Definitions and Diagnosis of Pulmonary Hypertension Hoeper, Marius M., MD; Bogaard, Harm Jan, MD; Condliffe, Robin, MD ...
Journal of the American College of Cardiology,
12/2013, Letnik:
62, Številka:
25
Journal Article, Conference Proceeding
Recenzirano
Odprti dostop
Pulmonary hypertension (PH) is defined by a mean pulmonary artery pressure ≥25 mm Hg at rest, measured during right heart catheterization. There is still insufficient evidence to add an exercise ...criterion to this definition. The term pulmonary arterial hypertension (PAH) describes a subpopulation of patients with PH characterized hemodynamically by the presence of pre-capillary PH including an end-expiratory pulmonary artery wedge pressure (PAWP) ≤15 mm Hg and a pulmonary vascular resistance >3 Wood units. Right heart catheterization remains essential for a diagnosis of PH or PAH. This procedure requires further standardization, including uniformity of the pressure transducer zero level at the midthoracic line, which is at the level of the left atrium. One of the most common problems in the diagnostic workup of patients with PH is the distinction between PAH and PH due to left heart failure with preserved ejection fraction (HFpEF). A normal PAWP does not rule out the presence of HFpEF. Volume or exercise challenge during right heart catheterization may be useful to unmask the presence of left heart disease, but both tools require further evaluation before their use in general practice can be recommended. Early diagnosis of PAH remains difficult, and screening programs in asymptomatic patients are feasible only in high-risk populations, particularly in patients with systemic sclerosis, for whom recent data suggest that a combination of clinical assessment and pulmonary function testing including diffusion capacity for carbon monoxide, biomarkers, and echocardiography has a higher predictive value than echocardiography alone.
The 4th World Symposium on Pulmonary Hypertension was the first international meeting to focus not only on pulmonary arterial hypertension (PAH) but also on the so-called non-PAH forms of pulmonary ...hypertension (PH). The term “non-PAH PH” summarizes those forms of PH that are found in groups 2 to 5 of the current classification of PH, that is, those forms associated with left heart disease, chronic lung disease, recurrent venous thromboembolism, and other diseases. Many of these forms of PH are much more common than PAH, but all of them have been less well studied, especially in terms of medical therapy. The working group on non-PAH PH focused mainly on 4 conditions: chronic obstructive lung disease, interstitial lung disease, chronic thromboembolic PH, and left heart disease. The medical literature regarding the role of PH in these diseases was reviewed, and recommendations regarding diagnosis and treatment of PH in these conditions are provided. Given the lack of robust clinical trials addressing PH in any of these conditions, it is important to conduct further studies to establish the role of medical therapy in non-PAH PH.
Imatinib is an oral inhibitor of several protein kinases implicated in the pathophysiology of pulmonary hypertension. Treatment with imatinib resulted in improved hemodynamics and exercise capacity ...in a controlled trial (Imatinib QTI571 in Pulmonary Arterial Hypertension, a Randomized Efficacy Study IMPRES), among pulmonary arterial hypertension (PAH) patients inadequately responsive to 2 to 3 PAH-specific therapies.
The long-term (up to 204 weeks) safety and efficacy of imatinib in this open-label extension study were reviewed until early study termination on April 16, 2014. Of 202 IMPRES-enrolled patients, 66 imatinib and 78 placebo recipients entered the extension.
Overall, 93.8% (135 of 144) of patients discontinued the extension study; administrative issues (i.e., sponsor termination; 32.6%) and adverse events (31.3%) were the primary reasons for discontinuation. Nine patients completed the extension study before it was terminated. Serious and unexpected adverse events were frequent. These included 6 subdural hematomas in the extension study and 17 deaths during or within 30 days of study end. Although the patients who tolerated imatinib and remained in the extension for a longer duration did experience an improvement in functional class and walk distance, most discontinued the drug and the study.
Severe adverse events, significant side effects, and a high discontinuation rate limit the utility of imatinib in the treatment of PAH. These risks outweigh any possible improvements in hemodynamics and walk distance seen in those patients able to remain on drug. The off-label use of this compound in PAH is discouraged.
Diagnosis and Assessment of Pulmonary Arterial Hypertension Badesch, David B., MD; Champion, Hunter C., MD, PhD; Gomez Sanchez, Miguel Angel, MD ...
Journal of the American College of Cardiology,
06/2009, Letnik:
54, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The diagnosis and assessment of pulmonary arterial hypertension is a rapidly evolving area, with changes occurring in the definition of the disease, screening and diagnostic techniques, and staging ...and follow-up assessment. The definition of pulmonary hypertension has been simplified, and is now based on currently available evidence. There has been substantial progress in advancing the imaging techniques and biomarkers used to screen patients for the disease and to follow up their response to therapy. The importance of accurate assessment of right ventricular function in following up the clinical course and response to therapy is more fully appreciated. As new therapies are developed for pulmonary arterial hypertension, screening, prompt diagnosis, and accurate assessment of disease severity become increasingly important. A clear definition of pulmonary hypertension and the development of a rational approach to diagnostic assessment and follow-up using both conventional and new tools will be essential to deriving maximal benefit from our expanding therapeutic armamentarium.
Since April 2010, extracorporeal membrane oxygenation (ECMO) has replaced cardiopulmonary bypass for intraoperative support during lung transplantation at our institution. The aim of this study was ...to present our 5-year experience with this technique.
Records of patients who underwent transplantation between April 2010 and January 2015 were retrospectively reviewed. Patients who underwent transplantation without ECMO formed Group A. Patients in whom the indication for ECMO support was set a priori before the beginning of the operation formed Group B. The remaining patients in whom the indication for ECMO support was set during transplantation formed Group C.
Among 595 patients, 425 (71%) patients (Group A) did not require intraoperative ECMO; the remaining 170 (29%) patients did. Among these patients, 95 (56%) patients formed Group B, and the remaining 75 (44%) patients comprised Group C. Pulmonary fibrosis and pre-operative dilated or hypertrophied right ventricle emerged as risk factors for the indication of non-a priori intraoperative ECMO. Patients in Groups B and C showed a higher pre-operative risk profile and higher prevalence of post-operative complications than patients in Group A. Overall survival at 1 year was 93%, 83%, and 82% and at 4 years was 73%, 68%, and 69% in Groups A, B, and C (p = 0.11). The intraoperative use of ECMO did not emerge as a risk factor for in-hospital mortality or mortality after hospital discharge.
Intraoperative ECMO filled the gap between pre-operative and post-operative ECMO in lung transplantation. Although complications and in-hospital mortality were higher in patients who received ECMO, survival was similar among patients who underwent transplantation with or without ECMO.
Extracorporeal membrane oxygenation (ECMO) is a well-established treatment for severe cardiopulmonary failure. Patients undergoing ECMO support through femoral vessels are prone to vascular ...complications. The aim of this study was to evaluate such complications to outline basic technical principles for their prevention.
From January 2005 to December 2009, 174 patients underwent ECMO support through cannulation of the femoral vessels. The primary outcome was any vascular complication. Secondary outcomes were 30-day mortality and 1-year survival. A logistic regression analysis including ECMO duration, peripheral arterial disease, ECMO access (percutaneous versus open), and diabetes mellitus identified predictors for vascular complications.
The venoarterial mode was used in 143 patients (82%), and venovenous in 31 patients (18%). Of the 17 (10%) observed vascular complications, 15 (88%) occurred in patients with venoarterial access, whereas 2 (12%) occurred after venovenous access (p=0.50) Two patients who had extremity ischemia required limb amputation. Thirty-day mortality and 1-year survival rates were 63% and 26%, respectively. Peripheral arterial disease was the only strong predictor of vascular complications (odds ratio, 6.95; 95% confidence interval, 1.89 to 25.59; p=0.003). Vascular complications were not associated with early or late mortality.
The incidence of vascular complications in venovenous cannulation was low, whereas in arterial cannulation, it is still considerable. Peripheral arterial disease remains a risk factor, and early involvement of vascular surgeons for open vascular exposure or alternative vascular access sites can be recommended. Vascular complications after ECMO support are not associated with higher mortality rates.
Objectives Our goal was to investigate the effect of treatment with the oral dual endothelin receptor antagonist bosentan on the hemodynamics and exercise capacity of patients with chronic ...thromboembolic pulmonary hypertension (CTEPH). Background CTEPH is characterized by vascular obstruction and remodeling, leading to increased pulmonary vascular resistance (PVR). Although pulmonary endarterectomy (PEA) is potentially curative, medical therapy is needed in patients with inoperable disease or persistent/recurrent pulmonary hypertension after PEA. Methods The BENEFiT (Bosentan Effects in iNopErable Forms of chronIc Thromboembolic pulmonary hypertension) study was a double-blind, randomized, placebo-controlled study in CTEPH including patients with either inoperable CTEPH or persistent/recurrent pulmonary hypertension after PEA (>6 months after PEA). Independent coprimary end points were change in PVR as a percentage of baseline and change from baseline in 6-min walk distance after 16 weeks of treatment with bosentan or placebo. Secondary end points included change from baseline in World Health Organization functional class and other hemodynamic parameters. Results One hundred fifty-seven patients were enrolled and randomized: 80 to placebo, 77 to bosentan. A statistically significant treatment effect (TE) of bosentan over placebo on PVR was demonstrated: −24.1% of baseline (95% confidence interval CI: −31.5% to −16.0%; p < 0.0001). Total pulmonary resistance (TE: −193 dyn·s·cm−5 ; 95% CI: −283 to −104 dyn·s·cm−5 ; p < 0.0001) and cardiac index (TE: 0.3 l·min−1 ·m−2 ; 95% CI: 0.14 to 0.46 l·min−1 ·m−2 ; p = 0.0007) improved. Mean TE on 6-min walk distance was +2.2 m (95% CI: −22.5 to 26.8 m; p = 0.5449). Bosentan treatment was well tolerated. Conclusions This study demonstrated a positive TE of bosentan on hemodynamics in this patient population. No improvement was observed in exercise capacity. Further trials are needed to define the role of medical therapy in patients with CTEPH (Bosentan Effects in Inoperable Forms of Chronic Thromboembolic Pulmonary Hypertension; NCT00313222 ).
Uncontrolled and controlled clinical trials with different compounds and procedures are reviewed to define the risk-benefit profiles for therapeutic options in pulmonary arterial hypertension (PAH). ...A grading system for the level of evidence of treatments based on the controlled clinical trials performed with each compound is used to propose an evidence-based treatment algorithm. The algorithm includes drugs approved by regulatory agencies for the treatment of PAH and/or drugs available for other indications. The different treatments have been evaluated mainly in idiopathic PAH, heritable PAH, and in PAH associated with the scleroderma spectrum of diseases or with anorexigen use. Extrapolation of these recommendations to other PAH subgroups should be done with caution. Oral anticoagulation is proposed for most patients; diuretic treatment and supplemental oxygen are indicated in cases of fluid retention and hypoxemia, respectively. High doses of calcium-channel blockers are indicated only in the minority of patients who respond to acute vasoreactivity testing. Nonresponders to acute vasoreactivity testing or responders who remain in World Health Organization (WHO) functional class III, should be considered candidates for treatment with either an oral phosphodiesterase-5 inhibitor or an oral endothelin-receptor antagonist. Continuous intravenous administration of epoprostenol remains the treatment of choice in WHO functional class IV patients. Combination therapy is recommended for patients treated with PAH monotherapy who remain in WHO functional class III. Atrial septostomy and lung transplantation are indicated for refractory patients or where medical treatment is unavailable.
Objectives Patients requiring extracorporeal cardiorespiratory support during lung transplantation can be treated with conventional cardiopulmonary bypass (CPB) or venoarterial extracorporeal ...membrane oxygenation (ECMO). In a retrospective analysis, we compared the postoperative course and outcomes of patients treated using these approaches. Methods Between August 2008 and September 2011, 92 consecutive patients underwent lung transplantation with extracorporeal support (CPB group, n = 46; and, since February 2010, ECMO group, n = 46) at our institution. We evaluated survival, secondary organ failure, bleeding complications, and the need for blood and platelet transfusions in these 2 patient populations. Results Intraoperatively, the CPB group required more packed red blood cell transfusions (12 ± 11 vs 7 ± 9 U; P = .01) and platelet concentrates (2.5 ± 1.6 vs 1.5 ± 1 U; P < .01) than the ECMO group. In-hospital mortality (39% vs 13%; P = .004), the need for hemodialysis (48% vs 13%; P < .01), and new postoperative ECMO support (26% vs 4%; P < .01) were greater in the CPB group than in the ECMO group, respectively. After propensity score analysis, multivariate analysis identified retransplantation (odds ratio, 7; 95% confidence interval, 1-43; P = .034) and transplantation with CPB support (odds ratio, 4.9; 95% confidence interval, 1.2-20; P = .026) as independent risk factors for in-hospital mortality. The survival rate at 3, 9, and 12 months was 70%, 59%, and 56% in the CPB group and 87%, 81%, and 81% in the ECMO group ( P = .004). Conclusions Intraoperative ECMO allows for better periprocedural management and reduced postoperative complications and confers a survival benefit compared with CPB, mainly because of lower in-hospital mortality. It is now the standard of care in our lung transplantation program.
Abstract Objectives This study sought to investigate the prognostic importance of a low diffusion capacity of the lung for carbon monoxide (DLCO) in patients with a catheter-based diagnosis of ...pulmonary hypertension due to heart failure with preserved ejection fraction (PH-HFpEF). Background In patients with pulmonary arterial hypertension, a low DLCO is associated with poor outcome. It is unclear whether the same is true in patients with PH-HFpEF. Methods This study retrospectively analyzed clinical characteristics, smoking history, lung function measurements, chest computed tomography, hemodynamics, and survival in 108 patients with PH-HFpEF. The presence of post-capillary PH was determined by right heart catheterization. Patients with moderate or severe lung function abnormalities were excluded. Results On the basis of previous studies and receiver-operating characteristic curve analysis, the study cohort was divided into patients with a DLCO <45% of the predicted value (DLCO<45% , low DLCO; n = 52) and patients with a DLCO ≥45% of the predicted value (DLCO≥45% ; n = 56). DLCO<45% was associated with male sex (odds ratio OR: 2.71; 95% confidence interval CI: 1.05 to 6.99; p = 0.039) and smoking history (OR: 5.01; 95% CI: 1.91 to 13.10; p < 0.001). There were no correlations between DLCO and other lung function parameters and hemodynamics. Compared with patients with DLCO≥45% , patients with DLCO<45% had a significantly worse outcome (survival rate at 3 years 36.5% vs. 87.8%, p < 0.001 by log-rank analysis). Cox proportional hazard analysis identified DLCO<45% as an independent predictor of death (hazard ratio: 6.6; 95% CI: 2.6 to 16.9; p < 0.001). Conclusions In patients with PH-HFpEF, a low DLCO is strongly associated with mortality.
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