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Background: Pulmonary endarterectomy (PEA) is a curative procedure for patients with chronic thromboembolic pulmonary hypertension. Body composition and exercise capacity have been associated with adverse outcomes in patients undergoing cardiothoracic operations, but their significance with PEA is unclear. We evaluated the association of body composition and 6-minute walk distance (6MWD) with disease severity, hospital length of stay, discharge disposition, and postoperative functional recovery., Methods: This was a retrospective, single-center cohort study of patients who underwent PEA (January 2014-December 2017). Body composition (skeletal muscle mass and adiposity cross-sectional area) was quantified using thoracic computed tomography with sliceOmatic (TomoVision, Magog, QC, Canada) software. Body mass index was calculated. Association of body composition measures and 6MWD with clinical outcomes was evaluated using multivariable regression models., Results: The study included 127 patients (42% men), aged 58 ± 14 years; body mass index was 31 ± 7 kg/m 2 and 6MWD was 361 ± 165 m). Muscle and 6MWD were associated with disease severity measures. Of those surviving hospitalization (n = 125), a greater 6MWD was associated with a shorter hospital stay (1.9 median days per 100 m; p < .001) and higher likelihood of being discharged directly home from hospital (odds ratio, 2.1 per 100 m; P = .004), independent of age, sex, and body mass index. Those with a lower preoperative 6MWD (per 100 m) had a greater increase in their postoperative 6MWD (52 m; P < .0001), independent of age, sex, and body mass index. Body composition measures were not associated with hospital outcomes or exercise capacity in the first year postoperatively., Conclusions: Exercise capacity was a more prognostic marker of PEA outcomes compared with body composition. Future research is needed to explore pre-PEA rehabilitation strategies., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Quantitative measurement of lung perfusion is a promising tool to evaluate lung pathophysiology as well as to assess disease severity and monitor treatment. However, this novel technique has not been adopted clinically due to various technical and physiological challenges; and it is still in the early developmental phase where the correlation between lung pathophysiology and perfusion maps is being explored. The purpose of this research work is to quantify the impact of pulmonary artery occlusion on lung perfusion indices using lung dynamic perfusion CT (DPCT). We performed Lung DPCT in ten anesthetized, mechanically ventilated juvenile pigs (18.6-20.2 kg) with a range of reversible pulmonary artery occlusions (0%, 40-59%, 60-79%, 80-99%, and 100%) created with a balloon catheter. For each arterial occlusion, DPCT data was analyzed using first-pass kinetics to derive blood flow (BF), blood volume (BV) and mean transit time (MTT) perfusion maps. Two radiologists qualitatively assessed perfusion maps for the presence or absence of perfusion defects. Perfusion maps were also analyzed quantitatively using a linear segmented mixed model to determine the thresholds of arterial occlusion associated with perfusion derangement. Inter-observer agreement was assessed using Kappa statistics. Correlation between arterial occlusion and perfusion indices was evaluated using the Spearman-rank correlation coefficient. Our results determined that perfusion defects were detected qualitatively in BF, BV and MTT perfusion maps for occlusions larger than 55%, 80% and 55% respectively. Inter-observer agreement was very good with Kappa scores > 0.92. Quantitative analysis of the perfusion maps determined the arterial occlusion threshold for perfusion defects was 50%, 76% and 44% for BF, BV and MTT respectively. Spearman-rank correlation coefficients between arterial occlusion and normalized perfusion values were strong (- 0.92, - 0.72, and 0.78 for BF, BV and MTT, respectively) and were statically significant (p < 0.01). These findings demonstrate that lung DPCT enables quantification and stratification of pulmonary artery occlusion into three categories: mild, moderate and severe. Severe (occlusion ≥ 80%) alters all perfusion indices; mild (occlusion < 55%) has no detectable effect. Moderate (occlusion 55-80%) impacts BF and MTT but BV is preserved.

Background Resting right heart catheterization can assess both left heart filling and pulmonary artery (PA) pressures to identify and classify pulmonary hypertension. Although exercise may further elucidate hemodynamic abnormalities, current pulmonary hypertension classifications do not consider the expected interrelationship between PA and left heart filling pressures. This study explored the utility of this relationship to enhance the classification of exercise hemodynamic phenotypes in pulmonary hypertension. Methods and Results Data from 36 healthy individuals (55, 50-60 years, 50% male) and 85 consecutive patients (60, 49-71 years, 48% male) with dyspnea and/or suspected pulmonary hypertension of uncertain etiology were analyzed. Right heart catheterization was performed at rest and during semiupright submaximal cycling. To classify exercise phenotypes in patients, upper 95% CIs were identified from the healthy individuals for the change from rest to exercise in mean PA pressure over cardiac output (ΔmPAP/ΔCO ≤3.2 Wood units [WU]), pulmonary artery wedge pressure over CO (ΔPAWP/ΔCO ≤2 mm Hg/L per minute), and exercise PA pulse pressure over PAWP (PP/PAWP ≤2.5). Among patients with a ΔmPAP/ΔCO ≤3.2 WU, the majority (84%) demonstrated a ΔPAWP/ΔCO ≤2 mm Hg/L per minute, yet 23% demonstrated an exercise PP/PAWP >2.5. Among patients with a ΔmPAP/ΔCO >3.2 WU, 37% had an exercise PP/PAWP >2.5 split between ΔPAWP/ΔCO groups. Patients with normal hemodynamic classification declined from 52% at rest to 36% with exercise. Conclusions The addition of PP/PAWP to classify exercise hemodynamics uncovers previously unrecognized abnormal phenotypes within each ΔmPAP/ΔCO group. Our study refines abnormal exercise hemodynamic phenotypes based on an understanding of the interrelationship between PA and left heart filling pressures.

Background and Objective: Osteopontin (OPN) is a pleiotropic cytokine involved in the proliferation of pulmonary artery smooth muscle cells (PA-SMC). OPN is upregulated in the lungs of patients with pulmonary hypertension (PH) associated with pulmonary fibrosis, suggesting that the lung is a source of OPN. We hypothesized that OPN lung expression is elevated in Group I pulmonary arterial hypertension (PAH) and is correlated to haemodynamics., Methods: Microarray analysis (Affymetrix) was performed after RNA was extracted from explanted lungs in 15 patients with Group I PAH who underwent lung transplantation (LTx) and 11 normal controls. PA pressure levels were recorded intraoperatively, immediately before starting LTx. Serum OPN levels were measured in subjects with PAH, Group II PH and normal controls on the day of right heart catheterization., Results: OPN was among the top five upregulated genes in PAH compared to normal controls, which was confirmed by reverse transcription polymerase chain reaction (RT-PCR). OPN expression was similar and equally elevated in different subtypes of PAH. A strong significant correlation was observed between mean pulmonary arterial pressure and OPN gene expression. Ingenuity pathway analysis showed the involvement of OPN in functions and networks relevant to angiogenesis, cell death and proliferation of PA-SMC. OPN serum levels did not differ in subjects with Group I PAH and Group II PH., Conclusion: In the lungs of patients with severe PAH, OPN is highly expressed and the level of expression is significantly correlated to disease severity. OPN may play an important role in the vascular remodelling process of PAH., (© 2019 Asian Pacific Society of Respirology.)

Aims: The assumption of equivalence between right ventricular (RV) and pulmonary arterial systolic pressure is fundamental to several assessments of RV or pulmonary vascular haemodynamic function. Our aims were to (i) determine whether systolic pressure gradients develop across the RV outflow tract in healthy adults during exercise, (ii) examine the potential correlates of such gradients, and (iii) consider the effect of such gradients on calculated indices of RV function., Methods and Results: Healthy untrained and endurance-trained adult volunteers were studied using right-heart catheterization at rest and during submaximal cycle ergometry. RV and pulmonary artery (PA) pressures were simultaneously transduced, and the cardiac output was determined by thermodilution. Systolic pressures, peak and mean gradients, and indices of chamber, vascular, and valve function were analysed offline. Summary data are reported as mean ± standard deviation or median (interquartile range). No significant RV outflow tract gradients were observed at rest [mean gradient = 4 (3-5) mmHg], and the calculated effective orifice area was 3.6 ± 1.0 cm2. The increase in right ventricular systolic pressure during exercise was greater than the PA systolic pressure. Accordingly, mean gradients were developed during light exercise [8 (7-9) mmHg] and increased during moderate exercise [12 (9-14) mmHg, P < 0.001]. The magnitude of the mean gradient was linearly related to the cardiac output (r2 = 0.70, P < 0.001)., Conclusions: In healthy adults without pulmonic stenosis, systolic pressure gradients develop during exercise, and the magnitude is related to the blood flow rate.

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is still largely underdiagnosed in the general population. Although transthoracic echocardiogram (TTE) is recommended to screen for CTEPH, it may not detect patients with chronic thromboembolic disease (CTED) and mild or exercise-induced pulmonary hypertension (PH) who could also benefit from pulmonary endarterectomy (PEA)., Methods: All patients referred to our CTEPH program with persistent mismatched perfusion defects on ventilation-perfusion (VQ) scan between January 2005 and June 2015 were divided into three groups according to TTE and right heart catheterization (RHC) as follows: (1) typical CTEPH group (PH on RHC and TTE), (2) TTE-negative (neg) CTEPH group (PH on RHC, but not TTE), or (3) CTED group (no PH on RHC and TTE)., Results: Of 225 patients with abnormal VQ scans, 188 (84%) had typical CTEPH, 15 had TTE-neg CTEPH, and 22 had CTED. PEA was performed in 179 patients (80%). Reasons for exclusion in CTEPH patients included primarily distal disease (n = 11) and comorbidities (n = 10). In contrast, the absence of functional limitation was the main cause of exclusion in CTED patients (75% versus 3% in CTEPH patients, p < 0.0001). The 90-day mortality rate after PEA was 4% in the typical CTEPH group and 0% in the TTE-neg CTEPH and CTED groups. Pulmonary arterial pressures and functional class significantly improved after PEA in all three groups., Conclusions: Patients with mild CTEPH can benefit from PEA, but may not be detected by TTE. Symptomatic patients with functional limitation and persistent mismatched perfusion defects on VQ scan should undergo further investigations with pulmonary angiogram and RHC., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Chronic thromboembolic pulmonary hypertension (CTEPH) is an underdiagnosed potential complication of acute or recurrent pulmonary thromboembolic disease. Multiple studies suggest that up to 5% of patients with acute pulmonary thromboembolic disease go on to develop CTEPH. The prognosis of untreated CTEPH is poor, but advances in medical and surgical treatments over the past few decades have improved patient outcomes. The gold standard and curative treatment for CTEPH is pulmonary endarterectomy; however, some patients are inoperable and others who have undergone pulmonary endarterectomy experience persistent or recurrent pulmonary hypertension despite medical therapy. In recent years, balloon pulmonary angioplasty has emerged as a primary and adjunctive treatment for these CTEPH patients at expert or specialized centers. This review outlines an approach to balloon pulmonary angioplasty for CTEPH, including clinical presentation and evaluation; patient selection and indications; treatment planning; equipment and technique; overcoming technical challenges; recognition and management of complications; postprocedural care and clinical follow-up; and expected outcomes., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: The clinical and prognostic significance of 'exaggerated' elevations in pulmonary artery wedge pressure (PAWP) during symptom-limited exercise testing is increasingly recognised. However, the paucity of normative data makes the identification of abnormal responses challenging. Our objectives was to describe haemodynamic responses that reflect normal adaptation to submaximal exercise in a group of community-dwelling, older, non-dyspnoeic adults., Methods: Twenty-eight healthy volunteers (16 men/12 women; 55±6 years) were studied during rest and two consecutive stages of cycle ergometry, at targeted heart rates of 100 bpm (light exercise) and 120 bpm (moderate exercise). Right-heart catheterisation was performed to measure pulmonary artery pressures, both early (2 min) and after sustained (7 min) exercise at each intensity., Results: End-expiratory PAWP at baseline was 11±3 mm Hg and increased to 22±5 mm Hg at early-light exercise (p<0.01). At sustained-light exercise, PAWP declined to 17±5 mm Hg, remaining elevated versus baseline (p<0.01). PAWP increased again at early-moderate exercise to 20±6 mm Hg but did not exceed the values observed at early-light exercise, and declined further to 15±5 mm Hg at sustained-moderate exercise (p<0.01 vs baseline). When analysed at 30 s intervals, mean and diastolic pulmonary artery pressures peaked at 180 (IQR=30) s and 130 (IQR=90) s, respectively, and both declined significantly by 420 (IQR=30) s (both p<0.01) of light exercise. Similar temporal patterns were observed at moderate exercise., Conclusions: The range of PAWP responses to submaximal exercise is broad in health, but also time-variant. PAWP may routinely exceed 20 mm Hg early in exercise. Initial increases in PAWP and mean pulmonary artery pressures do not necessarily reflect abnormal cardiopulmonary physiology, as pressures may normalise within a period of minutes., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: The outcome of patients with chronic thromboembolic pulmonary hypertension (CTEPH) undergoing pulmonary endarterectomy (PEA) after urgent hospitalization for decompensated right heart failure (DRHF) remains unclear., Methods: Among 120 consecutive patients undergoing PEA, 16 (13%) presented with a history of urgent hospitalization for DRHF (severe RHF group). This group was compared with the remaining 104 patients presenting with total peripheral vascular resistance (TPR) < 1,200 dynes · sec · cm(-5) (n = 78, control group) and >1,200 dynes · sec · cm(-5) (n = 26, high TPR group)., Results: DRHF occurred predominantly in patients with TPR > 1,200 dynes · sec · cm(-5) (prevalence of 32% vs 5% in patients with TPR < 1,200 dynes · sec · cm(-5), p < 0.0001). The overall in-hospital mortality after PEA was 4% (n = 5). All deaths occurred in patients with TPR > 1,200 dynes · sec · cm(-5) and DRHF. The proportion of patients with residual PH immediately after surgery was higher in the high TPR group (50%) and severe RHF group (56%) compared with the control group (29%; p = 0.04). In multivariate analysis, risk factors for residual PH after surgery were TPR > 1,200 dynes · sec · cm(-5), Jamieson disease Type III-IV, and female gender. A history of DRHF by itself was not a risk factor for residual PH after PEA. The overall 5-year survival was 87%. After a median follow-up of 20 months, the proportion of patients receiving medical therapy for residual PH was higher in patients with post-operative mean pulmonary artery pressure ≥35 mm Hg (61% vs 9%, p = 0.0007)., Conclusions: DRHF occurs more frequently in patients with TPR > 1,200 dynes · sec · cm(-5), increasing the operative risk in these patients. The outcome of patients with high TPR in the absence of DRHF is excellent. However, patients with residual mean pulmonary artery pressure ≥35 mm Hg frequently receive pulmonary hypertension therapy after PEA., (Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Although multiple gene and protein expression have been extensively profiled in human pulmonary arterial hypertension (PAH), the mechanism for the development and progression of pulmonary hypertension remains elusive. Analysis of the global metabolomic heterogeneity within the pulmonary vascular system leads to a better understanding of disease progression. Using a combination of high-throughput liquid-and-gas-chromatography-based mass spectrometry, we showed unbiased metabolomic profiles of disrupted glycolysis, increased TCA cycle, and fatty acid metabolites with altered oxidation pathways in the human PAH lung. The results suggest that PAH has specific metabolic pathways contributing to increased ATP synthesis for the vascular remodeling process in severe pulmonary hypertension. These identified metabolites may serve as potential biomarkers for the diagnosis of PAH. By profiling metabolomic alterations of the PAH lung, we reveal new pathogenic mechanisms of PAH, opening an avenue of exploration for therapeutics that target metabolic pathway alterations in the progression of PAH.

Background: Pulmonary endarterectomy (PEA) is the treatment of choice for patients with chronic thromboembolic pulmonary hypertension (PH). However, this surgery remains performed in few experienced centres only. The goal of the study is to review our overall experience since the implementation of our program in August 2005., Methods: Review all patients referred to our program between August 2005 and July 2011., Results: Among 84 consecutive patients referred to our program, 52 patients underwent elective PEA and 6 emergency PEA. After PEA, 74% patients were extubated within 2 days, 71% were discharged from the intensive care unit within 4 days and 64% were discharged from hospital within 15 days. One patient undergoing elective surgery and 2 patients undergoing emergency surgery died within 30 days of surgery for an operative mortality of 1.9% after elective pulmonary endarterectomy and an overall operative mortality of 5.2%, when the 6 emergency operative cases were included. The total pulmonary vascular resistance decreased from 965±445 to 383±162 dynes per second per cm(-5) and was associated with significant improvement in World Health Organization/New York Heart Association (WHO/NYHA) functional class, 6 minutes walk distance, echocardiographic findings, and brain natriuretic peptide level at 6 months after PEA. After a median follow-up of 23 months (1-65 months), 3 patients had to be started on targeted PH therapy for deterioration of their (WHO/NYHA) functional class., Conclusions: Elective PEA can be performed with limited risk, and results in excellent early and long-term outcome. All patients diagnosed with chronic thromboembolic PH should be referred for consideration of PEA in a specialized centre., (Copyright © 2011 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Despite a major reduction in pulmonary vascular resistance (PVR), patients with chronic thromboembolic pulmonary hypertension (CTEPH) do not always return to functional New York Heart Association (NYHA) class I after pulmonary endarterectomy (PEA). We hypothesized that residual abnormal compliance (Cp) after PEA is associated with incomplete functional recovery despite major improvement in PVR., Methods: The Cp of 34 consecutive patients with CTEPH was assessed before and after PEA. Cp was defined as stroke volume over pulse pressure and was divided into three groups: < 2.0 mL/mm Hg, 2.0 to 3.9 mL/mm Hg, and ≥ 4 mL/mm Hg. To establish predicted Cp after PEA, we collected an age- and gender-matched control group., Results: Before PEA, Cp was < 2.0 mL/mm Hg in 82% (n = 28) of the patients. After PEA, Cp improved to 2.0 to 3.9 mL/mm Hg in 11 patients and to ≥ 4.0 mL/mm Hg in 14 patients. Residual Cp < 2.0 mL/mm Hg was associated with delayed extubation and prolonged hospital stay. At 3 months' follow-up, 13 patients (93%) with postoperative Cp ≥ 4.0 mL/mm Hg returned to NYHA class I, whereas 45% with Cp of 2.0 to 3.9 mL/mm Hg and 25% with Cp < 2.0 mL/mm Hg returned to NYHA class I. In multivariate analysis, postoperative Cp ≥ 4.0 mL/mm Hg was the only predictor of functional recovery to NYHA class I. The group of patients with postoperative Cp ≥ 4.0 mL/mm Hg was also the only group to achieve hemodynamic parameters similar to those of their matched control subjects., Conclusions: Postoperative Cp is an important predictor of recovery after PEA. Residual vascular stiffness after PEA can be associated with persistent functional limitation and lack of complete remodeling of the right ventricle.

Blood transfusion requirements were reviewed for a consecutive series of 25 patients undergoing elective pulmonary endarterectomy (PEA) between August 2005 and March 2009 in our institution. Patients were divided into two groups based on the implementation of a conservative blood transfusion algorithm that combined antifibrinolytic therapy, intraoperative blood sequestration, blood salvage and lack of correction of coagulation parameters in the absence of ongoing bleeding. Despite similar perioperative coagulation profiles in the two groups, the introduction of a conservative blood transfusion algorithm was associated with a significant increase in the number of patients receiving no homologous blood products. Of 16 patients who underwent surgery after the introduction of the algorithm, nine (56%) required no homologous blood products and five (31%) required one or two units of homologous red blood cells only. The international normalized ratio normalized within six to 12 hours after discontinuation of cardiopulmonary bypass without transfusion of fresh frozen plasma or platelets in 13 of the 16 patients. In conclusion, a conservative blood transfusion strategy allows PEA to be safely performed with no or minimal blood product transfusions in a majority of patients despite deep hypothermic circulatory arrest.

Introduction: Idiopathic pulmonary arterial hypertension (IPAH) is characterized by pulmonary arteriolar narrowing and degeneration associated with in situ thrombosis. We hypothesized that microvascular endothelial injury and apoptosis may be an initiating mechanism in IPAH. Endothelial apoptosis generates endothelial microfragments (EMF), which can activate platelets. Platelets release both VEGF and angiostatin, which depending the balance can inhibit or induce endothelial apoptosis, respectively., Materials and Methods: We measured EMFs from blood of IPAH patients as index of endothelial cell apoptosis/injury and levels of pro- and anti- EC apoptotic factors found in platelets. EMFs and platelets in blood samples from control subjects and patients with IPAH were measured using a 4-color flow cytometry protocol, and platelet levels of VEGF and angiostatin were determined by ELISAs and immunoblotting., Results: Compared to controls, IPAH patients exhibited higher numbers of circulating EMFs and more activated/apoptotic platelets. IPAH patients also exhibited higher levels of platelet angiostatin; however, no significant difference was detected in platelet VEGF levels between the two groups., Conclusions: These results are consistent with an increase in EC dysfunction in patients with IPAH, possibly contributing to the progression of IPAH and its associated thrombosis., (Copyright 2009 Elsevier Ltd. All rights reserved.)

The role of thrombotic arteriopathy in the pathophysiology of idiopathic pulmonary arterial hypertension (IPAH) and the use of anticoagulants in the treatment of IPAH are currently controversial issues. This article reviews the evidence for a role of vascular thrombosis in the pathophysiology of IPAH. There is sufficient biological rationale to support the notion that thrombotic arteriopathy is an important pathophysiologic feature of pulmonary arterial hypertension (PAH) and that its progression materially contributes to disease progression. To date, the data from observational studies suggest that anticoagulation with warfarin is an effective intervention in patients with IPAH. Its efficacy in other causes of PAH remains speculative.

Mutations in the bone morphogenetic protein (BMP) receptor-2 (BMPR2) have been found in patients with idiopathic pulmonary arterial hypertension (IPAH); however, the mechanistic link between loss of BMPR2 signaling and the development of pulmonary arterial hypertension is unclear. We hypothesized that, contrary to smooth muscle cells, this pathway promotes survival in pulmonary artery endothelial cells (ECs) and loss of BMPR2 signaling will predispose to EC apoptosis. ECs were treated with BMP-2 or BMP-7 (200 ng/mL) for 24 hours in regular or serum-free (SF) medium, with and without addition of tumor necrosis factor alpha, and apoptosis was assessed by flow cytometry (Annexin V), TUNEL, or caspase-3 activity. Treatment for 24 hours in SF medium increased apoptosis, and both BMP-2 and BMP-7 significantly reduced apoptosis in response to serum deprivation to levels not different from serum controls. Transfection with 5 microg of small interfering RNAs for BMPR2 produced specific gene silencing assessed by RT-PCR and Western blot analysis. BMPR2 gene silencing increased apoptosis almost 3-fold (P=0.0027), even in the presence of serum. Circulating endothelial progenitor cells (EPCs) isolated from normal subjects or patients with IPAH were differentiated in culture for 7 days and apoptosis was determined in the presence and absence of BMPs. BMP-2 reduced apoptosis induced by serum withdrawal in EPCs from normal subjects but not in EPCs isolated from patients with IPAH. These results support the hypothesis that loss-of-function mutations in BMPR2 could lead to increased pulmonary EC apoptosis, representing a possible initiating mechanism in the pathogenesis of pulmonary arterial hypertension.

Exercise imposes increased pulmonary vascular afterload based on rises in pulmonary artery (PA) wedge pressure, declines in PA compliance, and resistance‐compliance time. In health, afterload stress stabilizes during steady‐state exercise. Our objective was to examine alterations of these exercise‐associated stresses in states of pre‐ and post‐capillary pulmonary hypertension (PH). PA hemodynamics were evaluated at rest, 2 and 7 min of steady‐state exercise at moderate intensity in patients who exhibited Pre‐capillary (n = 22) and post‐capillary PH (n = 22). Patients with normal exercise hemodynamics (NOR‐HD) (n = 32) were also studied. During exercise in all groups, PA wedge pressure increased at 2 min, with no further change at 7 min. In post‐capillary PH and NOR‐HD, increases in PA diastolic pressure and diastolic pressure gradient remained stable at 2 and 7 min of exercise, while in pre‐capillary PH, both continued to increase at 7 min. The behavior of the diastolic pressure gradient was linearly related to the duration of resistance‐compliance time at rest (r2 = 0.843) and exercise (r2 = 0.760). Exercise resistance‐compliance time was longer in pre‐capillary PH associated with larger increases in diastolic pressure gradient. Conversely, resistance‐compliance time was shortest in post‐capillary PH compared to pre‐capillary PH and NOR‐HD and associated with limited increases in exercise diastolic pressure gradient. During steady‐state, modest‐intensity exercise‐specific patterns of pulmonary vascular afterload responses were observed in pre‐ and post‐capillary PH relative to NOR‐HD. Longer resistance‐compliance time related to greater increases in PA diastolic pressure and diastolic pressure gradients in pre‐capillary PH, while shorter resistance‐compliance time appeared to limit these increases in post‐capillary PH. [ABSTRACT FROM AUTHOR]

Despite an expanded armamentarium of medical therapies, pulmonary arterial hypertension (PAH) remains a progressive disease associated with significant morbidity and premature mortality. Lung transplantation (LT) is the last safety net for patients failing medical therapy, providing excellent overall long-term survival and healthrelated quality-of-life outcomes in line with more common parenchymal lung disease indications. Waitlist mortality remains disproportionally elevated, however, reflecting an inability of the lung allocation score to completely capture PAH disease severity, and a propensity for PAH to deteriorate rapidly without warning, even in patients who appear externally "well." Early referral to a LT center can mitigate these risks and facilitate rapid listing if necessary. Several bridging therapies are available to support severely unwell patients to LT, such as extracorporeal life support (ECLS) and atrial septostomy. Unique perioperative considerations include higher rates of primary graft dysfunction and dynamic right ventricular outflow obstruction which may, at least in part, reflect rapid afterload reduction in the face of a conditioned right ventricle. Extending ECLS into the perioperative period may ameliorate these risks by allowing more gradual adaptation of both ventricles to their new loading conditions. Chronic lung allograft dysfunction, particularly bronchiolitis obliterans syndrome, remains a major cause of long-term morbidity and mortality, and complications from corticosteroid and immunosuppressive therapy are common. Nevertheless, the morbidity, mortality, and burden of disease management after LT continue to improve and compare favorably to that of refractory PAH in carefully selected patients. [ABSTRACT FROM AUTHOR]

Background: We aimed to determine the frequency and predictors of exercise limitation after pulmonary embolism (PE) and to assess its association with health-related quality of life (HRQoL) and dyspnea.Methods: One hundred patients with acute PE were recruited at five Canadian hospitals from 2010 to 2013. Cardiopulmonary exercise testing (CPET) was performed at 1 and 12 months. Quality of life (QoL), dyspnea, 6-min walk distance (6MWD), residual clot burden (perfusion scan, CT pulmonary angiography), cardiac function (echocardiography), and pulmonary function tests (PFTs) were measured during follow-up. The prespecified primary outcome was percent predicted peak oxygen uptake (Vo2 peak) < 80% at 1-year CPET.Results: At 1 year, 40 of 86 patients (46.5%) had percent predicted Vo2 peak < 80% on CPET, which was associated with significantly worse generic health-related QoL (HRQoL), PE-specific HRQoL and dyspnea scores, and significantly reduced 6MWD at 1 year. Predictors of the primary outcome included male sex (relative risk [RR], 3.2; 95% CI, 1.3-8.1), age (RR, 0.98; 95% CI, 0.96-0.99 per 1-year age increase), BMI (RR 1.1; 95% CI, 1.01-1.2 per 1 kg/m2 BMI increase), and smoking history (RR, 1.8; 95% CI, 1.1-2.9), as well as percent predicted Vo2 peak < 80% on CPET at 1 month (RR, 3.8; 95% CI,1.9-7.2), and 6MWD at 1 month (RR, 0.82; 95% CI, 0.7-0.9 per 30-m increased walking distance). Baseline or residual clot burden was not associated with the primary outcome. Mean PFT and echocardiographic results (pulmonary artery pressure, right and left ventricular systolic function) at 1 year were similarly within normal limits in both patients with exercise limitations and those without such limitations.Conclusions: Almost half of patients with PE have exercise limitation at 1 year that adversely influences HRQoL, dyspnea, and walking distance. CPET or 6MWD testing at 1 month may help to identify patients with a higher risk of exercise limitation at 1 year after PE. Based on our results, we believe that the deconditioning that occurs after acute PE could underlie this exercise limitation, but we cannot exclude the fact that this may have been present before PE.Trial Registry: ClinicalTrials.gov; No.: NCT01174628; URL: www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Key points A consistent inverse hyperbolic relationship has been observed between pulmonary vascular resistance and compliance, although changes in pulmonary artery wedge pressure (PAWP) may modify this relationship., This relationship predicts that pulmonary artery systolic, diastolic and mean pressure maintain a consistent relationship relative to the PAWP., We show that, in healthy exercising human adults, both pulmonary vascular resistance and compliance decrease in relation to exercise-associated increases in PAWP., Pulmonary artery systolic, diastolic and mean pressures maintain a consistent relationship with one another, increasing linearly with increasing PAWP., Increases in PAWP in the setting of exercise are directly related to a decrease in pulmonary vascular compliance, despite small decreases in pulmonary vascular resistance, thereby increasing the pulsatile afterload to the right ventricle., Abstract The resistive and pulsatile components of right ventricular afterload (pulmonary vascular resistance, Rp; compliance, Cp) are related by an inverse hyperbolic function, expressed as their product known as RpCp-time. The RpCp-time exhibits a narrow range, although it may be altered by the pulmonary artery wedge pressure (PAWP). Identifying the determinants of RpCp-time should improve our understanding of the physiological behaviour of pulmonary arterial systolic (PASP), diastolic (PADP) and mean (mPAP) pressures in response to perturbations. We examined the effect of exercise in 28 healthy non-athletic adults (55 ± 6 years) who underwent right heart catheterization to assess haemodynamics and calculate Rp and Cp. Measurements were made at rest and during two consecutive 8-10 min stages of cycle ergometry, at targeted heart-rates of 100 beats min-1 (Light) and 120 beats min-1 (Moderate). Cardiac output increased progressively during exercise. PASP, PADP, mPAP and PAWP increased for Light exercise, without any further rise for Moderate exercise. RpCp-time decreased for Light exercise (0.39 ± 0.08 to 0.25 ± 0.08, P < 0.001) without any further change for Moderate exercise, and the decrease in RpCp-time was related to changes in PAWP ( r2 = 0.26, P < 0.001). Changes in PASP ( r2 = 0.43, P < 0.001), PADP ( r2 = 0.47, P < 0.001) and mPAP ( r2 = 0.50, P < 0.001) were linearly correlated with changes in PAWP, although they were not significantly related to changes in cardiac output. In healthy adults, exercise is associated with decreases in Cp and a resultant decline in RpCp-time, indicating increased pulsatile right ventricular afterload. Changes in RpCp-time, PASP, PADP and mPAP were systematically related to increases in PAWP. [ABSTRACT FROM AUTHOR]

The article cites a study on the assessment of persistent pulmonary hypertension after acute pulmonary embolism (PE). It found that after the median of 18 weeks of anticoagulation, 17 of 10 patients showed residual pulmonary artery systolic pressure (PAsP) and eight were determined to be suitable candidates for pulmonary endarterectomy (PEA). It implied that the first group should be evaluated despite the absence of PE and the second group are at risk and must be monitored.

Study objectives: To review the clinical experience with high-frequency oscillatory ventilation (HFOV) in three medical-surgical ICUs in Toronto, ON, Canada, and to describe patient characteristics, HFOV strategies, and outcomes. Design and patients: Retrospective chart review of all patients treated with HFOV at three academic university-affiliated ICUs since 1998. The data extracted included patient demographics, etiology of respiratory failure, ventilator settings, and gas exchange and cardiovascular data from baseline to 72 h of treatment, as well as at the transition from HFOV to conventional ventilation (CV). Heart rate and BP were recorded at regular intervals in all patients, and hemodynamic data were recorded in 32 patients who had pulmonary artery catheters in place. Cointerventions and ICU mortality were also recorded. Measurements and results: A total of 156 adults (67 women and 89 men; mean 11± SDI age, 48 ± 18 years; mean acute physiology and chronic health evaluation [APACHE] II score, 23.8 ± 7.5) with severe ARDS (ie, mean PaO2/fraction of inspired oxygen [FIO2] ratio, 91 ± 48 mm Hg; mean oxygenation index [OI], 31 ± 14) who had received CV for a duration of 5.6 ± 7.6 days underwent 171 trials of HFOV. HFOV was discontinued within 4 h in 19 patients (12%) because of difficulties with oxygenation, ventilation, or hemodynamics. PaO2/FIO2 ratios and OI ([FIO2 × mean airway pressure × 100/PaO2) improved significantly with the application of HFOV, and this benefit persisted for the 72-h study duration. Significant changes in hemodynamics following HFOV initiation included an increase in central venous pressure and a reduction in cardiac output (throughout the 72 h), and an increase in pulmonary artery occlusion pressure (at 3 and 6 h). Patients were treated with HFOV for 5.1 ± 6.3 days. The 30-day mortality rate was 61.7%. Pneumothorax occurred in 2 1.8% of patients, 43.6% of patients were treated with inhaled nitric oxide, and 37.2% of patients were treated with steroids. Independent predictors of mortality on multivariate analysis were older age, higher APACHE II score, lower pH at the initiation of HFOV, and a greater number of days receiving CV prior to HFOV. Conclusions: HFOV has beneficial effects on PaO2/FIO2 ratios and OI, and may be an effective rescue therapy for adults with severe oxygenation failure. The early institution of HFOV may be advantageous. [ABSTRACT FROM AUTHOR]

Low frequency spectral power (PL) may estimate the independent contributions of the sympathetic nervous system to heart rate variability in healthy subjects, but patients with heart failure (HF) due to systolic dysfunction (a state of generalized sympathetic activation) exhibit an inverse rather than direct relationship between muscle sympathetic nerve activity (MSNA) and PL. Patients with pulmonary artery hypertension (PAH) have normal left ventricular (LV) systolic function and low total power (PT) due to right atrial tension secondary to high pulmonary vascular resistance. We therefore tested the hypothesis that PL relates inversely to MSNA in PAH. Heart rate (HR) and MSNA were recorded during 10 min of supine rest in 8 PAH patients (age: 45.6 ± 4.4 yrs, pulmonary capillary wedge pressure: 11 ± 2 mmHg, pulmonary artery mean pressure: 54 ± 4 mmHg, right atrial pressure: 7 ± 1 mmHg; mean ± SE). Coarse-graining spectral analysis was used to determine PL and PT. HR was 87.3 ± 8.4 beats/min and MSNA was 47.9 ± 9.1 bursts/min (mean ± SE). MSNA related inversely to both PL (r = -0.73), and PT (r = -0.72) (p = 0.04). Thus, in PAH patients with normal LV pressures, PT relates inversely to MSNA, i.e., it is the absence of PL that indicates sympathetic activation. As with HF, reductions rather than elevations in low frequency power should be used to infer between-subject differences in sympathetic outflow in PAH. [ABSTRACT FROM AUTHOR]

Introduction: Fontan operation is the procedure of choice for children born with single ventricle physiology. Despite successful pediatric survival, rates of morbidity and mortality are high in adult Fontan survivors due to a chronically low cardiac output (CO). Treatment options for Fontan failure are limited. While short-term augmentation of CO with negative pressure ventilation (NPV) immediately following Fontan surgery has been shown, the effects of NPV in the ambulatory setting have not been studied. Our aim is to explore safety, feasibility and efficacy of a novel, portable external NPV (United Hayek Medical) in the Fontan population. Hypothesis: NPV will improve CO as measured by cardiovascular magnetic resonance imaging (CMR). Methods: Inclusion criteria: Adults (> 18y) with lateral tunnel or extracardiac Fontan and a dominant left ventricle with age-matched healthy controls. Exclusion criteria: Patients with failing Fontan physiology, significant valve regurgitation/stenosis, obstruction within the Fontan circuit, SO2 <90%, obesity (BMI > 35 kg/m2), chest wall deformities and/or contraindications to CMR. CMR flow measurements were obtained at multiple locations (ascending(AsAo) & descending aorta (DaAo), pulmonary arteries (RPA & LPA), vena cavae and Fontan circuit) at baseline and at various time points and pressure settings (Figure 1). Flow measurements expressed in L/min/m2. Data analyzed using Wilcoxon Mann-Whitney test. Results: A total of 20 subjects were enrolled: 10 Fontan and 10 controls. At baseline, Fontan patients have decreased cardiac index (CI) compared to controls. Brief application (10 min) of NPV resulted in significant increase in CI from 2.65 to 3.26 L/min/m2 (23% mean increase) in the Fontan group as compared to no effect in controls (Figure 2). Among the two ventilator modes biphasic mode (BCV) is more effective and well tolerated (Figure 3). Conclusions: A significant improvement in CO can be achieved in adult Fontan patients using NPV in the ambulatory setting. [ABSTRACT FROM AUTHOR]