The potential for proarrhythmic responses to the class IC sodium channel-blocking drugs encainide and flecainide has not been well described in young patients. Therefore, data were retrospectively collected from 36 institutions regarding 579 young patients who were administered encainide or flecainide for treatment of supraventricular tachycardias (encainide 86 patients, flecainide 369 patients) or ventricular arrhythmias (encainide 21 patients, flecainide 103 patients) to assess the frequency of proarrhythmia, cardiac arrest and death during therapy (adverse events). The two drugs were similar in regard to efficacy (flecainide 71.4%, encainide 59.8%) and rate of proarrhythmic responses (flecainide 7.4%; encainide 7.5%). However, patients receiving encainide more frequently experienced cardiac arrest (encainide 7.5% vs. flecainide 2.3%, p less than 0.05) or died during treatment (encainide 7.5% vs. flecainide 2.1%, p less than 0.05). Detailed data were provided for 44 patients experiencing one or more adverse events. Patient age, previous drug trials, concomitant therapy and days of inpatient monitoring were similar for patients receiving encainide or flecainide. However, echocardiographic left ventricular shortening before treatment was lower among patients receiving encainide (0.23 +/- 0.09) than among those receiving flecainide (0.34 +/- 0.06, p less than 0.05). Plasma drug concentrations were rarely elevated. Cardiac arrest (12 patients) and deaths (13 patients) occurred predominantly among patients with underlying heart disease, particularly among patients receiving flecainide for supraventricular tachycardia (8.3% vs. 0.3%, p less than 0.001). Fifteen patients with an ostensibly normal heart and normal ventricular function experienced proarrhythmia during treatment for supraventricular tachycardia, but only 3 of the 15 had a cardiac arrest or died. The relatively high incidence of adverse events should be considered when contemplating treatment with encainide or flecainide, particularly among patients with underlying heart disease.

Familial ASD is a genetically heterogeneous disorder; one disease gene maps to chromosome 5p. Recognition of the heritable basis of familial ASD is complicated by low disease penetrance and variable expressivity. Identification of ASD or other congenital heart defects in more than one family member should prompt clinical evaluation of all relatives.

We conclude that the Ile593Arg missense mutation in HERG is the cause of LQT in this family because it segregates with disease, its presence was confirmed in three ways, and it is not found in normal individuals. The Ile593Arg mutation may result in a change in potassium selectivity and permeability leading to a loss of HERG function, thereby resulting in LQT.

These data suggest ambulatory FHR surveillance of anti-SSA-positive pregnancies is feasible, has a low false positive rate and is empowering to mothers.

Esmolol, a short-acting intravenous cardioselective beta-blocking agent, was evaluated for age-dependent pharmacodynamic and pharmacokinetic features in 17 young patients (6 months to 14 years). A loading dose (500 micrograms/kg/min) alternating with a maintenance dose (25-200 micrograms/kg/min, titrating by 25 micrograms/kg/min every 4 min) was infused until the heart rate or mean arterial pressure decreased 10%. Cardiac index, left ventricular shortening fraction, and systemic vascular resistance were measured at baseline, peak esmolol effect, and recovery. Serum esmolol concentrations were obtained to determine the half-life and the elimination rate constant. Esmolol reduced the heart rate, blood pressure, shortening fraction, and cardiac index in all patients, but it did not change systemic vascular resistance. Maintenance esmolol dose was 118 +/- 49 micrograms/kg/min, and the half-life was 2.88 +/- 2.67 min. Blood pressure and heart rate returned to normal within 2-16 min, but cardiac index and shortening fraction took longer to recover. There were no statistically significant age-dependent pharmacodynamic effects, but blood pressure decreased prior to heart rate and cardiac index took longer to recovery in patients who weighed < or = 15 kg. The pharmacokinetic profile in young patients was similar to that of older patients, but the half-life was shorter. The only side effect was transient nausea and vomiting in one patient. Esmolol is a safe and efficacious beta-blocking agent in young patients.

ABSTRACT. We evaluated the effect of increased heart rate on cardiac output and stroke volume in the stage 24 chick embryo (day 4 of a 21-day incubation). Blood flow was measured with a 20 MHz pulsed-Doppler flowmeter. Heart rate was increased by pacing with square wave stimuli (1 ms duration, <4 mA). The sinus venosus was paced from bipolar Teflon-coated silver electrodes in eight embryos and the ventricular apex was paced in three embryos. The pacing rates were at the intrinsic heart rate (P:I); 125% of intrinsic heart rate (P:125%1); and 150% of intrinsic heart rate (P:150%1). Physiologic measurements during pacing were compared to those obtained at the control intrinsic rate (I). We also evaluated the velocity profile of atrioventricular inflow and conotruncal outflow at intrinsic rate and during sinus venosus and ventricular pacing. With sinus venosus pacing, mean dorsal aortic blood flow was similar at control (1.07 f 0.05 mm3/s) and P:I (1.06 2 0.06 mm3/s) (2 f SEM). However, at P:125%I and P:150%1, mean dorsal aortic blood flow decreased significantly (P:125%1,0.88 f 0.05 mm3/s; P:150%I, 0.67 f 0.07 mm3/s) (p < 0.05). Stroke volume per beat also decreased with increasing heart rates (I, 0.41 2 0.02 mm3; P:I, 0.39 2 0.02 mm3; P:125%I, 0.28 f 0.02 mm3; P:150%I, 0.18 f 0.02 mm3) (p < 0.05). With rapid sinus venosus pacing, the atrioventricular blood flow velocity profile showed a rate-dependent decrease in passive ventricular filling while active filling remained the same or increased slightly. Thus, rate-dependent passive ventricular filling may be one reason for relatively slow heart rates during early embryonic development. During ventricular pacing at the intrinsic heart rate, mean dorsal aortic blood flow decreased to near zero presumably secondary to loss of normal atrioventricular synchrony. We speculate that atrial or ventricular tachycardia would be lethal to an embryo. (Pediatr Res 22: 442-444,1987) The heart begins to function early in embryonic development. In the chick embryo, heart rate is 90 bpm at the onset of blood flow and gradually increases during development to 2 10 bpm at hatching.The mechanisms that control heart rate in the embryo are not well defined. At the early stages, the sinus node and specialized conduction system are not histologically identifiable nor is the heart innervated by the autonomic nervous system. Yet, a chick embryo's heart rate responds to environmental factors. The heart rate slows with hypothermia (1) and increases with hyperthermia I?\ 1L.hWe hypothesized that heart rate and cardiac output are directly related to the preinnervated embryonic circulation. However, we found that a paced increase in heart rate decreased cardiac output and stroke volume by compromising the passive phase of ventricular filling. METHODSFertile white Leghorn chick eggs were incubated to Hamburger-Hamilton stage 24 (3). The shell and its membranes were opened to expose the embryo. Blood flow velocity was measured with a 20 MHz pulsed-Doppler meter from a 750 piezoelectric crystal po...

No abstract

Between 1970 and July 1980, wide QRS tachycardia due to re-entry confined to the AV node with bystander involvement of an accessory atrioventricular pathway (AAV) was documented in three of 290 patients with the Wolff-Parkinson-White syndrome studied at Duke Medical Center. In each of the patients, at least one transition between wide and narrow QRS morphology was recorded without change in either the cycle length of tachycardia or the atrial activation sequence. Two of the three patients had a single left-sided AAV (lateral, postero-lateral) showing antegrade conduction only. The third patient had two right-sided AAVs (free wall, septal), each capable of bidirectional conduction. Initiation and termination of repetitive concealed conduction into the ventricular insert of an AAV appeared to be one mechanism determining bystander AAV participation. Documentation of the retrograde sequence of atrial activation during tachycardia, and examination of the effects of interpolated premature depolarizations from both the ventricle and mid-line atrium are the most helpful features in resolving the differential diagnosis of wide QRS tachycardia in patients with W-P-W syndrome.