Prostanoids in pediatric pulmonary hypertension: clinical response, time-to-effect, and dose-response.

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.

Pulmonary Artery Banding in Post-tricuspid Congenital Cardiac Shunting Defects with High Pulmonary Vascular Resistance.

Reports of "treat and repair" of cardiac shunting lesions with inoperably high pulmonary vascular resistance (PVR) mostly concern pre-tricuspid defects; post-tricuspid lesions are different. We report our experience with pulmonary artery (PA) banding ± targeted pulmonary hypertension medications in five patients with a large VSD and inoperably high PVR, and review previous reports of PA banding with post-tricuspid defects. Three of our 5 patients had mean PAP > 50 mmHg after banding and no or only a transient fall in PVR. Two patients had mean PAP < 50 mmHg and lower PVR after banding; they had closure of their VSDs but have since had a progressive increase in PVR (follow-up after closure, 3.5 and 7.7 years). Previous reports have also documented difficulty in achieving sufficient band gradient. Of previously reported patients, only one became operable only after banding and targeted therapy, and was repaired; follow-up after repair was short-term (16 months). Our and previous experience demonstrate the difficulty in placing a PA band sufficiently tight to substantially reduce PA pressure. Reported attempts to "treat and repair" post-tricuspid defects are few and have met with limited success, and we found that PVR may increase significantly over time after repair. But more information is needed. Accurate interpretation of experience with "treat and repair" requires: careful characterization of the pulmonary circulation prior to "treating"; considering spontaneously reversible factors at pre-treatment catheterization before ascribing reduction in PVR to medical therapy; and long-term observation of PVR in patients who have had defect closure.

The impact of right ventricular pressure and function on survival in patients with pulmonary vein stenosis.

Pulmonary vein stenosis (PVS) is associated with pulmonary hypertension (PH), but there is little information regarding the impact of PH on right ventricular (RV) systolic function and survival. We conducted a retrospective cohort study of our patients to explore this and other aspects of pulmonary hemodynamics with PVS. RV function was assessed using qualitative two-dimensional echocardiography. The ratio of systolic pulmonary artery (PA) and aortic pressures (PA:Ao) at cardiac catheterization reflected pulmonary hemodynamics. Reactivity testing employed inhaled nitric oxide + 100% fiO2, or 100% fiO2 only; "reactivity" was a ≥ 20% decrease in PA:Ao. There were 105 PVS patients, although not all had data at every time point. (1) The mean PA:Ao at first cardiac catheterization (n = 77) was 0.79 ± 0.36; at last catheterization (n = 54), PA:Ao = 0.69 ± 0.30; 90% had systolic PAP > one-half systemic. Survival was shorter with PA:Ao > 0.5. (2) Differences in survival relative to RV dysfunction on the first echocardiogram were not significant, although they were using the last echocardiogram. (3) The magnitude of RV dysfunction was positively correlated with PA:Ao. (4) Balloon dilation of PV acutely decreased PA:Ao (-0.13 ± 0.37, P = 0.03 [n = 40 patients]). 5. Of 20 patients tested, 13 were acutely reactive to vasodilators. PH is a major feature of PVS. Reduced RV function and PA:Ao appear to be predictors of survival. Given the importance of PH in this disease, clinical studies of PVS treatments should include measures of PAP and RV function as important variables of interest.

Central venous line complications with chronic ambulatory infusion of prostacyclin analogues in pediatric patients with pulmonary arterial hypertension.

Chronic infusion of prostacyclin (PGI2) via a Broviac central venous line (CVL) is attended by risk of CVL-related complications, but we know of only one report regarding CVL-associated bloodstream infection (BSI) with PGI2 in children and none regarding other complications. We conducted a retrospective cohort study involving pediatric patients with pulmonary hypertension treated with chronic intravenous infusion of PGI2 at Boston Children's Hospital and determined the rate (per 1,000 line-days) of various CVL-related complications. We also determined how often complications necessitated line replacement and hospitalization, time to replacement of CVLs, and interpatient variability in the incidence of complications. From 1999 until 2014, 26 patients meeting follow-up criteria had PGI2 infusion, representing 43,855 line-days; mean follow-up was 56 months (range, 1.4-161 months). The CVL complication rates (per 1,000 line-days) were as follows: CVL-BSI, 0.25; superficial line infection, 0.48; impaired integrity, 0.59; occlusion, 0.09; and malposition, 0.32. The total complication rate was 1.73 cases per 1,000 line-days. All CVL-BSI and malposition cases were treated with CVL removal and replacement. Of CVLs with impaired integrity, 23 could be repaired and 3 required replacement. Six of 21 superficial CVL infections required replacement of the CVL. Three of 4 occluded CVLs were replaced. CVL complications occasioned 65 hospitalizations. There was marked interpatient variability in the rate of complications, much but not all of which appeared to be related to duration of CVL placement. We conclude that non-BSI complications are very significant and that efforts to teach and emphasize other aspects of line care are therefore very important.

Quality of life and parental adjustment in pediatric pulmonary hypertension.

BACKGROUND: This study examines the impact of pulmonary hypertension (PH) on the quality of life (QoL) of affected youth, as well as the relationships among PH disease severity, parental adjustment variables, and family relational functioning. METHODS: Subjects were 47 eligible parents of children with PH aged 2 to 18 years who were evaluated at Boston Children's Hospital. Measures of patient QoL and of parental stress, coping, and adjustment were administered to the caregivers. Clinicians rated illness severity and family relational functioning. RESULTS: Youth with PH scored significantly lower than healthy norms on a measure of parent-reported QoL (total, psychosocial, and physical QoL, each P < .0001). The parents reported encountering stressful events more frequently than published norms of parents of children with cancer (P < .0001). Thirty-four percent of parents of children with PH met criteria for presumed psychiatric diagnosis, and they reported using psychologic coping strategies significantly more often than a normative sample. A summary parental stress measure correlated inversely with child QoL, an effect that held true even after controlling for disease severity (P = .03). CONCLUSIONS: PH takes a major toll on children and their families. Decreased QoL among youth with PH was significantly associated with high levels of parental stress, over and above the effect of illness severity. These findings suggest that interventions to better support the caretakers of affected children and adolescents should accompany medical treatment advances so as to improve QoL for patients facing pediatric PH.