Outcomes of heart-lung transplantation in Eisenmenger syndrome compared to primary pulmonary hypertension.

OBJECTIVE: Heart-Lung Transplantation (HLTX) is required both in primary pulmonary hypertension (PPH) and Eisenmenger syndrome (ES) when there is associated end-stage heart disease. Although PPH is associated with an otherwise structurally normal heart, ES is associated with congenital heart defects, which may increase the complexity of the operation. This study analyzes if the diagnosis (PPH vs. ES) is related to short-term outcomes after HLTX. METHODS: Patients ≥18 years of age with PPH and ES who underwent HLTX were identified in the United Network for Organ Sharing database from 2005 to 2021. Patients were propensity score matched on heart and lung listing status at the time of transplant. Univariable, multivariable, and Kaplan-Meir survival analyses were performed. RESULTS: The unmatched cohort had 128 PPH and 44 ES patients, and the matched cohort had 44 patients in each group. PPH patients had lower waitlist times and PA pressures but higher FEV1, heart, and lung listing status and ECMO bridge. There were no differences in immediate postoperative outcomes such as dialysis, stroke, and airway dehiscence. PPH patients had a higher treatment rejection in the first year. The 30-day, 1-year, and 3-year survival were better in the PPH group. However, a landmark analysis excluding deaths within 30 days eliminated differences in survival between the groups. Post-transplant dialysis and postoperative mechanical ventilation >5 days were risk factors for 1-year mortality in ES. CONCLUSION: The short-term outcomes of HLTX are inferior in ES compared to PPH and much of the attrition in ES occurs in the immediate postoperative period.

Continuous cardiac monitoring in a patient with terminal pulmonary hypertension and eventual bilateral lung transplantation.

As pulmonary arterial hypertension (PAH) progress, arrhythmias are becoming an increasingly prominent phenomenon. Supraventricular tachycardias have been shown to have an incidence of up to 35% in pulmonary hypertension.Continuous cardiac monitoring was deployed in a patient with severe PAH 100 days before bilateral lung transplantation (BLTX). Despite being graded as WHO functional class IV, no arrhythmias were observed before BLTX. Furthermore, the case describes clinical improvement, along with a significant increase in heart rate variability (HRV) and decrease in night-time heart rate in the post-transplantation period.No arrhythmias were observed preoperatively during continuous monitoring in a 100-day period despite the patient's intrinsically high risk for arrhythmias. Increasing HRV and lower resting heart rate were observed after BLTX. Since these parameters correlate with the clinical condition, they might be valuable in risk assessment in patients with pulmonary hypertension.

Peripheral Blood T Cells of Patients with IPAH Have a Reduced Cytokine-Producing Capacity.

Pulmonary arterial hypertension (PAH) is rare disease that is categorized as idiopathic (IPAH) when no underlying cause can be identified. Lungs of most patients with IPAH contain increased numbers of T cells and dendritic cells (DCs), suggesting involvement of the immune system in its pathophysiology. However, our knowledge on circulating immune cells in IPAH is rather limited. We used flow cytometry to characterize peripheral blood DCs and T cells in treatment-naive IPAH patients, compared with connective-tissue disease-PAH (CTD-PAH) patients and healthy controls (HCs). At diagnosis, T-helper (Th) cells of IPAH patients were less capable of producing TNFα, IFNγ, IL-4 and IL-17 compared to HCs. IPAH patients showed a decreased frequency of Th2 cells and significantly enhanced expression of the CTLA4 checkpoint molecule in naive CD4+ T cells and both naive and memory CD8+ T cells. Frequencies and surface marker expression of circulating DCs and monocytes were essentially comparable between IPAH patients and HCs. Principal component analysis (PCA) separated IPAH patients-but not CTD-PAH patients-from HCs, based on T-cell cytokine profiles. At 1-year follow-up, the frequencies of IL-17+ production by memory CD4+ T cells were increased in IPAH patients and accompanied by increased proportions of Th17 and Tc17 cells, as well as decreased CTLA4 expression. Treatment-naive IPAH patients displayed a unique T-cell phenotype that was different from CTD-PAH patients and was characterized by reduced cytokine-producing capacity. These findings point to involvement of adaptive immune responses in IPAH, which may have an implication for the development of therapeutic interventions.

Distinct patterns of soluble leukocyte activation markers are associated with etiology and outcomes in precapillary pulmonary hypertension.

Activation of inflammatory processes has been identified as a major driver of pulmonary vascular remodeling that contributes to the development of precapillary pulmonary hypertension (PH). We hypothesized that circulating markers of leukocyte activation, reflecting monocytes/macrophages (sCD163, sCD14), T-cells (sCD25) and neutrophils (myeloperoxidase [MPO], neutrophil gelatinase-associated lipocalin [NGAL]) activity, could give prognostic information in precapillary PH. Circulating markers of leucocyte activation, sCD163, sCD14, sCD25, MPO and NGAL were measured by enzyme immunoassays in plasma from patients with idiopathic PAH (IPAH; n = 30); patients with PAH related to associated conditions (APAH; n = 44) and patients with chronic thromboembolic PH (CTEPH) (n = 32), and compared with 23 healthy controls. Markers of leucocyte activation were elevated in precapillary PH with particularly high levels in APAH. The elevated levels of monocyte/macrophage marker sCD163 was independently associated with poor long-term prognosis in the group as a whole, and elevated levels of sCD25 was associated with poor prognosis in APAH, while elevated levels of sCD163 and NGAL was associated with poor prognosis in IPAH and CTEPH. Our data show leucocyte activation in precapillary PH with different profiles and impact on prognosis according to etiology. The association of sCD163 with poor outcome in fully adjusted model may be of particular interest.

Smooth Muscle Phenotype in Idiopathic Pulmonary Hypertension: Hyper-Proliferative but not Cancerous.

Idiopathic pulmonary arterial hypertension (IPAH) is a complex disease associated with vascular remodeling and a proliferative disorder in pulmonary artery smooth muscle cells (PASMCs) that has been variably described as having neoplastic features. To decode the phenotype of PASMCs in IPAH, PASMCs from explanted lungs of patients with IPAH (IPAH-PASMCs) and from controls (C-PASMCs) were cultured. The IPAH-PASMCs grew faster than the controls; however, both growth curves plateaued, suggesting contact inhibition in IPAH cells. No proliferation was seen without stimulation with exogenous growth factors, suggesting that IPAH cells are incapable of self-sufficient growth. IPAH-PASMCs were more resistant to apoptosis than C-PASMCs, consistent with the increase in the Bcl2/Bax ratio. As cell replication is governed by telomere length, these parameters were assessed jointly. Compared to C-PASMCs, IPAH-PASMCs had longer telomeres, but a limited replicative capacity. Additionally, it was noted that IPAH-PASMCs had a shift in energy production from mitochondrial oxidative phosphorylation to aerobic glycolysis. As DNA damage and genomic instability are strongly implicated in IPAH development a comparative genomic hybridization was performed on genomic DNA from PASMCs which showed multiple break-points unaffected by IPAH severity. Activation of DNA damage/repair factors (γH2AX, p53, and GADD45) in response to cisplatin was measured. All proteins showed lower phosphorylation in IPAH samples than in controls, suggesting that the cells were resistant to DNA damage. Despite the cancer-like processes that are associated with end-stage IPAH-PASMCs, we identified no evidence of self-sufficient proliferation in these cells-the defining feature of neoplasia.

Circulating Plasma Metabolomic Profiles Differentiate Rodent Models of Pulmonary Hypertension and Idiopathic Pulmonary Arterial Hypertension Patients.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a severe progressive disease with systemic metabolic dysregulation. Monocrotaline (MCT)-induced and hypoxia-induced pulmonary hypertension (PH) rodent models are the most widely used preclinical models, however, whether or not these preclinical models recapitulate metabolomic profiles of PAH patients remain unclear. METHODS: In this study, a targeted metabolomics panel of 126 small molecule metabolites was conducted. We applied it to the plasma of the 2 preclinical rodent models of PH and 30 idiopathic pulmonary arterial hypertension (IPAH) patients as well as 30 healthy controls to comparatively assess the metabolomic profiles of PAH patients and rodent models. RESULTS: Significantly different metabolomics profiling and pathways were shown among the 2 classical rodent models and IPAH patients. Pathway analysis demonstrated that methionine metabolism and urea cycle metabolism were the most significant pathway involved in the pathogenesis of hypoxia-induced PH model and MCT-induced model, respectively, and both of them were also observed in the dysregulated pathways in IPAH patients. CONCLUSIONS: These 2 models may develop PAH through different metabolomic pathways and each of the 2 classical PH model resembles IPAH patients in certain aspects.

Idiopathic Pulmonary Hypertension After Liver Transplantation.

Pulmonary hypertension is one of the problems that can be encountered before liver transplantation. It is not expected in cases with no additional disease in postoperative period. Herein, we report on a 43-year-old woman who developed idiopathic pulmonary hypertension in the early postoperative period. Further investigation both pathologically and clinically is needed in patients undergoing living donor liver transplantation that may help to solve the problems such as pulmonary arterial hypertension before it occurs and manage complex hemodynamic changes successfully in the future.

Quantitative CT assessment of bronchial and vascular alterations in severe precapillary pulmonary hypertension.

BACKGROUND: Little is known about in vivo alterations at bronchial and vascular levels in severe pulmonary hypertension (PH) of different etiologies. We aimed to compare quantitative computed tomography (CT) data from the following three groups of severe precapillary PH patients: COPD, idiopathic pulmonary arterial hypertension (iPAH), and chronic thromboembolic PH (CTEPH). PATIENTS AND METHODS: This study was approved by the institutional review board. Severe PH patients (mean pulmonary arterial pressure [mPAP] ≥35 mmHg) with COPD, iPAH, or CTEPH (n=24, 16, or 16, respectively) were included retrospectively between January 2008 and January 2017. Univariate analysis of mPAP was performed in each severe PH group. Bronchial wall thickness (WT) and percentage of cross sectional area of pulmonary vessels less than 5 mm2 normalized by lung area (%CSA<5) were measured and compared using CT, and then combined to arterial partial pressure of oxygen (PaO2) to generate a "paw score" compared within the three groups using Kruskal-Wallis and its sensitivity using Fisher's exact test. RESULTS: WT was higher and %CSA<5 was lower in the COPD group compared to iPAH and CTEPH groups. Mosaic pattern was higher in CTEPH group than in others. In severe PH patients secondary to COPD, mPAP was positively correlated to %CSA<5. By contrast, in severe iPAH, this correlation was negative, or not correlated in severe CTEPH groups. In the COPD group, "paw score" showed higher sensitivity than in the other two groups. CONCLUSION: Unlike in severe iPAH and CTEPH, severe PH with COPD can be predicted by "paw score" reflecting bronchial and vascular morphological differential alterations.

Dendritic Cell Subsets and Effector Function in Idiopathic and Connective Tissue Disease-Associated Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a cardiopulmonary disease characterized by an incurable condition of the pulmonary vasculature, leading to increased pulmonary vascular resistance, elevated pulmonary arterial pressure resulting in progressive right ventricular failure and ultimately death. PAH has different underlying causes. In approximately 30-40% of the patients no underlying risk factor or cause can be found, so-called idiopathic PAH (IPAH). Patients with an autoimmune connective tissue disease (CTD) can develop PAH [CTD-associated PAH (CTD-PAH)], suggesting a prominent role of immune cell activation in PAH pathophysiology. This is further supported by the presence of tertiary lymphoid organs (TLOs) near pulmonary blood vessels in IPAH and CTD-PAH. TLOs consist of myeloid cells, like monocytes and dendritic cells (DCs), T-cells, and B-cells. Next to their T-cell activating function, DCs are crucial for the preservation of TLOs. Multiple DC subsets can be found in steady state, such as conventional DCs (cDCs), including type 1 cDCs (cDC1s), and type 2 cDCs (cDC2s), AXL+Siglec6+ DCs (AS-DCs), and plasmacytoid DCs (pDCs). Under inflammatory conditions monocytes can differentiate into monocyte-derived-DCs (mo-DCs). DC subset distribution and activation status play an important role in the pathobiology of autoimmune diseases and most likely in the development of IPAH and CTD-PAH. DCs can contribute to pathology by activating T-cells (production of pro-inflammatory cytokines) and B-cells (pathogenic antibody secretion). In this review we therefore describe the latest knowledge about DC subset distribution, activation status, and effector functions, and polymorphisms involved in DC function in IPAH and CTD-PAH to gain a better understanding of PAH pathology.

Recurrent chest pain and dyspnoea in a patient with pulmonary arterial hypertension.

Background: Pulmonary arterial hypertension (PAH) is a devastating, life-threatening disease with poor prognosis when left untreated. The long-term prognosis is definitely influenced by the natural progression of PAH but late disease-specific complications may also contribute. Case summary: We present a patient with a long-standing idiopathic PAH in whom progressive dilatation of pulmonary trunk and pulmonary arteries leads to compression of the left main coronary artery and the left atrium with hemodynamic compromise. Conclusion: With the current treatment options, survival in PAH has improved. Guidelines focus on more aggressive treatment with initial combination therapy and earlier referral for transplantation.

New cases of Glucose-6-Phosphate Dehydrogenase deficiency in Pulmonary Arterial Hypertension.

Pulmonary Arterial Hypertension (PAH) is a fatal disorder with limited treatment options and reduced life expectancy after diagnosis. Complex genetic backgrounds in PAH complicates identification of causative mutations that is essential for an understanding of the disease diagnostics and etiology especially for idiopathic PAH (iPAH). Hemolysis has been implicated as contributing to the pathobiology of PAH. Glucose-6-Phosphate Dehydrogenase (G6PD) expression and activity define erythrocyte's antioxidant capacity, and its decrease contributes to erythrocyte fragility. As G6PD deficiency was previously reported in a limited number of PAH cases, we tested whether iPAH patients exhibit underlying G6PD alterations in erythrocytes. A cohort of 22 PAH patients and 8 non-PAH patients were recruited for this study. DNA isolated from Peripheral Blood Mononuclear Cells (PBMC) was used for detection of mutations in the coding region of the G6PD gene. RNA isolated from PBMC was used for determination of G6PD mRNA expression level. G6PD activity was measured in Red Blood Cell (RBC) pellets. Three patients had missense mutations in G6PD (Val291Met, Asn126Asp, Asp194Glu), however, only one mutation (Val291Met) results in a severe G6PD deficiency. A single patient with mutation (Asn126Asp) showed a 21% decrease in G6PD activity, two subjects showed G6PD deficiency without mutations, and one patient had a decreased level of G6PD mRNA and reduced enzyme levels. This study demonstrates that a moderate decrease in G6PD activity is associated with PAH. Screening for G6PD activity and mutations in the G6PD gene may provide early detection of individuals predisposed to PAH.

Consequences of BMPR2 Deficiency in the Pulmonary Vasculature and Beyond: Contributions to Pulmonary Arterial Hypertension.

Since its association with familial pulmonary arterial hypertension (PAH) in 2000, Bone Morphogenetic Protein Receptor II (BMPR2) and its related signaling pathway have become recognized as a key regulator of pulmonary vascular homeostasis. Herein, we define BMPR2 deficiency as either an inactivation of the receptor, decreased receptor expression, or an impairment of the receptor's downstream signaling pathway. Although traditionally the phenotypic consequences of BMPR2 deficiency in PAH have been thought to be limited to the pulmonary vasculature, there is evidence that abnormalities in BMPR2 signaling may have consequences in many other organ systems and cellular compartments. Revisiting how BMPR2 functions throughout health and disease in cells and organs beyond the lung vasculature may provide insight into the contribution of these organ systems to PAH pathogenesis as well as the potential systemic manifestation of PAH. Here we review our knowledge of the consequences of BMPR2 deficiency across multiple organ systems.

Vascular Plugging for the Enlarging Pulmonary Arteriovenous Malformation in a Patient With Idiopathic Pulmonary Artery Hypertension.

The coexistence of idiopathic pulmonary artery hypertension with pulmonary arteriovenous malformation (PAVM) is challenging because although the PAVM causes hypoxia and polycythemia with potential thrombotic complications, closing the PAVM increases pulmonary artery pressure. We report on a lady with PAVM and idiopathic pulmonary artery hypertension who, within 2 years of diagnosis, had an ischemic stroke, PAVM enlargement from 20 × 20 × 30 mm to 30x × 40 × 40 mm and oximetry decrease to 90%. Transcatheter occlusion of PAVM with a vascular plug was successful. A year later, she had no flow via the PAVM and systemic oximetry improved to 97%, but pulmonary vascular resistance increased to 1.5-fold of baseline.

CCL21 as a Potential Serum Biomarker for Pulmonary Arterial Hypertension in Systemic Sclerosis.

OBJECTIVE: Systemic sclerosis (SSc) is a major cause of pulmonary arterial hypertension (PAH). Murine models indicate key roles for chemokines CCL19 and CCL21 and their receptor CCR7 in lung inflammation leading to PAH. The objective of this study was to assess the chemokine CCL19-CCL21 axis in patients with SSc-related PAH. METHODS: Serum samples obtained from 2 independent prospective SSc cohorts (n = 326), patients with idiopathic PAH (n = 12), and healthy control subjects (n = 100) were analyzed for CCL19/CCL21 levels, by enzyme-linked immunosorbent assay. The levels were defined as either high or low, using the mean + 2 SD value in controls as the cutoff value. Risk stratification at the time of PAH diagnosis and PAH-related events were performed. Descriptive and Cox regression analyses were conducted. RESULTS: CCL21 levels were higher in patients with SSc compared with controls and were elevated prior to the diagnosis of PAH. PAH was more frequent in patients with high CCL21 levels (≥0.4 ng/ml) than in those with low CCL21 levels (33.3% versus 5.3% [P < 0.001]). In multivariate analyses, CCL21 was associated with PAH (hazard ratio [HR] 5.1, 95% CI 2.39-10.76 [P < 0.001]) and occurrence of PAH-related events (HR 4.7, 95% CI 2.12-10.46, P < 0.001). Risk stratification at the time of PAH diagnosis alone did not predict PAH-related events. However, when risk at diagnosis was combined with high or low CCL21 level, there was a significant predictive effect (HR 1.3, 95% CI 1.03-1.60 [P = 0.027]). A high CCL21 level was associated with decreased survival (P < 0.001). CONCLUSION: CCL21 appears to be a promising marker for predicting the risk of SSc-related PAH and PAH progression. CCL21 may be part of a dysregulated immune pathway linked to the development of lung vascular damage in SSc.

Characteristics of exercise capacity in female systemic lupus erythematosus associated pulmonary arterial hypertension patients.

BACKGROUND: To study the oxygen uptake efficiency and determine usefulness of submaximal parameters of oxygen uptake in systemic lupus erythematosus associated pulmonary arterial hypertension (SLE PAH) on performing a cardiopulmonary exercise test (CPET). METHODS: CPET was performed in 21 SLE PAH patients, equal number of idiopathic pulmonary arterial hypertension (IPAH) patients and controls. Peak VO2, anaerobic threshold (AT), oxygen uptake efficiency slope (OUES) and oxygen uptake efficiency plateau (OUEP) and other CPET parameters were examined. All subjects had pulmonary function test (PFT) at rest, which included FEV1, FVC, FEV1/FVC, DLCO measurements. Right heart catheterization (RHC) was also done in SLE PAH and IPAH patients. CPET parameters were compared with RHC parameters to determine potential correlations. RESULTS: Peak VO2, PETCO2 and peak O2 pulse were lower in SLE PAH than IPAH and controls with OUE being lower during all stages of exercise in SLE PAH. DLCO and FVC values were significantly lower in SLE PAH (p < 0.05). Peak O2 pulse and VO2@AT in SLE PAH and IPAH was low (p < 0.05) and significant difference between SLE PAH and IPAH was seen (p < 0.05). PVR correlated with the lowest VE/VCO2, O2 pulse, peak PETCO2 and OUE in SLE PAH patients (all p < 0.05). CONCLUSIONS: SLE PAH patients have cardiopulmonary exercise limitation with reduced oxygen uptake efficiency. VO2@ at AT, peak O2 pulse and O2 pulse at AT were significantly reduced (p < 0.05). Key CPET parameters correlated with elevated pulmonary vascular resistance (PVR). Submaximal parameters of oxygen uptake are equally useful in SLE PAH.

Dyspnoea in lupus.

A 32-year-old woman suffering from systemic lupus erythematosus presented with a 6-week history of progressive dyspnoea and pleuritic chest pain. Examination was normal apart from reduced air entry at the lung bases.Arterial blood gases showed hypoxaemia and chest X-ray revealed raised hemidiaphragms without any pleural effusions. Lung function showed a restrictive pathology while high-resolution chest CT and CT pulmonary angiogram were negative. Echocardiography showed normal ventricular diameters and no pericardial effusion. Reduced lung volumes and a positive fluoroscopic sniff test lead to a diagnosis of shrinking lung syndrome. Symptoms improved following treatment with glucocorticoids and non-invasive ventilation, but there was no change in lung function.A year later, our patient presented again with worsening dyspnoea. This time echocardiography revealed severe mitral stenosis with pulmonary hypertension. Mitral valve replacement was performed and dyspnoea resolved. Histology showed Libman-Sachs endocarditis.

RV pressure overload: from hypertrophy to failure.

In pulmonary arterial hypertension (PAH), right ventricular (RV) adaptation is essential to overcome the chronic increases in RV pressure overload. Ultimately, RV compensatory mechanisms are not sufficient and patients succumb to RV failure. The processes underlying the transition of RV adaptation to RV failure are not well understood. In this review, we propose that important insights in RV adaptation processes can be obtained by comparing different etiologies of PAH, namely patients with PAH secondary to Eisenmenger syndrome, patients with PAH secondary to systemic sclerosis and patients where no cause is identified: idiopathic PAH. Although the amount of RV afterload does not differ between these patient groups, their prognosis is distinctly different. We will show that an adaptive RV phenotype, as is observed in Eisenmenger patients, coincides with RV hypertrophy, increased RV contractility, low RV fibrosis and low RV diastolic stiffness. Whereas a phenotype of RV failure, as is observed in patients with PAH-secondary to systemic sclerosis, is characterized by impaired contractile reserve, RV fibrosis and RV diastolic stiffness.

Early Experience of Macitentan for Pulmonary Arterial Hypertension in Adult Congenital Heart Disease.

BACKGROUND: Endothelin receptor antagonists (ERA) have been recognised as effective therapy for pulmonary arterial hypertension in congenital heart disease (CHD-PH), and Eisenmenger syndrome (ES) since The Bosentan Randomized Trial of Endothelin Antagonist Therapy-5 (Breathe 5) study. A new dual receptor antagonist - Macitentan - is currently undergoing trials to determine its efficacy in simple ES. To date there is little information on this therapy in CHD and we report our first experience, some with more complex diseases. METHODS: Data was collected prospectively from September 2014. Patients with CHD-PH were started on or converted to macitentan if they required therapy with phosphodiesterase 5 inhibitor (PDE5i) or if there was insufficient response or a reaction to bosentan, especially those with trisomy 21. Patients were seen approximately three months after starting therapy to assess echocardiography, six minute walk test, clinical response and tolerability. All patients underwent monthly liver tests initially, but this was reduced to three-monthly in Q4 2015. RESULTS: Fifteen patients with CHD-PH (eight male, seven female) were started on macitentan, median (range) age 38 (23-61) years, and eight patients with Down's syndrome. Eight patients had complex CHD with one having unoperated double inlet left ventricle with ventriculo-arterial discordance, one had double outlet right ventricle and six with complete atrio-ventricular septal defect. Six patients were ERA naïve and nine patients changed from bosentan to macitentan in order to achieve improved drug-drug interaction. Median length of time of treatment with macitentan is 289 (0-694) days to date. One discontinued due to rash and feeling unwell; one was unable to comply with medication due to learning difficulties and one died soon after commencing rescue therapy. This last patient was functional class IV with oxygen saturation of 67% at rest, with right heart failure and was unable to perform a walk test before commencing therapy. All patients who remained on therapy had significant increase in six minute walk test from median 286 (120-426) to 360m (150-450)(p <0.05), most notably in those treatment naïve. Functional class median remained at 3 but the range was reduced (1-3). Resting oxygen saturations improved from median 83 range (77-95%) at rest to 91 (77-96%) and at end walk from 78 (48-90%) to 79 (62-96%). Tricuspid regurgitant peak Doppler derived pressure drop did not change (as expected) at 4.6 (4.3-5.5)m/s. There were no episodes of liver dysfunction. CONCLUSIONS: The introduction of this new therapy has been simple and mostly well tolerated in our sick group of patients. With the usual reservations concerning the open-label nature of our observations, macitentan has good signals regarding oxygen saturations and encouraging signals relating to efficacy.

Gas exchange responses during 6-min walk test in patients with pulmonary arterial hypertension.

BACKGROUND AND OBJECTIVE: The 6-min walk test (6MWT) is the most widely utilized method of assessing exercise capacity in pulmonary arterial hypertension (PAH). Cardiopulmonary exercise testing has the advantage of providing additional physiological information over 6MWT. The goals of our study were to describe the addition of gas exchange measurements to 6MWT and to determine how these parameters were related to the severity of PAH in three major subgroups of PAH (idiopathic (IPAH), connective tissue disease-related (CTPAH) and congenital heart disease-related (CHPAH)). METHODS: Seventy-six PAH patients (IPAH, n = 28; CTPAH, n = 24; CHPAH, n = 24) completed the 6MWT with simultaneous gas exchange measurements. The 6-min walk distance (6MWD), oxygen uptake ( V ˙ O2 ), carbon dioxide production ( V ˙ CO2 ), oxygen saturation, minute ventilation to carbon dioxide output ( V ˙ E / V ˙ CO2 ) and end-tidal partial pressure for carbon dioxide (PET CO2 ) were compared between subgroups, different functional classes (FCs) and pharmacotherapy. RESULTS: Whilst no significant difference in 6MWT was observed, absolute V ˙ O2 and V ˙ CO2 were higher for IPAH (P < 0.05). Differences were removed when V ˙ O2 and V ˙ CO2 were expressed relative to body mass (i.e. mL/kg/min). CHPAH had the most significant desaturation during 6MWT (CPAH: 73 ± 15%; CTPAH: 90 ± 8%, IPAH: 92 ± 8%, P < 0.01). There was no difference in V ˙ E / V ˙ CO2 and PET CO2 between groups; however, New York Health Association (NYHA) FC II performed better than FC III subjects in 6MWT with lower V ˙ E / V ˙ CO2 and higher end-exercise PET CO2 . Similarly, individuals on more advanced pharmacotherapy (triple therapy vs monotherapy) had poorer gas exchange during exercise. CONCLUSION: Whilst 6MWT and gas exchange did not differentiate between PAH groups, individuals with more severe disease and on more advanced pharmacotherapy had poorer gas exchange during exercise.