Lower Pulmonary Vascular Resistance Research Articles

Intervention control of aerobic exercise in maintaining quality of life and pulmonary hypertension in hemodialysis patients.

Pulmonary hypertension is a serious complication in the treatment of maintenance hemodialysis patients, which seriously affects the quality of life of patients and threatens their life safety. Prevention, treatment and improvement of pulmonary hypertension are of great significance to improve the quality of life of patients. To investigate the intervention and control of pedal-powered bicycle in maintaining quality of life and pulmonary hypertension in hemodialysis patients. 73 patients with maintenance hemadialysis combined with pulmonary arterial hypertension at a hemodialysis center in a certain hospital from May 2021 to May 2022 are selected. Patients are divided into two groups, 37 cases in the control group (group C) and 36 cases in the intervention group (group I). Patients are divided into two groups, group C is treated with oral administration of betaglandin sodium combined with routine nursing care. Based on group C, group I conducts power cycling exercises. After treatment, group I patients had higher muscle strength, 36-Item Short Form Health Survey scores, and Kidney Disease Targets Areas scores; The 6-minute walk distance test index level was higher and the Borg score was lower; The group I had lower systolic blood pressure, greater vital capacity, higher positive emotion, lower systolic pulmonary artery pressure index level, higher arterial partial oxygen pressure level, lower pulmonary vascular resistance index level, and higher blood oxygen saturation level [158.91 ± 11.89 vs 152.56 ± 12.81, 1795.01 ± 603.18 vs 1907.20 ± 574.15, 24.00 (22.00, 29.00) vs 24.00 (22.00, 28.00), P < 0.001]. Aerobic exercise combined with Western medicine treatment can effectively improve patients' pulmonary hypertension, alleviate their negative emotions, and enable them to achieve a higher level of quality of life.

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.

Insights Into Differences in Pulmonary Hemodynamics in Hispanic Patients With Pulmonary Arterial Hypertension.

Emerging data suggest that Hispanic patients with pulmonary arterial hypertension (PAH) exhibit improved survival rates compared to individuals of other ethnicities with similar baseline hemodynamics. However, the underlying reasons for this survival advantage remain unclear. This study focused on comparing pulmonary hemodynamics in Hispanic and non-Hispanic PAH patients and how these differences may contribute to varied clinical outcomes. A retrospective analysis of right heart catheterization data was conducted on a treatment-naive PAH patient cohort from a single center. Over a 10-year period, a total of 226 PAH patients were identified, of which 138 (61%) were Hispanic and 88 (39%) were non-Hispanic. Hispanic patients presented with lower pulmonary artery pressures, lower pulmonary vascular resistance, and exhibited significantly higher pulmonary arterial compliance (PAc). Hispanic patients had better 5-year survival rates. This study highlights the importance of exploring phenotypic differences in ethnically diverse PAH cohorts.

Predictors Associated With Prognosis of Patients on the Waiting List for Heart Transplantation.

Aim To identify predictors associated with the prognosis of patients on the heart transplant waiting list (HTWL) corresponding to UNOS class 2.Material and methods A HTWL database for 2010-2021 was retrospectively evaluated. The study included patients (n=162) who at the time of inclusion into the HTWL met UNOS class 2 and reached the endpoint of death, heart transplantation (HT), or exclusion from the HTWL due to an improvement of their condition. Mean age was 48±13 (from 11 to 67) years, 80% (n=130) were men, and body weight index was 24.9±4.4 kg/m2. Patients were divided into two groups: group 1 (n=131), patients who left the HTWL (improvement of CHF functional class) and patients who maintained the UNOS class 2 until HT; group 2 (n=31), patients who transferred from UNOS class 2 to UNOS class 1B/1A or died while on the HTWL.Results Patients of group 2 had lower systolic BP compared to patients of group 1 (100±17, mm Hg vs. 107±17 mm Hg, respectively, p=0.03). In group 1 compared to group 2, there was a higher proportion of patients with obesity, 29 (22%) vs. 1 (3%) (p=0.02). Laboratory blood tests: absolute lymphocyte count (2.0±0.7×109/L and 1.6±0.9×109/L, p=0.03), serum albumin (42±5 g/l and 40±6 g/l, p=0.03), red cell distribution width (RDW) (16±4% and 18±4%, p=0.01); sodium concentration (139±4 and 136±4 mmol/l, p=0.009). Patients from group 2 had a higher pulmonary vascular resistance (PVR) (4.0±2.4 Wood units vs. 3.2±1.4 Wood units, p=0.01) at baseline. A predictive model (p&lt;0.001) was developed to determine a probability of prognosis in HTWL. The model sensitivity was 75% and the specificity was 67%. High PVR was a predictor that worsened the prognosis in HTWL; higher serum concentrations of sodium and albumin increased the probability of a favorable outcome in HTWL.Conclusion During the period of waiting for HT, 19% of patients that met UNOS class 2 experienced deterioration of their condition (transitioned to UNOS 1) or died. The most important predictors for a better outcome in patients on HTWL who meet UNOS class 2 were higher serum levels of sodium and albumin and low pulmonary vascular resistance.

Impact of Left Heart Disease Risk Factors on Outcomes in Pulmonary Arterial Hypertension Therapy

BackgroundCurrent guidelines recommend initial monotherapy for pulmonary arterial hypertension (PAH) with ‘cardiopulmonary comorbidities’, despite limited available evidence to guide management. Research QuestionDo left heart disease (LHD) risk factors have an impact on treatment response and influence applicability of risk assessment in a real-world cohort of PAH patients? Study Design and MethodsThe AMBITION trial criteria was used to define the phenotype of PAH patients with risk factors for LHD. Treatment strategy, functional outcome, long term survival and risk discrimination were compared with a reference PAH cohort using the PHSANZ registry. Results487 incident PAH patients diagnosed between 2011-2020 were included. Of these, 103 (21.1%) fulfilled the definition of PAH with LHD risk factors with 384 (78.9%) remaining as reference group. PAH with LHD risk factors were older (66±13 vs. 58±19years, p<0.001), had lower pulmonary vascular resistance (393±266 vs 708±391dynes/sec/cm-5, p=0.031) and worse 6-minute walk distance (286±130 vs. 327±136m, p=0.005) at diagnosis. PAH with LHD risk factors were less likely to receive less initial combination therapy (27% vs. 44%, p=0.02). Changes in 6-minute walk distance at 12-months were similar in both groups, 43±77 in PAH with LHD risk factors and 50±90m in reference group (p=0.5), including when stratified by initial treatment strategy (monotherapy: 40±81 vs. 38±95m p=0.87 and combination therapy: 53±78 vs. 64±106m, p=0.511; PAH with LHD risk factors vs. reference PAH). Functional class improvements were also similar in both groups. REVEAL 2.0 risk score effectively discriminated risk in both populations (C-statistic=0.756 for PAH with LHD risk factors and C-statistic=0.750 for reference PAH). There was no difference in survival between the two groups (log-rank test p=0.29). InterpretationIn a real-word cohort, PAH patients with LHD risk factors were less likely to be exposed to initial combination therapy. Nevertheless, selected PAH patients with LHD risk factors who were treated with initial combination therapy derived similar functional response compared to reference group. Further studies are needed to phenotype PAH patients with cardiopulmonary comorbidities who may benefit from initial combination therapy.

Analysis of prognostic predictors and differences between subgroups of pulmonary arterial hypertension associated with portal hypertension and HIV infection

Abstract Background Pulmonary arterial hypertension (PAH) represents a complication of both portal hypertension (Po-PAH) and HIV infection (HIV-PAH). Due to overlapping risk factors, it is frequent to have an overlap PAH form associated with both portal hypertension and HIV (HIV/Po-PAH). Methods We enrolled 204 patients with Po-PAH (128), HIV-PAH (41) and HIV/Po-PAH (35), with the aim of comparing the characteristics and identifying the prognostic determinants. At baseline, in patients with Po-PAH and HIV/Po-PAH, the severity of liver disease was estimated using the Child-Turcotte-Pugh (CTP) score, MELD score (Model for End-stage Liver Disease); instead, in patients with HIV-PAH and HIV/Po-PAH it was defined whether they received HAART (Highly Active Anti-Retroviral Therapy) and the CD4+ lymphocytes number. Data are expressed as median (interquartile range) and compared with Dunn’s test. Prognostic determinants were identified by univariate and multivariate Cox-regression analysis. Survival was assessed using Kaplan Meier method. Results HIV-infected patients [40 (37-43) years] and HIV/Po-PAH [44 (39-48) years] are younger than Po-PAH patients [53 (44-60) years]; the exercise capacity assessed by the 6-minute walking test of patients with HIV/Po-PAH [516 (432-571) m] was superior to both patients with Po-PAH [426 (366-504) m] and HIV-PAH [448 (370-510) m], presumably justified by the demographic and haemodynamic differences between these groups. In fact, patients with concomitant portal hypertension (Po-PAH and HIV/Po-PAH) have a better haemodynamic profile than patients with HIV-PAH, specifically, lower pulmonary vascular resistance [6.2 (4.9-8.8) and 7.0 (5.5-11.2) WU vs 8.9 (7.5-12.2) WU] and higher cardiac index [3.1 (2.6-3.8) and 3.0 (2.7-3.7) l/min/m2 vs 2.6 (2.2-2.9) l/min/m2] and mixed venous oxygen saturation [70 (65-75) and 67 (62-71) % vs 61 (55-66)%] values. Despite these differences, the survival of the three groups of patients was not statistically different (5-year survival of patients with Po-PAH was 41%; of patients with HIV/Po-PAH was 46%; and of patients with HIV-PAH was 51%; log-rank test p-value= 0.059) and the prognostic factors that emerge at the multivariate analysis are only parameters associated with the underlying disease. In particular, the parameters independently associated with prognosis are, in patients with Po-PAH, only the CTP score [HR 1.665 (CI 1.153-2.403), p= 0.007]; in patients with HIV-PAH only the treatment with HAART [HR 0.283 (CI 0.119-0.675), p= 0.004]; in patients with HIV/Po-PAH both MELD-Na+ [HR 1.224 (CI 1.064-1.408), p= 0.005] and trans-hepatic venous gradient [HR 1.125 (CI 1.026-1.235), p= 0.013]. Conclusions In patients with Po-PAH, HIV-PAH, and HIV/Po-PAH adequately treated with PAH medications, the prognosis seems to be related to the underlying disease. This may explain why their survival is not statistically different despite significant demographic, exercise and hemodynamic differences.

Clinical features and long-term survival in idiopathic pulmonary arterial hypertension with thyroid dysfunction: insights from a national multicentre prospective study.

Our objective was to clarify the characteristics and long-term survival of idiopathic pulmonary arterial hypertension (IPAH) patients with thyroid dysfunction and compare them with IPAH without thyroid dysfunction. A retrospective analysis was conducted using prospectively collected data. IPAH patients with thyroid dysfunction at baseline were included. Patients with other subgroups of PAH and Group 2-5 pulmonary hypertension were excluded. IPAH patients with euthyroid function were matched 1:1 to IPAH patients with thyroid dysfunction by age and sex. In total, 148 IPAH patients with thyroid dysfunction were included. Patients with hyperthyroidism, hypothyroidism, subclinical hyperthyroidism and subclinical hypothyroidism accounted for 16.2%, 18.9%, 8.1% and 56.8%, respectively. IPAH patients with hyperthyroidism showed the highest mixed venous oxygen saturation (SvO2) and the lowest pulmonary vascular resistance (PVR) at baseline among subgroups, while patients with subclinical hypothyroidism had the lowest SvO2 and highest PVR (p<0.05). Compared with IPAH without thyroid dysfunction, patients with hyperthyroidism (9.14 versus 13.86 WU; p<0.05) and hypothyroidism (10.70 versus 13.86 WU; p<0.05) showed significantly lower PVR. The haemodynamic profiles of patients with subclinical hypothyroidism were similar to IPAH with euthyroid function except for lower right atrial pressure (6 versus 8 mmHg; p=0.009). The long-term survival of patients with clinical thyroid dysfunction was better than IPAH without thyroid dysfunction, while that of those with subclinical diseases was comparable to the latter, even after adjusting for baseline haemodynamics and treatment. IPAH patients with clinical hyper- and hypothyroidism had better haemodynamics and survival than those without thyroid dysfunction, while patients with subclinical hypothyroidism had similar haemodynamics and survival profiles to the latter.

Pulmonary Vasodilator Therapy in Pediatric Patients on Ventricular Assist Device Support: A Single-Center Experience and Proposal for Use.

Pediatric precapillary pulmonary hypertension can develop in response to systemic atrial hypertension. Systemic atrial decompression following ventricular assist device (VAD) implantation may not sufficiently lower pulmonary vascular resistance (PVR) to consider heart transplant candidacy. Prostacyclins have been used in adult VAD patients with success, but pediatric data on safety and efficacy in this population are limited. We sought to describe our center's experience to show its safety and to present our current protocol for perioperative use. We reviewed our use of prostacyclin therapy in pediatric patients on VAD support with high PVR from 2016 to 2021. Of the 17 patients who met inclusion, 12 survived to transplant and 1 is alive with VAD in situ. All patients survived posttransplant. With continuous intravenous (IV) epoprostenol or treprostinil therapy, there were no bleeding complications or worsening of end-organ function. A significant reduction was observed in vasoactive inotropic scores by 49% in the first 24 hours post-prostacyclin initiation. The proportion of patients surviving to transplant in this high-risk cohort is favorable. In conclusion, prostacyclins may be safe to use in patients with elevated PVR as part of their VAD and transplant course and may provide a transplant option in those otherwise not candidates.

Natural history of chronic thromboembolic pulmonary disease with no or mild pulmonary hypertension

We describe baseline characteristics, disease progression and mortality in chronic thromboembolic pulmonary disease patients as a function of mean pulmonary artery pressure (mPAP) according to new and previous definitions of pulmonary hypertension. All patients diagnosed with chronic thromboembolic pulmonary disease between January, 2015 and December, 2019 were dichotomized according to initial mPAP: ≤20mmHg ('normal') vs 21-24mmHg ('mildly-elevated'). Baseline features were compared between the groups, and pairwise analysis performed to determine changes in clinical endpoints at 1-year, excluding those who underwent pulmonary endarterectomy or did not attend follow-up. Mortality was assessed for the whole cohort over the entire study period. One hundred thirteen patients were included; 57 had mPAP ≤20mmHg and 56 had mPAP 21-24mmHg. Normal mPAP patients had lower pulmonary vascular resistance (1.6 vs 2.5WU, p<0.01) and right ventricular end-diastolic pressure (5.9 vs 7.8mmHg, p<0.01) at presentation. At 3 years, no major deterioration was seen in either group. No patients were treated with pulmonary artery vasodilators. Eight had undergone pulmonary endarterectomy. Over 37 months median follow-up, mortality was 7.0% in the normal mPAP group and 8.9% in the mildly-elevated mPAP group. Cause of death was malignancy in 62.5% of cases. Chronic thromboembolic pulmonary disease patients with mild pulmonary hypertension have statistically higher right ventricular end-diastolic pressure and pulmonary vascular resistance than those with mPAP ≤20mmHg. Baseline characteristics were otherwise similar. Neither group displayed disease progression on non-invasive tests up to 3 years. Mortality over 37 months follow-up is 8%, and mainly attributable to malignancy. Further prospective study is required to validate these findings.

Long Covid as an Indication for Heart Transplantation and Its Characteristics

The post-acute cardiovascular manifestations of COVID-19, known as long COVID, have yet to be comprehensively characterized. There is also an increased risk of heart failure in individuals without cardiovascular disease before SARS-CoV-2 infection. The literature lacks information regarding the characteristics of patients with long COVID who developed advanced heart failure refractory to guideline-directedmedical therapy. We describe the characteristics of patients with long COVID (LC) who were listed for heart transplantation. The study population comprised 45 patients listed for heart transplantation, divided into 2 groups: patients with etiologies other than LC (n=41) and patients with LC (n=4) between January 2020 and March 2022. The endpoint of this study was the description of the characteristics of each group. The average duration of hospitalization after the acute infectious episode with SARS-CoV-2 was 150 ± 113 days, and all patients were hospitalized in New York Heart Association class IV. All LC patients were oligosymptomatic in the initial infection, did not require hospitalization in the acute phase, had a lower ejection fraction, used more intra-aortic balloon pumps, had lower pulmonary vascular resistance, and fewer comorbidities compared with other etiologies, suggesting a clinical feature compatible with low cardiac output rather than congestion. This study is an early investigation of patients listed for heart transplantation due to a complex syndrome of COVID-19. These preliminary findings warrant further large-scale investigation.

Analysis of clinical features between active and inactive patients of Takayasu's arteritis with pulmonary arteries involvement

BackgroundThe aim of this study was to investigate the clinical characteristics of patients between active and inactive Takayasu's arteritis with pulmonary artery involvement (PTA) and to identify better markers of disease activity in these patients. MethodsSixty-four PTA patients in Beijing Chao-yang hospital (2011 to 2021) were included. According to National Institutes of Health criteria, 29 patients were in active stage and 35 were in inactive stage. Their medical records were collected and analyzed. ResultsCompared with inactive group, patients in active group were younger. More patients in active stage presented fever (41.38% vs 5.71%), chest pain (55.17% vs 20%), increased C-reactive protein (2.91 vs 0.46 mg/L), erythrocyte sedimentation rate (35.0 vs 9 mm/h), and platelet count (291 vs 221 × 109/L). Pulmonary artery wall thickening was more common in active group (51.72% vs 11.43%). These parameters were restored after treatment. The incidence of pulmonary hypertension was comparable between groups (34.48% vs 51.43%), but patients in active group had lower pulmonary vascular resistance (PVR) (361.0 vs 891.0 dyn·s·cm−5) and higher cardiac index (2.76 ± 0.72 vs 2.01 ± 0.58 L/min/m2). On multivariate logistic regression analysis, chest pain [odds ratio (OR) 9.37, 95%CI (1.98–44.38), P = 0.005], increased platelet count (>242.5 × 109/L) [OR 9.03, 95%CI (2.10–38.87), P = 0.003] and pulmonary artery wall thickening [OR 7.08, 95%CI (1.44–34.89), P = 0.016] were independently associated with disease activity. ConclusionChest pain, increased platelet count, and pulmonary artery wall thickening are potential new indicators of disease activity in PTA. Patients in active stage may have lower PVR and better right heart function.

Pulmonary endarterectomy in chronic thromboembolic pulmonary hypertension: Relationship between treated branches and outcome

BackgroundIn patients with chronic thromboembolic pulmonary hypertension (CTEPH) undergoing pulmonary endarterectomy (PEA) it is important to minimize residual obstructions, in order to achieve low postoperative pulmonary vascular resistances and better clinical results. The aim of the study was to test the hypothesis that the greater the number of pulmonary artery branches treated at surgery, the better the hemodynamic and clinical outcome after PEA. MethodsIn 564 consecutive CTEPH patients undergoing PEA the count of the number of treated branches was performed directly on the surgical specimens. Post-operative follow-up visits were scheduled at 3 months and 12 months after surgery including right heart catheterization and modified Bruce test. ResultsThe population was divided into tertiles based on the number of treated branches: Group 1 (from 4 to 30 treated branches, n = 194 patients); Group 2 (from 31 to 43 treated branches, n = 190 patients); Group 3 (from 44 to 100 treated branches, n = 180 patients). At 3 and at 12 months after PEA, after adjustment for confounders, patients in the highest tertile of treated branches had significantly lower values of pulmonary vascular resistance and higher values of pulmonary arterial compliance as compared to the other two groups (p < 0.002). Hospital mortality was 3% in Group 3, 6% in Group 2 and 10% in Group 1 (overall p = 0.035). ConclusionsIn CTEPH patients undergoing PEA, a higher number of treated pulmonary artery branches is associated with a better hemodynamic and a better clinical outcome at 3 months and 12 months after surgery.

COUNTERPOINT: Pulmonary Vascular Resistance 2.0— Shedding Light or Casting Shadows?

COUNTERPOINT: Pulmonary Vascular Resistance 2.0— Shedding Light or Casting Shadows?

Impact of diastolic pulmonary gradient and pulmonary artery pulse index on outcomes in heart transplant patients-Results from the Eurotransplant database.

Predicting complications associated with pulmonary hypertension (PH) after cardiac transplantation is an important factor when considering cardiac transplantation. The transpulmonary gradient (TPG) is recommended to quantify PH in transplant candidates. Nonetheless, PH remains a common driver of mortality. The diastolic pressure gradient (DPG) and pulmonary vascular resistance (PVR) can differentiate post- from combined pre- and post-capillary PH and may improve estimation of PH-associated risks. We used a large European cohort of transplant candidates to assess whether the pulmonary pulsatility index (PAPi), improves prediction of graft failure and mortality compared to DPG and PVR. Out of all patients undergoing heart transplantation between 2009 and 2019 in Eurotransplant member states (n = 10,465), we analyzed the impact of PH (mPAP > 25 mmHg) and right heart catheter hemodynamic data on graft failure and mortality within 1-5 years. In 1,407 heart transplant patients with PH (79% male, median age 54 years, IQR 39-69 years), the median PVR was 2.5 WU (IQR 1.6 WU) with a median mPAP (pulmonary arterial pressure) of 32 mmHg (IQR 9 mmHg). Patients with low (< 3 mmHg) DPG had a better 5 year survival than those with higher DPG (log rank p = 0.023). TPG, mPAP, PAPi, and PVR did not improve prediction of survival. Low PAPi (OR = 2.24, p < 0.001) and high PVR (OR = 2.12, p = 0.005) were associated with graft failure. PAPI and PVR are associated with graft failure in patients with PH undergoing cardiac transplantation. DPG is associated with survival in this cohort.

100 ANALYSIS OF PROGNOSTIC PREDICTORS AND DIFFERENCES BETWEEN SUBGROUPS OF PULMONARY ARTERIAL HYPERTENSION ASSOCIATED WITH PORTAL HYPERTENSION AND HIV INFECTION

Abstract Background Pulmonary arterial hypertension (PAH) represents a rare complication of both portal hypertension (Po-PAH) and HIV infection (HIV-PAH). Due to overlapping risk factors, in the latter patients there may frequently be a hepatic involvement that can cause portal hypertension, resulting in an overlap PAH form associated with both portal hypertension and HIV (HIV/Po-PAH). Methods A retrospective analysis was conducted on 204 patients with Po-PAH (128), HIV-PAH (41) and HIV/Po-PAH (35) referred to our centre from 1993 to 2021, with the aim of describing the clinical, functional and haemodynamic characteristics and identifying the prognostic determinants. At baseline, in patients with Po-PAH and HIV/Po-PAH, the severity of liver disease was estimated using the Child-Turcotte-Pugh (CTP) score, MELD score (Model for End-stage Liver Disease); instead, in patients with HIV-PAH and HIV/Po-PAH it was defined whether they received HAART (Highly Active Anti-Retroviral Therapy) and the CD4+ lymphocytes number. Data are expressed as median (interquartile range) and compared with Dunn's test. Prognostic determinants were identified by univariate and multivariate Cox-regression analysis. Survival was assessed using Kaplan Meier method. Patients were treated according to ESC/ERS guidelines. Results HIV-infected patients [40 (37-43) years] and HIV/Po-PAH [44 (39-48) years] are younger than Po-PAH patients [53 (44-60) years]; the exercise capacity assessed by the 6-minute walking test of patients with HIV/Po-PAH [516 (432-571) m] was superior to both patients with Po-PAH [426 (366-504) m] and HIV-PAH [448 (370-510) m], presumably justified by the demographic and haemodynamic differences between these groups. In fact, patients with concomitant portal hypertension (Po-PAH and HIV/Po-PAH) have a better haemodynamic profile than patients with HIV-PAH, specifically, lower pulmonary vascular resistance [6.2 (4.9-8.8) and 7.0 (5.5-11.2) WU vs 8.9 (7.5-12.2) WU] and higher cardiac index [3.1 (2.6-3.8) and 3.0 (2.7-3.7) l/min/m2 vs 2.6 (2.2-2.9) l/min/m2] and mixed venous oxygen saturation [70 (65-75) and 67 (62-71) % vs 61 (55-66)%] values. Despite these differences, the survival of the three groups of patients was not statistically different (5-year survival of patients with Po-PAH was 41%;of patients with HIV/Po-PAH was 46%; and of patients with HIV-PAH was 51%; log-rank test p-value= 0.059) and the prognostic factors that emerge at the multivariate analysis are only parameters associated with the underlying disease. In particular, the parameters independently associated with prognosis are, in patients with Po-PAH, only the CTP score [HR 1.665 (CI 1.153-2.403), p= 0.007]; in patients with HIV-PAH only the treatment with HAART [HR 0.283 (CI 0.119-0.675), p= 0.004]; in patients with HIV/Po-PAH both MELD-Na+ [HR 1.224 (CI 1.064-1.408), p= 0.005] and trans-hepatic venous gradient [HR 1.125 (CI 1.026-1.235), p= 0.013]. Conclusions in patients with Po-PAH, HIV-PAH, and HIV/Po-PAH adequately treated with PAH medications, the prognosis seems to be related to the underlying disease. This may explain why their survival is not statistically different despite significant demographic, exercise and hemodynamic differences.

Anesthetic management of hepatectomy for the patient with Fontan circulation: a case series.

Hepatectomy for patients with Fontan circulation consists of high central venous pressure and low pulmonary vascular resistance, and is challenging for physicians. We performed anesthetic management for hepatectomy in three patients with Fontan circulation. Massive bleeding and transfusion as well as careful management were needed. Open abdominal surgery had to be conducted instead of laparoscopic surgery for controlling bleeding in one case. We successfully performed general anesthesia using nitric oxide and inotropes while monitoring arterial pressure and central venous pressure in all the cases. To maintain Fontan circulation during hepatectomy, it is important to manage central venous pressure and ensure appropriate circulatory volume.

Abstract 10715: Therapeutic Efficacy of Drpitor1a, a Novel Dynamin-Related Protein 1 (DRP1) Inhibitor, in Preclinical Pulmonary Arterial Hypertension

Introduction: Dynamin-related protein 1 (DRP1) is a large GTPase that mediates mitotic fission (the division of mitochondria which is coordinated with mitosis, ensuring equitable distribution of mitochondria to daughter cells). In pulmonary arterial hypertension (PAH) pulmonary artery smooth muscle cells (PASMC), mitotic fission, and DRP1 activity are increased, contributing to its hyperproliferative phenotype. We investigated the therapeutic efficacy of Drpitor1a, a novel, small molecule, Drp1 GTPase inhibitor, in a rat PAH model. Methods: A single dose of monocrotaline (MCT, 60mg/kg, SC) or PBS was injected to female Sprague-Dawley rats on day 0 (n=20 for MCT and n=15 for PBS). On day 14, the development of PAH was confirmed by echocardiography and the rats were randomized for treatments. An indwelling catheter was implanted through the left jugular vein on day 15. Drpitor1a (1mg/kg) or normal saline (NS) was administered by IV every 48 hours from day 17 to day 27. Right ventricular (RV) structure and function were assessed on day 28 with echocardiography. Pulmonary hemodynamics was evaluated on day 29 using right heart catheterization (RHC). Results: MCT rats developed PAH with RV dysfunction on day 14. There was no statistical difference between the Drpitor1a and NS groups at randomization. At the endpoint, MCT+Drpitor1a rats, vs. MCT+NS rats, had a significantly reduced severity of pulmonary hypertension evident as longer pulmonary artery acceleration time (PAAT) and lower pulmonary vascular resistance index. Drpitor1a also improved RV function, evident as greater RV free wall thickening (RVFWT%), increased tricuspid annular plane systolic excursion (TAPSE), and increased cardiac index (CI). Drpitor1a regressed pulmonary artery medial thickening and inhibited RV hypertrophy without hepatological, renal or hepatic toxicities. Conclusion: Drpitor1a is a safe and effective treatment for preclinical PAH.

Influence of 24 h Simulated Altitude on Red Blood Cell Deformability and Hematological Parameters in Patients with Fontan Circulation.

Patients with Fontan circulation are particularly dependent on low pulmonary vascular resistance because their lungs are passively perfused. Hypoxia drives pulmonary vasoconstriction; thus, red blood cell (RBC) deformability and stability of hematological parameters might be of particular importance, because alterations during hypoxia might further influence circulation. This study aimed to measure respective parameters in patients with Fontan circulation exposed to normobaric hypoxia. A total of 18 patients with Fontan circulation (16 to 38 years) were exposed to normobaric hypoxia (15.2% ambient oxygen). Blood samples were taken in normoxia, after 24 h in hypoxia, and 60 min after return to normoxia. Blood count, RBC age distribution, EPO, RBC deformability, marker of RBC nitric oxide, oxidative state, and RBC ATP were measured. Hypoxia increased oxidative stress in RBC, but without affecting RBC deformability. RBC age distribution remained unaffected, although EPO concentrations increased, followed by a rise in reticulocyte count at an already high hematocrit. NO metabolism was not affected by hypoxia. Modest normobaric hypoxia for 24 h did not impair RBC deformability in patients with Fontan circulation; however, the oxidative system seemed to be stressed. Given the high baseline Hct in these patients, hypoxia-induced erythropoiesis could adversely affect rheology with more prolonged hypoxia exposure.

Operability of atrial septal defect with borderline pulmonary vascular resistance index: A study in developing country.

Pulmonary arterial hypertension secondary to atrial septal defect (ASD) is an important determinant of morbidity and mortality in defect closure. We aimed to compare perioperative outcome between preoperative borderline and low pulmonary vascular resistance index (≥4 WU.m2 and <4 WU.m2, respectively) in surgical closure of secundum atrial septal defect with concomitant pulmonary arterial hypertension. This was a single-center retrospective cohort study between January 2015 and January 2020. We classified patients with low and borderline PVRI who underwent ASD closure and recorded the perioperative outcomes. We analyzed a total of 183 patients with atrial septal defect and pulmonary arterial hypertension; 92 patients with borderline PVRI and 91 patients with low PVRI. Borderline pulmonary vascular resistance index was not associated with increased risk of postoperative mortality (p = 0.621; OR0.48, 95% CI 0.04-5.48), but associated with higher risk of overall morbidity in bivariate analysis (p = 0.002; OR3.28, 95% CI 1.5-6.72). Multivariate analysis showed positive association of borderline pulmonary vascular resistance index (p = 0.045; OR2.63, 95% CI 1.02-6.77) and preoperative tricuspid valve gradient ≥64 mmHg (p = 0.034; OR2.77, 95% CI 1.08-7.13) with overall morbidity. There is no difference in incidence of in-hospital mortality between preoperative borderline and low pulmonary vascular resistance index patients. However, preoperative borderline pulmonary vascular resistance index and tricuspid valve gradient ≥64 mmHg are associated with increased overall morbidity after surgical closure in secundum atrial septal defect patients with pulmonary arterial hypertension.

Determinants for residual symptoms in chronic thromboembolic pulmonary hypertension patients with mean pulmonary arterial pressure &amp;lt;25 mmHg after balloon pulmonary angioplasty

Abstract Background Balloon pulmonary angioplasty (BPA) improves hemodynamics and exercise capacity in inoperable patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, some symptoms, such as dyspnea on exertion, had remained in more than half of the patients even after BPA could decrease mean pulmonary artery pressure (PAP) &amp;lt;25 mmHg in a Japanese multicenter registry. In addition, previous report indicated that impaired exercise capacity was observed in about half of the patients with CTEPH who achieved mean PAP &amp;lt;25 mmHg at rest after BPA. Lowering mean PAP alone would not be sufficient as a treatment goal of BPA to eliminate residual symptoms in the patients. Purpose The purpose of this study was to elucidate the determinants of residual symptom in patients who had achieved mean PAP &amp;lt;25 mmHg after BPA. Methods Among 310 CTEPH patients who received BPA in our center, 217 patients (70.0%) could achieve mean PAP &amp;lt;25mmHg at six months after the final BPA were enrolled in this study. The patients were divided into two groups based on the necessity of additional BPA due to residual symptoms; additional BPA group and non-additional BPA group. Clinical parameters including resting hemodynamics at 6 months follow up were retrospectively investigated between the two groups. Results Additional BPA had been underwent in 67 patients (30.9%). No significant differences in mean PAP were identified between the additional and non-additional BPA groups (20.4±2.5 mmHg vs. 19.7±2.7 mmHg, p=0.106). In additional BPA group, cardiac index (CI), heart rate (HR) and percutaneous oxygen saturation (SpO2) was lower than non-additional BPA group, and pulmonary vascular resistance (PVR) was higher than non-additional BPA group (CI, 2.51±0.41 L/min/m2 vs. 2.72±0.56 L/min/m2, p=0.016, HR, 62.9±9.7 bpm vs. 67.8±10.8 bpm, p=0.003, SpO2, 94.3±3.7% vs. 95.9±3.5%, p&amp;lt;0.001, PVR, 3.67±1.18 W.U. vs. 3.11±1.09 W.U. p=0.001). In a multivariate analysis, CI, SpO2 and PVR were associated with residual symptoms requiring additional treatment in patients with mean PAP &amp;lt;25mmHg after BPA (95% confidence interval: CI; 0.221–0.900, SpO2; 0.825–0.976, PVR; 1.000–1.785). Conclusion Low CI and SpO2 and High PVR were determinants for residual symptoms in CTEPH patients who could achieve mean PAP &amp;lt;25 mmHg after BPA. To eliminate the residual symptoms, treatment goals of BPA in inoperable CTEPH patients should be increasing CI and SpO2 and lowering PVR in addition to normalizing mean PAP. Funding Acknowledgement Type of funding sources: None.