BACKGROUND: Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), is an established treatment for heart failure (HF) with reduced left ventricular ejection fraction. It has not been rigorously compared with angiotensin-converting enzyme inhibitors in children. PANORAMA-HF (Prospective Trial to Assess the Angiotensin Receptor Blocker Neprilysin Inhibitor LCZ696 Versus Angiotensin-Converting Enzyme Inhibitor for the Medical Treatment of Pediatric HF) is a randomized, double-blind trial that evaluated the pharmacokinetics and pharmacodynamics (PK/PD), safety, and efficacy of sacubitril/valsartan versus enalapril in children 1 month to <18 years of age with HF attributable to systemic left ventricular systolic dysfunction (LVSD). METHODS: Children with HF attributable to LVSD were randomized to sacubitril/valsartan versus enalapril to assess the efficacy and safety of sacubitril/valsartan at 52 weeks of follow-up. The primary end point of the study was to determine whether sacubitril/valsartan was superior to enalapril for the treatment of pediatric patients with HF attributable to systemic LVSD, assessed using a primary global rank end point consisting of ranking patients from worst to best on the basis of clinical events such as death, listing for urgent heart transplant, mechanical life support requirement, worsening HF, New York Heart Association (NYHA)/Ross class, Patient Global Impression of Severity (PGIS), and Pediatric Quality of Life Inventory physical functioning domain. The change from baseline to 52 weeks in NT-proBNP (N-terminal pro–B-type natriuretic peptide) was an exploratory end point. RESULTS: A total of 375 children (mean age, 8.1±5.6 years; 52% female) were randomized to sacubitril/valsartan (N=187) or enalapril (N=188). At week 52, no significant difference was observed between the 2 treatment arms in the global rank end point (Mann-Whitney probability, 0.52 [95% CI, 0.47–0.58]; Mann-Whitney odds, 0.91 [95% CI, 0.72–1.14]; P =0.42). At week 52, clinically meaningful reductions were observed in both treatment arms in NYHA/Ross, PGIS, Patient Global Impression of Change, and NT-proBNP, without significant differences between groups. Adverse events were similar between treatment arms (incidence: sacubitril/valsartan, 88.8%; enalapril, 87.8%), and the safety profile of sacubitril/valsartan was acceptable in children. CONCLUSIONS: In this study, sacubitril/valsartan did not show superiority over enalapril in the treatment of children with HF attributable to systemic LVSD using the prespecified global rank end point. However, both treatment arms showed clinically meaningful improvements over 52 weeks. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02678312.

We present the results from the pediatric arm of the Polish Registry of Pulmonary Hypertension. We prospectively enrolled all pulmonary arterial hypertension (PAH) patients, between the ages of 3 months and 18 years, who had been under the care of each PAH center in Poland between 1 March 2018 and 30 September 2018. The mean prevalence of PAH was 11.6 per million, and the estimated incidence rate was 2.4 per million/year, but it was geographically heterogeneous. Among 80 enrolled children (females, n = 40; 50%), 54 (67.5%) had PAH associated with congenital heart disease (CHD-PAH), 25 (31.25%) had idiopathic PAH (IPAH), and 1 (1.25%) had portopulmonary PAH. At the time of enrolment, 31% of the patients had significant impairment of physical capacity (WHO-FC III). The most frequent comorbidities included shortage of growth (n = 20; 25%), mental retardation (n = 32; 40%), hypothyroidism (n = 19; 23.8%) and Down syndrome (n = 24; 30%). The majority of children were treated with PAH-specific medications, but only half of them with double combination therapy, which improved after changing the reimbursement policy. The underrepresentation of PAH classes other than IPAH and CHD-PAH, and the geographically heterogeneous distribution of PAH prevalence, indicate the need for building awareness of PAH among pediatricians, while a frequent coexistence of PAH with other comorbidities calls for a multidisciplinary approach to the management of PAH children.

December 2017 was the 230th anniversary of Jan Evangelista Purkinje's birth, which prompted us to review the life of this remarkable man who established the world's first department of physiology in Wroclaw and whose name is immortalized in the cardiologic eponym, Purkinje fibers. This paper offers an overview of Purkinje's life, legacy, and numerous scientific discoveries.

The clinical significance of B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in pediatric patients remains an area of evolving understanding, particularly regarding their utility in the presence or absence of pre-existing heart conditions. While clear cutoff values and established roles in heart failure are understood in adult patients, pediatric norms vary with age, complicating interpretation. Notably, the emergence of multi-system inflammatory syndrome in children (MIS-C) has highlighted the importance of these markers not only in the detection of acute heart failure but also as a marker of disease severity and even as a differential diagnosis tool. This review summarizes current knowledge on the utility of BNP and NT-proBNP in pediatric patients. Their unique physiology, including circulation and compensation mechanisms, likely influence BNP and NT-proBNP release, potentially even in non-heart failure states. Factors such as dynamic volemic changes accompanying inflammatory diseases in children may contribute. Thus, understanding the nuanced roles of BNP and NT-proBNP in pediatric populations is crucial for the accurate diagnosis, management, and differentiation of cardiac and non-cardiac conditions.