Management of pulmonary vascular disease associated with congenital left-to-right shunts: A single-center experience.

OBJECTIVE: The study objective was to describe the course and outcomes of children under 18 years of age, with left-to-right shunts and pulmonary arterial hypertension undergoing 1 of 2 management approaches: pulmonary arterial hypertension treatment before left-to-right shunt repair (Treat First) and left-to-right shunt repair first with or without subsequent pulmonary arterial hypertension treatment (Repair First). METHODS: We performed a retrospective single-center study, conducted from September 2015 to September 2021, of children with left-to-right shunts and pulmonary arterial hypertension (defined as indexed pulmonary vascular resistance ≥ 4 Wood units [WU]∗m2) but without Eisenmenger physiology. Patient characteristics, longitudinal hemodynamics data, pulmonary arterial hypertension management, left-to-right shunt repair, and outcomes were reviewed. RESULTS: Of 768 patients evaluated for left-to-right shunt closure, 51 (6.8%) had left-to-right shunts associated with pulmonary arterial hypertension (median age 1.1 [0.37-5] years, median indexed pulmonary vascular resistance 6 [5.2-8.7] WU∗m2). In the "Treat First" group (n = 33, 65%), 27 patients (82%) underwent left-to-right shunt closure and 6 patients (18%) did not respond to pulmonary arterial hypertension therapy and did not undergo left-to-right shunt closure. In the "Repair First" group (n = 18, 35%), 12 patients (67%) received pulmonary arterial hypertension therapy and 6 patients (33%) did not. Mortality rates were 6% in the "Treat First" group and 11% in "Repair First" group with follow-ups of 3.4 and 2.5 years, respectively. After left-to-right shunt closure, there was no significant change in indexed pulmonary vascular resistance over a median follow-up of 2 years after surgery (P = .77). CONCLUSIONS: In children with left-to-right shunts and associated pulmonary arterial hypertension, treatment with pulmonary arterial hypertension-targeted therapy before defect repair does not appear to endanger the subjects and may have some benefit. The response to pulmonary arterial hypertension-targeted therapy before shunt closure persists 2 to 3 years postclosure, providing valuable insights into the long-term management of these patients.

A single institution anesthetic experience with catheterization of pediatric pulmonary hypertension patients.

Cardiac catheterization remains the gold standard for the diagnosis and management of pediatric pulmonary hypertension (PH). There is lack of consensus regarding optimal anesthetic and airway regimen. This retrospective study describes the anesthetic/airway experience of our single center cohort of pediatric PH patients undergoing catheterization, in which obtaining hemodynamic data during spontaneous breathing is preferential. A total of 448 catheterizations were performed in 232 patients. Of the 379 cases that began with a natural airway, 274 (72%) completed the procedure without an invasive airway, 90 (24%) received a planned invasive airway, and 15 (4%) required an unplanned invasive airway. Median age was 3.4 years (interquartile range [IQR] 0.7-9.7); the majority were either Nice Classification Group 1 (48%) or Group 3 (42%). Vasoactive medications and cardiopulmonary resuscitation were required in 14 (3.7%) and eight (2.1%) cases, respectively; there was one death. Characteristics associated with use of an invasive airway included age <1 year, Group 3, congenital heart disease, trisomy 21, prematurity, bronchopulmonary dysplasia, WHO functional class III/IV, no PH therapy at time of case, preoperative respiratory support, and having had an intervention (p < 0.05). A composite predictor of age <1 year, Group 3, prematurity, and any preoperative respiratory support was significantly associated with unplanned airway escalation (26.7% vs. 6.9%, odds ratio: 4.9, confidence interval: 1.4-17.0). This approach appears safe, with serious adverse event rates similar to previous reports despite the predominant use of natural airways. However, research is needed to further investigate the optimal anesthetic regimen and respiratory support for pediatric PH patients undergoing cardiac catheterization.

Safety and tolerability of continuous inhaled iloprost in critically ill pediatric pulmonary hypertension patients: A retrospective case series.

Inhaled iloprost (iILO) has shown efficacy in treating patients with hypoxic lung disease and pulmonary hypertension, inducing selective pulmonary vasodilation and improvement in oxygenation. However, its short elimination half-life of 20-30 min necessitates frequent intermittent dosing (6-9 times per day). Thus, the administration of iILO via continuous nebulization represents an appealing method of drug delivery in the hospital setting. The objectives are: (1) describe our continuous iILO delivery methodology and safety profile in mechanically ventilated pediatric pulmonary hypertension patients; and (2) characterize the initial response of iILO in these pediatric patients currently receiving iNO. Continuous iILO was delivered and well tolerated (median 6 days; range 1-94) via tracheostomy or endotracheal tube using the Aerogen® mesh nebulizer system coupled with a Medfusion® 400 syringe pump. No adverse events or delivery malfunctions were reported. Initiation of iILO resulted in an increase in oxygen saturation from 81.4 ± 8.6 to 90.8 ± 4.1%, p < 0.05. Interestingly, prior iNO therapy for >1 day resulted in a higher response rate to iILO (as defined as a ≥ 4% increase in saturations) compared to those receiving iNO <1 day (85% vs. 50%, p = 0.06). When the use of iILO is considered, continuous delivery represents a safe, less laborious alternative and concurrent treatment with iNO should not be considered a contraindication. However, given the retrospective design and small sample size, this study does not allow the evaluation of the efficacy of continuous iILO on outcomes beyond the initial response. Thus, a prospective study designed to evaluate the efficacy of continuous iILO is necessary.

Hemodynamic assessment of transitioning from parenteral prostacyclin to selexipag in pediatric pulmonary hypertension.

Despite the increase in therapeutic options, parenteral prostacyclins remain the cornerstone in the medical management of pulmonary arterial hypertension (PAH). While the use of parenteral prostacyclins in pediatric patients is well documented, less is known about alternative drug delivery methods such as enteral administration. Given that parenteral routes of prostacyclin administration (IV or SC) are invariably accompanied by complicated logistics and lifestyle compromises, enteral prostacyclin administration represents an attractive treatment option. Selexipag (Uptravi®) was approved for adults PAH in 2015. There is limited data on the hemodynamic efficacy of transitioning from parenteral prostacyclins to selexipag, particularly in the pediatric population. We report 11 pediatric PAH patients who underwent this transition, in which 10 had complete cardiac catheterization data before and following the transition to selexipag. All patients/families reported an improvement in quality of life, and the transitions occurred without adverse effects. However, 3 of the 11 (27%) did not tolerate the transition; two for worsening hemodynamics, and one for acute right ventricular failure in the setting of an intercurrent illness. In addition, the transition to selexipag was associated with a modest increase in pulmonary vascular resistance index (6/10) and decrease in cardiac index (6/10) in some patients. Selexipag use in pediatric PAH represents a significant addition to our therapeutic arsenal, and its use provides a meaningful improvement in quality of life compared with other prostacyclin formulations. However, when goals of care include aggressive disease management, a decision between improved quality of life and possible adverse outcomes must be considered, and its substitution should include cautious, close, long-term follow-up.

Caveolin-1 associated with severe (pediatric-onset) presentation of pulmonary arterial hypertension.

There has been a growing interest in the role that genetic factors influence pediatric pulmonary vascular disease. In fact, data suggests that genetic factors contribute to ~42% of pediatric-onset pulmonary hypertension. Although animal and human studies suggest that aberrations in Caveolin1 (CAV1) signaling participate in the development of pulmonary vascular disorders, limited reports of CAV1-associated heritable pulmonary arterial hypertension (HPAH) exist. This is a case report of a 2-year-old female with late recognition of HPAH due to a CAV1 pathogenic variant: c.474del, (p.Leu159Serfs*22)(NM_001753.5). The pedigree demonstrates autosomal dominant transmission with reduced penetrance of PAH, suggestive that additional genetic or environmental factors modify PAH development. Genetic testing and the discovery of rare genetic alterations in PAH during infancy and childhood may aid in identifying disease etiologies, guide therapeutic decisions, and ultimately identify novel therapeutic targets. Moreover, CAV1 genetics implicate variable expressivity and incomplete penetrance for HPAH and underscores the utility of predictive genetic testing for unaffected family members no matter their age.

Genetics dictating therapeutic decisions in pediatric pulmonary hypertension? A case report suggesting we are getting closer.

Despite therapeutic advances over the past decades, pulmonary arterial hypertension (PAH) and related pulmonary vascular diseases continue to cause significant morbidity and mortality in neonates, infants, and children. Unfortunately, an adequate understanding of underlying biology is lacking. There has been a growing interest in the role that genetic factors influence pulmonary vascular disease, with the hope that genetic information may aid in identifying disease etiologies, guide therapeutic decisions, and ultimately identify novel therapeutic targets. In fact, current data suggest that genetic factors contribute to ~42% of pediatric-onset PH compared to ~12.5% of adult-onset PAH. We report a case in which the knowledge that biallelic ATP13A3 mutations are associated with malignant progression of PAH in young childhood, led us to alter our traditional treatment plan for a 21-month-old PAH patient. In this case, we elected to perform a historically high-risk Potts shunt before expected rapid deterioration. Short-term follow-up is encouraging, and the patient remains the only known surviving pediatric PAH patient with an associated biallelic ATP13A3 mutation in the literature. We speculate that an increased use of comprehensive genetic testing can aid in identifying the underlying pathobiology and the expected natural history, and guide treatment plans among PAH patients.

Hookups Among U.S. College Students: Examining the Association Between Hookup Motives and Personal Affect.

"Hooking up" is prevalent on college campuses and is related to both positive and negative outcomes for students. The current study was an exploratory examination of hookup motives, and positive and negative affect, related to the most recent hookup experience. Participants were 256 U.S. college students who reported hooking up in the last 12 months. Students completed a 30-min anonymous online survey assessing behaviors and cognitions during their most recent hookup, including alcohol use at the time of the hookup, motives for hooking up, and post-hookup affect. The model demonstrated that gender, conformity motives, and social-relationship motives significantly and positively predicted negative affect, whereas enhancement motives negatively predicted negative affect. Coping and enhancement motives significantly and positively predicted positive affect, whereas alcohol use negatively predicted positive affect. This study was a unique examination of hookup motives, with important findings that explained large portions of variance in post-hookup affect. The overall model explained approximately 23% of the variance in negative affect and 49% of the variance in positive affect. Findings highlight that, depending on the hookup motive, hooking up can be associated with positive outcomes, such as positive affect.

Weighing the Pros and Cons of Using Alcohol Protective Behavioral Strategies: A Qualitative Examination among College Students.

BACKGROUND: Alcohol protective behavioral strategies (PBS) are behaviors engaged in immediately prior to, during, after, or instead of drinking with the explicit goal of reducing alcohol use, intoxication, and/or alcohol-related harms. Despite the quantitative support for alcohol PBS as a protective factor among college student drinkers, we know of no qualitative research aimed at determining college student drinkers' perceptions regarding the advantages and disadvantages of using PBS. OBJECTIVES: In the style of a decisional balance exercise, we asked college student drinkers (analytic n = 113) to identify 5 reasons they would not use PBS (cons) and 5 reasons they would use PBS (pros). METHOD: Participants (majority female, 77.0%) were recruited from a psychology department participant pool at a large, southeastern university in the United States. Within our analytic sample, participants on average consumed 6.38 (SD = 8.16) drinks per typical week of drinking and reported consuming alcohol on average 7.5 days (SD = 5.83) in the last 30 days. RESULTS: Using a descriptive phenomenological approach, we identified 2 themes for pros (prevention of specific negative alcohol-related consequences and general safety) and 4 themes for cons (goal conflict, ineffectiveness, difficulty of implementation, and negative peer/social repercussions). Overall, participants reported more pros than cons and this discrepancy (i.e., number of PBS pros minus number of PBS cons) was positively related to self-reported frequency of PBS use. Conclusions/Importance: Taken together, we hope that clinicians/researchers will probe individual's reasons for choosing to use (or not use) PBS in order to tailor or improve existing PBS-based interventions.

Depressive Symptoms and Alcohol-Related Problems Among College Students: A Moderated-Mediated Model of Mindfulness and Drinking to Cope.

OBJECTIVE: In college student samples, the association between depressive symptoms and alcohol-related problems has been found to be mediated by drinking-to-cope motives. Mindfulness-based interventions suggest that mindfulness may attenuate the conditioned response of using substances in response to negative emotional states, and trait mindfulness has been shown to be a protective factor associated with experiencing fewer alcohol-related problems. In the present study, we examined trait mindfulness as a moderator of the indirect associations of depressive symptoms on alcohol-related problems via drinking-to-cope motives. METHOD: Participants were undergraduate students at a large, southeastern university in the United States who drank at least once in the previous month (n = 448). Participants completed an online survey regarding their personal mental health, coping strategies, trait mindfulness, and alcohol use behaviors. The majority of participants were female (n = 302; 67.4%), identified as being either White non-Hispanic (n = 213; 47.5%) or African American (n = 119; 26.6%), and reported a mean age of 22.74 (SD = 6.81) years. Further, 110 (25%) participants reported having a previous and/or current experience with mindfulness mediation. RESULTS: As hypothesized, the indirect effects from depressive symptoms to alcohol-related problems via drinking-to-cope motives were weaker among individuals reporting higher levels of mindfulness than among individuals reporting lower and average levels of mindfulness. CONCLUSIONS: The present study suggests a possible mechanism through which mindfulness-based interventions may be efficacious among college students: decoupling the associations between depressive symptoms and drinking-to-cope motives.