Resting Mean Pulmonary Artery Pressure Research Articles

Pulsed-Field Ablation Does Not Worsen Baseline Pulmonary Hypertension Following Prior Radiofrequency Ablations

BackgroundStudies have reported development of pulmonary hypertension (PH) secondary to reduced LA compliance following AF ablation. ObjectivesThis study aimed to compare the risk of worsening of baseline PH between non-paroxysmal AF patients undergoing pulsed-field ablation (PFA) and standard radiofrequency ablation (RFA). MethodsThis multicenter study included 28 nonparoxysmal AF patients with PH undergoing a PFA-based ablation procedure after >1 failed RFA. A cohort of 28 AF patients with PH, scheduled for repeat RFA, 1:1 propensity-score matched using a multivariable logistic model, were used as the comparator group. Right heart catheterization and echocardiography were performed before and after the procedure to assess the pulmonary artery pressure (PAP). PH was defined as resting mean PAP of >20 mm Hg. ResultsThe baseline characteristics of the PFA and propensity-matched RFA groups were comparable. The mean PAP assessments at baseline, follow-up, and change from baseline were analyzed. The groups had comparable baseline mean pulmonary artery pressures (mPAP) (P = 0.177). After adjustment for baseline mPAP in an analysis of covariance model, the least-squares means change at 3 months after ablation was −1.71 ± 1.03 mm Hg and 19.67 ± 1.03 mm Hg in PFA and RFA, respectively (P <0.001). ConclusionsIn this propensity-matched population, no worsening of mPAP was detected following pulsed-field ablation in patients with pre-existing PH undergoing a repeat procedure for recurrence.

Clinical impact of residual pulmonary hypertension based on revised criteria after balloon pulmonary angioplasty

Abstract Background Balloon pulmonary angioplasty (BPA) improves haemodynamics, exercise capacity, and prognosis in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). However, the treatment goal of BPA is not well established. The European Society of Cardiology guidelines published in 2022 revised the diagnosis of pulmonary hypertension from resting mean pulmonary arterial pressure (mPAP) ≥25 mmHg to mPAP &amp;gt;20 mmHg because mild elevation of pulmonary hypertension has decreased exercise capacity and worsened the prognosis. The clinical impact of normalization in resting pulmonary hypertension after balloon pulmonary angioplasty is not investigated. Purpose The purpose of this study is to clarify the clinical impact of mPAP normalization after BPA as a treatment goal in patients with CTEPH. Methods We retrospectively reviewed consecutive 236 CTEPH patients (68 [55,75] yrs., Male 52 (22%)) who completed BPA procedures from July 2009 to December 2020 and had haemodynamics evaluation after the procedures and had mPAP &amp;lt;30 mm Hg after BPA. We extracted two groups with mPAP &amp;lt;20 mmHg (Non-PH group) and 21≤ mPAP &amp;lt;30 mmHg (Residual-PH group) after BPA. Results The median follow-up period from the final BPA session was 38 [22,61] months. In both the Non-PH and Residual-PH groups, BPA significantly improved mPAP (37 [29,43] to 18 [16,19] mmHg, P&amp;lt;0.01 and 38 [34,45] to 23 [22,26], P&amp;lt;0.01, respectively) and cardiac index (CI) (2.15 [1.86,2.63] to 2.39 [2.11,2.80] L/min/m2, P&amp;lt;0.01 and 2.25 [1.87,2.63] to 2.50 [2.23,2.88] L/min/m2, P&amp;lt;0.01, respectively). There were no significant differences in CI after BPA between the Non-PH and Residual-PH groups. The 6-minute walk distance (6MWD) after BPA was shorter in the Residual-PH group than in the Non-PH group (435m and 480m, P&amp;lt;0.01). However, the estimated 5-year survival in the Non-PH and Residual-PH groups was comparable (96.3% and 99.1%, P=0.23, Figure 1). Patients in the Residual-PH group showed significantly shorter 6MWD and higher mPAP before BPA, and required more procedures (P&amp;lt;0.01, 0.02, 0.03, respectively). Additional multivariate logistic regression analysis revealed that shorter 6MWD before BPA was a significant predictor of residual PH (odds ratio=1.03, P=0.04). Conclusions The Residual-PH group had lower exercise capacity than the Non-PH group, although the prognosis in the Residual-PH group was similar to that in the Non-PH group.Figure 1

Risk of stiff left atrial syndrome following pulse-field-based ablation of atrial fibrillation in patients with pulmonary hypertension at baseline

Abstract Introduction Studies have reported development of stiff LA syndrome, defined as pulmonary hypertension (PH) secondary to reduced LA compliance, in some patients following AF ablation. Purpose We compared the risk of worsening of baseline PH in non-paroxysmal AF (persistent and long-standing persistent AF) patients undergoing repeat procedures, either pulse-field ablation (PFA) or standard radiofrequency ablation (RFA). Methods This multicenter study included 28 non-paroxysmal AF patients with PH, undergoing PFA-based ablation procedure after &amp;gt;1 failed radiofrequency ablations (RFA). A cohort of 28 AF patients with PH that were scheduled for repeat RF ablation were identified. Propensity scores were computed using multivariate logistic model. Twenty-eight patients from the RFA cohort were selected by 1:1 propensity score matching with the PFA group. Right heart catheterization was performed pre- and post-procedure to assess the Pulmonary artery pressure (PAP). PH was defined as resting mean PAP of ≥20 mmHg. The follow-up PAP and change from baseline were compared between PFA and RFA groups, after controlling for baseline PAP in an ANCOVA model. Results Baseline characteristics of PFA (age 62.21 ± 9.3 yrs, male 19 (67.9%), LAD 3.7 ± 0.66 cm) and propensity-matched RF groups (age 62.39 ± 9.3 yrs, male 18 (64.3%), LAD 3.7 ± 0.74 cm) were comparable. The mean pulmonary artery pressure (PAP) assessments at baseline, follow-up and change from baseline are presented in table below. The groups had comparable baseline PAP (p= 0.157). At follow-up, RF group reported 19.81 mm Hg increase in PAP (within-group p &amp;lt;0.001). In PFA group, follow-up PAP showed a decreasing trend (-1.67 mm Hg, within-group p= 0.114). Compared to PFA, the change was significantly higher in RFA (p &amp;lt;0.0001) after controlling for baseline PAP). Conclusion In this propensity-matched population, pulse-field ablation was demonstrated to be a safer option in terms of post-ablation worsening of PAP, compared to the RF ablation in AF patients with pulmonary hypertension at baseline.

Exercise Capacity and Ventilatory Efficiency in Patients With Pulmonary Arterial Hypertension.

Background The symptom for identification of pulmonary arterial hypertension (PAH) is dyspnea on exertion, with a concomitant decrease in exercise capacity. Even patients with hemodynamically improved PAH may have impaired exercise tolerance; however, the effect of central and peripheral factors on exercise tolerance remains unclear. We explored the factors contributing to exercise capacity and ventilatory efficiency in patients with hemodynamically normalized PAH after medical treatment. Methods and Results In total, 82 patients with PAH (age: median 46 [interquartile range, 39-51] years; male:female, 23:59) and mean pulmonary arterial pressure ≤30 mm Hg at rest were enrolled. The exercise capacity, indicated by the 6-minute walk distance and peak oxygen consumption, and the ventilatory efficiency, indicated by the minute ventilation versus carbon dioxide output slope, were assessed using cardiopulmonary exercise testing with a right heart catheter. The mean pulmonary arterial pressure was 21 (17-25) mm Hg, and the 6-minute walk distance was 530 (458-565) m, whereas the peak oxygen consumption was 18.8 (14.8-21.6) mLꞏmin-1ꞏkg-1. The multivariate model that best predicted 6-minute walk distance included peak arterial mixed venous oxygen content difference (β=0.46, P<0.001), whereas the best peak oxygen consumption predictors included peak cardiac output (β=0.72, P<0.001), peak arterial mixed venous oxygen content difference (β=0.56, P<0.001), and resting mean pulmonary arterial pressure (β=-0.25, P=0.026). The parameter that best predicted minute ventilation versus carbon dioxide output slope was the resting mean pulmonary arterial pressure (β=0.35, P=0.041). Quadriceps muscle strength was moderately correlated with exercise capacity (6-minute walk distance; ρ=0.57, P<0.001; peak oxygen consumption: ρ=0.56, P<0.001) and weakly correlated with ventilatory efficiency (ρ=-0.32, P=0.007). Conclusions Central and peripheral factors are closely related to impaired exercise tolerance in patients with hemodynamically normalized PAH.

Left atrial enlargement is associated with pulmonary vascular disease in heart failure with preserved ejection fraction.

Elevated left atrial (LA) pressure is a pathophysiologic hallmark of heart failure with preserved ejection fraction (HFpEF). Chronically elevated LA pressure leads to LA enlargement, which may impair LA function and increase pulmonary pressures. We sought to evaluate the relationship between LA volume and pulmonary arterial haemodynamics in patients with HFpEF. Data from 85 patients (aged 69 ± 8 years) who underwent exercise right heart catheterization and echocardiography were retrospectively analysed. All had symptoms of heart failure, left ventricular ejection fraction ≥50% and haemodynamic features of HFpEF. Patients were divided into LA volume index-based tertiles (≤34 ml/m2 , >34 to ≤45 ml/m2 , >45 ml/m2 ). A subgroup analysis was performed in patients with recorded LA global reservoir strain (n=60), with reduced strain defined as ≤24%. Age, sex, body surface area and left ventricular ejection fraction were similar between volume groups. LA volume was associated with blunted increases in cardiac output with exercise (padjusted <0.001), higher resting mean pulmonary artery pressure (padjusted =0.003), with similar wedge pressure (padjusted =1). Pulmonary vascular resistance (PVR) increased with increasing LA volume (padjusted <0.001). Larger LA volumes featured reduced LA strain (padjusted <0.001), with reduced strain associated with reduced PVR-compliance time (0.34 [0.28-0.40] vs. 0.38 [0.33-0.43], p=0.03). Increasing LA volume may be associated with more advanced pulmonary vascular disease in HFpEF, featuring higher PVR and pulmonary pressures. Reduced LA function, worse at increasing LA volumes, is associated with a disrupted PVR-compliance relationship, further augmenting impaired pulmonary haemodynamics.

972 PULMONARY HYPERTENSION AND EMBRYOLOGICAL REMNANT: WHAT DO THEY HAVE TO DO WITH EACH OTHER? A CASE REPORT

Abstract Background Pulmonary hypertension (PH) is defined as a resting mean pulmonary artery pressure of 20 mmHg or above. The importance of identifying the underlying causes of PH is well known for a correct management and treatment. In particular, any cardiac causes, included shunt, must be investigated. Case Summary A 73-year-old woman presented to the emergency room for asthenia and dyspnea. First line exams as ECG and X-ray were executed resulting normal. Laboratory assessment showed an elevated brain natriuretic peptide at 675 pg/ml and a D-dimer value of 1116 ng/mlFEU (n.v. &amp;lt; 500 ng/mlFEU) so with the suspect of pulmonary thromboembolism a CT-scan with contrast was performed. It was negative for acute thromboembolism, but it revealed an enlarged pulmonary artery (with a diameter of 39 mm), a possible defect of interatrial septum and an anomalous drainage of inferior vena cava (IVC) into the left atrium (LA). A transthoracic echocardiogram confirmed the anomalous drainage of IVC into the LA that appears dilated but was not diagnostic for the interatrial defect. Furthermore, PH was suspected (systolic peak tricuspid regurgitation velocity of 3,5 m/s, RA area of 24 cm2, tricuspid annular plane systolic excursion/systolic pulmonary arterial pressure of 0.26 mm/mmHg). A 6-minute walking distance was 376 m. The patient completed the exams with a transesophageal echocardiography that revealed an inferior-type caval vein defect and an over-developed Eustachian valve which divides the right atrium (RA) and connect the IVC with the LA directing the blood flow towards it through the inter-atrial septal defect. Discussion The Eustachian valve is an embryologic remnant at the junction of the IVC and RA. While it typically does not have any pathologic significance, veno-arterial shunting can rarely occur in patients with prominent eustachian valves and atrial septal defects.

Stress-induced pulmonary hypertension: definition and diagnosis

The first hemodynamic definition of pulmonary hypertension (PH) was given at the World Symposium on PH (WSPH, 1973) in Geneva as an increasebin resting mean pulmonary artery pressure (mPAP) &gt;25 mm Hg by heart chamber catheterization. Since 2004, in the definition of PH, in addition to an increase in resting mPAP, an 'exercise' criterion has also been included: mPAP at the peak of exercise &gt;30 mm Hg. However, at the 4th WSPH Symposium in 2008, due to uncertainty of the relationship between age-related changes in cardiac output (CO) and pulmonary vascular physiology, in particular pulmonary vascular resistance (PVR) under exercise, this criterion was excluded.Resting PH manifests only at the absence of ≥50 % of pulmonary microcirculation, so for the earliest diagnosis of the disease, it’s necessary to use factors that provoke an increase in CO and PVR. Moreover, in clinical practice, manifestations of PH are not uncommon on exercise. In the absence of consensus the definition of stress- induced PH is defined in individuals with normal mPAP (&lt; 25 mm Hg) at rest and elevated mPAP (&gt;30 mm Hg) and PVR&gt; 3 WU at the peak of exercise.

Strategizing Drug Therapies in Pulmonary Hypertension for Improved Outcomes.

Pulmonary hypertension (PH) is characterized by a resting mean pulmonary artery pressure (PAP) of 20 mmHg or more and is a disease of multiple etiologies. Of the various types of PH, pulmonary arterial hypertension (PAH) is characterized by elevated resistance in the pulmonary arterial tree. It is a rare but deadly disease characterized by vascular remodeling of the distal pulmonary arteries. This paper focuses on PAH diagnosis and management including current and future treatment options. Over the last 15 years, our understanding of this progressive disease has expanded from the concept of vasoconstrictive/vasodilatory mismatch in the pulmonary arterioles to now a better appreciation of the role of genetic determinants, numerous cell signaling pathways, cell proliferation and apoptosis, fibrosis, thrombosis, and metabolic abnormalities. While knowledge of its pathophysiology has expanded, the majority of the treatments available today still modulate the same three vasodilatory pathways that have been targeted for over 30 years (endothelin, nitric oxide, and prostacyclin). While modifying these pathways may help improve symptoms and quality of life, none of these directly modify the underlying disease pathogenesis. However, there are now studies ongoing with new drugs that can prevent or reverse these underlying causes of PAH. This review discusses the evidence base for the current treatment algorithms for PAH, as well as discusses novel therapies in development.

Different diagnostic criteria agreement for exercise pulmonary hypertension in chronic thromboembolic pulmonary disease

Abstract Background Hemodynamic changes during exercise have emerged as a diagnostic tool in patients with suspected pulmonary hypertension, considering that an abnormal response may reveal an incipient vasculopathy, particularly in chronic thromboembolic disease (CTED). Since mean arterial pressure (mPAP) is considered a flow-dependent variable, diagnosis of an abnormal pulmonary hemodynamic response has changed over time. Different methods to determine a pathological mPAP to Cardiac Output (CO) ratio have been proposed. Multipoint mPAP – CO Slope &amp;gt;3 mmHg/L/min has reached board consensus for determining an abnormal pulmonary response to exercise as this method can characterize mPAP–CO response across all exercise stages. Given the technic difficulties to obtain this parameter, other criteria have been proposed. Aim To investigate the diagnostic concordance and the reproducibility of the different abnormal pulmonary exercise hemodynamic response criteria in a cohort of patients with CTED. Methods We selected symptomatic patients with confirmed perfusion defects in lung scintigraphy despite optimal anticoagulant therapy for a minimum of 6 months after a pulmonary embolism. The thrombotic burden was assessed with computed tomography (CT). Lelf Heart Disease (LHD) and significant PH were ruled out with RHC (inclusion criteria implied resting mean pulmonary arterial pressure (mPAP) &amp;lt;25 mmHg and pulmonary vascular resistance (PVR) &amp;lt;3 uW and pulmonary arterial wedge pressure (PAWP) &amp;lt;15 mmHg). Exercise RHC was performed in supine position following an incremental stepwise protocol using a cycle ergometer. Pulmonary pressures and CO estimated by thermodilution were collected at each exercise level. Total pulmonary resistance (TPR) was calculated by dividing mPAP by CO. The abnormal hemodynamic response according to the more viable proposed criteria: 1) mPAP &amp;gt;30 mmHg and TPR &amp;gt;3uW at peak exercise, 2) ΔmPAP/ ΔCO &amp;gt;3 mmHg/L/min at rest and peak exercise; was compared to the pathological reference threshold multipoint PAPm/ CO slope &amp;gt;3 mmHg/L/min. Results 22 patients (median age of 54.5±14.8 years old) were recruited. Baseline characteristics and RHC values are summarized in Figure 1. Positive agreement was 93% (77% – 98%) in case of mPAP30peak+ TPR3peak versus mPAP/CO slope (k=0.810) and 91% (74% – 97%) in case of ΔmPAP/ΔCO versus mPAP/CO slope (k=0.801). Both criteria showed high diagnostic accuracy for an abnormal response diagnosis compared with the reference. Figure 2 summarizes their respective sensitivities and specificities. Patients misdiagnosed were those whose hemodynamic response was close to the reference cut-off values (mPAP/CO slope between 2 and 4 mmHg//L/min). Conclusion In a cohort of patients with CTED without significant PH at rest or LHD,the three methods proposed to diagnose an abnormal pulmonary exercise hemodynamic response show accurate concordance. Disagreement was higher in patients with a borderline pathological response. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Sociedad Española de Cardiologia

Alterations in Genes Associated with Bioactive Lipid Pathways during Development of Pulmonary Hypertension in Rat SU5416‐Hypoxia Model of Severe Pulmonary Arterial Hypertension

BackgroundPulmonary arterial hypertension (PAH) is a disease of the pulmonary vascular system characterized by sustained elevation in resting mean pulmonary arterial pressure (&gt;25 mmHg) with presence of occlusive vascular remodeling and progressive loss of microvasculature. PAH patients have a poor five‐year survival rate of only ~50% and the primary cause of death for PAH patients is the right (‐sided) heart failure. Better understanding of pathophysiology of PAH and RHF is required to find novel therapies. In this project, using a rat model of severe PAH, we explored the alterations in expression of genes involved in bioactive lipid pathways in the lungs and the right ventricle (RV) during development of PAH.MethodsAdult male Sprague Dawley rats were administered a single injection of SU5416 (SU; 20 mg/kg, subcutaneous) and subjected to 3 weeks of hypoxia (10% O2) followed by 4 weeks of normoxia (room air), SUHx model of sever PAH. Right ventricular systolic pressure (RVSP) was measured, and heart and lung samples were collected at 1, 3, 7, 21 and 49‐days post SU injection. Histological analysis was conducted to confirm vascular remodeling in the lungs and development of RV hypertrophy (RVH; RV/LV+S). RTqPCR was performed to evaluate gene expression changes in the genes related to bioactive lipids pathways.ResultsIn response to SUHx, progressive increase in RVSP and RVH was observed. Histology of lungs and heart samples confirmed pulmonary vascular and RV remodeling at 7 weeks post SU in the SUHx model. We observed increase in expression of ALOX‐5 in the RV and lungs of SUHx rats, compared to controls. Furthermore, alterations in various cytochrome P450 (CYP) isozymes were observed in the RV and lungs of SUHx rats compared to controls.ConclusionsTogether, we have identified unique changes in bioactive lipid pathway genes in the lungs and the RV that were associated with development of PAH and RV remodeling in SUHx model. Further studies are ongoing to confirm the role of the candidate genes in pathophysiology of PAH and development of RHF.

PH-ILD: Identification, Evaluation, and Monitoring: A Diagnostic View From Both Sides

PH-ILD: Identification, Evaluation, and Monitoring: A Diagnostic View From Both Sides

EXERCISE HEMODYNAMICS TO REVEAL LATENT PULMONARY VASCULAR ABNORMALITIES AMONG CHRONIC THROMBOEMBOLIC DISEASE PATIENTS

BACKGROUND Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by persistent and organized pulmonary thrombi and pulmonary hypertension (PH). Right heart catheterization (RHC) is the gold standard for diagnosis of PH, defined by a resting mean pulmonary artery pressure (mPAP) > 20 mmHg. Chronic organized thrombi, in the absence of PH at rest is termed chronic thromboembolic disease (CTED). Pulmonary endarterectomy (PEA) is indicated for CTEPH, however PEA is not routinely endorsed for CTED. Exercise is increasingly employed as a provocative maneuver during RHC to elicit abnormalities of pulmonary vascular and cardiac physiology in patients without PH at rest who are at risk of pulmonary vascular disease. Exercise RHC may expose abnormalities of pulsatile or resistive pulmonary vascular afterload in CTED patients and may potentially identify a subset of CTED patients who benefit from PEA surgery. We describe the proportion of CTED patients with latent pulmonary vascular hemodynamic abnormalities and their hemodynamic characteristics. METHODS AND RESULTS Consecutive patients with a resting mPAP ≤ 20 mmHg and CTED who completed an exercise hemodynamic study between November 2016 and September 2020 were included. We defined exercise abnormalities of pulmonary resistive load as mPAP/CO > 3 WU and exercise abnormalities of pulsatile load as the ratio of pulmonary pulse pressure to pulmonary artery wedge pressure (PP/PAWP) > 2.5. Thirty-seven CTED patients (32% female, 55±15 years) were analyzed. Resting hemodynamics for the entire cohort and exercise hemodynamics for patients with and without latent pulmonary vascular abnormalities are shown (Table 1). Twenty-two patients (59%) demonstrated latent pulmonary vascular abnormalities; 12 had an elevated pulsatile load (PP/PAWP 5.3±4.5), 5 had an elevated resistive load (mPAP/CO 3.7±0.7 WU) and 5 had both (mPAP/CO 3.7±0.5 WU, PP/PAWP 7.3±3.6). Patients with latent pulmonary vascular abnormalities exercised to lower work-rates (P=0.03) and had lower exercise PAWP (P=0.02). They were also characterized by higher pulmonary vascular resistance (P < 0.001) and impaired pulmonary artery compliance (P < 0.001) compared to patients without latent pulmonary vascular abnormalities. CONCLUSION Patients with CTED and resting mPAP ≤ 20mmHg, exercise demonstrated latent abnormal pulmonary vascular responses in over 50% of patients. These patients predominantly demonstrated abnormalities of pulsatile afterload relative to resistive afterload. Further study is required to understand if these patients benefit from PEA surgery. Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by persistent and organized pulmonary thrombi and pulmonary hypertension (PH). Right heart catheterization (RHC) is the gold standard for diagnosis of PH, defined by a resting mean pulmonary artery pressure (mPAP) > 20 mmHg. Chronic organized thrombi, in the absence of PH at rest is termed chronic thromboembolic disease (CTED). Pulmonary endarterectomy (PEA) is indicated for CTEPH, however PEA is not routinely endorsed for CTED. Exercise is increasingly employed as a provocative maneuver during RHC to elicit abnormalities of pulmonary vascular and cardiac physiology in patients without PH at rest who are at risk of pulmonary vascular disease. Exercise RHC may expose abnormalities of pulsatile or resistive pulmonary vascular afterload in CTED patients and may potentially identify a subset of CTED patients who benefit from PEA surgery. We describe the proportion of CTED patients with latent pulmonary vascular hemodynamic abnormalities and their hemodynamic characteristics. Consecutive patients with a resting mPAP ≤ 20 mmHg and CTED who completed an exercise hemodynamic study between November 2016 and September 2020 were included. We defined exercise abnormalities of pulmonary resistive load as mPAP/CO > 3 WU and exercise abnormalities of pulsatile load as the ratio of pulmonary pulse pressure to pulmonary artery wedge pressure (PP/PAWP) > 2.5. Thirty-seven CTED patients (32% female, 55±15 years) were analyzed. Resting hemodynamics for the entire cohort and exercise hemodynamics for patients with and without latent pulmonary vascular abnormalities are shown (Table 1). Twenty-two patients (59%) demonstrated latent pulmonary vascular abnormalities; 12 had an elevated pulsatile load (PP/PAWP 5.3±4.5), 5 had an elevated resistive load (mPAP/CO 3.7±0.7 WU) and 5 had both (mPAP/CO 3.7±0.5 WU, PP/PAWP 7.3±3.6). Patients with latent pulmonary vascular abnormalities exercised to lower work-rates (P=0.03) and had lower exercise PAWP (P=0.02). They were also characterized by higher pulmonary vascular resistance (P < 0.001) and impaired pulmonary artery compliance (P < 0.001) compared to patients without latent pulmonary vascular abnormalities. Patients with CTED and resting mPAP ≤ 20mmHg, exercise demonstrated latent abnormal pulmonary vascular responses in over 50% of patients. These patients predominantly demonstrated abnormalities of pulsatile afterload relative to resistive afterload. Further study is required to understand if these patients benefit from PEA surgery.

Correlation between Pulmonary Artery Hypertension Caused by Acyanotic CHD with Left to Right Shunt and Increased Level of Endothelin-1

Background: Pulmonary hypertension is defined as a resting mean pulmonary artery pressure (mPAP) of 25 mmHg or above. PAH is a frequent complication of congenital heart disease (CHD), particularly in patients with left-to-right (systemic-to-pulmonary) shunts. Objective: The present study aimed to investigate changes in the blood level of endothelin-1 (ET-1) in patients of PAH complicated by acyanotic CHD and to detect possible correlation with different hemodynamic parameters. Patient and methods: 48 children were recruited in Pediatric Cardiology Unit, Pediatrics Department in Zagazig University Hospitals after obtaining the required permissions and informed consent from the their caregivers. They were divided into Group (A), which included 24 children with acyanotic CHD with left to right shunt with PAH and Group B included 24 children with acyanotic CHD with left to right shunt but no PAH. All children were subjected to clinical and radiological examination, echocardiography and measurement of endothelin-1 level as well as correlation between the studied parameters were performed. Results: the present results showed that Group A was significantly associated with previous need of hospital admission and insignificantly associated with ICU need. Endothelin-1 was significantly negatively correlated with weight and oxygen saturation (SPO2) but significantly positively correlated with systolic blood pressure (SBP), heart rate (HR), respiratory rate (RR) and pulmonary blood pressure. Significant area under the curve (AUC) with cutoff value >1.55 with sensitivity 85.05 and specificity 91.1%. Conclusion: Pulmonary hypertension (PAH) complicated by CHD can be predicted by estimation of endothelin-1 (ET-1) as an indicator of endothelial injury.

Abstract 17136: Pulmonary Arterial and Venous Fractal Dimension as a Marker of Pulmonary Arterial Hypertension

Introduction: PAH is characterized by a loss of pulmonary vascular complexity. In this study, total, arterial, and venous vasculatures of patients with PAH and with ePAH were analyzed using fractal analysis and compared against controls Methods: Data from 1514 consecutive right heart catheterizations from 4/27/2011 to 10/2/2018 representing subjects referred to our dyspnea center were searched for availability of imaging. 388 CT angiography (CTA) scans were identified (used given retrospective availability of thin slice reconstructions). Three initial cohorts (no overlap) were identified from individuals in this set. Control patients had normal resting and exercise hemodynamics and no history of cardiopulmonary disease. The second group met the current definition of PAH (resting mean pulmonary arterial pressure &gt;20mmHg, pulmonary vascular resistance &gt;3 Wood Units, pulmonary capillary wedge pressure &lt;15mmHg). The third group (ePAH) had normal resting hemodynamics but age adjusted evidence of PAH with exercise. Pulmonary vascular trees were reconstructed; total, arterial, and venous trees were separated; and fractal dimensions were measured using a 3D box counting method for each tree. Comparisons were made using the Wilcoxon Rank Sum test (R 3.5). Results: Venous fractal dimensions of controls (2.10±0.07) were higher than those of PAH (2.03±0.08; p=3e-6) and of ePAH (2.04±0.13; p=0.008). Total fractal dimension also yielded higher values for controls (2.30±0.05) compared against PAH (2.28±0.07; p=0.009) and ePAH (2.26±0.10; p=0.04). No significant differences were found between arterial fractal dimensions of controls (2.17±0.04) against those of PAH (2.16±0.07; p=0.15) and of ePAH (2.15±0.10; p=0.14). Conclusions: Fractal dimension allows for non-invasive characterization of pulmonary vascular complexity. Using this method, patients with PAH or ePAH were found to have lower total and venous vascular complexities than controls without PAH or ePAH.

Optimizing diastolic pressure gradient assessment

AimsThe 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 (DPGNEG) 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 (PAWPY) influences the prevalence of DPGNEG and the prognostic value of the resultant DPGY.MethodsHundred and fifty-three consecutive HF patients referred for right heart catheterisation were enrolled prospectively. DPG, as currently recommended, was calculated. Subsequently, PAWPY was measured and the corresponding DPGY was calculated.ResultsDPGY 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 DPGY in only 15%. During follow-up (22 ± 14 months) 58 patients have undergone heart-transplantation or died. The predictive ability of DPGY ≥ 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 (PAPM). In contrast, conventional DPG did not comprise significant prognostic value following adjustment for PAPM.ConclusionInstantaneous pressures at the trough of Y-descent yield significantly fewer DPGNEG than conventional DPG and entail superior prognostic value in HF patients with and without PH.Graphic abstract

Borderline pulmonary hypertension is associated with exercise intolerance and increased risk for acute exacerbation in patients with interstitial lung disease

BackgroundPulmonary hypertension (PH) is traditionally defined as a resting mean pulmonary artery pressure (mPAP) of ≥25 mmHg, while mPAP in the range of 21 to 24 mmHg is recognized as “borderline PH.” Interstitial lung disease (ILD) is complicated by the development of PH, which is known to be linked with exercise intolerance and a poor prognosis. Even though it has recently been recommended that PH is redefined as a mPAP of > 20 mmHg, little is known about the clinical significance of borderline PH in ILD. We evaluated whether borderline PH has an impact on the exercise capacity, risk of acute exacerbation (AE), and mortality in patients with ILD.MethodsA total of 80 patients with ILD who underwent right heart catheterization (RHC) between November 2013 and October 2016 were included. The patients were divided into 3 groups according to the mPAP values: mPAP ≤20 mmHg (No-PH group; n = 56), 20 < mPAP < 25 mmHg (Bo-PH group; n = 18), and mPAP ≥25 mmHg (PH group; n = 6). The demographic, hemodynamic, spirometric, and 6-min walk test (6MWT) data of the patients were collected. In addition, the 1-year incidence of AEs and 1-year survival of the patients after the initial RHC were also evaluated.ResultsThere were no significant differences among the 3 groups in the mean age, pulmonary function parameters or the PaO2, however, 6-min walk distance was significantly lower in both the Bo-PH and PH groups (p < 0.001 for both) as compared to the No-PH group. The results of the Kaplan-Meier analysis revealed that while there was no significant difference in the 1-year survival rate among the three groups, the 1-year incidence of AEs was significantly higher in both the Bo-PH and PH groups (p < 0.001, p = 0.023, respectively) as compared to the No-PH group.ConclusionsThe current study suggested that borderline PH may be associated with poorer exercise tolerance and an increased risk of AEs in patients with ILD. Therefore, the physicians should pay close attention to the presence of even mild elevation of the mPAP at the initial evaluation in patients with ILD.

Pulmonary capillary surface area in supine exercising humans: demonstration of vascular recruitment.

In exercising humans, cardiac output (CO) increases, with minor increases in pulmonary artery pressure (PAP). It is unknown if the CO is accommodated via distention of already perfused capillaries or via recruitment of nonconcomitantly perfused pulmonary capillaries. Ten subjects (9 female) performed symptom-limited exercise. Six had resting mean PAP (PAPm) <20 mmHg, and four had PAPm between 21 and 24 mmHg. The first-pass pulmonary circulatory metabolism of [3H]benzoyl-Phe-Ala-Pro (BPAP) was measured at rest and at peak exercise, and functional capillary surface area (FCSA) was calculated. Data are means ± SD. Mean pulmonary arterial pressure rose from 18.8 ± 3.3 SD mmHg to 28.5 ± 4.6 SD mmHg, CO from 6.4 ± 1.6 to 13.4 ± 2.9 L/min, and pulmonary artery wedge pressure from 14 ± 3.3 to 19.5 ± 5 mmHg (all P ≤ 0.001). Percent BPAP metabolism fell from 74.7 ± 0.1% to 67.1 ± 0.1%, and FCSA/body surface area (BSA) rose from 2,939 ± 640 to 5,018 ± 1,032 mL·min-1·m-2 (all P < 0.001). In nine subjects, the FCSA/BSA-to-CO relationship suggested principally capillary recruitment and not distention. In subject 10, a marathon runner, resting CO and FCSA/BSA were high, and increases with exercise suggested distention. Exercising humans demonstrate pulmonary capillary recruitment and distention. At moderate resting CO, increasing blood flow causes principally recruitment while, based on one subject, when exercise begins at high CO, further increases appear to cause distention. Our findings clarify an important physiologic question. The technique may provide a means for further understanding exercise physiology, its limitation in pulmonary hypertension, and responses to therapy.

Reduced Right Ventricular Output Reserve in Patients With Systemic Sclerosis and Mildly Elevated Pulmonary Artery Pressure.

This prospective study was undertaken to evaluate right ventricular function and pulmonary arterial compliance (PAC; ratio of stroke volume to pulse pressure) at rest and during exercise in patients with systemic sclerosis (SSc) with normal mean pulmonary artery pressure (PAP), patients with SSc with mildly elevated mean PAP, and patients with SSc with manifest pulmonary hypertension (PH). Patients with SSc (n = 112) underwent clinical assessment and right-sided heart catheterization at rest and during exercise and were divided into 3 groups according to their resting mean PAP values: normal mean PAP (≤20 mm Hg), mildly elevated mean PAP (21-24 mm Hg), and PH (mean PAP ≥25 mm Hg). Results were compared between groups by analysis of variance followed by post hoc Student's t-test. Compared to patients with normal mean PAP, patients with mildly elevated mean PAP had a lower 6-minute walking distance (P = 0.008), lower cardiac index (P = 0.027) and higher pulmonary vascular resistance (P = 0.0002) during exercise, and lower PAC at rest (P = 0.016) and different stages of exercise (P = 0.033 for 25W and P = 0.024 for 75W). The results of this study suggest that impaired 6-minute walking distance in SSc patients with mildly elevated mean PAP might be caused by reduced PAC during exercise and reduced right ventricular output reserve, presumably due to impaired coupling between the right ventricle and the pulmonary vasculature. These findings provide further evidence of the clinical relevance of mildly elevated mean PAP in patients with SSc.

Non-invasive Multimodality Cardiovascular Imaging of the Right Heart and Pulmonary Circulation in Pulmonary Hypertension.

Pulmonary hypertension (PH) is defined as resting mean pulmonary arterial pressure (mPAP) ≥25 millimeters of mercury (mmHg) via right heart (RH) catheterization (RHC), where increased afterload in the pulmonary arterial vasculature leads to alterations in RH structure and function. Mortality rates have remained high despite therapy, however non-invasive imaging holds the potential to expedite diagnosis and lead to earlier initiation of treatment, with the hope of improving prognosis. While historically the right ventricle (RV) had been considered a passive chamber with minimal role in the overall function of the heart, in recent years in the evaluation of PH and RH failure the anatomical and functional assessment of the RV has received increased attention regarding its performance and its relationship to other structures in the RH-pulmonary circulation. Today, the RV is the key determinant of patient survival. This review provides an overview and summary of non-invasive imaging methods to assess RV structure, function, flow, and tissue characterization in the setting of imaging's contribution to the diagnostic, severity stratification, prognostic risk, response of treatment management, and disease surveillance implications of PH's impact on RH dysfunction and clinical RH failure.

＜Editors' Choice＞ Pulmonary Hypertension: Diagnosis, Management, and Treatment.

ABSTRACTPulmonary hypertension (PH) is a hemodynamic state that is characterized by a resting mean pulmonary artery pressure ≧ 25 mmHg. The common forms of PH are pulmonary arterial hypertension (PAH), chronic thromboembolic pulmonary hypertension (CTEPH), PH caused by left-heart disease, and PH due to lung disease. Previously regarded as untreatable, the treatment of PAH has dramatically advanced since the introduction of the drug epoprostenol in 1999, with three-year survival rates improving from 30%–40% to over 85%. Drugs available for the specific treatment of PAH include endothelin-receptor antagonists, phosphodiesterase type 5 inhibitors, soluble guanylate cyclase stimulators, prostacyclin analogs, and prostacyclin-receptor agonists. In the past decade, management and treatment of CTEPH have also improved. While pulmonary endarterectomy used to be the only option for the treatment of CTEPH, newer treatments include a soluble guanylate cyclase stimulator, which has proven to be an efficacious targeted therapy. Other cases benefit from balloon pulmonary angioplasty.