Bioreactance assessment of cardiac output lacks reliability for the follow-up of patients with pulmonary hypertension.

Cardiac output (CO) is one of the primary prognostic factors evaluated during the follow-up of patients treated for pulmonary hypertension (PH). It is recommended that it be measured using the thermodilution technique during right heart catheterization. The difficulty to perform iterative invasive measurements on the same individual led us to consider a non-invasive option. The aims of the present study were to assess the agreement between CO values obtained using bioreactance (Starling™ SV) and thermodilution, and to evaluate the ability of the bioreactance monitor to detect patients whose CO decreased by more than 15% during follow-up and, accordingly, its usefulness for patient monitoring. A prospective cohort study evaluating the performance of the Starling™ SV monitor was conducted in patients with clinically stable PH. Sixty patients referred for hemodynamic assessment were included. CO was measured using both the thermodilution technique and bioreactance during two follow-up visits. A total of 60 PH patients were included. All datasets were available at the baseline visit (V0) and 50 of them were usable during the follow-up visit (V1). Median [IQR] CO was 4.20 l/min [3.60-4.70] when assessed by bioreactance, and 5.30 l/min [4.57-6.20] by thermodilution (p<0.001). The Spearman correlation coefficient was 0.51 [0.36-0.64], and the average deviation on Bland-Altman plot was -1.25 l/min (95% CI [-1.48-1.01], p<0.001). The ability of the monitor to detect a variation in CO of more than 15% between two follow-up measurements, when such variation existed using thermodilution, was insufficient for clinical practice (AUC = 0.54, 95% CI [0.33-0.75]).

Retrospective evaluation of a right heart parameter score in the assessment of precapillary pulmonary hypertension in dogs (2017-2021): 135 cases.

OBJECTIVE: To determine if emergency and critical care residents can identify moderate to severe precapillary pulmonary hypertension on cardiologist-obtained cineloops using a pulmonary hypertension score (PHS) and report the interobserver variability of the PHS. DESIGN: Multicenter, retrospective, case-control study from 2017 to 2021. SETTING: Private referral center and veterinary teaching hospital. ANIMALS: One hundred and thirty-five client-owned dogs that underwent diagnostic echocardiography. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Medical records of dogs with stage B1 myxomatous mitral valve disease (MMVD) and dogs diagnosed with precapillary pulmonary hypertension (PCPH) via echocardiograms were reviewed. Dogs were categorized by a cardiologist into 5 groups (normal, B1 MMVD, mild, moderate, and severe PCPH) based on Doppler pulmonary pressure gradients and right heart morphology. Cineloops from each case were subjectively evaluated by emergency and critical care residents for the presence of right atrial and ventricular enlargement, right ventricular hypertrophy, interventricular septal flattening, and pulmonary artery and trunk enlargement to form a composite pulmonary hypertension score out of 8 (PHS8). When available, signs of peritoneal effusion and distention of the caudal vena cava were subjectively assessed to generate a pulmonary hypertension score out of 10 (PHS10). There was excellent discrimination of moderate to severe PCPH versus grouped absent to mild PCPH using PHS8 (area under the receiver operator curve [AUC] [95% confidence interval, CI] = 0.90 [0.84-0.95], P < 0.0001) and PHS10 (AUC [95% CI] = 0.89 [0.81-0.97], P < 0.0001). PHS8 ≥3 was 64% sensitive and 98% specific for moderate to severe PCPH (positive likelihood ratio [LR+] 32, negative likelihood ration [LR-] 0.37). PHS10 ≥ 3.3 was 64% sensitive and 92% specific for moderate to severe PCPH (LR+ 8, LR- 0.39). Interobserver agreement was good to excellent (intraclass correlation coefficient [ICC] = 0.74 [95% CI: 0.66-0.80], n = 135). CONCLUSIONS: Residents identified moderate to severe PCPH in dogs using PHS on cineloops previously obtained by a cardiologist. The interrater agreement was good to excellent with limited training. Prospective studies to determine if residents can obtain diagnostic images for PHS are warranted.

Risk assessment and real-world outcomes in chronic thromboembolic pulmonary hypertension: insights from a UK pulmonary hypertension referral service.

OBJECTIVES: This study was conducted to evaluate the ability of risk assessment to predict healthcare resource utilisation (HCRU), costs, treatments, health-related quality of life (HRQoL) and survival in patients diagnosed with chronic thromboembolic pulmonary hypertension (CTEPH). DESIGN: Retrospective observational study. SETTING: Pulmonary hypertension referral centre in the UK. PARTICIPANTS: Adults diagnosed with CTEPH between 1 January 2012 and 30 June 2019 were included. Cohorts were retrospectively defined for operated patients (received pulmonary endarterectomy (PEA)) and not operated; further subgroups were defined based on risk score (low, intermediate or high risk for 1-year mortality) at diagnosis. PRIMARY AND SECONDARY OUTCOME MEASURES: Demographics, clinical characteristics, comorbidities, treatment patterns, HRQoL, HCRU, costs and survival outcomes were analysed. RESULTS: Overall, 683 patients were analysed (268 (39%) operated; 415 (61%) not operated). Most patients in the operated and not-operated cohorts were intermediate risk (63%; 53%) or high risk (23%; 31%) at diagnosis. Intermediate-risk and high-risk patients had higher HCRU and costs than low-risk patients. Outpatient and accident and emergency visits were lower postdiagnosis for both cohorts and all risk groups versus prediagnosis. HRQoL scores noticeably improved in the operated cohort post-PEA, and less so in the not-operated cohort at 6-18 months postdiagnosis. Survival at 5 years was 83% (operated) and 49% (not operated) and was lower for intermediate-risk and high-risk patients compared with low-risk patients. CONCLUSIONS: Findings from this study support that risk assessment at diagnosis is prognostic for mortality in patients with CTEPH. Low-risk patients have better survival and HRQoL and lower HCRU and costs compared with intermediate-risk and high-risk patients.

Echocardiography Assessment of Left Ventricular Function in Extremely Preterm Infants, Born at Less Than 28 Weeks' Gestation, With Bronchopulmonary Dysplasia and Systemic Hypertension.

BACKGROUND: The survival of smaller and more immature premature infants has been associated with lifelong cardiorespiratory comorbidities. Infants with bronchopulmonary dysplasia (BPD) undergo routine screening echocardiography to evaluate for development of chronic pulmonary hypertension, a late manifestation of pulmonary vascular disease. METHODS: Our aim was to evaluate left ventricular (LV) performance in infants with BPD and pulmonary vascular disease who developed systemic hypertension. We hypothesized that infants with hypertension were more likely to have impaired LV performance. We present a single-center cross-sectional study of premature infants born at less than 28 0/7 weeks' gestational age with a clinical diagnosis of BPD. Infants were categorized by the systolic arterial pressure (SAP) at time of echocardiography as hypertensive (SAP ≥90 mm Hg) or normotensive (SAP <90 mm Hg). Sixty-four patients were included. RESULTS: Infants with hypertension showed altered LV diastolic function with prolonged tissue Doppler imaging-derived isovolumic relaxation time (54.2 ± 5.1 vs 42.9 ± 8.2, P < .001), lower E:A, and higher E:e'. Indices of left heart volume/pressure loading (left atrium:aorta and LV end-diastolic volume [6.1 ± 2 vs 4.2 ± 1.2, P < .001]) were also higher in the hypertensive group. Finally, infants in the hypertensive group had higher pulmonary vascular resistance index (4.42 ± 1.1 vs 3.69 ± 0.8, P = .004). CONCLUSIONS: We conclude that extremely preterm infants with BPD who develop systemic hypertension are at risk of abnormal LV diastolic dysfunction. Increased pulmonary vascular resistance index in the hypertensive group may relate to pulmonary venous hypertension secondary to LV dysfunction. This is an important consideration in this cohort when selecting the physiologically most appropriate treatment.

Impact of selexipag use within 12 months of pulmonary arterial hypertension diagnosis on hospitalizations and medical costs: A retrospective cohort study.

BACKGROUND: Oral selexipag, a prostacyclin pathway agent (PPA), is effective in patients with pulmonary arterial hypertension (PAH). The objective of this study is to assess the impact of initiating oral selexipag within 12 months of diagnosis on health outcomes. METHODS: This retrospective cohort study used data from Optum's de-identified Clinformatics® Data Mart Database. PAH patients between 1 October 2015 and 30 September 2019 were included. Patients were also required to have received PAH medication within 12 months of their initial diagnosis. Study groups included patients who initiated selexipag within 12 months of PAH diagnosis (SEL ≤ 12) and those who did not initiate any PPA within 12 months of PAH diagnosis (No PPA ≤ 12). Inverse probability of treatment weighting was used to remove potential confounding between groups. Cox and Poisson regression models were used to compare hospitalization and disease progression. Generalized linear model with gamma distribution and log link was used to compare costs. RESULTS: SEL ≤ 12 had lower rate of all-cause hospitalizations (rate ratio: 0.76, 95% confidence interval [CI]: 0.60, 0.96) versus no PPA ≤ 12, but no differences in PAH-related hospitalization rate (rate ratio: 1.03, 95% CI: 0.79, 1.33) or risk of disease progression (hazard ratio: 1.01, 95% CI: 0.71, 1.44). SEL ≤ 12 incurred lower all-cause (mean difference: -$23 623; 95% CI: -35 537, -8512) and PAH-related total medical costs (mean difference: -$12 927; 95% CI: -19 559, -5679) versus no PPA ≤ 12. CONCLUSION: Selexipag initiation within 12 months of PAH diagnosis demonstrated reductions in all-cause hospitalization rate and medical costs.

Impact of cancer on the prevalence, management, and outcome of patients with chronic thromboembolic pulmonary hypertension.

INTRODUCTION: Chronic thromboembolic pulmonary hypertension (CTEPH) results from unresolved thrombotic obstruction of the pulmonary vasculature. Cancer is a known risk factor for CTEPH. This study aimed to determine the impact of cancer on the prevalence, management, and outcomes of patients with CTEPH. MATERIALS AND METHODS: In this retrospective study involving 99 patients sequentially diagnosed with CTEPH in our hospital, the prevalence of 10 comorbid conditions including a past history of cancer at the time of CTEPH diagnosis were calculated. RESULTS: Among the 99 patients, 17 (17%) had a history of cancer. Breast cancer (n = 6) was the most common cancer type, followed by gastrointestinal cancer (n = 3), uterine cancer (n = 2), and malignant lymphoma (n = 2). Between patients with and without cancer, there were no differences in the demographics, severity of CTEPH, and management; however, the 5-year survival rate was lower for patients with cancer (65%) than for those without (89%). In addition, patients with cancer had significantly worse survival than those without (p = 0.03 by log-rank test). During follow-up, nine patients developed cancer after the diagnosis of CTEPH. Among the 99 patients, 13 died during follow-up, 6 (46%) of whom died of cancer. CONCLUSIONS: 17% of our patients with CETPH were diagnosed with cancer, with breast and gastrointestinal tract cancers being the most common. Cancer comorbidity was associated with a poor prognosis and contributed to death in 46% of deceased patients. The impact of cancer on CTEPH should be further evaluated in the future.

Cost-utility of ambrisentan and bosentan for pediatric pulmonary arterial hypertension.

INTRODUCTION: Despite the increasing evidence supporting the efficacy of ambrisentan and bosentan in improving functional classes among pediatric patients with pulmonary arterial hypertension (PAH), there is a lack of information regarding their cost implications. Therefore, the objective of this study is to assess the cost-utility of bosentan compared to ambrisentan for the treatment of pediatric patients with PAH in Colombia. METHODS: We employed a Markov model to estimate the costs and quality-adjusted life-years (QALYs) associated with the use of ambrisentan or bosentan in pediatric patients diagnosed with pulmonary arterial hypertension (PAH). To ensure the reliability of our findings, we conducted sensitivity analyses to assess the robustness of the model. In our cost-effectiveness analysis, we evaluated the outcomes at a willingness-to-pay (WTP) threshold of US$5,180. RESULTS: The expected annual cost per patient receiving ambrisentan was estimated to be $16,055 (95% CI 15,937 -16,172), while for bosentan it was $14,503 (95% CI 14,489 -14,615). The QALYs per person estimated for ambrisentan were 0.39 (95% CI 0.381-0.382), whereas for bosentan it was 0.40 (95% CI 0.401-0.403). CONCLUSION: Our economic evaluation shows that ambrisentan is not cost-effective regarding bosentan to in treating pulmonary arterial hypertension in C.

Continuous long-term heart rate variability and risk assessment in pulmonary hypertension.

OBJECTIVE: Current multimodal risk assessment for pulmonary hypertension (PH) has been redefined with a simplified assessment for follow-up in the new European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines. Follow-up risk assessment parameters include WHO functional class, 6 min walk test and N-terminal pro-brain natriuretic peptide. Although these parameters have prognostic implications assessment reflect data relating to specific time points. METHODS: Patients diagnosed with PH received an implantable loop recorder (ILR) to monitor daytime and night-time heart rate (HR), HR variability (HRV) and daily physical activity. Associations between the ILR measurements and established risk parameters were analysed using correlations, linear mixed models as well as logistical mixed models for addressing the ESC/ERS risk-score. RESULTS: 41 patients (median age: 56 years, range: 44-61.5 years) were included. Continuous monitoring had a median duration of 755 days (range: 343-1138 days), totalling 96 patient-years. In the linear mixed models, HRV and physical activity indexed by daytime HR (PAiHR) were significantly associated with the ERS/ERC risk parameters. In a logistical mixed model, HRV revealed a significant difference between 1-year mortality (<5% vs >5%) (p=0.027) with an OR of 0.82 for being in the group with 1-year mortality >5% for every increase by one HRV unit. CONCLUSIONS: Risk assessment in PH can be refined with continuous monitoring of HRV and PAiHR. These markers were associated with the ESC/ERC parameters. Our study with continuous risk stratification in PH demonstrated that a lower HRV predict worse prognosis.

Assessment of Right Ventricular Function-a State of the Art.

PURPOSE OF REVIEW: The right ventricle (RV) has a complex geometry and physiology which is distinct from the left. RV dysfunction and failure can be the aftermath of volume- and/or pressure-loading conditions, as well as myocardial and pericardial diseases. RECENT FINDINGS: Echocardiography, magnetic resonance imaging and right heart catheterisation can assess RV function by using several qualitative and quantitative parameters. In pulmonary hypertension (PH) in particular, RV function can be impaired and is related to survival. An accurate assessment of RV function is crucial for the early diagnosis and management of these patients. This review focuses on the different modalities and indices used for the evaluation of RV function with an emphasis on PH.

The Effect of Perioperative Fluid Management and Operative Modifications on Mortality and Morbidity in Patients Undergoing Pulmonary Endarterectomy.

INTRODUCTION: Chronic thromboembolic pulmonary hypertension (CTEPH) is a severe disease treated with pulmonary endarterectomy. Our study aims to reveal the differences in liquid modalities and operation modifications, which can affect the patients' mortality and morbidity. METHODS: One hundred twenty-five patients who were diagnosed with CTEPH and underwent pulmonary thromboendarterectomy (PTE) at our center between February 2011 and September 2013 were included in this retrospective study with prospective observation. They were in New York Heart Association functional class II, III, or IV, and mean pulmonary artery pressure was > 40 mmHg. There were two groups, the crystalloid (Group 1) and colloid (Group 2) liquid groups, depending on the treatment fluids. P-value < 0.05 was considered statistically significant. RESULTS: Although the two different fluid types did not show a significant difference in mortality between groups, fluid balance sheets significantly affected the intragroup mortality rate. Negative fluid balance significantly decreased mortality in Group 1 (P<0.01). There was no difference in mortality in positive or negative fluid balance in Group 2 (P>0.05). Mean duration of stay in the intensive care unit (ICU) for Group 1 was 6.2 days and for Group 2 was 5.4 days (P>0.05). Readmission rate to the ICU for respiratory or non-respiratory reasons was 8.3% (n=4) in Group 1 and 11.7% (n=9) in Group 2 (P>0.05). CONCLUSION: Changes in fluid management have an etiological significance on possible complications in patient follow-up. We believe that as new approaches are reported, the number of comorbid events will decrease.

Cost-Effectiveness Analysis of Macitentan in Comparison With Bosentan in the Treatment of Pulmonary Arterial Hypertension in Iran.

OBJECTIVES: Pulmonary arterial hypertension (PAH) is a chronic and progressive disease that, if left untreated, shortens the life expectancy of patients. Endothelin receptor antagonists, such as macitentan and bosentan, play an essential role in improving the patient's symptoms, quality of life, and life expectancy. This study aimed to evaluate the cost-utility of macitentan compared with bosentan in treating PAH from the health system perspective in Iran. METHODS: For evaluating the cost-effectiveness of macitentan, a Markov model consisting of 5 states, functional class (FC) I, FC II, FC III, FC IV, and death, was designed using the TreeAge software. The lifetime time horizon and a 3-month cycle length were set. Patients entered the model from FC II or FC III states based on the initial probabilities. Costs were measured in US dollars (USD), and outcomes were measured in terms of quality quality-adjusted life-years (QALYs). Consequently, the incremental cost-effectiveness ratio (ICER) was calculated. In addition, sensitivity analysis was performed to determine the robustness of the model by examining the possible effects of uncertainties on the final result. RESULTS: The costs of treatment with macitentan and bosentan in PAH in Iran were calculated at 19 429 and 17 246 USD, and the outcomes were 4.02 and 3.04 QALYs, respectively. Therefore, ICER was calculated at 2233.46 USD/QALY. One-way sensitivity analysis demonstrates that the model is robust; nevertheless, it is most sensitive to the price of macitentan and bosentan. CONCLUSION: Treatment with macitentan was associated with both higher costs and QALYs than bosentan. Nevertheless, it is considered the cost-effective treatment strategy in Iran given that the calculated ICER falls below the willingness to pay threshold.

Pulmonary Hypertension Phenotype Can Be Identified in Heart Failure With Reduced Ejection Fraction Using Echocardiographic Assessment of Pulmonary Artery Pressure With Supportive Use of Pressure Reflection Variables.

BACKGROUND: Pulmonary hypertension (PH) is frequent in patients with heart failure and reduced ejection fraction (HFrEF) with 2 different phenotypes: isolated postcapillary PH (IpcPH) and, with the worst prognosis, combined pre- and postcapillary PH (CpcPH). The aims of the present echocardiography study were to investigate (1) the ability to identify PH phenotype in patients with HFrEF using the newly adopted definition of PH (mean pulmonary artery pressure >20 mm Hg) and (2) the relationship between PH phenotype and right ventricular (RV) function. METHODS: One hundred twenty-four patients with HFrEF consecutively referred for heart transplant or heart failure workup were included with echocardiography and right heart catheterization within 48 hours. We estimated systolic pulmonary artery pressure (sPAPDoppler) and used a method to detect increased pulmonary vascular resistance (>3 Wood units) based on predefined thresholds of 3 pressure reflection (PRefl) variables (the acceleration time in the RV outflow tract [RVOT], the interval between peak RVOT and peak tricuspid regurgitant velocity, and the RV pressure augmentation following peak RVOT velocity). RESULTS: Using receiver operator characteristic analysis in a derivation group (n = 62), we identified sPAPDoppler ≥35 mm Hg as a cutoff that in a test group (n = 62) increased the likelihood of PH 6.6-fold. The presence of sPAPDoppler >40 mm Hg and 2 or 3 positive PRefl variables increased the probability of CpcPH 6- to 8-fold. A 2-step approach with primarily assessment of sPAPDoppler and the supportive use of PRefl variables in patients with mild/moderate PH (sPAPDoppler 41-59 mm Hg) showed 76% observer agreement and a weighted kappa of 0.63. The steady-state (pulmonary vascular resistance) and pulsatile (compliance, elastance) vascular loading are increased in both IpcPH and CpcPH with a comparable degree of RV dysfunction. CONCLUSIONS: The PH phenotype can be identified in HFrEF using standard echocardiographic assessment of pulmonary artery pressure with supportive use of PRefl variables in patients with mild to moderate PH.

Clinical assessment for pulmonary hypertension in interstitial lung disease.

BACKGROUND: Pulmonary hypertension (PH) is an important complication of interstitial lung disease (ILD), as its development confers a poor prognosis. There are no specific recommendations for methods of assessment for PH in ILD populations. AIMS: To determine current assessment practices for PH in an Australian ILD centre. METHODS: In the Austin Health ILD database, 162 consecutive patients with idiopathic pulmonary fibrosis or connective tissue disease-associated ILD were identified and retrospectively evaluated for methods of PH assessment with transthoracic echocardiography (TTE), serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and right heart catheterisation (RHC) in relation to patient demographic and physiological parameters. RESULTS: The median follow-up was 30 (14.4-56.4) months. At baseline, vital capacity was 80.0 ± 18.4% predicted, and diffusing capacity for carbon monoxide was 59.6 ± 15.2% predicted. Evaluation for PH was performed in 147 (90.7%) patients, among whom 105 (64.8%) had TTE performed at least once. At the initial TTE, 33.7% patients had high probability of PH, defined as RVSP >40 mmHg + RAp and/or right ventricular dysfunction. At the time of the most recent TTE, these criteria were met in 45 (52.3%) patients. Elevated serum NT-proBNP levels during the first year were observed in 47 (38.8%) patients. Only 14 (8.6%) patients had RHC. CONCLUSION: Our institutional PH assessment practice in ILD demonstrates a substantial prevalence of probable PH at baseline. As new therapies emerge for the treatment of PH in ILD, well-defined screening practices are important in this population for early identification and optimal management.

Characteristics, Long-term Survival, and Risk Assessment of Pediatric Pulmonary Arterial Hypertension in China: Insights From a National Multicenter Prospective Registry.

BACKGROUND: Registry-based studies of pediatric pulmonary arterial hypertension (PPAH) are scarce in developing countries, including China. The PPAH risk assessment tool needs further evaluation and improvement. RESEARCH QUESTION: What are the characteristics and long-term survival of PPAH in China and what is the performance of the PPAH risk model in Chinese patients? STUDY DESIGN AND METHODS: Patients with PAH were enrolled in the national prospective multicenter registry from August 2009 through December 2019. Children 3 months to 18 years of age at the time of PAH diagnosis were analyzed. RESULTS: A total of 247 children with PAH were enrolled. The median patient age was 14.8 years, and 58.3% of patients were female. Most patients had a diagnosis of PAH associated with congenital heart disease (CHD; 61.5%) and idiopathic or heritable PAH (37.7%). The median time from symptom onset to PAH diagnosis was 24 months. The mean pulmonary artery pressure and pulmonary vascular resistance index were 70.78 ± 19.80 mm Hg and 21.82 ± 11.18 Wood Units·m2, respectively. Patients with CHD-associated PAH experienced a longer diagnostic delay and demonstrated higher pulmonary artery pressure, but better cardiac performance, than those with idiopathic or heritable PAH. An increased number of patients received targeted therapy at the last follow-up compared with baseline. The 5- and 10-year survival rates of the entire cohort were 74.9% and 55.7%, respectively, with better survival in patients with CHD-associated PAH than in those with idiopathic or heritable PAH. Patients with low risk had better survival than those with high risk according to the simplified noninvasive risk score model with weight, function class, and echocardiographic right ventricular size, both at baseline and follow-up. INTERPRETATION: Patients with PPAH in China showed severely compromised hemodynamics with marked diagnostic delay. The long-term survival of PPAH is poor despite the increased usefulness of targeted drugs. The simplified noninvasive risk model demonstrated good performance for predicting survival in Chinese children with PAH. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01417338; URL: www. CLINICALTRIALS: gov.

Surgical Repair of Truncus Arteriosus: A Long-Term Hemodynamic Assessment.

Background: Unrepaired truncus arteriosus (TA) carries poor prognosis due to complications of unrestricted pulmonary flow, truncal valve insufficiency, and pulmonary vascular disease. Currently, the hemodynamic profile of adults late after TA repair is unknown. We reviewed the hemodynamics, prevalence, and pathophysiology of pulmonary hypertension (PH) in this population. Methods: Eighteen adult patients with repaired TA who underwent cardiac catheterization at Mayo Clinic, MN, between 1997 and 2021 were identified. PH was defined as either precapillary (mean pulmonary artery pressure [mPAP] ≥25 mm Hg, pulmonary artery wedge pressure [PAWP] ≤15 mm Hg, and pulmonary vascular resistance [PVR] >3 Wood units), isolated postcapillary (mPAP ≥25, PAWP >15, PVR ≤3), or combined (mPAP ≥25, PAWP >15, and PVR >3). Diastolic pressure and transpulmonary gradients were used as ancillary data for classification. Results: Mean age at catheterization was 34 ± 10 years. Mean right ventricular (RV) systolic pressure was 82 ± 22.6 mm Hg, mean right and left mPAPs 28.1 ± 16.2 and 27.9 ± 11.9 mm Hg, respectively. Seven patients (41.2%) had PAWP >15 mm Hg and, among those undergoing arterial catheterization, 7 (53.8%) had a left ventricular (LV) end-diastolic pressure >15 mm Hg. PH was diagnosed in 13 patients (72.2%): 6 (33.3%) precapillary, 4 (22.2%) isolated postcapillary, and 3 (16.7%) combined. PAWP >15 mm Hg was associated with male sex (P = .049),

Five year risk assessment and treatment patterns in patients with chronic thromboembolic pulmonary hypertension.

AIMS: Repeated risk assessments and treatment patterns over long time are sparsely studied in chronic thromboembolic pulmonary hypertension (CTEPH); thus, we aimed to investigate changes in risk status and treatment patterns in incident patients with CTEPH over a 5 year period. METHODS AND RESULTS: Descriptive and explorative study including 311 patients diagnosed with CTEPH 2008-2019 from the Swedish pulmonary hypertension registry, stratified by pulmonary endarterectomy surgery (PEA). Risk and PH-specific treatment were assessed in surgically treated (PEA) and medically treated (non-PEA) patients at diagnosis and up to 5 years follow-up. Data are presented as median (Q1-Q3), count or per cent. Prior to surgery, 63% in the PEA-group [n = 98, age 64 (51-71) years, 37% female] used PH-specific treatment and 20, 69, and 10% were assessed as low, intermediate or high risk, respectively. After 1 year post-surgery, 34% had no PH-specific treatment or follow-up visit registered despite being alive at 5 years. Of patients with a 5 year visit (n = 23), 46% were at low and 54% at intermediate risk, while 91% used PH-specific treatment. In the non-PEA group [n = 213, age 72 (65-77) years, 56% female], 28% were assessed as low, 61% as intermediate and 11% as high risk. All patients at high risk versus 50% at low risk used PH-specific treatment. The 1 year mortality was 6%, while the risk was unchanged in 57% of the patients; 14% improved from intermediate to low risk, and 1% from high to low risk. At 5 years, 27% had a registered visit and 28% had died. Of patients with a 5 year visit (n = 58), 38% were at low, 59% at intermediate and 1% at high risk, and 86% used PH-specific treatment. CONCLUSIONS: Risk status assessed pre-surgery did not foresee long-term post-PEA risk and pre-surgery PH-specific treatment did not foresee long-term post-PEA treatment. Medically treated CTEPH patients tend to remain at the same risk over time, suggesting a need for improved treatment strategies in this group.

Cardiopulmonary exercise testing for treatment effect assessment in chronic thromboembolic pulmonary hypertension patients.

Aim      To determine possibilities of the cardiopulmonary stress test (CPST) as an unbiassed, noninvasive method for evaluation of the effect of managing patients with chronic thromboembolic pulmonary hypertension (CTEPH).Material and methods  This study included 37 patients with CTEPH, 24 men (mean age, 53±15 years) and 13 women (mean age, 58±8.5 years). The diagnosis was verified and theCoperability was assessed according to 2015 European Society of Cardiology Clinical Guidelines for the Diagnosis and Treatment of Pulmonary Hypertension (PH). The surgical treatment was used in 65 % (n=24) of CTEPH patients: the group with pulmonary thromboendarterectomy constituted 35 % (n=13); the group with balloon pulmonary angioplasty 30% (n=11); and the conservative tactics was used in 27 % (n=10) of patients.Results Baseline CPST parameters significantly correlated with parameters of right heart catheterization (RHC): mixed venous oxygen saturation (SvO2) significantly positively correlated with V´O2peak (r=0.640, p<0.05), V´O2 / heart rate (HR) (r=0.557; p<0.001), PETCO2 peak (r=0.598, p<0.05), and V´E / V´CO2 (r=0.587; p<0.001); cardiac output (CO) correlated with V´O2 / HR (r=0.555, p<0.001), PETCO2peak (r= -0.476; p<0.05 and r=0.555, p<0.001 for ´E / V´CO2). In repeated testing, the physical working capacity (V´O2peak) increased only in patients after the surgical treatment of CTEPH. Importantly in this process, significant correlations remained between a number of CPST and RHC parameters: SvO2 correlated with V´O2peak (r=0.743; p<0.05), V´O2 /HR (r=0.627; p<0.001), PETCO2peak (r=0.538; p<0.05), and V´E / V´CO2 (r=0.597; p<0.001); V´O2 / HR, PETCO2peak, and V´E / V´CO2 significantly correlated with CO (r=0.645, p<0.001; r= -0.516, p<0.001, and r=0.555, p<0.001, respectively.Conclusion      CPST can be used as a noninvasive instrument for evaluation of the effect of CTEPH treatment, particularly in the absence of echocardiographic data for residual PH.

Risk assessment tools for survival prognosis: An era of new surrogacy endpoints for clinical outcome measurement in pulmonary arterial hypertension clinical trials?

Developing a new medication in a rare disease indication like pulmonary arterial hypertension (PAH) is very challenging. This is especially true now that clinical trials often employ time to clinical worsening (TTCW) as an endpoint (thus requiring a relatively large and lengthy trial) and since patients are more frequently prescribed combination therapy. During the last few decades, several tools have been developed to predict mortality in PAH and have demonstrated generally good discrimination. The objective of this review article is to assess the available data on the different tools and methods described in the literature and identify potential candidates that could be used as surrogate endpoints in pivotal randomized clinical trials in future. Some of these tools have been validated in various registries and in post-hoc analyses of clinical trial data, but none have been assessed in a prospective clinical trial and we still lack the evidence necessary for endorsement by health authorities. In this review, we identify several promising options that warrant further investigation as potential surrogate endpoints in clinical trials to replace TTCW or 6-minute walk distance. Prospective inclusion of such tools in new clinical trials may help build a stronger surrogacy for prognosis of disease progression and mortality.