scholarly journals Prostanoids in pediatric pulmonary hypertension: clinical response, time-to-effect, and dose–response

2020 ◽  
Vol 10 (4) ◽  
pp. 204589402094485
Author(s):  
Joseph B. Tella ◽  
Thomas J. Kulik ◽  
Julia E. McSweeney ◽  
Lynn A. Sleeper ◽  
Minmin Lu ◽  
...  
Keyword(s):  
Cardiac Index ◽  
Clinical Response ◽  
Dose Effect ◽  
Clinical Event ◽  
Time Interval ◽  
Hemodynamic Variable ◽  
Pulmonary Hemodynamic ◽  
Response Predictors ◽  
Pulmonary Arterial ◽  
High Doses

For pediatric pulmonary arterial hypertension (PAH) patients treated with parenteral prostanoids, response predictors, and the dose–effect relationship are ill defined. We determined the following: (1) which pulmonary vascular hemodynamic variable, after initiating prostanoids, best correlates with a significant clinical response; (2) the time interval after treatment when if no pulmonary hemodynamic improvement has occurred, none is ever likely to; and (3) the relationship between the prostanoid dose and its hemodynamic effects. This is a retrospective cohort study of 31 pediatric patients with Group 1 PAH treated with parenteral prostanoids. We found the following: (1) A fall in mean pulmonary arterial pressure (mPAP) of ≥25% predicted freedom from adverse clinical events with 80.7% accuracy and was also associated with improved functional class. (2) Thirty-three percent of patients who avoided an adverse clinical event demonstrated a ≥25% reduction in mPAP after 1 year of treatment, and 65% by 2 years. (3) Lower mPAP was seldom seen with doses of epoprostenol >60 ng/kg/min (100 ng/kg/min for treprostinil). Cardiac index was positively correlated with the dose of epoprostenol but not treprostinil; cardiac index >4 l/min/m2 was seen at modest as well as high doses. We conclude that a ≥25% fall in mPAP on prostanoids indicates a positive clinical response which, if validated in other studies, may be useful for patient management or clinical trials. Some patients take more than 2 years for this change. Exceptionally high doses were generally not more effective than lower, although we could not determine whether lower doses would have been as effective.

scholarly journals Replacing a phosphodiesterase-5 inhibitor with riociguat in patients with connective tissue disease-associated pulmonary arterial hypertension: a case series

2017 ◽  
Vol 7 (3) ◽  
pp. 741-746 ◽  
Author(s):  
Amresh Raina ◽  
Raymond L. Benza ◽  
Harrison W. Farber
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Connective Tissue ◽  
Arterial Hypertension ◽  
Clinical Response ◽  
Connective Tissue Disease ◽  
Case Series ◽  
Response To Treatment ◽  
Tolerability Profile ◽  
Phosphodiesterase Type 5 Inhibitors ◽  
Pulmonary Arterial

Patients with pulmonary arterial hypertension associated with connective tissue disease (PAH-PAH-CTD) such as systemic sclerosis (SSc) have a poorer response to treatment and increased mortality compared with patients with idiopathic PAH. Current treatment options for PAH-CTD include prostanoids, phosphodiesterase type-5 inhibitors (PDE-5i), endothelin receptor antagonists, and the soluble guanylate cyclase stimulator riociguat. In this case series, we describe three patients with PAH-CTD related to limited scleroderma who were switched from a PDE-5i to riociguat due to insufficient clinical response. The switch to riociguat was associated with an improvement in respiratory and hemodynamic parameters and a favorable tolerability profile. These cases demonstrate that switching to riociguat is a therapeutic option in patients with PAH-CTD who have not achieved a satisfactory clinical response to a PDE-5i.

scholarly journals Pulmonary hemodynamic and right ventricular responses to brief and prolonged exercise in middle-aged endurance athletes

2019 ◽  
Vol 316 (2) ◽  
pp. H326-H334 ◽  
Author(s):  
Tayler A. Buchan ◽  
Stephen P. Wright ◽  
Sam Esfandiari ◽  
Felipe C. Fuchs ◽  
Taylor Gray ◽  
...  
Keyword(s):  
Steady State ◽  
Right Ventricular ◽  
Exercise Intensity ◽  
Prolonged Exercise ◽  
Middle Aged ◽  
Functional Responses ◽  
Pulmonary Hemodynamic ◽  
Pulmonary Arterial ◽  
Wedge Pressure ◽  
Rv Function

Right ventricular (RV) function is closely coupled to pulmonary arterial (PA) hemodynamics and is believed to decline with prolonged exercise. A linear pressure-flow relationship is thought to exist between PA pressures and increasing exercise intensity in athletes, yet a paucity of directly measured pulmonary hemodynamic data exists supporting this contention. We sought to describe the PA pressure, PA wedge pressure (PAWP), and RV functional responses to brief and prolonged exercise in endurance-trained athletes. Twenty-one healthy athletes (54 ± 5 yr) underwent right heart catheterization to assess pulmonary hemodynamics during graded, submaximal exercise. Measurements were made at rest and during three stages of steady-state, semiupright cycle ergometry at heart rates of 100 beats/min (EX1), 130 beats/min (EX2), and 150 beats/min (EX3). Five athletes completed an additional 34 min at 130 beats/min for a total exercise time of 60 min [prolonged exercise (PLG)]. PA pressures and PAWP increased significantly at EX1 without a further rise at EX2, EX3, or PLG. PAWP adjusted for absolute work rate demonstrated a significant decline as exercise intensity increased from EX1 to EX2. The resistance compliance time constant decreased at EX1 without further changes at EX2, EX3, and prolonged exercise. RV function did not decline during PLG. After an initial rise in PA pressure and PAWP during early, nonsteady-state exercise, values remained constant despite increases in exercise intensity and duration. These data indicate that in healthy, middle-aged endurance-trained athletes, the PA and pulmonary venous/left atrial compartments rapidly accommodate high conduit flows produced during intensive and prolonged exercise while maintaining RV function. NEW & NOTEWORTHY The right ventricular (RV)-pulmonary arterial (PA) circulatory unit has not been well studied during prolonged exercise, and this study provides an ecological approach that reflects a typical bout of endurance training integrating a transition from rest to exercise with successive increases in intensity, progressing to steady-state, sustained exercise. We demonstrated a remarkably constant response of the PA and PA wedge pressure during incremental, steady-state exercise and that no changes occur in pulmonary pressures throughout prolonged exercise, concomitant to a preservation of RV performance.

Shear stress paradigm for perinatal fractal arterial network remodeling in lambs with pulmonary hypertension and increased pulmonary blood flow

2007 ◽  
Vol 292 (6) ◽  
pp. H3006-H3018 ◽  
Author(s):  
Zahra Ghorishi ◽  
Jay M. Milstein ◽  
Francis R. Poulain ◽  
Anita Moon-Grady ◽  
Theresa Tacy ◽  
...  
Keyword(s):  
Blood Flow ◽  
Pulmonary Hypertension ◽  
Shear Stress ◽  
High Resistance ◽  
Vascular Reactivity ◽  
Fractal Model ◽  
Pulmonary Hemodynamic ◽  
Pulmonary Arterial ◽  
Hemodynamic Reactivity ◽  
And Control

Congenital heart disease with increased blood flow commonly leads to the development of increased pulmonary vascular reactivity and pulmonary arterial hypertension by mechanisms that remain unclear. We hypothesized a shear stress paradigm of hemodynamic reactivity and network remodeling via the persistence and/or exacerbation of a fetal diameter bifurcation phenotype [parent diameter d0and daughters d1≥ d2with α < 2 in ( d1/ d0)α+ ( d2/ d0)αand area ratio β < 1 in β = ( d12+ d22)/ d02] that mechanically acts as a high resistance magnifier/shear stress amplifier to blood flow. Evidence of a hemodynamic influence on network remodeling was assessed with a lamb model of high-flow-induced secondary pulmonary hypertension in which an aortopulmonary graft was surgically placed in one twin in utero (Shunt twin) but not in the other (Control twin). Eight weeks after birth arterial casts were made of the left pulmonary arterial circulation. Bifurcation diameter measurements down to 0.010 mm in the Shunt and Control twins were then compared with those of an unoperated fetal cast. Network organization, cumulative resistance, and pressure/shear stress distributions were evaluated via a fractal model whose dimension D0≈ α delineates hemodynamic reactivity. Fetus and Control twin D0differed: fetus D0= 1.72, a high-resistance/shear stress amplifying condition; control twin D0= 2.02, an area-preserving transport configuration. The Shunt twin ( D0= 1.72) maintained a fetal design but paradoxically remodeled diameter geometry to decrease cumulative resistance relative to the Control twin. Our results indicate that fetal/neonatal pulmonary hemodynamic reactivity remodels in response to shear stress, but the response to elevated blood flow and pulmonary hypertension involves the persistence and exacerbation of a fetal diameter bifurcation phenotype that facilitates endothelial dysfunction/injury.

scholarly journals P528 Response to biologic therapy in operated Crohn’s disease patients

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S454-S454
Author(s):  
A C Georgieva ◽  
A Atanassova ◽  
M Mirchev
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Biological Treatment ◽  
Biological Therapy ◽  
Surgical Intervention ◽  
Mean Value ◽  
Subsequent Treatment ◽  
Time Interval ◽  
Faecal Calprotectin

Abstract Background About 70% of Crohn’s disease (CD) patients undergo surgery due to disease complication. According to the ECCO consensus, in such cases, the tumour necrosis factor-α (TNF-α) antagonists are a means of choice to prevent post-operative relapse. Methods The aim is to evaluate endoscopic, clinical and biochemical outcomes in CD patients, who have undergone surgery, in the course of the subsequent treatment with anti-TNFα mono/combination therapy—anti-TNFα + AZA. Among patients with CD who are undergoing biological treatment, we performed a retrospective analysis of the data of those who underwent surgical intervention associated with Crohn’s disease and subsequently started biological therapy. Results Of the 69 CD patients on biological therapy, surgical intervention was performed in 44.92% (n = 31) of cases prior to the initiation of the treatment. The prevalence of patients with right-sided hemicolectomy with subsequent ileotransverse anastomosis was 54.80%, followed by incision and abscess cavity drainage 22.6%, fistula excision 19.4% and left-sided hemicolectomy 3.2%. In 22 patients (71.0%) there was a clinical response (CDAI decline ≤ 100 points), with 66.66% of them achieving clinical remission (CDAI ≥ 150) (p = 0.001, strong correlation r = 0.596, p = 0.001). During the course of treatment, 23.80% lost clinical response after 18 months of treatment. We compared the mean value of the faecal calprotectin (FCP) before starting, and during the course of the biological treatment, we found that the FCP values decreased 1.5 times: 516.78 ± 273.93, (range 100 – 857)/330.46 ± 432.25, (range 5.32–1800). The activity of the disease measured by CDAI decreases twice during the course of the biological treatment: CDAI 378.00 ± 92.89 (range 258–695)/177.93 ± 116.38 (range 34–414) and CRP values decrease over four times: CRP 59.65 ± 64.52 (range 0.9–225)/13.14 ± 23.59 (range 0.13–116.10). During the course of the biological treatment, intestinal complications were observed in 33.33%, and 9.67% of the patients who had both progression and presence of intestinal complications had a subsequent surgery. In 33.33% of cases, the treatment was intensified. 16.70% of them had to switch to another biological drug. Perianal disease prior to biological treatment in operated patients is twice as common (x2 = 3.82, p = 0.050), which in turn appears to be a risk factor for surgical treatment (OR = 3.47 (0.953–12.685)). Conclusion In the follow up of the relationship between the occurrence of a clinical response and the onset of biological therapy, we found that the time interval was essential. The earlier the anti-TNFα therapy begins, the greater the likelihood of achieving a clinical and biochemical response (r = 0.326, p &lt; 0.05).

scholarly journals Transition from parental prostacyclin to selexipag: a case series of five pulmonary arterial hypertension patients

2019 ◽  
Vol 9 (3) ◽  
pp. 204589401986216 ◽  
Author(s):  
Nathan Holthaus ◽  
Kurt W. Prins ◽  
Lauren Rose ◽  
Sasha Prisco ◽  
Marc Pritzker ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Cardiac Index ◽  
Arterial Hypertension ◽  
Case Series ◽  
Central Line ◽  
Functional Class ◽  
Sociocultural Factors ◽  
Pulmonary Vascular Disease ◽  
Inpatient Setting ◽  
Pulmonary Arterial

Parental prostacyclin is the only therapy with a proven survival benefit in pulmonary arterial hypertension (PAH). However, some patients are unable to tolerate continuous prostacyclin infusion because of central line infection, side effects, or sociocultural factors. Selexipag is a recently approved prostacyclin receptor agonist that is able to blunt PAH disease progression. Although in the same molecular pathway, the interchangeability of selexipag with prostacyclin infusions is relatively unexplored. Here, we present a case series of five stable PAH patients who were functional class (FC) I or II that were transitioned from prostacyclin infusion to selexipag using a standardized protocol in the inpatient setting. We show that the transition to selexipag in five highly selected patients was tolerated with no significant changes in FC, minimal changes in pulmonary vascular disease severity, and no significant PAH-related complications. However, there was a trend for a reduction in cardiac index after transition to selexipag. These data suggest that a transition from prostacyclin infusion to selexipag can be achieved in clinically stable PAH patients who are unable to tolerate continuous prostacyclin infusion. However, this approach should only be selectively implemented at specialized centers with close follow-up due to the trend for a reduction in cardiac index after transition to selexipag.

Pulmonary vascular response to leukotriene D4 in unanesthetized sheep: role of thromboxane

1986 ◽  
Vol 60 (3) ◽  
pp. 765-769 ◽  
Author(s):  
T. C. Noonan ◽  
A. B. Malik
Keyword(s):  
Capillary Pressure ◽  
Pulmonary Veins ◽  
Thromboxane B2 ◽  
Base Line ◽  
Vascular Response ◽  
Leukotriene D4 ◽  
Pulmonary Hemodynamic ◽  
Pulmonary Capillary ◽  
Pulmonary Capillary Pressure ◽  
Pulmonary Arterial

We examined the pulmonary vascular response to an intravenous leukotriene D4 (LTD4) injection of (1 microgram X kg-1 X min-1 for 2 min) immediately followed by infusion of 0.133 microgram X kg-1 X min-1 for 15 min in awake sheep prepared with lung lymph fistulas. LTD4 resulted in rapid generation of thromboxane A2 as measured by an increase in plasma thromboxane B2 concentration. The thromboxane B2 generation was associated with increases in pulmonary arterial and pulmonary arterial wedge pressures while left atrial pressure did not change significantly. Pulmonary lymph flow (Qlym) increased (P less than 0.05) transiently from base line 6.87 +/- 1.88 (SE) ml/h to maximum value of 9.77 +/- 1.27 at 15 min following the LTD4 infusion. The maximum increase in Qlym was associated with an increase in the estimated pulmonary capillary pressure. The increase in Qlym was not associated with a change in the lymph-to-plasma protein concentration (L/P) ratio. Thromboxane synthetase inhibition with dazoxiben (an imidazole derivative) prevented thromboxane B2 generation after LTD4 and also prevented the increases in pulmonary vascular pressures and Qlym. We conclude that LTD4 in awake sheep increases resistance of large pulmonary veins. The small transient increase in Qlym can be explained by the increase in pulmonary capillary pressure. Thromboxane appears to mediate both the pulmonary hemodynamic and lymph responses to LTD4 in sheep.

The response of the pulmonary circulation to exercise during normoxia and hypoxia following pneumonectomy in the adult sheep

1989 ◽  
Vol 67 (3) ◽  
pp. 202-206 ◽  
Author(s):  
Michele Smith ◽  
Geoffrey Coates ◽  
J. Michael Kay ◽  
Hugh O'Brodovich
Keyword(s):  
Blood Flow ◽  
Arterial Pressure ◽  
Pulmonary Arterial Pressure ◽  
Hemodynamic Response ◽  
Pulmonary Hemodynamics ◽  
Vascular Reserve ◽  
Mean Pulmonary Arterial Pressure ◽  
Pulmonary Hemodynamic ◽  
Pulmonary Arterial ◽  
Increased Blood Flow

Pneumonectomy approximately halves the available pulmonary vascular bed. It is unknown whether the remaining lung has sufficient vascular reserve to cope with increased blood flow under stressful conditions without demonstrating abnormal pulmonary hemodynamics. To investigate this question, unanesthetized ewes with vascular catheters had hemodynamics assessed before and after a left pneumonectomy. Subsequently, on different days, the sheep were exercised on a treadmill under normoxic and hypobaric hypoxic (430 mmHg) (1 mmHg = 133.3 Pa) conditions. Pneumonectomy itself increased mean pulmonary arterial pressure by 4 mmHg. During normoxic or hypoxic exercise, the pneumonectomized sheep demonstrated a pulmonary hemodynamic response similar to normal sheep with two lungs. The pressure–flow relation for the right lung suggested the vascular reserve of the lung was not exceeded during exercise in the pneumonectomized sheep. Eighteen to 70 days after pneumonectomy there was no evidence of right ventricular hypertrophy, but there were small increases in the number of muscularized vessels less than 50 μm diameter and in the amount of muscle in normally muscularized pulmonary arteries. This study demonstrates that pneumonectomy slightly increases mean pulmonary arterial pressure. However, there is sufficient vascular reserve in the remaining lung to permit a normal hemodynamic response to exercise-induced increased blood flow even under hypoxic conditions.Key words: pulmonary hypertension, pneumonectomy, sheep.

scholarly journals Effectiveness of adalimumab in treating patients with active psoriatic arthritis and predictors of good clinical responses for arthritis, skin and nail lesions

2009 ◽  
Vol 69 (2) ◽  
pp. 394-399 ◽  
Author(s):  
F Van den Bosch ◽  
B Manger ◽  
P Goupille ◽  
N McHugh ◽  
E Rødevand ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Clinical Response ◽  
Health Assessment ◽  
Severity Index ◽  
Skin Lesions ◽  
Physician Global Assessment ◽  
Good Clinical Response ◽  
Open Label ◽  
Response Predictors ◽  
Male Sex

Objectives:To evaluate the effectiveness of adalimumab in patients with psoriatic arthritis (PsA) and identify predictors of good clinical response for joint and skin lesions.Methods:Patients received adalimumab 40 mg every other week in addition to standard therapy in this prospective, 12-week, open-label, uncontrolled study. Four definitions of good clinical response were used: ⩾50% improvement in American College of Rheumatology response criteria (ACR50), good response according to European League Against Rheumatism (EULAR) guidelines, a ⩾3-grade improvement in Physician Global Assessment of psoriasis (PGA) and a ⩾50% improvement in the Nail Psoriasis Severity Index (NAPSI). Response predictors were determined by logistic regression with backward elimination (selection level was 5%).Results:Of 442 patients, 94% completed 12 weeks of treatment. At week 12, 74%, 51% and 32% of the patients had achieved ACR20, 50 and 70, respectively; 87% and 61% experienced moderate and good responses according to EULAR criteria, respectively. The percentage of patients with PGA results of “clear/almost clear” increased from 34% (baseline) to 68%. The mean NAPSI score was reduced by 44%. No new safety signals were detected. A lower Health Assessment Questionnaire Disability Index (HAQ-DI) score, greater pain assessment, male sex and absence of systemic glucocorticoid therapy were strongly associated with achievement of ACR50 and good response according to EULAR criteria. In addition, greater C-reactive protein concentration and polyarthritis predicted ACR50, and non-involvement of large joints predicted a good response according to EULAR criteria.Conclusions:Adalimumab was effective in patients with PsA. Lower impairment of physical function, greater pain, male sex and no systemic treatment with glucocorticoids were factors that increased the chance of achieving a good clinical response.

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