Wood Units Research Articles

A prediction model of echocardiographic variables to screen for potentially correctable shunts in adult ASD-PAH patients

Background: Atrial septal defect (ASD) is a prevalent congenital heart condition in adults that leads to pulmonary hypertension (PAH) and right heart failure if left untreated. During a routine follow-up of adult ASD-PAH patients, the suitability of shunt closure depends on the invasive right heart catheterization (RHC). Nevertheless, performing RHC at every follow-up is impractical and may be harmful. The present retrospective cross-sectional study was designed to investigate which echocardiographic variables are related to pulmonary vascular resistance (PVR) in adult ASD-PAH patients and proposed a model using these variables to screen for patients with a correctable shunt. Methods: A total of 530 adult ASD-PAH patients with pulmonary arterial systolic pressure (PASP) of ≥60 mmHg measured using transthoracic echocardiogram (TTE) were included in the study. All RHCs were performed within 3 months after TTE. The correctable shunt was defined as PVR ≤3 wood units (WU). Multivariate regressions were performed utilizing echocardiographic variables. A scoring system was constructed based on the predictors of PVR ≤3 WU using multivariate logistic regression analysis. The scoring system was then examined using a receiver operating characteristic (ROC) analysis. In addition, clinical utility of the model was determined based on decision curve analysis and a calibration curve was used to evaluate model conformity. Results: Estimated pulmonary arterial systolic pressure, velocity through the pulmonary valve, tricuspid annulus early diastolic velocity, and maximum defect dimension were identified as independent predictors. The area under the ROC curve of the predictive value in the model was 0.905 [95% confidence interval (CI): 0.878–0.931, sensitivity: 84.3%, specificity: 83.6%]. The net benefit of the model was notable in terms of a wide-range probability threshold in decision curve analysis, indicating that the prediction model had good clinical applicability. The model’s calibration curve was close to an ideal diagonal line, showing good predictive accuracy between the actual and predictive probabilities. Conclusion: The study model was demonstrated to be valuable in predicting adult ASD-PAH patients with a correctable shunt, which may help clinicians to make appropriate treatment decision for follow-up patients.

Effects of systemic ventricular assist in failing Fontan patients: a theoretical analysis using a computational model

Mechanical circulatory support is a potential treatment for failing Fontan patients. In this study, we performed a theoretical analysis using a computational model to clarify the effects of systemic ventricular assist device (VAD) in failing Fontan patients. Cardiac chambers and vascular systems were described using the time-varying elastance model and modified Windkessel model, respectively. A VAD was simulated as a nonlinear function. In systolic and diastolic ventricular dysfunction and atrioventricular valve regurgitation models, systemic VAD increased the cardiac index and decreased the central venous pressure (CVP). However, in the high pulmonary vascular resistance model, CVP became extremely high above 15 mmHg to maintain the cardiac index when the pulmonary vascular resistance index (PVRI) was above 5 Wood units m2. In Fontan patients with ventricular dysfunction or atrioventricular valve regurgitation, systemic VAD efficiently improves the hemodynamics. In Fontan patients with PVRI of > 5 Wood units m2, systemic VAD seems ineffective.

Impact of new definition on the prognosis of patients with pulmonary hypertension compared to classic definition

Abstract Background The recent European Society of Cardiology (ESC)/European Respiratory Society (ERS) 2022 pulmonary hypertension (PH) guidelines have updated the definition of PH from a mean pulmonary arterial pressure (mPAP) ≥ 25mmHg to > 20mmHg, and the pulmonary vascular resistance (PVR) threshold for pre-capillary PH (Pre-PH) from > 3 wood units (WU) to > 2 WU. Little is known regarding the implication of this new criteria in all PH subgroups in Asia. Purpose In this study, we aim to evaluate the impact of the new PH definition on the prevalence and prognosis of PH subgroups in as Asian cohort. Methods A retrospective analysis of a single-center RHC registry (April 2016 - July 2023) was conducted. 314 patients (median age 62.5, 50.3% men) were included. Patients were categorized into PH subgroups as defined by both the classic and new criteria. The primary outcome included cardiovascular mortality or heart failure hospitalizations, assessed over a maximum follow-up period of 5 years. Clinical outcomes of different PH subgroups using the classic and new definitions were compared using Kaplan-Meier methods, log-rank tests, and Cox proportional hazards models. Continuous parameters were analyzed using restrictive cubic splines within Cox models. Results Based on the new cutoffs (mPAP > 20mmHg, PVR > 2 WU), 76 patents (24.2%) were reclassified. PH increased to 233 (+ 41, +13.1%), Pre-PH increased to 92 (+ 30, +9.6%), Ipc-PH decreased to 27 (- 21, -6.7%), and Cpc-PH increased to 108 (+33, +10.5%). Over a median follow-up of 238.5 days, 65 primary outcomes occurred. Under the new PH definition, 5-year survival rates for Pre-PH, Ipc-PH, and Cpc-PH are 73.2%, 57.5%, and 47.0%, improved from 67.0%, 53.3%, and 44.3% in the classic definition. In the Cox regression analysis, using the Non-PH as a reference, the risk of primary outcome for PH subgroups was lower in the new definition compared to the classic definition (Table 1). Using the classic mPAP cut-off [<25 vs. ≥25 mmHg], patients with PH had a significantly higher risk for primary outcome (HR 2.25, 95% CI 1.26-4.00, p=0.006) compared with patients without PH. However, using the new mPAP cut-off [<20 vs. ≥20 mmHg], it didn’t show significant difference between two groups (HR 1.62, 95% CI 0.86-3.04, p=0.132). Spline analyses suggested a linear relation between the risk of primary outcome and mPAP considering mPAP between 20 and 45mmHg, and a plateau of events for mPAP values over 45mmHg. In patients with PVR > 2 WU, we observed a linear relation between PVR and events for values and a plateau of events for PVR values over 7.5 WU (Figure 1). Conclusion The new definition increased the diagnosis of PH, particularly in Pre-PH and Cpc-PH. This definition faciliates earlier diagnosis, encompassing milder disease states, and demonstrated better prognosis in PH subgroups. However, it dose not identify additional patients at increased risk of primary outcomes.Table 1Figure 1

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

Assessment of structural and functional microvascular dysfunction using microvascular resistance reserve versus invasive exercise stress testing

Abstract Background Coronary microvascular dysfunction is an heterogenous entity with structural dysfunction present in about 60% of cases. Although Coronary Flow Reserve (CFR) is commonly used for diagnosis, this index is nonspecific to the microvasculature. The effectiveness of the recently introduced Microvascular Resistance Reserve (MRR) and absolute microvascular resistance (Rµ) in identifying microvascular dysfunction endotypes remains uncertain. Objective To evaluate whether MRR and hyperemic Rµ assessment are effective in dichotomizing functional and structural microvascular dysfunction as compared with Rµ and coronary blood flow (Q) monitoring during exercise. Methods Rµ and MRR were first assessed using continuous thermodilution with saline infusion at 10 mL/min (rest) and 20 mL/min (hyperemia) in the left anterior descending artery of consecutive patients with Angina and Non-Obstructive Coronary Arteries. An MRR<2.3 was considered the cutoff for coronary microvascular dysfunction. Q and Rµ were assessed during subsequent stress testing with an incremental workload of 30 watts every two minutes, using a dedicated supine cycling ergometer. Results Coronary microvascular dysfunction was observed in 36.6% of the participants with suspected Angina with Non-Obstructive Coronary Artery disease (11 out of 30). Median hyperemic Rµ was 561 [381; 684] Wood Unit (WU) among patients with microvascular dysfunction. Participants with structural dysfunction (MRR<2.3 and hyperemic Rµ>561WU), had a resting Rµ similar to participants without CMD (1286±410 versus 1231±291 WU) but exhibited both impaired reduction of Rµ (139 [64; 288] versus 191 [74; 317] WU per 30 watts) and increase of Q during exercise (20 [1; 37.5] versus 52 [15.5; 92.0] mL/min per 30 watts). Patients with functional dysfunction (MRR<2.3 and hyperemic Rµ<561WU) had lower resting Rµ (672±219 WU) and higher resting Q (152±39 versus 84±24 mL/min) with a similar increase of Q during exercise (55 [30.5; 103.0] than participants without CMD. Mean N-terminal pro B-type natriuretic peptide level was higher in the structural group (425±563 ng/L) as compared to the functional and normal groups (86±10 ng/L and 50±80 ng/L respectively). Conclusion The use of MRR combined to hyperemic Rµ, derived from continuous intracoronary thermodilution, enables the assessment of coronary microvascular dysfunction with an accurate distinction between functional and structural endotypes.Microvascular hemodynamic adaptationNTpBNP level

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

Efficacy and tolerability of triple sequential combination therapies with selexipag in patients with pulmonary arterial hypertension: insights from a single-centre study

Abstract Background and aims In this single-centre study we aimed to evaluate the efficacy and tolerability of prostacyclin receptor agonist selexipag in patients with pulmonary arterial hypertension (PAH). Methods The study included 110 out of the 1071 patients enrolled in the Evaluation of Pulmonary Hypertension Risk factors Associated with Survival study (EUPHRATES) and treated with selexipag added on background dual PAH therapies. The ESC/ERS 2022, SPAHR, French Registry, COMPERA 2.0 and REVEAL lite 2 models were used for risk predictions. Results Age (mean+SD) was 43.4+16.5 years and 84.5 % of patients were female. The PAH was idiopatic, and was associated with congenital heart disease (CHD), connective tissue disease (CTD) and drug in 47.2 %, 46.4 %, 5.5 % and 1 %, respectively. Background dual therapies, functional class (FC) was II, III and IV in 20 %, 65 %, and 15 % of patients. Six-minute walk distance (6MWD) was 314 + 134 m and serum N-terminal-pro-brain natriuretic peptide (NT-proBNP) level was 882+1732 ng/l. Tricuspid annular planary excursion (TAPSE) and tissue velocity (St), right atrial area and pulmonary arterial diameter were 2.02+0.48 cm,12.4+2.8 cm/sec,21.4+7.2 cm2 and 3.54+0.77 cm, respectively. Invasively evaluated pulmonary arterial mean pressure was 60.2±19.9 mm Hg, and pulmonary vascular resistance was 12.3±10.8 Wood units. COMPERA 2.0 1st, 2nd, 3rd and 4th risk strata were noted in 15.5 %, 31.8 %, 2.7 % and 10 %, and French Registry strata 0,1,2 and 3 were documented in 70 %, 14.5 %, 11 %, and 4.5 %, respectively. The SPAHR and REVEAL Lite 2 scores were 1.9+0.5 and 5.9+2.6, respectively. Background combinations were as follows; macitentan+tadalafil in 46.6 %, macitentan+sildenafil in13.6 %, macitentan+ riociguat in 6.8 %, bosentan +tadalafil in 8.7 %, bosentan+sildenafil in 16.5 %, bosentan+riociguat in 1 %, ambrisentan +tadalafil in 1.9 %, and ambrisentan+sildenafil in 2.9 % of patients. Maximally tolerable selexipag doses (ug)were 1600 bid in 21%, 1400 bid in 5 %, 1200 bid in 11%, 1000 bid in 17%, 800 bid in 12%, 600 bid in 9%, 400 bid in 14%, and 200 bid in 11%.Median follow-up period was 527( 278-831) days, and discontiuation rates of selexipag was 13.6 %. Headache, jaw-pain, diarrhoea, nausea, vomiting and flushing were main side effects. The changes in FC, 6MWD, Nt-pro-BNP and echocardiographic measures were not significant. French Registry score (p<0.001) and COMPERA 2.0 score (p<0.001) showed improvements, but SPAHR and REVEAL lite 2 did not. However, other PAH cohort compared with IPAH showed more pronounced improvements in REVEAL lite 2 and SPAHR scores. Clinical worsening and mortality rates were 23.6 % and 10.9 %, respectively. Survival for 1, 3 and 5 years were 95.8 %, 95.8 and 83.7 % in IPAH, and 92.6 %, 84.1 % and 78.8 % in other PAH patients. Conclusion Our results seem to be consistent with efficacy and tolerability of selexipag-included combinations in patients with PAH.

Prognosis in patients with residual pulmonary hypertension after transcatheter edge-to-edge repair for secondary mitral regurgitation

Abstract Background Pulmonary hypertension (PH) is an independent prognostic predictor in patients with heart failure (HF). Recently, transcatheter edge-to-edge repair (TEER) for secondary mitral regurgitation (MR) has been reported to reduce HF hospitalizations and mortality. Elevated pulmonary artery pressure (PAP) before TEER is associated with a poor prognosis; however, the impact of residual PH after TEER on clinical events has not been investigated. Purpose The purpose of this study is to clarify whether residual PH influences outcomes in patients with HF treated by TEER for secondary MR. Methods We included 63 patients who underwent TEER for severe secondary MR and post-procedural right heart catheterization in our institute from January 2016 to August 2023. Mean PAP after TEER was categorized as increased (>20mmHg) versus not increased (≤20mmHg), and we investigated the clinical outcomes between the two groups. The primary endpoint is a composite outcome of all-cause mortality and HF hospitalization. Results Among 63 patients, the average age was 78 years, and 60.3% were male. All patients had Secondary MR, and 52 patients (82.6%) had ventricular Secondary MR—right heart catheterization after TEER revealed a mean PAP of 21.6±7.7 mmHg, pulmonary vascular resistance (PVR) of 2.7±1.4 wood unit (WU), and pulmonary artery wedge pressure (PAWP) of 12.2±5.9 mmHg. Patients with residual PH had higher composite outcome rates of death from any cause or HF hospitalization compared to those without PH (56.1% vs. 19.5%; hazard ratio: 2.62; 95% confidence interval: 1.1 to 6.9; p=0.03). Multivariate Cox regression analysis showed that residual PH and higher PAWP after TEER were associated with higher mortality (hazard ratio: 1.14; 95% confidence interval: 1.03 to 1.28; p=0.01). Conclusion Our results suggest that patients with residual PH after TEER have a poor prognosis. Residual PH and high PAWP after TEER are associated with mortality.

Minimal coronary microvascular resistance: agreement between continuous and bolus thermodilution

Abstract Background Continuous thermodilution quantifies absolute microvascular resistance (Rµ, Woods units), the quintessential metric of microvascular function. Rµ is minimal during hyperaemia (Rµ,hyper) with increased Rµ,hyper suggestive of microvascular dysfunction. Bolus thermodilution measures the index of microcirculatory resistance (IMR), a dimensionless surrogate of Rµ,hyper. Purpose We compared Rµ,hyper measured by continuous thermodilution (invasive Rµ,hyper) with the gold standard [15O]H2O positron emission tomography (PET Rµ,hyper), and explored the correlation between invasive Rµ,hyper and uncorrected IMR. Methods The accuracy of invasive Rµ,hyper was assessed in a cohort of 24 patients in which both invasive and PET Rµ,hyper were measured (cohort 1). For both techniques, Rµ,hyper was assessed in both the left anterior descending artery (LAD) and the circumflex artery (LCX), corresponding to 46 measurement of Rµ,hyper in total (LAD=24, LCX=22). Agreement between invasive Rµ,hyper and IMR was evaluated in a cohort of 250 patients with angina and non-obstructive coronary arteries (ANOCA) evaluated in 3 European centres (cohort 2). All measurements in this cohort were performed in the LAD, with patients randomly assigned in a 1:1 ratio to undergo either bolus or continuous thermodilution first. Both techniques were performed by the same operator during the same procedure with a strict interval of 5 minutes between techniques. Results In cohort 1, invasive Rµ,hyper exhibited a strong correlation with PET Rµ,hyper (r=0.86 [95% CI 0.76-0.92], p<0.001), with excellent absolute agreement (ICC 0.82 [95% CI 0.70-0.90], p<0.001) (Figure 1). Furthermore, Passing-Bablok regression analysis found no significant systematic (intercept A: 54.53 [95% CI -18.95 to 120.96]) or proportional (slope B: 0.90 [95% CI 0.71 to 1.15]) bias between invasive Rµ,hyper and PET Rµ,hyper. However, in cohort 2, invasive Rµ,hyper exhibited no significant correlation with IMR (r=0.11 [95% CI -0.01 to 0.23], p=0.08) (Figure 2). Conclusion Invasive Rµ,hyper derived from continuous thermodilution exhibited excellent agreement with non-invasive Rµ,hyper measured by [15O]H2O PET, the current standard of reference. However, IMR exhibited no significant correlation with invasive Rµ,hyper in patients with stable coronary syndromes.Figure 1.PET vs invasive Rµ,hyperFigure 2.Invasive Rµ,hyper vs IMR

Assessment of circulating biomarkers and hemodynamic response during stress to detect early cardiopulmonary complications in systemic sclerosis

Abstract Background Systemic sclerosis (SSc) is characterised by persistent immune-inflammatory system activation and excessive extracellular matrix (ECM) accumulation leading to fibrosis. Exercise Doppler Echocardiography (EDE) is a promising method to detect the early changes of fibrosis-related pulmonary and myocardial complications, like elevated left ventricular filling pressure or stress-induced pulmonary hypertension (PH). Aims The study aims to assess the linkage between the activity of fibrosis markers and abnormal exercise haemodynamics during stress in patients with SSc. Methods A total of 18 patients with SSc were enrolled in the single-centre prospective study (age 54±15,5years, 94,4 % women). SSc patients with resting PH and moderate to severe pulmonary fibrosis were excluded. According to a standardised protocol, all subjects underwent resting and exercise echocardiography on a semi-recumbent cycle ergometer with an incremental (25 watts) workload up to the maximally tolerated workload. Measurements focused on the left ventricular diastolic function (E/e’) and right ventricular haemodynamics (estimated systolic pulmonary pressure: PASP, right ventricular coupling: TAPSE/PASP, pulmonary vascular resistance: PVR). Blood samples were taken immediately before the stress test, and the Matrix Metalloproteinase-9 and 2 (MMP-9, MMP-2) levels were assessed with gelatin zymography method. Results During the EDE, PASP from baseline increased significantly (24,6mmHg±11 vs 38±16mmHg, p <0,0001), also PVR (1,2±0,49 vs 1,5±0,15 Wood unit, p<0,001) RV coupling was decreased significantly (1,2±0,68 vs 0,93±0,5, p<0,001). Left ventricular E/e’ was also increased during the stress (8,2±2 vs 10,5±5,1, p<0,05). Enzymatically active MMP-9 level was significantly correlated with RV coupling at rest and stress (p<0,05, r 0,63 at rest and r 0,52 at stress) and negatively correlated with PASP (p<0,05, r:-0,62 at rest and r -0,5 at stress). MMP-2 level only negatively correlated with resting PASP (p<0,05, r:-0,527). The left ventricular parameters did not show any relationship with MMP levels. Conclusions The level of circulating MMP-9 predicts haemodynamic behaviour during stress in SSc. MMPs could be a promising marker for detecting early changes in the right ventricle-pulmonary circulation unit.

Acute vasoreactivity testing for severe pulmonary hypertension associated with lung disease

Abstract Background Pulmonary hypertension results in clinical deterioration and increases mortality risk in patients with lung disease (LD), including chronic obstructive pulmonary disease, interstitial lung disease and combined pulmonary fibrosis and emphysema. Though acute vasoreactivity testing predicts long term-survival of patients with pulmonary arterial hypertension (PAH), its clinical impact for patients with pulmonary hypertension associated with LD (LD-PH) remains unknown. Purpose The purpose of this study is to clarify the clinical impact of acute vasoreactivity testing using inhaled nitric oxide for severe LD-PH. Methods We retrospectively reviewed 65 consecutive patients with LD-PH between January 2014 and December 2022; 48 patients (73 [68–78] years; males, 81%; median follow-up period 23 [7–35] months) with severe pulmonary hypertension who underwent acute vasoreactivity testing were included. We divided the patients based on a median pulmonary vascular resistance (PVR) response (−15%) in acute vasoreactivity testing into the high-responder (PVR response ≦−15%) and the low-responder (PVR response >−15%) groups. Results Acute vasoreactivity testing significantly decreased mean pulmonary arterial pressure (mPAP) (from 41 [34–48] to 36 [31–40] mmHg, P<0.01) and PVR (from 10.7 [8.3–13.8] to 8.9 [6.6–11.4] Wood units, P<0.01). The high-responder group had better long-term survival than the low-responder group (P = 0.03). Univariate Cox regression analysis showed that the prognostic factors for better survival included younger age, high-responder to acute vasoreactivity testing, and PAH-specific therapy (P <0.01, 0.04, 0.03, respectively). There were correlations between the PVR response at acute vasoreactivity testing and improvement in mPAP (R=0.40, P=0.03) or PVR (R = 0.47, P <0.01) with PAH-specific therapy. Conclusions PVR response at acute vasoreactivity testing was associated with better long-term survival and haemodynamic improvement with PAH-specific therapy. Acute vasoreactivity testing may be useful to predict the responders to PAH-specific therapy and long-term survival in patients with severe LD-PH.

Exercise Doppler echocardiography to detect early changes in the right ventricular-pulmonary circulation unit after pulmonary embolism

Abstract Introduction After pulmonary embolism (PE), patients frequently complain about reduced exercise capacity and dyspnea on exertion, even without pulmonary hypertension (PH). The underlying condition is often chronic thromboembolic disease, which is caused by residual pulmonary obstruction with preserved resting pulmonary haemodynamics. The symptoms are the consequences of the increased dead space ventilation, exercise-induced PH and right ventricular (RV) dysfunction. We aimed to assess the pathologic differences in the echocardiographic parameters of the RV- pulmonary circulation unit among patients with previous PE and the healthy control group. Furthermore, an objective was to compare the hemodynamic response to stress after different treatment strategies (thrombolysis vs. heparin administration). Methods 21 patients after PE (mean age 58,5±12,1 years; 53% men) have been included in the study. All of them were effectively anticoagulated for at least three months, and none had any signs of PH on echocardiography at rest. The control group included 20 healthy volunteers (mean age 56,9±11,5 years; 55% men). Each patient underwent resting and exercise stress echocardiography on a semi-recumbent bicycle ergometer according to a standardised protocol until the maximally tolerated workload. Echocardiography was performed at rest, at 50 Watt workload and during peak stress. The measurements focused on the RV's systolic function (TAPSE), the estimated pulmonary artery systolic pressure (PASP), and the Doppler measurements in the RV and left ventricular outflow tracts. Pulmonary vascular resistance (PVR) and RV-pulmonary artery coupling (RV-PA) were calculated from the echocardiographic parameters. Results The post-PE group had significantly higher PASP (39,2 ±16,6 vs. 27,7±12,5 mmHg; p<0,05) and PVR (1,5±0,4 vs. 1,1±0,3 Wood Units; p<0,05) at peak stress, than the controls. 55% of post-PE patients remained symptomatic, but there were no significant differences between the symptomatic and asymptomatic groups regarding TAPSE, PASP, RV-PA coupling and PVR. 30% of post-PE patients had thrombolysis. In the patients where thrombolysis was performed, the coupling at peak stress was significantly higher than in heparin-treated patients (1,4±0,1 vs 0,9±0,4 mm/mmHg, p<0,05). Conclusion Post-PE patients without resting PH have higher PVR and PASP than the healthy control group, even after at least 3 months of adequate therapy. Post-PE patients treated with thrombolysis may have more preserved RV-PA coupling than the heparin-treated patients.

Prognosis of different hemodynamic classifications in patients with pulmonary hypertension due to left heart disease

Objective: To compare the prognostic values of different classification by using transpulmonary pressure gradient (TPG), diastolic pressure gradient (DPG) and pulmonary vascular resistance (PVR) in patients with pulmonary hypertension due to left heart disease (PH-LHD), and investigated hemodynamic and clinical factors associated with mortality in patients with PH-LHD. Methods: This was a single-center prospective cohort study. In-hospital patients diagnosed with PH-LHD via right heart catheterization at the Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, from September 2013 to December 2019 were enrolled. Patients were divided according to TPG (cutoff value 12 mmHg; 1 mmHg=0.133 kPa), DPG (cutoff value 7 mmHg), PVR (cutoff value 3 Wood Units), and the combination of TPG and PVR. Baseline characteristic was recorded. All patients were followed up until the occurrence of endpoint event, defined as all-cause death that occurred during the follow-up period, or until April 18, 2022. Receiver operating characteristic curves were used to compare the predictive value of 3 classification methods for all-cause death in PH-LHD patients. The optimal cutoff values were calculated using Jorden index. Survival analysis was performed using Kaplan-Meier analysis, and log-rank test was used to compare the predictive efficacy of classification methods based on optimal cutoff values or guidance-recommended thresholds for the survival of PH-LHD patients. Variables showing statistical significance in the univariate analysis were incorporated into multivariate Cox regression model to analyze the independent risk factors for all-cause mortality. Results: A total of 243 patients were enrolled, aged (54.9±12.7) years old, including 169 (69.5%) males. During a median follow-up of 57 months, there were 101 (41.6%) deaths occurred. Grouping results were as follows: (1) TPG: TPG≤12 mmHg group 115 patients, TPG>12 mmHg group 128 patients; (2) DPG: DPG<7 mmHg group 193 patients, DPG≥7 mmHg group 50 patients; (3) PVR: PVR≤3 Wood Units group 108 patients, PVR>3 Wood Units group 135 patients; (4) TPG and PVR: TPG≤12 mmHg and PVR≤3 Wood Units group 89 patients, TPG>12 mmHg and PVR>3 Wood Units group 109 patients. PVR (AUC=0. 698,95%CI:0.631-0.766) had better predictive value for all-cause mortality than TPG (AUC=0.596, 95%CI: 0.523-0.669) and DPG (AUC=0.526, 95%CI: 0.452-0.601) (all P<0.05). The optimal cutoff values for TPG, DPG, and PVR were13.9 mmHg, 2.8 mmHg, and 3.8 Wood Units, respectively. Kaplan-Meier analysis based on the optimal cutoff values or guidance-recommended thresholds showed that PVR and TPG were the predictors of survival (P<0.05), while DPG did not showed significance (P>0.05). Multivariate Cox regression analysis showed that age, PVR and log2N-terminal pro-B-type natriuretic peptide were independent risk factors for all-cause mortality in PH-LHD patients (all P<0.05). Conclusion: Classification according to PVR was most valuable in predicting all-cause death in PH-LHD patients, while TPG showed moderate predictive ability and DPG had no predictive value.

Pulmonary endarterectomy through inverted-T upper hemisternotomy

ObjectiveWe aimed to explore the feasibility of an inverted-T upper hemisternotomy approach for pulmonary endarterectomy (PEA) and report the results after 17 cases. MethodsPEA was conducted through a 7-cm skin incision using an inverted-T upper hemisternotomy across the third intercostal spaces. Cardiopulmonary bypass (CPB) was established through central arterial and percutaneous femoral dual-staged venous cannulation. Perioperative and hemodynamic data were compared with 17 previous conventional PEAs performed by the same surgeon. ResultsFrom July 2022 to September 2023, 22 PEAs were performed, 17 through inverted-T upper hemisternotomy. Contraindications were an inferior caval vein filter, concomitant coronary revascularization or mitral valve surgery, pulmonary artery intimal sarcoma, and an emergency. Compared with 17 preceding conventional PEAs, there was no significant difference in demographics or in CPB time (274 [256-301] vs 264 [250-274] minutes, P = .1629), deep hypothermic circulatory arrest time (56 [45-65] vs 54 [50-58] minutes, P = .9587), preoperative pulmonary vascular resistance (4.12 [3.10-4.79] vs 4.49 [3.25-6.24] Wood units, P = .5890), 6-month postoperative pulmonary vascular resistance (1.90 [1.40-2.56] vs 1.83 [1.44-2.20] Wood units, P = .6374), or hospital stay (10 [8-12] vs 11 [9-14] days, P = .3327). Intravenous opioid use 0.29 [0.21-0.83] vs 2.99 [1.31-4.33] mg, P < 1.10−4) was significantly lower. ConclusionsPEA using an inverted-T upper hemisternotomy approach is feasible and safe and obtains similar hemodynamic results compared with a full sternotomy approach without prolonging CPB and deep hypothermic circulatory arrest times. It offers bilateral treatment via a single incision and has few contraindications.

The relation between socioeconomic status and invasive haemodynamics at evaluation for advanced heart failure.

Socioeconomic deprivation is a risk marker for worse prognosis in patients with heart failure (HF), and a potential barrier to referral for advanced HF evaluation. The relationship between socioeconomic status (SES) and invasive haemodynamics in patients undergoing evaluation for advanced HF therapies is unknown. We combined a consecutive clinical registry of patients evaluated for advanced HF with patient-level data on SES (household income, education, workforce status, cohabitant status and distance from home to tertiary HF centre) derived from nationwide registries. Using this information, the cohort was divided into groups of low-, medium- and high degree of socioeconomic deprivation. The associations between SES and invasive haemodynamics were explored with multiple linear regression adjusted for age and sex. A total of 631 patients were included. The median age was 53years, and 23% were women. Patients in the highest income quartile versus the lowest (Q4 vs. Q1) were older (median age 57 vs. 50years) and more often male (83% vs. 67%), both P<0.001. Increasing household income (per 100000 Danish kroner,1 EUR=7.4 DKK) was associated with lower pulmonary capillary wedge pressure (PCWP)[-0.18mmHg, 95% confidence interval (CI) -0.36 to -0.01, P=0.036] but not significantly associated with central venous pressure (CVP) (-0.07mmHg, 95% CI -0.21 to 0.06, P=0.27), cardiac index (-0.004L/min/m2, 95% CI -0.02 to 0.01, P=0.60), or pulmonary vascular resistance (PVR) (-0.003 Wood units, 95% CI -0.37 to 0.16, P=0.84). Comparing the most deprived with the least deprived group, adjusted mean PVR was higher (0.35 Wood units, 95% CI 0.02 to 0.68, P=0.04), but PCWP (0.66mmHg, 95% CI -1.49 to 2.82, P=0.55), CVP (-0.26mmHg, 95% CI -1.76 to 1.24, P=0.73) and cardiac index (-0.03L/min/m2, 95% CI -0.22 to 0.17, P=0.78) were similar. Most haemodynamic measurements were similar across layers of SES. Nevertheless, there were some indications of worse haemodynamics in patients with lower household income or a high accumulated burden of socioeconomic deprivation. Particular attention may be warranted in socioeconomically deprived patients to ensure timely referral for advanced HF evaluation.

Discrepancy between pulmonary arterial wedge pressure and left ventricular end diastolic pressure in patients with interstitial lung disease

BackgroundRight heart catheterization (RHC) is the gold standard for diagnosing pulmonary hypertension (PH) in patients with interstitial lung disease (ILD). However, discrepancies between pulmonary arterial wedge pressure (PAWP) and left ventricular end-diastolic pressure (LVEDP) remain understudied in this population. MethodsWe conducted a retrospective analysis of data from ILD patients who underwent RHC and had concomitant LVEDP measurements. Pulmonary vascular resistance (PVR) was calculated using both PAWP and LVEDP. Patients were categorized based on PAWP and LVEDP values using a threshold of 15 mmHg and PVR values using a threshold of 2 or 3 Wood Units. After that patients were categorized as concordant or discordant if both values were on the same or opposite sides of these thresholds, respectively. A discordantly higher PAWP group (left atrial dysfunction, LAD) was defined as patients with a PAWP-LVEDP difference of more than 3mmHg. ResultsAmong 87 ILD patients, 9 patients (10.3%) showed discordance between PAWP and LVEDP. LAD was observed in 12 patients (13.8%) and was associated with lower forced vital capacity (Odd ratio [OR]: 0.956, p = 0.049) and a larger left atrium diameter (OR: 3.205, p = 0.033). Discordance in PVR values was also noted, with potential treatment targets for PH-specific therapy differing in 9 patients (22.0%) depending on whether PAWP or LVEDP was used. ConclusionsThis study highlights the clinical significance of PAWP-LVEDP discrepancies in suspected PH-ILD patients, emphasizing the need for comprehensive assessments incorporating LVEDP and clinical context for accurate diagnosis, risk stratification, and treatment decisions.

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 &gt; 20 mmHg) and elevated PVR (&gt; 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 &lt; 0.001). BMP10 and NT-proBNP were strongly associated with PVR (p &lt; 0.001), while NT-proBNP and ANG2 were strongly associated with PAWP (p &lt; 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

Neuraxial anesthesia for patients with severe pulmonary arterial hypertension undergoing urgent open abdominal surgeries: two case reports

BackgroundThere is no consensus regarding the choice of anesthetic method for patients with pulmonary hypertension (PH). We report two cases in which neuraxial anesthesia was safely performed without general anesthesia during open abdominal surgery in patients with severe PH.Case presentationCase 1: A 59-year-old woman had an atrial septal defect and a huge abdominal tumor with a mean pulmonary arterial pressure (PAP) of 39 mmHg and pulmonary vascular resistance (PVR) of 3.5 Wood units. Case 2: A 23-year-old woman who had hereditary pulmonary artery hypertension (mean PAP, 65 mmHg; PVR, 16.45 Wood units). Both patients underwent open abdominal surgery under neuraxial anesthesia without circulatory collapse with intraoperative administration of vasoconstrictors.ConclusionAlthough anesthetic care must be personalized depending on the pathology and severity of PH, neuraxial anesthesia may be an option for patients with severe PH undergoing abdominal surgery.

Phosphodiesterase 5 Inhibitor Treatment Is Associated With Improved Survival in Pulmonary Hypertension Associated With COPD in the Pulmonary Vascular Research Institute GoDeep Meta-Registry

BackgroundPatients with COPD frequently develop pulmonary hypertension (PH-COPD). Severe PH-COPD, identified by a pulmonary vascular resistance (PVR) >5 Wood Units (WU), is closely linked to impaired transplant-free survival. The impact of PH-targeting pharmacotherapy in this context remains unclear. Research QuestionIs PH-targeted therapy associated with improved transplant-free survival in PH-COPD? Study Design and MethodsThis study included PVRI GoDeep meta-registry patients with PH-COPD and available right heart catheterization at diagnosis. We investigated PH-targeted therapy prevalence and its association with transplant-free survival using diverse statistical methods, including Cox regression and subgroup analyses based on PH severity, comorbidities, and pulmonary function tests. Immortal time bias was addressed through a landmark approach. ResultsAs of December 2023, the GoDeep meta-registry included 26981 patients (28% PH-Group 1, 13% PH-Group 2, 12% PH-Group 3, 10% PH-Group 4, 2% PH-Group 5, 26% undefined and 9% control). Out of these, 836 patients were diagnosed as PH-COPD and included in this analysis, with median age 66 [59,73]years, FEV1 51 [34,69]%predicted, mPAP 35 [28,44]mmHg, PVR 5 [4,8]WU, cardiac index 2.5 [2.0,2.9]L/min.m2, and mostly WHO functional class III were included. 5-year transplant-free survival was 42%, significantly worse than group 1 PH. A multivariable Cox proportional hazards model identified PVR, but not FEV1 as a major predictor of outcome. 418 patients (50%) received phosphodiesterase-5 inhibitor (PDE5i) therapy, which was associated with significantly reduced mortality: hazard ratio 0.65 [0.57,0.75] for the entire PH-COPD cohort and 0.83 [0.74,0.94] when performing landmark analysis. This PDE5i effect was robustly reproduced when performing subgroup analyses for patients with moderate/severe PH, various comorbidities, and supplemental oxygen requirement, and when assessing the impact of unobserved confounders. InterpretationPH-COPD patients exhibit poor transplant-free survival, with PVR being a predictor of mortality. In this meta-registry, PDE5i therapy was associated with a significant reduction in mortality across all tested models.

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.