PICOLO trial results

Dosing of Clopidogrel for Platelet Inhibition in Infants and Young Children
Primary Results of the Platelet Inhibition in Children On cLOpidogrel (PICOLO) Trial
Jennifer S, Li et al. for the PICOLO Investigators

Circulation 2008;117:553-9

Background— Infants and young children with certain types of heart disease are at increased risk for thromboses. Clopidogrel 75 mg/d is used in adults to prevent thrombotic events. The dose to achieve similar platelet inhibition in children is unknown. The objectives of the present study were (1) to determine the dose of clopidogrel needed in infants and young children to achieve a mean 30% to 50% inhibition of 5-μmol/L ADP–induced platelet aggregation (ie, inhibition similar to that observed with 75 mg in adults) and (2) to assess the safety and tolerability of clopidogrel in infants and young children.

Methods and Results— We performed a prospective, multicenter, randomized, placebo-controlled trial evaluating the pharmacodynamics of clopidogrel in children (0 to 24 months) with a cardiac condition at risk for arterial thrombosis. Patients were randomized to clopidogrel versus placebo in a 3:1 ratio in 4 sequential groups (0.01, 0.10, 0.20, and 0.15 mg/kg) for 7 abd 28 days. Platelet aggregation was assessed at baseline and steady state by light-transmission aggregometry. Of 116 patients enrolled, 92 (50% neonates, 50% infants/toddlers) were randomized, and 73 completed the study. A total of 79% of the randomized and treated patients were taking aspirin.

Compared with placebo, clopidogrel 0.20 mg · kg−1 · d−1 resulted in a mean 49.3% (95% confidence interval 25.7% to 72.8%) inhibition of the maximum extent of platelet aggregation and a mean 43.9% (95% confidence interval 18.6% to 69.2%) inhibition of the rate of platelet aggregation. There was marked interpatient variability in the degree of platelet aggregation inhibition within each treatment-dose group and age group. No serious bleeding events occurred.

Conclusions— Clopidogrel 0.20 mg/kg/day in children 0 to 24 months of age achieves a platelet inhibition level similar to that in adults taking 75 mg/d. Clopidogrel is well tolerated in infants and young children at this dose.

Risk Stratification in Brugada Syndrome

Results of PRELUDE (PRogrammed ELectrical stimUllation preDictive valuE) Registry.

SG Priori et al.

JACC 2012;59:37-45.

Study of 247 men (Median age 44 yrs, Range 18-72 yrs)

Results: During a median follow-up of 34 months, 14 arrhythmic events (4.5%) occurred (13 appropriate shocks of the implantable defibrillator, and 1 cardiac arrest). Programmed electrical stimulation performed with a uniform and pre-specified protocol induced ventricular tachyarrhythmias in 40% of patients: arrhythmia inducibility was not a predictor of events at follow-up (9 of 14 events occurred in noninducible patients). History of syncope and spontaneous type I ECG (hazard ratio [HR]: 4.20), ventricular refractory period <200 ms (HR: 3.91), and QRS fragmentation (HR: 4.94) were significant predictors of arrhythmias.

Conclusions: Our data show that VT/VF inducibility is unable to identify high-risk patients, whereas the presence of a spontaneous type I ECG, history of syncope, ventricular effective refractory period <200 ms, and QRS fragmentation seem useful to identify candidates for prophylactic implantable cardioverter defibrillator.

Radiation Dose

Use of dose-dependent follow-up protocol and mechanism to reduce patient and staff radiation exposure in congenital and structural interventions.
Sawdy JM, et al. Cath Cardiovasc Interv 2011;78:136-42
Editorial: Cath Cardiovasc Interv 2011;78:143-4

Cath: Balloon Pulmonary Valvuloplasty

Predictors of reintervention in neonates with critical PS or PA-IVS.

Ghassan Shaath et al.

Cath Cardiovasc Interv 2012;79:659-664.

n=43 babies.

Mean f-up 19 mo.

36% required reintervention after at mean age of 7.4 mo.

Predictors of reintervention were the following:

1) Diagnosis of PA-IVS

2) Hospital stay > 7.5 days

3) TR gradient > 43 mmHg on the day after intervention

All were statistically-derived parameters. No good clinical explanation in the paper.

From discussion secton:

Humpl et al.Circ 2003;108:826-32 reported reintervention was more likely if TV z-score was < -5.

Fedderly et al. JACC 1995;25:460-5 reintervention was less likely if TV annulus > 11 mm and PV annulus > 7 mm.

Alwi et al. Cardiol Young 2005;15:141-7. PDA stenting is suggested if if small RV and TV z-score between -2.5 and -4.5.

ARBs for Marfan Syndrome

NEJM 2008;358_2787-95 (Free full text)

Angiotension II blockade and aortic root dilatation in Marfan syndrome.

Deficiency of fibrillin-1 in extracellular matrix leads to excessive signalling by TGF-beta. This may be the pathogenic mechanism for phenotypic features - including aortic root dilatation (mouse model). ARBs are known to inhibit TGF-beta. Therefore, in this non-randomized study, 18 children - mean age 6.5 yrs, range 1-16 yrs - who showed progressive dilatation of aortic root in spite of beta-blocker therapy were given ARBs.

Losartan started at 0.6 mg/kg/day x 3 weeks. If no side effects, dose was slowly increased to 1.4 mg/kg/day. (If the patient was receiving calcium-channel blocker, it was stopped when Losartan was started).

Or
Irbesartan at 1.4 mg/kg/day, increased upto 2 mg/kg/day.

Progression of aortic root dilatation was greatly reduced. See figure 2 in the article.

Prominent C-V wave in Severe Tricuspid Regurgitation

NEJM 2012 (Click here to see video in NEJM website)

Original Fontan Operation

January 2012 issue of the journal:
(Note: Apparently, this image is meant for an article, to be published in April 2012 issue. So, further description in this issue about this figure).