Andrzej Rudziński

A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study of Oral Sildenafil Citrate in Treatment-Naive Children With Pulmonary Arterial Hypertension

Background— Safe, effective therapy is needed for pediatric pulmonary arterial hypertension. Methods and Results— Children (n=235; weight ≥8 kg) were randomized to low-, medium-, or high-dose sildenafil or placebo orally 3 times daily for 16 weeks in the Sildenafil in Treatment-Naive Children, Aged 1–17 Years, With Pulmonary Arterial Hypertension (STARTS-1) study. The primary comparison was percent change from baseline in peak oxygen consumption (PV[Combining Dot Above]O2) for the 3 sildenafil doses combined versus placebo. Exercise testing was performed in 115 children able to exercise reliably; the study was powered for this population. Secondary end points (assessed in all patients) included hemodynamics and functional class. The estimated mean±SE percent change in PV[Combining Dot Above]O2 for the 3 doses combined versus placebo was 7.7±4.0% (95% confidence interval, −0.2% to 15.6%; P=0.056). PV[Combining Dot Above]O2, functional class, and hemodynamics improved with medium and high doses versus placebo; low-dose sildenafil was ineffective. Most adverse events were mild to moderate in severity. STARTS-1 completers could enter the STARTS-2 extension study; patients who received sildenafil in STARTS-1 continued the same dose, whereas placebo-treated patients were randomized to low-, medium-, or high-dose sildenafil. In STARTS-2 (ongoing), increased mortality was observed with higher doses. Conclusions— Sixteen-week sildenafil monotherapy is well tolerated in pediatric pulmonary arterial hypertension. Percent change in PV[Combining Dot Above]O2 for the 3 sildenafil doses combined was only marginally significant; however, PV[Combining Dot Above]O2, functional class, and hemodynamic improvements with medium and high doses suggest efficacy with these doses. Combined with STARTS-2 data, the overall profile favors the medium dose. Further investigation is warranted to determine optimal dosing based on age and weight. Clinical Trial Registration— http://www.clinicaltrials.gov. Unique identifier: NCT00159913.

Pierścień naczyniowy jako przyczyna zaburzeń połykania i nawracających infekcji dróg oddechowych u 5-letniej dziewczynki

Streszczenie Pierścien naczyniowy (vascular ring – VR) to wrodzona wada wielkich pni naczyniowych i ich odgalezien, charakteryzująca sie duzą roznorodnością postaci anatomicznych i objawow klinicznych. Objawy zalezą od stopnia ucisku na drogi oddechowe i/lub przelyk. Klasycznymi objawami pierścienia naczyniowego są zaburzenia oddechowe i trudności z przyjmowaniem pokarmow, wystepujące w ciągu pierwszych sześciu miesiecy zycia. Rzadziej pierścienie naczyniowe nie powodują objawow w pierwszym roku zycia, lecz pojawiają sie w poźniejszym wieku dziecka. W pracy opisano przypadek 5-letniej dziewczynki, u ktorej rozpoznano pierścien naczyniowy (podwojny luk aorty), a objawami klinicznymi byly zaburzenia polykania od pierwszego miesiąca zycia i nawracające infekcje drog oddechowych od 3. miesiąca zycia. Korekcje kardiochirurgiczną wady przeprowadzono w ciągu miesiąca od ustalenia rozpoznania.

P.1. Supraventricular Arrhythmias

The aim of the study was analysis of supraventricular tachycardia (SVT) in neonates and assessment of antiarrhythmic treatment efficacy. Study population consisted of 30 neonates – 6 females (20%) and 24 males (80%), aged from first to 29 day of life (mean age 16,2 d). All pts underwent standard 12-lead ECG and 24-hour Holter monitoring. Echocardiography with structural and functional assessment was also done in all children. Results Atrioventricular re-entry tachycardia with accessory pathway was diagnosed in 10 patients (33,3%), atrioventricular nodal re-entry tachycardia (AVNTR) in 4 neonates (13,3%), atrial ectopic tachycardia (AET) in 6 pts (20%), atrial flutter in 1 child (3,3%), sinus tachycardia in decursu of tyreotoxicosis in 1 patient (3,3%). The precise diagnose of SVT was not established in 8 patients (26,7%). In study population there were 23 children (76,7%) without any cardiac pathology, congenital heart disease was diagnosed in 4 pts (13,3%) (TOF, avs, S.Ebsteini, ASDII), tumor of right atrium (Tu) in 1 patient (3,33%), persisting pulmonary hypertension of neonates (PPHN), in 1 child (3,33%) and myocarditis (MC) in 1 patient (3,33%). Congestive heart failure was present in 13 pts (43,3%) – in 10 pts (33,3%) without structural heart disease and in 3 children (10%) with cardiac pathology (Tu, PPHN, MC). In anti-arrhythmic treatment for SVT termination adenosine was applied in 18 pts (60%) and in 10 pts (33,3%) SVT was finished. SVT was terminated also with digoxin in 2 pts (6,7%), propaphenon in 2 pts (6,7%), propranolol in 1 patient (3,3%), sotalol in 1 patient (3,3%), digoxin combined with propranolol in 9 pts (30%), digoxin with sotalol in 1 patient (3,3%). Electrical cardioversion was done in 2 pts (6,7%) and in following 2 pts (6,7%) SVT resolved after maneuvers (carotic massage, cold water). Conclusions 1.Supraventricular tachycardia in newborns is frequently complicated by congestive heart failure. 2. Digoxin is still useful and effective in SVT termination therapy. 3. Risk of SVT recurrence is rather low in neonates and connected mostly with structural heart disease.

P.1. Supraventricular ArrhythmiasP.1.1 Supraventricular Tachycardia in Neonates

The aim of the study was analysis of supraventricular tachycardia (SVT) in neonates and assessment of antiarrhythmic treatment efficacy. Study population consisted of 30 neonates – 6 females (20%) and 24 males (80%), aged from first to 29 day of life (mean age 16,2 d). All pts underwent standard 12-lead ECG and 24-hour Holter monitoring. Echocardiography with structural and functional assessment was also done in all children. Results Atrioventricular re-entry tachycardia with accessory pathway was diagnosed in 10 patients (33,3%), atrioventricular nodal re-entry tachycardia (AVNTR) in 4 neonates (13,3%), atrial ectopic tachycardia (AET) in 6 pts (20%), atrial flutter in 1 child (3,3%), sinus tachycardia in decursu of tyreotoxicosis in 1 patient (3,3%). The precise diagnose of SVT was not established in 8 patients (26,7%). In study population there were 23 children (76,7%) without any cardiac pathology, congenital heart disease was diagnosed in 4 pts (13,3%) (TOF, avs, S.Ebsteini, ASDII), tumor of right atrium (Tu) in 1 patient (3,33%), persisting pulmonary hypertension of neonates (PPHN), in 1 child (3,33%) and myocarditis (MC) in 1 patient (3,33%). Congestive heart failure was present in 13 pts (43,3%) – in 10 pts (33,3%) without structural heart disease and in 3 children (10%) with cardiac pathology (Tu, PPHN, MC). In anti-arrhythmic treatment for SVT termination adenosine was applied in 18 pts (60%) and in 10 pts (33,3%) SVT was finished. SVT was terminated also with digoxin in 2 pts (6,7%), propaphenon in 2 pts (6,7%), propranolol in 1 patient (3,3%), sotalol in 1 patient (3,3%), digoxin combined with propranolol in 9 pts (30%), digoxin with sotalol in 1 patient (3,3%). Electrical cardioversion was done in 2 pts (6,7%) and in following 2 pts (6,7%) SVT resolved after maneuvers (carotic massage, cold water). Conclusions 1.Supraventricular tachycardia in newborns is frequently complicated by congestive heart failure. 2. Digoxin is still useful and effective in SVT termination therapy. 3. Risk of SVT recurrence is rather low in neonates and connected mostly with structural heart disease.

Supraventricular Tachycardia in Neonates

The aim of the study was analysis of supraventricular tachycardia (SVT) in neonates and assessment of antiarrhythmic treatment efficacy. Study population consisted of 30 neonates – 6 females (20%) and 24 males (80%), aged from first to 29 day of life (mean age 16,2 d). All pts underwent standard 12-lead ECG and 24-hour Holter monitoring. Echocardiography with structural and functional assessment was also done in all children. Results Atrioventricular re-entry tachycardia with accessory pathway was diagnosed in 10 patients (33,3%), atrioventricular nodal re-entry tachycardia (AVNTR) in 4 neonates (13,3%), atrial ectopic tachycardia (AET) in 6 pts (20%), atrial flutter in 1 child (3,3%), sinus tachycardia in decursu of tyreotoxicosis in 1 patient (3,3%). The precise diagnose of SVT was not established in 8 patients (26,7%). In study population there were 23 children (76,7%) without any cardiac pathology, congenital heart disease was diagnosed in 4 pts (13,3%) (TOF, avs, S.Ebsteini, ASDII), tumor of right atrium (Tu) in 1 patient (3,33%), persisting pulmonary hypertension of neonates (PPHN), in 1 child (3,33%) and myocarditis (MC) in 1 patient (3,33%). Congestive heart failure was present in 13 pts (43,3%) – in 10 pts (33,3%) without structural heart disease and in 3 children (10%) with cardiac pathology (Tu, PPHN, MC). In anti-arrhythmic treatment for SVT termination adenosine was applied in 18 pts (60%) and in 10 pts (33,3%) SVT was finished. SVT was terminated also with digoxin in 2 pts (6,7%), propaphenon in 2 pts (6,7%), propranolol in 1 patient (3,3%), sotalol in 1 patient (3,3%), digoxin combined with propranolol in 9 pts (30%), digoxin with sotalol in 1 patient (3,3%). Electrical cardioversion was done in 2 pts (6,7%) and in following 2 pts (6,7%) SVT resolved after maneuvers (carotic massage, cold water). Conclusions 1.Supraventricular tachycardia in newborns is frequently complicated by congestive heart failure. 2. Digoxin is still useful and effective in SVT termination therapy. 3. Risk of SVT recurrence is rather low in neonates and connected mostly with structural heart disease.