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
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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.
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.
Background Right ventricular failure does not explain all cases of death in patients with chronic pulmonary hypertension. Searching for alternative explanations, we evaluated the prognostic ...significance of main pulmonary artery (PA) dilatation in patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH). Methods A retrospective outcome analysis was made of 264 patients (aged 46 ± 17 years; women, 69%; PAH, 82%) who underwent both CT scan measurement of the PA and right-sided heart catheterization (mean PA pressure, 57.6 ± 16.5 mm Hg) at initial evaluation. Results The diameter of the PA ranged from 28 to 120 mm (mean, 39 ± 8.6 mm; median, 38 mm) and was largest in patients with unrepaired congenital defects (42.6 ± 7.6 mm). Pulmonary pulse pressure ( P = .04), lower age ( P = .03), and duration of symptoms ( P < .001) were independently but weakly related to PA diameter. During follow-up (median, 38 months), 99 patients (37%) died. Of these 99 deaths, 73 (74%) were due to heart failure or comorbidities, and 26 (26%) were unexpected deaths (UE-Ds). PA diameter (hazard ratio HR, 1.06 per 1 mm; 95% CI, 1.03-1.08), heart rate (HR, 1.30 per 10 beats/min; 95% CI, 1.01-1.66), and systolic pulmonary arterial pressure (HR, 1.02 per 1 mm Hg; 95% CI, 1.01-1.04) were the only independent predictors of UE-D and differed from the usual predictors found in the study group for all-cause mortality. PA diameter ≥ 48 mm had 95% specificity and 39% sensitivity and carried 7.5 times higher risk of UE-D (95% CI, 3.4-16.5; P < .0001) during follow-up. Conclusions PA dilatation emerges as an independent risk factor for death unexplained by right ventricular failure or comorbidities in patients with PAH and CTEPH. The possible mechanisms include, but are not limited to, PA compression of the left main coronary artery, PA rupture, or dissection with cardiac tamponade.
Experimental studies in animals suggest that arterial hypertension may be a specific risk factor predisposing to anthracycline cardiotoxicity. The aim was determination of the effect of pre-existing ...arterial hypertension on the development of early left ventricular systolic dysfunction (LVSD) directly after rituximab, cyclophosphamide, doxorubicin, vincristin, prednisone (R-CHOP) chemotherapy in patients with lymphomas.The study included 208 patients with non-Hodgkin's lymphoma receiving conventional doxorubicin. LVSD was defined as a decrease of left ventricular ejection fraction below 50% and at least by 10 percentage points from baseline value. Patients with pre-existing hypertension more frequently developed new LVSD (19.7% vs. 6.6%; P = .004), pitting edema of the ankles (23.9% vs. 9.5%; P = .005), and nycturia (21.1% vs. 7.3%; P = .004) compared with patients without hypertension. As a consequence, the hypertension subgroup suffered from more delays of subsequent chemotherapy cycles (26.8% vs. 14.6%; P = .03), more reductions of doxorubicin doses (18.3% vs. 8.8%; P = .05), and premature discontinuations of chemotherapy (16.9% vs. 7.3%; P = .03). On logistic regression analyses, hypertension was one of the most important risk factors for developing new LVSD after (R)-CHOP chemotherapy.Arterial hypertension confers a significant risk of early LVSD in lymphoma patients treated with (R)-CHOP chemotherapy, interfering with its recommended schedule of administration.
Hemoptysis is a rarely reported complication of idiopathic pulmonary arterial hypertension (IPAH). We present the case of a 27-year-old woman with IPAH, who suffered from recurrent hemoptysis and who ...was treated with sitaxsentan and treprostinil and remained stable in World Health Organization functional class II. During several episodes of active hemoptysis, the patient underwent bronchial artery embolization (BAE), always with good immediate results. She developed severe respiratory insufficiency and died of electromechanical dissociation 2 days after another episode, despite effective bleeding control. Recurrent hemoptysis in patients with IPAH emerges as a potential indication for urgent placement on the lung transplant list, independent from the classic prognostic factors of functional class and indices of right-sided ventricular function. Repeated BAE should not be considered as a definitive treatment in patients with pulmonary arterial hypertension with recurrent bleeding, although it may help in bridging patients to lung transplant.
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 ).
Background For patients diagnosed with acute pulmonary embolism (PE), the prognostic significance of concomitant right heart thrombi (RHT) lacks clarity. Methods We performed a meta-analysis of ...studies that enrolled patients with acute PE to assess the prognostic value of echocardiography-detectable RHT for the primary outcome of short-term all-cause mortality and the secondary outcome of short-term PE-related mortality. Unrestricted searches were conducted of PubMed and Embase from 1980 through January 31, 2016, and used the terms “right heart thrombi,” “pulmonary embolism,” and “prognos.*” A random effects model was used to pool study results; Begg rank correlation method was used to evaluate for publication bias; and I2 testing was used to assess for heterogeneity. Results Six of 79 potentially relevant studies met the inclusion criteria (15,220 patients). Overall, 99 of 593 patients with echocardiography-detectable RHT died (16.7% 95% CI, 13.8-19.9) compared with 639 of 14,627 without RHT (4.4% 95% CI, 4.0-4.7). RHT had a significant association with short-term all-cause mortality in all patients (OR, 3.0 95% CI, 2.2 to 4.1; I2 = 20%) and with PE-related death (three cohorts, 12,955 patients; OR: 4.8 95% CI, 2.0-11.3; I2 = 76%). Results were consistent for the prospective (two cohorts, 514 patients; OR, 4.8 95% CI, 1.7-13.6; I2 = 56%) and the retrospective (four cohorts, 14,706 patients; OR, 2.8 95% CI, 2.1 to 3.8; I2 = 0%) studies. Conclusions In patients diagnosed with acute PE, concomitant RHT were significantly associated with an increased risk of death within 30 days of PE diagnosis. Trial Registry PROSPERO registry; No.: CRD42016033960; URL: https://www.crd.york.ac.uk/prospero/
Background Pulmonary arterial hypertension (PAH) leads to reduced health-related quality of life (HRQoL). The objectives of this analysis were to evaluate the effect of macitentan on HRQoL in ...patients with PAH in the Study with an Endothelin Receptor Antagonist in Pulmonary Arterial Hypertension to Improve Clinical Outcome (SERAPHIN) study. The association between baseline HRQoL and long-term outcomes was also investigated. Methods Patients were randomized to placebo, macitentan 3 mg, or macitentan 10 mg once daily. Patients aged 14 years or older completed the 36-Item Short Form Survey (SF-36) at baseline, at month 6 and month 12, and at the end of treatment (EOT). The absolute change from baseline to month 6 in SF-36 scores was calculated. The time to a clinically meaningful deterioration in the SF-36 physical component summary and mental component summary (PCS and MCS) scores and associations between baseline PCS/MCS scores and time to morbidity/mortality events were also assessed. Results At month 6, macitentan 10 mg significantly improved seven of eight SF-36 domains and the PCS and MCS scores vs placebo. Macitentan 10 mg significantly reduced the risk of a three-point or greater deterioration in PCS (hazard ratio HR, 0.60; 95% CI, 0.47-0.76; P < .0001) and MCS scores (HR, 0.76; 95% CI, 0.61-0.95; P = .0173) until EOT vs placebo. Patients with a baseline PCS score greater than the median baseline value had a significantly reduced risk of morbidity/mortality compared with patients with a PCS score less than the median; a similar result was observed for the MCS score. Conclusions Macitentan significantly improved HRQoL in patients with PAH compared with placebo and significantly reduced the risk of a clinically meaningful HRQoL deterioration. An association between better baseline HRQoL and improved long-term outcomes was shown. Trial Registry ClinicalTrials.gov; No.: NCT00660179 ; URL: clinicaltrials.gov.
Right Heart Adaptation to Pulmonary Arterial Hypertension Vonk-Noordegraaf, Anton, MD; Haddad, François, MD; Chin, Kelly M., MD ...
Journal of the American College of Cardiology,
12/2013, Letnik:
62, Številka:
25
Journal Article
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Survival in patients with pulmonary arterial hypertension (PAH) is closely related to right ventricular (RV) function. Although pulmonary load is an important determinant of RV systolic function in ...PAH, there remains a significant variability in RV adaptation to pulmonary hypertension. In this report, the authors discuss the emerging concepts of right heart pathobiology in PAH. More specifically, the discussion focuses on the following questions. 1) How is right heart failure syndrome best defined? 2) What are the underlying molecular mechanisms of the failing right ventricle in PAH? 3) How are RV contractility and function and their prognostic implications best assessed? 4) What is the role of targeted RV therapy? Throughout the report, the authors highlight differences between right and left heart failure and outline key areas of future investigation.
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