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Objective: Few reliable tools exist to predict weaning patient outcomes from venoarterial extracorporeal membrane oxygenation (ECMO; VA-ECMO). Pulmonary artery pulse pressure indexed on right atrial pressure (PAPi) reflects the ventricle-pulmonary coupling and may be representative of right ventricular recovery. Radial artery pulse pressure (rPP) may be representative of left ventricular recovery. We intended to explore the usefulness of these indices in the weaning from VA-ECMO., Design: Retrospective cohort study., Setting: Single center in a tertiary university hospital., Participants: Patients benefiting from a VA-ECMO for all-cause refractory cardiogenic shock between 2017 and 2021. Non-inclusion criteria were minor/pregnant patients and ECMO within 48 hours. Univariate and multivariate logistic regression analyses explored the relationship between PAPi and rPP with weaning success., Interventions: We explored the association between the pulmonary artery pulse pressure indexed on PAPi, rPP, and the success of weaning from VA-ECMO., Measurements and Main Results: We included 124 patients for rPP analysis and 82 patients for PAPi analysis. Higher rPP and PAPi (50.43 v 26.3 mmHg, p < 0.001: 1.78 v 0.88, p < 0.001, respectively) and shorter ECMO duration were associated with weaning success. Areas under ROC for rPP and PAPi were 0.85 and 0.88. The combination of rPP ≥ 40 mmHg and PAPi ≥ 1.09 predicted weaning with a sensitivity of 0.94, specificity of 1.00, positive predictive value of 1.00, and negative predictive value of 0.84., Conclusion: Higher PAPi and rPP were predictors of successful weaning from VA-ECMO in this retrospective study., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Systemic hemodynamics and specific ventilator settings have been shown to predict survival during venoarterial extracorporeal membrane oxygenation (ECMO). How the right heart (the right ventricle and pulmonary artery) affect survival during venoarterial ECMO is unknown. We aimed to identify the relationship between right heart function with mortality and the duration of ECMO support., Methods: Cardiac ECMO runs in adults from the Extracorporeal Life Support Organization Registry between 2010 and 2022 were queried. Right heart function was quantified via pulmonary artery pulse pressure (PAPP) for pre-ECMO and on-ECMO periods. A multivariable model was adjusted for modified Society for Cardiovascular Angiography and Interventions stage, age, sex, and concurrent clinical data (ie, pulmonary vasodilators and systemic pulse pressure). The primary outcome was in-hospital mortality., Results: A total of 4442 ECMO runs met inclusion criteria and had documentation of hemodynamic and illness severity variables. The mortality rate was 55%; nonsurvivors were more likely to be older, have a worse Society for Cardiovascular Angiography and Interventions stage, and have longer pre-ECMO endotracheal intubation times ( P <0.05 for all) than survivors. Increasing PAPP from pre-ECMO to on-ECMO time (ΔPAPP) was associated with reduced mortality per 2 mm Hg increase (odds ratio, 0.98 [95% CI, 0.97-0.99]; P =0.002). Higher on-ECMO PAPP was associated with mortality reduction across quartiles with the greatest reduction in the third PAPP quartile (odds ratio, 0.75 [95% CI, 0.63-0.90]; P =0.002) and longer time on ECMO per 10 mm Hg (beta, 15 [95% CI, 7.7-21]; P <0.001)., Conclusions: Early on-ECMO right heart function and interval improvement from pre-ECMO values were associated with mortality reduction during cardiac ECMO. Incorporation of right heart metrics into risk prediction models should be considered., Competing Interests: Dr Tonna is the Chair-elect of the Registry Committee of the Extracorporeal Life Support Organization (ELSO). Dr Brodie has been on the medical advisory boards for Abiomed, Xenios, Medtronic, Inspira, and Cellenkos. He is the President-elect of ELSO and the Chair of the Executive Committee of the International ECMO Network (ECMONet), and he writes for UpToDate.

Aim: To study effect of change in position (supine and standing) on pulmonary artery pressure (PAP) in ambulatory heart failure (HF) patients., Methods: Seventeen patients with CardioMEMS® sensor and stable heart failure were consented and included in this single center study. Supine and standing measurements were obtained with at least 5 min interval between the two positions. These measurements included PAP readings utilizing the manufacturer handheld interrogator obtaining 10 s data in addition to the systemic blood pressure and heart rate recordings., Results: Mean supine and standing readings and their difference (Δ) were as follows respectively: Systolic PAP were 33.4 (± 11.19), 23.6 (± 10) and Δ was 9.9 mmHg (p = 0.0001), diastolic PAP were 14.2 (± 5.6), 7.9 (± 5.7) and Δ was 6.3 mmHg (p = 0.0001) and mean PAP were 21.8 (± 7.8), 14 (± 7.2) and Δ was 7.4 mmHg (p = 0.0001) while the systemic blood pressure did not vary significantly., Conclusion: There is orthostatic variation of PAP in ambulatory HF patients demonstrating a mean decline with standing in diastolic PAP by 6.3 mmHg, systolic PAP by 9.9 mmHg and mean PAP by 7.4 mmHg in absence of significant orthostatic variation in systemic blood pressure or heart rate. These findings have significant clinical implications and inform that PAP in each patient should always be measured in the same position. Since initial readings at the time of implant were taken in supine position, it may be best to use supine position or to obtain a baseline standing PAP reading if standing PAP is planned on being used., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Aims: Ventricular-vascular coupling, the ratio between the right ventricle's contractile state (E es ) and its afterload (E a ), may be a useful metric in the management of paediatric pulmonary arterial hypertension (PAH). In this study we assess the prognostic capacity of the ventricular-vascular coupling ratio (E es /E a ) derived using right ventricular (RV) pressure alone in children with PAH., Methods: One hundred and thirty paediatric patients who were diagnosed with PAH via right heart catheterisation were retrospectively reviewed over a 10-year period. Maximum RV isovolumic pressure and end-systolic pressure were estimated using two single-beat methods from Takeuchi et al (E es /E a &#95;(Takeuchi)) and from Kind et al (E es /E a &#95;(Kind)) and used with an estimate of end-systolic pressure to compute ventricular-vascular coupling from pressure alone. Patients were identified as either idiopathic/hereditary PAH or associated PAH (IPAH/HPAH and APAH, respectively). Haemodynamic data, clinical functional class and clinical worsening outcomes-separated into soft (mild) and hard (severe) event categories-were assessed. Adverse soft events included functional class worsening, syncopal event, hospitalisation due to a proportional hazard-related event and haemoptysis. Hard events included death, transplantation, initiation of prostanoid therapy and hospitalisation for atrial septostomy and Pott's shunt. Cox proportional hazard modelling was used to assess whether E es /E a was predictive of time-to-event., Results: In patients with IPAH/HPAH, E es /E a &#95;(Kind) and E es /E a &#95;(Takeuchi) were both independently associated with time to hard event (p=0.003 and p=0.001, respectively) and when adjusted for indexed pulmonary vascular resistance (p=0.032 and p=0.013, respectively). Neither E es /E a &#95;(Kind) nor E es /E a &#95;(Takeuchi) were associated with time to soft event. In patients with APAH, neither E es /E a &#95;(Kind) nor E es /E a &#95;(Takeuchi) were associated with time to hard event or soft event., Conclusions: E es /E a derived from pressure alone is a strong independent predictor of adverse outcome and could be a potential powerful prognostic tool for paediatric PAH., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: The diastolic pressure gradient (DPG) has been proposed as a marker pulmonary vascular disease in the setting of left heart failure (HF). However, its diagnostic utility is compromised by the high prevalence of physiologically incompatible negative values (DPG NEG ) and the contradictory evidence on its prognostic value. Pressure pulsatility impacts on DPG measurements, thus conceivably, pulmonary artery wedge pressure (PAWP) measurements insusceptible to the oscillatory effect of the V-wave might yield a more reliable DPG assessment. We set out to investigate how the instantaneous PAWP at the trough of the Y-descent (PAWP Y ) influences the prevalence of DPG NEG and the prognostic value of the resultant DPG Y ., Methods: Hundred and fifty-three consecutive HF patients referred for right heart catheterisation were enrolled prospectively. DPG, as currently recommended, was calculated. Subsequently, PAWP Y was measured and the corresponding DPG Y was calculated., Results: DPG Y yielded higher values (median, IQR: 3.2, 0.6-5.7 mmHg) than DPG (median, IQR: 0.9, - 1.7-3.8 mmHg); p < 0.001. Conventional DPG was negative in 45% of the patients whereas DPG Y in only 15%. During follow-up (22 ± 14 months) 58 patients have undergone heart-transplantation or died. The predictive ability of DPG Y  ≥ 6 mmHg for the above defined end-point events was significant [HR 2.1; p = 0.007] and independent of resting mean pulmonary artery pressure (PAP M ). In contrast, conventional DPG did not comprise significant prognostic value following adjustment for PAP M ., Conclusion: Instantaneous pressures at the trough of Y-descent yield significantly fewer DPG NEG than conventional DPG and entail superior prognostic value in HF patients with and without PH.

In the management of venoarterial extracorporeal membrane oxygenation, some patients present persistently closed aortic valve. However, little is known about the variables that contribute to persistently closed aortic valve. We investigated the factors that could predict persistently closed aortic valve at the time of venoarterial extracorporeal membrane oxygenation initiation. We investigated 17 patients who presented closed aortic valve immediately after the introduction of venoarterial extracorporeal membrane oxygenation. Patients who presented closed aortic valve 24 h after introduction of venoarterial extracorporeal membrane oxygenation were defined as the Closed-AV group (n = 8), while those whose aortic valve remained opened after 24 h were defined as the Open-AV group (n = 9). All patients were managed by concomitant use of intra-aortic balloon pumping. At baseline, there were no significant differences between mean arterial blood pressure, central venous pressure, and left ventricular ejection fraction. However, Closed-AV group had significantly lower mean pulmonary artery pressure and pulmonary artery pulse pressure compared to those of Open-AV group (mean pulmonary artery pressure: 15 ± 6 mmHg vs 25 ± 8 mmHg, p = 0.01; pulmonary artery pulse pressure: 3 ± 2 mmHg vs 8 ± 3 mmHg, p < 0.01). Logistic regression analyses revealed that the lower mean pulmonary artery pressure and pulmonary artery pulse pressure had the predictive value of closed aortic valve within 24 h after venoarterial extracorporeal membrane oxygenation initiation (mean pulmonary artery pressure: odds ratio = 0.78, 95% confidence interval = 0.58-0.95, p < 0.01; pulmonary artery pulse pressure: odds ratio = 0.18, 95% confidence interval = 0.01-0.61, p < 0.01). Lower mean pulmonary artery pressure and pulmonary artery pulse pressure values could predict persistent closed aortic valve 24 h after venoarterial extracorporeal membrane oxygenation initiation. Left ventricular preload derived from right heart function may have a major impact on aortic valve status.

Background: To explore the association between the ratio of tricuspid annular plane systolic excursion (TAPSE) and pulmonary arterial systolic pressure (PASP), and long- and short-term outcomes in mechanically ventilated septic shock patients., Methods: Septic shock patients admitted to the intensive care unit (ICU) were screened for enrollment. Echocardiographic parameters including TAPSE and tricuspid regurgitation velocity, haemodynamic and respiratory parameters, and prognostic data were obtained., Results: One hundred eighteen subjects were enrolled in this study, among whom 75 survived and 43 died at the one-year follow-up. ROC curve analysis revealed that the TAPSE/PASP ratio was able to assess one-year all-cause mortality with an area under the curve of 0.817 (95% CI: 0.739-0.896, p < 0.001) and the optimal cutoff value was 0.50 mm/mmHg. Kaplan-Meier survival analysis showed that one-year all-cause mortality was significantly higher in patients with TAPSE/PASP ≤0.5 mm/mmHg than in patients with TAPSE/PASP > 0.5 mm/mmHg (log-rank 32.934, p < 0.001). According to the Cox regression survival analyses, the TAPSE/PASP ratio was independently associated with one-year all-cause mortality (HR 0.007, 95% CI:0.000-0.162, p = 0.002) and ICU mortality (HR 0.027, 95% CI:0.001-0.530, p = 0.017). According to the multivariable analysis, the TAPSE/PASP ratio was an independent variable associated with mechanical ventilation (MV) duration (standard coefficient - 0.240, p = 0.010)., Conclusion: The TAPSE/PASP ratio demonstrated prognostic value for one-year all-cause mortality, ICU mortality and MV duration in mechanically ventilated septic shock patients.

Objective: Right ventricle and pulmonary artery pressure have always received less attention in type 1 diabetes than left ventricle. The aim of this study is to compare the right heart performance and the estimated peak systolic pulmonary artery pressure (EPSPAP) in young type 1 diabetes patients with healthy controls., Patients and Methods: Subjects affected by type 1 diabetes without cardiovascular and respiratory diseases (n=93) and healthy controls (n=56) were evaluated with a comprehensive transthoracic echocardiography. The pulmonary peak systolic arterial pressure was calculated with an established formula based on pulmonary artery acceleration time., Results: The left ventricle's function was found to be normal in all the subjects under study. The estimated peak systolic pulmonary artery pressure was significantly higher in patients with type 1 diabetes compared to the controls (38.5 ± 8.6 vs. 35.4 ± 6.7, p = 0.019). The highest value of EPSPAP was observed in smoking female patients with type 1 diabetes. Basal and mid cavity diameter of the right ventricle were higher in patients with type 1 diabetes. Factors associated with EPSPAP were sex, body mass index, mid cavity diameter and, with an inverse correlation, HDL-cholesterol., Conclusions: The present study suggests that young, uncomplicated patients with type 1 diabetes have a higher estimated peak systolic pulmonary artery pressure. Further studies are needed to define the mechanisms underlying this alteration and its clinical consequences.

Background: Implantable invasive hemodynamic monitoring (IHM) using the CardioMEMS™ HF system has been shown to reduce heart failure (HF) hospitalizations. IHMs have not yet been used in congenital heart disease (CHD). We aimed to evaluate feasibility and mid-term outcomes of IHM use in the single ventricle/Fontan population., Methods: Six adult Fontan patients (>1 HF admission, NYHA FC >3) were enrolled (30 ± 7 years old, mean pulmonary artery pressure (mPA) 16 ± 4.7 mm Hg). Heart failure mediated events (HFME) were evaluated for 12 months: CV medication change, hospital admission, paracentesis, and change in orthotopic heart transplant (OHT) listing status., Results: The IHM device was successfully placed in all participants. In total there were 671 IHM transmissions and 25(3.7%) HFME. The mean PA pressure across all episodes was 18.2 ± 6.6 mm Hg (range 6-40 mm Hg). Higher mPA pressures were associated with greater odds of having a HFME (OR 1.17 [1.09, 1.25], p < 0.0001). Mean PA pressure had good ability to discriminate transmissions associated with HFME (AUC 0.76 [0.654, 0.866]), with mean PA pressures >24 mm Hg or individual mPA change >4 mm Hg, best discriminating transmissions associated with HFME., Conclusions: In the first feasibility series of adult Fontan patients undergoing CardioMEMS™ implantation we demonstrate early technical success and no device-related adverse events. We propose that ambulatory mean PA pressures >24 mm Hg or individual mPA change >4 mm Hg may be associated with more HFME. Further large-scale studies in this population are recommended., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Obstructive sleep apnea syndrome in childhood has aroused great interest due to its cardiovascular repercussions and its adverse effects on the quality of life of the affected individuals. However, fundamental aspects of the syndrome remain unknown., Objective: Herein we prospectively assessed pulmonary artery systolic pressure (PASP) and nasal flow in children with obstructive oral breathing with an indication for adenoidectomy and/or tonsillectomy and their relationship to the obstructive apnea and hypopnea index (OAHI)., Methods: Twenty-one children were evaluated at the time of the surgical indication (T0) and 18 months later (T1). Polysomnography, and rhinomanometry data were collected when we evaluated PASP., Results: Among the 21 children, 13 (61.9%) presented an altered OAHI at T0. Fourteen children (66.7%) underwent surgery. Of these, nine (64.3%) had an altered OAHI at T0 and seven (50.0%) at T1. Of the seven non-operated children, four (57.1%) had an altered OAHI at T0 and two (33.3%) at T1. Mean nasal flow increased in both groups independently of surgery (p- ≤ 0.001). PASP exhibited a significant reduction between T0 and T1 in the operated group (p ≤ 0.001). OAHI of the operated group did not show a significant decrease over time (p = 0.074). In the non-operated children, the average nasal flow increased (p < 0.001), the PASP values did not reduce (p = 0.99), and the OAHI increased and then decreased over time (p = 0.025)., Conclusion: PASP decreased significantly and OAHI did not normalize in the operated group. Mean nasal airflow increased in the operated and non-operated groups., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Pulmonary hypertension (PH) is a known complication of HCM and is a strong predictor of mortality. We aim to investigate the relationship between microvascular dysfunction measured by quantitative PET and PH in HCM patients., Methods: Eighty-nine symptomatic HCM patients were included in the study. Each patient underwent two 20-min 13N-NH3 dynamic PET scans for rest and stress conditions, respectively. A 2-tissue irreversible compartmental model was used to fit the segments time activity curves for estimating segmental and global myocardial blood flow (MBF) and myocardial flow reserve (MFR). Echocardiographic derived PASP was utilized to estimate PH., Results: Patients were categorized into two groups across PASP: PH (PASP > 36 mmHg) and no-PH (PASP ≤ 36 mmHg). patients with PH had larger left atrium, ratio of higher inflow early diastole (E) and atrial contraction (A) waves, E/A, and ratio of inflow and peak early diastolic waves, E/e', significantly reduced global stress MBF (1.85 ± 0.52 vs. 2.13 ± 0.56 ml/min/g; p = 0.024) and MFR (2.21 ± 0.57 vs. 2.62 ± 0.75; p = 0.005), while the MBFs at rest between the two groups were similar. There were significant negative correlations between global stress MBF/MFR and PASP (stress MBF: r = -0.23, p = 0.03; MFR: r = -0.32, p = 0.002); for regional MBF and MFR measurements, the highest linear correlation coefficients were observed in the septal wall (stress MBF: r = -0.27, p = 0.01; MFR: r = -0.31, p = 0.003). Global MFR was identified to be independent predictor for PH in multivariate regression analysis., Conclusion: Echocardiography-derived PASP is negatively correlated with global MFR measured by 13N-NH3 dynamic PET. Global MFR is suggested to be an index of PH in HCM patients., Competing Interests: The authors have declared that no competing interests exist.

Objectives: To evaluate the association between high estimated pulmonary artery systolic pressure (ePASP) obtained by echocardiography and 1-year mortality in patients with acute heart failure (HF), comparing findings in individuals aged 80 and older with those of individuals younger than 80., Design: Retrospective cohort study., Setting: Kyorin University Hospital., Participants: Individuals with acute decompensated HF (N = 335)., Measurements: High ePASP was defined as a tricuspid regurgitation pressure gradient greater than 47 mmHg (ePASP >50 mmHg). Potential risk factors for 1-year mortality were selected using univariate analysis followed by multivariate Cox regression analysis with backward stepwise selection of variables with P < .10 on univariate analysis to identify significant factors., Results: In individuals aged 80 and older, high ePASP (hazard ratio (HR)=3.07; 95% confidence interval (CI)=1.21-7.80), discharge medications without diuretics (HR=4.18, 95% CI=1.66-10.54), and discharge medications without renin-angiotensin-aldosterone system inhibitors (HR=3.38, 95% CI=1.29-8.81) were independent risk factors for 1-year mortality. In contrast, low systolic blood pressure at admission was the sole independent risk factor for 1-year mortality (HR=0.94, 95% CI=0.89-0.99) in those younger than 80., Conclusion: High ePASP is a significant predictor of 1-year mortality in individuals aged 80 and older with acute HF but not in those younger than 80. Elucidation of the pathophysiological mechanisms behind these findings should facilitate the development of more effective individualized therapies for older adults with acute HF. J Am Geriatr Soc 67:323-328, 2019., (© 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society.)

Single ventricle palliation relies on the pulmonary vasculature accommodating non-pulsatile systemic venous return. Mean pulmonary artery pressure (MPAP) and indexed pulmonary vascular resistance (PVRi) are two measures that impact pulmonary blood flow following bidirectional cavopulmonary connection (BCPC). The purpose of the study was to determine which hemodynamic features are associated with adverse outcomes after BCPC. Pre-operative hemodynamic data and post-operative morbidity and mortality in 250 patients undergoing BCPC at a single center from 2008 to 2014 were reviewed. Patients were then separated into 5 physiologic states based on MPAP, PVRi, and degree of pulmonary to systemic blood flow (Q p :Q s ). There were 9 (3.6%) deaths, and 49 patients (20%) sustained major morbidity. An ROC curve identified MPAP > 16 mmHg as an inflection point. Pre-BCPC sildenafil and oxygen use, ventricular dysfunction, and MPAP > 16 mmHg (OR 4.1 [95% CI 1.8-9.2]) were independently associated with morbidity. MPAP > 16 mmHg (OR 6.7 [95% CI 1.6-28]) and pre-BCPC oxygen use were associated with hospital mortality. PVRi was not associated with morbidity or mortality. Of the five physiologic states, patients with high MPAP, low PVRi, and low Q p :Q s fared the worst, with the highest risk of major morbidity (OR 8.6 [3.0-24.9]) and highest risk of mortality (OR 8.0 [1.5-41.3]) when compared to their reference groups (low MPAP, low PVRi). Elevated MPAP, need for pre-operative oxygen support, sildenafil use, and systemic ventricular systolic dysfunction predict morbidity following BCPC. Specifically, patients with elevated MPAP not due to elevated PVRi or pulmonary blood flow had the highest risk of morbidity and mortality.

The article's aim was to determine predictors for short- and long-term prognosis of patients with pulmonary embolism (PE). Cohort prospective study based on the National registry on venous thromboembolism. Eighty-four patients with PE, on age 60.3 + 12.5 years, were selected and followed up in a prospective study. Pulmonary embolism was confirmed by computed tomography angiography in all the patients, while deep venous thrombosis was confirmed by ultrasound in 21 patients. Study population was followed up for 6.7 months. Multivariate regression analysis was done where right ventricular (RV) diameter (mean 37.5 mm), systolic pulmonary artery pressure (68 ± 23 mm Hg) measured by echocardiography, d-dimer level at baseline 2654.5 ± 420.3 ng/mL, number of comorbidities (2.4 ± 0.7), and present symptoms (3.1 ± 0.9) entered the model. The model was age-adjusted. d-dimer level was revealed as a predictor for the length of hospitalization (β = .25, P = .05) and RV diameter as a factor for duration of anticoagulation (β = .29, P = .05). Our results imply that the baseline measurement of these parameters independently influence both the short-term and long-term prognosis of patients with nonfatal PE.

Surgical treatment of congenital heart disease (CHD) involves complex vascular reconstructions utilizing artificial and native surgical materials. A successful surgical reconstruction achieves an optimal hemodynamic profile through the graft in spite of the complex post-operative vessel growth pattern and the altered pressure loading. This paper proposes a new in silico patient-specific pre-surgical planning framework for patch reconstruction and investigates its computational feasibility. The proposed protocol is applied to the patch repair of main pulmonary artery (MPA) stenosis in the Tetralogy of Fallot CHD template. The effects of stenosis grade, the three-dimensional (3D) shape of the surgical incision and material properties of the artificial patch are investigated. The release of residual stresses due to the surgical incision and the extra opening of the incision gap for patch implantation are simulated through a quasi-static finite-element vascular model with shell elements. Implantation of different unloaded patch shapes is simulated. The patched PA configuration is pressurized to the physiological post-operative blood pressure levels of 25 and 45 mmHg and the consequent post-operative stress distributions and patched artery shapes are computed. Stress-strain data obtained in-house, through the biaxial tensile tests for the mechanical properties of common surgical patch materials, Dacron, Polytetrafluoroethylene, human pericardium and porcine xenopericardium, are employed to represent the mechanical behavior of the patch material. Finite-element model is experimentally validated through the actual patch surgery reconstructions performed on the 3D printed anatomical stenosis replicas. The post-operative recovery of the initially narrowed lumen area and post-op tortuosity are quantified for all modeled cases. A computational fluid dynamics solver is used to evaluate post-operative pressure drop through the patch-reconstructed outflow tract. According to our findings, the shorter incisions made at the throat result in relatively low local peak stress values compared to other patch design alternatives. Longer cut and double patch cases are the most effective in repairing the initial stenosis level. After the patch insertion, the pressure drop in the artery due to blood flow decreases from 9.8 to 1.35 mmHg in the conventional surgical configuration. These results are in line with the clinical experience where a pressure gradient at or above 50 mmHg through the MPA can be an indication to intervene. The main strength of the proposed pre-surgical planning framework is its capability to predict the intra-operative and post-operative 3D vascular shape changes due to intramural pressure, cut length and configuration, for both artificial and native patch materials.

Background: Portopulmonary hypertension (POPH) is characterized by pulmonary vasoconstriction, while hepatopulmonary syndrome (HPS) is characterized by vasodilation. Definite POPH is a risk factor for the survival after orthotopic liver transplantation (OLT), as the congestive pressure affects the grafted liver, while subclinical pulmonary hypertension (PH) has been acknowledged as a non-risk factor for deceased donor OLT. Given that PH measurement requires cardiac catheterization, the tricuspid regurgitation pressure gradient (TRPG) measured by echocardiography is used to screen for PH and congestive pressure to the liver. We investigated the impact of a subclinical high TRPG on the survival of small grafted living donor liver transplantation (LDLT)., Methods: We retrospectively analyzed 84 LDLT candidates. Patients exhibiting a TRPG ≥25 mmHg on echocardiography were categorized as potentially having liver congestion (subclinical high TRPG; n = 34). The mean pulmonary artery pressure (mPAP) measured after general anesthesia with FIO 2 0.6 (mPAP-FIO 2 0.6) was also assessed. Patients exhibiting pO 2  < 80 mmHg and an alveolar-arterial oxygen gradient (AaDO 2 ) ≥ 15 mmHg were categorized as potentially having HPS (subclinical HPS; n = 29). The clinical course after LDLT was investigated according to subclinical high TRPG., Results: A subclinical high TRPG (p = 0.012) and older donor age (p = 0.008) were correlated with a poor 40-month survival. Although a higher mPAP-FIO 2 0.6 was expected to correlate with a worse survival, a high mPAP-FIO 2 0.6 with a low TRPG was associated with high frequency complicating subclinical HPS and a good survival, suggesting a reduction in the PH pressure via pulmonary shunt., Conclusion: In cirrhosis patients, mPAP-FIO 2 0.6 may not accurately reflect the congestive pressure to the liver, as the pressure might escape via pulmonary shunt. A subclinical high TRPG is an important marker for predicting a worse survival after LDLT, possibly reflecting congestive pressure to the grafted small liver.

Pulmonary hypertension is a severe, incurable disease with a poor prognosis. Although treatment regimens have improved during the last 2 decades, current pharmacologic strategies are limited and focus on the modulation of only a few pathways related to endothelin, NO, and prostacyclin signaling. Therefore, the identification of novel molecular targets is urgently needed. We found that the β 2 adrenoceptor (AR) agonists terbutaline (TER) and salbutamol induced a dose-dependent vasorelaxation in large pulmonary arteries but not aortas of mouse. This effect was found to be independent of β ARs and the endothelium but was determined by the type of the preconstrictor. Vasodilation by β 2 AR agonists occurred after pretreatment of pulmonary arteries with phenylephrine and serotonin, both agonists of α 1 ARs, but was absent after preconstriction with the thromboxane analog U46619. These data indicated α-adrenolytic activity of β 2 AR agonists, which was confirmed by a right shift of the phenylephrine dose-response curve by TER. This effect was physiologically relevant because TER also relaxed small intrapulmonary arteries in lung slices and diminished pulmonary arterial pressure in an isolated perfused lung model under normoxia and hypoxia. Finally, TER applied as an aerosol also selectively decreased pulmonary arterial pressure without effects on systemic blood pressure and heart rate in mouse in vivo. Thus, β 2 AR agonists display α-adrenolytic activity in pulmonary arteries ex vivo and in vivo, and may provide a novel option to reduce pulmonary arterial pressure in pulmonary hypertension.-Neumann, V., Knies, R., Seidinger, A., Simon, A., Lorenz, K., Matthey, M., Breuer, J., Wenzel, D. The β 2 agonist terbutaline specifically decreases pulmonary arterial pressure under normoxia and hypoxia via α adrenoceptor antagonism.

Rationale: A hemodynamic relationship of pulmonary artery pressure (PAP) to pulmonary acceleration time (PAcT) has not yet been explicitly presented., Objective: We employed a logistic-based systolic model with a subtle modification for pulmonary circulation and provided a logical ground for the relationship between systolic PAP and PAcT using transthoracic echocardiography. Additionally, the logistic-based PAP estimation equation was deduced from the model to relate systolic PAP and PAcT., Methods and Results: This equation was statistically tested in comparison to existing PAP estimation equations. Results showed that the logistic-based PAP estimation equation was at least as accurate as previous equations with respect to previously published mean PAP versus PAcT values. After the subtle pulmonary modification of the model, the pulmonary blood flow velocity and pressure not only well reflected the underlying pulmonary circulation physiology, but could also be presented in harmony with systemic circulation physiology., Conclusions: A future clinical study with actual systolic PAP versus PAcT measurements is needed to test the application of the logistic-based PAP estimation equation., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Activity of rheumatoid arthritis (RA) has been evaluated by various biomarkers including matrix metalloproteinase (MMP)-3, but the relationship between the levels of biomarkers and elevation of pulmonary artery systolic pressure (PAs) has not been evaluated in detail. We sought to determine the utility of MMP-3 with other biomarkers for the prediction of PAs in patients with RA. Blood samples for biomarkers and echocardiography were obtained in 100 consecutive patients with RA. PAs was measured by continuous-wave Doppler echocardiography and was correlated with laboratory findings. PAs had a fair correlation with MMP-3 (r = 0.53, p < 0.001) and a weak correlation with KL (Krebs von den Lungen)-6 (r = 0.36, p < 0.001) and rheumatoid factor (r = 0.25, p = 0.011). MMP-3 had a fair correlation with pulmonary vascular resistance (r = 0.42, p < 0.001), but MMP-3 was not related to cardiac output (r = 0.09, p = 0.352). Thirty-nine patients had impaired left ventricular diastolic function. There was no significant differences in PAs and pulmonary vascular resistance (PVR) between the patients with and without impaired left ventricular diastolic function. When 5 variables (age, MMP-3, C-reactive protein, KL-6, and rheumatoid factor) were used in the multivariate analysis, MMP-3 (partial regression coefficient = 0.553, p < 0.001) emerged as the most important variable related to the elevation of PAs. Nine patients (9%) were diagnosed to have pulmonary hypertension by echocardiography. MMP-3 value of 245 ng/ml was the optimal cut-off value for the prediction of pulmonary hypertension (sensitivity: 100%, specificity: 67%, area under the curve 0.89). Thus, a close relation of MMP-3 with PAs and PVR indicate that rise in PAs in patients with RA was ascribed to increase in PVR due to underlying systemic inflammation-mediated pulmonary vascular remodeling.

Importance: Pulmonary hypertension (PH) is diagnosed by a mean pulmonary arterial pressure (mPAP) value of at least 25 mm Hg during right heart catheterization (RHC). While several studies have demonstrated increased mortality in patients with mPAP less than that threshold, little is known about the natural history of borderline PH., Objective: To test the hypothesis that patients with borderline PH have decreased survival compared with patients with lower mPAP and frequently develop overt PH and to identify clinical correlates of borderline PH., Design, Setting, and Participants: Retrospective cohort study from 1998 to 2014 at Vanderbilt University Medical Center, comprising all patients undergoing routine RHC for clinical indication. We extracted demographics, clinical data, invasive hemodynamics, echocardiography, and vital status for all patients. Patients with mPAP values of 18 mm Hg or less, 19 to 24 mm Hg, and at least 25 mm Hg were classified as reference, borderline PH, and PH, respectively., Exposures: Mean pulmonary arterial pressure., Main Outcome and Measures: Our primary outcome was all-cause mortality after adjusting for clinically relevant covariates in a Cox proportional hazards model. Our secondary outcome was the diagnosis of overt PH in patients initially diagnosed with borderline PH. Both outcomes were determined prior to data analysis., Results: We identified 4343 patients (mean [SD] age, 59 [15] years, 51% women, and 86% white) among whom the prevalence of PH and borderline PH was 62% and 18%, respectively. Advanced age, features of the metabolic syndrome, and chronic heart and lung disease were independently associated with a higher likelihood of borderline PH compared with reference patients in a logistic regression model. After adjusting for 34 covariates in a Cox proportional hazards model, borderline PH was associated with increased mortality compared with reference patients (hazard ratio, 1.31; 95% CI, 1.04-1.65; P = .001). The hazard of death increased incrementally with higher mPAP, without an observed threshold. In the 70 patients with borderline PH who underwent a repeated RHC, 43 (61%) had developed overt PH, with a median increase in mPAP of 5 mm Hg (interquartile range, -1 to 11 mm Hg; P < .001)., Conclusions and Relevance: Borderline PH is common in patients undergoing RHC and is associated with significant comorbidities, progression to overt PH, and decreased survival. Small increases in mPAP, even at values currently considered normal, are independently associated with increased mortality. Prospective studies are warranted to determine whether early intervention or closer monitoring improves clinical outcomes in these patients.

Background: Thoracic impedance (TI) decrease and pulmonary artery pressure (PAP) elevation precede acute decompensation in congestive heart failure (HF). However, the relationship between TI and PAP has been studied only in the context of acute decompensation., Methods: This prospective, observational study enrolled subjects with reduced ejection fraction HF, previously implanted with an ICD capable of measuring TI. Patients underwent implantation of a sensor for direct measurement of PAP (CardioMEMs™). Both TI and PAP were remotely monitored daily during follow up. Investigators were blinded to PAP values during the first three months, then PAP was used as a guide to therapy., Results: Ten patients were followed up for 405±141days (3720 patient-days). During hemodynamic guided therapy, diastolic PAP (dPAP) decreased from 27.8±10.2mmHg to 24.0±8.0mmHg (p<0.001); non-significant variations of TI were observed. A significant negative correlation was found between the variations of TI and PAP vs. baseline (p<0.001). Episodes of sustained increase of PAP preceded subsequent periods of TI decrease by 5.6±3.9days, but the former were poor predictors of the latter (sensitivity 0.37)., Conclusions: Our study confirms the strict correlation that exists between left ventricular filling pressures and lung water content, estimated by dPAP and TI, respectively. However, dPAP acute variation analysis showed a limited value in predicting subsequent episodes of TI decrease., (Copyright © 2017 Elsevier B.V. All rights reserved.)

We investigated the serum haptoglobin levels in patients with pulmonary arterial hypertension (PAH) based on the hypothesis that haptoglobin levels would reflect subclinical hemolysis due to microangiopathy in pulmonary arterioles.This cross-sectional study included 3 groups of patients attending Hokkaido University Hospital: PAH, chronic thromboembolic pulmonary hypertension (CTEPH), and connective tissue diseases (CTD) without PAH (CTD-non-PAH) group. Serum haptoglobin levels were measured by standardized turbidimetric immunoassay in all patients. Demographic data, laboratory results, right heart catheter, and echocardiographic findings were extracted from the medical records. Decreased haptoglobin levels were defined as below 19 mg/dL based on the 95th percentile of healthy controls.Thirty-five patients in PAH group including 11 with idiopathic PAH (IPAH) and 24 with CTD-associated PAH (CTD-PAH), 27 in CTEPH group, and 32 in CTD-non-PAH group were analyzed. Serum haptoglobin levels in PAH group (median 66 mg/dL) were significantly lower than those in CTEPH group (median 94 mg/dL, P = .03) and CTD-non-PAH group (median 79 mg/dL, P = .03). The prevalence of decreased haptoglobin levels was 26% in PAH group, 15% in CTEPH group, and 6% in CTD-non-PAH group. Serum haptoglobin levels had a significant negative correlation (r = -0.66, P < .001) with mean pulmonary artery pressure in PAH group, particularly in CTD-PAH subgroup (r = -0.74, P < .001), but no correlation in IPAH subgroup (r = -0.52, P = .13) and in CTEPH group (r = -0.17, P = .41). Follow-up cases of CTD-PAH showed lowering pulmonary artery pressure led to normalizing serum haptoglobin levels.Serum haptoglobin levels decreased in PAH patients and inversely correlated with pulmonary artery pressure in CTD-PAH patients, suggesting their potential as a surrogate marker for CTD-PAH.

Background: Echocardiographically estimated pulmonary artery systolic pressure (PASP) is a non-invasive widely available method that is used to estimate pulmonary arterial pressure. Although elevated PASP predicts mortality in patients with hypertrophic cardiomyopathy (HCM), the relationship between PASP and embolic events is unclear. This study aimed to determine whether elevated PASP is associated with stroke and systemic embolic events in a tertiary referral HCM cohort., Methods: This study included 374 clinically diagnosed patients with HCM. PASP was estimated from tricuspid regurgitant jet velocity using the modified Bernoulli equation., Results: The median (interquartile range) PASP was 33 (28-37) mm Hg, and elevated PASP (>40mmHg) was observed in 66 (17.6%) patients. Seventeen of the 66 (25.8%) patients with elevated PASP and 24 of the 308 (7.8%) patients without elevated PASP experienced stroke and systemic embolic events during the 10.3±7.4years of follow-up (log-rank P<0.001). Multivariable analysis showed that age at diagnosis, atrial fibrillation, and PASP >40mmHg (adjusted hazard ratio, 2.59; 95% confidence interval, 1.31-5.12; P=0.006) were independently associated with embolic events., Conclusions: In addition to age and atrial fibrillation, PASP estimated by Doppler echocardiography could help embolic risk stratification in patients with HCM., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Objective: Heart failure (HF) management guided by implantable hemodynamic monitoring reduces hospitalization rates. Hemodynamic data from the CardioMEMS ™ HF system includes device-averaged pulmonary artery pressures (PAP) and heart rate. Agreement of device-averaged values compared to the standard method of visual inspection of pressure waveforms at end-expiration is unknown. We evaluated the agreement between device-averaged and visually inspected end-expiratory PAP., Approach: Twenty-one patients implanted with the CardioMEMS ™ HF system were evaluated. Eight-hundred twenty-three PAP waveforms from the Merlin remote monitoring website were visually inspected and pulmonary artery systolic pressure (PASP) and pulmonary artery diastolic pressure (PADP) at end-expiration were recorded. Waveforms were evaluated for pressure variation (PV), defined as the difference between highest and lowest PASP measurement of  ⩾20 mmHg. Bland-Altman analysis quantified differences between device-averaged and visually inspected waveforms., Main Results: All patients were NYHA functional class III, mean age was 67  ±  15 years and 15 (71%) had AF. Bland-Altman analysis of all waveforms revealed a mean-difference in PADP of  -1.4 mmHg, indicating that visually inspected values were higher than device-averaged values. For PV  ⩾20 mmHg, this value increased to  -2.8 mmHg. The mean-difference comparing waveforms from patients with or without AF was  -1.3 and  -1.6 mmHg, respectively. The 95% limits of agreement were  >50% wider for waveforms from patients with versus without AF (10.3 versus 6.7 mmHg)., Significance: There is good agreement between device-averaged and visually inspected waveforms when pressure variation is  <20 mmHg and for patients without atrial fibrillation.

Calcification of the tunica media of the axial pulmonary arteries (PA) has been reported in a large proportion of racehorses. In humans, medial calcification is a significant cause of arterial stiffening and is implicated in the pathogenesis of cardiac, cerebral, and renal microvascular diseases. Pulse wave velocity (PWV) provides a measure of arterial stiffness. This study aimed to develop a technique to determine PA-PWV in horses and, secondarily, to investigate a potential association between PA-PWV and arterial fibro-calcification. A dual-pressure sensor catheter (PSC) was placed in the main PA of 10 sedated horses. The pressure waves were used to determine PWV along the PA, using the statistical phase offset method. Histological analysis of the PA was performed to investigate the presence of fibro-calcified lesions. The mean (±SD) PWV was 2.3 ± 0.7 m/s in the proximal PA trunk and 1.1 ± 0.1 m/s further distal (15 cm) in a main PA branch. The mean (±SD) of mean arterial pressures in the proximal PA trunk was 30.1 ± 5.2 mmHg, and 22.0 ± 6.0 mmHg further distal (15 cm) within the main PA branch. The mean (±SD) pulse pressure in the proximal PA trunk was 15.0 ± 4.7 mmHg, and 13.5 ± 3.3 mmHg further distal (15 cm) within the main PA branch. Moderate to severe lesions of the tunica media of the PAs were observed in seven horses, but a correlation with PWV could not be established yet. Pulmonary artery PWV may be determined in standing horses. The technique described may allow further investigation of the effect of calcification of large PAs in the pathogenesis of equine pulmonary circulatory disorders. NEW & NOTEWORTHY Pulmonary artery pulse wave velocity was determined safely in standing sedated horses. The technique described may allow further investigation of the effect of calcification of large pulmonary arteries in the pathogenesis of pulmonary circulatory disorders in horses., (Copyright © 2017 the American Physiological Society.)

Stable positioning of a transcatheter pulmonary valve (TPV) in native outflow tracts depends on a clear understanding of underlying anatomy and outflow tract dimensions. We hypothesized that restoration of pulmonary competence may acutely alter these dimensions. A retrospective single-center review of consecutive patients after TPV placement from 2007 to 2014 was performed. Patients with less than moderate pulmonary regurgitation were excluded. We reviewed acute catheterization data on 46 patients, most with tetralogy of Fallot (70%). Baseline and post-implant (7.5 ± 3 min post-deployment) measurements of central pulmonary arteries (PAs) were determined angiographically. The right PA diameter increased (20 ± 4-24 ± 6 mm systole*, 16 ± 4-21 ± 6 mm diastole*), as did the left PA (20 ± 6-24 ± 8 mm systole*, 16 ± 5-21 ± 7 mm diastole*). PA pressures increased from averages of 29.3/10.6 (17) to 29.8/15.1 (21) mmHg. We noted that pre-implant systolic PA diameter correlated with diastolic PA diameter post-implant (r = 0.9). On follow-up catheterization in seven patients [median 3 years; (1-8)], combined central PA diameter decreased an average of 20% (systole: 20% ± 12, diastole: 18% ± 11) as compared to post-implant measurements. Acute pulmonary valve competence in patients with at least moderate pulmonary regurgitation results in an immediate increase in PA diameter (20% systole and 30% diastole). The cause of this diameter change is unclear. This acute change may have implications for device and patient selection (*p < 0.001).

Objectives: Iron deficiency (ID) might augment chronic pulmonary hypertension in chronic obstructive pulmonary disease (COPD). This observational study investigates the association between ID and systolic pulmonary artery pressure estimated by echocardiography in non-anaemic COPD outpatients., Methods: Non-anaemic COPD patients (GOLD II-IV) with no history of cardiovascular disease were recruited from outpatient clinics. Iron deficiency was defined as ferritin<100μg/L. Pulmonary artery pressure was estimated from the tricuspid regurgitation maximum velocity (TR V max ). Tricuspid regurgitation V max indicative of pulmonary hypertension was considered present for values ≥ 2.9 m/s., Results: In a total of 75 included patients, 31 (41%) had ID. These patients had a significantly higher TR V max (3.02 vs. 2.77 m/s, p=0.01) and lower diffusion capacity of carbon monoxide (40% vs. 50% of predicted, p<0.01), though similar in age, sex, pack years, FEV 1 and high-sensitive CRP (p>0.05). Ferritin inversely correlated with TR V max in ID patients (-0.37 (p=0.04)). The prevalence of TR V max ≥ 2.9 m/s was twice as high in patients with ID (58% vs. 29%) and odds ratio of pulmonary hypertension in ID (compared to no ID) was 3.3 (95% CI 1.3-8.6, p=0.015)., Conclusion: Iron deficiency in non-anaemic COPD patients was associated with a modest increase in systolic pulmonary artery pressure and limitation of diffusion capacity., (Copyright © 2016 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Patient-specific biventricular computational models associated with a normal subject and a pulmonary arterial hypertension (PAH) patient were developed to investigate the disease effects on ventricular mechanics. These models were developed using geometry reconstructed from magnetic resonance (MR) images, and constitutive descriptors of passive and active mechanics in cardiac tissues. Model parameter values associated with ventricular mechanical properties and myofiber architecture were obtained by fitting the models with measured pressure-volume loops and circumferential strain calculated from MR images using a hyperelastic warping method. Results show that the peak right ventricle (RV) pressure was substantially higher in the PAH patient (65 mmHg versus 20 mmHg), who also has a significantly reduced ejection fraction (EF) in both ventricles (left ventricle (LV): 39% versus 66% and RV: 18% versus 64%). Peak systolic circumferential strain was comparatively lower in both the left ventricle (LV) and RV free wall (RVFW) of the PAH patient (LV: -6.8% versus -13.2% and RVFW: -2.1% versus -9.4%). Passive stiffness, contractility, and myofiber stress in the PAH patient were all found to be substantially increased in both ventricles, whereas septum wall in the PAH patient possessed a smaller curvature than that in the LV free wall. Simulations using the PAH model revealed an approximately linear relationship between the septum curvature and the transseptal pressure gradient at both early-diastole and end-systole. These findings suggest that PAH can induce LV remodeling, and septum curvature measurements may be useful in quantifying transseptal pressure gradient in PAH patients.

In a monocrotaline (MCT) induced-pulmonary arterial hypertension (PAH) rat animal model, the dynamic stress-strain relation was investigated in the circumferential and axial directions using a linear elastic response model within the quasi-linear viscoelasticity theory framework. Right and left pulmonary arterial segments (RPA and LPA) were mechanically tested in a tubular biaxial device at the early stage (1 week post-MCT treatment) and at the advanced stage of the disease (4 weeks post-MCT treatment). The vessels were tested circumferentially at the in vivo axial length with matching in vivo measured pressure ranges. Subsequently, the vessels were tested axially at the mean pulmonary arterial pressure by stretching them from in vivo plus 5% of their length. Parameter estimation showed that the LPA and RPA remodel at different rates: axially, both vessels decreased in Young's modulus at the early stage of the disease, and increased at the advanced disease stage. Circumferentially, the Young's modulus increased in advanced PAH, but it was only significant in the RPA. The damping properties also changed in PAH; in the LPA relaxation times decreased continuously as the disease progressed, while in the RPA they initially increased and then decreased. Our modeling efforts were corroborated by the restructuring organization of the fibers imaged under multiphoton microscopy, where the collagen fibers become strongly aligned to the 45 deg angle in the RPA from an uncrimped and randomly organized state. Additionally, collagen content increased almost 10% in the RPA from the placebo to advanced PAH.

Pulmonary hypertension (PH) resulting from left heart failure is an increasingly recognized clinical entity. To distinguish isolated postcapillary PH from combined post- and precapillary PH, the use of a diastolic pressure gradient (DPG = diastolic Pulmonary Artery Pressure - Pulmonary Arterial Wedge Pressure, dPAP - PAWP) has been advocated over the transpulmonary pressure gradient (TPG = mean Pulmonary Artery Pressure - PAWP, mPAP - PAWP) since DPG was suggested to be independent of cardiac output (CO) and only slightly related to PAWP, while TPG depends on both. We quantitatively derived and compared the DPG and TPG Using right heart catheterization data (n = 1054), we determined systolic pulmonary artery pressure (sPAP), dPAP and mPAP, PAWP, and CO From this data, we derived TPG and DPG and tested their dependence on PAWP and CO We found that dPAP and sPAP are proportional with mPAP over a wide range of PAWP (1-31 mmHg), with dPAP = 0.62mPAP and sPAP = 1.61mPAP As a consequence, TPG and DPG are equally dependent on PAWP: TPG = mPAP - PAWP, and DPG = 0.62mPAP - PAWP Furthermore, we showed that both TPG and DPG depend on CO The absolute increase in DPG with CO is 62% of the TPG increase with CO, but the relative dependence is the same. Both TPG and DPG depend on PAWP and CO Thus, in principle, there are no major advantages for using DPG to distinguish postcapillary pulmonary hypertension from combined post- and precapillary pulmonary hypertension., (© 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.)

Background: Patients with heart failure with preserved ejection fraction have functional impairment resulting in reduced quality of life. Specific pathological mechanisms underlying symptoms have not yet been defined., Objectives: The aim of this study was to identify hemodynamic and other patient-related variables that are associated with New York Heart Association (NYHA) functional class and to analyze functional class in perspective with other clinical, laboratory, imaging, and hemodynamic parameters with respect to its influence on outcomes., Methods: Between January 2011 and February 2015, 193 patients with confirmed heart failure with preserved ejection fraction were enrolled., Results: Those in more advanced NYHA functional classes (III and IV; n = 136) were older (p = 0.008), had higher body mass indexes (p = 0.004), and had higher levels of N-terminal pro-brain natriuretic peptide (p = 0.001) compared with less symptomatic patients (NYHA class II; n = 57). Furthermore, parameters reflecting left ventricular diastolic dysfunction were more pronounced in advanced NYHA classes (early mitral inflow velocity/early diastolic mitral annular velocity; p = 0.023) as well as parameters reflecting right ventricular afterload (diastolic pulmonary artery pressure; p < 0.001). By multivariate regression analysis, age (p = 0.007), body mass index (p = 0.002), N-terminal pro-brain natriuretic peptide (p < 0.001), early mitral inflow velocity/mitral peak velocity of late filling (p = 0.031), and diastolic pulmonary artery pressure (p < 0.001) were independently associated with advanced NYHA class. After 21.9 months of follow-up, 64 patients (33.2%) reached the combined endpoint, defined as hospitalization for heart failure and/or cardiac death. By multivariate Cox analysis, NYHA functional class was independently associated with outcome (hazard ratio: 2.133; p = 0.040), as well as N-terminal pro-brain natriuretic peptide (hazard ratio: 1.655; p < 0.001) and impaired right ventricular function (hazard ratio: 2.360; p = 0.001)., Conclusions: Symptoms of breathlessness in patients with heart failure with preserved ejection fraction are multifactorial and largely related to body mass index, left ventricular diastolic function, and the pulmonary vasculature. Clinically meaningful therapeutic interventions should target body weight, left ventricular stiffness, and concomitant pulmonary vascular disease., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Exaggerated pulmonary pressor response to hypoxia is a pathgonomic feature observed in high altitude pulmonary edema (HAPE) susceptible mountaineers. It was investigated whether measurement of basal pulmonary artery pressure (Ppa) and brain natriuretic peptide (BNP) could improve identification of HAPE susceptible subjects in a non-mountaineer population. We studied BNP levels, baseline hemodynamics and the response to hypoxia (FIo2 = 0.12 for 30 min duration at sea level) in 11 HAPE resistant (no past history of HAPE, Control) and 11 HAPE susceptible (past history of HAPE, HAPE-S) subjects. Baseline Ppa (19.31 ± 3.63 vs 15.68 ± 2.79 mm Hg, p < 0.05) and plasma BNP levels (52.39 ± 32.9 vs 15.05 ± 9.6 pg/ml, p < 0.05) were high and stroke volume was less (p < 0.05) in HAPE-S subjects compared to control. Acute hypoxia produced an exaggerated increase in heart rate (p < 0.05), mean arterial pressure (p < 0.05) and Ppa (28.2 ± 5.8 vs 19.33 ± 3.74 mm Hg, p < 0.05) and fall in peripheral oxygen saturation (p < 0.05) in HAPE-S compared to control. Receiver operating characteristic (ROC) curves showed that Ppa response to acute hypoxia was the best variable to identify HAPE susceptibility (AUC 0.92) but BNP levels provided comparable information (AUC 0.85). BNP levels are easy to determine and may represent an important marker for the determination of HAPE susceptibility.

Background: Mixed pulmonary hypertension (PH) in heart failure (HF) is defined by transpulmonary gradient ≥ 12 and/or pulmonary vascular resistance (PVR) ≥ 240 dyne/s/cm(-5), but diastolic pressure gradient (DPG) ≥ 7 mmHg has been proposed more recently. We evaluated the acute hemodynamic response to sodium nitroprusside (SNP) specifically in relation to the proposed DPG criterion ≥7 mmHg and the prognostic significance of response to SNP in patients with mixed PH and advanced HF., Methods: Ninety-eight consecutive patients with advanced HF and mixed PH underwent cardiac catheterization and acute SNP infusion. Baseline hemodynamic parameters included transpulmonary gradient, PVR, DPG, and pulmonary capacitance (PCap). Hemodynamic response to SNP was defined as a reduction in PVR of at least 20%. The composite endpoint was death/heart transplantation/mechanical circulatory support., Results: Sixty of the 98 patients were SNP responders. SNP resulted in significant reductions in filling pressures and PVR and increase in stroke volume and PCap. DPG (not baseline PVR) was significantly associated with hemodynamic response to SNP on logistic regression analysis. The sensitivity and specificity of a DPG ≥7 mmHg to identify nonresponders to SNP were 74% and 97%, respectively. At median follow-up of 218 (148-324) days, 13 and 19 patients of the SNP responders and nonresponders, respectively, met the composite endpoint (P = .021 by log-rank test). Hemodynamic response to SNP and PCap were independently associated with the composite outcome of survival free from transplantation/mechanical circulatory support., Conclusion: Baseline DPG ≥ 7 mmHg is associated with poor PVR response to SNP. PVR response to SNP and PCap are associated with a more favorable prognosis in patients with advanced HF and mixed PH., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Introduction: Right heart catheterization (RHC) remains the gold standard for hemodynamic assessment of the right heart and pulmonary artery. However, this is an invasive tool, and noninvasive alternatives such as transthoracic echocardiography (TTE) are preferable. Nonetheless, the correlation between measurements by TTE and RHC are debated. In this study, we prospectively examined the correlation between systolic and mean pulmonary artery pressures (sPAP and mPAP) measured by RHC and TTE in patients with hemodynamically significant rheumatic mitral stenosis (MS)., Material and Methods: Three hundred patients with hemodynamically significant MS undergoing TTE who were scheduled to undergo RHC within 24 hours were analyzed. PAP measurements were taken for all patients by RHC (sPAP(RHC), mPAP(RHC)). Maximum velocity of tricuspid regurgitation (TR) jet obtained by continuous-wave Doppler with adding right atrial (RA) pressure was used for measuring sPAP by TTE (sPAP(TRVmax)). Mean PAP was measured using either pulmonary artery acceleration time (mPAP(PAAT)) method or by adding RA pressure to velocity-time integral of TR jet (mPAP(TRVTI))., Results: A good correlation between sPAP(RHC) and sPAP(TRVmax) (r = 0.89, P < 0.001), between mPAP(RHC) and mPAP(PAAT) (r = 0.9, P < 0.001), and between mPAP(RHC) and mPAP(TRVTI) (r = 0.92, P < 0.001) was found. Sensitivity and specificity of sPAP(TRV) max in detecting pulmonary hypertension (PH) were 92.8% and 86.6% and of mPAP(PAAT) were 94.1% and 73.3%, respectively., Conclusion: The noninvasive assessment of sPAP and mPAP by TTE correlates well with invasive measurements and has an acceptable specificity and sensitivity in detecting PH in patients with hemodynamically significant MS., (© 2015, Wiley Periodicals, Inc.)

Objective: The aim of this study was to assess the prognostic value of systolic pulmonary artery pressure (sPAP) estimated by echocardiography in the multinational European League Against Rheumatism Scleroderma Trial and Research (EUSTAR) cohort., Methods: Data for patients with echocardiography documented between 1 January 2005 and 31 December 2011 were extracted from the EUSTAR database. Stepwise forward multivariable statistical Cox pulmonary hypertension analysis was used to examine the independent effect on survival of selected variables., Results: Based on our selection criteria, 1476 patients were included in the analysis; 87% of patients were female, with a mean age of 56.3 years (s.d. 13.5) and 31% had diffuse SSc. The mean duration of follow-up was 2.0 years (s.d. 1.2, median 1.9). Taking index sPAP of <30 mmHg as reference, the hazard ratio (HR) for death was 1.67 (95% CI 0.92, 2.96) if the index sPAP was between 30 and 36 mmHg, 2.37 (95% CI 1.14, 4.93) for sPAP between 36 and 40 mmHg, 3.72 (95% CI 1.61, 8.60) for sPAP between 40 and 50 mmHg and 9.75 (95% CI 4.98, 19.09) if sPAP was >50 mmHg. In a multivariable Cox model, sPAP and the diffusing capacity for carbon monoxide (DLCO) were independently associated with the risk of death [HR 1.833 (95% CI 1.035, 3.247) and HR 0.973 (95% CI 0.955, 0.991), respectively]. sPAP was an independent risk factor for death with a HR of 3.02 (95% CI 1.91, 4.78) for sPAP ≥36 mmHg., Conclusion: An estimated sPAP >36 mmHg at baseline echocardiography was significantly and independently associated with reduced survival, regardless of the presence of pulmonary hypertension based on right heart catheterization., (© The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: Recent clinical studies have shown conflicting results of the efficacy of renal sympathetic denervation (RSD) to mitigate hypertension. In this study, we compared electrical stimulation (ES) of autonomic nerves on the surface of the left pulmonary artery (LPA) and renal arteries (RAs) on heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP), and cardiac arrhythmias., Methods: In 16 pentobarbital anesthetized dogs, standard electrocardiography leads and blood pressure (BP) were continuously recorded. After a left thoracotomy, a circumferential multielectrode catheter was secured around the LPA. Atrial pacing was coupled to the ES applied around the LPA during the QRS complex to avoid ventricular excitation. Flank incisions allowed retroperitoneal expose of the RAs and the aortico-renal ganglia (ARG). HR and SBP/DBP were determined at baseline (BL) and during ES of LPA, RA, or ARG., Results: During ES applied to the LPA, HR was unchanged compared to BL values. In four of six animals, ventricular tachyarrhythmias were induced by ES. SBP increased significantly (BL vs ES, 129 ± 17 mm Hg vs 163 ± 21 mm Hg, P ≤ 0.05). ES applied to the RAs and ARG did not affect the HR, but significantly increased SBP/DBP (baseline: 134 ± 24/96 ± 18 mm Hg; RAs stimulation: 157 ± 26/114 ± 18 mm Hg; ARG stimulation: 207 ± 44/147 ± 26 mm Hg, P < 0.05)., Conclusion: ES of vascular autonomic nerves on LPA, RAs, and ARG significantly increased BP but without effects on HR. ES of ARG induced substantially greater hypertensive responses than ES of RAs, implying that ES of ARG may serve as a biomarker or ablation targets for RSD., (©2015 Wiley Periodicals, Inc.)

With the reduction in use of the pulmonary artery catheter, alternative methods of pulmonary pressure estimation are required. The use of echocardiographically-derived right ventricular systolic pressure has recently been questioned, but this technique has not been validated in anaesthetised surgical patients with transoesophageal echocardiography. One hundred measurements of right ventricular systolic pressure with transoesophageal echocardiography were compared with the pulmonary artery systolic pressure obtained simultaneously from a pulmonary artery catheter in patients undergoing cardiac surgery. Simultaneous right ventricular systolic pressure and pulmonary artery systolic pressure measurements were possible in all patients, and these measurements were strongly correlated (r = 0.98, p < 0.001), with minimal bias and narrow limits of agreement (approximately -5 to +5 mmHg), across a broad range of pulmonary pressures. Measurement of right ventricular systolic pressure using tranoesophageal echocardiography is readily achievable and closely correlates with pulmonary artery systolic pressure, with minimal bias, in cardiac surgical patients undergoing general anaesthesia and positive pressure mechanical ventilation of the lungs., (© 2014 The Association of Anaesthetists of Great Britain and Ireland.)

We have studied the effect of bronchodilator drugs representing three groups--b2-adrenomimetic (fenoterol), anticholinergic (ipratropium bromide), and combined preparation (fenoterol/ipratropium bromide)--on cardiohemodynamics in children with acute asthma exacerbation. It is established that incorrect choice of bronchodilator most significantly influences the parameters of blood pressure and blood flow rate in the pulmonary artery, mitral and tricuspid valves, and also contributes to the appearance of signs of diastolic dysfunction of the right and left ventricles. A model predicting the risk of cardiohemodynamic violations was created using the multiple regression method, which allows the probability of negative changes in the cardiovascular system on the background of bronchodilator therapy to be calculated within several minutes using data on the medical prehistory and the results of objective and instrumental examination of a patient. Using this model it is possible to optimize the bronchodilator treatment of acute asthma in children and also to prevent the formation of future complications of the cardiovascular system.

Background/aims: Patients on chronic hemodialysis have a high prevalence of heart disease and poor self-reported physical function. The association between structural heart disease and self-reported physical function in patients on hemodialysis is unknown., Methods: We studied the association between elevated pulmonary artery systolic pressure (PASP) and self-reported physical function in ESRD in 253 patients in the USRDS ACTIVE/ADIPOSE study between 2009 and 2011. We used multivariate linear regression with PASP obtained from clinical echocardiogram reports as the primary predictor and the Physical Function (PF) subscale of the SF-36 as the primary outcome. To determine whether associations between PASP and PF were driven by fluid overload or left ventricular hypertrophy, we assessed whether PASP was associated with bioimpedance spectroscopy (BIS)-derived extracellular water (ECW) and with left ventricular posterior wall thickness., Results: In a multivariable model, each 10 mm Hg higher PASP was associated with a 3.32-point lower PF score (95% CI -5.95, -0.68). In a multivariable model that included BIS estimates, both left ventricular posterior wall thickness (LVPW, per 5 mm) and ECW were associated with a higher PASP (LVPW 4.21 mm Hg, 95% 0.38-8.04; ECW 1.12 mm Hg per liter, 95% CI 0.07-2.18). Higher LVPW and ECW were independently associated with a lower PF score., Conclusion: Left ventricular hypertrophy and elevated pulmonary pressure are associated with worse self-reported physical function in patients on hemodialysis. The role of chronic volume overload on PASP and PF score should be evaluated in a prospective manner., (© 2015 S. Karger AG, Basel.)

Background: This study was undertaken to compare the immediate and long-term follow-up results of balloon pulmonary valvuloplasty (BPV) between the single balloon and Inoue balloon for isolated pulmonary valve stenosis (PS)., Methods: A retrospective analysis of outcomes following BPV in 38 children using the single balloon and 42 adults using the Inoue balloon at a single institution was performed., Results: The majority of children (76.3%) were asymptomatic while 26 adults (61.9%) presented with symptoms. The ratio of balloon size to pulmonary valve annulus was 1.23 ± 0.12 in the children group and 1.22 ± 0.10 in the adult group (P=0.641). The children group had a right ventricle-pulmonary artery systolic gradient of 52.79 ± 35.08 mmHg that decreased to 22.55 ± 12.92 mmHg following BPV (P<0.001). The adult group had a gradient of 94.79 ± 42.19 mmHg that decreased to 34.02 ± 15.00 mmHg following BPV (P<0.001). Mild pulmonary regurgitation occurred in eight children (21.1%) and 10 adults (23.8%) (P=0.768). During a median follow-up of 15 years, gradients were not significantly different from that obtained at one-month follow-up in children (P=0.280) and adults (P=0.373)., Conclusions: Adults can be treated with BPV using the Inoue balloon with encouraging immediate and long-term follow-up results that are similar to those in children using the single balloon., (Copyright © 2014. Published by Elsevier B.V.)

Macitentan is the most recently approved dual endothelin-receptor antagonist (ERA) for the treatment of symptomatic pulmonary arterial hypertension. Compared to other available ERAs, it demonstrates superior receptor-binding properties, with consequently improved tissue penetration, and a longer duration of action allowing for once-daily dosing. It has a favorable adverse-effect profile, with notably no demonstrable increase in the risk of hepatotoxicity or peripheral edema, but like other ERAs, it is potentially limited by significant anemia. Phase I data have demonstrated a favorable drug-drug interaction profile and no need for dose adjustment with hepatic and renal impairment. In the pivotal SERAPHIN study, treatment of symptomatic pulmonary arterial hypertension patients with macitentan led to statistically significant improvements in functional class, exercise tolerance, and hemodynamic parameters, in addition to a reduction in morbidity in an event-driven long-term trial.

A novel multiscale mathematical and computational model of the pulmonary circulation is presented and used to analyse both arterial and venous pressure and flow. This work is a major advance over previous studies by Olufsen et al. (Ann Biomed Eng 28:1281-1299, 2012) which only considered the arterial circulation. For the first three generations of vessels within the pulmonary circulation, geometry is specified from patient-specific measurements obtained using magnetic resonance imaging (MRI). Blood flow and pressure in the larger arteries and veins are predicted using a nonlinear, cross-sectional-area-averaged system of equations for a Newtonian fluid in an elastic tube. Inflow into the main pulmonary artery is obtained from MRI measurements, while pressure entering the left atrium from the main pulmonary vein is kept constant at the normal mean value of 2 mmHg. Each terminal vessel in the network of 'large' arteries is connected to its corresponding terminal vein via a network of vessels representing the vascular bed of smaller arteries and veins. We develop and implement an algorithm to calculate the admittance of each vascular bed, using bifurcating structured trees and recursion. The structured-tree models take into account the geometry and material properties of the 'smaller' arteries and veins of radii ≥ 50 μm. We study the effects on flow and pressure associated with three classes of pulmonary hypertension expressed via stiffening of larger and smaller vessels, and vascular rarefaction. The results of simulating these pathological conditions are in agreement with clinical observations, showing that the model has potential for assisting with diagnosis and treatment for circulatory diseases within the lung.

Rationale: Transfusion of erythrocytes stored for prolonged periods is associated with increased mortality. Erythrocytes undergo hemolysis during storage and after transfusion. Plasma hemoglobin scavenges endogenous nitric oxide leading to systemic and pulmonary vasoconstriction., Objectives: We hypothesized that transfusion of autologous blood stored for 40 days would increase the pulmonary artery pressure in volunteers with endothelial dysfunction (impaired endothelial production of nitric oxide). We also tested whether breathing nitric oxide before and during transfusion could prevent the increase of pulmonary artery pressure., Methods: Fourteen obese adults with endothelial dysfunction were enrolled in a randomized crossover study of transfusing autologous, leukoreduced blood stored for either 3 or 40 days. Volunteers were transfused with 3-day blood, 40-day blood, and 40-day blood while breathing 80 ppm nitric oxide., Measurements and Main Results: The age of volunteers was 41 ± 4 years (mean ± SEM), and their body mass index was 33.4 ± 1.3 kg/m(2). Plasma hemoglobin concentrations increased after transfusion with 40-day and 40-day plus nitric oxide blood but not after transfusing 3-day blood. Mean pulmonary artery pressure, estimated by transthoracic echocardiography, increased after transfusing 40-day blood (18 ± 2 to 23 ± 2 mm Hg; P < 0.05) but did not change after transfusing 3-day blood (17 ± 2 to 18 ± 2 mm Hg; P = 0.5). Breathing nitric oxide decreased pulmonary artery pressure in volunteers transfused with 40-day blood (17 ± 2 to 12 ± 1 mm Hg; P < 0.05)., Conclusions: Transfusion of autologous leukoreduced blood stored for 40 days was associated with increased plasma hemoglobin levels and increased pulmonary artery pressure. Breathing nitric oxide prevents the increase of pulmonary artery pressure produced by transfusing stored blood. Clinical trial registered with www.clinicaltrials.gov (NCT 01529502).

Objective: The aim of our study was to investigate subclinical cardiac disturbances in patients with symptoms due to adenotonsillar hypertrophy (ATH) and the impact of adenotonsillectomy (AT) using conventional and novel echocardiographic measures., Material and Methods: Thirty patients with grade 3 or 4 ATH (mean age: 7.86 ± 3.83 years; 10 females) and 30 healthy, age- and sex-matched volunteers (mean age, 8 ± 2.77; 14 females) were enrolled in the study. In addition to conventional two-dimensional and Doppler echocardiographic parameters, tissue Doppler parameters, including myocardial performance indices (MPIs) of both the right (RV) and left ventricle (LV), were studied. The severity of obstructive sleep apnea (OSA) was determined using the OSA-18 health quality questionnaire. The OSA-18 questionnaire and echocardiographic examination were repeated after AT in patients with ATH., Results: The total OSA-18 scores for the control, preoperative, and postoperative groups were 39.56 ± 19.98, 80.63 ± 22.32, and 44.10 ± 20.31, respectively. Conventional parameters were not different among the groups. The mean pulmonary artery pressure estimated using the Mahan formula was increased in the ATH group compared with that in the control group (21.72 ± 4.25 vs. 12.43 ± 3.83, respectively; p<0.001) and significantly improved after AT (21.72 ± 4.25 vs. 16.09 ± 4.53; p<0.001). The RV MPI was significantly different between the control and ATH groups (0.322 ± 0.052 vs. 0.383 ± 0.079, respectively; p=0.001). Both the LV and RV MPI significantly improved (0.515 ± 0.066 vs. 0.434 ± 0.052, p<0.001; and 0.383 ± 0.079 vs. 0.316 ± 0.058, p=0.018, respectively) after surgery for ATH., Conclusions: Our study revealed that the patients with OSA-specific symptoms due to ATH had higher pulmonary artery pressure and impaired RV function according to novel echocardiographic parameters. Surgery for ATH seems to have an important effect on both LV and RV function., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: In every pneumonectomy due to a malignant or benign pulmonary disease the pulmonary artery must be centrally ligated and dissected. If a thoracotomy is undertaken the vessel is usually doubly ligated with a non-absorbable suture and then dissected. Alternatively a vessel stapler can be used. In a thorascopic procedure only the stapler can be used. In the search for a cheaper alternative we investigated whether a bipolar instrument as employed in thorascopy could be used and reused. The aim of this study was to investigate the static pressure performance of the closed vessel in an ex vivo non-perfused vessel model., Material and Methods: From freshly slaughtered pigs the heart-lung block was removed. The central pulmonary artery was exposed. For sealing the vessel we used the bipolar sealing system MARSEAL®, Brothers Martin company (Tuttlingen, Germany), consisting of an HF generator and a MARSEAL slim instrument. Two groups were formed: group A (n = 49) Stromart SealSafe®, step G5 (automatic performance regulation, duration of use depending on impedance) and group B (n = 58) bipolar Stromart "Macrocoag" (power: 120 W, constant duration of use: 15 s). At the end of the pulmonary artery a pressure probe was implanted to digitally measure the pressure at the vessel sealing suture. After sealing the end of the artery, the vessel was slowly filled via an external source in order to determine the burst pressure. The burst pressure was reached as soon as the vessel suture started to leak. The average values of the 2 groups were then compared (t test for independent variables, significance set at p < 0.05)., Results: All examined vessels (n = 107) had the same vessel diameter of 15 ± 3 mm. The average value of the burst pressure in group A was 139.3 ± 62.17 mmHg, that in group B 124.8 ± 38.46 mmHg. The ranges of burst pressures were in group A 51-297.0 mmHg und in group B 60.75-244.5 mmHg. There was no significant difference between group A and group B (p = 0.071)., Conclusions: Satisfactory burst pressures in the central pulmonary artery can also be achieved with the bipolar sealing instrument MARSEAL® and the impedance-controlled Stromart SealSafe®. However, because of the large scattering of the measured values, further studies are required., (Georg Thieme Verlag KG Stuttgart · New York.)

Oxidative stress contributes to the development of pulmonary hypertension in experimental models, but this association in humans is unknown. We investigated the relationship between pulmonary artery systolic pressure measured by echocardiography and plasma aminothiol oxidative stress markers, with the hypothesis that oxidative stress will be higher in those with pulmonary hypertension. A group of 347 patients aged 65±12 years from the Emory Cardiovascular Biobank underwent echocardiographic assessment of left ventricular ejection fraction and pulmonary artery systolic pressure. Plasma aminothiols, cysteine, its oxidized form, cystine, glutathione, and its oxidized disulphide were measured and the redox potentials (Eh) of cysteine/cystine and glutathione/oxidized glutathione couples were calculated. Non-normally distributed variables were log transformed (Ln). Univariate predictors of pulmonary artery systolic pressure included age (P<0.001), sex (P=0.002), mitral regurgitation (P<0.001), left ventricular ejection fraction (P<0.001), left atrial size (P<0.001), diabetes mellitus (P=0.03), plasma Ln cystine (β=9.53; P<0.001), Ln glutathione (β=-5.4; P=0.002), and Eh glutathione (β=0.21; P=0.001). A multivariate linear regression model adjusting for all confounding variables demonstrated that Ln cystine (β=6.56; P=0.007), mitral regurgitation (β=4.52; P<0.001), statin use (β=-3.39; P=0.03), left ventricular ejection fraction (β=-0.26; P=0.003), and age (β=0.17; P=0.003) were independent predictors of pulmonary artery systolic pressure. For each 1% increase in plasma cystine, pulmonary artery systolic pressure increased by 16%. This association persisted in the subgroup with preserved left ventricular ejection fraction (≥50%) and no significant mitral regurgitation. Whether treatment of oxidative stress will improve pulmonary hypertension requires further study.

Hypertension, commonly recognized as high blood pressure, is a serious disease that affects millions of people worldwide. Similar to many physiological disorders, hypertension consists of several different cellular signaling pathways that involve various molecular messengers. Recent studies have shown that reactive oxygen species (ROS) play a substantial role in the development of both systemic and pulmonary hypertension, contributing to the pathology of this disease. However, the exact molecular mechanism of ROS in hypertension is not completely understood. In this review, we extensively examine and discuss the most recent experimental findings regarding the role of ROS in both pulmonary and systemic hypertension. Current studies show that excessive ROS not only promote JAK/STAT (janus kinase/signal transducers and activators of transcription)-mediated vascular remodeling in an angiotensin (ANG) II-induced hypertension model but also decrease the nitric oxide bioavailability. Furthermore, it has been shown that ROS generation can be mitigated through the inhibition of upstream ANG II or by blocking key ROS generators, such as nicotinamide adenine dinucleotide phosphate oxidase. Thus, various treatment options have been explored. Yet, as discussed in the current review, the regulation of ROS via novel antioxidant therapies may provide an alternative treatment for hypertension in the future.

Background and Aim of the Study: Remodeling of the pulmonary autograft upon exposure to systemic pressure can lead to progressive dilatation and aneurysmal pathology. Remodeling is driven by changes in autograft wall stress upon exposure to systemic pressure; however, the magnitude of these changes is unknown. Previously, a porcine autograft finite element model was developed to determine wall stress, but the porcine and human material properties differed significantly. Hence, the study aim was to understand human pulmonary autograft biomechanics that lead to remodeling by determining wall stress magnitudes immediately after the Ross procedure using finite element analysis (FEA)., Methods: Human pulmonary root was scanned by high-resolution microcomputed tomography to construct a realistic three-dimensional geometric mesh. Stress-strain data from biaxial stretch testing was incorporated into an Ogden hyperelastic model to describe autograft mechanical properties for an adult Ross patient. Autograft dilatation and wall stress distribution during pulmonic and systemic pressures prior to remodeling were determined using explicit FEA in LS-DYNA., Results: Human pulmonary autograft demonstrated non-linear material properties, being highly compliant in the low-strain region, and stiffening at high strain. The majority of dilatation occurred with < 20 mmHg pressurization. From pulmonary to systemic pressures, the increases in autograft diameter were up to 17%. Likewise, the maximal wall stress increased approximately 14.6-fold compared to diastolic pressures (from 13.0 to 190.1kPa), and six-fold compared to systolic pressures (from 48.6 to 289.6kPa)., Conclusion: The first finite element model of the human pulmonary autograft was developed and used to demonstrate how autograft material properties prevent significant dilatation upon initial exposure to systemic pressure. Mild dilatation was noted in the sinuses and sinotubular junction. Autograft wall stress was increased greatly when subjected to systemic pressures, and may trigger biomechanical remodeling of the autograft. Sustained exposure to higher wall stresses, coupled with inadequate remodeling, may lead to future autograft dilatation.

Background: Accurate determination of left ventricular filling pressure is essential for differentiation of pre-capillary pulmonary hypertension (PH) from pulmonary venous hypertension (PVH). Previous data suggest only a poor correlation between left ventricular end-diastolic pressure (LVEDP) and its commonly used surrogate, the pulmonary capillary wedge pressure (PCWP). However, no data exist on the diagnostic accuracy of PCWP in veterans. Furthermore, the effects of age and comorbidities on the PCWP-LVEDP relationship remain unknown., Methods: We investigated the PCWP-LVEDP relationship in 101 patients undergoing simultaneous right and left heart catherization at a large VA hospital. PCWP performance was evaluated using correlation and Bland-Altman analyses. Area under Receiver Operating Characteristics curves (AUROC) for PCWP were determined., Results: PCWP-LVEDP correlation was moderate (r = 0.57). PCWP-LVEDP calibration was poor (Bland-Altman limits of agreement -17.2 to 11.4 mmHg; mean bias -2.87 mmHg). 59 patients (58.4%) had pulmonary hypertension; 15 (25.4%) of those met pre-capillary PH criteria based on PCWP. However, if LVEDP was used instead of PCWP, 7/15 patients (46.6%) met criteria for PVH rather than pre-capillary PH. When restricting analysis to patients with a mean pulmonary artery pressure of ≥25 mmHg and pulmonary vascular resistance of >3 Wood units (n = 22), 10 patients (45.4%) were classified as pre-capillary PH based on PCWP ≤15 mmHg. However, if LVEDP was used, 4/10 patients (40%) were reclassified as PVH. Among patients with any type of pulmonary hypertension, PCWP discriminated moderately between high and normal LVEDP (AUROC, 0.81; 95%CI 0.69-0.94). PCWP-LVEDP correlation was particularly poor in patients with COPD or obesity., Conclusion: Reliance on PCWP rather than LVEDP results in misclassification of veterans as having pre-capillary PH rather than PVH in almost 50% of cases. This is clinically relevant, as misclassification may lead to inappropriate therapies and adverse events.