificity 95%, sensitivity 70%) consisted of ≥1 pulmonary hypertension (PH) diagnosis during 2015 and any of the following criteria over 2009-2015: (i) CTEPH interventional procedure, (ii) admission for PH and pulmonary embolism (PE), (iii) PE followed by hospitalization in competence centre then in reference centre, (iv) history of PE and right heart catheterization. Patients with conditions suggestive of pulmonary arterial hypertension were excluded. A total of 3,138 patients hospitalized for CTEPH was estimated for 2015 (47 cases/million, range 43 to 50 cases/million). Assuming that patients are hospitalized at least once a year, the present study provides an estimate of the minimal prevalence of CTEPH and confirms the heavy burden of this disease.

[Liver diseases and pulmonary vascular disorders]. / Hépatopathies et maladies vasculaires pulmonaires.

About 70% patients waiting for liver transplantation have a dyspnea. Two pulmonary vascular disorders can be associated with portal hypertension or chronic liver diseases: portopulmonary hypertension (PoPH) related to pulmonary small arteries remodeling and obstruction and hepatopulmonary syndrome (HPS) characterized by pulmonary capillaries dilatations and proliferations. PoPH is defined by the combination of pulmonary arterial hypertension (PAH) (mean pulmonary artery pressure [PAP]≥25mmHg, with normal pulmonary artery wedge pressure≤15mmHg and pulmonary vascular resistance [PVR]>3 Wood units [WU]) and portal hypertension. HPS is a triad of intrapulmonary vascular dilatations, hypoxemia (increased alveolar-arterial oxygen gradient) and liver disease or isolated portal hypertension. The pathophysiology of both syndromes is complex and poorly understood. PoPH and HPS have a negative impact on functional and vital prognosis in patients with portal hypertension. Liver transplantation is the established treatment standard in HPS. PoPH treatment is improved over the years with the use of specific PAH treatment despite the lack of randomized assay in this indication. Liver transplantation could be considered in PoPH leading to stabilization, improvement or recovery in selected patients (mean PAP<35mmHg without severe right ventricular dysfunction and PVR<4 WU).

[Evaluation of cardiac MRI in the follow up assessment of patients with pulmonary arterial hypertension]. / Évaluation de l'IRM cardiaque dans le suivi des patients ayant une hypertension artérielle pulmonaire (EVITA). IRM cardiaque dans le suivi de l'hypertension artérielle pulmonaire.

Haemodynamic follow up in pulmonary arterial hypertension (PAH) is currently based on right heart catheterisation (RHC). The primary objective of the EVITA study is to compare the use of cardiac magnetic resonance imaging (cMRI) with RHC in the identification of an unfavourable hemodynamic status. The secondary objectives are to determine the role of cMRI in the follow up process. Patients will undergo at diagnosis and at follow up visits both RHC and cMRI. Patients will be followed and treated according to the current guidelines. The primary endpoint will be an unfavourable haemodynamic status defined by cardiac index<2.5L/min/m2 or a right atrial pressure≥8mm Hg measured with RHC compared with a cardiac index<2.5L/min/m2 or right ventricle ejection fraction<35% or an absolute decrease of 10% from the previous measurement with cMRI. Exact values of sensitivity, specificity and 95% confidence intervals will be computed. A population of 180 subjects will have a power of 90% with an α risk of 5%. Univariate and multivariate Cox analysis will allow answering to the secondary objectives. We expect to demonstrate that cMRI could be partly used instead of RHC in the follow up of patients with PAH.

[Pulmonary veno-occlusive disease]. / La maladie veino-occlusive pulmonaire.

Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary hypertension (PH) characterized by preferential remodelling of pulmonary venules and angioproliferation. PVOD term includes idiopathic, heritable (biallelic mutations of EIF2AK4 gene), drugs and toxins induced (alkylating agents, organic solvents) and connectivite-associated forms (especially systemic-sclerosis associated form). PVOD and pulmonary arterial hypertension (PAH) share a similar clinical presentation. Lung biopsy is contraindicated in PVOD due to high risk of life-threatening bleeding. A noninvasive diagnostic approach, including oxygen parameters, low diffusing capacity for carbon monoxide and characteristic signs on high-resolution computed tomography of the chest, is used to support a diagnosis of PVOD. PVOD prognosis is worse than other forms of PAH. There is no evidence-based medical therapy for PVOD and life-threatening pulmonary edema may occur following PAH targeted therapy in PVOD. Lung transplantation remains the preferred definitive therapy for eligible patients.

[HIV-related pulmonary arterial hypertension]. / L'hypertension artérielle pulmonaire associée au VIH.

Pulmonary arterial hypertension (PAH) is a rare but potentially fatal complication of human immunodeficiency virus (HIV). It may occur in HIV-1 or 2 infection, irrespective of the route of transmission or the degree of immunosuppression. The improved survival of patients infected with HIV in the era of highly active antiretroviral therapy (HAART) justifies systematic screening for PAH according to an algorithm in patients with unexplained dyspnea. In all cases, right heart catheterization must be performed to establish the definitive diagnosis of pulmonary hypertension. The prevalence of PAH is about 0.5% in patients with HIV infection. A beneficial effect of HAART on the course of HIV-related PAH has not been clearly established. In contrast, PAH-specific therapies such as epoprostenol and bosentan have been demonstrated to be efficacious for short- and long-term outcomes in this context. Notably, some patients pulmonary hemodynamics and functional class normalized or near normalized with these treatments. Other PAH-specific therapies remain to be evaluated. The advent of HAART associated with the development of PAH-specific therapies has improved the prognosis of patients HIV-related PAH, with a survival rate of about 70% at 3 years.

Computed tomography findings of pulmonary venoocclusive disease in scleroderma patients presenting with precapillary pulmonary hypertension.

OBJECTIVE: Pulmonary venoocclusive disease (PVOD) is an uncommon form of pulmonary hypertension (PH) characterized by obstruction of small pulmonary veins. Pulmonary venous involvement has been reported in pathologic assessment of patients with systemic sclerosis (SSc) presenting with precapillary PH. High-resolution computed tomography (HRCT) of the chest is a noninvasive diagnostic tool used to screen for PVOD. No HRCT data are available on SSc patients with precapillary PH. We undertook this study to evaluate the frequency and effect on prognosis of HRCT signs of PVOD in SSc patients with precapillary PH. METHODS: We reviewed chest HRCT data from 26 SSc patients with precapillary PH and 28 SSc patients without pulmonary arterial hypertension (PAH) or interstitial lung disease (ILD). RESULTS: The radiographic triad of HRCT signs of PVOD (lymph node enlargement [57.7% versus 3.6%], centrilobular ground-glass opacities [46.2% versus 10.7%], and septal lines [88.5% versus 7.1%]) was significantly more frequent in SSc patients with precapillary PH than in SSc patients without PAH or ILD (all P < 0.005). Indeed, 61.5% of SSc patients with precapillary PH had ≥ 2 of these signs. Cardiomegaly (P < 0.0001), pulmonary artery enlargement (P < 0.0001), and pericardial effusion (P < 0.0005) were also significantly more frequent in SSc patients with precapillary PH. Pulmonary venous involvement was histologically confirmed in 2 patients with radiographic signs of PVOD. The presence of ≥ 2 radiographic signs of PVOD was associated with the occurrence of pulmonary edema after initiation of PAH-specific therapy (in 8 of 16 patients) and with more rapid progression from diagnosis of PH to death. CONCLUSION: HRCT signs of PVOD are frequently observed in SSc patients with precapillary PH, correlated with histologic assessment, and were associated with a high risk of pulmonary edema.

The association between resting and mild-to-moderate exercise pulmonary artery pressure.

The mean pulmonary artery pressure (P(pa)) achieved on mild-to-moderate exercise is age related and its haemodynamic correlates remain to be documented in patients free of pulmonary hypertension (PH). Our retrospective study involved patients free of PH investigated in our centre for possible pulmonary vascular disease between January 1, 2007 and October 31, 2009 who underwent right heart catheterisation at rest and during supine exercise up to 60 W. The 38 out of 99 patients aged <50 yrs were included and a P(pa) of 30 mmHg was considered the upper limit of normal on exercise. The 24 subjects who developed P(pa)>30 mmHg on exercise had higher resting P(pa) (19±3 versus 15±4 mmHg) and indexed pulmonary vascular resistance (PVRi; 3.4±1.5 versus 2.2±1.1 WU·m(2); p<0.05) than the remaining 14 subjects. Resting P(pa) >15 mmHg predicted exercise P(pa) >30 mmHg with 88% sensitivity and 57% specificity. The eight patients with resting P(pa) 22-24 mmHg all had exercise P(pa) >30 mmHg. In subjects aged <50 yrs investigated for possible pulmonary vascular disease and free of PH, patients with mild-to-moderate exercise P(pa) >30 mmHg had higher resting PVRi and higher resting P(pa), although there was no resting P(pa) threshold value that could predict normal response on mild-to-moderate exercise. The clinical relevance of such findings deserves further long-term follow-up studies.

Optimal management of severe pulmonary arterial hypertension.

Over the past decade, awareness among the medical profession of pulmonary arterial hypertension (PAH) being a treatable disease has increased. Despite this, approximately one-fifth of newly diagnosed patients are classified as being in the most severely compromised functional class (i.e. New York Health Association/World Health Organization functional class (NYHA/WHO FC) IV). The prognosis for patients in NYHA/WHO FC IV is poor, with 3-yr survival being around 40%, even with treatment. Poor prognosis coupled with severe functional impairment means it is vital that these patients receive optimal treatment. There are also subgroups of patients, who, although classified as NYHA/WHO FC III, may actually be severely haemodynamically compromised and at risk of rapid deterioration. Such subgroups include patients with PAH associated with systemic sclerosis or certain heritable mutations. These patients should be considered as being at the more severe end of the disease spectrum. In this article we will discuss the optimal management of patients with severe PAH. This includes newly emerging evidence from small-scale, open-label studies that use upfront combination therapy with intravenous epoprostenol plus oral PAH-specific drugs. We also review treatment strategies that may offer clinical benefits to patients with more severe PAH.

Current management approaches to portopulmonary hypertension.

Portopulmonary hypertension (PoPH) is a rare but life-threatening complication of portal hypertension that is characterised by proliferative changes in the pulmonary microvasculature indistinguishable from other forms of pulmonary arterial hypertension (PAH). Although PoPH is most commonly observed in the setting of cirrhosis, patients with non-cirrhotic portal hypertension are also at risk of developing the disorder. A definitive diagnosis requires invasive haemodynamic confirmation by right heart catheterisation and screening for PoPH should be routinely performed in all patients being considered for liver transplantation. Although severe PoPH is considered a contraindication to liver transplantation, there is now compelling data supporting the use of PAH-specific therapies with the aim of improving pulmonary haemodynamics to allow transplantation to be successfully performed. This review explores possible relevant aetiological factors and summarises current diagnostic and therapeutic approaches for PoPH patients.

Treat-to-target strategies in pulmonary arterial hypertension: the importance of using multiple goals.

Major advances have occurred in the treatment of pulmonary arterial hypertension (PAH) over the past decade. The advent of PAH-specific pharmacological treatments has offered hope to patients with a debilitating, progressive disease and a poor prognosis. Combined drug treatment offers improved benefits over monotherapy, and current treatment guidelines for PAH recommend a sequential add-on approach to combination therapy for patients in New York Heart Association (NYHA)/World Health Organization functional class (WHO FC) II-IV. Goal-oriented therapy determines the timing of treatment escalation by inadequate response to known prognostic indicators. Close monitoring of patients aids the early identification of inadequate response, so that treatment can be escalated promptly and before the patient's condition deteriorates further. Existing treatment goals are based on baseline values of prognostic indicators, but it is vital to identify risk factors that are both relevant during treatment and that can be assessed during follow-up appointments. Data from different PAH aetiologies indicate that NYHA/WHO FC is the most appropriate prognostic marker, with 6-min walk distance and several haemodynamic parameters representing alternatives. Future refinement of goal-oriented therapy could include the use of multiple prognostic markers, while additional, large clinical trials will answer questions concerning choice and combination of treatment goals.

Survival in incident and prevalent cohorts of patients with pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a progressive, fatal disease. We studied 674 consecutive adult patients who were prospectively enrolled in the French PAH registry (121 incident and 553 prevalent cases). Two survival analyses were performed. First, the cohort of 674 patients was followed for 3 yrs after study entry and survival rates described. Then, we focused on the subset with incident idiopathic, familial and anorexigen-associated PAH (n = 56) combined with prevalent patients who were diagnosed <3 yrs prior to study entry (n = 134). In the cohort of 674 patients, 1-, 2-, and 3-yr survival rates were 87% (95% CI 84-90), 76% (95% CI 73-80), and 67% (95% CI 63-71), respectively. In prevalent idiopathic, familial and anorexigen-associated PAH, 1-, 2-, and 3-yr survival rates were higher than in incident patients (p = 0.037). In the combined cohort of patients with idiopathic, familial and anorexigen-associated PAH, multivariable analysis showed that survival could be estimated by means of a novel risk-prediction equation using patient sex, 6-min walk distance, and cardiac output at diagnosis. This study highlights survivor bias in prevalent cohorts of PAH patients. Survival of idiopathic, familial and anorexigen-associated PAH can be characterised by means of a novel risk-prediction equation using patients' characteristics at diagnosis.

[Guidelines for the diagnosis and treatment of pulmonary hypertension]. / Diagnostic et prise en charge de l'hypertension pulmonaire en 2009. Commentaires sur les nouvelles recommandations de l'European Society of Cardiology (ESC) et de l'European Respiratory Society (ERS).

INTRODUCTION: A joint Task Force of the ESC and of the ERS has developed guidelines on the diagnosis and treatment of pulmonary hypertension (PH) to provide updated information on the management of patients with this condition. STATE OF THE ART: The term pulmonary hypertension (PH) describes a group of devastating and life-limiting diseases, defined by mean pulmonary artery pressure >25 mmHg at rest. The diagnosis of PH requires a series of investigations intended to confirm the diagnosis, clarify the clinical group and the specific aetiology and an algorithm for this is proposed. Several drugs are currently approved to try to correct endothelial dysfunction. They lead to a significant improvement in the prognosis of patients who are in NYHA functional class II, III or IV. The evaluation of the severity of PH has a pivotal role in the choice of initial treatment and evaluation of the response to therapy in individual patients. PERSPECTIVE: These guidelines should be widely disseminated and implemented in order to improve the management of patients with PH. CONCLUSION: These guidelines summarise recent advances in the understanding and management of PH.

Noncardiothoracic nonobstetric surgery in mild-to-moderate pulmonary hypertension.

The anaesthetic management and follow-up of well-characterised patients with pulmonary arterial hypertension presenting for noncardiothoracic nonobstetric surgery has rarely been described. The details of consecutive patients and perioperative complications during the period January 2000 to December 2007 were reviewed. Repeat procedures in duplicate patients were excluded. Longer term outcomes included New York Heart Association (NYHA) functional class, 6-min walking distance and invasive haemodynamics. A total of 28 patients were identified as having undergone major (57%) or minor surgery under general (50%) and regional anaesthesia. At the time of surgery, 75% of patients were in NYHA functional class I-II. Perioperative deaths occurred in 7%. Perioperative complications, all related to pulmonary hypertension, occurred in 29% of all patients and in 17% of those with no deaths during scheduled procedures. Most (n = 11, 92%) of the complications occurred in the first 48 h following surgery. In emergencies (n = 4), perioperative complication and death rates were higher (100 and 50%, respectively; p<0.005). Risk factors for complications were greater for emergency surgery (p<0.001), major surgery (p = 0.008) and a long operative time (193 versus 112 min; p = 0.003). No significant clinical or haemodynamic deterioration was seen in survivors at 3-6 or 12 months of post-operative follow-up. Despite optimal management in this mostly nonsevere pulmonary hypertension population, perioperative complications were common, although survivors remained stable. Emergency procedures, major surgery and long operations were associated with increased risk.