Pulmonary Hypertension Group Research Articles

Impact of the 2022 ESC/ERS revised hemodynamic definition on the diagnosis of pulmonary hypertension

Objectives: In the 2022 European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines, the hemodynamic definition of pulmonary hypertension (PH) was revised to mean pulmonary arterial pressure (mPAP)>20 mmHg (1 mmHg=0.133 kPa) at rest. This study aimed to evaluate the impact of the revised hemodynamic definition on the diagnosis of PH. Methods: Patients with dyspnea or highly suspected PH who underwent right heart catheterization (RHC) in Beijing Anzhen hospital affiliated to Capital Medical University from September 2021 to October 2022 were enrolled retrospectively. According to resting hemodynamics, the patients were divided into 3 groups: no-PH (mPAP≤20 mmHg) group, low-pressure PH (20 mmHg<mPAP<25 mmHg) group and high-pressure PH (mPAP≥25 mmHg) group. The diagnosis and classification of PH and the hemodynamic parameters in different groups were compared before and after the revision of diagnostic criteria. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of maximum of mPAP (mPAPmax) and mPAP/cardiac output (CO) slope of multi-point in PH. Results: A total of 117 patients were included for analysis, the age was (53.7±17.5) years, 37 (31.6%) patients were male. According to the 2022 ESC/ERS definition, 99 patients were diagnosed as PH, including 8 patients (6.8%) in the low-pressure PH group and 91 patients (77.8%) in the high-pressure PH group. There were 18 patients (15.4%) in the non-PH group. Comparing to the 2015 ESC/ERS definition, 8 patients were newly diagnosed as PH. Echocardiography indexes pulmonary systolic pressure (sPAP) [(57.6±7.3) vs (38.5±13.6) mmHg], max tricuspid regurgitation velocity (TRVmax) [(360.4±28.9) vs (271.4±52.2) cm/s] and RHC index mPAP [(22.2±1.3) vs (16.1±2.6) mmHg] in low-pressure PH group were higher than those in no-PH group (all P<0.05). However, further analysis of hemodynamics during exercise showed mPAPmax [(42.1±5.6) vs (35.6±4.7) mmHg, P=0.006] and mPAP/CO slope of multi-point [(4.9±1.3) vs (3.6±1.1) mmHg·L-1·min-1,P=0.024] in low-pressure PH group were higher than those in no-PH group. The ROC curve cut-off value of mPAPmax for the diagnosis of PH was 39 mmHg, with a sensitivity of 75.0%, a specificity of 76.5%, and the area under the curve (AUC) and 95%CI is 0.816 (0.638-0.994). The ROC curve cut-off value of mPAP/CO slope of multi-point for the diagnosis of PH was 4.44 mmHg·L-1·min-1,with a sensitivity of 75.0%, a specificity of 76.5%, and an AUC (95%CI) of 0.794 (0.606-0.983). Conclusion: After the revision of the hemodynamic definition of PH in the 2022 ESC/ERS guidelines, more PH patients with pulmonary vascular disease are detected, thereby facilitating early diagnosis and treatment.

Implication of heart rhythm complexity in predicting long-term outcomes in pulmonary hypertension

Pulmonary hypertension (PH) is a serious disease, however simple tools to predict outcomes are lacking. In our previous investigation, we found that heart rate variability (HRV) and heart rhythm complexity (HRC) were associated with the detection and severity of PH, however their association with PH mortality remains unclear.The aim of this study was to investigate these metrics as a tool for determining long-term outcomes in PH patients. We enrolled 74 Asian PH patients with WHO PH group 1 or 4 at a single hospital in Taiwan between March 2012 and June 2018. After a median follow-up duration of 58 months (to January 2023), 22 patients had died. The patients who died had a significantly lower lean body mass index (BMI), impaired renal function, higher N-terminal pro B-type natriuretic peptide (NT-proBNP) level, lower very low-frequency (VLF), lower short-term detrended fluctuation analysis α1 (DFAα1), and lower multiscale entropy scale 5 value. In multivariable analysis, BMI, VLF and multiscale entropy scale 5 were significantly associated with survival. The best cut-off VLF and scale 5 values were 115.13 and 0.738, respectively. We then categorized the study population into three groups: both elevated VLF/scale 5 (group 1), either depressed VLF or depressed scale 5 (group 2), and both depressed VLF/scale 5 (group 3). The results showed that group 1 had the best outcomes, whereas group 3 had the worst survival (P < 0.001).Combining HRV and HRC metrics appears to be a good non-invasive tool to predict the long-term outcomes of patients with PH.

Editorial for “3D Vortex‐Energetics in the Left Pulmonary Artery for Differentiating Pulmonary Arterial Hypertension and Pulmonary Venous Hypertension Groups Using 4D Flow MRI”

Editorial for “<scp>3D</scp> Vortex‐Energetics in the Left Pulmonary Artery for Differentiating Pulmonary Arterial Hypertension and Pulmonary Venous Hypertension Groups Using <scp>4D</scp> Flow <scp>MRI</scp>”

Clinical, echocardiographic and haemodynamic predictors of morbidity and mortality in pulmonary hypertension: a nation-wide registry

Abstract Background and aims In this retrospective analysis of a nation-wide registry on pulmonary arterial hypertension (PAH), group IV and V, we aimed to evaluate the clinical, echocardiographic,haemodynamic and neurohumoral predictors of morbidity and mortality. Methods This study included 903 patients enrolled from 24 cardiology centers participating in the RegiStry on clInical outcoMe and sUrvival in pulmonaRy hypertension Groups (SIMURG II). ESC/ERS 2022 risk scoring model was used for risk predictions at baseline assessment. Composite endpoint (CEP) definitions were adopted from the SERAPHIN and GRIPHON trials. Results Age was 51.27 + 21.37 years, and 72 % of patients were female. Incident cases were noted in 65.9 % of overall group. Idiopathic PAH (IPAH), PAH-associated with congenital heart diseases (CHD-PAH), PAH-associated with connective tissue diseases (CTD-PAH), porto-PAH, Group IV and V pulmonary hypertension (PH) were documented in 33 %, 33.5 %, 12 %, 1.6 %, 20 % and 1.7 % of overall patients, respectively. Background mono and dual targeted combinations, and sequential dual or triple combinations were noted in 17 %, 57 % and 26 % of patients, respectively. Baseline low-, intermediate- and high-risk were noted in 1.2 %, 14.1 %, and 84.7 %, respectively. Median follow-up time was 867 (412-1667) days. Overall rates of mortality and CEP were 26 % and 39%, respectively. Prevalent versus incident cases were associated signifinatly lower mortality and CEP rates (p=0.028 and p=0.024, respectively). Mortality and CEP rates were 31 % and 44 % in IPAH, 20 % and 39 % in CHD-PAH, 31 % and 43 % in CTD-PAH, and 25 % and 30 % in group IV patients, respectively. CHD-PAH compared with other groups was associated with a higher Kaplan-Meier (K-M) survival and CEP-free survival (p&amp;lt; 0.0001 and p=0.00023, respectively). Survival was associated with prevalent versus incident status, baseline functional class (FC) and six-minute walk distance (6MWD) in all subgroups (p&amp;lt;0.0001 for all), NT-brain natriuretic peptide and right atrial area in IPAH,CHD-PAH and CTD-PAH, and mixed venous O2 saturation % in IPAH and CHD-PAH (p varying from &amp;lt;0.0001 to 0.027). But, TAPSE / systolic pulmonary artery pressure ratio, right atrial-pulmonary capillary wedge pressure difference, pulmonary vascular resistance and its ratio to systemic vascular resistance, cardiac index were not related with survival. Baseline high versus intermediate /low risk was associated with a lower overall survival and CEP-free survival ( p=0.03 and p=0.003, respectively). Male sex [hazard ratio(HR):1.73;1.2-2,51,p = 0.004], 6MWD (p&amp;lt;0.001), FC III/IV (HR: 2.52;1.47-4.32, p&amp;lt;0.001) and baseline low-risk (HR:0.37;0.21-0.65, p&amp;lt;0.001) were independent predictors of mortality. Conclusions Our nation-wide data revealed current insights regarding the clinical, echocardiographic,haemodynamic and neurohumoral predictors of morbidity and mortality in PAH and group IV PH.

Improving morbidity and mortality in patients with pulmonary hypertension: insights from a nation-wide registry

Abstract Background and aims In this retrospective analysis of a nation-wide registry on pulmonary arterial hypertension (PAH), group IV and V, we evaluated management strategies, morbidity and mortality across three consecutive time periods. Methods This study included 903 patients enrolled from 24 cardiology centers participating in the RegiStry on clInical outcoMe and sUrvival in pulmonaRy hypertension Groups (SIMURG II). Patients were divided into three enrollment periods: before 2016, the era of monotherapy or sequential combination therapies; between 2016 and 2019, post-approval and re-imbursement of macitentan in our country, marking a shift towards more proactive sequential combinations; and after 2019, signifying the initiation of earlier sequential combinations with selexipag in PAH. ESC/ERS 2022, COMPERA 2.0 and REVEAL lite 2 models were used for risk predictions. Composite endpoint (CEP) definitions were adopted from the SERAPHIN and GRIPHON trials. Results Age (mean +SD) was 51.27 + 21.37 years, and 72 % were female. Incident cases were noted in 65.9 % of patients. Idiopathic PAH (IPAH), PAH-associated with congenital heart diseases (CHD-PAH), PAH-associated with connective tissue diseases (CTD-PAH), porto-PAH, Group IV and V pulmonary hypertension (PH) were documented in 33 %, 33.5 %, 12 %, 1.6 %, 20 % and 1.7 % of patients, respectively. Background mono and dual targeted combinations, and sequential triple combinations were noted in 17 %, 57 % and 26 % of patients, respectively. Baseline low-, intermediate-, and high-risk were noted in 1.2 %, 14.1 %, and 84.7 %, respectively. Median follow-up time (day) was 867 (412-1667). Overall rates of mortality and CEP were 26 % and 39%, respectively. There were increases in the % of PAH and group IV PH, and decreases in the % of CHD-PAH across the three periods. Prevalent versus incident cases were associated signifinatly lower mortality and CEP ( p=0.028 and p=0.024, respectively). Outcomes for mortality and CEP were predicted by three risk models (p&amp;lt;0.0001 for all). Mortality and CEP rates were 31 % and 44 % in IPAH, 20 % and 39 % in CHD-PAH, 31 % and 43 % in CTD-PAH, and 25 % and 30 % in group IV patients, respectively. In overall PH population, rates of mortality and CEP documented at 1st, 2nd and 3rd periods were 64 % and 67 %, 29 % and 31 %, and 3.5 % and 5.1 %, respectively (p&amp;lt; 0.001, for all). Mortality rates for 1st, 2nd and 3rd periods were 49 %, 39 % and 11 % in IPAH, 62 %, 33 % and 5.3 % in CHD-PAH, 47 %, 45 % and 7.7 in CTD-PAH, and 37 %, 52 % and 11 % in group IV, respectively (p&amp;lt; 0.001, for all). However, mortality curves showed sudden increases in 2020 that might be attributed to COVID-19. Conclusions Our nation-wide data revealed improving survival in the overall PH population, PAH and Group IV PH that might be associated with risk-based earlier targeted combination strategies. However, this trend seems to be counterbalanced with COVID-19 pandemic.

Multiparametric risk predictions for morbidity and mortality in patients with pulmonary arterial hypertension: insights from a nation-wide registry

Abstract Background and aims In this retrospective analysis of a nation-wide registry on pulmonary arterial hypertension (PAH), group IV and V, we aimed to evaluate risk predictions for morbidity and mortality. Methods This study included 903 patients enrolled from 24 cardiology centers participating in the RegiStry on clInical outcoMe and sUrvival in pulmonaRy hypertension Groups (SIMURG II). ESC/ERS 2022 risk scoring, COMPERA 2.0 and REVEAL lite 2 models were used for baseline risk predictions, and COMPERA 2.0 model was used for risk evaluation at follow-up. Composite endpoint (CEP) definitions were adopted from the SERAPHIN and GRIPHON trials. Results Age (mean +SD) was 51.27 + 21.37 years, and 72 % of patients were female. Incident cases were noted in 65.9 % of overall study group. Idiopathic PAH (IPAH), PAH-associated with congenital heart diseases (CHD-PAH), PAH-associated with connective tissue diseases (CTD-PAH), porto-PAH, Group IV and V pulmonary hypertension (PH) were documented in 33 %, 33.5 %, 12 %, 1.6 %, 20 % and 1.7 % of overall patients, respectively. Background mono and dual targeted combinations, and sequential dual or triple combinations were noted in 17 %, 57 % and 26 % of patients, respectively. According to the ESC/ERS 2022 baseline risk scoring, low-, intermediate-, and high-risk were noted in 1.2 %, 14.1 %, and 84.7 %, respectively. Median follow-up time was 867 (412-1667) days. Overall rates of mortality and CEP were 26 % and 39%, respectively. Prevalent versus incident cases were associated signifinatly lower mortality and CEP ( p=0.028 and p=0.024, respectively). Mortality and CEP rates were 31 % and 44 % in IPAH, 20 % and 39 % in CHD-PAH, 31 % and 43 % in CTD-PAH, and 25 % and 30 % in group IV patients, respectively. Baseline high versus intermediate /low risk status were associated with a lower survival estimates for mortality and CEP in patients with PAH ( p=0.03 and p=0.003, respectively). Baseline COMPERA 2.0 risk status revealed significant differences in overall survival and CEP-free survival among risk groups ( p&amp;lt;0.0001 for both), but 1st year COMPERA 2.0 score did not (p=0.39 and p=0.06, respectively) . As compared to baseline, 1st year COMPERA 2.0 score decreased in 31 %, and remained unchanged in 34 % of patients. Baseline REVEAL lite 2.0 score was associated with mortality (hazard ratio (HR): 1.14;1.08-1.2, p&amp;lt;0.0001) and CEP (HR:1.17;1.1-1.25, p&amp;lt;0.0001) risks. Male sex (HR: 1.73; 1.2-2.51, p = 0.004), six-minute walk distance (p&amp;lt;0.001), functional class III/IV (HR: 2.52;1.47-4.32, p&amp;lt;0.001) and baseline low-risk status (HR:0.37;0.21-0.65, p&amp;lt;0.001) were independent predictors of mortality. Conclusions Our nation-wide data revealed current insights concerning the multiparametric risk predictions for morbidity and mortality in PAH.

Idiopathic pulmonary arterial hypertension, associated with connective tissue disease and comorbidities: prognostic differences? Results the Spanish Registry of pulmonary hypertension (REHAP Registry)

Abstract Introduction Idiopathic pulmonary arterial hypertension (iPAH) and associated with connective tissue disease (PAH-SSc) are the most frequent groups of pulmonary arterial hypertension (PAH) but their long-term survival is usually unequal. Comorbidities, increasing in frequency in these patients, show prognostic influences but it is not known whether these differ in both groups of patients. Methods We collected patients diagnosed with iPAH, heritable, associated with drug or toxine exposure and PAH-SSc between 2014 and 2023 from the Spanish Registry of Pulmonary Hypertension. Patients are classifies into iPAH and PAH-SSc. We analyzed baseline characteristics and the distribution of the different comorbidities in the two groups. Survival analyses estimated by Kaplan-Meier analysis using the log-rank test were done according to PAH etiology and comorbidities and Cox proportional hazard analyses were performed to determine the effects of baseline characteristics on survival. Results Seven hundred and fifty-seven patients were selected for this study. The characteristics of the patients are shown in Table 1. Patients with PAH-SSc compared to iPAH were older (62 vs 56 years), more female (81.8% vs 62.4%), had a more favorable hemodynamic profile, TAPSE/sPAP ratio and lower NT-proBNP levels. No differences were found in functional class or 6MWT. We found a higher proportion of patients in a low and intermediate risk profile, according to ESC, in patients with PAH-SSC as opposed to PAHi (46.8/50.9% vs. 29.3/64.5%; p&amp;lt;0.001). Regarding comorbidities, history of smoking (27.1 vs 54%; p&amp;lt;0-001), obesity (17.1 vs 20.7%; p&amp;lt;0.001) and diabetes (9.4 vs 22.1%; p&amp;lt;0.001) are less frequent in PAH-SSc than in iPAH. There are no differences in the rest of the comorbidities studied in the two groups of patients. In a survival analysis, we found no differences between patients with iPAH and PAH-SSc at 7-year follow-up. Patients with ≥ 3 comorbidities had statistically significantly higher mortality (p&amp;lt;0.001) compared to those with 0 or 1-2 comorbidities in both etiologies. There were no differences between 0 and 1-2 comorbidities. (Figure 1). Variables associated with mortality were male sex (HR 1.9, 95% CI 1,28 – 2.8), age (HR 1.04, 95% CI 1.02 – 1.06), the intermediate risk profile (HR 2.64, 95% CI 1.62 – 4.32) and high risk profile (HR 9.97, 95% CI 4.36 – 18.47), but not etiology. The presence of connective tissue diseases, were not associated with increased mortality. Conclusions Patients with PAH-SSc show lower comorbidities, better hemodynamic profile, RV-PA coupling and risk profile than those with iPAH. Comorbidity has a great relevance in survival but without differences according to etiology. The presence of male sex, age, the intermediate and high risk profile is associated with worse survival, but not the connective tissue diseases.

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.

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%.

Longitudinal echocardiographic parameters for evaluation of pulmonary hypertension in preterm infants with very low birth weight.

Echocardiography is essential for the evaluation of pulmonary hypertension. We determined the feasible quantitative parameter for screening and monitoring pulmonary hypertension in preterm infants. This secondary analysis of a prospective cohort single-centre study was conducted between August 2019 and September 2020. Serial echocardiography was performed 7 and 28 days after birth and at 36 weeks postmenstrual age. The data of infants who developed pulmonary hypertension at 36 weeks postmenstrual age were compared with those without pulmonary hypertension. We also modelled the parameters' trend and performed an interaction test using multi-level Gaussian regression. Out of 30 infants enrolled in the study, 79 echocardiograms were analysed. Left ventricular eccentric index was obtainable in all infants, while tricuspid jet velocity was measurable in 44.1%. Left ventricular eccentric index correlated well with tricuspid regurgitation jet velocity (r = 0.77, P < 0.001). Six infants were diagnosed with newly developed or persistent pulmonary hypertension at 36 weeks postmenstrual age. Serial left ventricular eccentric index showed a significantly different increasing trend in the pulmonary hypertension group (change per day: +0.004; P = 0.090) from the decreasing trend among a non-pulmonary hypertension group (change per day: -0.001; P = 0.041) (P for interaction = 0.007). Right ventricular systolic function and right ventricular isovolumic systolic velocity revealed a reducing trend in the pulmonary hypertension group, which was different from the improving trend in non-pulmonary hypertension infants. Infants with low current weight, low postmenstrual age, and requiring high-flow oxygen therapy at day 28 of life trended to increase the risk of late pulmonary hypertension. Left ventricular eccentric index and right ventricular isovolumic systolic velocity were feasible for assessing pulmonary hypertension and should be incorporated into pulmonary hypertension evaluation. Serial left ventricular eccentric index and right ventricular isovolumic systolic velocity may help predict late pulmonary hypertension and early detection of right ventricular dysfunction.

Association between early pulmonary arterial pressure measurements and bronchopulmonary dysplasia or mortality in very preterm infants: a prospective cohort study

BackgroundPrematurity is a significant risk for bronchopulmonary dysplasia related pulmonary artery pressure.ObjectiveTo determine the association between pulmonary artery pressure in the early days of life and the development of bronchopulmonary...

Extracorporeal membrane oxygenation (ECMO) support for children with pulmonary hypertension: A single-institutional experience of outcomes.

Pediatric pulmonary arterial hypertension (PAH) can present with a wide spectrum of disease severity. Pulmonary hypertension (PH) crises can lead to acute decompensation requiring extracorporeal membrane oxygenation (ECMO) support, including extracorporeal cardiopulmonary resuscitation (eCPR). We evaluated outcomes for pediatric PH patients requiring ECMO. A single-institution retrospective review of pediatric PAH patients with World Symposium on PH (WSPH) groups 1 and 3 requiring ECMO cannulation from 2010 through 2022 (n = 20) was performed. Primary outcome was survival to hospital discharge. Secondary outcomes were survival to decannulation and 1-year survival. Of 20 ECMO patients, 16 (80%) survived to decannulation and 8 (40%) survived to discharge and 1 year follow up. Of three patients who had two ECMO runs; none survived. There were five patients who had eCPR for the first run; one survived to discharge. The univariate logistic regression model showed that venovenous ECMO was associated with better survival to hospital discharge than venoarterial ECMO, (OR: 0.12, 95% CI: 0.01-0.86, p = 0.046). PH medications (administered before, during, or after ECMO) were not associated with survival to discharge. For children with decompensated PAH requiring ECMO, mortality rate is high, and management is challenging. While VA ECMO is the main configuration for decompensated PH, VV ECMO could be considered if there is adequate ventricular function, presence of a systemic to pulmonary shunt, or an intercurrent treatable illness to improve survival to discharge. A multidisciplinary approach with requisite expertise should be utilized on a case-by-case basis until more reliable data is available to predict outcomes.

Global, regional, and national burden of pulmonary arterial hypertension, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Pulmonary arterial hypertension (PAH) is a vascular disease characterised by restricted flow and high pressure through the pulmonary arteries, leading to progressive right heart failure and death. This study reports the global burden of PAH, leveraging all available data and using methodology of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) to understand the epidemiology of this under-researched and morbid disease. Prior to the current effort, the burden of PAH was included in GBD as a non-specific contributor to "other cardiovascular and circulatory disease" burden. In this study, PAH was distinguished as its own cause of death and disability in GBD, producing comparable and consistent estimates of PAH burden. We used epidemiological and vital registry data to estimate the non-fatal and fatal burden of PAH in 204 countries and territories from 1990 to 2021 using standard GBD modelling approaches. We specifically focused on PAH (group 1 pulmonary hypertension), and did not include pulmonary hypertension groups 2-5. In 2021, there were an estimated 192 000 (95% uncertainty interval [UI] 155 000-236 000) prevalent cases of PAH globally. Of these, 119 000 (95 900-146 000) were in females (62%) and 73 100 (58 900-89 600) in males (38%). The age-standardised prevalence was 2·28 cases per 100 000 population (95% UI 1·85-2·80). Prevalence increased with age such that the highest prevalence was among individuals aged 75-79 years. In 2021, there were 22 000 deaths (18 200-25 400) attributed to PAH globally, with an age-standardised mortality rate of 0·27 deaths from PAH per 100 000 population (0·23-0·32). The burden of disease appears to be improving over time (38·2% improvement in age-standardised years of life lost [YLLs] in 2021 relative to 1990). YLLs attributed to PAH were similar to estimates for conditions such as chronic myeloid leukaemia, multiple sclerosis, and Crohn's disease. PAH is a rare but fatal disease that accounts for a considerable health-associated burden worldwide. PAH is disproportionally diagnosed among females and older adults. Cardiovascular Medical Research and Education Fund and the Bill & Melinda Gates Foundation.

Pulmonary hypertension and lung transplantation waitlist outcomes for hypersensitivity pneumonitis

RationaleHypersensitivity pneumonitis is an interstitial lung disease that can progress to pulmonary hypertension which increases mortality. The European Society of Cardiology recently reduced the diagnostic criteria for pre-capillary pulmonary hypertension from mean pulmonary artery pressure ≥25mmHg to ≥20mmHg and pulmonary vascular resistance from ≥3Wu to ≥2Wu. ObjectiveWe investigated the effect of the new criteria on hypersensitivity pneumonitis lung transplantation waitlist outcomes. MethodsWe conducted a retrospective cohort study of the Scientific Registry of Transplant Recipients.1175 hypersensitivity pneumonitis patients listed for lung transplantation were divided into three groups based on the presence of pre-capillary pulmonary hypertension; those with pre-capillary pulmonary hypertension based on old criteria, new criteria, and those without pre-capillary pulmonary hypertension based on either criterion. The individual components of pre-capillary pulmonary hypertension were also assessed with three mean pulmonary artery pressure groups (≤20mmHg, >20mmHg to <25mmHg, ≥25 mmHg) and three pulmonary vascular resistance groups (≤2Wu, >2Wu to <3Wu, ≥3Wu). Survival analysis was performed. Measurements and Main ResultsKaplan-Meier analysis showed a difference in waitlist survival probability among the mean pulmonary artery pressure groups and among the pulmonary vascular resistance groups driven by the most severe groups. Multivariate Cox regression showed no difference between the various pre-capillary pulmonary hypertension groups. Pulmonary vascular resistance ≥3Wu was associated with increased waitlist mortality. ConclusionsThe new thresholds of mean pulmonary artery pressure and pulmonary vascular resistance do not appear to prognosticate waitlist outcomes when combined. PVR ≥3Wu is associated with worse waitlist outcomes and may be useful in prognostication.

Analysis of clinical characteristics of patients with pulmonary hypertension in Chaya County, Chamdo, Tibet.

Pulmonary hypertension (PH) is a critical health issue marked by high blood pressure in the pulmonary arteries, with limited data on its clinical characteristics in the Tibetan population. The objective of this study was to examine the clinical characteristics of PH patients among Tibetan population residing in Chaya County, Changdu, Tibet. This was a retrospective cross-sectional study. A total of 94 PH patients diagnosed via echocardiography at the Internal Medicine Department of Chaya County People's Hospital in Changdu (Tibet, China) between March 2019 and October 2020 were included. Additionally, 52 non-PH inpatients were selected as the control group. Patient medical records were reviewed for demographic and clinical data, lab results, and echocardiographic findings. Student's t-test/chi-squared test between PH and control group, one-way analysis of variance (ANOVA) among control and PH subgroups, Pearson's and Spearman's correlation coefficient were used to analysis the results. Out of 1,689 inpatients in the Internal Medicine Department, 94 were identified as PH patients for analysis. The average hemoglobin level among PH patients (150.64±21.67 g/L) was similar to that observed in the normal population (146.65±17.51 g/L) at high altitude (P=0.28). Abnormal liver function indexes were observed, with 51.06% of PH patients exhibiting hyperuricemia (P<0.001 compared to control's 15.38%). The PH group demonstrated significantly elevated red blood cell distribution width (RDW)-standard deviation (50.59±6.49 vs. 43.67±3.40 fL, P<0.001) and RDW-coefficient of variation of (16.18%±3.04% vs. 13.52%±1.32%, P<0.001), along with a decreased platelet level compared to the control group [(202.55±73.67) vs. (256.63±72.85) ×109/L]. Furthermore, echocardiographic indicators related to right heart function showed correlations with red blood cell count, bilirubin, albumin, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol (multiple significant correlation coefficient r, magnitude from 0.22 to 0.54). Chronic pulmonary disease and left heart disease were identified as common etiologies of PH among Tibetan patients residing in high-altitude regions. The Tibetan population residing in high-altitude regions and diagnosed with PH displayed abnormal changes in numerous liver functional and metabolic indices, which were correlated with the morphological indices observed via cardiac ultrasound.

Epidemiology of supplemental oxygen in patients with pulmonary hypertension.

Patients with pulmonary hypertension (PH) may present with hypoxaemia at rest or during daily activities. There is no epidemiological data on the prescription of long-term oxygen therapy (LTOT) in patients with PH. The study sought to analyse the prevalence and incidence of LTOT prescription among patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) in Spain and to determine predictors for this prescription. A retrospective analysis was performed from the Spanish Registry of Pulmonary Arterial Hypertension (REHAP). Collected data included demographics and anthropometric measurements, functional class (FC), arterial blood gases, pulmonary function tests, haemodynamic measurements, six-minute walking distance (6MWD) and LTOT prescription. In addition, we assessed the prevalence and incidence of LTOT prescription by PH group and subtype and potential predictors for LTOT initiation in the first 5 years after diagnosis. We analysed 4533 patients (69.9% PAH and 30.1% CTEPH), mostly female (64.5%), with a mean age of 53.0 ± 18.3 years. The prevalence of LTOT was 19.3% for all patients. The incidence of LTOT prescriptions decreased from 5.6% to 1.6% between 2010 and 2019, respectively. Predictors for LTOT prescription, excluding those that represent the indication for oxygen therapy were: FC (HR: 1.813), 6MWD (HR: 1.002), mean pulmonary arterial pressure (mPAP) (HR: 1.014), cardiac index (CI) (HR: 1.253), pulmonary vascular resistance (PVR) (HR: 1.023) and diffusing capacity of carbon monoxide (DLCO) (HR: 1.294). The prevalence of LTOT in PAH and CTEPH patients is close to 20%. FC, 6MWD, mPAP, CI, PVR and DLCO were predictors for LTOT prescription.

Right Ventricular Strain With 4-Dimensional Computed Tomography Identifies Pulmonary Hypertension in Adults With Repaired Tetralogy of Fallot.

This study evaluated right ventricular (RV) volume, strain, and morphology using cardiac 4-dimensional computed tomography (4D-CT) to detect pulmonary hypertension (PH) in adults with repaired tetralogy of Fallot (TOF) scheduled for transcatheter pulmonary valve implantation (TPVI). Using cardiac 4D-CT data, we calculated RV strain in 3 different geometries and RV outflow tract (RVOT) mass in 42 patients with repaired TOF. We compared RV strain and RVOT mass between patients with and without PH. Receiver operating characteristic (ROC) analysis was conducted to evaluate the diagnostic performance of these measurements for identifying PH. Four-chamber (4ch) strain was significantly smaller for patients with (n=10) than without (n=32) PH (8.8±1.7% vs. 11.1±2.4%, respectively; P<0.01), whereas RVOT mass was significantly larger in the PH group (12.5±3.5 vs. 9.2±3.2 cm2; P<0.01). ROC analysis of the diagnostic performance revealed that the respective sensitivity and specificity was 70% and 84% (area under the curve [AUC]=0.784) for 4ch strain of 8.8%; 80% and 69% (AUC=0.766) for RVOT mass of 10.7 cm2; and 80% and 81% (AUC=0.844) for a 4ch strain/RVOT mass ratio of 0.97. RVOT mass and 4ch strain obtained from cardiac 4D-CT may be helpful for identifying PH in patients with repaired TOF.

Kidney Dysfunction, Hepatic Impairment, and Lipid Metabolism Abnormalities in Patients with Precapillary Pulmonary Hypertension.

Pulmonary hypertension (PH) is a global health issue that has profound medical and research implications. This retrospective study examined changes in renal and liver function, as well as lipid metabolism, over a 12-month period in 49 adult patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). All cases were admitted, managed, and followed up with in the PH Center, County Emergency Clinical Hospital of Targu Mures, Romania. Kidney dysfunction was observed in 12.24% of cases at baseline, decreasing to 8.16% at 12 months, and CTEPH patients were more affected. In particular, CTEPH patients exhibited an improvement in renal function, confirmed by an increase in their glomerular filtration rates. Hepatic impairment was present in 57.14% of subjects at baseline, declining to 42.86% at 12 months, with significant improvements noted in the PAH group. Lipid metabolic dysregulations were experienced by 22.45% of all patients at baseline, decreasing to 16.33% at 6 months, with a slow elevation to 24.49% at 12 months, but with no statistically significant differences. Pharmacological regimens were adjusted in accordance with the PH groups, a patient's functional and clinical response, and laboratory tests. Our results demonstrate the multi-organ damage in PH and the importance of individualized treatment approaches.

Outcome of Transcatheter Aortic Valve Replacement for Pure Native Aortic Regurgitation in Patients with Pulmonary Hypertension.

In recent years, transcatheter aortic valve replacement (TAVR) has emerged as a pivotal treatment for pure native aortic regurgitation (PNAR). Given patients with severe aortic regurgitation (AR) are prone to suffer from pulmonary hypertension (PH), understanding TAVR's efficacy in this context is crucial. This study aims to explore the short-term prognosis of TAVR in PNAR patients with concurrent PH. Patients with PNAR undergoing TAVR at Zhongshan Hospital, Affiliated with Fudan University, were enrolled between June 2018 to June 2023. They were categorized based on pulmonary artery systolic pressure (PASP) into groups with or without PH. The baseline characteristics, imaging records, and follow-up data were collected. Among the 103 patients recruited, 48 were afflicted with PH. In comparison to PNAR patients without PH, the PH group exhibited higher rates of renal dysfunction (10.4% vs. 0.0%, p = 0.014), increased Society of Thoracic Surgeons scores (6.4 1.9 vs. 4.7 1.6, p 0.001), and elevated Nterminal fragment of pro-brain natriuretic peptide (NT-proBNP). Transthoracic ultrasound examination revealed that patients with PH displayed lower left ventricular ejection fraction, larger left ventricle dimension, and more frequent moderate to severe tcuspid regurgitation (TR). Following TAVR, both groups experienced significant reductions in PASP, mitral regurgitation (MR) and TR. There were no significant differences in the incidence of postoperative adverse events in patients with or without PH. We found TAVR to be a safe and effective treatment for patients with PNAR and PH, reducing the degree of aortic regurgitation and PH without increasing the risk of postoperative adverse events.

Non-invasive prediction of pulmonary vascular disease-related exercise intolerance and survival in non-group 1 pulmonary hypertension.

The clinical utility of pulmonary hypertension (PH) risk scores in non-group 1 PH with pulmonary vascular disease (PVD) remains unresolved. We utilized the prospective multicenter PVDOMICS cohort with group 2, 3, 4 or 5 PH-related PVD and calculated group 1 PH risk scores (REVEAL 2.0, REVEAL Lite 2, French registry score and COMPERA 2). The c-statistic to predict death was compared separately in (i) pre-capillary PH groups 3/4/5, and (ii) combined post- and pre-capillary PH group 2. Exercise right heart catheterization reserve, ventricular interdependence and right ventricular-pulmonary artery (RV-PA) coupling were compared across risk categories. Among 449 individuals with group 3/4/5 PH, the REVEAL 2.0 risk score had the highest c-statistic for predicting death (0.699, 95% confidence interval [CI] 0.660-0.737, p < 0.0001) with comparable performance using the simpler REVEAL Lite 2 score (0.695, 95% CI 0.656-0.734, p < 0.0001). The French and COMPERA 2 risk scores were also predictive of mortality, but performance of both was statistically inferior to REVEAL 2.0 (c-statistic difference -0.072, 95% CI -0.123 to -0.020, p = 0.006, and -0.043, 95% CI -0.067 to -0.018, p = 0.0007, respectively). RV function and RV-PA coupling measures were prognostic in isolation, but did not add incremental value to REVEAL (p > 0.50 for all). Findings were similar in patients with group 2 PH (n = 239). Stratification by the REVEAL Lite 2 score non-invasively identified non-group 1 PH with more advanced PVD with worse exercise capacity, RV-PA uncoupling, ventricular interdependence and impaired cardiac output reserve (p < 0.05 for all). Non-invasive REVEAL risk predicts mortality in non-group 1 PH without incremental prognostic value from detailed RV function or RV-PA coupling assessment. Baseline REVEAL Lite 2 risk stratification non-invasively identifies greater pulmonary vascular dysfunction and right heart-related exercise limitation, which may help guide patient selection for targeted pulmonary vascular therapies in non-group 1 PH.