Therapeutic Strategies in Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a serious and life-threatening condition for which the prognosis remains poor. Treatment options include endothelial receptor antagonists, phosphodiesterase (PDE5) inhibitors and prostanoids. Despite all demonstrating good short-term efficacy, none of the currently available drug therapies are curative. Treatment with prostanoids is complex and requires careful monitoring and management through a specialist centre. Furthermore, clinical efficacy is dependent on adequate up-titration of the drug. Treatment should be individualised and modified according to clinical response, with the addition of other therapies if required. The importance of monitoring and modifying therapeutic regimes is discussed. There appears to be reluctance among patients and physicians to employ prostanoid therapy, though an aggressive first-line therapy may be appropriate in advanced cases

Efficacy of virtual patients in medical education: A meta-analysis of randomized studies

A meta-analysis was performed to assess the Effect Size (ES) from randomized studies comparing the effect of educational interventions in which Virtual patients (VPs) were used either as an alternative method or additive to usual curriculum versus interventions based on more traditional methods. Meta-analysis was designed, conducted and reported according to QUORUM statement on quality of reporting of meta-analyses. Twelve randomized controlled studies were retrieved, assessing a total of 25 different outcomes. Under a random-effect model, meta-analysis showed a clear positive pooled overall effect for VPs compared to other educational methods (Odds Ratio: 239; 95% C.I. 1.48 divided by 3.84). A positive effect has been documented both when VPs have been used as an additive resource (O.R.: 2.55; C.I. 1.36 divided by 4.79) and when they have been compared as an alternative to a more traditional method (O.R.: 2.19; 1.06 divided by 4.52). When grouped for type of outcome, the pooled ES for studies addressing communication skills and ethical reasoning was lower than for clinical reasoning outcome. There is evidence that VPs are effective but further research is needed to clarify which is their best possible integration in curricula and their value and cost/benefit ratio with respect to other active learning methods. (c) 2012 Elsevier Ltd. All rights reserved

Systemic sclerosis patients with and without pulmonary arterial hypertension: a nailfold capillaroscopy study

Objective. Pulmonary arterial hypertension (PAH) is a complication of SSc due to increased vascular resistance, and abnormal vascularity is a well-known feature of the disease as shown by nailfold video-capillaroscopy (NVC). This study investigated for specific NVC changes in SSc patients with and without PAH to assess any useful difference. Methods. Twenty-four SSc patients, 12 with PAH and 12 without, entered the study. Evidence of PAH was defined as increased systolic pulmonary artery pressure (PAP) (epsilon 35 mmHg), indirectly assessed by echocardiography and confirmed by right heart catheterization (mPAP > 25 mmHg). NVC was performed, and a semi-quantitative rating scale, a rating system for avascular areas and a specific NVC pattern evaluation, namely early, active and late, were used. Results. An NVC score > 1 was more frequently found in patients with PAH than those without, 11 cases (92%) vs 5 cases (42%) (P = 0.03); an avascular areas grade > 1 was present in 10 (83%) and 2 (17%) cases, respectively (P = 0.003); and a more severe NC pattern (active/late) was described in 11 (92%) and 5 (42%) patients, respectively (P = 0.03). When we compared the mPAP with NVC parameters, we found significant correlations between mPAP values and the NVC score (P < 0.005) and with the avascular areas score (P < 0.001). Conclusion. Our results underline the relevance of early microvascular assessment in patients at risk of developing a severe complication such as PAH that can amplify the systemic microvascular impairment in SSc. More severe NVC abnormalities should lead to strict cardiopulmonary surveillance and a complete NVC study is indicated

Right ventricular remodeling in idiopathic pulmonary arterial hypertension. adaptive versus maladaptive morphology

BACKGROUND: Although increased pulmonary pressure is caused by changes in the pulmonary vasculature, prognosis in idiopathic pulmonary arterial hypertension (IPAH) is strongly associated with right ventricular (RV) function. The aim of this study was to describe the best RV adaptive remodeling pattern to increased afterload in IPAH. METHODS: In 60 consecutive patients with IPAH, RV morphologic and functional features were evaluated by echocardiography and cardiac magnetic resonance imaging. To address the question of the best RV adaptation pattern, we divided the study population into two groups by the median value of RV mass/volume ratio (0.46) because this parameter allows the distinction between RV eccentric (≤0.46) and concentric hypertrophy (&gt;0.46). The two groups were compared for RV remodeling and systolic function parameters, World Health Organization class, pulmonary hemodynamics, and 6-minute walk test. RESULTS: Despite similar pulmonary vascular resistance, mean pulmonary pressure, and compliance, patients with eccentric hypertrophy had advanced World Health Organization class and worse 6-minute walk test, hemodynamics, RV remodeling, and systolic function parameters compared with patients with concentric hypertrophy. The group with concentric hypertrophy had higher RV to pulmonary arterial coupling compared with the group with eccentric hypertrophy (1.24 ± 0.26 vs 0.83 ± 0.33, p = 0.0001), indicating higher RV efficiency. A significant correlation was found between pulmonary vascular resistance and RV to pulmonary arterial coupling (r = -0.55, r(2) = 0.31, p = 0.0001), with patients with RV mass/volume ratio &gt; 0.46 at the higher part of the scatterplot, confirming more adequate RV function. CONCLUSIONS: Concentric hypertrophy might represent a more favorable RV adaptive remodeling pattern to increased afterload in IPAH because it is associated with more suitable systolic function and mechanical efficiency

Right ventricular dyssynchrony in idiopathic pulmonary arterial hypertension: determinants and impact on pump function

Background: Right ventricular (RV) dyssynchrony has been described in pulmonary arterial hypertension (PAH), but no evidence is available on its morphologic determinants and its effect on systolic function. The aim of this study was to evaluate the morphologic determinants of RV dyssynchrony by echocardiographic and cardiac magnetic resonance imaging and its effect on systolic function. Methods: In 60 consecutive idiopathic PAH (IPAH) patients with narrow QRS, RV dyssynchrony was evaluated by 2D speckle-tracking echocardiography, calculating the standard deviation of the times to peak systolic strain for the four mid-basal RV segments (RV-SD4). Patients were grouped by the median value of RV-SD4 (19 milliseconds) and compared for RV remodeling and systolic function parameters, WHO class, pulmonary hemodynamics and 6-minute walk test (6MWT). Results: Despite similar pulmonary vascular resistance and mean pulmonary arterial pressure, patients with RV-SD4 at &gt;19 milliseconds had advanced WHO class and worse 6MWT, RV hemodynamics, RV remodeling and systolic function parameters compared with patients at ≤19 milliseconds. The morphologic determinants of RV dyssynchrony resulted RV end-diastolic area, LV diastolic eccentricity index and RV mass volume ratio (r = 0.69, r(2) = 0.47, p &lt; 0.0001). Finally, we found a significant inverse correlation between RV mid-basal segments post-systolic shortening time and cardiac index (r = -0.64, r(2) = 0.41, p = 0.001), accounting for the significant correlation between RV-SD4 and cardiac index (r = 0.57, r(2) = 0.32, p = 0.003). Conclusions: In IPAH with narrow QRS, RV dyssynchrony is associated with RV dilation and eccentric hypertrophy pattern, suggesting a role of segmental wall stress heterogeneity as the major determinant of mechanical delay. Post-systolic shortening, as inefficient contraction, contributes to pump dysfunction

Right intraventricular dyssynchrony in idiopathic, heritable, and anorexigen-induced pulmonary arterial hypertension. Cllinical impact and reversibility

Objectives: The aim of this study was to determine the prevalence of right intraventricular dyssynchrony, its determinants and prognostic impact in idiopathic, heritable, and anorexigen-induced pulmonary arterial hypertension. Background: Right ventricular dyssynchrony has been described in pulmonary arterial hypertension, but no evidence is available on its prognostic impact and evolution after therapy. Methods: In 83 consecutive therapy-naïve patients, right ventricular dyssynchrony was evaluated by 2-dimensional speckle-tracking echocardiography calculating the standard deviation of the times to peak-systolic strain for the 4 mid-basal right ventricular segments (RV-SD4). After baseline (World Health Organization [WHO] class, pulmonary hemodynamics, 6-min walk test [6 MWT]), a second assessment was performed after 12 months or when clinical worsening occurred. Results: Patients with right ventricular dyssynchrony (RV-SD4 &gt;18 ms) had advanced WHO class, worse 6 MWT, right ventricular remodeling, and hemodynamic profile compared with patients ≤ 18 ms. Determinants of dyssynchrony included pulmonary vascular resistance, QRS duration, and right ventricular end-diastolic area (r(2) = 0.38; p &lt; 0.000001). At 12 months, 32.5% of patients presented clinical worsening (actuarial rates: 19% at 6 months, 31% at 1 year). Multivariable models for clinical worsening prediction showed that the addition of RV-SD4 to clinical and hemodynamic variables (WHO IV, 6 MWT, and cardiac index) significantly increased the prognostic power of the model (0.74 vs. 0.81; p = 0.005, 95% confidence interval [CI]: 0.02 to 0.11). Receiver operating characteristic analysis identified RV-SD4 ≥ 23 ms as the best cutoff value for clinical worsening prediction (95% negative predictive value). At 12 months, normalization of dyssynchrony was achieved in patients with a large reduction of pulmonary vascular resistance (-42 ± 4%). Conclusions: Right ventricular dyssynchrony is frequent in pulmonary arterial hypertension, is an independent predictor of clinical worsening, and might regress during effective treatments

Pulmonary Arterial Dilatation in Pulmonary Hypertension: Prevalence and Prognostic Relevance

Objectives: Pulmonary arterial dilatation is considered a consequence of chronic pulmonary hypertension (PH), but despite its relatively common detection, its prevalence and prognostic impact have not yet been systematically investigated. The aim of the study was to investigate these factors in a relatively large cohort of severe PH patients. Methods: One hundred and forty-one consecutive patients diagnosed with PH were monitored for a mean of 957 days. Data including functional class, exercise capacity, invasive hemodynamics and pulmonary artery (PA) echo/CT scan measurement were performed and outcomes prospectively collected. Results: PA dilatation is a common feature, present in the 76.6% of cases in this cohort of severe PH patients. Survival at 1, 2 and 3 years was 83, 71 and 58%, respectively. On univariate analysis, the baseline variables associated with a poor outcome were related to pulmonary arterial hypertension associated with connective tissue disease (CDT-PAH), New York Heart Association (NYHA) functional class, 6-min walk and right atrial pressure. On multivariate analysis only CDTPAH and NYHA functional class remained independently associated with poor survival. Conclusions: PA dilatation is commonly detected in severe PH patients and is not associated with an increased risk of death. Copyright (C) 2012 S. Karger AG, Base

Indicatori ambientali nello studio EpiAir2: I dati di qualit\ue0 dell'aria per la sorveglianza epidemiologica

OBIETTIVO: costruzione di indicatori ambientali di inquinamento aerodiffuso per finalit\ue0 di sorveglianza epidemiologica in 25 citt\ue0 italiane per il progetto EpiAir2 (2006-2010) e presentazione dei dati di dieci anni di sorveglianza in 10 citt\ue0 italiane (2001-2010). DISEGNO: sono stati raccolti dati di particolato (nelle frazioni PM10 e PM2.5 ), biossido di azoto (NO2 ) e ozono (O3 ), considerati fattori di rischio per la salute. I datimeteorologici considerati come confondenti nell\u2019analisi dell\u2019effetto degli inquinanti sono stati: temperatura, umidit\ue0 relativa (e la variabile derivata \u201ctemperatura apparente\u201d) e pressione barometrica. I criteri per la selezione delle stazioni dimonitoraggio e imetodi di calcolo per la costruzione di indicatori ambientali a partire dalle serie giornaliere disponibili sono stati scelti in continuit\ue0 con la precedente edizione di EpiAir. Per tutte le citt\ue0, \ue8 stata verificata l\u2019omogeneit\ue0 dei dati selezionati nel rappresentare l\u2019esposizione delle popolazioni. SETTING E PARTECIPANTI: il progetto EpiAir2 coinvolge per gli anni 2006-2010 le citt\ue0 diMilano,Mestre-Venezia,Torino, Bologna, Firenze, Pisa, Roma,Taranto,Cagliari e Palermo, gi\ue0 presenti nello studio EpiAir. A questo elenco vanno aggiunte le citt\ue0 di Treviso, Trieste, Padova, Rovigo, Piacenza, Parma, Ferrara, Reggio Emilia, Modena, Genova, Rimini, Ancona, Bari, Napoli e Brindisi. RISULTATI: nel periodo considerato \ue8 stato osservato un decremento delle concentrazioni di particolato nella maggior parte delle citt\ue0 in analisi, mentre non si pu\uf2 giungere a conclusioni cos\uec nette per NO2 e ozono. L\u2019analisi dell\u2019andamento temporale degli indicatori ha evidenziato valori medi annuali di PM10 superiori ai 40 \u3bcg/m3 in alcune citt\ue0 della Pianura Padana, e valori medi annuali di NO2 costantemente superiori ai 40 \u3bcg/m3 nelle citt\ue0 di Trieste, Milano, Padova, Torino, Modena, Bologna, Roma e Napoli. CONCLUSIONE: l\u2019ampliamento del progetto EpiAir, con l\u2019inclusione di ulteriori 13 citt\ue0, ha permesso di evidenziare peculiarit\ue0 legate alle differenti aree geografiche in studio e numerose situazioni di criticit\ue0 con superamenti dei valori di concentrazione limite fissati dalla legislazione corrente. I risultati dello studio EpiAir2 confermano la necessit\ue0 di un sistema di sorveglianza dell\u2019inquinamento aerodiffuso nei centri urbani e industriali al fine di ottenere stime affidabili dell\u2019esposizione della popolazione residente e di monitorarne l\u2019andamento nel tempo