Riociguat, a soluble guanylate cyclase stimulator, is approved for treatment of adults with pulmonary arterial hypertension (PAH). The safety, tolerability, and pharmacokinetics (PK) of oral riociguat in a pediatric population with PAH was assessed in PATENT–CHILD (NCT02562235), a multicenter, single‐arm, 24‐week, open‐label, Phase 3 study. Patients aged 6–17 years in World Health Organization functional class (WHO‐FC) I–III treated with stable endothelin receptor antagonists and/or prostacyclin analogs received riociguat equivalent to 0.5–2.5 mg three times daily in adults, as either oral pediatric suspension or tablets, based on bodyweight. Primary outcomes were safety, tolerability, and PK of riociguat. Twenty‐four patients (mean age 12.8 years), 18 of whom were in WHO‐FC II, were enrolled. Adverse events (AEs), mostly mild or moderate, were reported in 20 patients (83%). Four patients (17%) experienced a serious AE; all resolved by study end and two (8%) were considered study‐drug related. Hypotension was reported in three patients and hemoptysis in one (all mild/moderate intensity). Riociguat plasma concentrations in pediatric patients were consistent with those published in adult patients. From baseline to Week 24, mean ± standard deviation increase in 6‐minute walking distance was 23 ± 69 m (n = 19), and mean decrease in NT‐proBNP was –66 ± 585 pg/ml (n = 14). There was no change in WHO‐FC. Two patients experienced clinical worsening events of hospitalization for right heart failure. PK results confirmed a suitable riociguat dosing strategy for pediatric patients with PAH. The data suggest an acceptable safety profile with potential efficacy signals.

The role played by the right ventricular (RV) dysfunction has long been underestimated in clinical practice. Recent findings are progressively confirming that when the RV efficiency deteriorates both the right and the left circulation is (significantly) affected, but studies dedicated to a detailed description of RV hemodynamic role still lack. In response to such a gap in knowledge, this work proposes a numerical model that for the first time evaluates the effect of isolated RV dysfunction on the whole circulation. Lumped parameter modelling was applied to represent the physio-pathological hemodynamics. Different grades of impairment were simulated for three dysfunctions i.e., systolic, diastolic, and combined systolic and diastolic. Hemodynamic alterations (i.e., of blood pressure, flow, global hemodynamic parameters), arising from the dysfunctions, are calculated and analysed. Results well accord with clinical observations, showing that RV dysfunction significantly affects both the pulmonary and systemic hemodynamics. Successful validation against in vivo data proved the clinical potentiality of the model i.e., the capability of identifying the degree of RV impairment for given hemodynamic conditions. This study aims at contributing to the improvement of RV dysfunction recognition and treatment, and to the development of tools for the clinical management of pathologies involving the right heart.

Background This perspective, observational study evaluated safety and efficacy of the GORE® Cardioform ASD Occluder (WL Gore & Associates, Flagstaff, AZ), compliant and potentially innovative prosthesis recently approved for closure of ostium secundum atrial septal defects (ASD). Methods 100 unselected patients with significant ASD were submitted to trans–catheter closure with GORE® Cardioform ASD Occluder at two high–volume Italian Pediatric Cardiology centers. Primary endpoints were procedural success and safety. Secondary endpoints were closure rate and clinical safety at 1–month and 6–month follow–up. Results Patients‘age and weight were 7.8 (6.0–13.6)and 26.1 (20.0–54.0), respectively. ASD diameter was 17.4 + 4.4, resulting in QP/QS of 1.7 ± 0.7 (median 1.6). 33 patients presented an asd larger than 18mm in diameter. 58% of defects were considered complex based on the following characteristics: deficient rim(s) (except aortic rim), aneurismal/multi–fenestrated and ASD size/pt weight ratio >1.2. Device placement was successfully achieved in all but two patients (98%), in whom it embolized early after deployment, resulting in rescue surgical repair. No cross–over with different devices was recorded. Median procedure and fluoroscopy times were 54 and 11 min, respectively. Major adverse events were recorded in 7 pts. Complete closure rate was 87.3% at discharge, rising to 95.5% (39/42 pts) at 1 month evaluation, and 100% at 6 months without cardiac or extra–cardiac adverse events. “Complex” procedures were more time–consuming but as effective and safe as the “simple” ones. Conclusions The GORE® Cardioform ASD Occluder device was highly effective and versatile in closure of ASDs with different anatomy and size, even in challenging settings.