Change in health-related quality of life at early follow-up in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.

Symptoms associated with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) impact patient's health-related quality of life (HRQoL). Studies on change and if a minimal clinically important difference (MCID) in HRQoL is reached within a year after diagnosis are lacking. The aim was to investigate the change in HRQoL as well as the proportion of patients that reached MCID at an early postdiagnosis visit. The study included adult patients from the Swedish PAH & CTEPH registry, diagnosed 2008-2021, with Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) at time of diagnosis and a follow-up. Data were analyzed as total population and dichotomized for sex, age (<65 vs. ≥65 years), time of diagnosis (≤2015 vs. >2015) and pulmonary hypertension (PH) subgroups. Data reported as median, interquartile range (IQR), and proportions (%). There were 151 patients (PAH = 119, CTEPH = 32) with an available CAMPHOR score at diagnosis and follow-up. CAMPHOR total sum was 31 (IQR: 21-43) and 25 (14-36); (p < 0.001) at diagnosis and follow-up, respectively. At follow-up, 56% had reached MCID in total sum, while for domains activity, symptoms, and QoL 27%, 33%, and 39% reached MCID, respectively. These results were independent of PH subgroup, diagnosis before or after 2015 and sex. Age below 65 years was related to improvements in activity and worsening of symptoms. In conclusion on a group level, improvements in CAMPHOR total sum as well as all domains were seen in the first year after diagnosis, however, only slightly more than half of the patients reached MCID for CAMPHOR total sum.

Societal costs associated to chronic thromboembolic pulmonary hypertension: A study utilizing linked national registries.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare but serious complication after a pulmonary embolism. Healthcare resource utilization (HCRU; hospitalization, outpatient visits, and drug utilization) as well as productivity loss (sick leave and disability pension) before and after the CTEPH diagnosis is sparsely studied. By linking several Swedish national databases, this study estimated the societal costs in a national CTEPH cohort (n = 369, diagnosed with CTEPH in 2008-2019) 5 years before and 5 years after diagnosis (index date) and compared to an age, sex, and geographically matched control group (n = 1845, 1:5 match). HCRU and productivity loss were estimated per patient per year. Patients were stratified as operated with pulmonary endarterectomy (PEA group) or not operated (non-PEA group). Direct and indirect societal costs were 2.1 times higher before, and 8.1 times higher after the index date for patients with CTEPH compared to the matched control groups. The higher costs were evident already several years preceding the index date. The main cost driver before the index date in both the PEA and the non-PEA groups was productivity loss. The productivity loss remained high for both groups in the 5-year period following the index date, but the main cost drivers were prescribed drugs and hospitalizations for patients that underwent PEA and prescribed drugs in the non-PEA group. In conclusion, CTEPH was associated with large societal costs related to healthcare consumption and productivity loss, both before and after diagnosis.

Societal costs associated with pulmonary arterial hypertension: A study utilizing linked national registries.

Pulmonary arterial hypertension (PAH) is a progressive disease with no cure. Healthcare resource utilization (HCRU; hospitalization, outpatient visits, and drug utilization) before diagnosis and productivity loss (sick leave and disability pension) before and after PAH diagnosis are not well known. By linking several Swedish national databases, this study have estimated the societal costs in a national PAH cohort (n = 749, diagnosed with PAH in 2008-2019) 5 years before and 5 years after diagnosis and compared to an age, sex, and geographically matched control group (n = 3745, 1:5 match). HCRU and productivity loss were estimated per patient per year. The PAH group had significantly higher HCRU and productivity loss compared to the control group starting already 3 and 5 years before diagnosis, respectively. HCRU peaked the year after diagnosis in the PAH group with hospitalizations (mean ± standard deviation; 2.0 ± 0.1 vs. 0.2 ± 0.0), outpatient visits (5.3 ± 0.3 vs. 0.9 ± 0.1), and days on sick leave (130 ± 10 vs. 13 ± 1) significantly higher compared to controls. Total costs during the entire 10-year period were six times higher for the PAH group than the control group. In the 5 years before diagnosis the higher costs were driven by productivity loss (76%) and hospitalizations (15%), while the 5 years after diagnosis the main cost drivers were drugs (63%), hospitalizations (16%), and productivity loss (16%). In conclusion, PAH was associated with large societal costs due to high HCRU and productivity loss, starting several years before diagnosis. The economic and clinical burden of PAH suggests that strategies for earlier diagnosis and more effective treatments are warranted.

Prevalence of potential drug-drug interactions with disease-specific treatments in patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension: A registry study.

Polypharmacy increases the risk of drug-drug interactions that may disturb treatment effects. The aim of this study was to investigate the frequency of codispensing of potentially interacting or contraindicated drugs related to PH-specific treatment in the Swedish pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) population. All prescribed drugs, on an individual level, dispensed 2016-2017 at pharmacies to patients with PAH or CTEPH were obtained from The National Board of Health and Welfare's pharmaceutical registry. Potential drug-drug interactions were investigated using the Drug Interaction tool in the IBM Micromedex® database. There were 4785 different dispensed drugs from 572 patients (mean age 61 ± 16 years, 61% female, mean number of drugs per patient 8.4 ± 4.2) resulting in 1842 different drug combinations involving a PH-specific treatment. Of these drug combinations, 67 (3.5%) had a potential drug-drug interaction considered clinically relevant and it affected 232 patients (41%). The PH-specific drugs with the highest number of potential drug-drug interactions was bosentan (n = 23, affected patients = 171) while the most commonly codispensed, potentially interacting drug combination was sildenafil/furosemide (119 patients affected). Other common codispensed and potentially interacting drugs were anticoagulants (n = 11, affected patients = 100) and antibiotic treatment (n = 12, affected patients = 26). In conclusion, codispensing of PH-specific therapy and potentially interacting drugs was common, but codispensing of potentially contraindicated drugs was rare.

Long-term prognosis after a first myocardial infarction: eight years follow up of the case-control study PAROKRANK.

Objective. To explore long-term cardiovascular outcomes and mortality in patients after a first myocardial infarction (MI) compared with matched controls in a contemporary setting. Methods. During 2010-2014 the Swedish study PAROKRANK recruited 805 patients <75 years with a first MI and 805 age-, gender-, and area-matched controls. All study participants were followed until 31 December 2018, through linkage with the National Patient Registry and the Cause of Death Registry. The primary endpoint was the first of a composite of all-cause death, non-fatal MI, non-fatal stroke, and heart failure hospitalization. Event rates in cases and controls were calculated using a Cox regression model, subsequently adjusted for baseline smoking, education level, and marital status. Kaplan-Meier curves were computed and compared by log-rank test. Results. A total of 804 patients and 800 controls (mean age 62 years; women 19%) were followed for a mean of 6.2 (0.2-8.5) years. The total number of primary events was 211. Patients had a higher event rate than controls (log-rank test p < .0001). Adjusted hazard ratio (HR) for the primary outcome was 2.04 (95% CI 1.52-2.73). Mortality did not differ between patients (n = 38; 4.7%) and controls (n = 35; 4.4%). A total of 82.5% patients and 91.3% controls were event-free during the follow up. Conclusions. In this long-term follow up of a contemporary, case-control study, the risk for cardiovascular events was higher in patients with a previous first MI compared with their matched controls, while mortality did not differ. The access to high quality of care and cardiac rehabilitation might partly explain the low rates of adverse outcomes.

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

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

Atrioventricular plane displacement and regional function to predict outcome in pulmonary arterial hypertension.

To investigate if left and right atrioventricular plane displacement (AVPD) or regional contributions to SV are prognostic for outcome in patients with pulmonary arterial hypertension (PAH). Seventy-one patients with PAH and 20 sex- and age-matched healthy controls underwent CMR. Myocardial borders and RV insertion points were defined at end diastole and end systole in cine short-axis stacks to compute biventricular volumes, lateral (SVlat%) and septal (SVsept%) contribution to stroke volume. Eight atrioventricular points were defined at end diastole and end systole in 2-, 3- and 4-chamber cine long-axis views for computation of AVPD and longitudinal contribution to stroke volume (SVlong%). Cut-off values for survival analysis were defined as two standard deviations above or below the mean of the controls. Outcome was defined as death or lung transplantation. Median follow-up time was 3.6 [IQR 3.7] years. Patients were 57 ± 19 years (65% women) and controls 58 ± 15 years (70% women). Biventricular AVPD, SVlong% and ejection fraction (EF) were lower and SVlat% was higher, while SVsept% was lower in PAH compared with controls. In PAH, transplantation-free survival was lower below cut-off for LV-AVPD (hazard ratio [HR] = 2.1, 95%CI 1.2-3.9, p = 0.02) and RV-AVPD (HR = 9.8, 95%CI 4.6-21.1, p = 0.005). In Cox regression analysis, lower LV-AVPD and RV-AVPD inferred lower transplantation-free survival (LV: HR = 1.16, p = 0.007; RV: HR = 1.11, p = 0.01; per mm decrease). LV-SVlong%, RV-SVlong%, LV-SVlat%, RV-SVlat%, SVsept% and LV- and RVEF did not affect outcome. Low left and right AVPD were associated with outcome in PAH, but regional contributions to stroke volume and EF were not.

Respiratory rate modulation improves symptoms in patients with pulmonary hypertension.

BACKGROUND: Pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension are chronic diseases with a severe symptom burden. Common symptoms are dyspnoea at light activity and general fatigue that limits daily activities. Respiratory modulation by device-guided breathing decreased symptoms in patients with heart failure. The aim of this pilot study was to investigate if respiratory modulation could improve symptoms of dyspnoea in patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. METHOD: Adult patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension with symptoms of dyspnoea at rest or light activity performed home-based respiratory modulation by device-guided breathing 20 min a day for 3 months. Patients were on stable disease-specific treatment ⩾3 months and willing to undergo all study procedures. Dyspnoea score, World Health Organization class, physical status, N-terminal pro b-type natriuretic peptide, quality of life, respiratory rate and 6-min walk distance were assessed before and after 3 months with respiratory modulation. RESULTS: Nine patients with pulmonary arterial hypertension and five with chronic thromboembolic pulmonary hypertension completed the study protocol. Mean age was 71 ± 14 years, and 11 were women. After 3 months of respiratory modulation, dyspnoea score (-0.6, p = 0.014), respiratory rate at rest (-3 breaths/min, p = 0.013), World Health Organization class (-0.3, p = 0.040), quality of life (EuroQol Visual Analogue Scale +5 points, not significant) and decreased N-terminal pro b-type natriuretic peptide (-163 ng/L, p = 0.043) had improved. The fatigue and respiratory rate after the 6-min walk decreased while the 6-min walk distance remained unchanged. CONCLUSION: Patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension that used device-guided breathing for 3 months improved symptoms of dyspnoea and lowered the respiratory rate at rest and after exercise.

Early risk prediction in idiopathic versus connective tissue disease-associated pulmonary arterial hypertension: call for a refined assessment.

Despite systematic screening and improved treatment strategies, the prognosis remains worse in patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) compared to patients with idiopathic/hereditary pulmonary arterial hypertension (IPAH). We aimed to investigate differences in clinical characteristics, outcome and performance of the European Society of Cardiology (ESC)/ European Respiratory Society (ERS) risk stratification tool in these patient groups. This retrospective analysis included incident patients with CTD-PAH (n=197, of which 64 had interstitial lung disease, ILD) or IPAH (n=305) enrolled in the Swedish PAH Register (SPAHR) 2008-2019. Patients were classified as low, intermediate or high risk at baseline, according to the "SPAHR-equation". One-year survival, stratified by type of PAH, was investigated by Cox proportional regression. At baseline, CTD-PAH patients had lower diffusing capacity for carbon monoxide and lower haemoglobin but, at the same time, lower N-terminal prohormone-brain natriuretic peptide, longer 6 min walk distance, better haemodynamics and more often a low-risk profile. No difference in age, World Health Organisation functional class (WHO-FC) or renal function between groups was found. One-year survival rates were 75, 82 and 83% in patients with CTD-PAH with ILD, CTD-PAH without ILD and IPAH, respectively. The 1-year mortality rates for low-, intermediate- and high-risk groups in the whole cohort were 0, 18 and 34% (p<0.001), respectively. Corresponding percentages for CTD-PAH with ILD, CTD-PAH without ILD and IPAH patients were: 0, 26, 67% (p=0.008); 0, 19, 39% (p=0.004); and 0, 16, 29% (p=0.001), respectively. The ESC/ERS risk assessment tool accurately identified low-risk patients but underestimated the 1-year mortality rate of CTD-PAH and IPAH patients assessed as having intermediate risk at diagnosis.

The Odyssey from Symptom to Diagnosis of Pulmonary Hypertension from the Patients and Spouses Perspective.

INTRODUCTION/OBJECTIVE: Diagnostic delays in pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are related to increased morbidity and mortality. The risk of a delayed, or even a missed, diagnosis is high as the conditions are rare. The aim was to describe patients' and spouses' experiences of the journey from the first symptom to an established diagnosis. METHODS: A secondary analysis of 31 transcripts, based on 2 primary datasets containing interviews with 17 patients and 14 spouses, was carried out and analyzed according to qualitative content analysis. RESULTS: One overarching category was revealed from the content analysis; "The journey from doubt and hope to receive the diagnosis." Five subcategories were identified as: overall experiences; ignoring symptoms; seeking primary care/hospital specialty care; blame and stigma; and finding a pulmonary hypertension specialist clinic. The main finding was that both patients and spouses experienced that waiting for a diagnosis and the deteriorating state of health led to anxiety and frustration. The knowledge about rare diseases among health professionals needs to be improved to enable a timelier diagnosis and initiation of treatment. CONCLUSION: Patients' and spouses' lives were negatively affected by having to search for a correct diagnosis. In order for health care to identify rare diseases earlier, a well-functioning and responsive health care system, in primary care as well as in specialist care, is needed. Symptoms like breathlessness and fatigue are often unspecific but should not be ignored. Keeping the patient and spouse in the loop, and providing information that the search for an answer might take time is essential for health care providers to create trust.

Predicting mortality during long-term follow-up in pulmonary arterial hypertension.

The European Society of Cardiology (ESC) and European Respiratory Society (ERS) guideline recommendation of comprehensive risk assessments, which classify patients with pulmonary arterial hypertension (PAH) as having low, intermediate or high mortality risk, has not been evaluated during long-term follow-up in a "real-life" clinical setting. We therefore aimed to investigate the utility of risk assessment in a clinical setting for up to 5 years post diagnosis. 386 patients with PAH from the Swedish PAH Registry were included. Risk group (low/intermediate/high) and proportion of low-risk variables were investigated at 3-, 4- and 5-year follow-ups after time of diagnosis. In an exploratory analysis, survival rates of patients with low-intermediate or high-intermediate risk scores were compared. A low-risk profile was in multivariate Cox proportional hazards regressions found to be a strong, independent predictor of longer transplant-free survival (p<0.001) at the 3-, 4- and 5-year follow-ups. Also, for the 3-, 4- and 5-year follow-ups, survival rates significantly differed (p<0.001) between the three risk groups. Patients with a greater proportion of low-risk variables had better (p<0.001) survival rates. Patients with a high-intermediate risk score had worse survival rates (p<0.001) than those with a low-intermediate risk score. Results were similar when excluding patients with ≥3 risk factors for heart failure with preserved ejection fraction, atrial fibrillation and/or age >75 years at diagnosis. Our findings suggest that the ESC/ERS guideline strategy for comprehensive risk assessments in PAH is valid also during long-term follow-up in a "real-life" clinical setting.

Accuracy of echocardiographic estimates of pulmonary artery pressures in pulmonary hypertension: insights from the KARUM hemodynamic database.

Accurate assessment of pulmonary artery (PA) pressures is integral to diagnosis, follow-up and therapy selection in pulmonary hypertension (PH). Despite wide utilization, the accuracy of echocardiography to estimate PA pressures has been debated. We aimed to evaluate echocardiographic accuracy to estimate right heart catheterization (RHC) based PA pressures in a large, dual-centre hemodynamic database. Consecutive PH referrals that underwent comprehensive echocardiography within 3 h of clinically indicated right heart catheterization were enrolled. Subjects with absent or severe, free-flowing tricuspid regurgitation (TR) were excluded. Accuracy was defined as mean bias between echocardiographic and invasive measurements on Bland-Altman analysis for the cohort and estimate difference within ± 10 mmHg of invasive measurements for individual diagnosis. In 419 subjects, echocardiographic PA systolic and mean pressures demonstrated minimal bias with invasive measurements (+ 2.4 and + 1.9 mmHg respectively) but displayed wide limits of agreement (- 20 to + 25 and - 14 to + 18 mmHg respectively) and frequently misclassified subjects. Recommendation-based right atrial pressure (RAP) demonstrated poor precision and was falsely elevated in 32% of individual cases. Applying a fixed, median RAP to echocardiographic estimates resulted in relatively lower bias between modalities when assessing PA systolic (+ 1.4 mmHg; 95% limits of agreement + 25 to - 22 mmHg) and PA mean pressures (+ 1.4 mmHg; 95% limits of agreement + 19 to - 16 mmHg). Echocardiography accurately represents invasive PA pressures for population studies but may be misleading for individual diagnosis owing to modest precision and frequent misclassification. Recommendation-based estimates of RAPmean may not necessarily contribute to greater accuracy of PA pressure estimates.

Periodontitis, assessed using periodontal treatment as a surrogate marker, has no association with a first myocardial infarction in a Swedish population.

BACKGROUND: Periodontitis is suggested to be associated with a risk of cardiovascular events. Using periodontal treatment recorded in Swedish national registries as a surrogate marker, we aimed to investigate whether periodontitis was associated with a first myocardial infarction. METHODS: This nationwide case-control study, with data from national registries, involved 51,880 individuals with a first myocardial infarction in 2011 to 2013 (index date) and 246,978 controls matched 5:1 for age, gender, and geographic area. Periodontal treatment in the 3 years preceding the index date was classified as (1) no dental treatment, (2) no periodontal treatment, (3) one or more supragingival curettages, or (4) one or more treatments with scaling/root planing and/or periodontal surgery. Annual frequencies of treatment with scaling/root planing and/or periodontal surgery were also calculated. In all analyses, conditional logistic regression analyses estimated ORs for myocardial infarction with 95% CIs, adjusted for matched variables, income, education, and diabetes. RESULTS: Although fewer cases than controls received treatment with scaling/root planing and/or periodontal surgery (19.2% versus 19.8%, P < 0.001), annual frequencies for cases were higher. We found no association of scaling/root planing and/or periodontal surgery with a first myocardial infarction (OR = 1.02; 95% CI: 1.00, 1.05). We did observe a non-significant trend, however, between risk of a first myocardial infarction and a high frequency of scaling/root planing and/or periodontal surgery (OR 1.14; 95% CI: 1.00, 1.29). CONCLUSION: In the contemporary Swedish nationwide setting, no association between a first myocardial infarction and periodontitis, assessed as periodontal treatment, was found.

Underfilling decreases left ventricular function in pulmonary arterial hypertension.

To evaluate the association between impaired left ventricular (LV) longitudinal function and LV underfilling in patients with pulmonary arterial hypertension (PAH). Thirty-nine patients with PAH and 18 age and sex-matched healthy controls were included. LV volume and left atrial volume (LAV) were delineated in short-axis cardiac magnetic resonance (CMR) cine images. LV longitudinal function was assessed from atrio-ventricular plane displacement (AVPD) and global longitudinal strain (GLS) was assessed using feature tracking in three long-axis views. LV filling was assessed by LAV and by pulmonary artery wedge pressure (PAWP) using right heart catheterisation. Patients had a smaller LAV, LV volume and stroke volume as well as a lower LV-AVPD and LV-GLS than controls. PAWP was 6 [IQR 5--9] mmHg in patients. LV ejection fraction did not differ between groups. LV stroke volume correlated with LV-AVPD (r = 0.445, p = .001), LV-GLS (r = - 0.549, p < 0.0001) and LAVmax (r = .585, p < 0.0001). Furthermore, LV-AVPD (r = .598) and LV-GLS (r = - 0.675) correlated with LAVmax (p < 0.0001 for both). Neither LV-AVPD, LV-GLS, LAVmax nor stroke volume correlated with PAWP. Impaired LV longitudinal function was associated with low stroke volume, low PAWP and a small LAV in PAH. Small stroke volumes and LAV, together with normal LA pressure, implies that the mechanism causing reduced LV longitudinal function is underfilling rather than an intrinsic LV dysfunction in PAH.

Longitudinal changes in risk status in pulmonary arterial hypertension.

AIMS: Low-risk status in pulmonary arterial hypertension (PAH) predicts better survival. The present study aimed to describe changes in risk status and treatment approaches over multiple clinical assessments in PAH, taking age and comorbidity burden into consideration. METHODS AND RESULTS: The study included incident patients from the Swedish PAH registry, diagnosed with PAH in 2008-2019. Group A (n = 340) were ≤75 years old with <3 comorbidities. Group B (n = 163) were >75 years old with ≥3 comorbidities. Assessments occurred at baseline, first-year (Y1) and third-year (Y3) follow-ups. The study used an explorative and descriptive approach. Group A: median age was 65 years, 70% were female, and 46% had no comorbidities at baseline. Baseline risk assessment yielded low (23%), intermediate (66%), and high risk (11%). Among patients at low, intermediate, or high risk at baseline, 51%, 18%, and 13%, respectively, were at low risk at Y3. At baseline, monotherapy was the most common therapy among low (68%) and intermediate groups (60%), while dual therapy was the most common among high risk (69%). In patients assessed as low, intermediate, or high risk at Y1, 66%, 12%, and 0% were at low risk at Y3, respectively. Of patients at intermediate or high risk at Y1, 35% received monotherapy and 13% received triple therapy. In low-risk patients at Y1, monotherapy (40%) and dual therapy (43%) were evenly distributed. Group B: median age was 77 years, 50% were female, and 44% had ≥3 comorbidities at baseline. At baseline, 8% were at low, 80% at intermediate, and 12% at high risk. Monotherapy was the most common therapy (62%) in Group B at baseline. Few patients maintained or reached low risk at follow-ups. CONCLUSIONS: Most patients with PAH did not meet low-risk criteria during the 3 year follow-up. The first year from diagnosis seems important in defining the longitudinal risk status.

Risk stratification in chronic thromboembolic pulmonary hypertension predicts survival.

OBJECTIVES: To investigate if the pulmonary arterial hypertension (PAH) risk assessment tool presented in the 2015 ESC/ERS guidelines is valid for patients with chronic thromboembolic pulmonary hypertension (CTEPH) when taking pulmonary endarterectomy (PEA) into account. Design. Incident CTEPH patients registered in the Swedish PAH Registry (SPAHR) between 2008 and 2016 were included. Risk stratification performed at baseline and follow-up classified the patients as low-, intermediate-, or high-risk using the proposed ESC/ERS risk algorithm. Results. There were 250 CTEPH patients with median age (interquartile range) 70 (14) years, and 53% were male. Thirty-two percent underwent PEA within 5 (6) months. In a multivariable model adjusting for age, sex, and pharmacological treatment, patients with intermediate-risk or high-risk profiles at baseline displayed an increased mortality risk (Hazard Ratio [95% confidence interval]: 1.64 [0.69-3.90] and 5.39 [2.13-13.59], respectively) compared to those with a low-risk profile, whereas PEA was associated with better survival (0.38 [0.18-0.82]). Similar impact of risk profile and PEA was seen at follow-up. Conclusion. The ESC/ERS risk assessment tool identifies CTEPH patients with reduced survival. Furthermore, PEA improves survival markedly independently of risk group and age. Take home message: The ESC/ERS risk stratification for PAH predicts survival also in CTEPH patients, even when taking PEA into account.

Adherence to disease-specific drug treatment among patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) require lifelong treatment. The aim of the present study was to investigate adherence to disease-specific treatment in patients with PAH or CTEPH. METHODS: The study comprised an adult population diagnosed with PAH (n=384) or CTEPH (n=187) alive in 2016-2017. The study utilised three registries: the Swedish PAH registry, the National Board of Health and Welfare, and Statistics Sweden. Withdrawals from pharmacies of disease-specific oral treatments were studied. Adherence was assessed as: 1) Number of days covered defined as the difference between the total number of daily dosages dispensed and the total number of days covered; and 2) Manual assessment by two persons that independently reviewed each patient's prescription fill history to detect anomalies or patterns of deteriorating or improving adherence over time. RESULTS: The mean age was 61±16 years, 61% were female and mean time since diagnosis was 4.6 years. Adherence was 62% using the Number of days covered method and 66% by the Manual assessment method. Drug-specific adherence varied from 91% for riociguat to 60% for sildenafil. Good adherence was associated with shorter time since diagnosis in patients with PAH and with lower number of concomitant other chronic treatments in patients with CTEPH. Age, sex, socioeconomic status or number of pulmonary hypertension (PH) treatments were not associated with adherence. CONCLUSION: Adherence to oral disease-specific treatment was 60-66% and associated with time since diagnosis and number of concomitant chronic treatments. Sex, age or socioeconomic factors did not affect adherence.

Poor outcome of patients with pulmonary arterial hypertension with insufficient response to phosphodiesterase-5 inhibitors alone or in combination with other specific therapy: a registry-based study.

Phosphodiesterase-5 inhibitors are commonly used in pulmonary arterial hypertension but, as suggested by the RESPITE study, phosphodiesterase-5 inhibitor therapy (mono-/combination) does not always have a satisfactory treatment effect. This study aimed to investigate the clinical course of pulmonary arterial hypertension patients not at treatment goal after at least 90 days of treatment with phosphodiesterase-5 inhibitors, alone or in combination with other pulmonary arterial hypertension therapies. The study included 106 incident patients from the Swedish Pulmonary Arterial Hypertension Registry, treated with phosphodiesterase-5 inhibitors for ≥90 days, who were not at a pre-specified treatment goal, i.e. in World Health Organisation functional class III, with 6-min walking distance 165-440 m, and N-terminal prohormone of brain natriuretic peptide >300 ng/L. Changes in World Health Organisation functional class, 6-min walking distance, N-terminal prohormone of brain natriuretic peptide, and risk group between index and follow-up were assessed. Of patients with complete follow-up data, (n = 53) 77% were on combination therapy and risk assessment yielded 98% at intermediate risk at index. At follow-up, 11 patients transitioned from World Health Organisation functional class III to World Health Organisation functional class II, the median (Q1; Q3) change in 6-min walking distance was 6 (-30; 42) meters and in N-terminal prohormone of brain natriuretic peptide 47 (-410; 603) ng/L, while 89% remained at an intermediate risk. Of those without complete follow-up data, 11 patients died and 2 underwent lung transplantation. In conclusion, pulmonary arterial hypertension patients treated with phosphodiesterase-5 inhibitors, as single or combination therapy and not achieving the pre-specified treatment goals after ≥90 days have an unfavourable clinical course.

Cardiac Magnetic Resonance Imaging in Pulmonary Arterial Hypertension: Ready for Clinical Practice and Guidelines?

PURPOSE OF REVIEW: Pulmonary arterial hypertension (PAH) is a progressive disease with high mortality. A greater understanding of the physiology and function of the cardiovascular system in PAH will help improve survival. This review covers the latest advances within cardiovascular magnetic resonance imaging (CMR) regarding diagnosis, evaluation of treatment, and prognostication of patients with PAH. RECENT FINDINGS: New CMR measures that have been proven relevant in PAH include measures of ventricular and atrial volumes and function, tissue characterization, pulmonary artery velocities, and arterio-ventricular coupling. CMR markers carry prognostic information relevant for clinical care such as treatment response and thereby can affect survival. Future research should investigate if CMR, as a non-invasive method, can improve existing measures or even provide new and better measures in the diagnosis, evaluation of treatment, and determination of prognosis of PAH.

Correction to: Cardiac Magnetic Resonance Imaging in Pulmonary Arterial Hypertension: Ready for Clinical Practice and Guidelines?

The original version of this article contains error in the text.