Showing papers on "Pulmonary artery published in 2013"
TL;DR: 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 has a higher predictive value than echocardiography alone.
1,372 citations
TL;DR: The current state of art regarding to epidemiologic aspects of PH, diagnostic approaches and the current classification of PH are discussed as well as future treatments.
Abstract: Pulmonary arterial hypertension (PAH) is a chronic and progressive disease leading to right heart failure and ultimately death if untreated. The first classification of PH was proposed in 1973. In 2008, the fourth World Symposium on PH held in Dana Point (California, USA) revised previous classifications. Currently, PH is devided into five subgroups. Group 1 includes patients suffering from idiopathic or familial PAH with or without germline mutations. Patients with a diagnosis of PAH should systematically been screened regarding to underlying mutations of BMPR2 gene (bone morphogenetic protein receptor type 2) or more rarely of ACVRL1 (activine receptor-like kinase type 1), ENG (endogline) or Smad8 genes. Pulmonary veno occusive disease and pulmonary capillary hemagiomatosis are individualized and designated as clinical group 1'. Group 2 'Pulmonary hypertension due to left heart diseases' is divided into three sub-groups: systolic dysfonction, diastolic dysfonction and valvular dysfonction. Group 3 'Pulmonary hypertension due to respiratory diseases' includes a heterogenous subgroup of respiratory diseases like PH due to pulmonary fibrosis, COPD, lung emphysema or interstitial lung disease for exemple. Group 4 includes chronic thromboembolic pulmonary hypertension without any distinction of proximal or distal forms. Group 5 regroup PH patients with unclear multifactorial mechanisms. Invasive hemodynamic assessment with right heart catheterization is requested to confirm the definite diagnosis of PH showing a resting mean pulmonary artery pressure (mPAP) of ≥ 25 mmHg and a normal pulmonary capillary wedge pressure (PCWP) of ≤ 15 mmHg. The assessment of PCWP may allow the distinction between pre-capillary and post-capillary PH (PCWP > 15 mmHg). Echocardiography is an important tool in the management of patients with underlying suspicion of PH. The European Society of Cardiology and the European Respiratory Society (ESC-ERS) guidelines specify its role, essentially in the screening proposing criteria for estimating the presence of PH mainly based on tricuspid regurgitation peak velocity and systolic artery pressure (sPAP). The therapy of PAH consists of non-specific drugs including oral anticoagulation and diuretics as well as PAH specific therapy. Diuretics are one of the most important treatment in the setting of PH because right heart failure leads to fluid retention, hepatic congestion, ascites and peripheral edema. Current recommendations propose oral anticoagulation aiming for targeting an International Normalized Ratio (INR) between 1.5-2.5. Target INR for patients displaying chronic thromboembolic PH is between 2–3. Better understanding in pathophysiological mechanisms of PH over the past quarter of a century has led to the development of medical therapeutics, even though no cure for PAH exists. Several specific therapeutic agents were developed for the medical management of PAH including prostanoids (epoprostenol, trepoprostenil, iloprost), endothelin receptor antagonists (bosentan, ambrisentan) and phosphodiesterase type 5 inhibitors (sildenafil, tadalafil). This review discusses the current state of art regarding to epidemiologic aspects of PH, diagnostic approaches and the current classification of PH. In addition, currently available specific PAH therapy is discussed as well as future treatments.
923 citations
Université libre de Bruxelles1, Technion – Israel Institute of Technology2, University of Barcelona3, University of Pittsburgh4, Royal Free Hospital5, Claude Bernard University Lyon 16, University of California, San Francisco7, University of Bologna8, National Institutes of Health9, University of Michigan10, Harvard University11, University of Paris-Sud12, University of Giessen13
TL;DR: In this paper, a change in terminology and a new definition of pulmonary hypertension due to LHD was proposed, and the authors suggest to abandon "out-of-proportion" PH and to distinguish "isolated post-capillary PH" from "post-CAPillary PH with a precapillary component" based on the pressure difference between diastolic pulmonary artery pressure and pulmonary artery wedge pressure.
535 citations
TL;DR: It is suggested that "safe dose" thrombolysis is safe and effective in the treatment of moderate PE, with a significant immediate reduction in the pulmonary artery pressure that was maintained at 28 months.
Abstract: The role of low-dose thrombolysis in the reduction of pulmonary artery pressure in moderate pulmonary embolism (PE) has not been investigated. Because the lungs are very sensitive to thrombolysis, we postulated that effective and safe thrombolysis might be achieved by a lower dose of tissue plasminogen activator. The purpose of the present study was to evaluate the role of this “safe dose” thrombolysis in the reduction of pulmonary artery pressure in moderate PE. During a 22-month period, 121 patients with moderate PE were randomized to receive a “safe dose” of tissue plasminogen activator plus anticoagulation (thrombolysis group [TG], n [ 61 patients) or anticoagulation alone (control group [CG], n [ 60). The primary end points consisted of pulmonary hypertension and the composite end point of pulmonary hypertension and recurrent PE at 28 months. Pulmonary hypertension and the composite end point developed in 9 of 58 patients (16%) in the TG and 32 of 56 patients (57%) in the CG (p <0.001) and 9 of 58 patients (16%) in the TG and 35 of 56 patients (63%) in the CG (p <0.001), respectively. The secondary end points were total mortality, the duration of hospital stay, bleeding at the index hospitalization, recurrent PE, and the combination of mortality and recurrent PE. The duration of hospitalization was 2.2 – 0.5 days in the TG and 4.9 – 0.8 days in the CG (p <0.001). The combination of death plus recurrent PE was 1 (1.6%) in TG and 6 (10%) in the CG (p [ 0.0489). No bleeding occurred in any group, and despite a positive trend in favor of a “safe dose” thrombolysis, no significant difference was noted in the rate of individual outcomes of death and recurrent PE when assessed independently. In conclusion, the results from the present prospective randomized trial suggests that “safe dose” thrombolysis is safe and effective in the treatment of moderate PE, with a significant immediate reduction in the pulmonary artery pressure that was maintained at 28 months. 2012 Elsevier Inc. All rights reserved. (Am J Cardiol 2012;-:-e-)
462 citations
TL;DR: Echocardiography is valuable in assessing prognosis and treatment options, monitoring the efficacy of specific therapeutic interventions, and detecting the preclinical stages of disease.
Abstract: Pulmonary arterial hypertension is most often diagnosed in its advanced stages because of the nonspecific nature of early symptoms and signs. Although clinical assessment is essential when evaluating patients with suspected pulmonary arterial hypertension, echocardiography is a key screening tool in the diagnostic algorithm. It provides an estimate of pulmonary artery pressure, either at rest or during exercise, and is useful in ruling out secondary causes of pulmonary hypertension. In addition, echocardiography is valuable in assessing prognosis and treatment options, monitoring the efficacy of specific therapeutic interventions, and detecting the preclinical stages of disease.
394 citations
TL;DR: In this article, the prognostic value of diastolic pulmonary vascular pressure gradient (DPG) was used to better prognosticate death in patients with out-of-proportion pulmonary hypertension.
311 citations
TL;DR: An APLN-dependent miRNA-FGF signaling axis needed for the maintenance of pulmonary vascular homeostasis is identified.
Abstract: Pulmonary arterial hypertension is characterized by vascular remodeling associated with obliteration of pulmonary arterioles and formation of plexiform lesions comprised of hyperproliferative endothelial and vascular smooth muscle cells. Here, we describe a novel, microRNA-dependent association between APLN and FGF2 pathways in the pulmonary artery endothelial cells (PAECs), where disruption of APLN signaling results in a robust increase in FGF2 expression. We show that this link is mediated by two microRNAs, miR-424 and miR-503, that are regulated by APLN and significantly downregulated in PAH. MiR-424 and miR-503 exert anti-proliferative effects by targeting FGF2 and FGFR1. Overexpression of miR-424 and miR-503 in PAECs promoted cellular quiescence and inhibited the capacity of PAEC conditioned media to induce proliferation of pulmonary artery smooth muscle cells. We show that reconstitution of miR-424 and miR-503 can ameliorate pulmonary hypertension in experimental models. These studies demonstrate the importance of APLN-miR-424/503-FGF axis in maintaining pulmonary vascular homeostasis.
303 citations
TL;DR: Although the group definitions for PH are helpful, in clinical practice, it is not uncommon for patients to have >1 disease associated with PH and to have both precapillary and postcapillary components, so called multifactorial PH.
Abstract: Pulmonary hypertension (PH), regardless of the pathobiology and site of functional changes, is characterized by an asymptomatic or a latent phase followed by a gradual reduction in exercise capacity related to decreasing right ventricular (RV) contractile reserve.1,2 In addition to right heart and pulmonary vascular function, other factors including ventilation/perfusion mismatch, hypoxemia, peripheral oxygen transportation/utilization, and impaired skeletal muscle function, may significantly influence the functional status of patients with PH.3
Guidelines provide a clinical classification system that categorizes PH into 5 groups with specific pathogenesis, pathologies, and clinical characteristics.1,2 The natural history of the disease is determined by the rapidity of increase in resting mean pulmonary artery pressure (mPAP) and the ability of the RV to compensate and hypertrophy, which differs depending on the pathobiology and related diseases.1,2 The definition of PH and PH groups is based on clinical assessment and invasive hemodynamics. Precapillary PH (groups 1 and 3–5) is characterized as a resting mPAP of ≥25 mm Hg and pulmonary capillary wedge pressure (PCWP) or left ventricular (LV) end-diastolic pressure ≤15 mm Hg. Postcapillary PH (group 2) is associated with an elevated pulmonary venous pressure (>15 mm Hg) related to left heart disease, which may involve abnormalities of the LV, mitral valve, or aortic valve.2 Although the group definitions for PH are helpful, in clinical practice, it is not uncommon for patients to have >1 disease associated with PH and to have both precapillary and postcapillary components, so called multifactorial PH (eg, aortic stenosis, systemic sclerosis, chronic thromboembolic disease) or out-of-proportion PH for a given condition (eg, chronic lung disease, chronic heart failure).
The concept that symptoms associated with cardiopulmonary diseases would be associated with an abnormal increase in mPAP with exercise was …
300 citations
TL;DR: Although the primary end point of the study was not met, riociguat was well tolerated in patients with pulmonary hypertension caused by systolic left ventricular dysfunction and improved cardiac index and pulmonary and systemic vascular resistance.
Abstract: Background—Pulmonary hypertension caused by systolic left ventricular dysfunction is associated with significant morbidity and mortality; however, no treatment is approved for this indication. We hypothesized that riociguat, a novel soluble guanylate cyclase stimulator, would have beneficial hemodynamic effects in patients with pulmonary hypertension caused by systolic left ventricular dysfunction. Methods and Results—Overall, 201 patients with heart failure resulting from pulmonary hypertension caused by systolic left ventricular dysfunction were randomized to double-blind treatment with oral placebo or riociguat (0.5, 1, or 2 mg 3 times daily) for 16 weeks in 4 parallel arms. The primary outcome was the placebo-corrected change from baseline at week 16 in mean pulmonary artery pressure. Although the decrease in mean pulmonary artery pressure in the riociguat 2 mg group (−6.1±1.3 mm Hg; P<0.0001 versus baseline) was not significantly different from placebo (P=0.10), cardiac index (0.4 L·min−1·m−2; 95% co...
282 citations
TL;DR: Among stable HFREF outpatients, PH was associated with markers of greater disease severity and risk of death, however, the presence of pulmonary arterial disease (mixed PH) carries incremental risk.
Abstract: Objectives The purpose of this study was to assess the clinical, functional, and hemodynamic characteristics of passive and mixed pulmonary hypertension (PH), compare outcomes, and contrast conventional and novel hemodynamic partition values in patients with chronic heart failure of reduced left ventricular ejection fraction (HFREF). Background PH in HFREF may develop from left-sided venous congestion (passive PH) or the combination of pulmonary arterial disease and venous congestion (mixed PH). Subgroup outcomes are not well defined, and the partition values used to define risk are based largely on consensus opinion rather than outcome data. Methods Ambulatory patients referred for hemodynamic catheterization were analyzed retrospectively (N = 463). Results Comparing patients with no PH to those with passive PH and mixed PH, a progressive gradient of more severely deranged hemodynamics, diastolic dysfunction, and mitral regurgitation was observed. In multivariate analysis, the presence of any PH or mixed PH was associated with older age, diuretic use, atrial fibrillation, and lower pulmonary artery compliance (PAC). Over a median follow-up of 2.1 years, patients with PH displayed greater risk of death (hazard ratio [HR]: 2.24; confidence limits [95% CL]: 1.39, 3.98; p 4 Wood units, systolic pulmonary artery pressure >35 mm Hg, pulmonary wedge pressure >25 mm Hg, and PAC Conclusions Among stable HFREF outpatients, PH was associated with markers of greater disease severity and risk of death. However, the presence of pulmonary arterial disease (mixed PH) carries incremental risk. Abnormalities in pulmonary vascular resistance and compliance may serve as novel therapeutic targets.
251 citations
TL;DR: Recent studies suggest that exercise-induced increase in PAP to a mean higher than 30 mm Hg may be associated with dyspnea-fatigue symptomatology and postexercise measurements are unreliable because of the rapid return of pulmonary vascular pressures and flows to the baseline resting state.
Abstract: Exercise stresses the pulmonary circulation through increases in cardiac output (.Q) and left atrial pressure. Invasive as well as noninvasive studies in healthy volunteers show that the slope of mean pulmonary artery pressure (mPAP)-flow relationships ranges from 0.5 to 3 mm Hg.min.L(-1). The upper limit of normal mPAP at exercise thus approximates 30 mm Hg at a .Q of less than 10 L.min(-1) or a total pulmonary vascular resistance at exercise of less than 3 Wood units. Left atrial pressure increases at exercise with an average upstream transmission to PAP in a close to one-for-one mm Hg fashion. Multipoint PAP-flow relationships are usually described by a linear approximation, but present with a slight curvilinearity, which is explained by resistive vessel distensibility. When mPAP is expressed as a function of oxygen uptake or workload, plateau patterns may be observed in patients with systolic heart failure who cannot further increase .Q at the highest levels of exercise. Exercise has to be dynamic to avoid the increase in systemic vascular resistance and abrupt changes in intrathoracic pressure that occur with resistive exercise and can lead to unpredictable effects on the pulmonary circulation. Postexercise measurements are unreliable because of the rapid return of pulmonary vascular pressures and flows to the baseline resting state. Recent studies suggest that exercise-induced increase in PAP to a mean higher than 30 mm Hg may be associated with dyspnea-fatigue symptomatology.
TL;DR: BPA may offer an alternative form of treatment in selected CTEPH patients and while prognostic markers such as haemodynamics, functional capacity and biomarkers improve, significant periprocedural complications must be recognised.
Abstract: Objective To examine the effect of balloon pulmonary angioplasty (BPA) on chronic thromboembolic pulmonary hypertension (CTEPH) in patients with inoperable disease or persistent pulmonary hypertension after pulmonary endarterectomy. Design Observational cohort study. Setting Referred patients with inoperable or persistent CTEPH. Patients Twenty consecutive CTEPH patients (10 females), aged 60±10 years. Interventions BPA. Main outcome measures Right heart catheterisation, functional capacity (cardiopulmonary exercise testing (CPET) and NYHA class) and blood sampled biomarkers N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin T examined at the time of diagnosis and repeated in all patients 3 months after the last BPA. Results Seventy-three catheterisations were performed with 18.6±6.1 BPAs per patient on segmental and subsegmental arteries. Two deaths occurred following the first BPA, with an overall 10% periprocedural death rate. Reperfusion oedema complicated seven procedures. Comparisons before and after BPA showed significant haemodynamic improvements, including decreased mean pulmonary artery pressure (mPAP) (45±11 mm Hg vs 33±10 mm Hg; p Conclusions BPA may offer an alternative form of treatment in selected CTEPH patients. While prognostic markers such as haemodynamics, functional capacity and biomarkers improve, significant periprocedural complications must be recognised. Randomised trials are warranted.
TL;DR: RV dysfunction is worse in SScPAH compared with IPAH at similar afterload, and may be because of intrinsic systolic function rather than enhanced pulmonary vascular resistive and pulsatile loading.
Abstract: Background—Systemic sclerosis–associated pulmonary artery hypertension (SScPAH) has a worse prognosis compared with idiopathic pulmonary arterial hypertension (IPAH), with a median survival of 3 years after diagnosis often caused by right ventricular (RV) failure. We tested whether SScPAH or systemic sclerosis–related pulmonary hypertension with interstitial lung disease imposes a greater pulmonary vascular load than IPAH and leads to worse RV contractile function. Methods and Results—We analyzed pulmonary artery pressures and mean flow in 282 patients with pulmonary hypertension (166 SScPAH, 49 systemic sclerosis–related pulmonary hypertension with interstitial lung disease, and 67 IPAH). An inverse relation between pulmonary resistance and compliance was similar for all 3 groups, with a near constant resistance×compliance product. RV pressure–volume loops were measured in a subset, IPAH (n=5) and SScPAH (n=7), as well as SSc without PH (n=7) to derive contractile indexes (end-systolic elastance [Ees] an...
TL;DR: An overview of the histological abnormalities observed in humans with pulmonary hypertension and in preclinical models is provided and insights gained regarding several key signaling pathways contributing to the remodeling process are discussed, focusing on ion homeostasis, endothelin-1, serotonin, bone morphogenetic proteins, Rho kinase, and hypoxia-inducible factor 1.
Abstract: Pulmonary hypertension is a complex, progressive condition arising from a variety of genetic and pathogenic causes. Patients present with a spectrum of histologic and pathophysiological features, likely reflecting the diversity in underlying pathogenesis. It is widely recognized that structural alterations in the vascular wall contribute to all forms of pulmonary hypertension. Features characteristic of the remodeled vasculature in patients with pulmonary hypertension include increased stiffening of the elastic proximal pulmonary arteries, thickening of the intimal and/or medial layer of muscular arteries, development of vaso-occlusive lesions, and the appearance of cells expressing smooth muscle-specific markers in normally non-muscular small diameter vessels, resulting from proliferation and migration of pulmonary arterial smooth muscle cells and cellular transdifferentiation. The development of several animal models of pulmonary hypertension has provided the means to explore the mechanistic underpinnings of pulmonary vascular remodeling, although none of the experimental models currently used entirely replicates the pulmonary arterial hypertension observed in patients. Herein, we provide an overview of the histological abnormalities observed in humans with pulmonary hypertension and in preclinical models and discuss insights gained regarding several key signaling pathways contributing to the remodeling process. In particular, we will focus on the roles of ion homeostasis, endothelin-1, serotonin, bone morphogenetic proteins, Rho kinase, and hypoxia-inducible factor 1 in pulmonary arterial smooth muscle and endothelial cells, highlighting areas of cross-talk between these pathways and potentials for therapeutic targeting.
TL;DR: Exercise-induced PASP increase is of high clinical and prognostic relevance in pulmonary hypertension patients and may indicate right ventricular contractile reserve, and stress Doppler echocardiography may be a useful tool for prognostic assessment inmonary hypertension patients.
Abstract: Background—This study sought to analyze a new approach to assess exercise-induced pulmonary artery systolic pressure (PASP) increase by means of stress Doppler echocardiography as a possible measure of right ventricular contractile reserve in patients with severe pulmonary hypertension and right heart failure. Methods and Results—In this prospective study, patients with invasively diagnosed pulmonary arterial hypertension or inoperable chronic thromboembolic pulmonary hypertension and impaired right ventricular pump function despite a stable targeted pulmonary arterial hypertension medication underwent a broad panel of noninvasive assessments, including stress echocardiography and cardiopulmonary exercise testing. On the basis of the assumption that exercise-induced PASP is a measure of right ventricular contractile reserve, patients were classified into 2 groups according to an exercise-induced PASP increase above or below the median. Patients were followed up for 3.0±1.8 years. Univariate and multivaria...
TL;DR: Doppler echocardiography allows for accurate measurements of the pulmonary circulation, but with moderate precision, which explains why the procedure is valid for population studies but cannot be used for the individual diagnosis of pulmonary hypertension.
TL;DR: It is shown that impaired RV systolic function, hypertrophy, and dilation were present even at a slight increase of mPAP, which indicates an early impact on RV function and structure in patients with COPD.
TL;DR: In this paper, the authors identify variables that predict outcome in patients with pulmonary hypertension, including mixed venous oxygen saturation, carbon monoxide diffusion, World Health Organization functional class and age, but not severity of airflow obstruction.
Abstract: The phenotype and outcome of severe pulmonary hypertension in chronic obstructive pulmonary disease (COPD) is described in small numbers, and predictors of survival are unknown. Data was retrieved for 101 consecutive, treatment-naive cases of pulmonary hypertension in COPD. Mean ± SD follow-up was 2.3 ± 1.9 years. 59 patients with COPD and severe pulmonary hypertension, defined by catheter mean pulmonary artery pressure ≥40 mmHg, had significantly lower carbon monoxide diffusion, less severe airflow obstruction but not significantly different emphysema scores on computed tomography compared to 42 patients with mild-moderate pulmonary hypertension. 1- and 3-year survival for severe pulmonary hypertension, at 70% and 33%, respectively, was inferior to 83% and 55%, respectively, for mild-moderate pulmonary hypertension. Mixed venous oxygen saturation, carbon monoxide diffusion, World Health Organization functional class and age, but not severity of airflow obstruction, were independent predictors of outcome. Compassionate treatment with targeted therapies in 43 patients with severe pulmonary hypertension was not associated with a survival benefit, although improvement in functional class and/or fall in pulmonary vascular resistance >20% following treatment identified patients with improved survival. Standard prognostic markers in COPD have limited value in patients with pulmonary hypertension. This study identifies variables that predict outcome in this phenotype. Despite poor prognosis, our data suggest that further evaluation of targeted therapies is warranted.
TL;DR: The current results suggested the importance of the initial evaluation of PH for patients with IPF and the body mass index, %FVC, %DLCO, baseline PaO2, modified Medical Research Council score, 6-minute walk distance, and lowest SpO2 of the 6-min walk test were significantly predictive of survival.
Abstract: Background: The impact of pulmonary hypertension (PH) on survival has been demonstrated in severe cases with idiopathic pulmonary fibrosis (IPF) who were referred for transplantation. However, whether PH is a predictor of survival remains unclear in milder cases. Objectives: To evaluate the survival impact of pulmonary artery pressure measured during the initial evaluation in patients with IPF. Methods: We retrospectively analyzed the initial evaluation data of 101 consecutive IPF patients undergoing right heart catheterization. Patients evaluated with supplemental oxygen were excluded. Predictors of 5-year survival were analyzed using the Cox proportional model. Results: The mean forced vital capacity (FVC) % predicted, diffusing capacity of the lung for carbon monoxide (DLCO) % predicted, and mean pulmonary artery pressure (MPAP) were 70.2 ± 20.1%, 47.9 ± 19.5%, and 19.2 ± 6.5 mm Hg, respectively. A univariate Cox proportional hazard model showed that the body mass index, %FVC, %DLCO, baseline PaO2, modified Medical Research Council score, 6-min walk distance, and lowest SpO2 of the 6-min walk test were significantly predictive of survival. The MPAP and pulmonary vascular resistance of right heart catheterization were also significant. With stepwise, multivariate Cox proportional analysis, MPAP (HR = 1.064; 95% CI 1.015-1.116, p = 0.010) and %FVC (HR = 0.965, 95% CI 0.949-0.982, p 20 mm Hg to be optimal for predicting the prognosis. Conclusions: Higher MPAP and lower %FVC at the initial evaluation were significant independent prognostic factors of IPF. The current results suggested the importance of the initial evaluation of PH for patients with IPF.
TL;DR: Pulmonary Flow Grade score is useful in determining therapeutic efficacy, and PEPSI is highly supportive to reduce the risk of RPE after PTPA using these 2 indexes, PTPA could become a safe and common therapeutic strategy for CTEPH.
Abstract: Objectives: This study sought to identify useful predictors for hemodynamic improvement and risk of reperfusion pulmonary edema (RPE), a major complication of this procedure.Background: Percutaneou...
TL;DR: In this paper, the safety and efficacy of pulmonary artery denervation (PADN) for patients with idiopathic PA hypertension (IPAH) not responding optimally to medical therapy was evaluated.
TL;DR: It is likely that chronic thromboembolic pulmonary hypertension (CTEPH) is more prevalent than currently recognised and imaging studies are fundamental to decision making with respect to operability.
Abstract: It is likely that chronic thromboembolic pulmonary hypertension (CTEPH) is more prevalent than currently recognised. Imaging studies are fundamental to decision making with respect to operability. All patients with suspected CTEPH should be referred to an experienced surgical centre. Currently, there is no risk scoring stratification system to guide operability assessment and it is predominantly based on surgical experience. The aim of pulmonary endarterectomy (PEA) is the removal of obstructive material to immediately reduce pulmonary vascular resistance. PEA affords the best chance of cure, but is difficult to perfect. Recognition and clearance of distal segmental and subsegmental disease is the main problem. The basic surgical techniques include: median sternotomy incision, cardiopulmonary bypass, arteriotomy incisions within pericardium, and a true endarterectomy with meticulous full distal dissection. Deep hypothermic circulatory arrest is recommended as the best means of reducing blood flow in the pulmonary artery to allow a clear field for dissection. In the recent PEACOG (PEA and COGnition) trial there was no evidence of cognitive impairment post-PEA. Reperfusion pulmonary oedema and residual pulmonary hypertension are unique post-operative complications post-PEA and are associated with increased mortality. However, in-hospital mortality is now <5% in experienced centres.
TL;DR: It is indicated that borderline mean PAP and an elevated TPG in patients with SSc predict progression to pulmonary hypertension, and these patients should be monitored closely for the development of PH.
Abstract: OBJECTIVE: To determine whether patients with systemic sclerosis (SSc) and borderline mean pulmonary artery pressure (PAP) at cardiac catheterization are more likely to develop pulmonary hypertension (PH) than those in whom pulmonary pressure is normal. METHODS: Patients with SSc in whom PH and significant interstitial lung disease had been excluded at baseline were enrolled in our prospective cohort. Analysis of followup data identified patients who met prespecified criteria prompting repeat catheterization to reassess for possible PH. Using Kaplan-Meier, receiver operating characteristic, and Cox regression methods, we studied the development of PH and death. RESULTS: Of 228 patients in this study, 86 had borderline mean PAP (21-24 mm Hg) at baseline. Following prespecified criteria, 76 patients underwent repeat catheterization, and 29 of these developed PH. Two cases were related to disease of the left side of the heart. The average mean PAP increased from baseline (20.2 mm Hg) to followup (24.3 mm Hg) (P<0.05 by Student's t-test). Patients with borderline mean PAP were more likely to develop PH than patients with mean PAP≤20 mm Hg (P<0.001 by log rank test, hazard ratio [HR] 3.7). A transpulmonary gradient (TPG)≥11 mm Hg at baseline also predicted PH (P<0.001 by log rank test, HR 7.9). Incident development of pulmonary arterial hypertension (PAH) was not benign, with a mortality of 18% within 3 years. CONCLUSION: Our findings indicate that borderline mean PAP and an elevated TPG in patients with SSc predict progression to PH. These patients should be monitored closely for the development of PH. Our findings indicate that catheterization data are useful in patients considered at risk of PAH.
TL;DR: Percutaneous insertion of an IABP through the left axillary artery is a feasible and relatively well-tolerated strategy to bridge patients with end-stage heart failure to heart transplantation.
Abstract: Objectives This study evaluated the feasibility, tolerability, and efficacy of a strategy for percutaneous intra-aortic balloon pump (IABP) placement through the left axillary-subclavian artery to provide mechanical circulatory support in patients with end-stage heart failure as a bridge to heart transplantation. Background The transfemoral approach to IABP placement is associated with major disadvantages, including the risk for infection and limitation of patient mobility in those requiring extended support. Methods We developed a percutaneous technique for placing IABPs in the left axillary artery that permits upright sitting and ambulation. We performed a retrospective review of data from patients who had undergone left axillary IABP implantation between 2007 and 2012. Results Fifty patients who received a left axillary IABP as a bridge to transplantation were identified, of whom 42 (84%) underwent heart or heart–multiorgan transplantation. Cumulative survival on IABP support was 92%, and post-transplant 90-day survival was 90%. Median duration of support was 18 days. Four of 50 patients (8%) died while on IABP support, and 3 (6%) received greater mechanical circulatory support. Four patients (8%) had clinically significant thromboembolic or bleeding events without long-term sequelae. The most common minor adverse event was IABP malposition, in 22 patients (44%). Prolonged IABP support in the heart-transplantation cohort was associated with significant improvements in mean pulmonary artery pressure and in creatinine and total bilirubin concentrations. Conclusions Percutaneous insertion of an IABP through the left axillary artery is a feasible and relatively well-tolerated strategy to bridge patients with end-stage heart failure to heart transplantation. This form of mechanical-device treatment permits upright sitting and ambulation in those requiring extended support.
TL;DR: Attenuating ER stress with clinically used chemical chaperones may be a novel therapeutic strategy in pulmonary hypertension with high translational potential.
Abstract: Background—Evidence suggestive of endoplasmic reticulum (ER) stress in the pulmonary arteries of patients with pulmonary arterial hypertension has been described for decades but has never been therapeutically targeted. ER stress is a feature of many conditions associated with pulmonary arterial hypertension like hypoxia, inflammation, or loss-of-function mutations. ER stress signaling in the pulmonary circulation involves the activation of activating transcription factor 6, which, via induction of the reticulin protein Nogo, can lead to the disruption of the functional ER-mitochondria unit and the increasingly recognized cancer-like metabolic shift in pulmonary arterial hypertension that promotes proliferation and apoptosis resistance in the pulmonary artery wall. We hypothesized that chemical chaperones known to suppress ER stress signaling, like 4-phenylbutyrate (PBA) or tauroursodeoxycholic acid, will inhibit the disruption of the ER-mitochondrial unit and prevent/reverse pulmonary arterial hypertensio...
TL;DR: CMR imaging can accurately estimate mean pulmonary artery pressure in patients with suspected pulmonary hypertension and calculate PVR by estimating all major pulmonary hemodynamic metrics measured at RHC.
Abstract: Objectives The aim of this study was to develop a composite numerical model based on parameters from cardiac magnetic resonance (CMR) imaging for noninvasive estimation of the key hemodynamic measurements made at right heart catheterization (RHC) Background Diagnosis and assessment of disease severity in patients with pulmonary hypertension is reliant on hemodynamic measurements at RHC A robust noninvasive approach that can estimate key RHC measurements is desirable Methods A derivation cohort of 64 successive, unselected, treatment naive patients with suspected pulmonary hypertension from the ASPIRE (Assessing the Spectrum of Pulmonary Hypertension Identified at a Referral Centre) Registry, underwent RHC and CMR within 12 h Predicted mean pulmonary arterial pressure (mPAP) was derived using multivariate regression analysis of CMR measurements The model was tested in an independent prospective validation cohort of 64 patients with suspected pulmonary hypertension Surrogate measures of pulmonary capillary wedge pressure (PCWP) and cardiac output (CO) were estimated by left atrial volumetry and pulmonary arterial phase contrast imaging, respectively Noninvasive pulmonary vascular resistance (PVR) was calculated from the CMR-derived measurements, defined as: (CMR-predicted mPAP – CMR-predicted PCWP)/CMR phase contrast CO Results The following composite statistical model of mPAP was derived: CMR-predicted mPAP = –46 + (interventricular septal angle × 023) + (ventricular mass index × 163) In the validation cohort a strong correlation between mPAP and MR estimated mPAP was demonstrated (R2 = 067) For detection of the presence of pulmonary hypertension the area under the receiver-operating characteristic (ROC) curve was 096 (092 to 100; p Conclusions CMR imaging can accurately estimate mean pulmonary artery pressure in patients with suspected pulmonary hypertension and calculate PVR by estimating all major pulmonary hemodynamic metrics measured at RHC
TL;DR: PVH had high prevalence in the scleroderma-pulmonary hypertension population and was haemodynamically, echocardiographically and demographically closer to the PVH group than the PAH group.
Abstract: Our study aimed to determine the prevalence of occult left-heart disease in patients with scleroderma and pulmonary hypertension. In patients with pulmonary hypertension (mean pulmonary artery pressure (mean PAP) ≥25 mmHg), differentiation between pre- and post-capillary pulmonary hypertension has been made according to pulmonary artery wedge pressure (PAWP) less than or more than 15 mmHg, respectively. We performed a retrospective chart review of 107 scleroderma patients. All patients with suspected pulmonary hypertension had routine right or left heart catheterisation with left ventricular end-diastolic pressure (LVEDP) measurement pre-/post-fluid challenge. We extracted demographic, haemodynamic and echocardiographic data. Patients were classified into one of four groups: haemodynamically normal (mean PAP 15 mmHg); occult PVH (mean PAP≥25 mmHg, PAWP≤15 mmHg, LVEDP>15 mmHg before or after fluid challenge); and pulmonary arterial hypertension (PAH) (mean PAP≥25 mmHg, PAWP≤15 mmHg and LVEDP≤15 mmHg before or after fluid challenge). 53 out of 107 patients had pulmonary hypertension. Based on the PAWP-based definition, 29 out of 53 had PAH and 24 out of 53 had PVH. After considering the resting and post-fluid-challenge LVEDP, 11 PAH patients were reclassified as occult PVH. The occult PVH group was haemodynamically, echocardiographically and demographically closer to the PVH group than the PAH group. PVH had high prevalence in our scleroderma-pulmonary hypertension population. Distinguishing PAH from PVH with only PAWP may result in some PVH patients being misclassified as having PAH.
TL;DR: Therapy with continuous positive airway pressure is associated with lower blood pressure, atrial size, and ventricular mass, and a lower risk of AF recurrence after pulmonary venous isolation (PVI).
Abstract: Background Sleep apnea (SA) is associated with an increased risk of atrial fibrillation (AF). We sought to determine the effect of SA on cardiac structure in patients with AF, whether therapy for SA was associated with beneficial cardiac structural remodelling, and whether beneficial cardiac structural remodelling translated into a reduced risk of recurrence of AF after pulmonary venous isolation (PVI). Methods and Results A consecutive group of 720 patients underwent a cardiac magnetic resonance study before PVI. Patients with SA (n=142, 20%) were more likely to be male, diabetic, and hypertensive and have an increased pulmonary artery pressure, right ventricular volume, atrial dimensions, and left ventricular mass. Treated SA was defined as duration of continuous positive airway pressure therapy of >4 hours per night. Treated SA patients (n=71, 50%) were more likely to have paroxysmal AF, a lower blood pressure, lower ventricular mass, and smaller left atrium. During a follow-up of 42 months, AF recurred in 245 patients. The cumulative incidence of AF recurrence was 51% in patients with SA, 30% in patients without SA, 68% in patients with untreated SA, and 35% in patients with treated SA. In a multivariable model, the presence of SA (hazard ratio 2.79, CI 1.97 to 3.94, P 0.0001) and untreated SA (hazard ratio 1.61, CI 1.35 to 1.92, P 0.0001) were highly associated with AF recurrence. Conclusions Patients with SA have an increased blood pressure, pulmonary artery pressure, right ventricular volume, left atrial size, and left ventricular mass. Therapy with continuous positive airway pressure is associated with lower blood pressure, atrial size, and ventricular mass, and a lower risk of AF recurrence after PVI.
Tohoku University1, Mie University2, Kurume University3, Yokohama City University4, University of Tokyo5, Hiroshima University6, Kanazawa University7, Hamamatsu University School of Medicine8, Nagoya City University9, National Defense Medical College10, Asahikawa Medical University11, Chiba University12, Dokkyo Medical University13
TL;DR: Mid-term treatment with oral AT-877ER showed additional improvement in pulmonary hemodynamics in patients with PAH, and serum levels of hydroxyfasudil, an active metabolite of AT-799ER tended to correlate with improvements in the cardiac index and mean pulmonary artery pressure.
Abstract: Background: We have previously demonstrated that long-term inhibition of Rho-kinase ameliorates pulmonary arterial hypertension (PAH) in animal models. In the present study, we examined the clinical effects of mid-term oral treatment with an extended release formulation of AT-877 (fasudil hydrochloride), a specific Rho-kinase inhibitor (AT-877ER) on PAH. Methods and Results: 23 PAH patients were treated with either placebo (10/2 females/males, 51±16 years, idiopathic PAH (IPAH) in 6, PAH associated with connective tissue disease (CTD-PAH) in 3, PAH with congenital heart disease (CHD-PAH) in 2, and portal PAH in 1) or AT-877ER (6/5 females/males, 47±14 years, IPAH in 2, CTD-PAH in 5, and CHD-PAH in 4); 3 patients were excluded. We performed a 6-min walk test and right heart catheterization in the remaining 20 patients, before and 3 months after the treatment (placebo n=11, AT-877ER n=9). Although there were no significant differences between the 2 groups for the 6-min walk distance, pulmonary hemodynamics tended to be improved in the AT-877ER group, especially the prevalence of improved cardiac index from baseline, which was significantly higher in the AT-877ER than in the placebo group. In the AT-877ER group, serum levels of hydroxyfasudil, an active metabolite of AT-877ER tended to correlate with improvements in the cardiac index and mean pulmonary artery pressure. Conclusions: Mid-term treatment with oral AT-877ER showed additional improvement in pulmonary hemodynamics in patients with PAH. (Circ J 2013; 77: 2619–2625)
TL;DR: Balloon occlusion of the left pulmonary interlobar artery led to a significant increase of haemodynamic parameters of the pulmonary artery and the pressure responses were completely abolished by the PADN treatment at the main bifurcation area of theleft pulmonary artery.
Abstract: AIMS The study sought to assess the effect of percutaneous pulmonary artery denervation (PADN) on balloon-occlusion-induced acute pulmonary arterial hypertension (PAH) in vivo. The PADN is a minimally invasive and endovascular catheter-based interventional therapy using radiofrequency ablation to abolish the pulmonary arterial baroreceptors to pressure response. METHODS AND RESULTS To examine the efficacy of balloon-occlusion-induced PAH, twenty Mongolian dogs were randomly assigned to one of two groups: group 1 (left distal pulmonary basal trunk occlusion) and group 2 (left pulmonary interlobar artery occlusion). Afterwards, PADN treatment at the main pulmonary artery bifurcation level with left pulmonary interlobar artery occlusion in all 20 dogs was conducted. Haemodynamic parameters were measured at baseline and during balloon occlusion as well as the PADN treatment at different time points: one, two, three, five, and ten minutes. Before the PADN treatment, most haemodynamic parameters of the pulmonary artery remained unchanged in group 1 with distal pulmonary basal trunk occlusion. However, in group 2 with the occlusion of the left pulmonary interlobar artery, mean pulmonary arterial pressure, mean right ventricular pressure, and pulmonary vessel resistance gradually increased, and mean absolute difference reached peak at five minutes (Δ16.6 mmHg, Δ14.1 mmHg and Δ1,144 dye/s/cm5, respectively; each p<0.01). These haemodynamic parameters at five minutes induced by left pulmonary interlobar artery occlusion were completely abolished with the PADN treatment compared to baseline (Δ0.3 mmHg, Δ0.2 mmHg, and Δ34 dye/s/cm5, respectively). CONCLUSIONS Balloon occlusion of the left pulmonary interlobar artery led to a significant increase of haemodynamic parameters of the pulmonary artery. The pressure responses were completely abolished by the PADN treatment at the main bifurcation area of the left pulmonary artery.