[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.

[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.

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.

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.

Prognostic factors of acute heart failure in patients with pulmonary arterial hypertension.

Acute right ventricular failure in the setting of pulmonary arterial hypertension (PAH) often requires hospitalisation in intensive care units (ICU) to manage the subsequent low cardiac output and its consequences. There are very few data on these acute events. We recorded demographic, clinical and biological data and therapy in consecutive patients suffering from acute right heart failure requiring catecholamine treatment in the ICU of the French referral centre for pulmonary hypertension. These variables were analysed according to the survival status in ICU. 46 patients were included, the mean age was 50.3 yrs. ICU mortality was 41%. We found no difference in terms of demographics, clinical data, last haemodynamic measurements at admission. Systemic arterial pressure was significantly lower in the subgroup of patients whose clinical course was fatal. Plasma brain natriuretic peptide (BNP), C-reactive protein (CRP), serum sodium and creatinine at admission correlated with survival. Demonstration of an infection during the ICU stay was associated with a worse prognosis. These preliminary results underline the importance of some simple clinical and biological parameters in the prognostic evaluation of acute heart failure in the setting of PAH. Whether these parameters can guide therapy needs to be further investigated.

Cautious epoprostenol therapy is a safe bridge to lung transplantation in pulmonary veno-occlusive disease.

Pulmonary veno-occlusive disease (PVOD) carries a poor prognosis and lung transplantation is the only curative treatment. In PVOD, epoprostenol therapy is controversial, as this condition may be refractory to specific therapy with an increased risk of pulmonary oedema. We retrospectively reviewed clinical, functional and haemodynamic data of 12 patients with PVOD (10 with histological confirmation) treated with continuous intravenous epoprostenol and priority listed for lung transplantation after January 1, 2003. All PVOD patients had severe clinical, functional and haemodynamic impairment at presentation. Epoprostenol was used at low dose ranges with slow dose increases and high dose diuretics. Only one patient developed mild reversible pulmonary oedema. After 3-4 months, improvements were seen in the New York Heart Association functional class (class IV to III in seven patients), cardiac index (1.99+/-0.68 to 2.94+/-0.89 L x min(-1) x m(-2)) and indexed pulmonary vascular resistance (28.4+/-8.4 to 17+/-5.2 Wood units x m(-2); all p<0.01). A nonsignificant improvement in the 6-min walk distance was also observed (+41 m, p = 0.11). Two patients died, one patient was alive on the transplantation waiting list on December 1, 2008 and nine patients were transplanted. Cautious use of continuous intravenous epoprostenol improved clinical and haemodynamic parameters in PVOD patients at 3-4 months without commonly causing pulmonary oedema, and may be a useful bridge to urgent lung transplantation.

Pulmonary veno-occlusive disease.

Pulmonary veno-occlusive disease (PVOD) is currently classified as a subgroup of pulmonary arterial hypertension (PAH) and accounts for 5-10% of cases initially considered to be idiopathic PAH. PVOD has been described as idiopathic or complicating other conditions, including connective tissue diseases, HIV infection, bone marrow transplantation, sarcoidosis and pulmonary Langerhans cell granulomatosis. PVOD shares broadly similar clinical presentation, genetic background and haemodynamic characteristics with PAH. Compared to PAH, PVOD is characterised by a higher male/female ratio, higher tobacco exposure, lower arterial oxygen tension at rest, lower diffusing capacity of the lung for carbon monoxide, and lower oxygen saturation nadir during the 6-min walk test. High-resolution computed tomography (HRCT) of the chest can be suggestive of PVOD in the presence of centrilobular ground-glass opacities, septal lines and lymph node enlargement. Similarly, occult alveolar haemorrhage is associated with PVOD. A noninvasive diagnostic approach using HRCT of the chest, arterial blood gases, pulmonary function tests and bronchoalveolar lavage could be helpful for the detection of PVOD patients and in avoiding high-risk surgical lung biopsy for histological confirmation. PVOD is characterised by a poor prognosis and the possibility of developing severe pulmonary oedema with specific PAH therapy. Lung transplantation is the treatment of choice. Cautious use of specific PAH therapy can, however, be helpful in some patients.

Long-term effects of bosentan in patients with HIV-associated pulmonary arterial hypertension.

Bosentan has proven 4-month efficacy in patients with HIV-associated pulmonary arterial hypertension (PAH-HIV). Herein, the long-term outcome of unselected PAH-HIV patients treated with first-line bosentan is described. Data for 59 consecutive World Health Organization (WHO) functional class II-IV PAH-HIV patients treated with first-line bosentan between May 2002 and July 2007 were analysed. HIV status, 6-min walk distance and haemodynamics were assessed at baseline, after 4 months and every 6-12 months thereafter. After 4 months, 6-min walk distance increased from 358+/-98 to 435+/-89 m and pulmonary vascular resistance decreased from 737+/-328 to 476+/-302 dyn x s x cm(-5). At the final evaluation (29+/-15 months), 6-min walk distance remained stable and pulmonary vascular resistance decreased further to 444+/-356 dyn x s x cm(-5). Haemodynamics normalised in 10 patients. At their last evaluation, these 10 patients were in WHO functional class I, with a 6-min walk distance of 532+/-52 m. Overall survival estimates were 93, 86 and 66% at 1, 2 and 3 yrs, respectively. Bosentan was safe when combined with highly active antiretroviral therapy, with no negative impact on HIV infection control. The present data confirm the long-term benefits of bosentan therapy in HIV-associated pulmonary arterial hypertension patients with improvements in symptoms, 6-min walk distance and haemodynamics, and with favourable overall survival.

Implementing the ESC/ERS pulmonary hypertension guidelines: real-life cases from a national referral centre.

Pulmonary hypertension (PH) comprises a heterogeneous group of disorders characterised by increased pulmonary vascular resistance that results in progressive right ventricular failure. In order to translate current evidence into routine clinical practice, the European Society of Cardiology (ESC) and the European Respiratory Society (ERS) have recently jointly proposed evidence-based guidelines for the optimal management of different PH patient groups. This article describes a series of clinical cases of PH due to various aetiologies that were referred to a large national PH expert referral centre. In each case, the assessment and therapeutic approach undertaken is described in the context of the new ECS/ERS guidelines. The routine diagnostic work-up of suspected idiopathic pulmonary arterial hypertension (PAH) and recommended treatments for patients with functional class II, III and IV disease is emphasised. Familial screening and management of heritable PAH is discussed. Appropriate investigation and therapeutic strategies for patients with chronic thromboembolic disease and PH that is associated with congenital heart disease, pulmonary veno-occlusive disease and systemic sclerosis are also highlighted.

[Diagnosis and care of postembolic pulmonary hypertension: the role of the pneumologist]. / Diagnostic et prise en charge de l'hypertension pulmonaire postembolique : le rôle du pneumologue.

The prognosis of postembolic pulmonary hypertension, a rare and serious disease, has been transformed with the curative intervention of pulmonary endarteriectomy. The screening is based on two key non invasive examinations, the cardiac ultrasound and ventilation-perfusion scintigraphy. The confirmation of the diagnosis and the determination of the best therapeutic options then relies on the expertise of the national reference centre, based on the haemodynamics and the morphological data provided by pulmonary angiography and spiral computerised tomography. Although the technique of endarteriectomy is fully validated, a drug approach is in the assessment process, both in the inoperable forms or when confronted with persistent postsurgical pulmonary hypertension.

Pulmonary arterial hypertension masquerading as severe refractory asthma.

Once the diagnosis of pulmonary arterial hypertension is established, wheezing and chronic cough are rarely described during the course of the disease. The present study reports on two nonsmoking patients with severe pulmonary arterial hypertension, confirmed by right-heart catheterisation, who developed chronic cough, wheezing and irreversible obstructive lung disease masquerading as adult-onset severe refractory asthma. In both cases, extrinsic proximal airway obstruction by dilated pulmonary arteries was demonstrated by fibreoptic bronchoscopy and computed tomography of the chest. The present observations add dilatation of the central pulmonary arteries with compression of the mainstem bronchi to the list of masqueraders of asthma in patients with pulmonary arterial hypertension.

Pulmonary arterial hypertension associated with fenfluramine exposure: report of 109 cases.

The aim of the present study was to describe a large cohort of fenfluramine-associated pulmonary arterial hypertension (fen-PAH) and its possible prognostic markers. The records of all patients with a diagnosis of fen-PAH evaluated at the present authors' centre from 1986-2004 were retrospectively studied. Baseline clinical and haemodynamic data were collected, as well as survival times. The median duration of fenfluramine exposure was 6 months, with a median of 4.5 yrs between exposure and onset of symptoms. Nine (22.5%) out of 40 patients evaluated resulted positive for the presence of germline bone morphogenetic protein receptor (BMPR) type 2 mutations. In these patients, the duration of exposure to fenfluramine was significantly lower than in patients without mutation. The median survival was 6.4 yrs, without significant difference between fen-PAH and a control group of idiopathic and familial pulmonary arterial hypertension patients referred to the present authors' centre during the same time frame and treated identically. Duration of fenfluramine exposure showed no relation to survival, while cardiac index was the only independent predictor of multivariate analysis. Fenfluramine-associated pulmonary arterial hypertension shares clinical, functional, haemodynamic and genetic features with idiopathic pulmonary arterial hypertension, as well as overall survival rates. Therefore, the present authors conclude that fenfluramine exposure characterises a potent trigger for pulmonary arterial hypertension without influencing its clinical course.

[Postembolic pulmonary hypertension]. / Hypertension pulmonaire postembolique.

INTRODUCTION: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare disease characterized by the persistence of thromboemboli obstructing the pulmonary arteries as an organized tissue. The consequence is an increase in pulmonary vascular resistance resulting in pulmonary hypertension (PH) and progressive right heart failure. BACKGROUND: It is difficult to recognize the postembolic nature of PH because there is no known history of thromboembolic disease in more than 50% of cases. Diagnosis is based on the presence of mismatched segmental defects in the ventilation-perfusion scanning. When CTEPH is suspected, pulmonary angiography and high-resolution CT scan are required to establish the diagnosis and to assess the operability. Pulmonary angiography is always performed in conjunction with a diagnostic right heart catheterization, which is required to confirm the diagnosis of PH and to determine the degree of hemodynamic impairement. If there is a good correlation between the pulmonary vascular resistance and the anatomical obstruction, pulmonary endarterectomy (PEA) must be proposed. Otherwise, vasodilator and antiproliferative treatments and lung transplantation represent interesting alternatives. VIEWPOINT AND CONCLUSION: PEA remains the treatment of choice for eligible patients. Nevertheless, there is a need to conduct randomized trials to assess the efficacy of novel medical therapies in some situations: (1) in inoperable CTEPH due to distal lesions, (2) before PEA (therapeutic bridge) in patients who are considered "high risk" due to extremely poor hemodynamics, (3) in patients with persistent pulmonary hypertension after surgery.