scholarly journals Early experience with selexipag for the treatment of adults with pulmonary arterial hypertension associated with congenital heart disease

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Van Dissel ◽  
M Post ◽  
G.T Sieswerda ◽  
H.W Vliegen ◽  
A.P.J Van Dijk ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Side Effects ◽  
Congenital Heart ◽  
Funding Source ◽  
Walk Distance ◽  
Titration Phase ◽  
Pulmonary Arterial ◽  
Minute Walk Distance ◽  
Minute Walk

Abstract Background Recently, selexipag, a new orally available and selective prostacyclin receptor agonist, has become available for treatment of pulmonary arterial hypertension (PAH), but experience in patients with PAH associated with congenital heart disease (CHD) is limited to patients with closed defects. Purpose We present our early multi-centre experience using selexipag in the heterogeneous PAH-CHD population. Methods We prospectively evaluated adults with PAH-CHD from five PAH-CHD expert centres who were treated with selexipag. Patients were titrated to highest tolerable individualized dose (200 to 1,600 μg twice daily), after which patients entered the maintenance phase. Data on functional class (FC), 6-minute walk distance (6MWD), imaging and biochemical (N terminal pro-brain natriuretic peptide [NT-proBNP]) parameters were collected. Results Thirty-four patients (age 43±14 years, 56% female, 60% Eisenmenger syndrome, 22% Down syndrome, 60% dual PAH therapy) were started on selexipag. All patients experienced at least 2 side effects during the initial uptitration phase. Most side effects were manageable and diminished after reaching the maintenance dose, but eight patients discontinued treatment due to side effects during the titration phase. The most frequent side effects were consistent with the known side effects of prostacyclins, including headache, nausea, diarrhoea and jaw pain. Majority (68%) of patients reached lower maintenance doses of 200–600 μg. At 12 months, FC improved in three patients and remained unchanged in the others. 6-minute walk distance remained stable throughout follow-up (475 to 470 m; p=n.s.) in patients who remained on-treatment compared to patients who stopped selexipag (485 to 370 m). NT-proBNP levels remained stable in patients on-treatment (520 to 600 ng/L) but worsened in patients who stopped (700 to 1000 ng/L). One patient died during follow-up from end-stage heart failure. Conclusion There is a promising role for selexipag in the treatment of adults with PAH-CHD. However, based on our experience, the use is challenging due to complexity in dosing and side effect profiles, which limit patients' tolerability and acceptance during the titration phase. Funding Acknowledgement Type of funding source: Other. Main funding source(s): Actelion Pharmaceuticals

scholarly journals Effect of Bosentan on Exercise Capacity and Clinical Worsening in Patients with Dual down and Eisenmenger Syndrome

2013 ◽  
Vol 7 ◽  
pp. CMC.S10237 ◽  
Author(s):  
Giorgio Serino ◽  
Marco Guazzi ◽  
Angelo Micheletti ◽  
Carlo Lombardi ◽  
Rossella Danesi ◽  
...  
Keyword(s):  
Doppler Echocardiography ◽  
Laboratory Tests ◽  
Functional Class ◽  
Walk Distance ◽  
Pulmonary Arterial ◽  
Minute Walk Distance ◽  
Minute Walk ◽  
Clinical Worsening

This single-center, retrospective analysis evaluated long-term bosentan treatment in adult patients (n = 7) with both Down and Eisenmenger syndromes (DS-ES). Laboratory tests, 6-minute walk distance (6MWD), functional class, and Doppler echocardiography were assessed at baseline and during 2 years' follow-up. Improvements or maintenance of 6MWD were observed (68 m improvement from baseline at month 12) after bosentan initiation. 6MWD was maintained up to year 2. Overall, 6 patients experienced a significant improvement in functional class during 2 years' therapy ( P = 0.01). There were no significant changes in parameters measured by Doppler echocardiography. None of the patients required either hospitalization or additional pulmonary arterial hypertension (PAH) therapy because of PAH progression. Bosentan treatment was generally well tolerated; no liver function abnormalities or serious adverse drug reactions were noted. In this DS-ES cohort, bosentan seemed to be well tolerated and clinically effective.

scholarly journals Clinical and Hemodynamic Characterization Super Responders to IV Prostacyclin

2020 ◽  
Author(s):  
Adrienne K Conger ◽  
Steven J Halliday ◽  
Meredith E Pugh ◽  
Ivan M Robbins ◽  
Anna R Hemnes
Keyword(s):  
Right Ventricular ◽  
Ventricular Function ◽  
Right Ventricular Function ◽  
Walk Distance ◽  
Free Survival ◽  
Mean Pulmonary Arterial Pressure ◽  
Pulmonary Arterial ◽  
Minute Walk Distance ◽  
Minute Walk

Abstract BackgroundParenteral prostacyclins are the only therapy proven to extend survival in pulmonary arterial hypertension (PAH), yet at the bedside clinicians have no tools to predict which patients are most likely to benefit from this medication class. MethodsWe retrospectively analyzed all PAH patients treated with IV epoprostenol therapy at our center from 1/1/1996 to 12/31/2016. We analyzed survival in patients and defined the 90 th percentile of survival. Patients were divided into those who survived past this point (super responders) and those who had had an event prior to this time point after initiation of iv epoprostenol (usual responders).ResultsThe median survival after IV epoprostenol initiation was 4.32 years, and the 90 th percentile of event-free survival was 11.09 years. Fourteen patients met criteria for super responder and 45 had a survival <90 th percentile, comprising the usual responder group. Super responders tended to be younger, have longer six-minute walk distances and higher mean pulmonary arterial pressure (p<0.05 for all). In follow up, super responders continued to have a higher six-minute walk distance and were more likely to have achieved normal or only mildly impaired right ventricular function, though no differences in hemodynamics were observed.ConclusionsThere may be a super responder phenotype that can be defined in patients with PAH by >90 th percentile of survival. Super responders were more likely that usual responders to be younger and were more likely to have achieved favorable right ventricular function at follow up, however, differences in hemodynamics were not observed.

Bosentan for the treatment of pulmonary arterial hypertension associated with congenital cardiac disease

2006 ◽  
Vol 16 (3) ◽  
pp. 268-274 ◽  
Author(s):  
Eugene Kotlyar ◽  
Raymond Sy ◽  
Anne M. Keogh ◽  
Fiona Kermeen ◽  
Peter S. Macdonald ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Functional Class ◽  
Walk Distance ◽  
Specific Therapy ◽  
Eisenmenger’S Syndrome ◽  
Pulmonary Arterial ◽  
Minute Walk Distance ◽  
Minute Walk

Aims:Bosentan is efficacious in idiopathic pulmonary arterial hypertension, and the variants associated with connective tissue disease, but not currently approved for treatment of pulmonary arterial hypertension due to Eisenmenger's syndrome. We sought to evaluate its effect in adults with Eisenmenger's syndrome.Methods:We administered bosentan on the basis of compassionate use in 23 patients with Eisenmenger's syndrome, aged 37 plus or minus 14 years. Of the patients, 17 had never received specific treatment for pulmonary arterial hypertension, five were transitioned from treprostinil, and one from beraprost to bosentan. We measured functional class, saturation of oxygen, haemoglobin levels and six-minute walk distance at baseline, one, six months and at most recent follow-up.Results:Baseline functional class was IV in three, III in fifteen, and II in five patients. At follow-up, with a mean of 15 plus or minus 10 months, 13 of the 23 patients (57%) had improved by at least one functional class, from a median baseline of III to II (p equal to 0.016), mean saturation of oxygen at rest had increased from 81% to 84% (p equal to 0.001), and levels of haemoglobin had decreased from 178 plus or minus 26 grams per litre to 167 plus or minus 19 grams per litre (p equal to 0.001). Overall, the six-minute walk distance did not change from baseline of 335 metres. The distance walked by those not previously receiving specific therapy, however, improved from 318 plus or minus 129 to 345 plus or minus 123 metres (p equal to 0.03).Conclusion:Treatment of adults with Eisenmenger's syndrome using bosentan significantly improved functional class, saturation of oxygen at rest, and decreased levels of haemoglobin. Treatment with bosentan was associated with improvement in six-minute walk distance in those not previously receiving specific therapy. In patients already in receipt of specific therapy, transition to bosentan resulted in no clinical deterioration.

scholarly journals Characteristics and health status of patients with and without confirmed HFpEF

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Deaton ◽  
F Forsyth ◽  
J Mant ◽  
D Edwards ◽  
R Hobbs ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Primary Care ◽  
Cohort Study ◽  
Health Status ◽  
Functional Impairment ◽  
Funding Source ◽  
Walk Distance ◽  
Minute Walk Distance ◽  
Minute Walk

Abstract Aims Patients with heart failure with preserved ejection fraction (HFpEF) are usually older and multi-morbid and diagnosis can be challenging. The aims of this cohort study were to confirm diagnosis of HFpEF in patients with possible HFpEF recruited from primary care, to compare characteristics and health status between those with and without HFpEF, and to determine factors associated with health status in patients with HFpEF. Methods Patients with presumed HFpEF were recruited from primary care practices and underwent clinical assessment and diagnostic evaluation as part of a longitudinal cohort study. Health status was measured by Montreal Cognitive Assessment (MOCA), 6-minute walk test, symptoms, and the Kansas City Cardiomyopathy Questionnaire (KCCQ), and quality of life (QoL) by EQ-5D-5L visual analogue scale (VAS). Results 151 patients (mean age 78.5±8.6 years, 40% women, mean EF 56% + 9.4) were recruited and 93 (61.6%) were confirmed HFpEF (those without HFpEF had other HF and cardiac diagnoses). Patients with and without HFpEF did not differ by age, MOCA, blood pressure, heart rate, NYHA class, proportion with atrial fibrillation, Charlson Comorbidity Index, or NT-ProBNP levels. Patients with HFpEF were more likely to be women, overweight or obese, frail, and to be more functionally impaired by 6 minute walk distance and gait speed than those without. Although not statistically significant, patients with HFpEF had clinically significant differences (&gt;5 points) on the physical limitations, symptom burden and clinical summary subscales of the KCCQ, but did not differ by other subscales or by EQ-5D-5L VAS (70±17 vs 73±19, p=0.385). More patients with HFpEF reported daytime dyspnoea (63% vs 46%, p=0.035) and fatigue (81% vs 61%, p=0.008), but not other symptoms compared to those without HFpEF. For both groups BMI was moderately negatively correlated with KCCQ subscale scores, and 6 minute walk distance was positively correlated with KCCQ subscales. Conclusions Nearly 40% were not confirmed as HFpEF indicating the challenges of diagnosis. Patients with confirmed HFpEF differed by sex, overweight/obesity, frailty, functional impairment, and symptoms but not by age or comorbidities from those without HFpEF. These differences were reflected in some subscale scores of the KCCQ, but not how patients reported their quality of life on the KCCQ QoL subscale and EQ-5D-5L VAS. Older patients with HFpEF reported relatively high QoL despite poor health status by functional impairment, frailty and symptoms. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Institute of Health Research School of Primary Care Research

scholarly journals Contemporary use of Selexipag in pulmonary arterial hypertension associated with congenital heart disease: a case series

2020 ◽  
Author(s):  
Sarah Blissett ◽  
David Blusztein ◽  
Vaikom S Mahadevan
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Pulmonary Arterial Hypertension ◽  
Side Effects ◽  
Arterial Hypertension ◽  
Exercise Capacity ◽  
Congenital Heart ◽  
Pulmonary Veins ◽  
Case Series ◽  
Pulmonary Arterial

Abstract Background There are significant risks of parenteral prostacyclin use in patients with pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD), which may limit their use. Selexipag is an oral, selective prostacyclin analogue that has been shown to reduce disease progression and improve exercise capacity in patients with PAH-CHD. Administering Selexipag in patients with PAH-CHD could potentially overcome some of the risks of parenteral therapy while improving clinical outcomes. Case summary We report five cases highlighting the clinical uses of Selexipag in patients with PAH-CHD. In the first two cases, Selexipag was initiated as part of a Treat-to-close strategy. In the third case, initiation of Selexipag improved symptoms and objective exercise capacity in a patient with Eisenmenger syndrome. In the fourth and fifth cases, rapid cross-titration protocols were used to transition from parenteral prostacyclins to Selexipag. In the fourth case, Selexipag was initiated in the context of significant side effects limiting parenteral prostacyclin use. In the fifth case, Selexipag was used to down-titrate from parenteral prostacyclins following closure of a sinus venosus atrial septal defect and redirection of anomalous pulmonary veins. Discussion Selexipag is a promising oral therapy for patients with at various stages of the spectrum of PAH-CHD to improve symptoms, exercise capacity and, in some cases, haemodynamics. Our cases also highlight practical aspects of Selexipag use including targeting the individualized maximally tolerated dose for each patient, managing side effects and managing dose interruptions.

Survival of Patients with High-Risk Pulmonary Arterial Hypertension Associated with Congenital Heart Disease

2021 ◽  
Vol 104 (6) ◽  
pp. 895-901
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
High Risk ◽  
Congenital Heart ◽  
First Year ◽  
Pulmonary Arterial ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Background: Pulmonary arterial hypertension (PAH) is a common complication of congenital heart disease (CHD) with uncorrected left-to-right shunts. Currently, no consensus guideline exists on the management of PAH-CHD in children, especially those who do not meet operability criteria. Objective: To compare survival between three groups of high-risk PAH-CHD, group 1: total correction including both surgical and percutaneous intervention, group 2: palliative treatment, and group 3: conservative with medical treatment group. Materials and Methods: All pediatric patients with PAH-CHD that underwent cardiac catheterization between January 1, 2008 and December 31, 2017 were retrospectively reviewed. Inclusion criteria were high risk PAH-CHD patients who had pulmonary vascular resistance (PVR) greater than 6 Wood unit·m² and PVR-to-SVR ratio greater than 0.3 evaluated in room air. Exclusion criteria were younger than three months of age, severe left side heart disease with pulmonary capillary wedge pressure greater than 15 mmHg, obstructive total pulmonary venous return, and single ventricle physiology. The Kaplan-Meier analysis was performed from the date of PAH diagnosis to the date of all-cause mortality or to censored date at last follow-up. Results: Seventy-six patients with a median age at diagnosis of 27.5 months (IQR 14.5 to 69.0 months) were included in this study. The patients were divided into three subgroups and included 38 patients (50.0%) in group 1, six patients (7.9%) in group 2, and 32 patients (42.1%) in group 3. The median follow-up time was 554 days (IQR 103 to 2,133 days). The overall mortality was 21.7%. One-year survival in patients with simple lesion in group 1 and 3 were 79.5% and 87.5% and patients with complex lesions in group 1, 2, and 3 were 93.8%, 83.3%, and 73.1%, respectively. The results showed that most mortalities occurred in the first year. There were no statistically significant differences in survival among difference types of treatment (log rank test, p=0.522). Conclusion: The mortality of high-risk PAH-CHD patients were not different among those who underwent corrective surgery, palliative, or conservative treatment. The mortality was high in the first year after PAH diagnosis and remain stable afterward. Management decision for an individual with high-risk PAH-CHD patients requires comprehensive clinical assessment to balance the risks and benefits before making individualized clinical judgment. Keywords: Pulmonary hypertension; Congenital heart disease; High-risk patients

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.

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