Pulmonary arterial hypertension associated with a congenital heart defect:Advanced medium-term medical treatment stabilizes clinical condition

Objective. Pulmonary arterial hypertension (PAH) associated with congenital heart defect (CHD), and especially Eisenmenger syndrome, is associated with impaired exercise tolerance and reduced quality of life. In this study, we describe medium-term follow-up of adult patients with PAH associated with CHD, treated in a single center with different types of advanced medication.Design. The treatment and clinical course of 15 patients (11 female, median age 53, range 28-74 years) with PAH associated with CHD is retrospectively described. Data on patient characteristics, exercise test, right-heart catheterization, and type of advanced therapy were collected from medical files. Advanced medical therapy consisted of either intravenous prostacyclin, or endothelin receptor antagonists, or phosphodiesterase-5-inhibitors. Additional therapy was started in case of persistent clinical deterioration or insufficient improvement with monotherapy.Results. All patients (10 patients with Eisenmenger syndrome, 5 patients with a closed defect and PAH) were exposed to different durations of advanced medication. Median period of treatment was 2.5 (range 0.7-6.3) years. Atrial septal defect, type secundum, was the most frequent underlying diagnosis (n = 10). Most patients (n = 9) received a combination of advanced medical therapy. Six-minute walk distance (6-MWD) remained unchanged with an increase of 44 ± 78 m (P = 0.2) and 41 ± 80 m (P = 0.3) compared with baseline after respectively 1 and 2 years of treatment. Younger age was associated with better performance (β = -7 m per year, P &lt; 0.05), patients younger than 45 years showed a greater improvement in 6-MWD after 2 years of treatment (P &lt; 0.05). During a mean follow-up of 23 (range 4-58) months, mean pulmonary arterial pressure (53 ± 24-49 ± 17 mmHg, P = 0.3) and pulmonary vascular resistance (770 ± 1090-650 ± 444dyness/cm5, P = 0.7) showed no deterioration.Conclusion. Advanced treatment strategies in patients with PAH associated with CHD are useful. The treatment effect seems to be one of disease stabilization and decreasing the rate of deterioration. Younger age was associated with a greater improvement of 6-MWD.</p

Pulmonary arterial hypertension associated with a congenital heart defect:Advanced medium-term medical treatment stabilizes clinical condition

Objective. Pulmonary arterial hypertension (PAH) associated with congenital heart defect (CHD), and especially Eisenmenger syndrome, is associated with impaired exercise tolerance and reduced quality of life. In this study, we describe medium-term follow-up of adult patients with PAH associated with CHD, treated in a single center with different types of advanced medication.Design. The treatment and clinical course of 15 patients (11 female, median age 53, range 28-74 years) with PAH associated with CHD is retrospectively described. Data on patient characteristics, exercise test, right-heart catheterization, and type of advanced therapy were collected from medical files. Advanced medical therapy consisted of either intravenous prostacyclin, or endothelin receptor antagonists, or phosphodiesterase-5-inhibitors. Additional therapy was started in case of persistent clinical deterioration or insufficient improvement with monotherapy.Results. All patients (10 patients with Eisenmenger syndrome, 5 patients with a closed defect and PAH) were exposed to different durations of advanced medication. Median period of treatment was 2.5 (range 0.7-6.3) years. Atrial septal defect, type secundum, was the most frequent underlying diagnosis (n = 10). Most patients (n = 9) received a combination of advanced medical therapy. Six-minute walk distance (6-MWD) remained unchanged with an increase of 44 ± 78 m (P = 0.2) and 41 ± 80 m (P = 0.3) compared with baseline after respectively 1 and 2 years of treatment. Younger age was associated with better performance (β = -7 m per year, P &lt; 0.05), patients younger than 45 years showed a greater improvement in 6-MWD after 2 years of treatment (P &lt; 0.05). During a mean follow-up of 23 (range 4-58) months, mean pulmonary arterial pressure (53 ± 24-49 ± 17 mmHg, P = 0.3) and pulmonary vascular resistance (770 ± 1090-650 ± 444dyness/cm5, P = 0.7) showed no deterioration.Conclusion. Advanced treatment strategies in patients with PAH associated with CHD are useful. The treatment effect seems to be one of disease stabilization and decreasing the rate of deterioration. Younger age was associated with a greater improvement of 6-MWD.</p

Pulmonary arterial hypertension associated with a congenital heart defect:Advanced medium-term medical treatment stabilizes clinical condition

Objective. Pulmonary arterial hypertension (PAH) associated with congenital heart defect (CHD), and especially Eisenmenger syndrome, is associated with impaired exercise tolerance and reduced quality of life. In this study, we describe medium-term follow-up of adult patients with PAH associated with CHD, treated in a single center with different types of advanced medication.Design. The treatment and clinical course of 15 patients (11 female, median age 53, range 28-74 years) with PAH associated with CHD is retrospectively described. Data on patient characteristics, exercise test, right-heart catheterization, and type of advanced therapy were collected from medical files. Advanced medical therapy consisted of either intravenous prostacyclin, or endothelin receptor antagonists, or phosphodiesterase-5-inhibitors. Additional therapy was started in case of persistent clinical deterioration or insufficient improvement with monotherapy.Results. All patients (10 patients with Eisenmenger syndrome, 5 patients with a closed defect and PAH) were exposed to different durations of advanced medication. Median period of treatment was 2.5 (range 0.7-6.3) years. Atrial septal defect, type secundum, was the most frequent underlying diagnosis (n = 10). Most patients (n = 9) received a combination of advanced medical therapy. Six-minute walk distance (6-MWD) remained unchanged with an increase of 44 ± 78 m (P = 0.2) and 41 ± 80 m (P = 0.3) compared with baseline after respectively 1 and 2 years of treatment. Younger age was associated with better performance (β = -7 m per year, P &lt; 0.05), patients younger than 45 years showed a greater improvement in 6-MWD after 2 years of treatment (P &lt; 0.05). During a mean follow-up of 23 (range 4-58) months, mean pulmonary arterial pressure (53 ± 24-49 ± 17 mmHg, P = 0.3) and pulmonary vascular resistance (770 ± 1090-650 ± 444dyness/cm5, P = 0.7) showed no deterioration.Conclusion. Advanced treatment strategies in patients with PAH associated with CHD are useful. The treatment effect seems to be one of disease stabilization and decreasing the rate of deterioration. Younger age was associated with a greater improvement of 6-MWD.</p

Pulmonary arterial hypertension associated with a congenital heart defect:Advanced medium-term medical treatment stabilizes clinical condition

Objective. Pulmonary arterial hypertension (PAH) associated with congenital heart defect (CHD), and especially Eisenmenger syndrome, is associated with impaired exercise tolerance and reduced quality of life. In this study, we describe medium-term follow-up of adult patients with PAH associated with CHD, treated in a single center with different types of advanced medication.Design. The treatment and clinical course of 15 patients (11 female, median age 53, range 28-74 years) with PAH associated with CHD is retrospectively described. Data on patient characteristics, exercise test, right-heart catheterization, and type of advanced therapy were collected from medical files. Advanced medical therapy consisted of either intravenous prostacyclin, or endothelin receptor antagonists, or phosphodiesterase-5-inhibitors. Additional therapy was started in case of persistent clinical deterioration or insufficient improvement with monotherapy.Results. All patients (10 patients with Eisenmenger syndrome, 5 patients with a closed defect and PAH) were exposed to different durations of advanced medication. Median period of treatment was 2.5 (range 0.7-6.3) years. Atrial septal defect, type secundum, was the most frequent underlying diagnosis (n = 10). Most patients (n = 9) received a combination of advanced medical therapy. Six-minute walk distance (6-MWD) remained unchanged with an increase of 44 ± 78 m (P = 0.2) and 41 ± 80 m (P = 0.3) compared with baseline after respectively 1 and 2 years of treatment. Younger age was associated with better performance (β = -7 m per year, P &lt; 0.05), patients younger than 45 years showed a greater improvement in 6-MWD after 2 years of treatment (P &lt; 0.05). During a mean follow-up of 23 (range 4-58) months, mean pulmonary arterial pressure (53 ± 24-49 ± 17 mmHg, P = 0.3) and pulmonary vascular resistance (770 ± 1090-650 ± 444dyness/cm5, P = 0.7) showed no deterioration.Conclusion. Advanced treatment strategies in patients with PAH associated with CHD are useful. The treatment effect seems to be one of disease stabilization and decreasing the rate of deterioration. Younger age was associated with a greater improvement of 6-MWD.</p

Pulmonary arterial hypertension associated with a congenital heart defect:Advanced medium-term medical treatment stabilizes clinical condition

Objective. Pulmonary arterial hypertension (PAH) associated with congenital heart defect (CHD), and especially Eisenmenger syndrome, is associated with impaired exercise tolerance and reduced quality of life. In this study, we describe medium-term follow-up of adult patients with PAH associated with CHD, treated in a single center with different types of advanced medication.Design. The treatment and clinical course of 15 patients (11 female, median age 53, range 28-74 years) with PAH associated with CHD is retrospectively described. Data on patient characteristics, exercise test, right-heart catheterization, and type of advanced therapy were collected from medical files. Advanced medical therapy consisted of either intravenous prostacyclin, or endothelin receptor antagonists, or phosphodiesterase-5-inhibitors. Additional therapy was started in case of persistent clinical deterioration or insufficient improvement with monotherapy.Results. All patients (10 patients with Eisenmenger syndrome, 5 patients with a closed defect and PAH) were exposed to different durations of advanced medication. Median period of treatment was 2.5 (range 0.7-6.3) years. Atrial septal defect, type secundum, was the most frequent underlying diagnosis (n = 10). Most patients (n = 9) received a combination of advanced medical therapy. Six-minute walk distance (6-MWD) remained unchanged with an increase of 44 ± 78 m (P = 0.2) and 41 ± 80 m (P = 0.3) compared with baseline after respectively 1 and 2 years of treatment. Younger age was associated with better performance (β = -7 m per year, P &lt; 0.05), patients younger than 45 years showed a greater improvement in 6-MWD after 2 years of treatment (P &lt; 0.05). During a mean follow-up of 23 (range 4-58) months, mean pulmonary arterial pressure (53 ± 24-49 ± 17 mmHg, P = 0.3) and pulmonary vascular resistance (770 ± 1090-650 ± 444dyness/cm5, P = 0.7) showed no deterioration.Conclusion. Advanced treatment strategies in patients with PAH associated with CHD are useful. The treatment effect seems to be one of disease stabilization and decreasing the rate of deterioration. Younger age was associated with a greater improvement of 6-MWD.</p

Pulmonary arterial hypertension associated with a congenital heart defect:Advanced medium-term medical treatment stabilizes clinical condition

Objective. Pulmonary arterial hypertension (PAH) associated with congenital heart defect (CHD), and especially Eisenmenger syndrome, is associated with impaired exercise tolerance and reduced quality of life. In this study, we describe medium-term follow-up of adult patients with PAH associated with CHD, treated in a single center with different types of advanced medication.Design. The treatment and clinical course of 15 patients (11 female, median age 53, range 28-74 years) with PAH associated with CHD is retrospectively described. Data on patient characteristics, exercise test, right-heart catheterization, and type of advanced therapy were collected from medical files. Advanced medical therapy consisted of either intravenous prostacyclin, or endothelin receptor antagonists, or phosphodiesterase-5-inhibitors. Additional therapy was started in case of persistent clinical deterioration or insufficient improvement with monotherapy.Results. All patients (10 patients with Eisenmenger syndrome, 5 patients with a closed defect and PAH) were exposed to different durations of advanced medication. Median period of treatment was 2.5 (range 0.7-6.3) years. Atrial septal defect, type secundum, was the most frequent underlying diagnosis (n = 10). Most patients (n = 9) received a combination of advanced medical therapy. Six-minute walk distance (6-MWD) remained unchanged with an increase of 44 ± 78 m (P = 0.2) and 41 ± 80 m (P = 0.3) compared with baseline after respectively 1 and 2 years of treatment. Younger age was associated with better performance (β = -7 m per year, P &lt; 0.05), patients younger than 45 years showed a greater improvement in 6-MWD after 2 years of treatment (P &lt; 0.05). During a mean follow-up of 23 (range 4-58) months, mean pulmonary arterial pressure (53 ± 24-49 ± 17 mmHg, P = 0.3) and pulmonary vascular resistance (770 ± 1090-650 ± 444dyness/cm5, P = 0.7) showed no deterioration.Conclusion. Advanced treatment strategies in patients with PAH associated with CHD are useful. The treatment effect seems to be one of disease stabilization and decreasing the rate of deterioration. Younger age was associated with a greater improvement of 6-MWD.</p

EPITOME-2: An open-label study assessing the transition to a new formulation of intravenous epoprostenol in patients with pulmonary arterial hypertension.

Background Continuous infusion of epoprostenol is the treatment of choice in patients with pulmonary arterial hypertension in functional classes III to IV. However, this treatment's limitations include instability at room temperature. A new epoprostenol formulation offers improved storage conditions and patient convenience. Methods The EPITOME-2 trial was an open-label, prospective, multicenter, single-arm, phase IIIb study. Patients with pulmonary arterial hypertension on long-term, stable epoprostenol therapy were transitioned from epoprostenol with glycine and mannitol excipients (Flolan; GlaxoSmithKline, Durham, NC) to epoprostenol with arginine and sucrose excipients (Veletri; Actelion Pharmaceuticals Ltd, Allschwil, Switzerland). Patients were followed up for 3 months, and dose adjustments were recorded. Efficacy measures included the 6-minute walk distance, hemodynamics assessed by right heart catheterization, and New York Heart Association functional class. Safety and tolerability of the transition were also evaluated. Quality of life was assessed using the Treatment Satisfaction Questionnaire for Medication. Results Forty-two patients enrolled in the study, and 1 patient withdrew consent before treatment; thus, 41 patients received treatment and completed the study. Six patients required dose adjustments. There were no clinically relevant changes from baseline to month 3 in any of the efficacy end points. Adverse events were those previously described with intravenous prostacyclin therapy. Treatment Satisfaction Questionnaire for Medication scores showed an improvement from baseline to month 3 in the domain of treatment convenience. Conclusions Transition from epoprostenol with glycine and mannitol excipients to epoprostenol with arginine and sucrose excipients did not affect treatment efficacy, raised no new safety or tolerability concerns, and provided patients with an increased sense of treatment convenience

Characteristics of Interstitial Fibrosis and Inflammatory Cell Infiltration in Right Ventricles of Systemic Sclerosis-Associated Pulmonary Arterial Hypertension

Objective. Systemic sclerosis-associated pulmonary arterial hypertension (SScPAH) has a disturbed function of the right ventricle (RV) when compared to idiopathic PAH (IPAH). Systemic sclerosis may also affect the heart. We hypothesize that RV differences may occur at the level of interstitial inflammation and—fibrosis and compared inflammatory cell infiltrate and fibrosis between the RV of SScPAH, IPAH, and healthy controls. Methods. Paraffin-embedded tissue samples of RV and left ventricle (LV) from SScPAH (n = 5) and IPAH (n = 9) patients and controls (n = 4) were picrosirius red stained for detection of interstitial fibrosis, which was quantified semiautomatically. Neutrophilic granulocytes (MPO), macrophages (CD68), and lymphocytes (CD45) were immunohistochemically stained and only interstitial leukocytes were counted. Presence of epi- or endocardial inflammation, and of perivascular or intimal fibrosis of coronary arteries was assessed semiquantitatively (0–3: absent to extensive). Results. RV's of SScPAH showed significantly more inflammatory cells than of IPAH (cells/mm2, mean ± sd MPO 11 ± 3 versus 6 ± 1; CD68 11 ± 3 versus 6 ± 1; CD45 11 ± 1 versus 5 ± 1 , P < .05) and than of controls. RV interstitial fibrosis was similar in SScPAH and IPAH (4 ± 1 versus 5 ± 1%, P = .9), and did not differ from controls (5 ± 1%, P = .8). In 4 SScPAH and 5 IPAH RV's foci of replacement fibrosis were found. No differences were found on epi- or endocardial inflammation or on perivascular or intimal fibrosis of coronary arteries. Conclusion. SScPAH RVs display denser inflammatory infiltrates than IPAH, while they do not differ with respect to interstitial fibrosis. Whether increased inflammatory status is a contributor to altered RV function in SScPAH warrants further research

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase 3 randomized trials. The EXPosurE Registry RiociguaT in patients with pulmonary hypertension (EXPERT) study was designed to monitor the long-term safety of riociguat in clinical practice. Methods: EXPERT was an international, multicenter, prospective, uncontrolled, non-interventional cohort study of patients treated with riociguat. Patients were followed for at least 1 year and up to 4 years from enrollment or until 30 days after stopping riociguat treatment. Primary safety outcomes were adverse events (AEs) and serious adverse events (SAEs) coded using Medical Dictionary for Regulatory Activities preferred terms and System Organ Classes version 21.0, collected during routine clinic visits and collated via case report forms. Results: In total, 956 patients with CTEPH were included in the analysis. The most common AEs in these patients were peripheral edema/edema (11.7%), dizziness (7.5%), right ventricular (RV)/cardiac failure (7.7%), and pneumonia (5.0%). The most common SAEs were RV/cardiac failure (7.4%), pneumonia (4.1%), dyspnea (3.6%), and syncope (2.5%). Exposure-adjusted rates of hemoptysis/pulmonary hemorrhage and hypotension were low and comparable to those in the long-term extension study of riociguat (Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase-Stimulator Trial [CHEST-2]). Conclusion: Data from EXPERT show that in patients with CTEPH, the safety of riociguat in routine practice was consistent with the known safety profile of the drug, and no new safety concerns were identified

Riociguat treatment in patients with pulmonary arterial hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension following Phase 3 randomized trials. The EXPosurE Registry RiociguaT in patients with pulmonary hypertension (EXPERT) study was designed to monitor the long-term safety of riociguat in clinical practice. Methods: EXPERT was an international, multicenter, prospective, uncontrolled, non-interventional cohort study of patients treated with riociguat. Patients were followed for at least 1 year and up to 4 years from enrollment or until 30 days after stopping riociguat treatment. Primary safety outcomes were adverse events (AEs) and serious adverse events (SAEs) coded using Medical Dictionary for Regulatory Activities preferred terms and System Organ Classes version 21.0, collected during routine clinic visits (usually every 3-6 months) and collated via case report forms. Results: In total, 326 patients with PAH were included in the analysis. The most common AEs in these patients were dizziness (11.7%), right ventricular (RV)/cardiac failure (10.7%), edema/peripheral edema (10.7%), diarrhea (8.6%), dyspnea (8.0%), and cough (7.7%). The most common SAEs were RV/cardiac failure (10.1%), pneumonia (6.1%), dyspnea (4.0%), and syncope (3.4%). The exposure-adjusted rate of hemoptysis/pulmonary hemorrhage was 2.5 events per 100 patient-years. Conclusion: Final data from EXPERT show that in patients with PAH, the safety of riociguat in clinical practice was consistent with clinical trials, with no new safety concerns identified and a lower exposure-adjusted rate of hemoptysis/pulmonary hemorrhage than in the long-term extension of the Phase 3 trial in PAH