Post-capillary Pulmonary Hypertension Research Articles

A Triple Threat: A Case Report Detailing Surgical Management for Hypertrophic Cardiomyopathy, Flail Mitral Valve and Severe Pulmonary Hypertension

The combination of hypertrophic cardiomyopathy with outflow tract obstruction, severe pre-capillary and post-capillary pulmonary hypertension, and severe primary mitral regurgitation is rare and presents distinct management challenges. Background and Clinical Significance: Pulmonary hypertension is an independent predictor of all-cause mortality in patients with hypertrophic cardiomyopathy managed medically and often precludes patients from undergoing cardiopulmonary bypass due to increased surgical morbidity and mortality. In studies specifically evaluating surgical myectomy, however, survival is favorable in patients with moderate-to-severe pulmonary hypertension. Case Presentation: We present a case of a 74-year-old male with six months of dyspnea with minimal exertion. A diagnostic work-up with transthoracic echocardiogram showed asymmetric left ventricular hypertrophy, left ventricular outflow tract obstruction with a peak gradient of 200 mmHg, right ventricular systolic pressure of 99 mmHg, systolic anterior motion of the mitral valve and flail anterior mitral leaflet. The patient was evaluated by a multi-disciplinary team and underwent extended septal myectomy and mitral valve repair with significant improvement in functional capacity post-operatively. Conclusions: While pulmonary hypertension increases the risk of morbidity and mortality during cardiopulmonary bypass, moderate-to-severe pulmonary hypertension in hypertrophic cardiomyopathy with outflow tract obstruction is a unique indication for septal reduction therapy that may not be associated with higher surgical mortality.

Clinical Management and Transplant Considerations in Pediatric Pulmonary Hypertension Due to Left Heart Disease: A Scientific Statement From the American Heart Association.

Children with left heart disease are at risk for developing pulmonary hypertension, initially secondary to pulmonary venous hypertension that can progress to include elevated pulmonary vascular resistance, known as combined pre- and postcapillary pulmonary hypertension. Elevated pulmonary vascular resistance may pose a risk to the right ventricle of a newly transplanted heart because of increased afterload and is an important consideration for heart transplant eligibility. However, the epidemiology, pathophysiology, optimal diagnostic and treatment approaches, and thresholds for pulmonary vascular resistance in pulmonary hypertension associated with left heart disease remain unclear because of lack of evidence, particularly in pediatrics. The result is heterogeneity with respect to hemodynamic assessment, use of pulmonary vasodilator therapies, and heart transplant listing. This scientific statement aims to synthesize the available data and highlight areas of general consensus as well as important knowledge gaps.

The importance of assessing and correcting hydration status prior to right heart catheterisation: a pilot study.

We evaluated whether fluid status could be accurately assessed (and corrected if necessary) prior to right heart catheterisation (RHC), to diagnose accurately post-capillary pulmonary hypertension (PHT) in patients with left heart disease risk factors. A non-invasive measure of fluid status prior to RHC identified fluid-depleted patients. Baseline RHC measurements were performed, and a novel provocation technique (passive leg raise) was compared to a 'one-dose-fits-all' fluid challenge and found to be equivalent.

Abstract 4133846: Even Mild Increase in Pulmonary Arterial Pressure Following Kidney Transplantation is Associated with Increased Mortality

Background: In end-stage renal disease (ESRD), elevated systolic pulmonary artery pressure (sPAP) is common, attributed to post-capillary pulmonary hypertension (PH) and associated with adverse outcomes. Kidney transplantation (KT) may mitigate ESRD-PH. We aimed to profile sPAP trajectory in a national cohort of ESRD patients pre- and post-KT, and link findings to clinical outcome. Methods: We analyzed retrospectively all patients within the Veterans Affairs Healthcare System undergoing KT between 2000-2019 with sPAP recorded pre- and post-KT by echocardiography. PH was defined by >35mmHg. Patients were assigned to one of the following groups: Never PH, New PH post-KT, Resolved PH post-KT, and Persistent PH. Spline curve and Kaplan-Meier analyses were used to test the association of sPAP or PH group with all-cause mortality, adjusted for age and sex. Results: From 631 patients (median 62 [IQR 58-65]yr; 97% male), there were 231 (36.6%), 184 (29.2%), 133 (21.1%), and 83 (13.1%) patients in the Persistent PH, Never PH, Resolved PH, and New PH groups, respectively. Never PH, Resolved PH and New PH had, overall, similar cardiopulmonary comorbidities ( Tab. 1 ). By contrast, Persistent PH had the highest rate of congestive heart failure, atrial fibrillation, and impaired diastolic relaxation assessed by E/E’. Creatinine post-KT, indicative for graft function, was stable in Never PH, Resolved PH and Persistent PH, but significantly increased in New PH. Of all groups, Resolved PH was associated with the most favorable survival rate (HR 0.73 [95%CI 0.51-1.05], p=0.087). New PH and Persistent PH were associated with a 51% (HR=1.51 [95%CI 1.06-2.15], p=0.023) and 37% (HR=1.37 [95%CI 1.03-1.82], p=0.029; referent group for all: Never PH) increase in adjusted mortality risk post-KT ( Fig. 1a ). Overall, we observed 21% (HR=1.21 [95%CI 1.11-1.31], p<0.001) increase in mortality hazard adjusted for age, sex and baseline sPAP, per 10mmHg increment increase in sPAP from pre-KT to post-KT whereas a 10mmHg sPAP decrease was associated a 17% decrease in mortality (HR=0.83 [95%CI 0.76-0.90], p<0.001) ( Fig. 1b ). Conclusion: These data suggest that PH is common post-KT and includes a sizeable group of patients without PH pre-KT. Increased PAP or failure for PH to resolve post-KT were independently associated with mortality. Overall, these data warrant prospective studies in sex-balanced cohorts that use PH to stratify KT candidacy and PAP as a longitudinal biomarker of graft function post-KT.

Misfortune never comes singly: an unusual case of a patient with type 1 diabetes mellitus and widespread cardiac fibrosis with restrictive phenotype, mitral stenosis and postcapillary pulmonary hypertension.

Misfortune never comes singly: an unusual case of a patient with type 1 diabetes mellitus and widespread cardiac fibrosis with restrictive phenotype, mitral stenosis and postcapillary pulmonary hypertension.

The impact of the 2022 definition of pulmonary hypertension on long-term clinical outcomes in patients with heart failure with preserved ejection fraction

Abstract @ Backgrounds: In recent years, the definitions of pulmonary hypertension (PH) have been revised for early diagnosis and risk stratification of patients with PH. Using the 2015 definitions, the development of a precapillary component of PH in addition to a postcapillary PH was associated with right heart dysfunction and poor prognosis in patients with heart failure (HF) with preserved ejection fraction (HFpEF). However, the prognostic impact of revised definitions of PH in patients with HFpEF has not been fully evaluated. Purpose We investigated the impact of the 2018 and 2022 ESC/ERS definitions of PH on long-term clinical outcomes using data from a prospective, multicenter, observational study of patients with HFpEF (PURSUIT-HFpEF). Methods A total of 250 patients hospitalised with acute HF who underwent right heart catheterisation after initial HF treatment were divided into PH categories according to the 2018 and 2022 definitions: isolated postcapillary PH (Ipc-PH), precapillary PH, combined postcapillary and precapillary PH (Cpc-PH), and unclassified PH. The incidence of the composite endpoint of all-cause death and HF rehospitalisation after discharge was compared across the PH categories. Results The overall prevalence of PH defined as a mPAP > 20 mmHg was 54%. Applying the 2022 definition, 42 patients (17%) were reclassified as either precapillary PH or Cpc-PH, resulting in a significant increase in the propotion of patients classified as having PH with a precapillary component (precapillary PH and Cpc-PH) compared with the 2018 definition (26% vs. 11%, p<0.0001). At a median follow-up of 822 days after discharge, PH with a precapillary component was associated with poor clinical outcomes according to the 2018 definition (Figure 1A), but according to the 2022 definition, clinical outcomes did not differ across the PH categories (Figure 1B). PVR ≥3 Wood units (WU) was a significant prognostic indicator, but there was no significant difference between the PVR 2-3 WU and PVR ≤2 WU categories (Figure 2). Conclusions The 2022 definition showed no association between PH classification and clinical outcomes. In patients with HFpEF, PVR ≥3 WU was identified as the key factor increasing the risk of all-cause death and HF hospitalisation.Figure 1Figure 2

TAPSE/sPAP by echocardiography to detect elevated pulmonary vascular resistance> 4 WU in postcapillary pulmonary hypertension patients: insights from the French PH HF registry

Abstract Background Post-capillary pulmonary hypertension (pcPH) lacks effective treatment options. Patients with a PVR > 4 WU, known as combined pcPH (cpcPH), may benefit from investigational drugs like sotatercept. Identifying cpcPH patients suitable for vasodilation therapy in echocardiography labs is critical. Purpose To pinpoint an echocardiographic parameter capable of detecting cpcPH patients with a PVR above 4WU, addressing a common challenge in clinical practice. Methods In this study, 225 participants from the French PH-HF registry, all diagnosed with heart failure and a preserved ejection fraction, were examined. These patients underwent right heart catheterization and got ultrasound examinations within a 24-hour timeframe. The pulmonary vascular resistance were calculated using previously established methods, and data from standard echocardiography, including assessments of diastolic function, were gathered. Results 69 patients exhibited a pulmonary vascular resistance (PVR) greater than 4 WU, while 156 patients had a PVR ≤ 4 WU. Age averaged 69±12 years. Mean pulmonary artery pressure, wedge pressure, cardiac output, and pulmonary vascular resistance were 39±9 mm Hg, 22±4 mm Hg, 5.1±1.7 l/min, and 3.5±2.0 WU, respectively. Comparative analysis between patients with PVR ≤ 4 WU and those with PVR > 4 WU revealed similar ejection fraction (EF), left atrial volume index, and E/A ratio by echocardiography (p=0.97, p=0.69, p=0.43, respectively). However, patients with PVR > 4 WU showed elevated E/e’ (p=0.008), higher systolic pulmonary artery pressure (sPAP, p=0.001), but reduced myocardial S and e’ tissue Doppler velocities (p=0.001) and tricuspid annular plane systolic excursion (TAPSE) (p=10^-5). Notably, the relationship between TAPSE/sPAP and PVR > 4 was curvilinear and strong (p=0.001, FIG 1). Using ROC curve analysis, patients with TAPSE/sPAP < 0.38 mm/mmHg were identified to have PVR > 4 WU with a sensitivity and specificity of 68%. Conclusion Within the scope of postcapillary pulmonary hypertension, right ventricular arterial coupling is a simple ultrasound parameter potentially effective in identifying individuals exhbiting PVR > 4 WU with a good sensitivityFigure 1:PRV and coupling plotFigure 2:RV coupling ROC

Left atrial strain demonstrates the ability to distinguish patients with pre and post-capillary pulmonary hypertension

Abstract Background The characterization of pulmonary hypertension (PH) patients into pre or postcapillary (pcPH)phenotypes poses a challenge during screening due to the ambiguity surrounding their comorbidities. This distinction is crucial as it influences treatment decisions and prognostication. Purpose Investigating Left Atrial Strain as a Discriminant Marker for Distinguishing Pre and Post-Capillary PH. Methods Out of 164 patients exhibiting both pre- and post-capillary phenotypes, 97 had optimal left atrial 2D strain. Left atrial 2D strain was performed with a GE Vivid9 ultrasound machine equipped with dedicated software, ensuring meticulous attention to image quality and region of interest thickness restricted to a maximum of 6 mm. Subsequently, the peak left atrial strain during reservoir function was quantified as part of the investigation. To determine the optimal cut-off value, ROC curve analysis was employed. Results 60 patients had pcPH while 37 had pre-capillary PH. Mean age was 65±12y. Mean pulmonary artery pressure, wedge pressure, cardiac output and pulmonary vascular resistance averaged 40,9±10,7 mm Hg, 15,7±8,7 mm Hg, 5,9±2,0 l/min and 4,7±3,1 WU, respectively. Left atrial 2D strain ranged from +2,5% to 60%, with a mean of +18,2±11,2%. From ROC cure analysis, patients with LA 2D strain > +19,1% had a precapillary phenotype with a sensitivity and a specifity of 93% and 88% respectively (Fig 1). Left atrial 2D strain demonstrates higher sensitivity compared to various parameters, such as scores from the European Society of Respiratory Disease, left ventricular end-diastolic pressure estimation from the American Society of Echocardiography, HFA-PEFF score, and H2FPEF from the AHA. Conclusion Left atrial 2D strain demonstrates superior sensitivity in distinguishing between patients with pre and post-capillary pulmonary hypertension compared to other assessment methods.FIG 1:Left atrial 2D strainFig 2:SENS of parameters and scores

Echocardiographic profiles of patients with CPCPH and IPCPH in HFpEF: insights from the PHHF study

Abstract Background The 2022 ESC/ERS guidelines changed the definition of post-capillary pulmonary hypertension (pcPH) in heart failure (HF) by lowering the level of mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR). Yet, the echocardiographic profile of HF with preserved ejection fraction (PEF) patients according to their mPAP and RVP is not known. Objectives To investigate the echocardiographic profile of HFPEF patients according to their mPAP and RVP. Methods Stable HF patients with the need for right heart catheterization were enrolled from 2010 to 2018 and prospectively followed-up in this multicenter study. All patients had a right heart catheterization and an echocardiography within the 24 hours. PcPH was characterized by a pulmonary wedge pressure exceeding 20 mm Hg and mean mPAP greater than 20 mm Hg, from an isolated state when PVR was less than 2 Wood units (WU, IpcPH) to a combined form when PVR exceeded 2 WU (CpcPH). Results Out of 662 HF patients included in PHHF study, 268 (40%) were classified as having HFpEF (35% male, median age 71 yo). Compared to IpcPH patients, CpcPH patients had higher tricuspid regurgitation peak velocity (sPAP, 3.53 vs 3.00 m/s, p<0.01), lower S tricuspid tissue Doppler velocity (10 vs. 11 cm/s, p 0.01) and TAPSE (18 vs. 21 mm, p< 0.01) and lower TAPSE/sPAP ratio (0.3 vs. 0.4, p<0.01). There were no differences between groups regarding both right ventricle and right atrial diameter and area. Conclusion In HFpEF patients with PH, CpcPH patients had worse right ventricular function despite similar remodeling when compared to IpcPH patients

Exercise postcapillary pulmonary hypertension in patients with chronic thromboembolism. Role of multimodal resting and exercise assessment

Abstract Introduction Chronic thromboembolic pulmonary disease refers to the presence of thrombotic material after a pulmonary embolism (PE), exercise limitation and the absence of resting pulmonary hypertension (PH) but impaired right ventricular and pulmonary vascular reserve during exercise causing exercise precapillary PH (exprecapPH). However, in some patients, PH arises from an abnormal increase in pulmonary arterial wedge pressure (PAWP) with exercise in relation to underlying diastolic dysfunction, with thrombotic material not playing a substantial role. Whether these patients present distinct non-invasive and resting invasive parameters remains largely unknown. Purpose To compare the different exercise hemodynamic profiles of patients with chronic thromboembolism to identify clinical, echocardiographic, functional and hemodynamic parameters associated with exercise postcapillary PH (expostcapPH). Methods Data come from a prospective cohort of 71 symptomatic patients with perfusion defects in lung scintigraphy and computed tomographic confirmation of chronic thrombi despite anticoagulation ≥3 months after PE without or mild resting PH, undergoing exercise cardiac catheterization via supine cycle ergometry. A multipoint mean pulmonary artery pressure (mPAP)/cardiac output (CO) and mean PAWP/CO slope were calculated. Simultaneous stress echocardiography was available in 43 patients. Cardiopulmonary exercise test (CPET) was performed 24 hours before catheterization. Results Mean age was 53±13.9 years, 46 (64.8%) were males. 37 patients showed normal exercise hemodynamics, while 26 developed exprecapPH and 8 expostcapPH. Mean mPAP/CO slope was 3.1±1.6 mmHg/L/min, mean PAWP/CO slope 1.5±0.9 mmHg/L/min. Patients with expostcapPH were older, had a higher body mass index and hypertension. Comparison of hemodynamics, CPET and resting echocardiography is depicted in the table. Patients with expostcapPH, similar to those without exercise PH, had significantly lower resting pulmonary pressures and pulmonary vascular resistance than those with exprecapPH. These differences remained at peak exercise; however, while resting PAWP did not differ between groups, a significant increase in PAWP was unmasked in patients with expostcapPH compared to the other groups, and accordingly a significant difference in the PAWP/CO slope. Regarding CPET, patients with expostcapPH had higher baseline systolic blood pressure and lower functional capacity (VO2 max, VO2 at VT1, O2 pulse, OUES). Resting TAPSE/PASP was higher in patients with expostcapPH compared to those with exprecapPH. Conclusions Patients with chronic thromboembolism and expostcapPH exhibit distinct clinical features and have lower functional capacity, while resting PAWP did not allow differentiation between groups. Further studies are warranted to delineate characteristic elements of patients with underlying diastolic dysfunction due to its distinct prognosis and treatment.

Does the presence of severe pulmonary hypertension affect survival at 5 years follow-up in patients who underwent TAVI for severe aortic stenosis?

Abstract Background Pulmonary hypertension (PH) is common in patients with severe aortic stenosis (AS) and is associated with increased mortality after transcatheter aortic valve implantation (TAVI) as well as surgical aortic valve replacement (SAVR). Preprocedural systolic pulmonary artery pressure (sPAP) often improves after TAVI because the most common type of PH is postcapillary PH secondary to left-sided heart disease, which potentially improves after treatment for AS. However, there are limited data regarding the prognostic impact on outcomes after TAVI and their predictors. Purpose The aim of this study is to compare survival at 5 years between patients with severe PH against those who did not have severe PH who underwent TAVI. Methods Between January 2012 until December 2022, we carried out a retrospective study of all patients who underwent TAVI at our hospital. Severe PH was defined as the presence of sPAP >40mmHg on echocardiography. Patients with aortic regurgitation and mixed aortic valve disease were excluded. Co-morbid pulmonary disease was defined as the presence of any significant pulmonary disease including COPD and Asthma. Co-morbid neurological disease was defined as the presence of any significant neurological disease including CVA/ TIA. Diabetes mellitus was defined as per WHO and included patients who were diet, medication and insulin controlled. Survival status and date of death were ascertained from our electronic health records. Counts and incidence rates of clinical outcomes at 5-year follow-up were computed from Kaplan-Meier analysis (See Figure 1). A Cox proportional hazards model was used to compute HRs and 95% CIs for the study outcomes. Results Of the 274 patients available for analysis, 115 (14%) patients had severe PH. The mean age was 84 years in both cohorts whilst patients in the severe PH cohort were frailer by Katz Index Score. Death occurred in 67 patients out of 115 patients who had severe PH and in 87 out of 158 patients who did not have severe PH after a median follow-up time of 4.1 years (58% vs 55%; adjusted HR: 1.04; 95% CI: 0.71-1.51; P = 0.86). Conclusion Our data shows that presence of severe pulmonary hypertension in severe aortic disease patients who had undergone TAVI did not affect survival at 5 years follow up compared to patients without severe pulmonary hypertension undergoing TAVI. Determining predictors of mortality in this high-risk cohort is likely to be complex and multifactorial, owing to the severe multi-comorbidity precluding them from SAVR.

CILP1 and NTproBNP in pulmonary hypertension and right ventricular pressure overload: a translational experimental study

Abstract Introduction Cartilage intermediate layer protein 1 (CILP1) has emerged as a novel marker of right ventricular (RV) dysfunction in pulmonary hypertension (PH), although there is still little evidence on its role in different scenarios of RV pressure overload. The aim of our study was to analyze CILP1 as a biomarker of RV remodeling and PH severity, and compare it with N-terminal pro-brain natriuretic peptide (NTproBNP), in different experimental models of RV pressure overload. Methods Three different experimental models of RV pressure overload compared to a sham procedure were evaluated in 24 Yucatan pigs: chronic postcapillary PH by pulmonary vein banding (M1, n=6); chronic PH by aorto-pulmonary shunting (M2, n=6); RV pressure overload by PA banding (thus without PH) (M3, n=6); and sham procedure (M0, n=6). Animals were evaluated at 8 months after surgery by right heart catheterization, cardiac magnetic resonance (CMR), and blood/histological sampling. Levels of CILP1 and NTproBNP at the RV myocardium and blood were determined with dedicated ELISA and compared among groups by Wilcoxon test with Bonferroni correction. Associations between biomarkers and RV performance indices and pulmonary arterial pressure (PAP) were assessed with Spearman correlation test. Results M1 animals developed chronic postcapillary PH with normal left ventricular (LV) performance and RV maladaptive hypertrophy (RV fibrosis and systolic dysfunction). M2 animals developed chronic precapillary PH associated with LV dilatation and RV maladaptive hypertrophy. On contrast, M3-animals developed severe RV pressure overload (without PH) and hypertrophy but maintained normal RV systolic function. CILP1 and NTproBNP levels were moderately correlated (R=0.56, p=0.002). CILP1 levels in RV myocardium and plasma were significantly higher in M1, whereas NTproBNP plasma levels were significantly higher in M2 (Figure 1). CILP1 in plasma and RV myocardium significantly correlated with PAP, while myocardial CILP1 levels also correlated with RV extracellular volume (RV-ECV) by CMR (Figure 2). NTproBNP myocardial levels correlated with RV ejection fraction and RV-ECV and plasmatic levels correlated with PAP (Figure 2). Conclusions CILP1 levels were increased in the presence of PH and isolated RV dysfunction, whereas NTproBNP levels were increased in the model of PH, RV dysfunction and LV remodeling. Myocardial levels of both peptides correlated with diffuse fibrosis, estimated by CMR, whereas plasmatic levels of both biomarkers correlated with PAP. This suggests that CILP1 may be a more specific marker of RV dysfunction in PH, being less dependent of LV parameters.CILP1 and NTproBNP levels among modelsCorrelation with PAP & RV remodeling

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<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<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

Impact of Pulmonary Hypertension on Outcomes After Transcatheter Tricuspid Valve Edge-to-Edge Repair

BackgroundData regarding the association of pulmonary hypertension (PH) and outcomes in patients undergoing transcatheter tricuspid valve edge-to-edge repair (T-TEER) are scarce. ObjectivesThe aims of this study were 1) to investigate the impact of PH on outcomes after T-TEER; and 2) to shed further light on the role of pre- and postcapillary PH in patients undergoing T-TEER for relevant tricuspid regurgitation (TR). MethodsThe study included patients from the EuroTR (European Registry of Transcatheter Repair for Tricuspid Regurgitation) registry (NCT06307262) who underwent T-TEER for relevant TR from 2016 until 2023 with available invasive evaluation of systolic pulmonary artery pressure (sPAP) using right heart catheterization. Study endpoints were procedural TR reduction, improvement in NYHA function class, and a combined endpoint of death or heart failure hospitalization (HFH) at 2 years. ResultsAmong a total of 1,230 patients (mean age 78.6 ± 7.0 years, 51.4% women), increasing sPAP was independently associated with increasing rates of 2-year death or HFH (HR: 1.027; 95% CI: 1.003-1.052; P = 0.030; median survival follow-up 343 days [Q1-Q3: 114-645 days]). No significant survival differences were observed for patients with pre- vs postcapillary PH. Sensitivity analysis revealed an sPAP value of 46 mm Hg as the optimized threshold for the prediction of death or HFH. Being observed in 526 patients (42.8%), elevated sPAP (>46 mm Hg) was associated with more severe heart failure symptoms at baseline and follow-up. Importantly, NYHA functional class significantly improved and TR severity was significantly reduced irrespective of PH. ConclusionsPH is an important outcome predictor in patients undergoing T-TEER for relevant TR. In contrast to previous studies, no significant differences were observed for patients with pre- and postcapillary PH in terms of survival free from HFH.

Hemodynamic markers independent of pulmonary capillary wedge pressure can discriminate between pre and postcapillary exercise-induced pulmonary hypertension.

The discrimination between pre and postcapillary exercise-induced pulmonary hypertension relies on accurate measurement of pulmonary capillary wedge pressure, which can be unreliable. We found that exercise pulmonary artery compliance and right atrial pressure (AUC 0.88, 0.89, respectively) can differentiate subtypes of exercise-induced pulmonary hypertension in the absence of wedge pressure.

BMP10 reflects pre-capillary pulmonary hemodynamics: association of biomarkers and hemodynamic parameters in pulmonary hypertension

Abstract Background and aims The role of biomarkers in diagnosing pulmonary hypertension (PH) and distinguishing between pre- and post-capillary PH remains poorly understood. We aimed to identify biomarkers with a strong association with mean pulmonary arterial pressure, mPAP (PH diagnosis) and pulmonary vascular resistance, PVR (pre-capillary component), but not with pulmonary arterial wedge pressure, PAWP (post-capillary component). Methods Blood samples were collected in patients undergoing right heart catheterization within a prospective cross-sectional study. Biomarkers measured included BMP10, NT-proBNP, ANG2, ESM1/endocan, FGF23, GDF15, IGFBP7, IL6, MyBPC3, proC3, and proC6/endotrophin. Primary outcomes were mPAP, PVR, and PAWP, while secondary outcomes included PH diagnosis (mPAP > 20 mmHg) and elevated PVR (> 2 Wood units). Multivariable linear and logistic regression models were used to assess the relationship between biomarkers and outcomes. Results Of the 127 patients included (age 66 ± 13 years, 54% female), 73% were diagnosed with PH. BMP10, NT-proBNP, ANG2, MyBPC3, and FGF23 showed a strong association with mPAP (p < 0.001). BMP10 and NT-proBNP were strongly associated with PVR (p < 0.001), while NT-proBNP and ANG2 were strongly associated with PAWP (p < 0.001). NT-proBNP had the strongest association with the diagnosis of PH (area under the curve = 0.76). BMP10 was the only biomarker associated with elevated PVR (OR 1.60, 95%CI 1.01–2.54, p = 0.04) but not with PAWP (p = 0.86). Conclusions Several biomarkers were strongly associated with mPAP, PAWP, and PVR. BMP10 was the only biomarker strongly associated with mPAP and PVR, but not with PAWP, thus reflecting the pre-capillary PH component. Measurement of BMP10 along with NT-proBNP may aid in diagnosing PH. Graphical abstract

The spectrum of systemic sclerosis-associated pulmonary hypertension: Insights from the ASPIRE registry

There are limited data assessing the spectrum of systemic sclerosis-associated pulmonary hypertension (PH). Data for 912 systemic sclerosis patients assessed between 2000and 2020 were retrieved from the Assessing the Spectrum of Pulmonary hypertension Identified at a REferral centre (ASPIRE) registry and classified based on 2022 European Society of Cardiology/European Respiratory Society(ESC/ERS) guidelines and multimodality investigations. Reduction in pulmonary vascular resistance (PVR) diagnostic threshold to >2WU resulted in a 19% increase in precapillary PH diagnoses. Patients with PVR ≤2WU had superior survival to PVR >2-3WU which was similar to PVR >3-4WU. Survival in pulmonary arterial hypertension (PAH) was superior to PH associated with lung disease. However, patients with mild parenchymal disease on CT had similar characteristics and outcomes to patients without lung disease. Combined pre- and postcapillary PH had significantly poorer survival than isolated postcapillary PH. Patients with mean pulmonary arterial wedge pressure (PAWP) 13-15mmHg had similar haemodynamics and left atrial volumes to those with PAWP>15mmHg. Unclassified-PH had more frequently dilated left atria and higher PAWP than PAH. Although Unclassified-PH had a similar survival to No-PH, 36% were subsequently diagnosed with PAH or PH associated with left heart disease. The presence of 2-3 radiological signs of pulmonary veno-occlusive disease was noted in 7% of PAH patients and was associated with worse survival. Improvement in incremental shuttle walking distance of ≥30m following initiation of PAH therapy was associated with superior survival. PAH patients diagnosed after 2011 had greater use of combination therapy and superior survival. A number of systemic sclerosis PH phenotypes can be recognized and characterized using haemodynamics, lung function and multimodality imaging.

Definition, classification and diagnosis of pulmonary hypertension.

Pulmonary hypertension (PH) is a haemodynamic condition characterised by elevation of mean pulmonary arterial pressure (mPAP) >20 mmHg, assessed by right heart catheterisation. Pulmonary arterial wedge pressure (PAWP) and pulmonary vascular resistance (PVR) distinguish pre-capillary PH (PAWP ≤15 mmHg, PVR >2 Wood Units (WU)), isolated post-capillary PH (PAWP >15 mmHg, PVR ≤2 WU) and combined post- and pre-capillary PH (PAWP >15 mmHg, PVR >2 WU). Exercise PH is a haemodynamic condition describing a normal mPAP at rest with an abnormal increase of mPAP during exercise, defined as a mPAP/cardiac output slope >3 mmHg/L/min between rest and exercise. The core structure of the clinical classification of PH has been retained, including the five major groups. However, some changes are presented herewith, such as the re-introduction of "long-term responders to calcium channel blockers" as a subgroup of idiopathic pulmonary arterial hypertension, the addition of subgroups in group 2 PH and the differentiation of group 3 PH subgroups based on pulmonary diseases instead of functional abnormalities. Mitomycin-C and carfilzomib have been added to the list of drugs with "definite association" with PAH. For diagnosis of PH, we propose a stepwise approach with the main aim of discerning those patients who need to be referred to a PH centre and who should undergo invasive haemodynamic assessment. In case of high probability of severe pulmonary vascular disease, especially if there are signs of right heart failure, a fast-track referral to a PH centre is recommended at any point during the clinical workup.

Long-term Efficacy of Pulmonary Artery Desnervation Treatment in Heart Failure With Preserved Ejection Fraction: A Subgroup Analysis of 3-year Results From the PADN-5 Study

Objective: The Pulmonary Arterial Denervation in Patients With Pulmonary Hypertension Associated With the Left Heart Failure (PADN-5) study proved that pulmonary artery denervation (PADN) is associated with significant improvements in hemodynamic and clinical outcomes in patients with combined pre- and post-capillary pulmonary hypertension (CpcPH). This study aimed to assess the 3-year clinical results of PADN in patients who had heart failure with preserved ejection fraction (HFpEF) developing into CpcPH (HFpEF-CpcPH). Methods: In this post hoc analysis of the PADN-5 trial, 38 patients with HFpEF were included in screening out of 98 patients with CpcPH who were randomly assigned to treatment with sildenafil and sham PADN (sham PADN (plus sildenafil) group, abbreviated as sham group) or PADN (PADN group). HFpEF in the PADN-5 trial was defined as a left ventricular ejection fraction ≥50%, and CpcPH was defined as a mean pulmonary arterial pressure ≥25 mmHg, a pulmonary arterial wedge pressure >15 mmHg, and a pulmonary vascular resistance >3.0 WU. The changes in the 6-minute walk distance (6-MWD) and the plasma concentration of N-terminal pro-brain natriuretic peptide (NT-proBNP) at 6-month and 3-year follow-up, as well as the clinical endpoint of the occurrence of clinical worsening, defined as cardiopulmonary-related death, rehospitalization, or heart or lung transplantation at 3-year follow-up were examined. Results: Thirty-eight patients with HFpEF-CpcPH were assigned to the PADN group (n = 19) or the sham group (n = 19). At the 6-month follow-up, 6-MWD (433 (275, 580)m vs. 342 (161, 552)m), and reductions in NT-proBNP (−47% (−99%, 331%) vs. −12% (−82%, 54%)) were significantly improved in the PADN group (all P < 0.05). Over the 3-year follow-up period, PADN treatment resulted in marked increases in 6-MWD (450 (186, 510)m vs. 348 (135, 435)m) and reductions in NT-proBNP (−55% (−99%, 38%) vs. −10% (−80%, 95%)) (all P < 0.05). Clinical worsening was experienced by 12 patients (63%) in the sham group, but by only 5 patients (26%) in the PADN group (hazard ratio = 0.149, 95% confidence interval: 0.038–0.584, P = 0.006). The 6-MWD and PADN treatments were independent predictors of clinical deterioration in patients with HFpEF-CpcPH. Conclusions: PADN therapy is associated with improvements in exercise capacity and clinical outcomes. PADN therapy may have a potential role in patients with HFpEF-CpcPH for whom current treatment options are limited.

The effects of bolus isosorbide dinitrate on pulmonary hypertension with cardiopulmonary comorbidities.

Lowering mean pulmonary arterial pressure (mPAP) without reducing cardiac output is essential in treating pulmonary hypertension (PH). Isosorbide dinitrate (ISDN) potentially achieves this in post-capillary PH but can decrease cardiac output and blood pressure (BP), especially in pre-capillary PH. However, post-capillary PH and pre-capillary PH can overlap, and their clear discrimination is difficult. The aim of the study was to examine to what extent bolus ISDN injection reduces mPAP and BP, and changes mixed venous oxygen saturation (SvO2), an indicator of cardiac output in PH with various cardiopulmonary comorbidities in the context of treatment modifications. We retrospectively examined the hemodynamic effects of bolus ISDN injection in patients with PH who underwent right heart catheterization and their subsequent treatment modification. Our sample comprised 13 PH patients. In seven with pre-capillary PH, ISDN significantly lowered mPAP from the median 34 (interquartile range 32-39) to 28 (28-30) mmHg and the mean BP (mBP) from 90 (79-92) to 72 (68-87) mmHg. In six with post-capillary PH, ISDN lowered mPAP from 40 (29-44) to 27 (23-31) mmHg and mBP from 91 (87-110) to 87 (82-104) mmHg. There was a significant decrease in SvO2 from 69.8% (64.9%-78.1%) to 63.9% (60.5%-71.5%) in pre-capillary PH, but not in post-capillary PH including combined post- and pre-capillary PH and some patients showed a large increase in SvO2. In all patients showing an SvO2 increase, diuretics or hemodialysis were up-titrated or continued. Bolus ISDN injection lowered mPAP. However, in pre-capillary PH, it caused a significant decrease in SvO2 and a notable reduction in blood pressure. In post-capillary PH, including combined post- and pre-capillary PH, it clarified whether systemic preload and afterload reduction increased or decreased SvO2 in each patient, which may aid in treatment modification.