Pulmonary Arterial Bed Research Articles

Tolerability and clinical efficacy of inhaled treprostinil in patients with group 1 pulmonary arterial hypertension.

Treprostinil is a prostacyclin analogue that directly vasodilates pulmonary and systemic arterial vascular beds. The United States Food and Drug Administration approved inhaled treprostinil in July 2009 for the treatment of group 1 pulmonary arterial hypertension. Inhaled treprostinil avoids issues with continuous infusion prostanoids. This study describes a single institutional experience with inhaled treprostinil. This was a retrospective review of group 1 pulmonary arterial hypertension patients receiving inhaled treprostinil from July 2009 through September 2015. Patient demographics, vital signs, prognostic indicators, pulmonary arterial hypertension assessments, treprostinil dosing, pulmonary arterial hypertension medications, and physician assessment were collected. Prognostic indicators and the physician assessment were used to assess treatment response. A modified Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management (REVEAL) risk score was calculated prior to and after initiation of inhaled treprostinil. The mean time on inhaled treprostinil for the 16 patients was 21 ± 17 months. A total of 31% discontinued treatment. The New York Heart Association Functional Class, right ventricular size, and right ventricular function improved after inhaled treprostinil. Directional improvement in B-type natriuretic peptide, 6-minute walk distance, right arterial pressure and mean pulmonary artery pressure were also observed. The mean modified REVEAL risk score (RRS) was 7 ± 3 at baseline. The RRS decreased in 7 of the 11 patients that improved and remained stable in 2 patients. The majority of patients in this consecutive series receiving inhaled treprostinil tolerated treatment. Most patients remained on therapy for over 12 months. Clinical assessments of disease severity all changed directionally toward improvement and the overall risk assessment was improved or stable in 56% by the RRS.

Left Ventricular Assist Devices in Pulmonary Hypertension Group 2 With Significantly Elevated Pulmonary Vascular Resistance: A Bridge to Cure

Pulmonary hypertension secondary to left heart disease (WHO Group 2) is a known risk factor in patients with heart failure. The favourable effect of left ventricular assist devices (LVAD) on pulmonary hypertension has been demonstrated before, although this effect has not been well-studied in advanced pulmonary arterial bed disease with a significant elevation in pulmonary vascular resistance. We reviewed the records of 258 LVAD patients in our institution. Patients with elevated mean pulmonary artery pressure (mPAP>25mmHg) and elevated pulmonary vascular resistance (PVR ≥3 Wood units) were included in the study. Patients were divided into two groups based on their baseline PVR (PVR=3-5 Wood units (WU) vs. PVR>5WU). The groups were studied for the changes in their pulmonary haemodynamics after the placement of LVAD. Fifty-one (51) patients were included in the study. All patients showed a significant improvement in their pulmonary haemodynamic parameters post LVAD placement. In the group with the higher PVR, mPAP dropped from a baseline of 43±7mmHg to 22±6mmHg post LVAD placement (p<0.001), while PVR dropped from 6.3±1.2 Wood units to 2.2±1.1 Wood units (p<0.001). In a subgroup of patients who underwent cardiac transplantation post LVAD (n=14), all patients maintained a normalised PVR (<3WU) one year post cardiac transplantation. Left ventricular assist devices can reverse pulmonary hypertension WHO Group 2 with significantly elevated PVR; this effect is not dependent on the baseline PVR, and is maintained up to one year post cardiac transplantation.

Regional Distribution of Pulmonary Blood Volume with Dual-Energy Computed Tomography: Results in 42 Subjects

The noninvasive approach of lung perfusion generated from dual-energy computed tomography acquisitions has entered clinical practice. The purpose of this study was to analyze the regional distribution of iodine within distal portions of the pulmonary arterial bed on dual-source, dual-energy computed tomography examinations in a cohort of subjects without cardiopulmonary pathologies. The study population included 42 patients without cardiorespiratory disease, enabling quantitative and qualitative analysis of pulmonary blood volume after administration of a 40% contrast agent. Qualitative analysis was based on visual assessment. Quantitative analysis was obtained after semiautomatic division of each lung into 18 areas. The iodine concentration did not significantly differ between the right (R) and left (L) lungs (P = .49), with a mean attenuation of 41.35 Hounsfield units (HU) and 41.14 HU, respectively. Three regional gradients of attenuation were observed between: (a) lung bases and apices (P < .001), linked to the conditions of examination (mean Δ: 6.23 in the R lung; 5.96 in the L lung); (b) posterior and anterior parts of the lung (P < .001) due to gravity (mean Δ: 11.92 in the R lung ; 15.93 in the L lung); and (c) medullary and cortical lung zones (P < .001) (mean Δ: 9.35 in the R lung ; 8.37 in the L lung). The intensity of dependent-nondependent (r = 0.42; P < .001) and corticomedullary (r = 0.58; P < .0001) gradients was correlated to the overall iodine concentration. Distribution of pulmonary blood volume is influenced by physiological gradients and scanning conditions.

Retrograde Pulmonary Embolectomy for Acute Pulmonary Embolism: A Simplified Technique

Surgical embolectomy in acute pulmonary embolism is usually reserved for patients with massive pulmonary embolism presenting with cardiogenic shock, or for whom thrombolysis is absolutely contraindicated or has failed. Incomplete removal of thrombotic material lodged in the distal pulmonary arterial bed is considered an important cause of persistent pulmonary hypertension. Retrograde pulmonary embolectomy is an adjunct to conventional pulmonary embolectomy, resulting in more complete embolectomy, specifically of material lodged in the distal pulmonary arterial bed. We describe our simplified technique of retrograde pulmonary embolectomy as a safe adjunct to conventional pulmonary embolectomy.

Clinical-Physiological Considerations in Patients Undergoing Staged Palliation for a Functionally Single Ventricle.

The objectives of this review are to discuss the pathophysiology of the circulation with a functionally univentricular heart, with a focus on the unique physiologic characteristics, which provide the underpinnings for the management of these complex patients. MEDLINE and PubMed. The circulation of the patient with a functionally univentricular heart displays unique physiologic characteristics, which are quite different from those of the normal biventricular circulation. There are profound differences within the heart itself in terms of ventricular function, interventricular interactions, and myocardial architecture, which are likely to have significant implications for the efficiency of ventricular ejection and metabolism. The coupling between the systemic ventricle and the aorta also displays unique features. The 3D orientation of the Fontan anastomosis itself can profoundly impact cardiac output, although the "portal" pulmonary arterial bed is a crucial determinant of overall cardiovascular function. As a result, disease-specific approaches to improve cardiovascular function are required at all stages during the care of these complex patients.

Expression and role of connexin-based gap junctions in pulmonary inflammatory diseases.

Connexins are transmembrane proteins that can generate intercellular communication channels known as gap junctions. They contribute to the direct movement of ions and larger cytoplasmic solutes between various cell types. In the lung, connexins participate in a variety of physiological functions, such as tissue homeostasis and host defence. In addition, emerging evidence supports a role for connexins in various pulmonary inflammatory diseases, such as asthma, pulmonary hypertension, acute lung injury, lung fibrosis or cystic fibrosis. In these diseases, the altered expression of connexins leads to disruption of normal intercellular communication pathways, thus contributing to various pathophysiological aspects, such as inflammation or tissue altered reactivity and remodeling. The present review describes connexin structure and organization in gap junctions. It focuses on connexins in the lung, including pulmonary bronchial and arterial beds, by looking at their expression, regulation and physiological functions. This work also addresses the issue of connexin expression alteration in various pulmonary inflammatory diseases and describes how targeting connexin-based gap junctions with pharmacological tools, synthetic blocking peptides or genetic approaches, may open new therapeutic perspectives in the treatment of these diseases.

Controlled Release Inhalable Polymeric Microspheres for Treatment of Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a chronic ailment of the lungs, exhibiting elevated arterial pressure and vascular resistance; with a mean arterial pressure above 25 mmHg at rest and above 30 mmHg during exercise. It is associated with poor prognosis, and its prevalence is estimated to be 15 cases per one million. The current treatment options for PAH are discussed with the prostanoid class of drugs being the most effective. The latter drugs act by dilating systemic and pulmonary arterial vascular beds and, with sustained long-term usage, altering pulmonary remodelling. They are administered as IV infusions or inhalation solutions. Despite their clinical effectiveness, prostanoids have short half-lives requiring frequent administration of 6-9 times daily and thus suffer from poor compliance. Controlled release inhalation delivery systems for treatment of PAH, ranging from liposomes, biodegradable nano- and microparticles, formation of co-precipitates and complexation with cyclodextrins, are explored. Arising from these formulation strategies, we developed novel polymeric microspheres for inhalation to reduce dosing frequency and improve medication compliance. These microspheres are designed with release modifiers, to reside in the lung which is the site of drug action for a longer duration so as to release the drug slowly and consistently over a prolonged period. This could lead to the development of the first commercially available controlled release inhalation product.

CLOSING OF INTERVENTRICULAR SEPTUM DEFECT IN ONE-STEP AND STEPWISE SURGICAL TREATMENT IN PATIENTS WITH PULMONARY ATRESIA AND AORTO-PULMONARY COLLATERALS

Pulmonary atresia with defect of interventricular septum and collateral pulmonary blood flow refers to complicated congenital malformation of the heart. Surgical treatment represents itself as very difficult task because of anatomical variability of this abnormality. The main problem of surgery is a definitive repair of the defect including correction of maldistributions of pulmonary arterial bed (unifocalization of pulmonary blood flow), reconstruction of outflow tract of the right ventricle and closing of interventricular septum defect. The performance of closing interventricular septum defect could be successful in patients with pulmonary atresia and collateral pulmonary blood flow in case of stepwise and one-step surgical treatment. The combination of maximal number of pulmonary segments and sufficient development of central pulmonary arteries facilitates to progress of assigned task. Patients with the level of pulmonary-arterial index more than 170 mm/m2 and integrity of pulmonary arterial bed, centralization of pulmonary segments (minimum 15) could be considered as a candidate for definite repair of the defect.

Assessment of systemic and pulmonary arterial remodelling in women with systemic sclerosis

Objectives: Systemic sclerosis (SSc) leads to pulmonary circulation dysfunctionand there are some indications of systemic circulation impairment. We evaluated the influence of SSc on the elastic properties of large systemic arterial walls and potential correlations between systemic and pulmonary circulation involvement.Method: We examined 75 consecutive women (mean age 53.13 ± 10.1 years) with confirmed SSc [mean disease duration (DD) 7.1 ± 9.1 years] and 21 age-matched female volunteers (mean age 52.6 ± 8.3 years, ns). Pulse wave velocity (PWV) and transthoracic echocardiography were performed. SSc patients were divided into two groups according to the median of DD: ≤ 3 years (39 patients) and > 3 years (36 patients).Results: Patients with DD > 3 years had higher PWV than those with DD ≤ 3 years and controls (log PWV: 2.23 ± 0.23 vs. 2.13 ± 0.16 and vs. 2.11 ± 0.16 m/s; p = 0.028 and 0.029, respectively). In addition, echocardiographic indices showed impaired right ventricular (RV) function in the patients with DD > 3 years. Also in these SSc patients, PWV correlated with clinical and echocardiographic parameters of pulmonary circulation: age (r = 0.64, p < 0.0001), acceleration time of pulmonary ejection (AcT; r = −0.38, p = 0.021), and tricuspid regurgitation peak gradient (TRPG; r = 0.34, p = 0.04). Multiple linear regression analysis showed that PWV was independently associated with DD (β = 0.22, p = = 0.02), AcT (β = −0.215, p = 0.03), and age (β = 0.44, p < 0.001).Conclusions: In patients with SSc lasting more than 3 years, the disease is characterized by increased stiffness of the large systemic arteries. Longer duration of SSc leads simultaneously to the increased stiffness of the large systemic arteries and to the progressive impairment of RV function and its coupling to the pulmonary arterial bed.

Management of severe pulmonary hypertension in patients undergoing mitral valve surgery.

Pulmonary hypertension (PH) is simply defined as a mean pulmonary artery pressure greater than 25mmHg at rest; however, may result from varying combinations of abnormal pulmonary artery (PA) blood flow, pulmonary vascular resistance (PVR), PA compliance, and pulmonary venous pressure. Mitral regurgitation (MR) allows for partial transmission of systemic arterial pressure into the pulmonary venous system. Mitral stenosis (MS) prevents pulmonary venous drainage into the left ventricle. In either case, the direct result is marked pressurization of the pulmonary venous system, with the primary cause of PH in significant mitral valve disease (PHMVD) being pulmonary venous hypertension (PVH). Chronic and severe PVH may then lead to muscularization of the pulmonary arterial bed, with a rise in PVR and loss of pulmonary arterial compliance that follows ("reactive" pulmonary vascular disease). Right heart dysfunction ensues once the PVR rises and the compliance falls to a point in which the right ventricle (RV) cannot overcome the increased afterload. However, it is worth emphasizing that in the setting of PHMVD, no matter the degree of mismatch between RV afterload and RV function, the root condition in the patient and cause of the PH remains severe MV disease. Without correction of the primary condition, the patient's heart failure (HF), PH, PVR, and RV dysfunction will remain or progress. Moreover, direct PH medical therapies are ineffective and may actually worsen left heart congestion in the setting of unremediated MVD. Therefore, although surgery may be a higher risk in some patients with PHMVD, the potential benefits justify the risks in the majority of cases. If needed, direct medical management of PH is far simpler and more effective once the MVD is corrected, given the degree of left heart congestion often improves dramatically. Therefore, corrective mitral valve intervention should be considered as the main and definitive treatment for these patients.

Pulmonary Arterial Hypertension Associated With Tetralogy of Fallot

Pulmonary arterial hypertension (PAH) is a common postoperative complication in patients with congenital heart disease (CHD). Although the recent clinical classification of pulmonary hypertension divided PAH associated with CHD (PAH-CHD) into several subclasses, the anatomical and hemodynamic features of postoperative PAH-CHD vary enormously. Therefore, it is still difficult to obtain clinical evidence supporting the indication of pulmonary vasodilators for PAH-CHD. We often encounter patients with PAH occurring after surgical treatment of tetralogy of Fallot (TOF), especially patients with major aortopulmonary collateral arteries (MAPCAs). PAH might be caused by pulmonary agenesis, hypoplasia and/or thrombosis, inadequate closure of the ventricular septal defect, relief of the pulmonic stenosis, or an excessively large prior systemic-to-pulmonary shunt. Moreover, patients with TOF and MAPCAs who are diagnosed as inoperable because of the presence of PAH show similar hemodynamic and clinical features to patients with Eisenmenger syndrome. The MAPCAs in these patients usually show hypoplastic and abnormal arborization. Based on our experience, we believe that PAH-targeted therapies are effective in some patients with PAH occurring after surgical treatment of TOF and MAPCAs, especially as an adjunct to percutaneous pulmonary angioplasty. To help classify patients with PAH associated with TOF, especially with MAPCAs, we propose several new subclassifications: "PAH due to hypoplastic pulmonary arterial beds", "PAH due to abnormal pulmonary arborization", or "segmental PAH associated with CHD." A multicenter registry of patients using a unified protocol is essential to explore the indications and efficacy of pulmonary vasodilators for postoperative PAH-CHD.

Lung scintigraphy in the diagnosis of pulmonary embolism: pathophysiological and practical evidence

The protean clinical presentation of pulmonary embolism (PE) is the consequence of a complex series of haemodynamic and respiratory changes caused by the impact of thrombi within the pulmonary vasculature. Haemodynamic changes result from obstruction of the pulmonary arterial bed leading to increased pulmonary vascular resistances and they are manifested clinically as dyspnoea, engorgement of neck veins, and systemic arterial hypotension. Respiratory changes are characterised by lung volume reduction, hypocapnia and hypoxaemia. Reduced lung volume is mainly due to pulmonary consolidation, atelectasis and decreased distension of the thoracic cage due to chest pain. These pathophysiological changes affect both perfusion and ventilation and could explain the low sensitivity of the ventilation/perfusion (V/Q) mismatch scintigraphic approach in diagnosing PE. Acute PE causes redistribution of pulmonary blood flow from non-perfused areas and, to a lesser extent, of ventilation; this is a further factor arguing against the use of V/Q mismatch for the scintigraphic diagnosis of the disease. Hypoxaemia is primarily the consequence of V/Q abnormalities, namely the development of areas with a low V/Q ratio. On a Q scan this can easily be appreciated from hyperperfused lung areas that, by themselves, are a marker for the scintigraphic diagnosis of PE. In conclusion, a Q scan without a V scan, when properly interpreted according to the prospective investigative study of acute pulmonary embolism diagnosis methodology (presence or absence of wedge-shaped perfusion defects) and combined with the formulation of a pre-test clinical probability, can be used in most patients with clinical suspicion of PE, reducing costs and radiation load, increasing the practicality of the examination, and providing diagnostic accuracy comparable to that of CT angiography.

Pulmonary arteriovenous malformations: haemodynamics and shunt closure

The first description of pulmonary arteriovenous malformations (PAVM) was made already in 1897 by Churton [1]. PAVM are abnormal vascular structures that connect the pulmonary arterial bed directly to the pulmonary venous bed, thereby bypassing the pulmonary capillaries and resulting in an intrapulmonary shunt which, depending on number and size of the PAVM, may result in arterial desaturation and paradoxical systemic embolisation [2]. Because the PAVM are thin-walled vascular structures, they are prone to rupture, resulting in haemoptysis. A major step forward in the treatment of PAVM was the use of percutaneous transcatheter embolisation, using femoral venous access [3]. This procedure is safe and reduces the risk of paradoxical thromboembolisation and haemoptysis. Moreover, by reducing shunt flow, arterial oxygen saturation increases. Although percutaneous closure of PAVM has been performed for years, and a surprisingly small effect on pulmonary haemodynamics has been shown [4], the study by Vorselaars and co-workers in the present issue of the Netherlands Heart Journal [5] is the first to investigate the immediate consequences of PAVM closure on systemic haemodynamics. Using Finapres technology, which derives changes in stroke volume and systemic pressure from the pressure wave form as measured on a finger, they describe an overall decrease in stroke volume and cardiac output that corresponds in magnitude with the overall decrease in shunt fraction. This decrease in stroke volume is similar to the decrease in stroke volume, as measured directly by right heart catheterisation, observed in a case study at 4 months follow-up after PAVM [6]. It was speculated that such a decrease in stroke volume helped to explain the absence of an increase in pulmonary artery pressures [4], despite the fact that pulmonary vascular resistance should obviously increase as a consequence of the closure of the low resistance PAVM. The mechanism behind the observed decrease in stroke volume is unclear. It could be speculated that shunt closure and the accompanying increase in pulmonary vascular resistance result in a slight increase in right ventricular afterload, which limits right ventricular output. It is, however, more likely to assume that oxygen is regulated to fulfil the oxygen demand of peripheral tissues; shunt closure increases the oxygen content of arterial blood and hence for the same oxygen delivery, in the presence of improved oxygenation, less flow is required. The latter explanation is in accordance with the observation that the shunt fraction prior to embolisation (14 %) is similar in magnitude to the decrease in cardiac output (10 %) [5]. As pulmonary artery pressure increases during exercise, the driving pressure for the shunt flow increases, resulting in an increased shunt flow, which is accompanied by augmented arterial desaturation during exercise [7–9]. However, exercise capacity is surprisingly well-maintained in patients with PAVM, potentially due to the capability of the right heart to deal with volume overload. Indeed, although most patients report an increased exercise capacity and quality of life following shunt closure, an objective increase in exercise capacity is not found in all patients [10]. It is possible that changes in pulmonary and systemic haemodynamics upon shunt closure, which are relatively small under resting conditions, are exacerbated during exercise. Thus, while the study by Vorselaars in the present issue of the Netherlands Heart Journal provides an important observation in resting patients [5], a comprehensive evaluation of shunt flow, pulmonary and systemic haemodynamics and oxygen saturation during exercise prior to and following shunt closure would be of great benefit to enhance our understanding of the implications of shunt closure on exercise capacity.

Metabolomics Reveals Metabolite Changes in Acute Pulmonary Embolism

Pulmonary embolism (PE) is a common cardiovascular emergency which can lead to pulmonary hypertension (PH) and right ventricular failure as a consequence of pulmonary arterial bed occlusion. The diagnosis of PE is challenging due to nonspecific clinical presentation, which results in relatively high mortality. Moreover, the pathological factors associated with PE are poorly understood. Metabolomics can provide new highlights which can help in the understanding of the processes and even propose biomarkers for its diagnosis. In order to obtain more information about PE and PH, acute PE was induced in large white pigs and plasma was obtained before and after induction of PE. Metabolic fingerprints from plasma were obtained with LC-QTOF-MS (positive and negative ionization) and GC-Q-MS. Data pretreatment and statistical analysis (uni- and multivariate) were performed in order to compare metabolic fingerprints and to select the metabolites that showed higher loading for the classification (28 from LC and 19 from GC). The metabolites found differentially distributed among groups are mainly related to energy imbalance in hypoxic conditions, such as glycolysis-derived metabolites, ketone bodies, and TCA cycle intermediates, as well as a group of lipidic mediators that could be involved in the transduction of the signals to the cells such as sphingolipids and lysophospholipids, among others. Results presented in this report reveal that combination of LC-MS- and GC-MS-based metabolomics could be a powerful tool for diagnosis and understanding pathophysiological processes due to acute PE.

The influence of gap junction network complexity on pulmonary artery smooth muscle reactivity in normoxic and chronically hypoxic conditions

Experiments on intrapulmonary arteries (IPAs) isolated from rats maintained in normoxia and chronic hypobaric hypoxia showed that in normoxia, the IPA contractile sensitivity to KCl was not modified by gap junction inhibition. In contrast, chronic hypoxia induced an endothelium-independent hypersensitivity, which was suppressed by gap junction inhibition. For the theoretical analysis of these results, we developed a model of interconnected myocytes. Given that smooth muscle cells in IPAs are known to communicate via gap junctions, we regard the cytoarchitecture of the IPA as a spatial network, in which nodes represent individual smooth muscle cells and the links signify intercellular communication. A single-cell model that drives the dynamics of individual nodes includes the major elements of voltage-dependent Ca(2+) signalling. In addition, interindividual variability of SMCs is introduced by distributing the reversal potentials for K(+). Cell-to-cell connection consists of passive Ca(2+) diffusion and electrical coupling, and connection between cells is determined by the topology of the intercellular network. Model predictions indicate that the experimental results can be explained by topological modifications and not by changes in the number of gap junctions. According to the model, in normoxia the myocytes are connected in a complex network, whereas chronic hypoxia is related to loss of complexity, leading to hypersensitivity. Our results thus indicate that chronic hypoxia entails gap junction network rearrangements, leading to disturbances in the intercellular communication pathways.

Giant aorto-pulmonary collaterals in pulmonary atresia and ventricular septal defect

The association of pulmonary atresia and ventricular septal defect (PA/VSD) can be considered the most severe form of tetralogy of Fallot. The main feature of this congenital heart disease is represented by discontinuity between the right ventricle and pulmonary trunk or its branches; the anatomy of central pulmonary arteries is often abnormal, consequently the type and the amount of sources of pulmonary blood flow are variable. Due to evolution in surgical techniques, definitive correction is now also considered in more complex cases. A small rate of unoperated patients with PA/VSD can survive until adulthood and the arterial blood supply to the lungs, provided by major aorto-pulmonary collateral arteries (MAPCAs), is one of the main determinants of survival. We report two unoperated cases of PA/VSD and MAPCAs with long-term survival. Giant MAPCAs can occasionally be found by chest radiography in adults with unrepaired PA/VSD. Moreover, non-invasive assessment of the pulmonary arterial bed with computer tomography or MRI is helpful in these patients during follow-up. Finally, we discuss the use of oral anticoagulants and/or 5-phosphodiesterase inhibitors in these patients.

Left ventricular dysfunction with pulmonary hypertension: part 2: prognosis, noninvasive evaluation, treatment, and future research.

Pulmonary hypertension (PH) secondary to left-sided heart disease (Group 2 PH) is a frequent complication of heart failure (HF) that worsens exercise capacity, risk for hospitalization, and survival independent of left-ventricular ejection fraction (LVEF) or stage of HF. Increased pulmonary artery pressure (PAP) in patients with HF often represents a combination of increased left-sided filling pressures (passive component) and elevated pulmonary vascular resistance (PVR) attributable to functional and structural abnormalities of the pulmonary vascular bed (reactive component). The latter may be reversible with standard HF treatment in the earlier stages, when remodeling of the pulmonary vasculature has not set in, and abnormalities in pulmonary arterial tone are the major driver for elevated PVR. However, chronic exposure to elevated pulmonary capillary wedge pressure (PCWP) may lead to permanent changes in the pulmonary arterial bed (irreversible or fixed PH).1 Considering that a number of drug classes have successfully modified the natural history of pulmonary arterial hypertension (Group 1 PH) and demonstrated that intervention is possible even after pulmonary vascular remodeling has occurred,2 Group 2 PH is a natural target for screening and potential intervention in patients with HF. In the second part of this 2-part review, we discuss the prognostic impact of PH in HF, the contemporary diagnostic and evaluation approaches, the current evidence from clinical studies in Group 2 PH, the challenges of appropriate patient selection in clinical trials, and potential ways to overcome these challenges in trial designs. ### Echocardiographic Studies Studies using either right heart catheterization (RHC) or echocardiography for determination of PAP have consistently shown that PH considerably worsens prognosis in HF. Abramson et al3 first reported that tricuspid regurgitation jet velocity >2.5 m/s was associated with 3.4 times higher mortality in 108 patients with dilated cardiomyopathy followed for up to 28 months; hospitalization rate for HF was …

Pulmonary Arterial Bed Reperfusion Induces Regression of Distal Vasculopathy in a Chronic Thromboembolic Pulmonary Hypertension Piglet Model

Purpose Chronic Thromboembolic Pulmonary Hypertension (CTEPH) is due to occlusion of pulmonary arteries (PA) and to distal pulmonary vasculopathy in occluded and non-occluded territories. Persistent pulmonary hypertension, the main complication after pulmonary endarterectomy, may be due to remaining distal pulmonary vasculopathy.The aim was to assess whether distal pulmonary vasculopathy regresses in occluded and non-occluded territories after pulmonary endarterectomy. Methods and Materials CTEPH was induced in piglets 5 weeks after left PA ligation followed by weekly right lower lobe artery embolization. Animals were studied 5 weeks later, after reperfusion of the left PA mimicking pulmonary endarterectomy (R-HYPPE group, n=5) or not (HYPPE group, n=5). Left lung (LL) was studied as occluded territories and right upper lobe (RUL) as non-occluded territories. All groups were compared to Sham operated animals (n=5). Results At 5 weeks, mean PA pressure (mPAP) and indexed total pulmonary resistances (iTPR) increased in HYPPE and R-HYPPE groups when compared to baseline values (p Conclusions Distal pulmonary vasculopathy regresses after surgical treatment of CTEPH in previously occluded and non-occluded territories.

Flash Pulmonary Edema in Multiple Sclerosis

BackgroundNeurogenic pulmonary edema (NPE) occurs in the setting of an acute neurological insult and in the absence of a primary cardiopulmonary cause. No unifying theory on NPE pathogenesis exists. NPE triggered by a discrete neurological lesion is rare, but such cases offer valuable insight into NPE pathogenesis. ObjectiveTo describe an unusual and instructive case of NPE in multiple sclerosis. Case ReportA young woman with multiple sclerosis presented to the Emergency Department in acute respiratory failure. She was cyanotic centrally, hypertensive, and tachycardic. The chest X-ray study suggested pulmonary edema. She required non-invasive mechanical ventilation for 12 h. Echocardiography revealed left ventricular hypokinesis. The asymmetrical pulmonary infiltrate raised the suspicion of pneumonia; she was given intravenous antibiotics. By 36 h, she had persistent dyspnea, paroxysmal tachycardia, nausea, and facial flushing; carcinoid syndrome was excluded. By 48 h, she had facial numbness and ataxia. Magnetic resonance imaging (MRI) revealed a demyelinating lesion at the rostromedial medulla. Her symptoms promptly resolved with intravenous steroids, as did the perilesional edema on follow-up MRI. ConclusionLife-threatening pulmonary edema can complicate medullary demyelination. Lack of awareness of this diagnostic possibility and an asymmetrical pulmonary infiltrate culminated in diagnostic delay in this case. The case provides clinico-radiological evidence of the pathogenic link between medullary lesions and NPE. The pathogenesis is likely to rely on lesion involvement of the nucleus tractus solitarius or its immediate pathways. Non-uniform vasoconstriction of the pulmonary arterial bed might account for the other peculiarity of this case: the asymmetrical pulmonary infiltrate. Timely diagnosis of NPE is essential because the condition is best managed by nullifying the “neurogenic” trigger.

World Health Organization Pulmonary Hypertension Group 2: Pulmonary hypertension due to left heart disease in the adult—a summary statement from the Pulmonary Hypertension Council of the International Society for Heart and Lung Transplantation

Pulmonary hypertension associated with left heart disease is the most common form of pulmonary hypertension encountered in clinical practice today. Although frequently a target of therapy, its pathophysiology remains poorly understood and its treatment remains undefined. Pulmonary hypertension in the context of left heart disease is a marker of worse prognosis and disease severity, but whether its primary treatment is beneficial or harmful is unknown. An important step to the future study of this important clinical problem will be to standardize definitions across disciplines to facilitate an evidence base that is interpretable and applicable to clinical practice. In this current statement, we provide an extensive review and interpretation of the current available literature to guide current practice and future investigation. At the request of the Pulmonary Hypertension (PH) Council of the International Society for Heart and Lung Transplantation (ISHLT), a writing group was assembled and tasked to put forth this document as described above. The review process was facilitated through the peer review process of the Journal of Heart and Lung Transplantation and ultimately endorsed by the leadership of the ISHLT PH Council.