Association of non-insulin-based insulin resistance indices with disease severity and adverse outcome in idiopathic pulmonary arterial hypertension: a multi-center cohort study.

BACKGROUND: Insulin resistance (IR) plays an important role in the pathophysiology of cardiovascular disease. Recent studies have shown that diabetes mellitus and impaired lipid metabolism are associated with the severity and prognosis of idiopathic pulmonary arterial hypertension (IPAH). However, the relationship between IR and pulmonary hypertension is poorly understood. This study explored the association between four IR indices and IPAH using data from a multicenter cohort. METHODS: A total of 602 consecutive participants with IPAH were included in this study between January 2015 and December 2022. The metabolic score for IR (METS-IR), triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, triglyceride and glucose (TyG) index, and triglyceride-glucose-body mass index (TyG-BMI) were used to quantify IR levels in patients with IPAH. The correlation between non-insulin-based IR indices and long-term adverse outcomes was determined using multivariate Cox regression models and restricted cubic splines. RESULTS: During a mean of 3.6 years' follow-up, 214 participants experienced all-cause death or worsening condition. Compared with in low to intermediate-low risk patients, the TG/HDL-C ratio (2.9 ± 1.7 vs. 3.3 ± 2.1, P = 0.003) and METS-IR (34.5 ± 6.7 vs. 36.4 ± 7.5, P < 0.001) were significantly increased in high to intermediate-high risk patients. IR indices correlated with well-validated variables that reflected the severity of IPAH, such as the cardiac index and stroke volume index. Multivariate Cox regression analyses indicated that the TyG-BMI index (hazard ratio [HR] 1.179, 95% confidence interval [CI] 1.020, 1.363 per 1.0-standard deviation [SD] increment, P = 0.026) and METS-IR (HR 1.169, 95% CI 1.016, 1.345 per 1.0-SD increment, P = 0.030) independently predicted adverse outcomes. Addition of the TG/HDL-C ratio and METS-IR significantly improved the reclassification and discrimination ability beyond the European Society of Cardiology (ESC) risk score. CONCLUSIONS: IR is associated with the severity and long-term prognosis of IPAH. TyG-BMI and METS-IR can independently predict clinical worsening events, while METS-IR also provide incremental predictive performance beyond the ESC risk stratification.

Prognostic Value of Follicle-Stimulating Hormone Levels in Predicting Survival in Men With Idiopathic Pulmonary Arterial Hypertension.

The objective of the study was to assess the association between changes in plasma follicle-stimulating hormone (FSH) and the potential effect on idiopathic pulmonary arterial hypertension (IPAH) in male patients. A total of 116 male patients with IPAH and 53 healthy controls were included from XX Hospital. Plasma FSH concentration was assessed in all participants. Receiver operating characteristic curves were used to assess the mortality risk. Kaplan-Meier curve and Cox regression analyses were used to predict the value of FSH on the survival rate of male IPAH patients. The plasma FSH concentration in the IPAH group was significantly higher than that in the control group (p = .017). Nonsurvivors had significantly higher levels of FSH than survivors (p < .0001). FSH levels were positively correlated with World Health Organization Functional Class, mean pulmonary artery pressure, and pulmonary vascular resistance (PVR; p = .023, p < .0001, and p < .0001, respectively) and negatively correlated with 6-min walk distance (6MWD) and cardiac output (CO; p = .004 and p = .010). Cox regression model analysis showed that the levels of FSH were also the independent factors of mortality in male IPAH patients (p < .0001). The IPAH patients with higher FSH levels had higher PVR, lower 6MWD, CO, and a lower survival rate (p = .042, p = .003, p = .029, and p < .0001, respectively). Therefore, we identified that increased FSH levels were associated with disease severity in male patients with IPAH and independently predicted risk of disease and poor survival rate.

New prognostic markers in pulmonary arterial hypertension: CRP to albumin ratio and uric acid.

INTRODUCTION: Idiopathic pulmonary hypertension(IPAH) is a rare disease that causes severe morbidity and mortality despite advances in treatment management. Evaluating the prognosis of the disease is critical in determining therapeutic approaches. We aimed to evaluate the prognostic significance of C-reactive protein/albumin ratio (CAR) and uric acid, which is an easily applicable and inexpensive parameter in patients with IPAH. METHODS: Seventy-two IPAH patients and 99 consecutive non-IPAH patients as a control group were enrolled in the study retrospectively. Right heart catheterization(RHC), echocardiography, and laboratory parameters of the two groups and those who died and survived among the IPAH patients were compared. RESULTS: IPAH and control group were compared at the first stage and CAR (1.98(0.28-10.74), 0.75(0.22-4.7),respectively;p < 0.01) and uric acid (0.33(0.19-0.87), 0.3(0.11-0.48) mmol/L, respectively; p = 0.03) values were significantly higher in the pulmonary hypertension group compared to the control group. Compared with the surviving IPAH patients, CAR (4.60(1.39-10.74),1.54(0.28-6.74),respectively;p < 0.001) and uric acid levels (0.458(0.26-0.87), 0.315(0.19-0.56) mmol/L, respectively; p < 0.001) were significantly higher in the group of patients who died. In the multivariate Cox regression models uric acid(p < 0.001) and CAR(p < 0.001) were found to be associated with survival time. Receiver operating characteristic curves (ROC) analyses showed that > 1.54 CAR value (AUC = 0.81,Sens:85.7%,Spec:56.9%,p < 0.001) and > 5.85 mg/dL (>0.348 mmol/L) uric acid value (AUC = 0.864, Sens:85.7%, Spec:78.4%, p < 0.001) are strong predictors for mortality. CONCLUSION: In this study, we showed that simple markers such as CAR, which augment the inflammation marker feature of CRP, and uric acid can give prognostic information in PAH patients.

Predictive value of chest HRCT for survival in idiopathic pulmonary arterial hypertension.

BACKGROUND: Little attention has been paid to chest high resolution computed tomography (HRCT) findings in idiopathic pulmonary arterial hypertension (IPAH) patients so far, while a couple of small studies suggested that presence of centrilobular ground-glass opacifications (GGO) on lung scans could have a significant negative prognostic value. Therefore, the aims of the present study were: to assess frequency and clinical significance of GGO in IPAH, and to verify if it carries an add-on prognostic value in reference to multidimensional risk assessment tool recommended by the 2015 European pulmonary hypertension guidelines. METHODS: Chest HRCT scans of 110 IPAH patients were retrospectively analysed. Patients were divided into three groups: with panlobular (p)GGO, centrilobular (c)GGO, and normal lung pattern. Association of different GGO patterns with demographic, functional, haemodynamic, and biochemical parameters was tested. Survival analysis was also performed. RESULTS: GGO were found in 46% of the IPAH patients: pGGO in 24% and cGGO in 22%. Independent predictors of pGGO were: positive history of haemoptysis, higher number of low-risk factors, and lower cardiac output. Independent predictors of cGGO were: positive history of haemoptysis, younger age, higher right atrial pressure, and higher mixed venous blood oxygen saturation. CGGO had a negative prognostic value for outcome in a 2-year perspective. This effect was not seen in the longer term, probably due to short survival of cGGO patients. CONCLUSIONS: Lung HRCT carries a significant independent prognostic information in IPAH, and in patients with cGGO present on the scans an early referral to lung transplantation centres should be considered.

Prognostic Significance of Systemic Arterial Stiffness Evaluated by Cardio-Ankle Vascular Index in Patients with Idiopathic Pulmonary Hypertension.

BACKGROUND: In a previous study, the cardio-ankle vascular index (CAVI) was increased significantly in idiopathic pulmonary arterial hypertension (IPAH) patients compared to the healthy group and did not much differ from one in systemic hypertensives. In this study the relations between survival and CAVI was evaluated in patients with IPAH. PATIENTS AND METHODS: We included 89 patients with new-diagnosed IPAH without concomitant diseases. Standard examinations, including right heart catheterization (RHC) and systemic arterial stiffness evaluation, were performed. All patients were divided according to CAVI value: the group with CAVI ≥ 8 (n = 18) and the group with CAVI < 8 (n = 71). The mean follow-up was 33.8 ± 23.7 months. Kaplan-Meier and Cox regression analysis were performed for the evaluation of our cohort survival and the predictors of death. RESULTS: The group with CAVI≥8 was older and more severe compared to the group with CAVI< 8. Patients with CAVI≥8 had significantly reduced end-diastolic (73.79±18.94 vs 87.35±16.69 mL, P<0.009) and end-systolic (25.71±9.56 vs 33.55±10.33 mL, P<0.01) volumes of the left ventricle, the higher right ventricle thickness (0.77±0.12 vs 0.62±0.20 mm, P < 0.006), and the lower TAPSE (13.38±2.15 vs 15.98±4.4 mm, P<0.018). RHC data did not differ significantly between groups, except the higher level of the right atrial pressure in patients with CAVI≥ 8-11.38±7.1 vs 8.76±4.7 mmHg, P<0.08. The estimated overall survival rate was 61.2%. The CAVI≥8 increased the risk of mortality 2.34 times (CI 1.04-5.28, P = 0.041). The estimated Kaplan-Meier survival in the patients with CAVI ≥ 8 was only 46.7 ± 7.18% compared to patients with CAVI < 8 - 65.6 ± 4.2%, P = 0.035. At multifactorial regression analysis, the CAVI reduced but saved its relevance as death predictor - OR = 1.13, CI 1.001-1.871. SUMMARY: We suggested the CAVI could be a new independent predictor of death in the IPAH population and could be used to better risk stratify this patient population if CAVI is validated as a marker in a larger multicenter trial.

Prognostic Value of Early Risk Stratification in Pediatric Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a life-threatening disease with risk stratification-based treatment strategy in adults. Although the risk factors have been studied individually in children, effective risk stratification is still lacking. We have tested the prognostic accuracy of pediatric PAH risk factors in our patient group. PATIENTS AND METHODS: Records of 58 PAH patients treated between 1995 and 2019 were reviewed retrospectively. Median age at diagnosis was 4.2 years (range, 0.1-16.1 years), and follow-up was 5.4 years (range, 0.01-24.1 years). Data collected at diagnosis were demographics, World Health Organization functional class, evidence of right ventricular failure, and parameters of echocardiography and cardiac catheterization. RESULTS: Mortality was 29% and 33% reached the composite endpoint. Patients with idiopathic PAH (n = 12) had increased risk of mortality compared with the congenital heart disease-associated PAH group (n = 32) (P = .0024). Neither the initial World Health Organization functional class staging nor the echocardiographic parameters significantly predicted the prognosis. The number of risk factors had no significant prognostic value either. In contrast, patients with higher pulmonary vascular resistance index (PVRI) had significantly increased risk (each 10 Wood units ⋅ m2 increase in PVRI being associated with 49.1% higher hazard, P = .0048). CONCLUSIONS: Survival analysis showed that PAH etiology might be an important determinant in pediatric PAH risk stratification. We confirmed that PVRI has predictive value in prognostic assessment. We could not establish the prognostic value of nonweighted single risk factors or their combination to predict pediatric PAH outcome due to the low sample size, but these results indicate that such studies are warranted.

Plasma irisin levels are associated with hemodynamic and clinical outcome in idiopathic pulmonary arterial hypertension patients.

Irisin has been considered to reflect oxidative stress. This study aimed to show whether plasma irisin levels are correlated with hemodynamic dysfunction and predict the clinical outcome of patients with idiopathic pulmonary arterial hypertension (IPAH). A total of 68 adult IPAH patients were prospectively recruited in the present study. Plasma irisin levels were measured by the ELISA method in enrolled IPAH patients. Baseline clinical characteristics, and hemodynamic and clinical outcome were compared according to different plasma irisin levels. IPAH patients were divided into high irisin group (irisin ≥ 7.3 µg/ml) and low irisin group (irisin < 7.3 µg/ml) according to median values of irisin levels. Total plasma cholesterol levels (P = 0.027) and low-density lipoprotein cholesterol (LDL-C) levels (P = 0.042) were higher in high irisin group and were positively correlated with plasma irisin levels. IPAH patients in low irisin group had a significantly higher mean pulmonary artery pressure (mPAP, P = 0.047), systolic pulmonary artery pressure (sPAP, P = 0.022), systolic right-ventricular pressure (sRVP, P = 0.007), mean right atrial pressure (mRAP, P = 0.043), and systolic right atrial pressure (sRAP, P = 0.020). mRAP, sRAP, and diastolic right atrial pressure (dRAP) were negatively correlated with plasma irisin levels. Low irisin group predicts adverse hemodynamic status and poor free of event survival rate (P = 0.030, log-rank test). Multivariate analysis indicates plasma irisin levels to be an independent predictor of prognosis in IPAH patients after adjusting for related covariates (HR 0.786; 95% CI 0.584, 0.957; P = 0.038). Plasma irisin levels may serve as a novel biomarker in IPAH patients for hemodynamic severity assessment and clinical outcome evaluation.

Idiopathic pulmonary arterial hypertension phenotypes determined by cluster analysis from the COMPERA registry.

The term idiopathic pulmonary arterial hypertension (IPAH) is used to categorize patients with pre-capillary pulmonary hypertension of unknown origin. There is considerable variability in the clinical presentation of these patients. Using data from the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension, we performed a cluster analysis of 841 patients with IPAH based on age, sex, diffusion capacity of the lung for carbon monoxide (DLCO; <45% vs ≥45% predicted), smoking status, and presence of comorbidities (obesity, hypertension, coronary heart disease, and diabetes mellitus). A hierarchical agglomerative clustering algorithm was performed using Ward's minimum variance method. The clusters were analyzed in terms of baseline characteristics; survival; and response to pulmonary arterial hypertension (PAH) therapy, expressed as changes from baseline to follow-up in functional class, 6-minute walking distance, cardiac biomarkers, and risk. Three clusters were identified: Cluster 1 (n = 106; 12.6%): median age 45 years, 76% females, no comorbidities, mostly never smokers, DLCO ≥45%; Cluster 2 (n = 301; 35.8%): median age 75 years, 98% females, frequent comorbidities, no smoking history, DLCO mostly ≥45%; and Cluster 3 (n = 434; 51.6%): median age 72 years, 72% males, frequent comorbidities, history of smoking, and low DLCO. Patients in Cluster 1 had a better response to PAH treatment than patients in the 2 other clusters. Survival over 5 years was 84.6% in Cluster 1, 59.2% in Cluster 2, and 42.2% in Cluster 3 (unadjusted p < 0.001 for comparison between all groups). The population of patients diagnosed with IPAH is heterogenous. This cluster analysis identified distinct phenotypes, which differed in clinical presentation, response to therapy, and survival.

Mixed Venous Oxygen Saturation Is a Better Prognosticator Than Cardiac Index in Pulmonary Arterial Hypertension.

BACKGROUND: European Society of Cardiology (ESC) and European Respiratory Society (ERS) guidelines include thermodilution cardiac index (TDCI) and mixed venous oxygen saturation (SvO2) as two of the three hemodynamic determinations used in risk assessment of patients with pulmonary arterial hypertension (PAH). SvO2 may be a better measurement than TDCI to assess prognosis in patients with either idiopathic or heritable PAH. RESEARCH QUESTION: What is the concordance between TDCI and SvO2 ESC/ERS risk group allocation and their prognostic value in patients with PAH? STUDY DESIGN AND METHODS: In this retrospective study, we assessed the correlation between SvO2 and TDCI in patients with idiopathic and heritable PAH. We determined concordance in the ESC/ERS risk group allocation and association with survival, both at baseline and follow-up. RESULTS: A total of 158 patients (mean age, 58 ± 17 years; 72% women) with idiopathic (91%) and heritable (9%) PAH were included. There was moderate association between TDCI and SvO2 (r = 0.50; 95% CI, 0.37-0.62). Weighted kappa revealed a fair agreement between TDCI and SvO2 (κ = 0.30; 95% CI, 0.18-0.42), with concordance in risk group allocation in 49% of patients. During a median follow-up of 45 months (interquartile range, 23-105), 62 patients (39%) died. Using Kaplan-Meier analysis, survival was impacted by the SvO2 (log rank = 0.002) but not by the TDCI risk group allocation (log-rank = 0.51). Using the Cox proportional hazard model, adjusted for age and sex, SvO2 (but not TDCI) was associated with mortality (hazard ratio per 1% change, 0.94; 95% CI, 0.91-0.97; P < .001). INTERPRETATION: When using the cutoffs proposed by the ESC/ERS guidelines, we noted poor concordance in risk score allocation between TDCI and SvO2. In patients with idiopathic or heritable PAH, SvO2 measurements are superior to TDCI in predicting long-term mortality.

The Impact of Airway Complications on Survival Among Lung Transplant Recipients.

INTRODUCTION: Long-term outcomes of airway complications (AC) after lung transplantation are unknown. The incidence of AC varies from 1.6% to 32% with the related mortality rate of 2% to 4%. The management of most AC is based on endobronchial methods, including balloon bronchoplasty, endobronchial stent placement, and ablative techniques. The aim of the study was to assess the connection between airway complications treated by bronchial intervention (BI) and the survival of lung transplant recipients. MATERIALS AND METHODS: The single-center retrospective study reviewed the cases of 165 patients (63 women [38.18%], 103 men [61, 82%]; median age at referral for lung transplantations (LTx), 41 years [range, 15-68 years]). The cohort was stratified into 2 groups comprising those whose procedures were complicated by ACs and those without. The primary outcome measured was mortality, with survival endpoints calculated at 6 months. RESULTS: The comparison of the survival of recipients regarding underlying disease (cystic fibrosis [CF], chronic obstructive pulmonary disease [COPD], idiopathic pulmonary artery hypertension [IPAH], and others) with the use of the Kaplan-Meier estimator indicated that the only statistically significant (P = .0194) differences between patients who underwent BI and patients without BI performed were observed in CF patients (Fig 1). In any other diagnosis, the results were not statistically significant (P > .05). CONCLUSIONS: Bronchoscopic intervention because of airway complications after lung transplantation are often-used procedures, but they have no impact on the survival of patients with cystic fibrosis.

Schistosomiasis-associated pulmonary arterial hypertension: a systematic review.

Schistosomiasis-associated pulmonary arterial hypertension (Sch-PAH) is a life-threatening complication of chronic hepatosplenic schistosomiasis. It is suggested to be the leading cause of pulmonary arterial hypertension (PAH) worldwide. However, pathophysiological data on Sch-PAH are scarce. We examined the hypothesis that there are pronounced similarities in pathophysiology, haemodynamics, and survival of Sch-PAH and idiopathic PAH (iPAH).This systematic review and meta-analysis was registered in the PROSPERO database (identifier CRD42018104066). A systematic search and review of the literature was performed according to PRISMA guidelines for studies published between 01 January 1990 and 29 June 2018.For Sch-PAH, 18 studies evaluating pathophysiological mechanisms, eight studies on haemodynamics (n=277), and three studies on survival (n=191) were identified. 16 clinical registries reporting data on haemodynamics and survival including a total of 5792 patients with iPAH were included for comparison. Proinflammatory molecular pathways are involved in both Sch-PAH and iPAH. The transforming growth factor (TGF)-ß signalling pathway is upregulated in Sch-PAH and iPAH. While there was no difference in mean pulmonary artery pressure (54±17 mmHg versus 55±15 mmHg, p=0.29), cardiac output (4.4±1.3 L·min-1 versus 4.1±1.4 L·min-1, p=0.046), and cardiac index (2.6±0.7 L·min-1·m-2 versus 2.3±0.8 L·min-1·m-2, p<0.001) were significantly higher in Sch-PAH compared to iPAH, resulting in a lower pulmonary vascular resistance in Sch-PAH (10±6 Woods units versus 13±7 Woods units, p<0.001). 1- and 3-year survival were significantly better in the Sch-PAH group (p<0.001).Sch-PAH and iPAH share common pathophysiological mechanisms related to inflammation and the TGF-ß signalling pathway. Patients with Sch-PAH show a significantly better haemodynamic profile and survival than patients with iPAH.

Association Between High FSH, Low Progesterone, and Idiopathic Pulmonary Arterial Hypertension in Women of Reproductive Age.

BACKGROUND: While sex differences characterize susceptibility and severity of idiopathic pulmonary arterial hypertension (IPAH), our understanding of the relationship between levels of gonadotropins and sex hormones in fertile women and the disease is limited. We aimed to investigate whether gonadotropin and sex hormone levels in women of reproductive age were associated with risk and mortality of IPAH. METHODS: We did a matched case-control study. Cases were reproductive female patients with idiopathic pulmonary arterial hypertension admitted in Shanghai Pulmonary Hospital (Tongji University School of Medicine, Shanghai, China) during 2008-2014. Healthy controls were matched on age and body mass index. We also did a prospective cohort study to assess the effects of hormone levels on mortality in IPAH fertile female patients. RESULTS: One hundred sixty-four cases and 133 controls were included. After adjustment for age and body mass index, the odds ratios of having IPAH for follicle-stimulating hormone, testosterone, and progesterone as expressed on natural log scale were 1.51 (95% confidence interval: 1.06, 2.16), 0.42 (0.31-0.57), and 0.52 (0.43-0.63), respectively. In the cohort study with a median follow-up of 77 months, the hazard ratios for dying after adjustment for baseline characteristics and treatments among IPAH patients were 2.01 (95% confidence interval: 1.22-3.30) and 0.78 (95% confidence interval: 0.62-0.98) for follicle-stimulating hormone and progesterone in natural log scale, respectively. CONCLUSIONS: In reproductive women with IPAH, high follicle-stimulating hormone and low progesterone tended to be associated with high risk of IPAH and mortality among patients.

Right ventricular systolic to diastolic duration ratio: A novel predictor of outcome in adult idiopathic pulmonary arterial hypertension.

BACKGROUND: The systolic to diastolic (SD) duration ratio reflects global RV performance in pulmonary arterial hypertension (PAH) yet limited data exists on its application to adult non-congenital PAH. We measured SD ratios on echocardiogram in idiopathic PAH (IPAH) to establish its response to pulmonary vasodilator therapy and prognostic value at diagnosis and follow up. METHODS: Incident patients with IPAH undergoing echocardiogram, haemodynamic and exercise assessments were identified within our centre between 2005 and 2018. SD ratios were adjusted for heart rate at diagnosis and follow up. RESULTS: In 98 patients at diagnosis, the mean SD ratio was 1.03 ±â€¯0.37 decreasing to 0.85 ±â€¯0.25, p < 0.001 at follow-up echocardiogram performed at a median interval of 9.0 months. The SD ratio at diagnosis correlated weakly with RV basal diameter (r = 0.24, p = 0.04) and 6MWD (r = 0.23, p = 0.04). At follow up, the mean SD ratio was lower in those receiving combination vs monotherapy pulmonary vasodilator treatment (71 ±â€¯25 vs 92 ±â€¯22% baseline respectively, p < 0.001). After a median follow-up of 4.8 years, 3 patients were transplanted and 23 patients died. The SD ratio at diagnosis and follow up predicted an increased risk of death/transplantation (HR 2.41 (1.09-5.29), p = 0.03; HR 5.02 (1.27-19.77), p = 0.02 respectively), retaining its predictive value at diagnosis in bivariate models with 6MWD (HR 2.18 (1.06-4.08)), WHO Functional Class (HR 2.33 (1.04-5.21)) and TAPSE (HR 2.36 (1.07-5.19)), all p < 0.05. CONCLUSIONS: The SD ratio carries prognostic value at diagnosis and follow up in IPAH. Its further evaluation alongside current PAH risk stratification parameters should be considered.

Outcomes of lung disease-associated pulmonary hypertension and impact of elevated pulmonary vascular resistance.

BACKGROUND: The clinical characteristics, hemodynamic changes and outcomes of lung disease-associated pulmonary hypertension (LD-PH) are poorly defined. METHODS: A prospective cohort of PH patients undergoing initial hemodynamic assessment was collected, from which 51 patients with LD-PH were identified. Baseline characteristics and long-term survival were compared with 83 patients with idiopathic pulmonary arterial hypertension (iPAH). RESULTS: Mean age (±standard deviation) of LD-PH patients was 64 ±â€¯10 years, 30% were female and 78% were New York Heart Association class III-IV. The LD-PH group was older than the iPAH group (64 ±â€¯10 vs 56 ±â€¯18 years, respectively, P = 0.003) with a lower percentage of women (30% vs 70%, P = 0.007). LD-PH patients had smaller right ventricular sizes (P = 0.02) and less tricuspid regurgitation (P = 0.03) by echocardiogram, and lower mean pulmonary arterial pressures (mPAP) (P = 0.01) and pulmonary vascular resistance (PVR) (P = 0.001) at catheterization. Despite these findings, mortality was equally high in both groups (P = 0.16). 5-year survival was lower in patients with interstitial lung disease compared to those with obstructive pulmonary disease (P = 0.05). Among the LD-PH population, those with mild to moderately elevated mPAP and those with PVR <7 Wood units demonstrated significantly improved survival (P = 0.04 and P = 0.001, respectively). Vasoreactivity was not associated with improved survival (P = 0.64). A PVR ≥7 Wood units was associated with increased risk of mortality (hazard ratio (95% confidence interval), 3.59 (1.27-10.19), P = 0.02). CONCLUSIONS: Despite less severe PH and less right heart sequelae, LD-PH has an equally poor clinical outcome when compared to iPAH. A PVR ≥7 Wood units in LD-PH patients was associated with 3-fold higher mortality.

Risk Analysis of Perioperative Death in Lung Transplant Patients With Severe Idiopathic Pulmonary Hypertension.

OBJECTIVE: To investigate the risk factors for perioperative mortality in patients with severe idiopathic pulmonary hypertension (IPAH) undergoing lung transplantation (LTx). METHODS: Twenty-two IPAH patients were included in the study and were divided 2 groups: a case group with early death post LTx (n = 5, 22.7%) and the remaining 17 recipients (87.3%), who did not die at perioperative time (the control group). All the preoperative clinical data and surgical procedures were analyzed using an independent t-test and Fisher's exact probability test. RESULTS: All the patients had over class III heart function rated by World Health Organization classification. Both groups had significantly reduced capacity of 6-min walking distance (6 MWD), decreased oxygen saturation, increased N-terminal probrain natriuretic peptide (NT-proBNP), certain frequent syncope, hemoptysis, and lower extremity edema. In addition, cardiac catheterization examination demonstrated that all patients had elevated pulmonary artery systolic pressure, mean pulmonary artery systolic pressure, and right atrial pressure. Furthermore, reduced mixed venous oxygen saturation and partial pressure of oxygen were seen in oxygen inhalation in a dose of 5 L/min in both groups. Cardiovascular morphological changes in both groups by cardiac ultrasonography included dilated diameter of the right ventricle and the main pulmonary artery. However, the right ventricular ejection fraction and stroke volume were notedly dropped. Distended inferior vena cava and enhanced frequency of hypertensive tricuspid regurgitation velocity response to stress were seen, and pericardial effusion was developed in both groups of patients. Nevertheless, a paired t-test (n = 5 vs n = 17) showed no significance between groups (P > .05), while there was a significant difference in frequencies of brief loss of consciousness (P < .01). Serum sodium concentration, cardiac index (CI), inner diameter of the left ventricle at end diastolic phase, and inner diameter ratio of RV/LV were 116.80 ± 5.76 mmol/L vs 29.88 ± 7.28 mmol/L (P = .002), 1.30 ± 0.07 L/min/m2 vs 1.58 ± 0.26 L/min/m2 (P = .030), 28.80 ± 3.70 mm vs 34.76 ± 5.43 mm (P = .033) and 1.81 ± 0.28 mmol/L vs 1.43 ± 0.26 (P = .011) between case and control group, respectively. CONCLUSIONS: All patients with IPAH waiting for lung transplantation were in critical condition. The highest death risks at perioperative time in IPAH patients were high frequencies of syncope, hyponatremia, lower CI, inner diameter of the left ventricle, and upward RV/LV ratio.

Exercise energy expenditure in patients with idiopathic pulmonary arterial hypertension: Impact on clinical severity and survival.

Patient with idiopathic pulmonary hypertension (IPAH) develop peripheral inefficiency which could lead to an increase total energy expenditure and that could have a significant prognostic impact. To test the hypothesis, fifty-five consecutive stable IPAH patients (mean age 51±17 years) and 24 matched controls underwent an incremental exercise test and followed for a 5 years' period. Total energy expenditure was assessed as the ratio between total [Formula: see text] uptake (during both effort and recovery) and total external work ( [Formula: see text] ). Patients with IPAH had a lower exercise capacity and a significantly higher [Formula: see text] than controls ( [Formula: see text] 0.33 ± 0.09 ml/j vs 0.22 ± 0.04 ml/j, p < 0.0001). Among patients, [Formula: see text] was higher in whom died during follow up compared to survivors (0.41 ± 0.11 ml/j vs 0.30 ± 0.06 ml/j, p < 0.0001). In multivariate Cox regression analysis [Formula: see text] , gender, PETCO2 peak, [Formula: see text] were independent risk factors for death. Patients with IPAH have shown a less efficient muscular oxygen utilization than controls. Notably the high energy expenditure has a relevant independent prognostic impact.

Clinical Effects of Syncope on Disease Severity and Adverse Outcomes in Children with Idiopathic and Heritable Pulmonary Arterial Hypertension.

Syncope is more common in children with idiopathic pulmonary arterial hypertension (PAH) than in adults with PAH. Although syncope is associated with a poor prognosis in adult PAH, the clinical effects of syncopal events on disease severity and outcome in children have not been carefully investigated. This study assessed the prevalence of syncope in pediatric PAH and examined its clinical, hemodynamic, and prognostic importance. This retrospective study assessed clinical data, including syncope status, from 78 children (37 girls) with idiopathic and heritable PAH (median age at diagnosis, 11 years). Patients were classified as syncopal or non-syncopal, and clinical data from the two groups were compared. The primary outcome was a composite of lung transplantation and cardiac mortality. Overall, 31 (38%) children had a history of syncope at presentation. Median age at diagnosis, sex ratio, brain natriuretic peptide level, and 6-min walk distance at diagnosis did not differ between groups. The hemodynamic parameters of initial right heart catheterization were similar between the syncope and non-syncope group (mean pulmonary artery pressure, 67 versus 71 mm Hg; cardiac index, 2.9 versus 2.9 l/min/m2, respectively). There was not significantly difference in event-free survival rate between two groups. Although syncopal events are common in children with PAH, our findings suggest that syncope may not be correlated with disease severity or outcome in pediatric PAH.

Increased Pulmonary-Systemic Pulse Pressure Ratio Is Associated With Increased Mortality in Group 1 Pulmonary Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is characterised by remodelling of the pulmonary vasculature leading to right ventricular (RV) failure. The failing RV, through interventricular uncoupling, deleteriously impacts the left ventricle and overall cardiac efficiency. We hypothesised that the ratio of the pulmonary artery pulse pressure to the systemic pulse pressure ("pulmonary-systemic pulse pressure ratio", or PS-PPR) would be associated with mortality in PAH. METHODS: We conducted a retrospective analysis of 262 patients in the National Institute of Health Primary Pulmonary Hypertension Registry (NIH-PPH). We evaluated the association between the PS-PPR and mortality after adjustment for the Pulmonary Hypertension Connection (PHC) risk equation. RESULTS: Among 262 patients (mean age 37.5±15.8years, 62.2% female), median PS-PPR was 1.04 (IQR 0.79-1.30). In the Cox proportional hazards regression model, each one unit increase in the PS-PPR was associated with more than a two-fold increase in mortality during follow-up (HR 2.06, 95% CI 1.40-3.02, p=0.0002), and this association of PS-PPR with mortality remained significant in the multivariable Cox model adjusted for the PHC risk equation, mean pulmonary artery pressure, and body mass index (BMI) (adjusted HR 1.81, 95% CI 1.13-2.88, p=0.01). Furthermore, PS-PPR in the upper quartile (>1.30) versus quartiles 1-3 was associated with a 68% increase in mortality after adjustment for these same covariates (adjusted HR 1.68, 95% CI 1.13-2.50, p=0.01). CONCLUSIONS: Pulmonary-systemic pulse pressure ratio, a marker of biventricular efficiency, is associated with survival in PAH even after adjustment for the PHC risk equation. Further studies are needed on the wider applications of PS-PPR in PAH patients.

Thrombocytopenia independently predicts death in idiopathic PAH.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a progressive vascular disorder with a high mortality. Clinical experience and small case series suggest thrombocytopenia may be frequent in this population and associated with a poor prognosis. We sought to estimate the prevalence of thrombocytopenia in patients with PAH and characterize its association with disease characteristics and patient outcome. METHODS: Single center cohort study of 714 incident adult patients with Group 1 PH who were evaluated for baseline platelet count at the time of diagnosis. Pts were stratified into three groups: normal platelet count (>150 × 109/L), Grade 1 thrombocytopenia (75-149 × 109/L) and Grade 2-4 thrombocytopenia (<75 × 109/L). RESULTS: The median platelet count was 209 × 109/L (IQR 163, 264). There were 572 (80%) pts without thrombocytopenia, 107 (15%) with Grade 1 and 35 (5%) with Grade 2-4 thrombocytopenia. The median pt age was 55 years (IQR 44-65) with no difference between platelet groups (p = 0.85). Men were more likely to have thrombocytopenia (62, 34%) than women (80, 15%, p < 0.0001). Thrombocytopenia was frequent with portopulmonary PAH (84%) as opposed to idiopathic PAH (iPAH; 14%) or connective tissue disease associated PAH (12%). Platelet counts were not associated with functional class symptoms, the degree of right ventricular enlargement or dysfunction or tricuspid regurgitation by echocardiography. Invasive hemodynamics of right atrial pressure, mean pulmonary artery pressure and pulmonary vascular resistance were also similar between platelet groups. Thrombocytopenia was associated with higher mortality in iPAH patients (age- and sex-adjusted 5 year mortality [HR 1.95 (1.20, 3.08) p = 0.008] but not in other etiology groups. In a multivariate model of iPAH patients (adjusted for age, sex, DLCO, PVR, creatinine and 6MW distance) thrombocytopenia was most predictive of 5-year mortality [HR 1.68 (1.32, 2.12), p < 0.0001]. CONCLUSION: Thrombocytopenia in the context of iPAH portends a poor prognosis and is a simple independent factor to consider in judging severity of disease.