Postcapillary Postcapillary Pulmonary Hypertension Research Articles

Increased left atrial pressure distorts pulmonary arterial impedance estimates in the low-range of frequency in rats

BACKGROUD: Post-capillary pulmonary hypertension (PH), characterized as increased downstream pressure such as left atrial pressure (LAP), is the most prevalent type of PH and a significant contributor to right heart failure. Accurate estimation of pulmonary arterial characteristics, serving as right ventricular afterload, is crucial for management of PH. These characteristics can be captured comprehensively through pulmonary arterial impedance (PAZ), which elucidates pulmonary arterial pressure-flow relationship within the frequency domain. Although LAP waveforms are potential to affect the contours of pulmonary arterial pressure (PAP) and flow (PAF) waveforms, it remains unknown whether increased LAP affects the accuracy of PAZ measurement. This study aimed to investigate the impact of LAP on the accuracy of PAZ using an acute rodent model. METHODS: We measured pulmonary arterial blood flow (PAF), PAP, and LAP simultaneously in eight male Sprague-Dawley rats. PAZ was calculated as a reciprocal of admittance. Admittance was calculated in the following two ways: 1) one-input (PAP) and one-output (PAF) analysis (I1O1 analysis): the ratio of PAP(f) to PAF(f) at each frequency, where PAP(f) and PAF(f) are frequency spectra of PAP and PAF, respectively, and 2) two-input (PAP and LAP) and one-output (PAF) analysis (I2O1 analysis): excluding the potential effect of LAP from PAP and PAF. We measured PAZ under both normal physiological condition and post-capillary PH condition. To induce acute post-capillary PH by raising LAP >15 mmHg, we ligated aortic arch at the site between brachiocephalic artery and left common carotid artery and performed blood transfusion from a donor rat (TAL/BT). The accuracy of PAZ was examined as the coherence function representing the linearity between the input and output signals. Results: TAL/BT significantly increased LAP from 3 ± 1mmHg to 21 ± 4 mmHg and PAP from 17 ± 3 mmHg to 34 ± 3 mmHg (p<0.01 for both). The I2O1 analysis provided a consistently accurate estimation of PAZ under both normal and elevated LAP conditions with high coherence function (>0.9) in the wide range of frequency between 0.12 and 10.7 Hz. The I1O1 analysis also estimated the PAZ accurately in normal condition with high coherence function (>0.9) in the wide range of frequency, however, the I1O1 analysis overestimated PAZ in the low-range frequency between 0.12 and 1.0 Hz compared with the I2O1 analysis (I1O1: 0.32±0.10 vs. I2O1 0.23±0.06 mmHg/ml/min, p<0.01), with significantly lower coherence function (I1O1: 0.77±0.05 vs. I2O1: 0.96±0.01, p<0.01). CONCLUSION: Increased LAP may have the impact on the accuracy of PAZ estimation in the low-range frequency. The I2O1 analysis can lead to more accurate assessment of right ventricular afterload in post-capillary PH, compared with the I1O1 analysis. Grant-in-Aid for Young Scientists of the Japanese Society of Cardiovascular Anesthesiologists Project Number 2271000048. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Predictive value of left atrial volumes assessed using real-time three-dimensional echocardiography for pulmonary hypertension in dogs with myxomatous mitral valve disease.

Left atrial volume (LAV) obtained using real-time three-dimensional echocardiography (RT3DE) is an independent predictor of post-capillary pulmonary hypertension (PH) in humans; however, no studies have investigated LAV obtained using RT3DE as a predictor of post-capillary PH in dogs with myxomatous mitral valve disease (MMVD). Therefore, we aimed to evaluate the clinical applicability of LAV obtained using RT3DE compared to that obtained using two-dimensional echocardiography (2DE) in dogs with MMVD, with or without PH. Medical records and echocardiographic images of 237 privately owned dogs with naturally occurring MMVD with or without PH were retrospectively reviewed. A total of 49 privately owned dogs with naturally occurring MMVD, with or without PH, were finally included (35 MMVD without PH, 14 MMVD with PH). The LAV and left ventricular volumes were obtained using 2DE and RT3DE. Echocardiographic parameters were analyzed to identify independent predictors of post-capillary PH. We found that the left atrial and left ventricular volumes obtained using 2DE and RT3DE indexed to body weight and several 2DE-derived variables were univariately associated with post-capillary PH. Furthermore, multivariable logistic regression analysis revealed that the RT3DE minimum LAV indexed to body weight (LAVi min) was the only significant independent predictor of post-capillary PH (odds ratio, 12.86; 95% confidence interval [CI], 2.40-68.99; p = 0.003), with the highest area under the curve value of 0.86 (95% CI, 0.75-0.96; p < 0.001). In conclusion, LAV indexed to body weight obtained using 2DE and RT3DE, can be a useful predictor of post-capillary PH in dogs with MMVD. In particular, the RT3DE LAVi min was observed to be the strongest predictor of post-capillary PH.

Validation of the OPTICS and H2FPEF risk scores for post-capillary pulmonary hypertension in an asian cohort

Abstract Background The differentiation between pre- and post-capillary pulmonary hypertension (PH) plays a significant impact in the management of PH patients. Right heart catheterization (RHC) serves as an important test to facilitate this differentiation. However, the RHC is invasive and oftentimes in Asia, the uptake and availability of the RHC due to costs and other considerations may be limited. The OPTICS score was previously developed to predict a raised pulmonary capillary wedge pressure (PCWP) in patients with PH. The H2FPEF score is typically used to predict heart failure with preserved ejection fraction (HFpEF) but has been suggested to be able to predict raised PCWP as well. Both scores have been validated in European cohorts, however the utility of this score in an Asian population is unknown. Purpose We aim to validate the utility of the OPTICS and H2FPEF scores in predicting the presence of a raised PCWP in an Asian population. Methods Available data from patients admitted to a tertiary cardiac center in Asia who had received a RHC between July 2018 to June 2022 were included. The established cut offs for the OPTICS and H2FPEF scores of ≥104 and ≥6 respectively were applied retrospectively to predict the presence of raised PCWP (defined as ≥15 mmHg) and the results compared to the actual PCWP from RHC. The receiver operating characteristic (ROC) curves and area under curves (AUC) were calculated. A sensitivity analysis was performed with the exclusion of patients with mixed PH (PCWP ≥15 mmHg with pulmonary vascular resistance ≥3 WU). Results 433 patients were included, of which 274 had a raised PCWP ≥15 mmHg and 159 had a PCWP &amp;lt;15 mmHg. With a cut-off of ≥104, the OPTICS risk score had a specificity of 96%, sensitivity of 20%, positive predictive value (PPV) of 90%, negative predictive value (NPV) of 41%, and accuracy of 48%. With a cut-off of ≥6, the H2FPEF score had a specificity of 86%, sensitivity of 30%, PPV of 79%, NPV of 42%, and accuracy of 51%. The OPTICS and H2FPEF scores had an AUC of 0.69 and 0.66 respectively (Figure 1). Sensitivity analysis excluding patients with mixed PH (n=173) was performed and similar results were obtained. Conclusion In our Asian cohort, the high specificity of the OPTICS score may help in better identifying a subset of PH patients with postcapillary PH, potentially reducing the need of RHC in this group and guiding overall management. The lower sensitivity of both scores suggest that these scores should not be used as routine screening tools.ROC curves of OPTICS vs H2FPEF scores

Can Inhaled Nitric Oxide Response Predict Tolerance to Therapies and Survival in Patients With Combined Precapillary and Postcapillary Pulmonary Hypertension?

Inhaled nitric oxide (iNO) relaxes the pulmonary circulation and variably increases the left ventricular preload and pulmonary artery wedge pressure (PAWP)-hemodynamic information that may help guide treatment decisions and assess prognosis in patients with combined precapillary and postcapillary pulmonary hypertension (PH). We included consecutive patients with combined precapillary and postcapillary PH (mean pulmonary artery pressure >20mm Hg, PAWP >15mm Hg, and pulmonary vascular resistance [PVR] >2 Woods unit [WU]) who underwent right-sided cardiac catheterization with iNO at the Cleveland Clinic Pulmonary Vascular Disease program between 2017 and 2022. We included 104 patients with baseline PAWP and PVR of 22.2 ± 4.2mm Hg and 6.1 ± 3.2 WU, respectively. Pulmonary arterial hypertension (PAH) with postcapillary component and PH left heart disease with precapillary component were identified in 27 (26%) and 77 patients (74%), respectively. No side effects were noted during the administration of iNO. During iNO, the PVR decreased 1.1 ± 1.4 WU and the PAWP increased 1.3 ± 3.7mm Hg. A more pronounced increase in PAWP with iNO was associated with a decrease in PVR (R -0.35, p <0.001) and increase in stroke volume (R 0.20, p=0.046). Tolerance to PAH-specific medications, overall survival, and heart failure hospitalizations were not significantly associated with the change in PAWP or PVR with iNO. In conclusion, in patients with combined precapillary and postcapillary PH, iNO challenge is safe and caused a significant decrease in PVR, with an increase in PAWP. The changes in PAWP and PVR during iNO administration were not associated with tolerance to PAH-specific medications, heart failure-related hospitalization, or survival.

Phenotype of patients with pulmonary hypertension due to left heart disease: features of pathophysiology and differential diagnosis

The cohort of patients with postcapillary pulmonary hypertension (PH), associated with the left heart diseases, is the most numerous, but is still not fully understood. This review presents the pathophysiological aspects of the PH group 2 development as well as the influence of comorbid pathology on the course of the PH. The features of the differential diagnosis of post-capillary PH and combined post-/ precapillary PH, as well as methods of the differential diagnosis of these forms of PH with pulmonary arterial hypertension using modern non-invasive and invasive approaches are discussed.

Alterations of pulmonary vascular afterload in exercise‐induced pre‐ and post‐capillary pulmonary hypertension

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

Liver Transplant Outcomes in Patients With Postcapillary Pulmonary Hypertension.

Background.Postcapillary pulmonary hypertension (PH) can be seen in cirrhosis. Research and treatment goals exist for patients with portopulmonary hypertension but not for postcapillary PH. The aim of this study was to investigate outcomes after liver transplant (LT) for patients with postcapillary PH.Methods.This was a retrospective cohort study of 1173 patients who underwent LT at our center between 2010 and 2020. Using a propensity score matched analysis followed by multivariable Cox modeling on matched patients, we compared post-LT survival between patients with and without postcapillary PH. We also compared several post-LT outcomes between patient with different types of PH.Results.Sixty-eight patients had PH, and 50 had postcapillary PH. The median age was 59 y and the sample was 54% male. There was no significant difference in mortality between patients with postcapillary PH and patients without PH (hazard ratio, 1.72; 95% confidence interval, 0.90-3.31; P = 0.10). There was no significant difference in survival between patients with any type of PH and those without PH. There was no significance difference in post-LT survival, acute kidney injury, or pulmonary edema between patients with different types of PH. Patients with postcapillary PH who survived had a higher cardiac output than those who died (11 L/min in patients who lived, as compared with 8 L/min in patients who died; P = 0.03).Conclusions.Postcapillary PH does not appear to convey a negative impact on post-LT survival. A higher cardiac output may be protective against mortality in patients with postcapillary PH.

Cine magnetic resonance imaging detects shorter cardiac rest periods in postcapillary pulmonary hypertension.

A shorter cardiac rest period within a cardiac cycle is usually thought to be a result of a fast heart rate, and its clinical relevance has long been ignored. The aim of the present study was to test the hypothesis that the length of cardiac rest periods is altered in postcapillary pulmonary hypertension (PH). Twenty-six patients with postcapillary PH and 20 healthy controls were recruited for cardiac magnetic resonance imaging (MRI) scans. All participants had a heart rate no higher than 80 beats/minute. Cine magnetic resonance imaging (MRI, acquired at a four-chamber view) was analyzed to determine the length of cardiac rest periods at end-systole and mid-to-late diastole. PH patients had a shorter rest period at mid-to-late diastole than controls (17.5 ± 8.7% vs. 24.2 ± 4.2%, P = 0.003). Receiver operating characteristic (ROC) curves showed that the proportion of the rest period in diastole (defined as the length of diastasis/diastole) can discriminate PH patients from controls [area under the curve (AUC) = 0.83, 95% confidence interval (CI): 0.71-0.96]. The existence of postcapillary PH was a significant contributor (β = -5.537, P = 0.023) to shorter cardiac rest periods at mid-to-late diastole after adjusting for potential confounders, including age, sex, heart rate, and blood pressure. Postcapillary PH is independently associated with shorter cardiac rest periods at mid-to-late diastole. The length of cardiac rest periods has the potential to become a novel quantitative imaging biomarker for indicating cardiovascular health.

Patient–Prosthesis Mismatch Associated With Somatic Growth After Mechanical Mitral Valve Replacement in Small Children: Metrics for Reoperation and Outcomes

Reoperation after pediatric mitral valve replacement (MVR) is inevitable due to patient-prosthesis mismatch (PPM) associated with somatic growth. We analyzed potential metrics for PPM and outcomes of redo MVR for valve upsizing. Between 1999 and 2018, 15 children without obstructive left heart lesions other than mitral stenosis underwent initial MVR with a 16-mm ATS-Advanced Performance valve. We analyzed hemodynamic data from 28 postoperative catheterizations and concomitant echocardiograms. The median age and body weight at initial MVR were 4.9 months (25th, 75th percentile: 3.6, 6.6) and 5.9 kg (5.0, 7.3). Redo MVR was planned when patients had congestive heart failure and postcapillary pulmonary hypertension (PH) due to PPM: systolic pulmonary arterial pressure (SPAP) >35 mm Hg and pulmonary capillary wedge pressure (PCWP) >15 mm Hg on catheterization. Indexed effective orifice area (iEOA) and mean transmitral pressure gradient (TMPG) were strongly correlated with SPAP (r = -0.72, P < 0.001 and r = 0.75, P < 0.001) and PCWP (r = -082, P < 0.001 and r = 0.84, P < 0.001). Cut-off values for detecting postcapillary PH due to PPM were 1.0 cm2/m2 for iEOA and 18 mm Hg for mean TMPG. Nine patients underwent redo MVR for postcapillary PH due to PPM at a median postoperative interval of 10 years (9.2, 11.9). All the patients survived, and PH was improved one year after surgery. iEOA and mean TMPG can be metrics for PPM in children after MVR. Careful follow-up is required to confirm the improvement of preoperatively existing PH after redo MVR for valve upsizing.

Pulmonary Vascular Resistance Estimated by Echocardiography in Dogs With Myxomatous Mitral Valve Disease and Pulmonary Hypertension Probability.

Post-capillary pulmonary hypertension (PH) is a life-threatening complication in dogs with myxomatous mitral valve disease (MMVD). An increase in pulmonary vascular resistance (PVR) is associated with post-capillary PH progression. In humans, PVR estimated by echocardiography (PVRecho) enables the non-invasive assessment of PVR in patients with PH. This study aimed to evaluate the clinical utility of PVRecho in dogs with MMVD, PH probability, and right-sided congestive heart failure (R-CHF). Dogs with MMVD and detectable tricuspid valve regurgitation were included in the study. Dogs were classified into three PH probability groups (low/intermediate/high) and according to the presence or absence of R-CHF. All dogs underwent echocardiographic measurements for right ventricular (RV) morphology and function. PVRecho was calculated by two methods using tricuspid valve regurgitation velocity and velocity–time integral of the pulmonary artery flow (PVRecho and PVRecho2). RV size indicators were significantly higher with a higher probability of PH. RV strain and velocity–time integral of the pulmonary artery flow in the high probability group were significantly lower than those in the other groups. Tricuspid valve regurgitation velocity, PVRecho, and PVRecho2 were significantly higher with an increase in PH probability. Logistic regression analysis revealed a significant association between the presence of R-CHF and increased PVRecho2 and end-diastolic RV internal dimension normalized by body weight. PVRecho and PVRecho2 showed significant differences among the PH probability groups. These non-invasive variables may be useful for the diagnosis and stratification of PH and the determination of the presence of R-CHF in dogs with MMVD.

Wedge Pressure vs Left Ventricular End-Diastolic Pressure for Pulmonary Hypertension Classification and Prognostication in Severe Aortic Stenosis

BackgroundDifferentiation between precapillary and postcapillary pulmonary hypertension (PH) classically relies on mean pulmonary artery wedge pressure (mPAWP). The left ventricular end-diastolic pressure (LVEDP) is proposed as an equivalent alternative. However, mPAWP and LVEDP may differ substantially. We compared the impact of the choice of using the mPAWP vs the LVEDP on PH classification and mortality prediction in patients with severe aortic stenosis (AS) undergoing valve replacement. MethodsIn 335 patients with severe AS , both mPAWP and LVEDP were measured. A mean pulmonary artery pressure ≥ 25 mm Hg was used to define PH, and either mPAWP or LVEDP was used to differentiate between precapillary and postcapillary PH (≤ 15 vs > 15 mm Hg). Mortality after a median follow-up of 1484 days after aortic valve replacement was assessed. ResultsOverall, mPAWP was lower than LVEDP (16 ± 8 mm Hg vs 21 ± 8 mm Hg; P < 0.001). Among 140 patients (42%) with PH, the PAWP-based classification revealed 76 (54% of those with PH) with isolated postcapillary PH, 48 (34%) with combined pre- and postcapillary PH, and 16 (12%) with precapillary PH. When the LVEDP was used, 59 patients (42%) were differently classified. These patients had higher mortality than those who were not differently classified [hazard ratio 2.79 (95% confidence interval, 1.17-6.65); P = 0.02]. Higher mPAWP was associated with increased mortality [hazard ratio 1.07 (95% confidence interval, 1.03-1.11) per 1 mm Hg; P = 0.001], whereas higher LVEDP was not. ConclusionsUse of LVEDP rather than mPAWP results in a divergent PH classification in nearly every second patient with severe AS. These patients have higher mortality after aortic valve replacement. The mPAWP, but not the LVEDP, predicts mortality.

Cine MRI characterizes HFpEF and HFrEF in post-capillary pulmonary hypertension

PurposeTo test the hypothesis that cine MRI can be used to characterize features of left and right ventricles in post-capillary pulmonary hypertension (PH) caused by heart failure (HF) with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF). MethodsWith the approval of institution review board (IRB), 28 consecutive post-capillary PH patients (11 males, 62.1 ± 13.4 years old, range 39–89 years old) underwent cine MRI scans. Cine MRI-derived left ventricular (LV) ejection fraction (LVEF) and other function, motion, and deformation indices (acquired with heart deformation analysis [HDA]) were compared between PH-HFpEF (defined as LVEF ≥ 50 %]) and PH-HFrEF (LVEF < 50 %) patients and were related with right ventricular (RV) indices and right heart catheterization (RHC)-derived pulmonary artery measurements. ResultsTotally 19 patients (68 %, 95 % confident interval [CI] 49 %–86 %) were assigned to PH-HFpEF group while 9 (32 %) was assigned to the PH-HFrEF group. There were differences of LV and right ventricular (RV) global functional indices, LV mass, LV displacement, velocity, strain and strain rate between the two patient groups. Cine MRI-derived LV indices had broad associations with RV indices and RHC measurements. LVEF was negatively correlated with pulmonary capillary wedge pressure (PCWP) (r = -0.5, p = 0.007). LV cardiac index (LVCI) was associated with systolic pulmonary artery pressure (sPAP) (r = 0.443, p = 0.018). ConclusionsPH-HFpEF and PH-HFrEF patients present dissimilar function, motion and deformation features in LV and RV. Cine MRI-derived LV measures are correlated with hemodynamic abnormalities of PH.

Cine MRI detects elevated left heart pressure in pulmonary hypertension.

Cine magnetic resonance imaging (MRI) is an emerging modality for evaluating left ventricular (LV) motion/deformation patterns, which may have potential to identify LV dysfunctions underlying postcapillary pulmonary hypertension (PH). The aim of this study was to test the hypothesis that cine MRI-derived LV motion/deformation indices can be used to identify an elevated left heart pressure in PH. This was a retrospective study, which included 26 precapillary and 28 postcapillary PH patients (23 males, 58.9 ± 13.5 years old). All patients underwent right heart catheterization (the "reference standard") and cardiac MRI. Balanced steady-state free precession cine sequence acquired at 1.5 T was used. Cine MRI datasets were analyzed by using heart deformation analysis. LV motion/deformation indices were measured through 25 phases within a cardiac cycle. Peak LV displacement, velocity, strain, and strain rates at systole, early and late diastole were compared between the two patient groups using t-tests. The Pearson correlation coefficient (r) was used to investigate the association between cine MRI-derived indices and pulmonary capillary wedge pressure (PCWP). Multivariable linear and logistic regression models were applied to assess the ability of MRI-derived parameters to predict PCWP and postcapillary PH. Compared to 26 precapillary PH patients, the 28 postcapillary PH patients had lower peak late radial diastolic displacement (0.43 ± 0.19 cm vs. 0.64 ± 0.18 cm) and velocity (12.2 ± 5.8 mm/s vs. 18.9 ± 5.6 mm/s) and peak late radial (52.1 ± 32.7%/s vs. 97.1 ± 38%/s) and circumferential (38 ± 19.8%/s vs. 63.1 ± 22.9%/s) strain rates. PCWP was correlated with peak late radial diastolic displacement (r=-0.54) and velocity (r=-0.57) and peak late radial (r=-0.63) and circumferential diastolic (r=-0.63) strain rates. Peak late radial strain rate could predict PCWP (β=-0.09) and postcapillary PH (β=-0.036). All p < 0.05. Cine MRI-derived LV late diastolic motion/deformation properties can be used to estimate elevated left heart pressure in PH. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 1.

Abstract 17191: Left Atrial Volume Index and E/E’ Predict Predominance of Post-Capillary Pulmonary Hypertension With Exercise Hemodynamics

Introduction: Post-capillary pulmonary hypertension (PH) is diagnosed with rest hemodynamics and requires management of left heart disease. However, in subclinical PH and mixed PH (mixed pre- and post-capillary), it is imperative to identify a predominant post-capillary phenotype with exercise (aka. Pulmonary venous hypertension). Hypothesis: In suspected subclinical and mixed PH, greater left atrial volume index (LAVI; &gt;35) and E/E’ (&gt;8) on echocardiogram can reliably predict a predominant post-capillary PH with exercise, assessed with invasive cardiopulmonary exercise testing (iCPET). Methods: We reviewed clinical, echocardiographic and iCPET data for 37 patients undergoing exercise right heart catheterization and then analyzed the data with receiver operator curve (ROC) and area under the curve (AUC) analysis to estimate the different echo parameters to identify post-capillary PH. Results: Within the cohort, mean age (± SD) was 63.6±11.3 years, and 19 subjects were female (51%). On ROC analysis, LAVI and E/E’ had high predictive ability to identify a pulmonary venous hypertension response with exercise (AUC=0.860, p=0.003 for LAVI, and AUC=0.788, p=0.014) with optimal cut-offs identified as: LAVI &gt;35 and E/E’ &gt;8. These variables also notably had a significant association with PCWP/CO&gt;2. To understand the hemodynamics associated with these differentiable echo features, we divided the overall cohort (n=37) into 2 groups: group 1 ( Abnormal-LA group ) =LAVI&gt;35 and/or E/E’ &gt;8, group 2 ( Normal-LA group )=LAVI≤ 34 and E/E’≤8. The LAVI in group 1 vs group 2 was: 44.3±15.2 vs 23.1±4.4 (p&lt;0.001) and E/E’ was: 15.8±9.9 vs 7.7±1.95 (p&lt;0.01). Results are summarized in Table 1. Conclusions: Among individuals with suspected PH, LAVI&gt;35 and E/E’ &gt;8 are reliable non-invasive markers to identify post-capillary PH. In a patient with a new diagnosis of PH based on screening echocardiogram, LAVI≤ 34 and E/E’≤8 may identify a patient who is likely to benefit from PH drugs.

Response to fluid challenge in patients with atrial septal defect

Abstract Background A fluid challenge test (FCT) with a rapid infusion of saline allows for discrimination between pre- and post-capillary pulmonary hypertension (PH) and may unmask hidden post-capillary PH. Patients with atrial septal defect (ASD) may develop pre- or post-capillary PH after shunt closure respectively in case of pulmonary vascular disease or left ventricular disease. Aim To evaluate the haemodynamic changes of the pulmonary circulation in ASD patients undergoing percutaneous closure with indicated according to the current ESC guidelines. Methods Twenty-three patients (mean age 42.9±12.4 years; 15 female) underwent right heart catheterization in basal conditions and after FCT (volume loading with rapid saline infusion of 7 ml/kg in 10 min) before percutaneous closure of the ASD. Right atrial pressure (RAP), systolic, mean and diastolic pulmonary arterial pressure (sPAP, mPAP and dPAP), pulmonary arterial wedge pressure (PAWP), cardiac output (CO), pulmonary vascular resistance (PVR), systemic vascular resistance (SVR) and the ratio between pulmonary and systemic flow (QP/QS) were calculated four times: before and after inflating the sizing balloon both at baseline and immediately after FCT (Fig. 1). Results The patients had an increase in pressures and flows after FCT with open ASD: mPAP (18.7±4.4 vs 16.7±4.6 mmHg, p&amp;lt;0.001), PAWP (11.3±3.1 vs 9.2±3.0 mmHg, p&amp;lt;0.001), QP (12.5±2.3 vs 10.3±2.0 l/min, p&amp;lt;0.001), and QS (6.6±1.4 vs 5.9±1.2 l/min, p&amp;lt;0.001) but RAP remained unchanged (8.7±3.0 vs 8.3±2.4 mmHg, p=0.35). PVR (0.2±0.4 vs 0.8±0.3 Wood Units, p&amp;lt;0.001) and SVR (11.2±3.2 vs 12.5±3.2 Wood Units, p=0.02) decreased, and PVR/SVR (0.06±0.02 vs 0.06±0.3, p=0.25) remained unchanged. QP/QS increased in all patients after FCT (mean±SD: 2.0±0.4 vs 1.8±0.4, p&amp;lt;0.001). During a temporary ASD closure by sizing balloon, the patients had increases of RAP (9.0±2.6 vs 7.6±2.6 mmHg, p&amp;lt;0.001) mPAP (19.5±4.0 vs 17.4±3.7 mmHg, p&amp;lt;0.001), PAWP (13.2±2.1 vs 11.2±2.9 mmHg, p&amp;lt;0.001), and CO (7.7±2.7 vs 6.8±2.3 l/min, p&amp;lt;0.001) after FCT. PVR remained unchanged (0.9±0.4 vs 1.1±0.6, p=0.12) and SVR reduced (9.8±2.7 vs 11.3±2.9, p&amp;lt;0.001) after FCT. Conclusions None of the reported ASD patients presented with FCT criteria of post-capillary PH (that is a PAWP &amp;gt;18 mmHg). The FCT was associated with an increase in QP/QS suggesting that the patients still had a distensible pulmonary circulation. Further studies are needed to explore the relevance of a FCT in ASD patients, particularly those with higher PVR values. Figure 1 Funding Acknowledgement Type of funding source: None

Effect of sildenafil on right ventricular performance in an experimental large-animal model of postcapillary pulmonary hypertension

Right ventricle (RV) dysfunction is a main determinant of morbidity and mortality in postcapillary pulmonary hypertension (PH). However, currently there are not available therapies. Since reduced nitric oxide (NO) availability and cyclic guanylate monophosphate (cGMP) levels are central in this disease, therapies targeting the NO pathway might have a beneficial effect on RV performance. In this regard, sildenafil has shown contradictory results. Our objective was to evaluate the effect of sildenafil on RV performance in an experimental pig model of postcapillary PH induced by a fixed banding of the venous pulmonary confluent. Animals were evaluated by right heart catheterization and cardiac magnetic resonance before randomization and after 8 weeks on sildenafil (n = 8) or placebo (n = 8), and myocardial tissues were analyzed with histology and molecular biology. At the end of the study, animals receiving sildenafil showed better RV performance as compared with those on placebo (improvement in RV ejection fraction of 7.3% ± 5.8% versus -0.6% ± 5.0%, P= 0.021) associated with less apoptotic cells and gene expression related with reduced oxidative stress and increased anti-inflammatory activity in the myocardium. No differences were observed in pulmonary hemodynamics. In conclusion, in a translational large animal model of chronic postcapillary PH, sildenafil improved RV systolic function independently of afterload. Further research with pharmacological approaches able to manipulate the NO-cGMP axis are needed to confirm this potential cardioprotective effect.

1231 Left atrial septal and lateral wall strains contain different pressure information: Utility in pulmonary hypertension

Abstract Funding Acknowledgements South-Eastern Norway Regional Health Authority Background Reduced left atrial (LA) reservoir strain is a marker of elevated LA pressure. Thus it could be a potential non-invasive marker to differentiate pre- and post-capillary pulmonary hypertension (PH) as the latter is defined by elevated pulmonary capillary wedge pressure (PCWP) &amp;gt; 15 mmHg. However, in pre-capillary PH patients with elevated right atrial pressure (RAP), the atrial septal geometry may be abnormal. This could lead to lower regional LA septal strain, making LA lateral wall strain more accurately reflect PCWP. Purpose We investigated if LA lateral wall strain can differentiate between pre- and post-capillary PH, and how LA lateral wall strain and LA septal strain are both affected by elevated RAP in pre-capillary PH. Furthermore we investigated if LA septal strain can be used in pre-capillary PH patients to identify those with elevated RAP. Methods We analysed 63 patients with PH, 28 pre-capillary and 35 post-capillary, who underwent right heart catheterisation. Echocardiography was performed simultaneously with or within 24 hours of the invasive pressure measurements. Regional LA septal strain and lateral wall strain were measured from the apical four chamber view. Results Pulmonary artery pressure was 39.5 ± 11.1 mmHg (mean ± SD) in the pre-capillary PH patients and 37.0 ± 10.1 mmHg in the post-capillary PH patients (p = ns). Mean PCWP was 9.9 ± 2.5 mmHg and 24.5 ± 6.0 mmHg (p &amp;lt; 0.001), respectively. LA lateral wall strain was significantly lower in patients with post-capillary PH compared to pre-capillary PH (11.9 ± 7.7% vs 26.6 ± 9.9%, p &amp;lt; 0.001) (Fig. a,b). At a cut-off value of 18.0%, LA lateral wall strain could predict elevated PCWP &amp;gt; 15 mmHg with AUC = 0.88, sensitivity = 85.7% and specificity = 76.3%. In the 28 patients with pre-capillary PH, we classified mean RAP ≥ 10 mmHg as elevated and &amp;lt; 10 mmHg as normal. Seven of these patients had elevated RAP and showed significantly reduced LA septal strain compared to the 21 patients with normal RAP (13.0 ± 6.2% vs 22.1 ± 7.6%, p &amp;lt; 0.01). LA lateral wall strain showed no difference in these groups of pre-capillary PH patients (25.8 ± 10.1% vs 28.9 ± 9.4%) (Fig. c). Conclusions LA lateral wall strain can be used for differentiating between pre- and post-capillary PH. In addition, LA septal strain may be used in pre-capillary PH patients to identify those with elevated RAP. Abstract 1231 Figure

P297 Left atrial volume index is the best predictor of post-capillary pulmonary hypertension in patients with pure mitral valve stenosis

Abstract Background Mitral stenosis (MS) is characterized by a reduced mitral valve area (MVA) and an increased transmitral pressure gradient, with direct consequences on left atrial (LA) remodelling and pulmonary arterial systolic pressure (PASP). Post-capillary pulmonary hypertension (PH) has a main impact on the outcome in patients with MS. Purpose To evaluate determinants of post-capillary PH in patients with pure MS by using a combined approach of standard and advanced echocardiography. Methods From January 2018 to January 2019, 52 consecutive patients with MS were enrolled. Concomitant hemodynamically significant valve heart disease, primary PH, coronary artery and congenital heart diseases, primary cardiomyopathies, prosthetic valves and permanent/persistent atrial fibrillation were exclusion criteria. Twenty-three "pure" MS were selected (age: 63.9 ± 11.6 years, F/M= 17/6). Twenty-three healthy controls, matched by age and sex, were recruited as the control group. All participants underwent a complete echocardiographic examination, including determination of left ventricular ejection fraction (LVEF), speckle tracking derived global longitudinal strain (GLS, in absolute values), LA volume index (LAVi) and PASP. MS severity was assessed by continuous wave Doppler derived mean transmitral pressure gradient (MPG), pressure half time (PHT) and functional mitral valve area (MVA). Data were analysed offline by a dedicated workstation. Results No significant difference of body mass index, systolic and diastolic blood pressure was found between the two groups, while heart rate was higher in MR (p &amp;lt; 0.0001). In the pooled MS population, MPG was 5.7 ± 2.4 mmHg, PHT 127.7 ± 26.9 msec and MVA 1.76 ± 0.36 cm². Twelve patients (52.1%) had mild MS, 10 (43.5%) moderate MS and one (4.3%) severe MS. Patients with MS had larger LA volumes (LAVi = 45.0 ± 12.7 vs. 28.3 ± 7.3 ml/m², p &amp;lt; 0.0001), higher PASP (36.4 ± 8.9 vs. 30.4 ± 6.7 mmHg, p &amp;lt; 0.01), lower LVEF (58.5 ± 6.1 vs. 66.0 ± 3.5%. p &amp;lt; 0.0001) and lower GLS (18.8 ± 4.6 vs. 21.7 ± 2.5%, p &amp;lt; 0.01) than the healthy controls. By analyzing the MS group, LAVi had a significant univariate relation with MPG degree (r = 0.69, p &amp;lt; 0.002). PASP correlated with LAVi (r = 0.60, p = 0.003) and MPG (r = 0.51, p &amp;lt; 0.01) but not with PHT (r = 0.28, p = 0.54) and functional MVA (r=-0.31, p = 0.33). By a multlinear regression analysis, including heart rate, MPG, LVEF and GLS as potential determinants, LAVi (standardized beta coefficient =0.65, p= &amp;lt;0.02) and GLS (beta =-0.62, p = 0.03) were both independently associated with PASP degree, whereas the association of MPG and PASP was not significant (cumulative R²=0.47, SEE = 5.9 mmHg, p &amp;lt; 0.01) in the MS group. Conclusions In patients with pure MS, by using a multi-parametric echocardiographic approach, LA dilation appears to be the best predictor of post-capillary PH, independent on the magnitude of LV systolic dysfunction and valvular disease severity. Particular care should be devoted to determine LA size in this clinical setting. Abstract P297 Figure. Relation between LAVi and PASP in MS

The additive value of echocardiographic pulmonary to left atrial global strain ratio in the diagnosis of pulmonary hypertension

BackgroundThe distinction between pre-capillary and post-capillary pulmonary hypertension (PH) is central to accurate diagnosis and appropriate therapy. We aimed to investigate the ability of the novel echocardiographic pulmonary to left atrial global strain ratio (ePLAGS) to distinguish pre-capillary from post-capillary PH and compare its discriminatory strength with the echocardiographic pulmonary to left atrial ratio (ePLAR). MethodsConsecutive subjects with unexplained dyspnea or heart failure underwent echocardiography immediately followed by right heart catheterization. Subjects who did not satisfy the ESC/ERS criteria for PH, in atrial fibrillation or under pacemaker therapy, or with significant concomitant valvular disease were excluded. ePLAGS was calculated as peak tricuspid regurgitation velocity divided by left atrial global reservoir strain. ResultsOne hundred and thirty PH subjects, as defined by right heart catheterization, were included in the analysis (pre-capillary: n = 64, post-capillary: n = 66). ePLAGS was lower in pre-capillary compared with post-capillary PH (0.19 ± 0.14 vs. 0.45 ± 0.58 m/s/%; p = 0.02) and significantly different between combined post- and pre-capillary PH (Cpc-PH) and isolated post-capillary PH (Ipc-PH) (0.62 ± 0.85 vs. 0.32 ± 0.19 m/s/%; p = 0.04). ePLAR was higher in pre-capillary as compared with post-capillary PH (0.37 ± 0.16 vs. 0.20 ± 0.08; p < 0.001) but did not differ between Ipc-PH and Cpc-PH. ePLAGS demonstrated stronger discriminating power than ePLAR to distinguish pre-capillary from post-capillary PH (AUC = 0.80 vs. 0.70). In the setting of post capillary PH, ePLAGS showed reasonable ability to distinguish Ipc-PH from Cpc-PH (AUC = 0.65). ePLAR, however, did not differentiate these two groups (AUC = 0.49; p > 0.05). ConclusionsePLAGS accurately differentiates pre-capillary from post-capillary PH and demonstrates higher diagnostic ability than ePLAR.

Effect of pulmonary artery denervation in postcapillary pulmonary hypertension: results of a randomized controlled translational study.

There is scarce evidence for pulmonary artery denervation (PADN) as a potential treatment for chronic postcapillary pulmonary hypertension (PH). We aimed to perform a proof-of-concept of PADN in a translational model of chronic PH. Nineteen pigs with chronic postcapillary PH (secondary to pulmonary vein banding) were randomized to surgical-PADN (using bipolar radiofrequency clamps) or sham procedure. Additionally, 6 healthy animals underwent percutaneous-PADN to compare the pulmonary artery (PA) lesion generated with both approaches. In the surgical-PADN arm, hemodynamic evaluation and cardiac magnetic resonance (CMR) were performed at baseline and at 2 and 3-month follow-up. Histological assessment was carried out at the completion of the protocol. Eighteen pigs (6 following surgical-PADN, 6 sham and 6 percutaneous-PADN) completed the protocol. A complete transmural PA lesion was demonstrated using surgical clamps, whereas only focal damage to adventitial fibers was observed after percutaneous-PADN. In the surgical-PADN arm, the hemodynamic profile did not significantly differ between groups neither at baseline [mean pulmonary artery pressure (mPAP) median values of 32.0 vs. 27.5mmHg, P = 0.394 and indexed pulmonary vascular resistance (iPVR) 5.9 vs. 4.7WUm2, P = 0.394 for PADN/sham groups, respectively] nor at any follow-up (mPAP of 35.0 vs. 35.0mmHg, P = 0.236 and iPVR of 8.3 vs. 6.7WUm2, P = 0.477 at third month in PADN/sham groups, respectively). Surgical-PADN was not associated with any benefit in RV anatomy or function on CMR/histology. In a large-animal model of chronic postcapillary PH, transmural PADN with surgical clamps was associated with a neutral pulmonary hemodynamic effect.