Prevalence and clinical significance of conduction disease in patients with idiopathic pulmonary arterial hypertension.

Anatomical and physiological changes in the right heart as a direct consequence of the upstream pressure overload characteristic of idiopathic pulmonary hypertension (IPAH) are likely to lead to conduction disease in these patients. However, the prevalence and clinical implications of atrioventricular conduction disease in IPAH patients are not well-characterized. In this observational cohort study, we show that conduction disease is far more prevalent in a cohort of 175 IPAH patients than a group of matched comparators (37.1% vs 10.8%), and is associated with older age, male sex and more severe right heart dilatation. However, conduction disease is independently associated with worse functionality and higher mortality in this patient group. Prospective study is required to substantiate this, and whether intervention such as prophylactic pacing could restore prognosis.

Gene panel diagnostics reveals new pathogenic variants in pulmonary arterial hypertension.

BACKGROUND: A genetic predisposition can lead to the rare disease pulmonary arterial hypertension (PAH). Most mutations have been identified in the gene BMPR2 in heritable PAH. However, as of today 15 further PAH genes have been described. The exact prevalence across these genes particularly in other PAH forms remains uncertain. We present the distribution of mutations across PAH genes identified at the largest German referral centre for genetic diagnostics in PAH over a course of > 3 years. METHODS: Our PAH-specific gene diagnostics panel was used to sequence 325 consecutive PAH patients from March 2017 to October 2020. For the first year the panel contained thirteen PAH genes: ACVRL1, BMPR1B, BMPR2, CAV1, EIF2AK4, ENG, GDF2, KCNA5, KCNK3, KLF2, SMAD4, SMAD9 and TBX4. These were extended by the three genes ATP13A3, AQP1 and SOX17 from March 2018 onwards following the genes' discovery. RESULTS: A total of 79 mutations were identified in 74 patients (23%). Of the variants 51 (65%) were located in the gene BMPR2 while the other 28 variants were found in ten further PAH genes. We identified disease-causing variants in the genes AQP1, KCNK3 and SOX17 in families with at least two PAH patients. Mutations were not only detected in patients with heritable and idiopathic but also with associated PAH. CONCLUSIONS: Genetic defects were identified in 23% of the patients in a total of 11 PAH genes. This illustrates the benefit of the specific gene panel containing all known PAH genes.

Risk assessment in pulmonary hypertension based on routinely measured laboratory parameters.

BACKGROUND: γ-glutamyl transferase (GGT), the aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, and the neutrophil-to-lymphocyte ratio (NLR) are prognostic biomarkers in several cardiovascular diseases, but their relevance in pulmonary hypertension (PH) is not fully understood. We aimed to assess their prognostic value in patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic PH (CTEPH). METHODS: We retrospectively analyzed 731 incident patients with idiopathic PAH or CTEPH who entered the Giessen PH registry during 1993-2019. A risk stratification score based on GGT, AST/ALT ratio, and NLR tertiles was compared with a truncated version of the European Society of Cardiology/European Respiratory Society (ESC/ERS) risk stratification scheme. Associations with survival were evaluated using Kaplan-Meier and Cox regression analyses. External validation was performed in 311 patients with various types of PAH or CTEPH from a second German center. RESULTS: GGT levels, AST/ALT, and NLR independently predicted mortality at baseline and during follow-up. The scoring system based on these biomarkers predicted mortality at baseline and during follow-up (both log-rank p < 0.001; hazard ratio [95% confidence interval], high vs low risk: baseline, 7.6 [3.9, 15.0]; follow-up, 13.3 [4.8, 37.1]). Five-year survival of low, intermediate, and high risk groups was 92%, 76%, and 51%, respectively, at baseline and 95%, 78%, and 50%, respectively, during follow-up. Our scoring system showed characteristics comparable to the ESC/ERS scheme, and predicted mortality in the validation cohort. CONCLUSION: GGT, AST/ALT, and NLR were reliable prognostic biomarkers at baseline and during follow-up, with predictive power comparable to the gold standard for risk stratification.

The features of rare pathogenic BMPR2 variants in pulmonary arterial hypertension: Comparison between patients and reference population.

BACKGROUND: Mutations in the gene encoding bone morphogenetic protein receptor type 2 (BMPR2) are the most common genetic risk factors underlying pulmonary arterial hypertension (PAH). However, the features of PAH-related BMPR2 rare variants remain unclear. We propose that the discrepancy of BMPR2 rare variants landscape between patients with PAH and reference population would be important to address the genetic background of PAH-related variants. METHODS: We genotyped BMPR2 rare variants in 670 Chinese patients with pulmonary arterial hypertension. The BMPR2 rare variants were screened in 10,508 reference people from two exome databases. RESULTS: The prevalence of rare BMPR2 variants in patients with PAH was significantly higher compared to the reference population (21.5%, 144/670 vs 0.87%, 91/10508, p = 1.3 × 10-118). In patients with PAH, 49% of identified BMPR2 rare variants were loss-of-function or splicing. These BMPR2 rare variants were only observed in 1% of the reference population (p = 9.0 × 10-12). Arg491, which is absent in the reference population, represented as hot-spot site (14.6%, 21/144) in PAH patients. BMPR2 missense mutations in PAH patients were more likely distributed in extracellular ligand-binding domain (ECD, 29.7% vs 11.1%, p < 0.001). Compared with Non-PAH-related variations, PAH-related missense variants tend to alter the amino acid electric status (51.4% vs 23.3%, p < 0.001). CONCLUSIONS: BMPR2 variants located in extracellular ligand-binding domain or altered the amino acid electric status are more pathogenic.

Extracorporeal membrane oxygenation and lung transplantation: initial experience at a single brazilian center

OBJECTIVE: To report initial experience from the use of extracorporeal membrane oxygenation (ECMO) in patients who received lung transplantation. METHODS: Retrospective study of a single tertiary center in the Brazilian state of São Paulo, a national reference in lung transplantation, based on the prospective collection of data from electronic medical records. The period analyzed extended from January 2009 (beginning of the program) until December 2018. RESULTS: A total of 75 lung transplants were performed, with ECMO used in 8 (10.7%) cases. Of the patients, 4 (50%) were female. The mean age was 46.4±14.3 years. The causes of the end-stage lung disease that led to transplantation were pulmonary arterial hypertension in 3 (37.5%) patients, bronchiectasis in 2 (25%) patients, pulmonary fibrosis in 2 (25%) patients, and pulmonary emphysema in 1 (12.5%) patient. In our series, 7 (87.5%) cases were sequential bilateral transplantations. Prioritization was necessary in 4 (50%) patients, and in 1 patient, ECMO was used as a bridge to transplantation. The ECMO route was central in 4 (50%), peripheral venovenous in 2 (25%) and peripheral venoarterial in 2 (25%) patients. The mean length of the intensive care unit (ICU) stay was 14±7.5 days and of the hospital stay was 34.1±34.2 days. The mean ECMO duration was 9.3±6.6 days with a 50% decannulation rate. Three patients were discharged (37.5%). CONCLUSION: Lung transplantation requires complex treatment, and ECMO has allowed extending the indications for transplantation and provided adjuvant support in the clinical management of these patients.

Genotypes and Phenotypes of Chinese Pediatric Patients With Idiopathic and Heritable Pulmonary Arterial Hypertension-A Single-Center Study.

BACKGROUND: The relationship between clinical outcomes and gene mutations in Chinese pediatric patients with idiopathic and heritable pulmonary arterial hypertension (PAH) is unclear. METHODS: We retrospectively studied the clinical characteristics and outcomes of pediatric patients who visited Beijing Anzhen Hospital from September 2008 to December 2018. RESULTS: Eighty-two pediatric patients were included. Forty-two gene mutations were identified in 41 patients (50%), including 25 mutations in BMPR2, 5 mutations in ACVRL1, 3 mutations each in ABCA3 and NOTCH3, 2 mutations each in KCNK3 and HTR2B, 1 mutation in ENG, and 1 mutation in EIF2AK4. The mean age at diagnosis of PAH was 86.4 ± 55.1 months. Forty-eight patients (twenty-eight mutation carriers) underwent cardiac catheterization examinations, with acute vasodilator testing performed simultaneously. Results showed that mutation carriers demonstrated a higher pulmonary vascular resistance index (P = 0.037). Patients with gene mutations responded poorly to vasodilators (P = 0.001). The 1-, 2-, and 3-year survival rates of mutation noncarriers were 95.1%, 87.8%, and 82.5% respectively; while for mutation carriers, the proportions were 86.6% (P = 0.216), 63.8% (P = 0.021), and 52.2% (P = 0.010), respectively. Cardiac index was an independent predictor of death (P = 0.005; odds ratio [OR] 2.16, 95% confidence interval [CI] 1.258-3.704), as well as RAP (P = 0.01; OR 1.26, 95% CI 1.056-1.503). CONCLUSIONS: In our cohort of Chinese pediatric patients, those with an identified gene mutation demonstrated worse clinical outcomes. Therefore, early gene screening for pediatric patients with idiopathic and heritable PAH is recommended, and more aggressive treatment for mutation carriers may be advisable.

Retrospective observational analysis of hospital discharge database to characterize primary pulmonary hypertension and its outcomes in Spain from 2004 to 2015.

To examine trends in the incidence, characteristics and outcomes, and to identify factors associated with in-hospital mortality (IHM) of patients hospitalized for primary pulmonary hypertension (PPH) in Spain (2004-2015).We included all patients hospitalized with PPH and included in the Spanish National Hospital Discharge Database.We analyzed 46,883 discharges of patients (7.14% with PPH as their primary diagnosis). Incidence rates decreased from 6.15 cases per 100,000 inhabitants in 2004-06 to 3.40 in 2013-15 (P < .001). Mean age rose from 66.43 ±â€Š21.28 to 69.73 ±â€Š21.12 years (P < .001) and the proportion of females increased over the study period (58.44% vs 60.71%; P < .001). Comorbidity using the Charlson Comorbidity Index (CCI) also increased with 16.07% having CCI ≥3 in 2004-06 vs 21.795 in 2013-15. Median length of hospital stay (LOHS) was 1 day longer in period 2004-06, than in 2013-15 (9 vs 8 days; P < .001). The proportion of patients who were considered a readmission and the mean costs increased from 15.7% and 3712.46&OV0556; in the first period to 17.14% and 4040.28&OV0556; in 2013-15 (P < .001). IHM increased from 8.2% in 2004-06 to 9.93% in 2013-15 (P < .001). The predictors' of IHM among PPH patients included comorbidity and use of mechanical ventilation. Primary diagnosis of PPH did not predict higher IHM (OR 1.07; 95%CI 09-1.26).Our data indicates that the incidence of hospitalizations decreased in Spain between 2004 and 2015. Parallel, LOHS also decreased during this period. By contrast, comorbidity increased over time in PPH patients, as well as readmission rates, costs and IHM.

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.

Prevalence of auto-antibodies associated to pulmonary arterial hypertension in scleroderma - A review.

The prevalence of auto-antibodies associated to pulmonary arterial hypertension in scleroderma patients was reviewed, based on reports cited in two major scientific databases. Data were collected on the following types of antibodies: antinuclear, anti-double-stranded DNA, anticentromere, anti-CENP-A, anti-CENP-B, anti-bicaudal D2, anti-nucleolar, anti-Scl-70 (anti-topoisomerase I), anti-topoisomerase II α, anti-RNP, anti-U1RNP, anti-U3RNP, anti-RNA polymerase III, anti-Th/To, anti-histone, antiphospholipid, anti-PmScl, anti-Sm, anti SSA (anti-Ro),anti SSB (La), anti-Ro52 (TRIM 21), anti-Ku, anti-B23, anti-RuvBL1, anti-RuvBL2, anti-fibrin bound tissue plasminogen activator, anti-endothelial cell, anti-phosphatidylserine-prothrombin complex, anti-endothelin-1 type A receptor, anti-angiotensin II type 1 receptor, anti­carbonic anhydrase II, anti-fibroblast, anti-cyclic citrullinated peptide, anti-4-sulfated N-Acetyl-lactosamine, class I and II anti-human leukocyte antigen. Auto-antibodies were shown by different authors to be associated to this condition, with different prevalence values for each type of auto-antibody. Antinuclear antibodies, anti-centromere antibodies, antiphospholipid antibodies, anti-U3 RNP antibodies and anti-Th/To antibodies would appear to show a particularly important prevalence in scleroderma patients with pulmonary hypertension, appearing in about 8/10 (antinuclear), 1/ 2 (anti-centromere, anti-phospholipid), and 1/4 (anti-U3RNP, anti-Th/To) of patients. The available evidence points in the direction of a strong association between auto-immune mechanisms and pulmonary hypertension in the setting of scleroderma.

Management of Adults With Congenital Heart Disease and Pulmonary Arterial Hypertension in the UK: Survey of Current Practice, Unmet Needs and Expert Commentary.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a well-recognised complication of adult congenital heart disease (CHD). However, management is not currently standardised between centres and specific guidelines are lacking. In order to identify and understand the unmet needs related to PAH associated with CHD (PAH-CHD), a survey of physicians was performed. METHODS: An electronic survey was sent to two physician groups: (1) cardiologists registered in a UK cardiology directory; (2) specialist pulmonary hypertension (PH) physicians known to manage patients with adult PAH-CHD. The questions related to referral pathways, screening, therapy and palliative care. RESULTS: 821 surveys were distributed and 106 were returned. Respondents included a broad mix of specialist physicians with many patients along with general cardiologists managing only a small number of PAH-CHD patients. Although 97% of respondents have access to a specialist PH centre, patients are still being managed in non-specialist settings. Shared care arrangements are widespread but only 41% have formal shared care protocols. Palliative care services are limited and general cardiologists rarely perform 6-minute walk tests (6MWT) or quality of life assessments. People with PAH-CHD are often undertreated, with 39% of respondents reporting that fewer than 25% of these patients were receiving PAH-specific therapies. CONCLUSIONS: The survey revealed gaps and inconsistencies in the management of patients with PAH-CHD therefore patient-specific guidance is needed for many of these aspects.

Genetics in pulmonary arterial hypertension in a large homogeneous Japanese population.

Pulmonary arterial hypertension (PAH) is a rare but serious disease with a grave prognosis. Bone morphogenetic protein type 2 receptor (BMPR2) gene is a strong pathogenic factor for PAH. As a collaborative team from Kyorin University and Keio University in Japan, we have analyzed the BMPR2 gene in 356 probands and more than 50 family members, including secondary patients. Importantly, the study population is a racially, ethnically, and socially homogeneous population. In PAH patients, there is a high incidence of unique mutations in BMPR2, and several mutations are frequently observed in the Japanese population, suggesting that these common and recurring mutations may be highly pathogenic or have high penetrance, explaining why they are found frequently throughout the world. We have also mapped each breakpoint of exonic deletions/duplications and found that most break and rejoining points are in the Alu elements. Reviewing the distribution of the reported mutations on each exon of BMPR2 revealed that the number and frequency of mutations are imbalanced among exons. The penetrance of BMPR2 gene mutations was 3-fold higher in females than males. Full elucidation of BMPR2-mediated pathogenic mechanisms in PAH requires persistent efforts to achieve precision or individualized medicine as a therapeutic strategy for PAH.

Idiopathic and Systemic Sclerosis-Associated Pulmonary Arterial Hypertension: A Comparison of Demographic, Hemodynamic, and MRI Characteristics and Outcomes.

BACKGROUND: Previous studies have identified survival in systemic sclerosis (SSc)-associated pulmonary arterial hypertension (SSc-PAH) as being worse than in idiopathic pulmonary arterial hypertension (IPAH). We investigated differences between these conditions by comparing demographic, hemodynamic, and radiological characteristics and outcomes in a large cohort of incident patients. METHODS: Six hundred fifty-one patients diagnosed with IPAH or SSc-associated precapillary pulmonary hypertension were included. Patients with pulmonary disease or two or more risk factors for left heart disease were identified, leaving a primary analysis set of 375 subjects. Subgroup analysis using cardiac magnetic resonance (CMR) imaging was performed. RESULTS: Median survival was 7.8 years in IPAH and 3 years in SSc-PAH (P < .001). Patients with SSc-PAH were older with less severe hemodynamics but lower gas transfer (diffusing capacity for carbon monoxide [Dlco]). Independent prognostic factors were age, SSc, Dlco, pulmonary artery saturation, and stroke volume. After excluding patients with normal or only mildly elevated resistance, there was no difference in the relationship between pulmonary vascular resistance (PVR) and compliance in IPAH and SSc-PAH. The relationship between mean pulmonary arterial pressure (mPAP) and systolic pulmonary arterial pressure (sPAP) in IPAH was identical to that previously reported (mPAP = 0.61 sPAP + 2 mm Hg). The relationship in SSc-PAH was similar: mPAP = 0.58 sPAP + 2 mm Hg (P value for difference with IPAH = 0.095). The correlation between ventricular mass index assessed at CMR imaging and PVR was stronger in SSc-PAH. CONCLUSIONS: The reasons for poorer outcomes in SSc-PAH are likely to be multifactorial, including but not limited to older age and reduced gas transfer.

Interleukin-6 -572C/G polymorphism is associated with serum interleukin-6 levels and risk of idiopathic pulmonary arterial hypertension.

Interleukin 6 (IL-6) is a multifunctional proinflammatory cytokine that is elevated in patients with pulmonary arterial hypertension (PAH). Single nucleotide polymorphisms in the promoter region of IL-6 have been reported to transcriptional regulate the expression of IL-6. The aim of the present study is to investigate the roles of two common polymorphisms (-572C/G [rs1800796] and -6331T/C [rs10499563]) of IL-6 in idiopathic PAH (IPAH). A total of 338 IPAH patients and 352 age- and gender-matched healthy controls were enrolled. Genotyping of the two polymorphisms was performed by polymerase chain reaction and direct sequencing. Serum IL-6 levels were determined by ELISA assay. The frequencies of -572C/G genotypes CC, CG, and GG were found to be 63.6%, 32.3%, and 4.1% in IPAH patients group and 51.7%, 39.5%, and 8.8% in the controls, respectively. Compared with the individuals carrying the common genotype CC, the individuals carrying the GG genotype had a decreased risk of IPAH (adjusted odds ratio, 0.40; 95% confidence interval, 0.20-0.77; P = .006). The CG genotype and G allele carriers (CG/GG genotypes) were also observed to be associated with decreased risks of IPAH. Moreover, we found that individuals harboring -572GG or GC genotype showed significantly lower IL-6 levels than those harboring the -572CC genotype. No association between -6331T/C polymorphism and risk of IPAH or IL-6 levels was found. These results suggest that IL-6 promoter polymorphism -572C/G, but not -6331T/C, is associated with serum IL-6 levels and risk of IPAH.

Pulmonary Hypertension Registry of Kerala (PROKERALA) - Rationale, design and methods.

BACKGROUND: Pulmonary hypertension (PH) is a disease associated with a high morbidity and mortality. There is paucity of data regarding PH from the developing countries including India. Idiopathic pulmonary arterial hypertension is the most important etiological factor in the western world, but PH secondary to rheumatic heart disease, chronic obstructive pulmonary disease and untreated congenital heart disease could well be the predominant causes in developing countries like India. The main objective of the PROKERALA study - Pulmonary hypertension Registry Of Kerala is to collect data regarding the etiology, practice patterns and one-year outcomes of patients diagnosed to have PH. METHODS: The study is a hospital-based registry in the state of Kerala supported and funded by the Cardiological Society of India, Kerala Chapter. A total of 77 hospitals have agreed to participate in the registry. PH was defined as systolic pulmonary artery pressure derived by echocardiography of more than 50mmHg (by tricuspid regurgitation jet) or mean PA pressure more than 25mmHg obtained at cardiac catheterization. A detailed questionnaire is administered which includes the demographic characteristics, risk factors, family history, ECG data, 6 minute walk test distance, chest X ray findings and echocardiographic data. Details of PH specific therapy and one-year follow-up data are collected. From a preliminary survey in the region, we estimated that we will be able to collect 2000 cases over a period of one year.

The causes, treatment, and outcome of pulmonary hypertension in Africa: Insights from the Pan African Pulmonary Hypertension Cohort (PAPUCO) Registry.

BACKGROUND: Epidemiology, aetiology, management and outcome data for various forms of pulmonary hypertension (PH) in Africa are scarce. METHODS: A prospective, multinational cohort registry of 220 consecutive patients (97% of African descent) from 9 specialist centres in 4 African countries. The antecedents, characteristics and management of newly diagnosed PH plus 6-month survival were studied. RESULTS: There were 209 adults (median age 48years [IQR 35, 64]) and 11 children (age range 1 to 17years). Most adults had advanced disease - 66% WHO Functional Class III-IV, median 6-minute walk test distance of 252m (IQR 120, 350) and median right ventricular systolic pressure 58mmHg (IQR 49, 74). Adults comprised 16% pulmonary arterial hypertension, 69% PH due to left heart disease, 11% PH due to lung disease and/or hypoxia, 2% chronic thromboembolic pulmonary hypertension, and 2% PH with unclear multifactorial mechanism. At 6-months, 21% of adults with follow-up data had died. On an adjusted basis (independent of sub-groups) mortality was associated with increasing functional impairment (p=0.021 overall - WHO Class IV versus I, OR 1.68 [95% CI 0.13, 4.36]) and presence of combined right atrial and ventricular hypertrophy (46% - OR 2.88, 95% CI 1.45, 5.72). Children commonly presented with dyspnoea, fatigue, cough, and palpitations with six and three children, respectively diagnosed with concurrent PH associated congenital heart disease and left heart disease. CONCLUSIONS: These data provide new insights into PH from an African perspective, with clear opportunities to improve its prevention, treatment and outcomes. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02265887).

Characteristics and survival of adult Swedish PAH and CTEPH patients 2000-2014.

OBJECTIVES: The Swedish Pulmonary Arterial Hypertension Register (SPAHR) is an open continuous register, including pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) patients from 2000 and onwards. We hereby launch the first data from SPAHR, defining baseline characteristics and survival of Swedish PAH and CTEPH patients. DESIGN: Incident PAH and CTEPH patients 2008-2014 from all seven Swedish PAH-centres were specifically reviewed. RESULTS: There were 457 PAH (median age: 67 years, 64% female) and 183 CTEPH (median age: 70 years, 50% female) patients, whereof 77 and 81%, respectively, were in functional class III-IV at diagnosis. Systemic hypertension, diabetes, ischaemic heart disease and atrial fibrillation were common comorbidities, particularly in those >65 years. One-, 3- and 5-year survival was 85%, 71% and 59% for PAH patients. Corresponding numbers for CTEPH patients with versus without pulmonary endarterectomy were 96%, 89% and 86% versus 91%, 75% and 69%, respectively. In 2014, the incidence of IPAH/HPAH, associated PAH and CTEPH was 5, 3 and 2 per million inhabitants and year, and the prevalence was 25, 24 and 19 per million inhabitants. CONCLUSION: The majority of the PAH and CTEPH patients were diagnosed at age >65 years, in functional class III-IV, and exhibiting several comorbidities. PAH survival in SPAHR was similar to other registers.

Health-related quality of life of patients with pulmonary arterial hypertension associated with CHD: the multicentre cross-sectional ACHILLE study.

BACKGROUND: The aim of this study was to assess health-related quality of life in patients with pulmonary arterial hypertension associated with CHD and correlations with clinical status. METHODS: This prospective cross-sectional observational study included CHD patients with pulmonary arterial hypertension in 14 tertiary-care centres in France. We used two health-related quality of life questionnaires - SF-36 and Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) - and one anxiety/depression Hospital Anxiety and Depression Scale (HADS) questionnaire. RESULTS: Clinical data were collected for the 208 included patients (mean age: 42.6 years, range from 15.1 to 85.8 years, 69.7% female). Most patients were in NYHA functional class II (48.1%) and III (37.5%). Patients' phenotype was classified as Eisenmenger syndrome (70.7%), pulmonary arterial hypertension associated with systemic-to-pulmonary shunts (12.0%), with small defects (3.4%), or after corrective cardiac surgery (13.9%). In total, 76.4% of the patients were receiving pulmonary arterial hypertension-specific treatments. SF-36 scores showed impairment compared with normalised data. Health-related quality of life scores were significantly lower in females than in males for most dimensions of both questionnaires and were independent of the patients' phenotype, even after gender adjustment - except for CAMPHOR functioning - but significantly depended on NYHA functional class. The Hospital Anxiety and Depression Scale (HADS) scores suggested anxiety and depression associated with increasing NYHA functional class but independent of patients' phenotype. NYHA functional class, 6-minute walk distance, HADS, gender, and recent stressful event significantly affected quality of life in the multivariate analysis. CONCLUSIONS: This study showed impairment of quality of life in a large cohort of patients with pulmonary arterial hypertension associated with CHD with both generic and specific questionnaires. NYHA functional class and HADS scores were predictive of most quality of life scores.

Six-minute walking distance and decrease in oxygen saturation during the six-minute walk test in pediatric pulmonary arterial hypertension.

OBJECTIVE: To investigate the prognostic value of the 6-minute walking distance (6-MWD), transcutaneous saturation (tcSO2) and heart rate (HR) obtained during the 6-minute walk test (6-MWT) in pediatric pulmonary arterial hypertension (PAH). METHODS: This was an observational study with forty-seven pediatric PAH patients, aged ≥7 years, and diagnosed and followed at the national referral center for pediatric PAH in the Netherlands. All patients performed a comprehensive 6-minute walk test (6-MWT), which measures 6-MWD and tcSO2 and HR before ("baseline"), during ("exercise") and 5 min after ("recovery") the walk test. RESULTS: The 6-MWD expressed either in meters or in sex- and age-corrected z-scores, was associated with transplant-free survival, independently from sex, age, and the presence of a shunt-defect. Shorter 6-MWD correlated with higher WHO-FC and increased NT-pro-BNP. Absolute tcSO2 at exercise and tcSO2-decrease during 6-MWT were associated with transplant-free survival, independent from 6-MWD. Combining tcSO2-decrease with 6-MWD provided the strongest prognostic model. Patients with 6-MWD>352 m (the median 6-MWD) had a better outcome than those with smaller 6-MWD. A large tcSO2-decrease during 6-MWT (>19% for patients with and >5% for patients without a shunt defect) identified patients with worse transplant-free survival both in patients with a 6-MWD above and below the median 6-MWD. CONCLUSIONS: The 6-MWD is an independent predictor of prognosis in pediatric PAH, that reflects disease severity and clinically relevant exercise-tolerance and therefore qualifies as a treatment goal. The magnitude of tcSO2-decrease during 6-MWT, adjusted for the presence of a shunt, indicates an additional risk factor for prognosis in children with PAH.