Identification of treatment goals in paediatric pulmonary arterial hypertension

2014 ◽  
Vol 44 (6) ◽  
pp. 1616-1626 ◽  
Author(s):  
Mark-Jan Ploegstra ◽  
Johannes M. Douwes ◽  
Marcus T.R. Roofthooft ◽  
Willemijn M.H. Zijlstra ◽  
Hans L. Hillege ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Treatment Strategies ◽  
World Health ◽  
Treatment Goals ◽  
Predictive Values ◽  
Free Survival ◽  
Pulmonary Arterial ◽  
Induced Changes

To be able to design goal-oriented treatment strategies in paediatric pulmonary arterial hypertension (PAH), we aimed to identify treatment goals by investigating the prognostic value of treatment-induced changes in noninvasive predictors of transplant-free survival.66 consecutive, treatment-naïve paediatric PAH patients in the Dutch National Network for Paediatric Pulmonary Hypertension who started taking PAH-targeted drugs between January 2000 and April 2013 underwent prospective, standardised follow-up. Clinical, biochemical and echocardiographic measures were longitudinally collected at treatment initiation and follow-up, and their respective predictive values for transplant-free survival were assessed. Furthermore, the predictive values of treatment-induced changes were assessed.From the identified set of baseline predictors, the variables World Health Organization functional class (WHO-FC), N-terminal pro-brain natriuretic peptide (NT-proBNP) and tricuspid annular plane systolic excursion (TAPSE) were identified as follow-up predictors in which treatment-induced changes were associated with survival. Patients in whom these variables improved after treatment showed better survival (p<0.002).Therefore, WHO-FC, NT-proBNP and TAPSE are not only predictors of transplant-free survival in paediatric PAH but can also be used as treatment goals, as treatment-induced improvements in these variables are associated with improved survival. The identification of these variables allows for the introduction of goal-oriented treatment strategies in paediatric PAH.

scholarly journals COVID-19 pandemic challenges: on the way to overcome obstacles in realization of PAH-specific therapy treatment goals

2021 ◽  
pp. 80-86
Author(s):  
E. A. Rezukhina ◽  
I. Z. Korobkova ◽  
N. M. Danilov ◽  
V. V. Gramovich ◽  
T. V. Martynyuk
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
High Risk ◽  
Arterial Hypertension ◽  
Exercise Tolerance ◽  
World Health ◽  
Treatment Goals ◽  
Specific Therapy ◽  
Risk Status ◽  
Pulmonary Arterial ◽  
Clinical Worsening

Our observation demonstrates a case of a 40-year-old female with idiopathic pulmonary arterial hypertension World Health Organization functional class III, who was admitted to NMRC of Cardiology repeatedly due to disease progression including dyspnea worsening and exercise tolerance decrease after previous COVID-19 infection on riociguat (7.5 mg daily), macitentan (10 mg daily) and selexipag (1600 mcg daily) therapy. Clinical examination demonstrated high-risk status according to the expected 1-year mortality. Due to unreleased treatment goals and high-risk status, we performed transition from selexipag to inhale iloprost. After therapy escalation the patient demonstrated a significant improvement in clinical condition, dyspnea reduction and exercise tolerance increase. The current treatment strategy for pulmonary arterial hypertension is based on regular multiparametric risk stratification approach in PAH patients. The impact of COVID-19 may become an important cause of clinical worsening in PAH patients during COVID-19 pandemic. Directed on vasodilatation and antiproliferation mechanisms of action of PAH-specific drugs are supposed to be protective in COVID-19 patients. However, the probability of clinical worsening in PAH patients despite PAH-specific therapy intake needs to be closely monitored to perform timely treatment correction in order to achieve low-risk status and to improve the prognosis of PAH patients.

scholarly journals 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

2020 ◽  
Vol 10 (3) ◽  
pp. 204589402095855
Author(s):  
Clara Hjalmarsson ◽  
Oisin Butler ◽  
Roger Hesselstrand ◽  
Katsiaryna Holl ◽  
Kjell Jansson ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
World Health Organisation ◽  
Functional Class ◽  
World Health ◽  
Walking Distance ◽  
Phosphodiesterase 5 Inhibitors ◽  
Pulmonary Arterial ◽  
Phosphodiesterase 5

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.

scholarly journals Haemodynamics and serial risk assessment in systemic sclerosis associated pulmonary arterial hypertension

2018 ◽  
Vol 52 (4) ◽  
pp. 1800678 ◽  
Author(s):  
Jason Weatherald ◽  
Athénaïs Boucly ◽  
David Launay ◽  
Vincent Cottin ◽  
Grégoire Prévot ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Systemic Sclerosis ◽  
Pulmonary Arterial Hypertension ◽  
Cardiac Index ◽  
Arterial Hypertension ◽  
Arterial Compliance ◽  
Functional Class ◽  
Free Survival ◽  
Pulmonary Arterial

The prognostic importance of follow-up haemodynamics and the validity of multidimensional risk assessment are not well established for systemic sclerosis (SSc)-associated pulmonary arterial hypertension (PAH).We assessed incident SSc-PAH patients to determine the association between clinical and haemodynamic variables at baseline and first follow-up right heart catheterisation (RHC) with transplant-free survival. RHC variables included cardiac index, stroke volume index (SVI), pulmonary arterial compliance and pulmonary vascular resistance. Risk assessment was performed according to the number of low-risk criteria: functional class I or II, 6-min walking distance (6MWD) >440 m, right atrial pressure <8 mmHg and cardiac index ≥2.5 L·min−1·m−2.Transplant-free survival from diagnosis (n=513) was 87%, 55% and 35% at 1, 3 and 5 years, respectively. At baseline, 6MWD was the only independent predictor. A follow-up RHC was available for 353 patients (median interval 4.6 months, interquartile range 3.9–6.4 months). The 6MWD, functional class, cardiac index, SVI, pulmonary arterial compliance and pulmonary vascular resistance were independently associated with transplant-free survival at follow-up, with SVI performing better than other haemodynamic variables. 1-year outcomes were better with increasing number of low-risk criteria at baseline (area under the curve (AUC) 0.63, 95% CI 0.56–0.69) and at first follow-up (AUC 0.71, 95% CI 0.64–0.78).Follow-up haemodynamics and multidimensional risk assessment had greater prognostic significance than at baseline in SSc-PAH.

scholarly journals Upfront triple combination therapy in severe paediatric pulmonary arterial hypertension

2020 ◽  
pp. 2001120
Author(s):  
Meindina G. Haarman ◽  
Marilyne Lévy ◽  
Marcus T.R. Roofthooft ◽  
Johannes M. Douwes ◽  
Theresia R. Vissia-Kazemier ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Combination Therapy ◽  
Arterial Hypertension ◽  
World Health ◽  
Walking Distance ◽  
Triple Combination ◽  
Triple Combination Therapy ◽  
Long Term Outcome ◽  
Pulmonary Arterial

IntroductionTreatment strategies in paediatric pulmonary arterial hypertension (PAH) have evolved over the last years, but survival is still poor. Recently, in adults with severe PAH, upfront triple combination therapy (uTCT) from diagnosis has been reported to show significant clinical improvement and excellent long-term outcome. This retrospective, observational study aimed to assess the efficacy of uTCT in paediatric PAH.MethodsChildren diagnosed with PAH between 2010 and 2019 and started with uTCT were included. World Health Organization Functional Class (WHO-FC), haemodynamics, echocardiography, six-minute walking distance, and serum level of N-terminal-Pro-Brain-Natriuretic-Peptide were assessed at baseline, after three and 6 months and at last available follow-up. Events were defined as death, lung transplantation or Potts shunt.ResultsTwenty-one children (median age 4.8 years (2.5–12.8), 57% females) were included. All children except one were in WHO-FC III or IV (28% and 67%, respectively). After 3 months, one child had died and one child had received a Potts shunt. The remaining 19 children showed clinical and echocardiographic improvement, which persisted at 6 months. Children with idiopathic and heritable PAH showed one-, two-, and three-year transplant-free survival estimates of 100%, 94%, and 87%, albeit 47% of them receiving a Potts shunt during follow-up.ConclusionsChildren with severe PAH, but not pulmonary veno-occlusive disease, improved significantly with uTCT and showed beneficial up to 3-year survival rates, albeit 47% of them receiving a Potts shunt during follow-up. The role of a Potts shunt in conjunction to uTCT in paediatric PAH needs to be further established.

scholarly journals Clinical and Hemodynamic Characterization Super Responders to IV Prostacyclin in Pulmonary Arterial Hypertension

2021 ◽  
Author(s):  
Adrienne K Conger ◽  
Steven J Halliday ◽  
Meredith E Pugh ◽  
Ivan M Robbins ◽  
Anna R Hemnes
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Right Ventricular ◽  
Ventricular Function ◽  
Right Ventricular Function ◽  
Free Survival ◽  
Mean Pulmonary Arterial Pressure ◽  
Pulmonary Arterial ◽  
Minute Walk

Abstract Background: Parenteral 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. Methods: We 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). Results: The 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. Conclusions: There 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.

scholarly journals Interventional and Surgical Treatments for Pulmonary Arterial Hypertension

2021 ◽  
Vol 10 (15) ◽  
pp. 3326
Author(s):  
Tomasz Stącel ◽  
Magdalena Latos ◽  
Maciej Urlik ◽  
Mirosław Nęcki ◽  
Remigiusz Antończyk ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Interdisciplinary Approach ◽  
Left Ventricular ◽  
Free Survival ◽  
Atrial Septostomy ◽  
Surgical Options ◽  
Pulmonary Arterial ◽  
Va Ecmo ◽  
Surgical Treatments

Despite significant advancements in pharmacological treatment, interventional and surgical options are still viable treatments for patients with pulmonary arterial hypertension (PAH), particularly idiopathic PAH. Herein, we review the interventional and surgical treatments for PAH. Atrial septostomy and the Potts shunt can be useful bridging tools for lung transplantation (Ltx), which remains the final surgical treatment among patients who are refractory to any other kind of therapy. Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) remains the ultimate bridging therapy for patients with severe PAH. More importantly, VA-ECMO plays a crucial role during Ltx and provides necessary left ventricular conditioning during the initial postoperative period. Pulmonary denervation may potentially be a new way to ensure better transplant-free survival among patients with the aforementioned disease. However, high-quality randomized controlled trials are needed. As established, obtaining the Eisenmenger physiology among patients with severe pulmonary hypertension by creating artificial defects is associated with improved survival. However, right-to-left shunting may be harmful after Ltx. Closure of the artificially created defects may carry some risk associated with cardiac surgery, especially among patients with Potts shunts. In conclusion, PAH requires an interdisciplinary approach using pharmacological, interventional, and surgical modalities.

Pulmonary arterial hypertension in families with hereditary hemorrhagic telangiectasia: a 13-year follow-up study

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
Y.-P Zhou ◽  
X Jiang ◽  
Y.-X Zhang ◽  
K Sun ◽  
T.-Y Lian ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Hereditary Hemorrhagic Telangiectasia ◽  
Clinical Status ◽  
Development Program ◽  
Resistance Index ◽  
Walking Distance ◽  
Funding Source ◽  
Free Survival ◽  
Pulmonary Arterial

Abstract Background Pulmonary arterial hypertension (PAH) can occur in families with hereditary hemorrhagic telangiectasia (HHT), but it has not been well-characterized. Purpose This study sought to characterize the genetic defects, clinical and hemodynamic features, and outcomes of PAH patients in HHT families. Methods All HHT families with at least one case of PAH investigated in our center from January 2006 to December 2018 were enrolled in the study. We did whole-exome sequencing (WES) or whole-genome sequencing (WGS) to every proband and available family members. The clinical data, hemodynamic features and outcomes of PAH patients were reviewed. Results A total of 64 PAH patients in 57 families were enrolled. Only 7 (12.3%) families had more than one case of PAH. Activin-receptor-like kinase 1 (ALK-1) mutation and Endoglin (ENG) mutation were confirmed in 49 (86.0%) and 3 (5.3%) families and other 5 (8.8%) had no known mutation associated with HHT or PAH. The median age when PAH diagnosis was 22 [9–33] years and female was dominant (70.3%). Most patients (84.4%) had signs of HHT and anemia was recorded in 14 (21.9%) patients. Remarkably, these patients showed severely compromised hemodynamics with elevated mean pulmonary artery pressure (62 [51, 77] mm Hg) and pulmonary vascular resistance index (17.0 [11.2, 22.8] Wood units*m2). Also, impaired exercise capacity was recorded at diagnosis with decreased six-minute walking distance (410 [342–485] meters) and over half (54.7%) were in WHO functional class III or IV. The 1-, 3-, 5- and 10-year transplantation-free survival for the overall PAH patients was 95.0%, 75.9%, 67.1% and 36.4%, respectively. Anemia (HR: 4.24 [1.32–13.65], p=0.016) and CI &lt;2.5 l/min/m2 (HR: 4.39 [1.20–16.09], p=0.026) were independent risk factors for mortality. Conclusions PAH in HHT families is a devastating condition characterized by a young age at PAH diagnosis, poor clinical status and outcomes mainly underlying ALK-1 mutation, which emphasizes the importance to pay attention to this group of patients. Transplantation-free survival Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): The Beijing Natural Science Foundation (7181009), the National Key Research and Development Program of China (2016YFC0901502)

Change of myocardial fluorodeoxyglucose uptake distribution after specific therapy of pulmonary arterial hypertension patients

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
R Kazimierczyk ◽  
P Szumowski ◽  
L.M Malek ◽  
P Blaszczak ◽  
D Jurgilewicz ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Glucose Uptake ◽  
Funding Source ◽  
Hemodynamic Parameters ◽  
Fdg Uptake ◽  
Baseline Visit ◽  
Pulmonary Arterial ◽  
Rv Function

Abstract Background Right ventricular (RV) function is a major determinant of survival in patients with pulmonary arterial hypertension (PAH). In our previous study, we confirmed that increased RV fluorodeoxyglucose (FDG) uptake in positron emission tomography (PET) (presented as higher ratio of FDG uptake of RV to LV) was associated with progressive RV dysfunction and preceded hemodynamic and clinical deterioration in PAH patients. Now, we obtained second PET/MRI assessments of the study group after 2-years of PAH-targeted treatment. Aim The aim of the study was to obtain change of cardiac FDG uptake in PAH patients after follow-up period and to indicate factors mainly affecting this change. Methods Twenty-eight PAH patients (51.32±15.91 years) had simultaneous PET/MRI scans performed during baseline visit. FDG was used and its uptake was quantified as mean standardized uptake value (SUV) for both left (LV) and RV. Second PET/MRI assessments were done after 2 years in the group of twenty patients (four deaths, four patients did not agree to perform additional scans). Results After follow-up period, we observed significant change of MRI-derived RV ejection fraction (45±10% to 51.2±12.7%, p=0.03), and improvement in hemodynamic parameters obtained from right heart catheterization (RHC) e.g. mean pulmonary artery pressure, mPAP (48.5±17.2 to 41.8±17.1 mmHg, p=0.01) and pulmonary vascular resistance, PVR (8.7±5.3 to 7.0±4.2 WU, p=0.04). Follow-up SUVRV/SUVLV ratio significantly correlated with follow-up RV hemodynamic parameters confirming relationship between RV function and cardiac metabolic alterations (Table 1). Interestingly, patients who had improvement in SUVRV/SUVLV (lower follow-up value than baseline, n=11) had significantly higher mPAP at baseline visit (58.9±18.7 vs 40.3±11.8 mmHg, p=0.02), suggesting that RV FDG accumulation in advanced PAH may decrease after the PAH-specific treatment in accordance with the degree of reduction in the pulmonary vascular resistance. Conclusion Impaired RV function is associated with increased glucose uptake of RV myocytes estimated by FDG PET in PAH patients. Targeted treatment may improve RV function and thus affect previously altered cardiac glucose uptake. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Polish National Science Centre

Reliability and responsiveness of incremental shuttle walk test to estimate exercise capacity in patients with pulmonary arterial hypertension

2020 ◽  
Vol 16 (3) ◽  
pp. 179-185
Author(s):  
R. Ishrat ◽  
A. Mujaddadi ◽  
M.S. Ali ◽  
D. Talwar ◽  
M.E. Hussain
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Exercise Capacity ◽  
Intraclass Correlation ◽  
World Health ◽  
Minimal Detectable Change ◽  
Walk Test ◽  
Cross Sectional ◽  
Suitable Alternative ◽  
Pulmonary Arterial

The purpose of the present study was to evaluate the reliability and responsiveness of the incremental shuttle walk test (ISWT) to estimate exercise capacity in patients with pulmonary arterial hypertension (PAH). This was a cross-sectional longitudinal study performed on stable PAH patients (n=30, mean age ± standard deviation, 60±13.6 years) with World Health Organization functional class II & III. Reliability was assessed by comparing the distance covered between ISWT-1 (initial) and ISWT-2 (retest). Responsiveness was determined by comparing the distance covered in the ISWT-3 post pulmonary rehabilitation (PR) to the ISWT-1. The distance covered between ISWT-1 (177±87.85 m) and ISWT-2 (191.67±96.39 m) was not statistically significant. The result of the relative reliability has shown to be excellent with an intraclass correlation coefficient (ICC2,1 = 0.98, 95%CI = 0.95-0.99). Absolute reliability was evaluated through the standard error of the measurement and minimal detectable change at a 95% confidence interval (MDC95) were 12.29 and 33.9 m, respectively. Bland Altman plot showed good agreement between the two ISWTs. Following PR, the effect size (ES=0.78) and standardised response mean (SRM=1.50) were moderate and large respectively. ISWT is considered to be a reliable and responsive measure to estimate exercise capacity in patients with PAH. The ISWT may be considered a suitable alternative tool over a 6-min walk test and in the absence of equipment availability or expertise for conducting cardiopulmonary exercise test for the assessment of exercise capacity in these patients.

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