Right Heart Catheterization Research Articles

Hemodynamic effects of vericiguat in symptomaticHFrEF patients: insights from right heart catheterization study

Abstract Background Vericiguat is recommended in the guidelines as Class IIb for patients with heart failure with reduced ejection fraction (HFrEF) who continue to have persistent symptoms despite receiving standard therapy. However, the precise effects of vericiguat on pulmonary and systemic hemodynamics and cardiac performance remain unclear. Purpose This study aimed to investigate the hemodynamic impact of vericiguat in 12 symptomatic HFrEF patients who experienced worsening HF despite receiving standard therapy with the four foundational heart failure medications, using right heart catheterization (RHC). Methods On day 1, RHC was performed via the right internal jugular vein and a balloon-tripped pulmonary artery thermodilution catheter was placed. On day 2 and 3, RHC data were measured at 15min before and 30min, 1hr, 2hr, 3hr and 5hr after intake of 2.5mg vericiguat. RHC data on day 2 and 3 were averaged and the catheter was removed after the RHC measurements on day 3. RHC was repeated on a median day of 105(quartiles 37,168). The acute hemodynamic effects of vericiguat were assessed using a comparison of six RHC measures, including pulmonary artery wedge pressure (PAWP), mean pulmonary artery pressure (MPAP), mean arterial blood pressures (MABP), pulmonary (PVR) and systemic vascular resistances (SVR) and cardiac index (CI), at 15minutes before intake of vericiguat 2.5mg with those at 30minutes to 5hours after that. The chronic hemodynamic effects of vericiguat were evaluated by comparing the six RHC measures on day 1 with those on day 105(37,168). Results Participant characteristics on day 1 were age 63.5(53.5,70)yrs., 16.7%(N=2) women, height 164.3(155,171.3)cm, weight 64.6(54.8,75.1)kg, body mass index 23.8(20,26.3), systolic 101.5(90.5,111.5)mmHg and diastolic blood pressures 60.2(53.5,65)mmHg, heart rate 65.5(56,72)bpm, New York Heart Association functional class Ⅱ 50%(N=6), Ⅲ 16.7%(N=2) and Ⅳ 33.3%(N=4), estimated glomerular filtration rate 44.5(34.5,53.5)mL/min/1.73m2, left-ventricular ejection fraction 19.9(14.5,24.5)% and diastolic diameter 68(60.5,72.5)mm, left-atrial diameter 45(36.5,50.5)mm and brain natriuretic peptide level 419(254,479)pg/mL. Oral intake of vericiguat 2.5mg decreased PAWP (11[7.5,15]mmHg) and MPAP (19.3[14.3,26.8]mmHg) before the intake to PAWP (9.3[6.8,14]mmHg) and MPAP (17.5[12.5,24]mmHg) at 30min after that (both P<0.05[crude P<0.0017])(Figure A) while comparable changes in MABP, PVR, SVR and CI and the other timepoints (all P>0.05[crude P<0.0017]). Vericiguat was titrated to 2.5mg 25% (N=3), 5mg 50% (N=6) and 10mg 25% (N=3) on day 105 (37,168), in which PAWP (9.5[6.5,12.5]mmHg) was decreased from PAWP (14.5[9.5,19.5]mmHg) on day 1 (P<0.05[crude P<0.0083])(Figure B) while comparable changes in the other RHC parameters (all P>0.05[crude P<0.0083]). Conclusions The consistent reduction in PAWP underscores vericiguat's well-tolerated nature and potential to enhance cardiac performance in patients with HFrEF.

Accuracy of right atrial pressure estimation by transthoracic echocardiography

Abstract Background/Introduction Transthoracic echocardiography provides an estimate of right atrial pressure (RAP) using the guideline-recommend method of measuring inferior vena cava (IVC) diameter and collapsibility. Despite being ubiquitously reported and necessary for the estimation pulmonary artery systolic pressure, the accuracy of this method for RAP estimation has not been rigorously validated. Purpose To evaluate the accuracy of the guideline-recommended method for the estimation of RAP by TTE. Methods A single center, retrospective chart review of patients who had a TTE and right heart catheterization (RHC) within 48 hours of each other from January 2018 to December 2020. Maximum and minimum IVC diameter were measured by trained study personnel. Accuracy was then stratified by the presence/absence of a history of two variables that could modify IVC diameter independent of RAP—syncope, which is associated with more dilated IVC in some studies and liver disease, which could result in compression (from parenchymal fibrosis surrounding the IVC) or dilation (from diversion of portal blood flow through the IVC among other mechanisms) of the IVC. Results The 117 patients who met inclusion criteria had a median age of 67 years old (interquartile range [IQR] 58 – 75) and median RAP of 13 mmHg (IQR 8 – 18) on RHC. The median time between TTE and RHC was 9.6 hours (IQR 3.8 – 24.5 hours) during which 24 (20.5%) patients received intravenous fluids (median 220 mL administered; IQR 145 – 320). Forty-three (35.9%) received diuretics between the studies with most patients receiving either 1 (26 patients, 61.9% of those who received diuretics) or 2 (13 patients, 31.0%) diuretic doses. In evaluating accuracy, only 26 patient’s (20.5%) RAP by RHC fell within estimated RAP range by TTE (Figure 1). After excluding the 60 patients who received fluids and/or diuretics between the TTE and RHC, the TTE estimate was still only accurate in 13 (22.8%) patients. When analyzing how each subcomponent of the TTE guidelines for RAP estimation correlated with RAP via RHC, maximum IVC diameter and percent collapsibility had Pearson’s correlation coefficients of 0.47 and 0.24 respectfully (Figure 2A and 2B). Past medical history was significant for syncope in 16 patients (13.7%) and liver disease in 8 patients (6.8%). Compared to those without each factor, the absolute accuracy of the TTE estimate was lower when stratified by a history of syncope (12.5% accurate vs 21.8%, p = 0.60) and liver disease (12.5% vs 21.2%, p = 0.90) though neither were statistically significant. Conclusion In this retrospective chart review, RAP estimation by TTE using the guideline-recommended method had limited accuracy. Prospective evaluation with minimal time between RHC and TTE is needed to validate the accuracy of the TTE guidelines.Accuracy of TTE for RAP estimationCorrelation between RAP & TTE Variables

The added value of cardiopulmonary exercise testing in the diagnosis of heart failure with preserved ejection fraction

Abstract Background Diagnosing heart failure with preserved ejection fraction (HFpEF) is challenging. Two validated algorithms, the HFA-PEFF and H2FPEF scores, have been proposed to guide our clinical practice. Many patients are categorized into an intermediate probability for HFpEF, representing a diagnostic "gray zone." This necessitates further evaluation, including right heart catheterization (RHC) at rest and possibly during exercise, to confirm or exclude the diagnosis. RHC, while informative, is resource-consuming and requires execution in specialized centers. Cardiopulmonary exercise testing (CPET) may offer a non-invasive and cost-effective alternative for differential dyspnea diagnosis. Purpose To evaluate the role of CPET in the diagnostic algorithm of unexplained dyspnea/suspected HFpEF. Methods This single-center retrospective study analyzed patients with a left ventricular ejection fraction (LVEF) ≥ 50% who underwent CPET for unexplained dyspnea from 2016 to 2020. We assessed HFpEF probability using the H2FPEF score and the HFA-PEFF algorithm. We hypothesized that specific CPET parameters (VO2 peak< 80% of predicted and/or VE/VCO2 slope > 35) might provide complementary information to the HFpEF probability scores. Additionally, we hypothesized that CPET could help identifying HFpEF in patients with intermediate probability in a subcohort of patients who underwent exercise RHC. Results Out of 103 patients, 61 (59%) were categorized as intermediate probability of HFpEF according to the HFA-PEFF score, and 59 (57%) according to the H2FPEF score. CPET results (VO2 peak and VE/VCO2 slope) were not associated with the pre-test probability of HFpEF as defined by either of the two scores. Exercise RHC was performed in 26 (43%) and in 27 (46%) patients with intermediate HFA-PEFF score and intermediate H2FPEF score, respectively. Among these patients with intermediate HFpEF probability, VO2 peak < 80% and/or VE/VCO2 slope > 35 had a good specificity and positive predictive value for HFpEF, as compared with exercise RHC (Table). Conclusions CPET provides complementary information to HFA-PEFF and H2FPEF scores. In particular, our results suggest that CPET may reclassify as HFpEF over 25% of patients with an intermediate HFpEF probability according to either the HFA-PEFF score or the H2FPEF score, potentially obviating the need for RHC. Thus, CPET might be incorporated into the HFpEF diagnostic algorithms.Table

3D Vortex-Energetics in the Left Pulmonary Artery for Differentiating Pulmonary Arterial Hypertension and Pulmonary Venous Hypertension Groups Using 4D Flow MRI.

Pulmonary hypertension (PH) is a life-threatening. Differentiation pulmonary arterial hypertension (PAH) from pulmonary venous hypertension (PVH) is important due to distinct treatment protocols. Invasive right heart catheterization (RHC) remains the reference standard but noninvasive alternatives are needed. To evaluate 4D Flow MRI-derived 3D vortex energetics in the left pulmonary artery (LPA) for distinguishing PAH from PVH. Prospective case-control. Fourteen PAH patients (11 female) and 18 PVH patients (9 female) diagnosed from RHC, 23 healthy controls (9 female). 1.5 T; gradient recalled echo 4D flow and balanced steady-state free precession (bSSFP) cardiac cine sequences. LPA 3D vortex cores were identified using the lambda2 method. Peak vortex-contained kinetic energy (vortex-KE) and viscous energy loss (vortex-EL) were computed from 4D flow MRI. Left and right ventricular (LV, RV) stroke volume (LVSV, RVSV) and ejection fraction (LVEF, RVEF) were computed from bSSFP. In PH patients, mean pulmonary artery pressure (mPAP), pulmonary capillary wedge pressure (PCWR) and pulmonary vascular resistance (PVR) were determined from RHC. Mann-Whitney U test for group comparisons, Spearman's rho for correlations, logistic regression for identifying predictors of PAH vs. PVH and develop models, area under the receiver operating characteristic curve (AUC) for model performance. Significance was set at P < 0.05. PAH patients showed significantly lower vortex-KE (37.14 [14.68-78.52] vs. 76.48 [51.07-120.51]) and vortex-EL (9.93 [5.69-25.70] vs. 24.22 [12.20-32.01]) than PVH patients. The combined vortex-KE and LVEF model achieved an AUC of 0.89 for differentiating PAH from PVH. Vortex-EL showed significant negative correlations with mPAP (rho = -0.43), PCWP (rho = 0.37), PVR (rho = -0.64). In the PAH group, PVR was significantly negatively correlated with LPA vortex-KE (rho = -0.73) and vortex-EL (rho = -0.71), and vortex-KE significantly correlated with RVEF (rho = 0.69), RVSV, (rho = 0.70). In the PVH group, vortex-KE (rho = 0.52), vortex-EL significantly correlated with RVSV (rho = 0.58). These preliminary findings suggest that 4D flow MRI-derived LPA vortex energetics have potential to noninvasively differentiate PAH from PVH and correlate with invasive hemodynamic parameters. 1 TECHNICAL EFFICACY: Stage 3.

Predictors of Right vEntricular Failure aftER LVAD implantation: PREFER LVAD study

Abstract Introduction The use of left ventricular assist devices (LVAD) is increasing both as bridge-to-transplantation or destination therapy, considering the lack of heart donors for transplantation in advanced heart failure (AHF) population. Right ventricular post-implantation failure, major bleedings and infective events remain the principal adverse events in LVAD carriers, thus an accurate selection of candidates is needed. Purpose To identify between clinical, laboratory, standard and advanced (Speckle Tracking, STE) echocardiography, and right heart catheterization (RHC) indices, the best predictors of outcome after LVAD implantation. Materials and Methods We screened in our third-level center 30 patients with AHF, followed up from May 2013 to February 2022, for the assessment of LVAD implantation suitability. They all underwent a complete cardiological history collection, electrocardiography, standard and STE left ventricular (LV) and left atrial (LA) size and function assessment. Regarding the right ventricle, SIENA score parameters, including RV sphericity index, RV free wall longitudinal strain (LS), right ventricular fractional area change (RVFAC), and 3D ejection fraction were used for exclude RV disfunction. RHC was performed on the same day of echocardiography. Follow-up was conducted at 1, 3, 6, 9 and 12 months repeating all the assessments, for the occurrence of RV failure, all-causes mortality, hemorrhagic events and re-hospitalization for heart failure. With a univariate and multivariate statistical analysis, we went to test among all the parameters the possible predictors of outcome. Results The final population consists of 29 patients (93% male, mean age of 63±11 years), in NYHA class III or IV and a severe reduction of left ventricular (LV) ejection fraction (EF), in whom arterial hypertension and smoking, present or previous, were present in 58% and 65% of cases, respectively. The population was divided into two groups according to the occurrence of at least one cardiovascular event. 11 major events were recorded: including 4 hemorrhagic events, 3 all-causes mortality and 4 hospital admission for HF. No RV failure occurred in the first 12 months of follow-up. No differences were identified between the two groups in terms of echocardiographic indices and RV function, including RVFAC or RV-FWLS. At univariate analysis (see Table 1), the only parameter able to predict major CV events was central venous pressure (CVP)/pulmonary capillary wedge pressure (PCWP) ratio, obtained by RHC, an index of balance between right and left heart filling pressure. Conclusions A careful application of SIENA score indices before LVAD implantation can significantly reduce the incidence of post-operative RV failure, as in our small population. Our results also confirmed the paramount role of RHC in the diagnostic work up of AHF.

Functional status is associated with mean right atrial pressure derived from cardiac MRI

Abstract Background Right atrial pressure (RAP) is a key metric in haemodynamic assessment. Elevated RAP is associated with poor prognosis in heart failure and pulmonary hypertension and physiologically with fluid overload. RAP can be measured invasively or non-invasively, but Cardiac MRI (CMR) currently cannot estimate RAP. Purpose To develop a model to estimate RAP from CMR from paired right heart catheter (RHC) and CMR assessments. Assess correlation to WHO functional status prior to prospective clinical validation studies. Methods Patients were recruited to a registry of those referred for assessment of dyspnoea between 2012 and 2020. Inclusion criteria were age &amp;gt;18 years, signs and symptoms of heart failure and adequate CMR image quality. Patients diagnosed with pulmonary arterial hypertension were excluded. RHC and CMR were performed on the same day. CMR 2- and 4- chamber cines were used to measure chamber dimensions, strain, ejection fraction and stroke volume with operator reviewed AI contours in MASS research software. Pearson’s product-moment correlation coefficient (r ) was used to assess relationships between CMR metrics and invasive mRAP. Variables were then included in stepwise multiple linear regression models to predict mRAP. These were compared with receiver-operator curve analysis and DeLong’s test. Kruskal-Wallis test compared median mRAP between WHO functional class groups. Results The cohort of 672 patients was divided based upon invasive mRAP ≤ 8mmHg (44%) and mRAP &amp;gt; 8mmHg (56%). Higher mRAP was associated with increased age, male sex and a higher diastolic blood pressure but there was no difference in rates of heart failure types although the majority had preserved ejection fraction (51% vs 52%) with few having reduced ejection fraction (4.1% vs 8%). Right atrial (RA) dimensions, strain and ejection fraction had the strongest correlation with mRAP with moderate correlation to right ventricular (RV) measurements. Multivariable models contained simple RA dimensions (model 1), RA dimensions and strain (model 2), RA and RV dimensions (model 3) and RA end systolic volume corrected for body mass index and sex (model 4). All models had similar predictive capability (Figure 1 Panel A). RA end systolic volume was isolated in model 1 as the only variable required for mRAP prediction (coefficient = 0.06, p &amp;lt; 0.001). Using a threshold of mRAP &amp;gt;8mmHg ROC analysis demonstrated an area under the curve of 0.78 (95% Confidence interval 0.75 to 0.81) (Figure 1 Panel B). Worse WHO functional Class at time of assessment was significantly associated with increased CMR derived mRAP (P&amp;lt;0.001) (Figure 2). Conclusions mRAP can be estimated with moderate confidence from CMR RA end systolic volume. Limited available clinical data suggest functional status may be predicted by CMR derived mRAP. Further studies on wider populations are required to validate this model externally, refine it and determine its prognostic clinical significance.

Randomized trial assessing worsening renal function with dapagliflozin addition in acute decompensated heart failure: ROAD-ADHF trial

Abstract Background Dapagliflozin (DAPA), a sodium-glucose co-transporter 2 inhibitor, has shown to reduce cardiovascular mortality in patients with chronic heart failure.1) In addition, DAPA can enhance diuresis in patients with acute decompensated heart failure (ADHF).2) However, there is little known how early initiation of DAPA might impact the worsening renal function (WRF) when combined with standard decongestive therapy for ADHF. Purpose We aimed to evaluate the impact of initiating DAPA within 24 hours after ADHF admission on WRF, compared to standard decongestive therapy with loop diuretics alone. Methods We enrolled consecutive ADHF patients with a left ventricular ejection fraction (LVEF) less than 50%. The patients were prospectively randomized to either the DAPA group who received DAPA at a dose of 10 mg once daily within 24 hours of admission or the conventional therapy group (CON group) who received loop diuretics alone. Furosemide, loop diuretic, dosage was adjusted by increase or decrease of 10 mg to maintain urine output between a 1-2 mL/kg/hour.3) The primary endpoint was the incidence of WRF, which was defined as an increase in the serum creatinine of ≥ 0.3 mg/dL from baseline within 7 days of admission.4) Additionally, right heart catheterization (RHC) was performed before discharge if the consent was obtained. Results From May 2021 to May 2023, we analyzed a total of 114 patients (56 in the DAPA group and 58 in the CON group). The mean age was 73 years, 35% were female, and the mean LVEF was 32.5%. There was no significant difference in the incidence of WRF between two groups (16.1% in the DAPA group vs. 12.1% in the CON group, P=0.54, Figure 1). The cumulative loop diuretics dose over 7 days was lower in the DAPA group than CON group (184 ± 9.64 mg vs. 214 ± 9.81 mg, P=0.03, Figure 2). RHC before discharge was performed in 54 patients (96.4%) in the DAPA group and in 54 (93.1%) in the CON group. There were no significant differences in the pulmonary artery wedge pressure, pulmonary artery pressure, right atrial pressure, and cardiac index by the thermodilution method or the Fick method between two groups. Conclusion This randomized prospective trial revealed the early initiation of DAPA within 24 hours of admission for ADHF reduced loop diuretic demand without inducing WRF compared to standard decongestive therapy.Figure 1Figure 2

Prognostic value of follow-up hemodynamics after initial treatment in pulmonary arterial hypertension

Abstract Background Hemodynamic variables such as right atrial pressure (RAP), cardiac index (CI) and mixed venous oxygen saturation (SvO2) have consistently been associated with survival in pulmonary arterial hypertension (PAH). The prognostic importance of hemodynamics after treatment initiation seems to be superior to baseline evaluation and stroke volume index (SVI) emerged as an independent prognostic parameter. New PAH treatments are, however, able to improve exercise capacity without increasing CI or SVI. Purpose The aim of this work was to define the prognostic role of follow-up hemodynamic parameters in a population of patients with idiopathic, hereditary, drug-induced PAH (I/H/D-PAH) and PAH associated with connective tissue disease (CTD-PAH) and congenital heart disease (CHD-PAH). Methods Treatment naïve PAH patients were assessed at baseline and at 1st follow-up (3-4 months after starting PAH-specific therapy; 1st F-UP) with 6-minute walk distance (6MWD), World Health Organization functional class (WHO-FC) and right heart catheterization (RHC). Collected hemodynamic parameters were: RAP, systolic, diastolic and mean pulmonary artery pressure (s/d/mPAP), CI, SVI, SvO2, pulmonary vascular resistance (PVR), pulmonary arterial compliance (PAC), cardiac efficiency (CE), pulmonary arterial elastance (Ea), resistance–compliance product (RC), right ventricular (RV) power, and RV stroke work index (RVSWI). The primary outcome was all cause death. We used stepwise Cox regression to assess variables obtained at baseline and at 1st F-UP. Results 794 patients with PAH were enrolled (54% I/H/D, 28% CTD, 18% CHD). A primary outcome occurred in 54% of patients over a median follow-up duration of 5.8 (2.4–11) years. In a multivariable model considering only baseline variables, no hemodynamic variables independently predicted prognosis but RAP. At first follow-up RHC (n=706), WHO-FC, 6-minute walk distance, RAP, and Ea were independently associated with death, adjusted for age, gender, and etiology of PAH. Because hemodynamic variables were highly correlated, we compared multivariable Cox regression models adding only variables with a correlation coefficient &amp;lt;0.6. In these models, RAP, Ea, PAC, CE, PVR, SvO2, CI, and SVI at follow-up RHC were independent predictors of death (Table). Conclusions Ea and right atrial pressure were the hemodynamic variables independently associated with death at 1st F-UP RHC after initial PAH treatment. These findings suggest that beyond improving RV function, RV afterload reduction can be considered a further treatment target.Table

Hemodynamic profiles and survival in chronic advanced heart failure patients evaluated for heart replacement therapy

Abstract Background Advanced heart failure (HF) is associated with dismal prognosis despite optimal medical therapy. Invasive assessment with right heart catheterization (RHC) is a valuable tool to assess transplant candidates and hemodynamic profiling is crucial to stratify prognosis and select patients for advanced therapies. Purpose This study aims to examine the relationship between hemodynamic profiles based on cardiac index (CI) and filling pressures and survival in ambulatory patients with advanced HF evaluated for heart replacement therapy (HRT) such as heart transplantation (HT) and left ventricular assist device (LVAD) implant. Methods We analyzed adult ambulatory advanced HF patients evaluated for HRT with an available baseline RHC from 2003 to 2022. Hemodynamic data were classified using a CI &amp;lt; 2.2 l/min/m2 as marker of reduced cardiac output ("cold" profile opposed to the "warm" profile) and increased filling pressure, defined as right atrial pressure ≥ 10 mmHg and/or pulmonary capillary wedge pressure (PCWP) ≥ 15 mmHg as a marker for congestion ("wet" profile opposed to the "dry" profile). Study endpoint was death or urgent HT or LVAD implant at 5 years. Results Study population included 610 patients (mean age 53±10 years, 79% males). According to hemodynamic criteria, 332 patients (55%) exhibited a "wet cold" hemodynamic profile, 117 (19%) a "cold dry", 91 (15%) a "warm wet" and 66 (11%) a "warm dry" phenotype. The "wet" patients showed a significantly higher prevalence of pulmonary hypertension (96% wet cold, 94% wet warm vs 21% dry warm, 19% dry cold; p&amp;lt;0,001), a lower pulmonary artery pulsatility index (4,0 wet cold, 4,1 wet warm vs 7,4 dry warm, 6,9 dry cold; p&amp;lt;0,001). No differences were found in etiology of HF. Both reduced CI [OR 1,6 (1-2,4), p=0.003] and increased filling pressures [OR 1,9, (1,2-2,8) p=0.007] were associated with worse outcomes. Survival differed significantly among hemodynamic profiles, with a survival rate of 48% in the "cold wet" profile compared to 68% in the "cold dry" [OR 1,9 (1,2-3,1) p=0,007] and 65% in the "warm dry" [OR 2,2 (1,1-4,2), p=0.01]. The difference between "cold wet" and "warm wet" was borderline significant (p=0.07). Further stratification between right and left ventricular filling pressures showed that isolated right ventricular congestion was rare and associated with low event rate, while in patients with preserved CI, biventricular congestion was associated with borderline worse survival as compared to isolated left ventricular increased filling pressures (p=0.06). Conclusions Hemodynamic profiles assessed with RHC stratify prognosis in ambulatory patients with advanced HF referred for HRT. Evaluation of hemodynamic phenotype may help identify subgroups of patients at high risk and guide therapeutic decisions. Further studies are needed to confirm these findings and develop personalized management strategies to improve clinical outcomes in this population.Survival-hemodynamic phenotypeSurvival-filling pressures

Echocaridographic assessment of pulmonary hypertension: improving the probability

Abstract Introduction Pulmonary hypertension (PH) is a cardio-pulmonary disorder characterised by raised pulmonary artery pressure (mPAP &amp;gt;20mmHg) leading to right ventricular failure, and death if left untreated. Transthoracic echocardiography (TTE) assessment of PH uses a probability-based approach, combining peak tricuspid regurgitant velocity with other supporting signs. We evaluated the latest ESC TTE PH guidelines in a real-world UK dataset and identified markers that may improve the sensitivity of the existing algorithm. Method Retrospective analysis of 447 patients referred for initial PH assessment. This was a select population of patients who underwent both TTE and right heart catheter (RHC) (mean time to RHC = 40±30 days). In addition to current TTE PH probability markers we analysed right ventricular free wall strain (RVFWS). Measurements were made by a single operator using Tomtec Arena 2020. Crosstabulation, ROC curve analysis and T-tests were used to compare variables between PH and no PH. Results Mean sample age was 64±15 yrs (61% female). 6.9% (n=4) of the no PH group had pulmonary mid-systolic notching, which may be due to pseudo-notching attributable to incomplete Doppler envelope. Sensitivity and specificity of current ESC TTE probability guidelines were 83%, and 65% respectively (95% C.I.). However, within the low probability group (i.e. those felt to be less likely to have PH) 62% (n=63) had confirmed PH at RHC (mPAP = 28±9). The addition of RVFWS as an additional marker to the existing supporting signs of PH (Table 1) resulted in an improvement of the sensitivity of the algorithm to 92% with a mild reduction in specificity (63%). The number of false negatives were reduced by 51%. Of these, the majority were in the low TTE probability group (n = 32). Conclusions Using current PH TTE probability algorithms classifies a significant proportion of those with PH as having a low TTE PH probability. The addition of RVFWS improves the sensitivity of the existing algorithm to 92% and reduces false negatives by 51%.

In vivo study of pulmonary artery remodeling and pulsatility in long Fontan patient

Abstract Background Pulmonary vasculopathy associated with Fontan circulation is a relatively unexplored entity that could have clinical and therapeutic implications. Purpose Our aim was to evaluate the physiology of the pulmonary artery in patients with Fontan circulation using conventional right heart catheterization (RHC) and intravascular ultrasound (IVUS). Methods From December 2022 to January 2024, data from all consecutive Fontan patients undergoing RHC were prospectively collected at a tertiary referral center for adult congenital heart disease. Pressures and pulmonary artery wall high-definition IVUS recordings (OptiCrossTM, 60 MHz, Boston Scientific) were recorded at rest and during apnea. Pathological Fontan pressure was defined when as exceeding 15 mmHg. IVUS pulsatility index was defined as [(systolic lumen area - diastolic lumen area)/(diastolic lumen area) ×100], Peterson's elastic modulus as (pulmonary pulse pressure/IVUS pulsatility index), and area of wall thickness as [(wall area - lumen area)/(lumen area) x100)]. In the literature, the mean ± standard deviation (SD) normal values of elastic modulus and wall thickness area have been reported as 21 ± 1.7 mmHg and 1.4 ± 1.3%, respectively, in healthy patients without pulmonary hypertension (1: doi: 10.1186/s12931-017-0568-z). We define an alteration in intrinsic pulmonary arterial wall viscoelastic properties as an elastic modulus &amp;gt; 70 mmHg, and we define structural pulmonary wall remodeling as an increase in wall thickness area greater than 5%. Results 13 patients were studied. Median age was 28.1 years interquartile range (IQR) (25.6- 41.4), 7 (53.9%) were female, and 4 (30,8%) were in functional New York Heart Associtation (NYHA) class I. RHC and pulmonary arterial wall IVUS values are presented in Figure 1. 6 (46.2%) had Fontan abnormal pressures at rest. All patients showed minimal pulse pressure in the pulmonary arteries synchronized with heart rate, median pulmonary pulse pressure (IQR) 3 (2-4) mmHg. This pulsatility was detected in the IVUS study in all patients, pulsatility index (median (IQR) 4.8 (3.3-10.1)) and elastic modulus (median (IQR) 51.5 (20.5-101.6) mmHg). All of them had some degree of structural pulmonary wall remodeling (&amp;gt;5% wall thickness area), and 10 (76.9%) of them had marked remodeling (&amp;gt; 10%). The median (IQR) of wall thickness area was 13.6 (10.5-18.3) % (Figure 2). We think that the pseudo-normality of the elastic modulus is due to a low pulmonary pulse pressure, however, structural remodeling could be secondary to the endothelial dysfunction present and described in arteries with very low pulsatility. Conclusions The IVUS evaluation of the pulmonary artery in Fontan patients may be useful for revealing significant information regarding pulmonary physiology. Pulmonary wall thickening has been observed, providing insight into altered structural remodeling of the pulmonary arteries in this population.

CMR predictors of acute right heart failure after LVAD implantation

Abstract Background Acute right heart failure (RHF) is one of the most dangerous complications after placement of left ventricular assisted device (LVAD), having a significant impact on prognosis, and is estimated to be around 3 to 35%. Even though right ventricular evaluation with hemodynamical and echocardiographic measurements is a key aspect prior to LVAD implantation, prediction of RHF remains a challenge in daily clinical practice. Purpose To identify cardiac magnetic resonance (CMR) predictors of RHF after LVAD placement. Methods We retrospectively enrolled patients referred to our centre for implantation who also underwent CMR scan prior to LVAD implantation. Acute RHF was defined according to Mechanical Circulatory Support Academy Research Consortium (MRC ARC) criteria. Baseline characteristics, preoperative laboratory, echocardiographic, right heart catheterization (RHC) and CMR parameters were obtained. Patients were divided into two groups based on the development of acute RHF. The variables showing significant differences between the two groups were analysed with the receiver operating characteristic (ROC) curves to find the best cut-offs and then combined into a risk score. Results We enrolled 54 patients who underwent continuous-centrifugal flow LVAD implantation from 2013 to 2021 in whom a CMR within median time of 30 days pre-implantation was available. Four patients were excluded due to low quality images. Among the final cohort of 50 patients, 15 (28%) developed acute RHF. Patients who developed RHF showed worse INTERMACS class, worse renal and liver function, higher central venous pressure at RHC, worse TAPSE at echocardiography and overall smaller left ventricles at the CMR analysis when compared to those who had not acute RHF. No CMR derived right ventricle parameters nor moderate to severe tricuspid regurgitation at echocardiography were different among the two groups. We found that CMR-derived LV mass indexed &amp;lt; 65 g/m2, left ventricular end diastolic diameter (LVEDD) &amp;lt; 70 mm, and LV eccentricity index &amp;gt;1,12 were independent predictors of acute RHF. A CMR-derived score with these three parameters was built (1 point for each). This CMR score has shown to be an independent predictor of acute RHF at multivariate analysis with an odds ratio of 7,084 (CI 95%1.614-37.734) when corrected for other clinical and instrumental predictors of acute RHF. Conclusions Our study proposes a simple scoring system based on three CMR- derived parameters (LVEDD, LV mass indexed and LV eccentricity index) to screen for acute RHF prior LVAD implantation. This score shows promise to be an independent predictor of acute RHF, even when adjusted for clinical, echocardiographic, and haemodynamic parameters. Our model is built on CMR measurement of the LV, showing how patients with smaller ventricles and a left displacement of the interventricular septum (expressed with a higher LV eccentricity index) are at higher risk of developing acute RHF.ROC curves

Prognostic value of MELD-XI score and hemodynamic parameters in patients undergoing transcatheter tricuspid valve intervention

Abstract Background Hepatorenal dysfunction is a strong prognostic predictor in patients with tricuspid regurgitation. Patients are often hospitalized with acute heart failure due to volume overload and peripheral hypoperfusion. End-organ dysfunction is associated with the development of right ventricular failure related to hemodynamic changes such as low cardiac output and passive congestion from increased right ventricular filling pressures. Purpose This study aimed to investigate the prognostic value of hepatorenal dysfunction using the Model for End-stage Liver Disease (MELD) Score, the modified version of the score, MELD-XI, and of parameters determined during right-heart catheterization in patients undergoing transcatheter tricuspid valve intervention. Methods In this single-center prospective cohort study, data from patients undergoing edge-to-edge repair or heterotopic minimal invasive tricuspid valve repair were analyzed. Serum creatinine, INR and bilirubin were measured and the MELD score as well as the MELD XI score was calculated. All patients underwent right heart catheterization before the intervention. Receiver operator characteristics with calculation of the area under the curve (AUC) were performed to determine the predictive value of MELD (XI) score and hemodynamic parameters for the combined endpoint of rehospitalization due to decompensated heart failure and mortality within 3 months. Results Data from 36 consecutive patients were analyzed. 28 patients underwent edge-to-edge repair and 8 patients heterotopic minimal invasive tricuspid valve repair. Mean age of patients was 80.2 ± 5.9 years; 33.3% (12/36) were male. Baseline characteristics are shown in table 1. Rehospitalization due to decompensated heart failure occurred in 9/36 patients (25%). Mortality within the first 3 months was 11% (4/36). The predictive value for the composite endpoint of the modified MELD IX score was AUC 0.82 (95 % CI 0.63-0.99; p=0.009), while the conventional MELD score had an AUC of 0.77 (95 % CI 0.55-0.99; p = 0.059) (figure 1). RV pressure (AUC 0.84, 95% CI 0.66-1.00, p= 0.012) and RA pressure (AUC 0.83, 95% CI 0.67-0.98, p=0.016) showed a good predictive value for the composite endpoint (figure 2). The combination of MELD XI (at admission) and RV or PA pressure improved the AUC (MELD XI + RV: AUC 0.85; MELD XI + PA: AUC 0.84). Conclusion In this pilot-study, the modified MELD XI score, as indicator of hepatorenal dysfunction, was identified as a potential marker for short-term outcome after interventional tricuspid valve treatment.

Vmax as an Index of right ventricular function in pulmonary hypertension

Abstract Background For assessing right ventricular function in pulmonary hypertension (PH), the optimal approach is through the use of load-independent parameters. While pressure-volume (PV) loops are not feasible in clinical settings, the maximum velocity of the contractile element under no load, known as Vmax, serves as an alternative measure that could be derived only from right-heart catheterization (RHC). Objectives To determine Vmax in patients undergoing RHC and to evaluate its correlation with echocardiographic parameters. Methods 15 PH patients scheduled for risk stratification were subjected to RHC and echocardiography. The contractile velocity element (VCE) was calculated as VCE = 1 / (28.8 x P) x dP/dt, with P representing RV pressure in mm Hg and dP/dt its first derivative in mmHg/s. The P vs. VCE plot displays a peak VCE value, leading into a linear slope (red line, figure 1A) with Vmax as the zero-pressure intercept. Vmax was compared with 6 different echocardiographic parameters of RV function. Results They were six females and 9 males aging 61±6 y. Mean PH was 37,6±10,1 mm Hg and Vmax averaged 2,1±0,9 length/s (range from 0,8 to 4,4 length/s). Figure 1B illustrates 3 patients with deteriorated, mildly reduced and normal VCE. When compared to Vmax, tricuspid peak systolic tissue Doppler velocity and TAPSE shown the best correlation while RV fractional area change demonstrated the worse correlation (figure 2). Conclusion Vmax, an indicator of right ventricular systolic function that does not depend on load, can be obtained through right heart catheterization. Both tissue Doppler peak systolic velocity and tricuspid annular plane systolic excursion (TAPSE) have demonstrated a strong correlation with Vmax.Invasive pressureECHO parameters

Cardiopulmonary exercise testing in long-term calcium channel blockers responders, does it normalize in the same way as pulmonary vascular resistance?

Abstract Background and aims Long-term calcium channel blockers (CCB) responders represent &amp;lt;10% of pulmonary arterial hypertension (PAH) patients and are known to have an excellent prognosis on high dose CCB. The few reports of lung histology of these patients suggest a predominant muscular thickening of the precapillary arterioles. Nevertheless, the classic intimal proliferation characteristic of PAH has also been reported, although to a lesser extent. Hence, we hypothesized that long-term CCB responders are likely to exhibit some degree of ventilatory inefficiency as a result of their impaired alveolo-capillary membrane. In this study, we aimed to evaluate the exercise performance of a contemporary cohort of long-term responders to CCB in terms of both exercise capacity and ventilatory efficiency, and whether there are differences depending on the haemodynamic severity. Methods We evaluated all long-term CCB responders with regular follow-up at our institution between 1996 to 2024 with at least one cardiopulmonary exercise test (CPET) and a right heart catheterization (RHC) within a three-year period, provided they had remained clinically stable without changes in pulmonary vasodilator treatment. Patients with additional PAH specific treatment were excluded. For data analysis purposes, the population was divided into 2 groups according to pulmonary vascular resistance (PVR). The cut-off point for PVR was set at ≥3. Results Twenty-four patients (91,6% female) with complete data were retrospectively enrolled. Baseline characteristics were as follows: median age 45.5 years (59-33) median mean pulmonary artery pressure of 26 mmHg (29-24) and median PVR of 3 WU (3-2.6). Regarding the whole cohort, peak oxygen consumption (pVO2) revealed mild impairment of functional capacity (mean pVO2: 1281 ± 245 ml/kg – 75 ± 15% of predicted). Ventilatory efficiency parameters were also mildy affected with low end-tidal carbon dioxide pressure at the anaerobic threshold (PETCO2@AT) (33.7±3.6mmHg), and increased minute ventilation (VE)/carbon dioxide output (VCO2) slope (33.5±4.5). The subgroup analysis depending on PVR showed no significant differences between groups in terms of pVO2 (1291.9 ±240 Vs. 1150 ±350 ml/kg, p:0.29 / 79%±16 vs 67%±12, p:0.8), VE/VCO2 slope (33 Vs. 34, p:0.21), or PETC02@AT (35 Vs. 33 mmHg, p:0.25). All CPET parameters by subgroups are displayed in Table 1. Conclusions Long-term CCB responders exhibit mildly reduced functional capacity. Moreover, they often fail to normalize the ventilatory efficiency parameters in most of the cases, even when PVR reaches close to normal values, suggesting persistent endothelial impairment.Results according to PVR

Endarterectomy in CTEPH: hemodynamic improvement and RV-PA coupling

Abstract Introduction Pulmonary artery endarterectomy (PAE) remains the gold standard in treating chronic thromboembolic pulmonary hypertension (CTEPH). Reducing the thrombotic burden and mechanical obstruction of the pulmonary artery (PA) leads to significant hemodynamic improvement, allowing for favorable right ventricular (RV) remodeling. Methods Single center retrospective study, including 30 pts submitted to PEA over a 7-year period. Hemodynamic assessment was performed by right heart catheterization (RHC) before PEA, immediately after and at 6-month follow-up (FUP). Echocardiographic assessment of RV function was acquired at baseline and 6m FUP. Mean absolute differences were calculated before and after PEA. Differences between groups were assessed with ANOVA analysis and ROC curve analysis allowed us to define a cut-off point in mPAP reduction to predict favorable RV remodeling. Results We included 30 pts with a mean age of 57,9 ± 13 years old and slight predominance of female sex (57%). Regarding risk assessment with the 4 strata tool at baseline, 23% of pts were high risk, 20% intermediate high, 27% intermediate low and 6% at low risk. Pulmonary hemodynamics improved immediately after PEA, as indicated by a mean reduction of 28,3 ±17 mmHg in mPAP; 44,4±27,6mmHg in sPAP; 8±3,4 Wu in PVR and an increase in CO of 0,5±1 l/min. This improvement was sustained at 6-m post PEA assessment, with a mean reduction of 31,5 ±26,7 mmHg in mPAP; 48,3±41,2mmHg in sPAP; 6,3±6,2Wu in PVR and a 0,5±1 l/min increase in CO. Regarding RV remodeling at 6m post PEA, an increase of 0.15±0.2mm/mmHg in TAPSE/PSAP ratio and 3±2,8cm/s in Tricuspid S’ were recorded. RV/PA uncoupling, defined as TAPSE/PSAP &amp;lt;0,31 mm/mmHg, was evident in 73% of pts at baseline, 25% of which recovered at 6m follow-up. There were no significant differences between groups, according to the 4 strata risk assessment at baseline, regarding pulmonary hemodynamics and RV remodeling. Through ROC curve analysis, we were able to define a cut-off point of 37mmHg in immediate mPAP post-op reduction to predict RV-RA coupling normalization at 6-m FUP (sensitivity 70%, specificity 89%). Conclusions PEA remains a cornerstone of CTEPH treatment. It’s impact on improving pulmonary hemodynamics is immediate and maintained at 6-month FUP. This improvement may be expected regardless of risk assessment at baseline. Reducing RV afterload allows favorable remodeling and an immediate post operative reduction of mPAP &amp;gt; 37mmHg may predict normalization of RV-PA coupling.

Volume-pressure loop hemodynamic characterization of pulmonary hypertension

Abstract Background Pulmonary hypertension (PH) includes a wide spectrum of pathologies with different pathological bases and a variety of clinical scenarios in which right ventricular (RV)-pulmonary artery (PA) coupling has relevant prognostic implications. Currently, diagnosis and hemodynamic severity of PH is typically based on mean pulmonary arterial pressure (mPAP), pulmonary capillary wedge pressure (PCWP), and pulmonary vascular resistance (PVR). However, this conception does not take into consideration the evolution of these parameters throughout the cardiac cycle. We hypothesized that not only the magnitude but also the dynamics over time plays an important role in RV adaptation to pressure overload (i.e., constant fixed resistances throughout the cycle will have a different impact than a fluctuating resistances). Purpose To assess PA hemodynamic patterns throughout the cardiac cycle and their association with RV remodelling, by combining right heart catheterization (RHC) and cardiac magnetic resonance imaging (CMR) data. Methods 66 patients with PH (38 women, aged 63.59±14.70years, BMI 28.49±6.21 kg.m2) who underwent RHC in the supine position with a 7.5-FrSwan-Ganz catheter under fluoroscopic guidance (37 precapillary, 17 combined pre-postcapillary, 12 isolated postcapillary PH) and CMR with flow-encoded phase-contrast sequence were included. Pressure and flow tracings at the level of the main PA were integrated to obtain volume-pressure loops throughout the cardiac cycle. The resulting patterns based on morphology (Image 1) and slope (Pattern 1 mean slope 16,11% vs Pattern 2 mean slope 10,37%) were analysed and classified into 2 groups: Pattern 1 and Pattern 2. RV end-systolic (iRVESV) and end-diastolic volumes (iRVEDV), RV ejection fraction, RV mass and presence of late gadolinium enhancement (LGE) at the RV insertion points were compared between groups using parametric and non-parametric tests. Results Patients with Pattern 1 showed significantly higher mPAP (46.03±11.62 vs. 35.77±8.10 mmHg) and iPVR (746.22±584.54 vs 319.56±306.21 dynes.s.cm-5.m2) and lower PCWP (11.8±7.6 vs 17.7±7.2 mmHg). Precapillary PH patients more frequently presented a Pattern 1 (n=27; 77.1% vs 10; 32.3%). In addition, patients with Pattern 1 had higher RV volumes (iRVEDV= 105.45±34.62 ml/m2 vs 84.22±35.0 ml/m2, p=0,002; iRVESV 65.05±27.59 ml/m2 vs 44.63±25.09 ml/m2, p=0,001), poorer RV function (RVEF 39.81±11.33% vs 48.96±10.90%; p=0,001), larger RV mass (27.95±9.46 vs 23,44±7.46 g/m2, p=0,045) and smaller left atrial size (24.18±11.47 vs 34.06±19.15 cm2, p&amp;lt;0,001) than patients with Pattern 2. The quantification of LGE was also higher in Pattern 1 as compared with Pattern 2 (5.4±2.4% vs 3.0±2.3%, p&amp;lt;0.001). Conclusion Volume-pressure loops at the level of the main PA may differentiate patterns of PA hemodynamic fluctuations that have different impact on RV performance regardless the PH severity within the wide spectrum of PH.Volume-pressure loop patterns

Hemodynamic effects of right and biventricular pacing during exercise in hypertrophic obstructive cardiomyopathy

Abstract Background One third of patients with hypertrophic cardiomyopathy present with dynamic left ventricular outflow tract obstruction (LVOTO), referred to as hypertrophic obstructive cardiomyopathy (HOCM). Symptomatic treatment aims at reducing LVOTO with either medications, invasive septal reduction, or pacing. The importance of pacing site is unclear, and effects of pacing during physical activity have not been investigated. Purpose To determine the effect of right ventricular (RV) and biventricular (BiV) pacing, respectively, on LVOTO and cardiac output (CO) during exercise in patients with HOCM. Methods Patients with symptomatic HOCM, sinus rhythm, and no bundle branch block, scheduled for alcohol septal ablation (ASA), were eligible for inclusion. The day before ASA, we placed temporary pacing leads in the right atrium, the RV apex, and on the left ventricle’s lateral wall via the coronary sinus. LVOTO was assessed by echocardiography, and CO was measured by thermodilution with a pulmonary artery catheter. Patients performed supine cycling for 2 minutes until heart rate (HR) increased ≥20 bpm. We measured LVOTO and CO in sinus rhythm, and during cycling with atrial sensed RV pacing, and atrial sensed BiV pacing. The order of pacing sites was randomized, and the personnel performing echocardiography and CO measurements were blinded to the order of pacing. Results We included six patients (54±15 years) with a mean maximal left ventricular wall thickness of 16.7±1.8 mm. Resting LVOTO was 55.7±30.9 mmHg. The figures show LVOTO and CO in sinus rhythm (HR 85±10 bpm), RV pacing (HR 90±10 bpm), and BiV pacing (HR 91±9 bpm) during supine cycling. The LVOTO declined from 56±34 mmHg in sinus rhythm to 27±12 mmHg and 25±5 mmHg respectively for atrial sensed RV and BiV pacing. CO remained unchanged during sinus rhythm (9.0±1.2 L/min), atrial sensed RV pacing (9.0±1.7 L/min), and BiV pacing (8.9±1.5 L/min). Conclusion In this ongoing study evaluating cardiac pacing in HOCM, preliminary data indicate that both RV and BiV pacing are effective in reducing LVOTO during exercise, without compromising CO.

Clinical utility of fibrosis-4 index in predicting increased right atrial pressure

Abstract Introduction Fibrosis-4 (FIB-4) index, derived from serum aspartate transaminase, alanine aminotransferase, platelet count and age, is an easily measurable marker reflecting hepatic fibrosis. Recently, FIB-4 index has been reported to be associated with cardiac events in heart failure (HF) patients. We examined whether FIB-4 index was useful in predicting elevated right atrial pressure (RAP) in comparison with directly measured RAP. Methods We studied consecutive 293 HF patients who underwent right heart catheter (RHC) examinations at our institution between Sep 2021 and May 2023. The exclusion criteria were as follows: viral or metabolic chronic hepatic diseases, thrombocytopenia. The subjects received RHC examination and blood test on the same day, and echocardiography within 3 days from the RHC examination. On top of FIB-4 index, diameter of inferior vena cava (IVC) and its respiratory changes were measured as a conventional method to estimate RAP. Results A total of 252 patients (mean 64.7 years of age, 52.8% men) were eligible for this study. FIB-4 index was significantly correlated with mean RAP (r = 0.39, p &amp;lt; 0.001). ROC curve analysis revealed that 1.80 was the optimal cutoff value of FIB-4 index to predict increased RAP &amp;gt; 10mmHg (AUC 0.74, p &amp;lt; 0.001, sensitivity 76.1%, specificity 74.0%). As shown in Figure, the diagnostic accuracy increased when FIB-4 index was combined with IVC diameter (AUC 0.77), which was significantly higher than the combination (AUC 0.71) of IVC diameter alone (AUC 0.71, p &amp;lt; 0.001, cutoff 17mm, sensitivity 67.6%, specificity 71.8%) and IVC respiratory changes alone (AUC 0.61, p = 0.005, cutoff 53%, sensitivity 77.5%, specificity 44.2%). Conclusions FIB-4 index was clinically useful in predicting increased RAP, especially when it was combined with IVC diameter.

Transpulmonary proteome gradients identify inflammatory pathways involved in the development of pulmonary vasculopathy in heart failure

Abstract Background Some, but not all, patients with heart failure (HF) develop pulmonary vascular disease (PVD), which contributes to poor prognosis. Mechanisms leading to PVD in HF are poorly understood. Unbiased analysis of transpulmonary gradients may identify not only markers but also mediators of PVD by identifying proteins that may be consumed or elaborated across the lungs. Purpose Examine hemodynamics and transpulmonary proteome gradients in HFrEF and controls. Methods 21 non-HF controls and 160 patients with advanced HFrEF underwent pulmonary artery (PA) catheterization with blood sampling from the PA catheter in the wedged position (02sat &amp;gt; 90%, indicating pulmonary venous blood) and the un-wedged position to obtain transpulmonary proteome gradients. Samples from controls and HF from the highest quartile (Q4, n=40) and lowest quartile (Q1, n=40) of pulmonary vascular resistance (PVR) were analyzed using proteomic PEA assay of 275 proteins (Olink Target 96, panels CVII, CVIII, Inflammation). Pulmonary artery concentrations ("markers") or transpulmonary fold-change gradients (i.e. putative "mediators") of normalized protein expression (NPX) were plotted against significance; Benjamini–Hochberg FDR&amp;lt;0.05 considered as significant. Results Patients displayed typical characteristics of HFrEF (age 56±8y, NYHA 3.0 ±0.6, 87% males, LVEF 24±9.6%), Controls had similar anthropometrics, gender and age. Comparing all HF to Con, 38 markers of HF were identified (NPX fold-change&amp;gt;2), including 33 up (top 5: NTproBNP, BNP, GDF15, FGF23, IL8) and 5 down. HF patients in Q1 had median PVR 1.5 (IQR: 0.3-1.7) WU and those in Q4 had PVR 5.4 (4.3-6.6) WU. Comparison of Q1 and Q4 identified 3 protein markers of high PVR in PA blood from HF: chemokine CCL3, TNFRSF13B and surfactant protein-D (PSP-D). Examination of protein gradients from HF lungs (Figure) showed significant uptake of 14 protein mediators, most of which were associated with inflammatory responses (top 5: OSM, MMP9, CCL19, BNP, TR), and release of 8 mediators (top 4: IL-6, IL33, CCL4, CXCL10). In contrast, protein gradients were negligible in controls. Patients in Q4 PVR group were characterized by the highest pulmonary uptake of OSM (Oncostatin-M), lymphatic chemokine CCL19, BNP, MMP9, and had more significant transpulmonary release of IL6 and IL33. Across all patients, OSM lung uptake was the strongest correlate of transpulmonary pressure gradient (r=-0.3, p&amp;lt;0.001). Conclusions Lungs of patients with HF, and particularly those with high PVR, display abnormal uptake and release of proinflammatory CC and CXC chemokines and cytokines from IL1 and IL6 family, along with increased pulmonary uptake of IL6-type cytokine Oncostatin-M, a known mediator of lung inflammation and fibrosis, that acts via gp130/JAK/STAT, suggesting a novel role in PVD due to HF.Transpulmonary proteome in HF patients