Baseline Pulmonary Vascular Resistance Research Articles

Survival comparison in adults with congenital systemic to pulmonary shunt and borderline elevated pulmonary vascular resistance versus Eisenmenger syndrome

Pulmonary arterial hypertension (PAH) associated with congenital heart disease (PAH-CHD) is a consequence of unrepaired large systemic-to-pulmonary shunts. The long-term data of adult patients who have PAH-CHD with elevated pulmonary vascular resistance (PVR) are limited. We aimed to investigate the survival of adults who had PAH-CHD with predominantly left-to-right (L-R) shunts with (1) borderline-to-high PVR and (2) treat-and-repair compared with those with Eisenmenger syndrome (ES). From 1995 to 2021, 99 adults with ES (age 34.1 ± 11.2 years) and 118 adults with PAH-CHD with predominantly L-R shunts (age 39.1 ± 13.7 years) were eligible. The PVR in the ES group was 21.0 ± 13.1 WU. Most ES patients (97%) received pulmonary vasodilator therapy. Among the 118 patients with PAH-CHD with predominantly L-R shunts, the baseline PVR was 7.6 ± 4.6 WU, and 78 patients (66.1%) had borderline to high PVR (≥ 5 WU). In the group, 105 patients (88.9%) underwent repair; 84 had defect closure, and 21 had fenestrated closure. Treat-and-repair was used to treat 53 patients with a preoperative final PVR of 3.58 ± 2.63 WU. No early postoperative deaths were reported. At a median follow-up time of 5.4 years (range 0.1–23.6 years), the 10- and 15-year survival rates of adults with borderline PVR were 82.3% and 82.3%, respectively, which were not inferior to the rates for patients with ES, which were 77.8% and 71.2%, respectively (p = 0.41). The survival rate of patients who underwent treat-and-repair was slightly better than that of patients who underwent ES, although the difference was not statistically significant (p = 0.19). Independent mortality risk factors were functional class III-IV at initial presentation (hazard ratio 5.7, 95% CI 1.2–26.6; p = 0.02) and oxygen saturation < 94% at the most recent visit (hazard ratio 9.4, 95% CI 2.1–42.9; p = 0.004).Trial registration: TCTR20200420004.

Prognostic Implications and Reversibility of Pulmonary Vascular Resistance Derived by Echocardiography in Patients Undergoing Tricuspid Annuloplasty.

Pulmonary vascular resistance (PVR) intimately correlates with right ventricular afterload and the development of secondary tricuspid regurgitation (sTR). We sought to investigate the prognostic roles of PVR derived by echocardiography in patients with sTR undergoing tricuspid annuloplasty (TA). Data from 322 TA patients [median age (interquartile range): 65.0 (59.0-70.0) years; 35.7% males] were obtained from a prospective registry to determine the impact of PVR on the composite outcome (including all-cause mortality and heart failure hospitalization). PVR was calculated by dividing the peak TR velocity by time-velocity integral of the right ventricular outflow tract followed by adding 0.16. During a median follow-up of 5.2 years, 108 adverse events occurred including 48 deaths and 60 heart failure readmissions. Baseline PVR ≥2 WU was independently associated with a higher risk of composite outcome (HR:1.674, 95% CI: 1.028-2.726, P=0.038). Baseline PVR outperforms both pulmonary artery systolic pressure (PASP) and the ratio of tricuspid annulus plane systolic excursion to PASP in terms of outcome prediction, with pronounced improvement of global model fit, reclassification, and discrimination. In 150 patients who received short-term echocardiograms after surgery, the presence of postoperative PVR ≥2 WU (n=20, 13.3%) was independently associated with composite outcome (HR: 2.621, 95% CI: 1.292-5.319, P=0.008). PVR derived by echocardiography is an independent determinant of outcomes in patients undergoing TA for sTR. The inclusion of noninvasive PVR may provide valuable information to improve patient selection and postoperative management in this population.

Echocardiographic pulmonary vascular resistance in patients undergoing tricuspid annuloplasty: prognostic implications and reversibility

Abstract Background Pulmonary vascular resistance (PVR) intimately connects with right ventricular afterload and the development of secondary tricuspid regurgitation (sTR). Objectives We sought to investigate the prognostic roles of PVR derived from echocardiography in patients who underwent tricuspid annuloplasty (TA) for sTR. Methods Data from 322 patients who underwent TA [median age (interquartile range): 65.0 (59.0-70.0) years; 35.7% males] were obtained from a prospective registry to determine the impact of PVR on the composite outcome (including all-cause mortality and heart failure hospitalization). PVR was calculated by dividing the peak TR velocity by time-velocity integral of the right ventricular outflow tract and then adding 0.16. Results During a median follow-up of 5.2 (interquartile range: 2.2-8.2) years, 108 adverse events occurred including 48 deaths and 60 heart failure readmissions. Baseline PVR ≥ 2.0WU was independently associated with a higher risk of composite outcome (adjusted HR[KY1] [u2] :1.674, 95% CI: 1.028-2.726, P=0.038). Baseline PVR outperforms pulmonary artery systolic pressure (PASP) and the ratio of tricuspid annulus plane systolic excursion to PASP in terms of outcome prediction, with pronounced improvement of global model fit, reclassification, and discrimination. In 150 patients who received echocardiograms after surgery, the presence of post-operative PVR ≥ 2.0WU (n=20, 13.3%) was independently associated with the composite outcome (adjusted HR: 2.621, 95% CI: 1.292-5.319, P=0.008). Conclusion PVR measured on echocardiography is an independent determinant of clinical outcomes in patients undergoing TA. The inclusion of echocardiographic PVR assessment may provide valuable additional information for patient selection and risk stratification in this population.Kaplan-Meier CurveChange of PVR after Surgery

Efficacy and safety of selexipag in patients with inoperable or persistent/recurrent CTEPH (SELECT randomised trial).

SELECT was the first global randomised controlled trial of selexipag with standard of care in patients with inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension. SELECT was a multicentre, randomised, double-blind, placebo-controlled, parallel-group, group-sequential, phase 3 study (ClinicalTrials.gov: NCT03689244). Adults aged ≤85 years in World Health Organization Functional Class I-IV, with a 6-min walk distance of 100-450 m, were randomised (1:1) to receive selexipag (200-1600 µg twice daily titration until individual maximum tolerated dose)+standard of care or placebo+standard of care. Patients were recruited into the haemodynamic set (first 91 randomised patients to undergo right heart catheterisation (RHC); week 20) or non-haemodynamic cohort (remaining patients, no RHC required). The primary end-point was percent of baseline pulmonary vascular resistance (PVR; week 20). Safety was also assessed. Of 321 patients screened, 128 were randomised (haemodynamic set n=91 (selexipag n=47; placebo n=44)). In the haemodynamic set, 29 (31.9%) patients had previous pulmonary endarterectomy (PEA), 20 (22.0%) balloon pulmonary angioplasty (BPA), and 14 (15.4%) both PEA and BPA; 28 (30.8%) were inoperable. The independent data monitoring committee recommended to stop the study for futility as no statistically significant difference was observed for the primary end-point (between-treatment geometric least squares mean ratio of PVR: 0.95, 95% CI 0.84-1.07; p=0.412). Adverse events were reported in 63 (98.4%) and 53 (82.8%) patients for selexipag and placebo, respectively. SELECT was discontinued for futility, as no treatment effect on the primary end-point (PVR) was observed. Safety data were consistent with the established safety profile of selexipag, with no new safety signals identified.

Effect of Preoperative Mitral Regurgitation on LVAD Outcomes in Patients with Elevated Pulmonary Vascular Resistance.

In patients with end-stage heart failure who undergo left ventricular assist device (LVAD) implantation, higher pulmonary vascular resistance (PVR) is associated with higher right heart failure rates and ineligibility for heart transplant. Concomitant mitral regurgitation (MR) could potentially worsen pulmonary hemodynamics and lead to worse outcomes; however, its effects in this patient population have not been specifically examined. Using an institutional database spanning November 2003 to August 2017, we retrospectively identified patients with elevated PVR who underwent LVAD implantation. Patients were stratified by concurrent MR: moderate/severe (PVR + MR) vs. mild/none (PVR - MR). Cumulative incidence functions and Fine-Gray competing risk regression were performed to assess the effect of MR on heart transplant rates and overall survival during index LVAD support. Of 644 LVAD recipients, 232 (171 HeartMate II, 59 HeartWare, 2 HeartMate III) had baseline PVR > 3 Woods units; of these, 124 (53%) were INTERMACS 1-2, and 133 (57%) had moderate/severe MR (≥ 3 +). Patients with PVR + MR had larger a baseline left ventricular end-diastolic diameter than patients with PVR - MR (87.9 ± 38.2 mm vs. 75.9 ± 38.0 mm; P = 0.02). Median clinical follow-up was 18.8 months (interquartile range: 4.7-36.4 months). Moderate/severe MR was associated with lower mortality rates during index LVAD support (adjusted hazard ratio 0.64, 95% CI 0.41-0.98; P = 0.045) and higher heart transplant rates (adjusted odds ratio 2.86, 95% CI 1.31-6.25; P = 0.009). No differences in stroke, gastrointestinal bleeding, or right heart failure rates were observed. Among LVAD recipients with elevated preoperative PVR, those with moderate/severe MR had better overall survival and higher transplant rates than those with mild/no MR. These hypothesis-generating findings could be explained by incremental LVAD benefits resulting from reduction of MR and better LV unloading in a subset of patients with larger ventricles at baseline. In patients with preoperative elevated PVR, MR severity may be a prognostic sign that can inform patient selection for end-stage heart failure therapy.

Seralutinib in adults with pulmonary arterial hypertension (TORREY): a randomised, double-blind, placebo-controlled phase 2 trial

Morbidity and mortality in pulmonary arterial hypertension (PAH) remain high. Activation of platelet-derived growth factor receptor, colony stimulating factor 1 receptor, and mast or stem cell growth factor receptor kinases stimulates inflammatory, proliferative, and fibrotic pathways driving pulmonary vascular remodelling in PAH. Seralutinib, an inhaled kinase inhibitor, targets these pathways. We aimed to evaluate the efficacy and safety of seralutinib in patients with PAH receiving standard background therapy. The TORREY trial was a phase 2, randomised, multicentre, multinational, double-blind, placebo-controlled study. Patients with PAH from 40 hospital and community sites were randomly assigned 1:1 via interactive response technologies to receive seralutinib (60 mg twice daily for 2 weeks, then increased to 90 mg twice daily as tolerated) or placebo by dry powder inhaler twice daily for 24 weeks. Randomisation was stratified by baseline pulmonary vascular resistance (PVR; <800 dyne·s/cm5 and ≥800 dyne·s/cm5). Patients were eligible if classified as WHO Group 1 PH (PAH), WHO Functional Class II or III, with a PVR of 400 dyne·s/cm5 or more, and a 6 min walk distance of between 150 m and 550 m. The primary endpoint was change in PVR from baseline to 24 weeks. Analyses for efficacy endpoints were conducted in randomly assigned patients (intention-to-treat population). Safety analyses included all patients who received the study drug. TORREY was registered with ClinicalTrials.gov (NCT04456998) and EudraCT (2019-002669-37) and is completed. From Nov 12, 2020, to April 20, 2022, 151 patients were screened for eligibility, and following exclusions, 86 adults receiving PAH background therapy were randomly assigned to seralutinib (n=44; four male, 40 female) or placebo (n=42; four male, 38 female), and comprised the intention-to-treat population. At baseline, treatment groups were balanced except for a higher representation of WHO Functional Class II patients in the seralutinib group. The least squares mean change from baseline to week 24 in PVR was 21·2 dyne·s/cm5 (95% CI -37·4 to 79·8) for the placebo group and -74·9 dyne·s/cm5 (-139·7 to -10·2) for the seralutinib group. The least squares mean difference between the seralutinib and placebo groups for change in PVR was -96·1 dyne·s/cm5 (95% CI -183·5 to -8·8; p=0·03). The most common treatment-emergent adverse event in both treatment groups was cough: 16 (38%) of 42 patients in the placebo group; 19 (43%) of 44 patients in the seralutinib group. Treatment with inhaled seralutinib significantly decreased PVR, meeting the primary endpoint of the study among patients receiving background therapy for PAH. Gossamer Bio.

(857) - Improvements in Pulmonary Artery Compliance After Balloon Pulmonary Angioplasty Depend on Baseline Pulmonary Vascular Resistance

(857) - Improvements in Pulmonary Artery Compliance After Balloon Pulmonary Angioplasty Depend on Baseline Pulmonary Vascular Resistance

Inhaled treprostinil in patients with pulmonary hypertension associated with interstitial lung disease with less severe haemodynamics: a post hoc analysis of the INCREASE study

BackgroundInhaled treprostinil (iTre) is the only treatment approved for pulmonary hypertension due to interstitial lung disease (PH-ILD) to improve exercise capacity. This post hoc analysis evaluated clinical worsening and PH-ILD...

Pulmonary Vascular Resistance to Predict Right Heart Failure in Patients Undergoing Left Ventricular Assist Device Implantation.

Right heart failure (RHF) is associated with poor outcomes, especially in patients undergoing left ventricular assist device (LVAD) implantation. The aim of this study was to identify predictors of RHF after LVAD implantation. Of 129 consecutive patients (mean age 56 ± 11 years, 89% male) undergoing LVAD implantation, 34 developed RHF. Compared to patients without RHF, those with RHF required longer invasive mechanical ventilation and had longer intensive care unit and hospital stays (p < 0.01). One-year all-cause mortality was significantly higher in patients with versus without RHF after LVAD implantation (29.4% vs. 1.2%; hazard ratio 35.4; 95% confidence interval 4.5-277; p < 0.001). Mortality was highest in patients with delayed RHF after initial LVAD-only implantation (66.7%). Patients who did versus did not develop RHF had significantly higher baseline pulmonary vascular resistance (PVR; 404 ± 375 vs. 234 ± 162 dyn/s/cm5; p = 0.01). PVR > 250 dyn/s/cm5 was a significant predictor of survival in patients with RHF after LVAD implantation. These data confirm the negative impact of RHF on morbidity and mortality after LVAD implantation. Preoperative PVR > 250 dyn/s/cm5 determined using invasive right heart catheterization was an independent predictor of developing RHF after LVAD implantation, and of subsequent mortality, and could be used for risk stratification in the setting for deciding between single or biventricular support strategy.

Pulmonary vascular resistance/systemic vascular resistance (PVR/SVR) ratio changes after sildenafil therapy in uncorrected congenital heart disease-associated pulmonary arterial hypertension

Pulmonary vascular resistance (PVR) to systemic vascular resistance (SVR) ratio is a prognostic predictor in congenital heart disease (CHD)-associated pulmonary arterial hypertension (PAH) after defect correction. Sildenafil, widely used as a PAH drug, can decrease PVR with minimal or without changes in SVR, resulting in decreased PVR/SVR ratio after treatment. However, there is limited evidence that PVR/SVR ratio reduced after sildenafil therapy in uncorrected CHD-associated PAH patients. This study aimed to investigate the decreasing of the PVR/SVR ratio after ≥ 1-year oral sildenafil therapy in adult uncorrected CHD-associated PAH. A total of 30 uncorrectable CHD-associated PAH subjects derived from the COHARD-PH registry were included in this study. Right heart catheterization (RHC) was performed during the first visit and further evaluations were conducted after ≥1-year oral sildenafil therapy. The PVR/SVR ratio at the baseline and after the evaluation was collected. The primary outcome of this study was the changes in PVR/SVR ratio from baseline to evaluated RHC. Characteristic analysis of subjects with decreased PVR or PVR/SVR ratio was perforemd as the secondary outcome. The mean PVR and SVR were not different from baseline and evaluated RHC (15.98± 10.67 vs. 18.38±13.93 WU, p=0.206 and 36.65±13.99 vs. 39.34±15.46 WU, p=0.262). There was no significant difference in the baseline PVR/SVR ratio and the evaluated PVR/SVR ratio after ≥1-year sildenafil therapy (0.48 ±0.32 vs. 0.49±0.36; p=0.882). As much as 15 subjects (50%) experienced decreased PVR/SVR ratio. However, there was no significant difference in the characteristics, including age, Eisenmenger syndrome, type of shunts, baseline PVR, PAH-specific treatment, and baseline NT-proBNP level (p&gt;0.05). In conclusion, sildenafil therapy does not change PVR/SVR ratio in adults with uncorrected CHD-associated PAH.

Long-term outcomes in health-related quality of life influence chronic disease management in patients with pulmonary hypertension.

Significantly improved survival in patients with pulmonary hypertension (PH) has raised interest in maintaining a good quality of long-term survivorship. In this study, health-related quality of life (HRQOL) measurement was used to assess the long-term changes of physical and mental outcomes. A total of 559 consecutive inpatients with PH completed generic HRQOL (Short Form-36) who were diagnosed with PH by right heart catheterization. Assessments were carried out at short-term (1 year), midterm (3 years), and long-term (5 years) follow-ups. Patients with PH suffered more severe impairments in both physical and emotional domains than the U.S. population normative values. Patients with PH due to chronic lung disease had the worst physical component summary (PCS) score, but there was no difference in mental component summary (MCS) score among different PH types. A reduced PCS score was correlated with WHO FC severity and pulmonary vascular resistance (PVR). The Z score showed that the changing trend of mental conditions continuously declined from baseline to midterm and long-term follow-ups, but the PCS score seemed to be stable or improved. Cox regression analysis indicated increased baseline PVR and WHO FC III and IV, and decreased physical subscale of role physical, mental subscale of social functioning, and the MCS score have increased risk of mortality in the long-term follow-up. Patients with PH have poor HRQOL. The long-term change of physical status seemed to be stable, but the mental state was continuously worse. These suggested identifying and intervening mental health progresses is a noteworthy issue in PH chronic management.

Mortality rates and cause of mortality in patients with mildly elevated pulmonary pressures versus PH: insights from the retrospective EVIDENCE-PAH study

Abstract Background Normal mean pulmonary artery pressure (mPAP) does not exceed 20 mmHg and normal pulmonary vascular resistance (PVR) does not exceed 2 Wood Units (WU). The thresholds used to define pre-capillary pulmonary hypertension (PH) – mPAP ≥25 mmHg and PVR &amp;gt;3 WU – are being evaluated. It is unclear if treatment would benefit patients with mildly elevated mPAP (≥21–&amp;lt;25 mmHg). Purpose The EVIDENCE-PAH study aims to describe mortality and hospitalisation outcomes, clinical characteristics, therapies, and quality of life during long-term follow-up of a national cohort of patients with different levels of mPAP and PVR. We report preliminary analyses focusing on mortality and its cause in patients stratified by their baseline (BL) mPAP. Methods This retrospective analysis included PAH-treatment-naïve patients with suspected PH who received a first right heart catheterisation (RHC) between 2009 and 2017 at any of the 7 UK tertiary PH centres, which assess all PH patients in the UK. A sample of patients with BL mPAP ≥25 mmHg (stratified by PVR and treatable versus non-treatable PH) was used as a control in this analysis. Baseline characteristics, mortality and cause of mortality were stratified by mPAP (&amp;lt;21, ≥21–&amp;lt;25, ≥25 mmHg) at BL (first RHC). Mortality was also stratified by BL PVR (&amp;lt;1, 1–&amp;lt;2, 2–&amp;lt;3, 3–&amp;lt;6, ≥6 WU). Mortality analysis was done without matching cohorts. Mortality data were obtained from the Office for National Statistics, NHS Digital. Results In total, 2926 patients were analysed (968, 689 and 1269 with mPAP &amp;lt;21, ≥21–&amp;lt;25, ≥25 mmHg, respectively). Mean observation was 6.1 years. BL characteristics are in Table. Survival worsened with increasing mPAP (p&amp;lt;0.0001) and increasing PVR (p&amp;lt;0.01) (Figure). After 5 years of follow-up, 187 (27.1%) patients with mPAP ≥21–&amp;lt;25 mmHg had died, compared with 162 (16.7%) and 595 (46.9%) patients in the lower and higher mPAP groups, respectively. In patients with mPAP ≥21–&amp;lt;25 mmHg, the most common main cause of death was respiratory disease (36.4%) – with scleroderma lung disease and interstitial lung disease accounting for 69.1% of these deaths – followed by cardiac disease (16.6%) and malignancy (15.0%) (Table). PH was the main cause of death for only 1.6% of patients with mildly elevated mPAP and it was a contributor to death in 6.8% (BL mPAP &amp;lt;21 mmHg), 10.2% (≥21–&amp;lt;25 mmHg), and 40.2% (≥25 mmHg) of cases. Conclusion Long-term survival in patients with mPAP ≥21–&amp;lt;25 mmHg was worse than in those with normal mPAP, and better than in those with the current definition of PH. While the main cause of death was mostly unrelated to PH and further analysis is needed to understand the impact of underlying disease, mildly elevated mPAP appears to confer a worse prognosis and should be closely monitored. These data show the relevant disease burden in patients with mPAP ≥21–&amp;lt;25 mmHg and the need to understand if they could benefit from treatment. PVR may be key in determining patients who might benefit. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Actelion Pharmaceuticals Ltd., a Janssen pharmaceutical company of Johnson &amp; Johnson.

Complications of balloon pulmonary angioplasty for inoperable chronic thromboembolic pulmonary hypertension: Impact on the outcome.

Balloon pulmonary angioplasty (BPA) is an emerging interventional treatment for inoperable chronic thromboembolic pulmonary hypertension (CTEPH) that targets subsegmental branches of the pulmonary artery. As the reported complication rates are high, the aim of the present study was to evaluate the effects of certain complications on the outcome after treatment. From March 2014 to December 2019, a total of 235 patients with inoperable CTEPH underwent BPA. Of these patients, 140 were included who completed a follow-up examination 6 months after the last intervention; another 2 patients deceased due to complications of BPA. A high baseline pulmonary vascular resistance (PVR) >6.6 WU correlated with a higher rate of complications (mostly pulmonary artery perforations). Wire perforation during BPA did not correlate with worse outcome in terms of PVR reduction. The complication rate per intervention decreased from 21% to 14% during the 5 year period of the study. Complications are frequently observed in BPA, but the mortality rate is very low in expert centers. Importantly, the occurrence of complications does not portend a worse outcome.

Balloon pulmonary angioplasty versus riociguat for the treatment of inoperable chronic thromboembolic pulmonary hypertension (RACE): a multicentre, phase 3, open-label, randomised controlled trial and ancillary follow-up study

Riociguat and balloon pulmonary angioplasty (BPA) are treatment options for inoperable chronic thromboembolic pulmonary hypertension (CTEPH). However, randomised controlled trials comparing these treatments are lacking. We aimed to evaluate the efficacy and safety of BPA versus riociguat in patients with inoperable CTEPH. In this phase 3, multicentre, open-label, parallel-group, randomised controlled trial done in 23 French centres of expertise for pulmonary hypertension, we enrolled treatment-naive patients aged 18-80 years with newly diagnosed, inoperable CTEPH and pulmonary vascular resistance of more than 320 dyn·s/cm5. Patients were randomly assigned (1:1) to BPA or riociguat via a web-based randomisation system, with block randomisation (block sizes of two or four patients) without stratification. The primary endpoint was change in pulmonary vascular resistance at week 26, expressed as percentage of baseline pulmonary vascular resistance in the intention-to-treat population. Safety analyses were done in all patients who received at least one dose of riociguat or had at least one BPA session. Patients who completed the RACE trial continued into an ancillary 26-week follow-up during which symptomatic patients with pulmonary vascular resistance of more than 320 dyn·s/cm5 benefited from add-on riociguat after BPA or add-on BPA after riociguat. This trial is registered at ClinicalTrials.gov, NCT02634203, and is completed. Between Jan 19, 2016, and Jan 18, 2019, 105 patients were randomly assigned to riociguat (n=53) or BPA (n=52). At week 26, the geometric mean pulmonary vascular resistance decreased to 39·9% (95% CI 36·2-44·0) of baseline pulmonary vascular resistance in the BPA group and 66·7% (60·5-73·5) of baseline pulmonary vascular resistance in the riociguat group (ratio of geometric means 0·60, 95% CI 0·52-0·69; p<0·0001). Treatment-related serious adverse events occurred in 22 (42%) of 52 patients in the BPA group and five (9%) of 53 patients in the riociguat group. The most frequent treatment-related serious adverse events were lung injury (18 [35%] of 52 patients) in the BPA group and severe hypotension with syncope (two [4%] of 53 patients) in the riociguat group. There were no treatment-related deaths. At week 52, a similar reduction in pulmonary vascular resistance was observed in patients treated with first-line riociguat or first-line BPA (ratio of geometric means 0·91, 95% CI 0·79-1·04). The incidence of BPA-related serious adverse events was lower in patients who were pretreated with riociguat (five [14%] of 36 patients vs 22 [42%] of 52 patients). At week 26, pulmonary vascular resistance reduction was more pronounced with BPA than with riociguat, but treatment-related serious adverse events were more common with BPA. The finding of fewer BPA-related serious adverse events among patients who were pretreated with riociguat in the follow-up study compared with those who received BPA as first-line treatment points to the potential benefits of a multimodality approach to treatment in patients with inoperable CTEPH. Further studies are needed to explore the effects of sequential treatment combining one or two medications and BPA in patients with inoperable CTEPH. Programme Hospitalier de Recherche Clinique of the French Ministry of Health and Bayer HealthCare. For the French translation of the abstract see Supplementary Materials section.

Early and long-term results of ventricular septal defect repair in children with severe pulmonary hypertension and elevated pulmonary vascular resistance by the double or traditional patch technique.

In upper-income countries, infants undergo low-risk ventricular septal defect (VSD) repair. Children in low- and middle-income countries frequently present at older ages with elevated pulmonary vascular resistance (PVR) and pulmonary arterial hypertension (PAH). Expensive interventions for pulmonary hypertensive crisis are not available, and children are often denied an operation due to the mortality risk. We report our early and late experiences with these patients who underwent VSD closure by traditional patch (TP) or double patch (DP) techniques. We extracted data from patients with VSD and PAH who underwent VSD closure operations from 1996 to 2016. Information regarding cardiac catheterizations, operations, time in the intensive care unit and follow-up information was found. We identified 129 children and analysed the differences between the TP (89/129) and the DP (40/129) in unidirectional groups. After 2005, the patients were pretreated with sildenafil 3 months before catheterization. The TP group was younger (P < 0.001). Hospital mortality (2.5%, DP; 10.1%,TP) was not significantly different (P = 0.17) between the 2 groups despite significant differences in baseline PVR, PVR/systemic vascular resistance and the number of children with a saturation less than 90%. The long-term survival and regression of PAH were better in the DP group (survival over 97% vs 93% in the TP group). Moreover, 61% of children with DP and 75% of those with TP had normal to mild elevations in pulmonary artery pressures at the last follow-up examination (P = 0.046). The DP operation is a low-risk procedure. Moreover, the long-term outcome with the use of this technique in high-risk patients with VSD and high PVR and PAH is favourable with respect to survival and showed a decrease in PAH at the last follow-up.

Hemodynamic Changes After Left Ventricular Assist Device Implantation Among Heart Failure Patients With and Without Elevated Pulmonary Vascular Resistance

BackgroundLeft ventricular assist devices (LVADs) may reverse elevated pulmonary vascular resistance (PVR) which is associated with worse prognosis in heart failure (HF) patients. We aim to describe the temporal changes in hemodynamic parameters before and after LVAD implantation among patients with or without elevated PVR.MethodsHF patients who received continuous-flow LVAD (HeartMate 2&3) at a tertiary medical center and underwent right heart catheterization with PVR reversibility study before and after LVAD surgery. Patients were divided into 3 groups: normal PVR (<4WU); reversible PVR (initial PVR ≥4WU with positive reversibility); and non-reversible (persistent PVR ≥4WU).ResultsOverall, 85 LVAD patients with a mean age of 58 years (IQR 49–64), 65 patients (76%) were male; 60 patients had normal PVR, 20 patients with reversible and 5 patients with non-reversible PVR pre-LVAD. All patients with elevated PVR (≥4WU) had higher pulmonary pressures (PP) and increased trans-pulmonary gradient (TPG) compared to patients with normal PVR (p < 0.05). Patients with non-reversible PVR were more likely to have a significantly lower baseline cardiac output (CO) compared to all other groups (p ≤ 0.02). Hemodynamic parameters and PVR post LVAD were similar in all study groups. Patients with baseline elevated PVR (reversible and non-reversible) demonstrated a significant improvement in PP and TPG compared to patients with normal baseline PVR (p ≤ 0.05). The improvement in CO and PVR post-LVAD in the non-reversible PVR group was significantly greater compared to all other groups (p < 0.01). There were no significant differences between study groups in post LVAD and post heart transplantation course.ConclusionHemodynamic parameters improved after LVAD implantation, regardless of baseline PVR and reversibility, and enabled heart transplantation in patients who were ineligible due to non-reversible elevated PVR. Our findings suggest that mitigation of elevated non-reversible PVR is related to reduction in PP and increase in CO.

Pulmonary Hypertension and Diastolic Heart Failure in an Adolescent African-American Cantú Syndrome Patient

<h3>Introduction</h3> Cantú syndrome is a rare congenital condition characterized by hypertrichosis, coarse facial features, cardiomegaly, skeletal abnormalities, and tortuous vasculature. While progress has been made in the understanding of the molecular basis of this disease, there is still much to be uncovered regarding its natural history. Here, we present the clinical course of an African-American male with Cantú syndrome. <h3>Case Report</h3> A 4-month-old African-American male presented to the hospital with respiratory distress. A large pericardial effusion was identified, which required a pericardial window. Cardiac catheterization revealed pulmonary hypertension. At age 4, a diagnosis of Cantú syndrome was made on the basis of developmental delay, cardiomegaly, history of pericardial effusion, pulmonary hypertension, coarse facial features, hypertrichosis, wide/thickened ribs, and osteopenia. He developed chronic diastolic heart failure secondary to cardiomegaly and chronic hypercarbic respiratory failure requiring home oxygen and nocturnal bi-level positive airway pressure (BiPAP) therapy. Pulmonary hypertension treatment was initiated with sildenafil at age 13, resulting in significant improvement in exercise tolerance. Cardiac catheterization at 17 years of age demonstrated worsening pulmonary hypertension with baseline RV pressures of 85/18 mmHg and pulmonary artery (PA) pressures of 85/40 mmHg. Baseline pulmonary vascular resistance (PVR) was 15.7 Woods Units/m2. Vasoreactivity to O2 and inhaled nitric oxide was demonstrated with PVR decreasing to 6.6 and 5.5 Woods Units/m2 respectively. Carvedilol and cardiac rehabilitation therapy were initiated at age 19. On a recent admission, he required milrinone support due to worsening right ventricular (RV) dysfunction which was weaned prior to discharge. <h3>Summary</h3> Cantú syndrome is a rare genetic condition and its prevalence and prognosis are still unknown. Interestingly, nearly all patients in the International Cantú Syndrome Registry are Caucasian while our patient is African-American. Additionally, with no family history of the disease, it is possible that his case represents a sporadic mutation. Unfortunately, our patient exhibited progressive heart failure, pulmonary hypertension, and hypercarbic respiratory failure during his adolescent years.

International Practice Heterogeneity in Pediatric Left Heart Disease Related Pulmonary Hypertension

<h3>Purpose</h3> Elevated pulmonary vascular resistance (PVR) in left heart disease contributes to poor outcomes after pediatric heart transplant (HT). Medical management of high PVR pre-HT is controversial and insufficiently described. <h3>Methods</h3> We sought to characterize practice internationally by surveying physicians at pediatric HT centers via ISHLT and other networks. <h3>Results</h3> We received 49 complete responses from 39 centers in 16 countries. The majority of respondents were pediatric cardiologists (90%) practicing at centers offering pediatric heart (86%) and lung (55%) transplant. In patients with left heart failure and elevated baseline PVR, most centers (88%) perform acute vasoreactivity testing (AVT) during catheterization. Only half (51%) have established a maximum PVR for transplant eligibility, with most citing 6 WU*m² or lower (80%) [range 4-8 WU], obtained after AVT (84%). The highest post-AVT PVR ever listed ranged from 4-14.4, median 6 WU*m² (Figure). Pre-HT, phosphodiesterase 5 inhibitors are most frequently used to treat high PVR (65%); however, 31% never use pulmonary vasodilators. Implantation of a left ventricular assist device (LVAD) increases likelihood of medical therapy for PVR, though timing of initiation (pre- vs post-HT) and duration of therapy varies. Case scenarios demonstrate HT listing with post-transplant pulmonary vasodilator therapy is the favored approach for restrictive cardiomyopathy and elevated PVR, whereas LVAD +/- pulmonary vasodilators is favored for patients with dilated cardiomyopathy or postop LV dysfunction and high PVR, regardless of vasoreactivity. Most continue vasodilator therapy until PVR normalizes or short term (<6 months) post-transplant. <h3>Conclusion</h3> Practice regarding medical management of elevated PVR in children awaiting HT is heterogenous, with variable use of pulmonary vasodilators and a wide range of acceptable PVR cutoffs. Evidence-based guidelines are needed to ensure standardized care and equitable organ allocation.

Right heart catheterization in advanced systolic heart failure. What are the most useful haemodynamic parameters for risk stratification?

Previous studies have shown that pulmonary hypertension is a predictor of mortality in patients with systolic heart failure (SHF). Persistent pulmonary hypertension after a reactivity test is associated with a worse outcome after transplantation. Recent studies have shown the utility of different haemodynamic parameters. To define best haemodynamic parameters for risk stratification in patients with advanced systolic heart failure. We included 425 consecutive patients who underwent a right heart catheterization with an inotropic challenge if indicated. During a median (interquartile range) follow-up of 1.67 (0.49-4.49) years, there were 151 major cardiac events (126 cardiovascular deaths and 25 postoperative deaths after ventricular assist device implantation or heart transplantation). The most powerful independent predictors of major cardiac events were baseline right atrial pressure (RAP) (hazard ratio [HR]: 1.09, 95% confidence interval [CI]: 1.06-1.12; P<0.0001) and baseline pulmonary vascular resistance (PVR) (HR: 1.10; 95% CI: 1.03-1.17; P=0.002). After inotropic challenge, the only independent predictor was mean pulmonary arterial pressure (mPAP) (HR: 1.06; 95% CI: 1.03-1.09; P<0.0001). The combination of PVR (≤or>3 Wood units), RAP (<or≥9mmHg) and mPAP after the inotropic challenge (≤or>30mmHg) was the best predictor of major events. We suggest using a simple algorithm based on baseline PVR, baseline RAP and mPAP after the inotropic challenge for the risk stratification of stable patients with advanced systolic heart failure.

Pulmonary artery capacitance and pulmonary vascular resistance as prognostic indicators in acute pulmonary embolism.

AimsThe non-invasive calculation of right ventricular (RV) haemodynamics as pulmonary artery (PA) capacitance (PAC) and pulmonary vascular resistance (PVR) have proved to be feasible, easy to perform, and of high prognostic value. We, therefore, evaluated whether baseline PAC and PVR could predict clinical outcomes for patients with acute pulmonary embolism (PE).Methods and resultsWe prospectively followed 373 patients [mean (standard deviation) age, 64.1 (14.9) years; 58.4% were men, and 27.9% had cancer] who had acute PE and transthoracic echocardiography within 1 day of diagnosis from 1 March 2013 through 30 June 2020. Pulmonary artery capacitance was calculated as left ventricular stroke volume/(PA systolic pressure − PA diastolic pressure). Pulmonary vascular resistance was calculated as (tricuspid regurgitant velocity/RV outflow tract velocity time integral) × 10 + 0.16. These two variables were calculated retrospectively from the values obtained with transthoracic echocardiography. Pulmonary artery capacitance was acquired in 99 (27%) patients and PVR in 65 (17%) patients. Univariable and bivariable logistic regression analyses, and receiver operating characteristic curves were used to evaluate the ability of these haemodynamic measurements to predict mortality up to 6 months. After using bivariable models to adjust individually for age, cancer, and pulmonary hypertension. Pulmonary vascular resistance was associated with all-cause mortality at 3 months [area under the curve (AUC) 0.75, 95% confidence interval (CI) 0.61–0.86; P = 0.01], and 6 months (AUC 0.81; 95% CI 0.69–0.91; P≤ 0.03). Pulmonary artery capacitance was associated with all-cause mortality at 30 days (AUC 0.95; 95% CI 0.82–0.99; P < 0.001) and 3 months (AUC 0.84; 95% CI 0.65–0.99; P = 0.003).ConclusionNon-invasive measurement of RV haemodynamics could provide prognostic information of patients with acute PE. Pulmonary artery capacitance and PVR are potentially important predictors of all-cause mortality in these patients and should be explored in future studies.