scholarly journals Idiopathic pulmonary arterial hypertension and co-existing lung disease: is this a new phenotype?

2020 ◽  
Vol 10 (1) ◽  
pp. 204589402091485 ◽  
Author(s):  
Andrew J. Peacock ◽  
Yi Ling ◽  
Martin K. Johnson ◽  
David G. Kiely ◽  
Robin Condliffe ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Lung Disease ◽  
Idiopathic Pulmonary Arterial Hypertension ◽  
Walk Distance ◽  
Pulmonary Arterial ◽  
Minute Walk Distance ◽  
Minute Walk ◽  
Group 1

Patients classified as idiopathic pulmonary arterial hypertension (defined as Group 1 on European Respiratory Society (ERS)/European Cardiac Society (ESC) criteria) may have evidence of minor co-existing lung disease on thoracic computed tomography. We hypothesised that these idiopathic pulmonary arterial hypertension patients ( IPAH lung disease) are a separate subgroup of idiopathic pulmonary arterial hypertension with different phenotype and outcome compared with idiopathic pulmonary arterial hypertension patients without co-existing lung disease ( IPAH no lung disease). Patients with ‘ IPAH lung disease’ have been eligible for all clinical trials of Group 1 patients because they have normal clinical examination and normal spirometry but we wondered whether they responded to treatment and had similar survival to patients with ‘ IPAH no lung disease’. We described the outcome of the cohort of patients with ‘ IPAH no lung disease’ in a previous paper. Here, we have compared incident ‘ IPAH lung disease’ patients with ‘ IPAH no lung disease’ patients diagnosed concurrently in all eight Pulmonary Hypertension centres in the UK and Ireland between 2001–2009. Compared with ‘ IPAH no lung disease’ ( n = 355), ‘ IPAH lung disease’ patients ( n = 137) were older, less obese, predominantly male, more likely to be current/ex-smokers and had lower six-minute walk distance, lower % predicted diffusion capacity for carbon monoxide, lower mean pulmonary arterial pressure and lower pulmonary vascular resistance index. After three months of pulmonary hypertension-targeted treatment, six-minute walk distance improved equally in ‘ IPAH lung disease’ and ‘ IPAH no lung disease’. However, survival of ‘ IPAH lung disease’ was lower than ‘ IPAH no lung disease’ (one year survival: 72% compared with 93%). This survival was significantly worse in ‘ IPAH lung disease’ even after adjusting for age, gender, smoking history, comorbidities and haemodynamics. ‘ IPAH lung disease’ patients had similar short-term improvement in six-minute walk distance with anti-pulmonary arterial hypertension therapy but worse survival compared with ‘ IPAH no lung disease’ patients. This suggests that ‘ IPAH lung disease’ are a separate phenotype and should not be lumped with ‘ IPAH no lung disease’ in clinical trials of Group 1 pulmonary arterial hypertension.

scholarly journals Prognostic value of six-minute walk distance at a South American pulmonary hypertension referral center

2020 ◽  
Vol 10 (2) ◽  
pp. 204589401988842
Author(s):  
Gabriela O.S. Costa ◽  
Roberta P. Ramos ◽  
Rudolf K.F. Oliveira ◽  
Angelo Cepêda ◽  
Elaine B. Vieira ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Survival Rates ◽  
Walk Distance ◽  
Hypertension Guidelines ◽  
All Cause Mortality ◽  
Pulmonary Arterial ◽  
Minute Walk Distance ◽  
Minute Walk

Six-minute walk distance (6MWD) assessment is recommended for pulmonary arterial hypertension multidimensional risk stratification. However, current 6MWD cut-off values were mainly derived from North American and European pulmonary arterial hypertension registries. Therefore, it is unknown if such cut-off values broadly apply to other geographical populations. In this study, we aimed to identify 6MWD cut-off values for Brazilian pulmonary arterial hypertension patients and to contrast our findings to current international Pulmonary Hypertension guidelines recommendations. One-hundred four consecutive pulmonary arterial hypertension patients were allocated in groups according to their 6MWD, considering 50 m as a clinically relevant 6MWD difference. Next, patients were categorized into different 6MWD ranges based on similar survival rates in each group: < 250 m, 250–400 m, and >400 m. The study outcome was all-cause mortality and transplantation according to the 6MWD range. Survival was truncated at five years. Median follow-up period was 4.35 years (0.48–5.00). Survival rates at 1, 2, 3, and 5 years were 96%, 89%, 81%, and 73%, respectively. Cox analyses adjusted for age, sex, and pulmonary arterial hypertension etiology showed that 6MWD < 250 m and >400 m were associated with higher and lower risk of all-cause mortality and transplantation. According to Harrell's c-statistic, the prognostic discrimination of the 6MWD cut-off value identified by the current study was 0.70 while international Pulmonary Hypertension guidelines 6MWD cut-offs value was 0.61. In conclusion, our findings suggest that 6MWD geographical variations should be considered when assessing risk stratification in pulmonary arterial hypertension.

scholarly journals Novel dose–response analyses of treprostinil in pulmonary arterial hypertension and its effects on six-minute walk distance and hospitalizations

2020 ◽  
Vol 10 (3) ◽  
pp. 204589402092395
Author(s):  
Gautam Ramani ◽  
Steven Cassady ◽  
Eric Shen ◽  
Meredith Broderick ◽  
Allie Wasik ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Dose Response ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Walk Distance ◽  
Pulmonary Arterial ◽  
Higher Doses ◽  
Minute Walk Distance ◽  
Minute Walk

Treprostinil is a prostacyclin analogue approved for the treatment of pulmonary arterial hypertension. Apart from the inhaled formulation, there is neither a target dose nor a ceiling dose to guide clinicians using treprostinil; doses are individualized for each patient based upon tolerability and clinical improvement. Using combined data from the pivotal subcutaneous and oral treprostinil studies, we evaluated the effect of treprostinil dose on hospitalization and exercise capacity to better define the treprostinil dose–response relationship. Data from the pivotal subcutaneous and oral treprostinil studies were combined by converting oral doses to weight-based continuous doses (ng/kg/min) accounting for patient weight and bioavailability. Patients were divided into dose tertiles (lowest, middle, highest 33%) and retrospectively analyzed. Analysis 1 assessed the effect of dose on pulmonary arterial hypertension-related and all-cause hospitalizations. Analysis 2 evaluated the effects of dose on six-minute walk distance, Borg dyspnea score, and World Health Organization functional class. Results showed that, in Analysis 1, higher doses of treprostinil were associated with significantly longer times to first pulmonary arterial hypertension-related and all-cause hospitalization. In Analysis 2, there was a trend toward improvements in six-minute walk distance with higher doses. In patients with pulmonary arterial hypertension on systemic treprostinil therapy, higher doses were associated with significantly longer time to first pulmonary arterial hypertension-related and all-cause hospitalization. There was a trend toward improvements in six-minute walk distance. Collectively, these results underscore the importance of managing prostacyclin adverse events in order to achieve appropriate dose titration. Further studies are required to confirm these findings and to better characterize the dose–response relationship of treprostinil.

scholarly journals Do Changes of 6-Minute Walk Distance Predict Clinical Events in Patients With Pulmonary Arterial Hypertension?

2012 ◽  
Vol 60 (13) ◽  
pp. 1192-1201 ◽  
Author(s):  
Gianluigi Savarese ◽  
Stefania Paolillo ◽  
Pierluigi Costanzo ◽  
Carmen D'Amore ◽  
Milena Cecere ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Walk Distance ◽  
Clinical Events ◽  
Pulmonary Arterial ◽  
Minute Walk Distance ◽  
Minute Walk

scholarly journals Long-term study of oral treprostinil to treat pulmonary arterial hypertension: dosing, tolerability, and pharmacokinetics

2020 ◽  
Vol 10 (4) ◽  
pp. 204589401986633 ◽  
Author(s):  
R. James White ◽  
Keyur Parikh ◽  
Roblee Allen ◽  
Jeremy Feldman ◽  
Carlos Jerjez-Sanchez ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Adverse Events ◽  
Arterial Hypertension ◽  
Total Daily Dose ◽  
Walk Distance ◽  
Long Term Study ◽  
Pulmonary Arterial ◽  
One Year ◽  
Minute Walk Distance ◽  
Minute Walk

Oral treprostinil may be an option for low- and intermediate-risk patients with pulmonary arterial hypertension, a rare lung vascular disease. This open-label extension study collected data on participants who completed previously reported, placebo-controlled oral treprostinil studies. Eligible participants had completed the prospective parent studies and took increasing doses of oral treprostinil twice daily; some later transitioned to three times daily dosing. Investigators measured 6-minute walk distance at Month 12 as the sole efficacy measure but collected adverse events throughout the study. A single center measured pharmacokinetics in 13 subjects who changed dosing from twice daily to three times daily. Eight hundred and ninety-four participants enrolled and 71% completed one year of therapy, with a median total daily dose of 7 mg and a median 6-minute walk distance increase of 22 m (interquartile range, −14 to 67 m). Subjects achieving higher doses had larger increases in 6-minute walk distance; 42% of participants completed three years of therapy. Adverse events were typical for prostacyclin class therapy, but prostacyclin-type adverse events may have been better tolerated with three times daily dosing in 105 participants. In 13 participants transitioned to three times daily dosing with pharmacokinetic measurements before and after, trough drug levels were higher with three times daily dosing. Oral treprostinil is associated with modest but durable, dose-responsive effects on exercise tolerance for those who remained on therapy at one year in this prospective, uncontrolled study. Three times daily dosing was associated with higher trough levels and better tolerability. The recently completed Freedom-EV study will provide further insights into the utility of oral treprostinil ( https://clinicaltrials.gov/show/NCT01560624 ).

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