Reduction In Pulmonary Vascular Resistance Research Articles

Riociguat as bridging therapy to pulmonary endarterectomy in patients with chronic thromboembolic pulmonary hypertension: a retrospective cohort study.

In operable chronic thromboembolic pulmonary hypertension (CTEPH) patients, the utilization of bridging therapy with targeted medications prior to pulmonary endarterectomy (PEA) remains a topic of controversy, despite being common in cases of severe hemodynamic impairment. This study aims to assess the impact of riociguat as a bridging therapy on postoperative hemodynamics and outcomes. We conducted a retrospective study involving patients undergoing PEA from December 2016 to November 2023. Patients were categorized into two groups based on the use of riociguat before PEA. Pulmonary vascular resistance (PVR) following riociguat administration was assessed pre-PEA. Postoperative outcomes, including mortality, complications, and hemodynamics, were compared, employing propensity score matching analysis. Among the patients, 41.8% (n=56) received riociguat as bridging therapy. In patients with PVR ≥800 dynes·sec·cm-5, riociguat resulted in a reduction in PVR {1,207 [974-1,698] vs. 1,125 [928-1,486] dynes·sec·cm-5, P<0.01}, while no significant difference was observed in patients with PVR <800 dynes·sec·cm-5 {641 [474-740] vs. 600 [480-768] dynes·sec·cm-5, P=0.46}. After propensity score matching, each group included 26 patients. The overall perioperative mortality rate was 2.6%. Postoperative PVR {326 [254-398] vs. 361 [290-445] dynes·sec·cm-5, P=0.35} was similar in the riociguat group compared to the control group. The incidence of residual pulmonary hypertension (PH) and other postoperative outcomes were also comparable. The use of riociguat as bridging therapy demonstrated hemodynamic improvement before PEA in patients with high preoperative PVR. However, no additional benefits in postoperative mortality or hemodynamics were observed.

Insufficiency of quality of life as the treatment endpoint for balloon pulmonary angioplasty in inoperable chronic thromboembolic pulmonary hypertension.

The ability of a quality of life (QoL) to guide balloon pulmonary angioplasty (BPA) among patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) has not been fully investigated. This study explored the relationship between QoL scores and hemodynamics in CTEPH patients after BPA and examined whether QoL could be applied as a treatment endpoint. This cohort study included patients with inoperable CTEPH who had undergone at least four sessions of BPA. The patients' demographic and clinical data as well as hemodynamic parameters and scores from the RAND 36-item short-form QoL questionnaire were recorded and compared before and after BPA. After BPA treatments, clinical characteristics, hemodynamic parameters, as well as QoL score improved significantly. A physical component summary (PCS) score of 35 or 46 can be used as the cutoff value for predicting better World Health Organization functional classification (WHO FC). Patients who had a higher PCS would have longer 6-min walk distance (6MWD), lower pulmonary vascular resistance (PVR), and better cardiac output (CO) both before and after BPA. However, 19 patients (55.9%) with a higher PCS score after BPA did not achieve the goal of mean pulmonary arterial pressure (mPAP) ≤30 mmHg. During the follow-up period, a significant reduction of PVR was observed, but the PCS score improved a little. QoL is a useful tool for assessing the exercise endurance of patients with inoperable CTEPH treated with BPA, but is insufficient to serve as a treatment endpoint for BPA.

Effect of Acute Vasodilator Testing Using Oxygen in Pulmonary Hypertension Due to Left Heart Disease.

Pulmonary vasodilators, including oxygen, have not shown consistent beneficial effects on pulmonary hypertension due to valvular heart disease (PH-VHD). Therefore, the study aimed to assess the effect of 100% fractional inspiration of oxygen (FiO2) on pulmonary and systemic hemodynamics in patients with combined pre- and post-capillary pulmonary hypertension (CpcPH) and isolated post-capillary pulmonary hypertension (IpcPH) due to PH-VHD. This prospective study was conducted among patients with PH-VHD undergoing mitral or aortic valve replacement or repair. The study was conducted after induction of anesthesia and pulmonary artery catheterization. Cardiac output was obtained using thermodilution and all direct, and derived hemodynamic variables were obtained at 30% and 100% FiO2. The patients were stratified a priori into responders {(≥10mmHg fall in mean pulmonary artery pressure (MPAP)} and non-responders. Fifty-seven patients completed the acute vasodilator test. The mean age and body mass index of the study population was 41.8 ± 14.1years and 21.4 ± 4.6kg/m2, respectively. There was a significant decrease in MPAP (40.77 ± 12.07mmHg vs 36.74 ± 13.3mmHg; P < .001) and pulmonary vascular resistance (PVR) {(median; Interquartile range (IQR); 388; 371 vs 323; 362dynes sec.cm-5; P < .001) at 100% FiO2. Transpulmonary gradient (TPG) and diastolic pulmonary gradient (DPG) also decreased significantly (P < .001 and P < .001). Cardiac output did not change significantly. The magnitude of decrease in MPAP, PVR, TPG, DPG, and pulmonary artery compliance (PAC) between CpcPH and IpcPH was comparable. Responders did not show a significantly greater fall in MPAP, PVR, TPG, DPG, and PAC after surgery. Hyperoxia may lead to reduction in MPAP and PVR in both hemodynamic phenotypes of PH-VHD. A larger sample size is required to support or refute the findings of this study.

Pulmonary Vasodilator Therapy in Severe Pulmonary Hypertension Due to Chronic Obstructive Pulmonary Disease (Severe PH-COPD): A Systematic Review and Meta-Analysis.

Background: Chronic obstructive pulmonary disease-associated pulmonary hypertension (PH-COPD) results in a significant impact on symptoms, quality of life, and survival. There is scant and conflicting evidence about the use of pulmonary hypertension (PH) specific therapy in patients with PH-COPD. Study Design and Methods: PubMed, OVID, CINAHL, Cochrane, Embase, and Web of Science were searched using various MESH terms to identify randomized controlled trials (RCTs) or observational studies investigating PH-specific therapies in patients with severe PH-COPD, defined by mean pulmonary artery pressure (mPAP) of more than 35 mm Hg or pulmonary vascular resistance (PVR) of more than 5 woods units on right heart catheterization. The primary outcome was a change in mPAP and PVR. Secondary outcomes were changes in six-minute walk distance (6MWD), changes in the brain-natriuretic peptide (BNP), New York Heart Association (NYHA) functional class, oxygenation, and survival. Results: Thirteen studies satisfied the inclusion criteria, including a total of 328 patients with severe PH-COPD. Out of these, 308 patients received some type of specific therapy for PH. There was a significant reduction in mPAP (mean difference (MD) -3.68, 95% CI [-2.03, -5.32], p < 0.0001) and PVR (MD -1.40 Wood units, 95% CI [-1.97, -0.82], p < 0.00001). There was a significant increase in the cardiac index as well (MD 0.26 L/min/m2, 95% CI [0.14, 0.39], p < 0.0001). There were fewer patients who had NYHA class III/lV symptoms, with an odds ratio of 0.55 (95% CI [0.30, 1.01], p = 0.05). There was no significant difference in the 6MWD (12.62 m, 95% CI [-8.55, 33.79], p = 0.24), PaO2 (MD -2.20 mm Hg, 95% CI [-4.62, 0.22], p = 0.08), or BNP or NT-proBNP therapy (MD -0.15, 95% CI [-0.46, 0.17], p = 0.36). Conclusion: The use of PH-specific therapies in severe PH-COPD resulted in a significant reduction in mPAP and PVR and increased CI, with fewer patients remaining in NYHA functional class III/IV. However, no significant difference in the 6MWD, biomarkers of right ventricular dysfunction, or oxygenation was identified, demonstrating a lack of hypoxemia worsening with treatment. Further studies are needed to investigate the use of PH medications in patients with severe PH-COPD.

Contribution of pressure and flow changes to resistance reduction after pulmonary arterial hypertension treatment: a meta-analysis of 3898 patients.

Pulmonary arterial hypertension (PAH)-targeted therapies exert significant haemodynamic changes; however, systematic synthesis is currently lacking. We searched PubMed, CENTRAL and Web of Science for studies evaluating mean pulmonary artery pressure (mPAP), cardiac index/cardiac output (CI/CO) and pulmonary vascular resistance (PVR) of PAH-targeted therapies either in monotherapy or combinations as assessed by right heart catheterisation in treatment-naïve PAH patients. We performed a random-effects meta-analysis with meta-regression. We included 68 studies (90 treatment groups) with 3898 patients (age 47.4±13.2 years, 74% women). In studies with small PVR reduction (<4 WU), CI/CO increase (R2=62%) and not mPAP reduction (R2=24%) was decisive for the PVR reduction (p<0.001 and p=0.36, respectively, in the multivariable meta-regression model); however, in studies with large PVR reduction (>4 WU), both CI/CO increase (R2=72%) and mPAP reduction (R2=35%) contributed significantly to the PVR reduction (p<0.001 and p=0.01, respectively). PVR reduction as a percentage of the pre-treatment value was more pronounced in the oral+prostanoid intravenous/subcutaneous combination therapy (mean difference -50.0%, 95% CI -60.8- -39.2%), compared to oral combination therapy (-41.7%, -47.6- -35.8%), prostanoid i.v./s.c. monotherapy (-31.8%, -37.6- -25.9%) and oral monotherapy (-21.6%, -25.4- -17.8%). Changes in haemodynamic parameters were significantly associated with changes in functional capacity of patients with PAH as expressed by the 6-min walking distance. Combination therapies, especially with the inclusion of parenteral prostanoids, lead to remarkable haemodynamic improvement in treatment-naïve PAH patients and may unmask the contribution of mPAP reduction to the overall PVR reduction in addition to the increase in CO.

The efficacy of the treat-repair-treat strategy for severe pulmonary arterial hypertension associated with congenital heart disease: a meta-analysis

BackgroundThis meta-analysis was conducted to evaluate the efficacy of the treat-repair-treat (TRT) strategy in the treatment of severe pulmonary arterial hypertension with congenital heart disease (PAH-CHD).MethodsPubMed, EMBASE, Cochrane and Web of Science online databases were searched by two independent investigators for studies that used the TRT strategy for PAH-CHD, and the retrieved studies were reviewed by a third investigator. The main outcomes were pulmonary artery pressure (PAP), pulmonary vascular resistance (PVR), 6-minute walk distance (6MWD), and transcutaneous oxygen saturation (SpO2). The changes were compared between follow-up and baseline. Stata version 14.0 was used for data analysis. A random-effects model was selected for meta-analysis. Subgroup analysis and meta-regression were used to find the source of heterogeneity.ResultsA total of 335 patients from 9 single-arm studies were included. Meta-analysis showed significant reductions in PAP and PVR and improvements in 6MWD and SpO2 (PAP: SMD -2.73 95% CI -2.97, − 2.50 p = < 0.001; PVR: SMD -1.27 95% CI -1.53, − 1.02 p = < 0.001; 6MWD: SMD 1.88 95% CI 1.49, 2.27 p = < 0.001; SpO2: SMD 3.72 95% CI 3.13, 4.32 p = < 0.001). Subgroup analysis showed that younger patients had better efficacy, and the change in SpO2 was an indication for patient selection. The combined mortality rate was 5% at follow-up.ConclusionsIn this meta-analysis, we demonstrated that the TRT strategy may have positive effects on haemodynamics and cardiac function in patients with severe PAH-CHD at short-term follow-up. Our analysis suggests that changes in age and SpO2 may be related to patient prognosis.Trial registrationThe protocol was registered on the PROSPERO website with the registration number CRD42022366552. The relevant registration information can be obtained from the website https://www.crd.york.ac.uk/prospero/#searchadvanced.

Revisiting Pulmonary Hypertension in the Era of Temporary Mechanical Circulatory Support – Literature Review and Case-Based Discussion

Pulmonary arterial hypertension (PAH) is characterized by persistently increased pressure in the pulmonary arteries. New defining criteria for the different hemodynamic types of pulmonary hypertension (PH) that occur with left heart disease have been proposed by the task force on PH. After consideration of the changes in the general definition of PH in left heart disease, the proposed hemodynamic definition was: (1) isolated postcapillary PH: pulmonary artery wedge pressure >15 mm Hg and mean pulmonary arterial pressure (mPAP) >20 mm Hg and pulmonary vascular resistance (PVR) <3 Woods units (WU); and (2) combined post- and precapillary PH: pulmonary artery wedge pressure >15 mm Hg, mPAP >20 mm Hg, and PVR ≥3 WU. Secondary PH is initially reversible, but eventually, it can become fixed because of the remodeling process of the pulmonary vascular system. Limitations in defining both the time for and amount of reversibility lack clarity. We discuss a case of PH as a framework to better understand these key principles in addressing patients' candidacy for heart or heart-lung transplantation. We performed a literature search for all available contemporary data with the following terms: "pulmonary hypertension," "reversal," "Impella 5.5," "temporary mechanical support," and "LVAD" using the National Library of Medicine - PubMed and PubMed Central between 2019 and 2023. A total of 14 published papers were found with these search. From these, 3 addressed the issue of PH and reversibility in the setting of LHD after durable LVAD placement. No papers were found using Impella 5.5 and PH during this timeframe. Given the paucity of data in the field regarding temporary mechanical circulatory support and pulmonary hypertension, we present a case-based discussion to guide the reader in understanding the potential impact of this method in patients with WHO Class 2 Pulmonary hypertension. A 49-year-old woman with a medical history of acute on chronic biventricular systolic and diastolic heart failure, American College of Cardiology stage D, Stevenson profile C, New York Heart Association class IV (ejection fraction 18%) secondary to nonischemic cardiomyopathy after cardiac resynchronization therapy, pulmonary hypertension, bilateral deep vein thrombosis, and segmental pulmonary embolism presented for heart transplant evaluation. Her cardiac output and central hemodynamics were measured, and she was found to have a pulmonary artery (PA) pressure of 78/38 with a mean PA pressure of 51, pulmonary capillary wedge pressure (PCWP) 30, transpulmonary pressure gradient (TPG) 21, thermodilution cardiac output (CO) 3.35 L/min, and cardiac input (CI) 1.75 L/min/m2. Her PVR was 6.2 WU. Provocative pharmacologic testing for reversibility of PH was performed using sodium nitroprusside, which resulted in a blood pressure of 83/57 (92), heart rate 92/min, and PA pressure of 71/31, with a mean PA pressure of 44 PCWP 22, TPG 22, CO 4.8 L/min, and CI of 2.48 L/min/m2 with a PVR of 4.5 WU. Following this, the patient underwent Impella 5.5 placement through the right axillary artery to optimize afterload reduction and improve end-organ perfusion. Post-Impella hemodynamics on milrinone 0.5 mcg/kg/min demonstrated the following: blood pressure 90/66 (74), heart rate 53/min, and PA pressure of 56/29, with a mean PA pressure of 38, PCWP 24, TPG 14, CO 6 L/min, and CI of 2.9 L/min/m2 with a PVR of 2.3 WU. Left ventricular assist device support with Impella 5.5 is associated with a reduction in mPAP and PVR over weeks to months and thus plays a crucial role as a bridge to transplant. Our case and this review highlights the characteristics of PH resulting from heart failure with reduced ejection fraction and discusses the important clinical issues related to the treatment of these patients. We have shown that left ventricular assist device therapy with Impella 5.5 can effectively reduce left-sided filling pressures and lead to PH improvement. We demonstrate the potential benefits of Impella 5.5 in the management of patients with WHO 2 PH and cardiogenic shock with impaired hemodynamics.

Analysis of the effect of CPAP on hemodynamics using clinical data and a theoretical model: CPAP therapy decreases cardiac output mechanically but increases it via afterload reduction

BackgroundNoninvasive positive pressure ventilation (NIPPV) has been established as an effective treatment for heart failure. Positive airway pressure such as continuous positive airway pressure (CPAP) increases cardiac output (CO) in some patients but decreases it in others. However, the mechanism behind such unpredictable responses remains undetermined. Methods and resultsWe measured hemodynamic parameters of 38 cases using Swan-Ganz catheter before and after CPAP in chronic heart failure status. In those whose CO increased by CPAP, pulmonary vascular resistance (PVR) was significantly decreased and SpO2 significantly increased, but the other parameters were not changed. On the other hand, PVR was not changed, but systemic vascular resistance (SVR) was increased in those whose CO decreased by CPAP. To explain this phenomenon, we simulated the cardiovascular system using a cardiac model of time-varying elastance. In this model, it was indicated that CPAP decreases CO irrespective of cardiac function or filling status under constant PVR condition. However, when reduction of PVR by CPAP was taken into account, an increase in CO was expected especially in the hypervolemic and low right ventricle (RV) systolic function cases. ConclusionsCPAP would increase CO only where PVR can be reduced by CPAP therapy, especially in the case with hypervolemia and/or low RV systolic function. Understanding the underlying mechanism should help identify the patients for whom NIPPV would be effective.

Effects of inhaled seralutinib on right ventricular-pulmonary arterial (RV-PA) coupling and right heart function in pulmonary arterial hypertension (PAH)

Abstract Background Impaired RV-PA coupling portends a poor prognosis in PAH, and right ventricular free wall strain/systolic pulmonary artery pressure (RVFWS/sPAP) has been reported as a measure of RV-PA coupling. Furthermore, increased RVFWS and right atrial area (RAA), as well as decreased pulmonary artery compliance (PAC) are associated with increased mortality risk in PAH. Seralutinib is a novel, small molecule kinase inhibitor that targets PDGFR, CSF1R, and c-KIT administered via dry powder inhaler. TORREY, a phase 2, double-blind, randomised, placebo-controlled study of inhaled seralutinib in patients with PAH (NCT04456998) met its primary endpoint, demonstrating a significant reduction in pulmonary vascular resistance (PVR) from baseline (BL) to Week 24 compared to placebo. In addition, seralutinib significantly decreased NT-proBNP. Purpose To test the hypothesis that seralutinib would improve RVFWS/sPAP and other measures of right heart function after 24 weeks of treatment compared to placebo in the TORREY study. Methods Eighty-six patients with WHO Group 1 PH (Functional Class II, III), ages ≥18 years, pulmonary vascular resistance ≥400 dyne*s/cm5, and on stable PAH standard of care therapy (the majority of whom were on double and triple therapy with approved PAH medications) were enrolled. Right heart catheterisation (RHC) and full echocardiography were performed at BL and Week 24 and at BL, Week 12, and Week 24, respectively; both were analysed in a blinded central laboratory. To calculate RVFWS/sPAP, the pulmonary artery systolic pressure from RHC was used. PAC was calculated from RHC data with the formula (SV/(PAS-PAD)). Statistical analysis was performed using ANCOVA. Results At Week 24, the change in RVFWS/sPAP was lower in the seralutinib group compared to placebo (Table). The changes in RVFWS and RAA were lower in the seralutinib group vs placebo at Week 12 and Week 24 (Table). Change in NT-proBNP correlated with change in RAA (r = 0.43). At Week 24, change in PAC was greater in the seralutinib group (-0.02 ± 0.085 placebo, 0.19 ± 0.089 seralutinib; LSMD 0.22 (0.104) p = 0.04). There was no effect of seralutinib on left ventricular ejection fraction. Conclusion Treatment with seralutinib was associated with a significant reduction of RVFWS/sPAP. In addition, significant differences in RVFWS itself, RAA, and PAC were observed. These treatment effects support improved RV-PA coupling and right heart function. In conjunction with concordant reductions in PVR and NT-proBNP, these data suggest potential favourable effects of seralutinib in PAH. Seralutinib is in clinical development as a potential new treatment option for patients with PAH.

Abstract 17599: Sotatercept for the Treatment of Pulmonary Arterial Hypertension: A Systematic Review and Single-Arm Meta-Analysis

Introduction: Pulmonary arterial hypertension (PAH) is associated with progressive clinical worsening and a 50% 5-year survival rate with current PAH therapies. Sotatercept is a first-in-class fusion protein with promising results in preclinical trials, but clinical evidence on its role in treating PAH remains limited. Hypothesis: Sotatercept may provide clinical benefits for patients with symptomatic PAH. Aims: To assess the efficacy of sotatercept in addition to background PAH therapy in this population. Methods: We searched PubMed, Embase, Cochrane and Clinicaltrials.gov in April 2023 for clinical trials assessing efficacy outcomes of sotatercept in patients with PAH. Using a random-effects model, we performed a single-arm meta-analysis of proportions for binary outcomes and applied generic inverse variance weighting formulas to pool arithmetic means and least squares means for continuous outcomes. Statistical analyses were performed using Review Manager 5.4.1 and R software 4.2.2. Results: We included three clinical trials comprising 254 patients with WHO functional class II or III PAH. At 24 weeks, only 2% of patients on sotatercept experienced symptoms of clinical worsening (95% CI 1 to 5; Fig. 1A). Sotatercept was also associated with a reduction in pulmonary vascular resistance (mean change from baseline -199.92 dyn·sec·cm -5 ; 95% CI -256.83 to -143.0; Fig. 1B), while improving 6-minute walk distance (mean change from baseline 45.86 m; 95% CI 28.54 to 63.18; Fig. 1C). Conclusions: These findings suggest that sotatercept may improve exercise capacity while decelerating clinical worsening and attenuating pulmonary vascular resistance in patients with mild to moderate PAH.

Development and validation of a nomogram for predicting hemodynamic response to balloon pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension

BackgroundBalloon pulmonary angioplasty (BPA) can effectively alleviate pulmonary hypertension in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Identifying predictors of unfavorable hemodynamic response to BPA is essential to guide clinical practice. Therefore, our objective was to construct and validate a nomogram to facilitate clinicians predicting hemodynamic response to BPA. MethodsPatients with CTEPH and underwent BPA from May 2018 to April 2022 were retrospectively collected. Favorable hemodynamic response to BPA was defined as a mean pulmonary arterial pressure ≤30 mmHg and/or a reduction in pulmonary vascular resistance ≥30 % at follow-up. ResultsA total of 155 patients were included. At baseline, patients with favorable hemodynamic response had significantly lower proportion of occlusive lesions (11.11 % vs. 26.32 %, P = 0.017), higher diffusing capacity of the lungs for carbon monoxide (63.77 % ± 14.10 % vs. 59.11 % ± 11.78 %, P = 0.039), and better cardiac morphology than counterparts. LASSO regression and random forest were used to construct prediction models respectively. The LASSO regression model demonstrated better predictive ability and accuracy than the random forest model, as evidenced by higher area under curve (0.745 vs. 0.740) and lower Brier score (0.192 vs. 0.195). A nomogram was constructed based on the LASSO regression model, consisting of right ventricular end-diastolic diameter/left ventricular end-diastolic diameter, number of treated pulmonary vessels and proportion of occlusion lesions. High predictive ability of the LASSO model was preserved in validation (C index 0.744). ConclusionsThe current study constructed a nomogram with high accuracy in predicting BPA hemodynamic outcome, which could facilitate decision-making in clinical practice.

Inhaled Nitric Oxide in Patients with Cardiogenic Shock Treated with Veno-arterial Extracorporeal Membrane Oxygenation and Impella

Background: Inhaled nitric oxide (iNO) is a pulmonary vasodilator that can reduce the right ventricular afterload. We aimed to determine the clinical significance of iNO on right ventricular function in patients with cardiogenic shock (CS) treated with combined veno-arterial extracorporeal membrane oxygenation and Impella (ECPELLA). Methods: Pulmonary artery (PA) catheter parameters were obtained before and 24 hours after iNO introduction for eight CS patients receiving ECPELLA and three patients receiving Impella. The causes of CS were MI in six patients, heart failure deterioration in three patients, and myocarditis in two patients. An Impella CP was mainly used (n=9). Results: Before iNO introduction, the mean ± SD PA pulsatility index (0.83 ± 0.56 versus 2.73 ± 1.00; p=0.002) and Impella flow rate (2.0 ± 1.1 versus 3.1 ± 0.1 l/min; p=0.038) were lower in patients receiving ECPELLA than in those receiving Impella. Both the PA pulsatility index (+0.81 ± 0.82; p=0.013) and Impella flow rate (+0.65 ± 0.58 l/min; p=0.008) increased 24 hours after iNO introduction without a worsening of pulmonary congestion in patients receiving ECPELLA. A reduction in pulmonary vascular resistance was the only characteristic haemodynamic change in patients receiving Impella. Conclusion: Right ventricular-specific haemodynamics and Impella flows were improved during iNO treatment. Therefore, the addition of iNO for CS patients with right ventricular dysfunction supported with ECPELLA can be a useful therapeutic option.

Restoration of right ventricular function in the treatment of pulmonary arterial hypertension

ObjectiveA 45% threshold of right ventricular ejection fraction (RVEF) is proposed clinically relevant in patients with pulmonary arterial hypertension (PAH). We aim to determine treatment response, long-term right ventricular (RV)...

Efficacy and Safety of Balloon Pulmonary Angioplasty for Patients With Chronic Thromboembolic Pulmonary Hypertension and Comorbid Chronic Obstructive Pulmonary Disease.

Background Balloon pulmonary angioplasty (BPA) is a promising treatment modality for nonoperable chronic thromboembolic pulmonary hypertension (CTEPH). However, BPA for atypical CTEPH with concurrent chronic obstructive pulmonary disease (COPD) remains controversial owing to the risk of exacerbation of ventilation-perfusion mismatch. We aimed to evaluate the efficacy and safety of BPA for CTEPH with moderate or severe COPD. Methods and Results Data from 149 patients with CTEPH, who underwent BPA from March 2011 to June 2021, were retrospectively analyzed. Patients were divided based on COPD comorbidity: the COPD group (n=32, defined as forced expiratory volume in 1 second/forced vital capacity <70% and forced expiratory volume in 1 second <80% predicted) and the non-COPD group (n=101); patients with mild COPD (n=16) were excluded. Hemodynamic and respiratory parameters were compared between the groups. Hemodynamics improved similarly in both groups (reduction in pulmonary vascular resistance): -55.6±29.0% (COPD group) and -58.9±21.4% (non-COPD group); P=nonsignificant. Respiratory function and oxygenation improved in the COPD group (forced expiratory volume in 1 second/forced vital capacity [61.8±7.0% to 66.5±10.2%, P=0.02] and arterial oxygen partial pressure [60.9±10.6 mm Hg to 69.3±13.6 mm Hg, P<0.01]). Higher vital capacity (P=0.024) and higher diffusing capacity for lung carbon monoxide (P=0.028) at baseline were associated with greater improvement in oxygenation in the multivariable linear analysis. Lung injury per BPA session was 1.6% in the COPD group. Conclusions The efficacy and safety of BPA for nonoperable CTEPH in patients with comorbid COPD were similar to those in patients without COPD. Oxygenation and forced expiratory volume in 1 second/forced vital capacity improved in patients with COPD. BPA should be considered in patients with CTEPH with concurrent COPD.

Hemodynamic Response to Oral Vasodilator Therapy in Systemic Sclerosis-Related Pulmonary Hypertension.

Although classified as group 1 pulmonary arterial hypertension (PAH), patients with systemic sclerosis-related pulmonary hypertension (SSc-PH) experience poorer clinical response to PAH therapy and increased mortality compared to those with idiopathic PAH. Due to heterogeneity in phenotypes, identifying patients likely to respond to therapy is challenging. The goal of this study was to determine clinical factors associated with hemodynamic response, defined by a > 20% reduction in pulmonary vascular resistance on repeat right heart catheterization. We applied a time-to-event model using a retrospective cohort of 39 patients with precapillary SSc-PH, defined by a mean pulmonary artery pressure of ≥ 25mmHg and pulmonary arterial wedge pressure (PAWP) ≤ 15mmHg on right heart catheterization. Patients with PAWP ≤ 8mmHg were nearly fourfold more likely to achieve a hemodynamic response compared to those with PAWP > 8mmHg (HR 3.88; 95% CI: 1.20, 12.57); each 1mmHg increase in PAWP was associated with a decreased hazard for hemodynamic response (HR 0.84; 95% CI: 0.70, 1.00). In patients with precapillary SSc-PH, PAWP was associated with time to hemodynamic response, suggesting the importance of subclinical cardiac disease in determining hemodynamic response to oral vasodilator therapy.

Anaesthetic management Of Cerebral abscess drainage In a child with uncorrected Double outlet right ventricle (DORV) a case report

Introduction: Double Outlet Right Ventricle is a cyanotic congenital heart disease where both the great arteries, aorta and pulmonary artery arise from the morphologic right ventricle and a ventricular septal defect(VSD) is present. Children with uncorrected DORV can present for non-cardiac surgeries. Such patients are at a higher risk to develop cerebral abscess because of right to left shunting of blood and absence of pulmonary clearance of microorganisms. Such cases pose a significant challenge for the anesthesiologists. Case summary: I present a case of six years female child with uncorrected DORV with multiple cerebral abscess, grade 4 clubbing with presence of central cyanosis and peripheral oxygen saturation of 73% on room air. Central nervous system examination revealed a drowsy child with features of raised ICP and a GCS of E4V2M5. The child underwent drainage of brain abscess under general anesthesia with controlled mechanical ventilation and invasive monitoring and had uneventful recovery. Conclusion: The mainstay of anaesthetic management of a patient with uncorrected congenital cyanotic heart disease aims at maintaining systemic vascular resistance(SVR) higher than pulmonary vascular resistance(PVR). Reduction in PVR can be achieved by increasing inspired oxygen concentration, countering acidosis by elective hyperventilation, avoiding hypothermia, hypercarbia and acidosis. Keywords: brain abscess; congenital; double outlet right ventricle

121 RELEVANCE OF COMORBIDITIES ON INITIAL COMBINATION THERAPY IN PULMONARY ARTERIAL HYPERTENSION

Abstract Rationale Demographic characteristics of pulmonary arterial hypertension (PAH) patients have changed over time, but the effects of cardiovascular risk factors on risk status and pulmonary vascular resistance (PVR) reduction with initial oral combination therapy are not known. Therefore, we tested the relevance of cardiovascular comorbidities in this setting. Methods The study enrolled 181 treatment-naive PAH patients with a 6- months (IQR 144-363 days) right heart catheterization and risk assessment after initial oral combination therapy. Results Group-A, 96 (53.0%) patients without cardiac comorbidities; Group-B, 54 (29.8%) patients with one cardiac comorbidity; Group-C, 31 (17.1%) patients with ≥2 cardiac comorbidities. Group-C patients were older with a balanced gender distribution. There was a significant difference in PVR reduction moving from the absence to one or ≥2 cardiac comorbidities, respectively, median -45.0%, -30.3%, -24.3%. A ERS/ESC low-risk status was present at first follow-up in 50 (52.0%) patients in Group-A, 19 (35.1%) in Group-B, and 9 (29.0%) in Group-C; a REVEAL 2.0 low-risk status was present at first follow-up in 41 (42.0%) patients in Group-A, 15 (27.7%) in Group-B, and 7 (22.6%) in Group-C. Group-A patients were 2.3 times more likely to achieve/maintain a low risk status compared with Group-B and -C (OR 2.27, 95% C.I. 1.15-4.54, p=0.02). No significant difference was observed between patients with non-cardiac comorbidities and those without comorbidities. Conclusion Initial oral combination therapy seems associated with a less effective response for patients with cardiovascular comorbidities compared with the others, related to the magnitude of treatment- induced decrease in PVR.

Effects of an inhaled soluble guanylate cyclase (sGC) stimulator MK-5475 in pulmonary arterial hypertension (PAH)

BackgroundNovel therapeutics for pulmonary arterial hypertension (PAH) with improved safety/tolerability profiles are needed to address continued high rates of morbidity/mortality. MethodsThis Phase 1 study evaluated efficacy/safety of inhaled single-dose MK-5475, an investigational, small-molecule stimulator of soluble guanylate cyclase designed for inhaled delivery via a dry-powder inhaler device, in participants with PAH (Clinicaltrials.gov: NCT03744637). Eligible participants were 18–70 years of age; body mass index ≤35 kg/m2; diagnosis of PAH (Group 1 pulmonary hypertension). In Part 1, participants received double-blind MK-5475 or placebo for safety assessment (primary outcome). In Part 2, 4 panels participated in ≤3 open-label periods. Part 2/Period 1 assessed safety/tolerability. Part 2/Periods 2 and 3, respectively, involved functional respiratory imaging for measuring pulmonary blood volume (secondary outcome) and right heart catheterization for measuring pulmonary vascular resistance (primary outcome). ResultsMK-5475 was generally well tolerated without systemic side effects on blood pressure or heart rate up to 24 h post dose. With respect to the primary pharmacodynamic outcome, mean reductions in pulmonary vascular resistance ranged from 21% to 30% across 120 μg and 360 μg doses. ConclusionsTreatment with inhaled single-dose MK-5475 showed rapid and sustained reductions in pulmonary vascular resistance and increases in pulmonary blood volume. MK-5475 was generally well tolerated versus placebo without vasodilatory systemic side effects. The promising pulmonary selectivity and favorable safety/tolerability profile of MK-5475 seen in this study of adult participants with PAH lays the foundation for further clinical development.

Relevance of comorbidities on initial combination therapy in pulmonary arterial hypertension.

Demographic characteristics of pulmonary arterial hypertension (PAH) patients have changed over time, but the effects of cardiovascular risk factors on risk status and pulmonary vascular resistance (PVR) reduction with initial oral combination therapy are not known. Therefore, we tested the relevance of cardiovascular comorbidities in this setting. The study enrolled 181 treatment-naive PAH patients with a 6-month (IQR 144-363 days) right heart catheterisation and risk assessment after initial oral combination therapy. Group A included 96 (53.0%) patients without cardiac comorbidities; Group B included 54 (29.8%) patients with one cardiac comorbidity; Group C included 31 (17.1%) patients with two cardiac comorbidities or more. Group C patients were older with a balanced sex distribution. There was a significant difference in PVR reduction moving from the absence to one or at least two cardiac comorbidities, respectively: median -45.0%, -30.3%, -24.3%. A European Respiratory Society/European Society of Cardiology low-risk status was present at first follow-up in 50 (52.0%) patients in Group A, 19 (35.1%) in Group B and 9 (29.0%) in Group C; a REVEAL 2.0 low-risk status was present at first follow-up in 41 (42.0%) patients in Group A, 15 (27.7%) in Group B and 7 (22.6%) in Group C. Group A patients were 2.3 times more likely to achieve/maintain a low-risk status compared with Group B and C (OR 2.27, 95% CI 1.15-4.54, p=0.02). No significant difference was observed between patients with non-cardiac comorbidities and those without comorbidities. Initial oral combination therapy seems associated with a less effective response for patients with cardiovascular comorbidities compared with the others, related to the magnitude of treatment-induced decrease in PVR.

Exercise and hypoxia unmask pulmonary vascular disease and right ventricular dysfunction in a 10- to 12-week-old swine model of neonatal oxidative injury.

Prematurely born young adults who experienced neonatal oxidative injury (NOI) of the lungs have increased incidence of cardiovascular disease. Here, we investigated the long‐term effects of NOI on cardiopulmonary function in piglets at the age of 10–12 weeks. To induce NOI, term‐born piglets (1.81 ± 0.06 kg) were exposed to hypoxia (10–12% FiO2), within 2 days after birth, and maintained for 4 weeks or until symptoms of heart failure developed (range 16–28 days), while SHAM piglets were normoxia raised. Following recovery (>5 weeks), NOI piglets were surgically instrumented to measure haemodynamics during hypoxic challenge testing (HCT) and exercise with modulation of the nitric‐oxide system. During exercise, NOI piglets showed a normal increase in cardiac index, but an exaggerated increase in pulmonary artery pressure and a blunted increase in left atrial pressure – suggesting left atrial under‐filling – consistent with an elevated pulmonary vascular resistance (PVR), which correlated with the duration of hypoxia exposure. Moreover, hypoxia duration correlated inversely with stroke volume (SV) during exercise. Nitric oxide synthase inhibition and HCT resulted in an exaggerated increase in PVR, while the PVR reduction by phosphodiesterase‐5 inhibition was enhanced in NOI compared to SHAM piglets. Finally, within the NOI piglet group, prolonged duration of hypoxia was associated with a better maintenance of SV during HCT, likely due to the increase in RV mass. In conclusion, duration of neonatal hypoxia appears an important determinant of alterations in cardiopulmonary function that persist further into life. These changes encompass both pulmonary vascular and cardiac responses to hypoxia and exercise. Key points Children who suffered from neonatal oxidative injury, such as very preterm born infants, have increased risk of cardiopulmonary disease later in life.Risk stratification requires knowledge of the mechanistic underpinning and the time course of progression into cardiopulmonary disease.Exercise and hypoxic challenge testing showed that 10‐ to 12‐week‐old swine that previously experienced neonatal oxidative injury had increased pulmonary vascular resistance and nitric oxide dependency.Duration of neonatal oxidative injury was a determinant of structural and functional cardiopulmonary remodelling later in life.Remodelling of the right ventricle, as a result of prolonged neonatal oxidative injury, resulted in worse performance during exercise, but enabled better performance during the hypoxic challenge test.Increased nitric oxide dependency together with age‐ or comorbidity‐related endothelial dysfunction may contribute to predisposition to pulmonary hypertension later in life.