Design and results of the antiarrhythmics vs implantable defibrillators (AVID) registry. The AVID Investigators.

BACKGROUND: The Antiarrhythmics Versus Implantable Defibrillators (AVID) Study compared treatment with implantable cardioverter-defibrillators versus antiarrhythmic drugs in patients with life-threatening ventricular arrhythmias (VAs). AVID maintained a Registry on all patients, randomized or not, with any VA or unexplained syncope who could be considered for either of the treatment strategies. Trial-eligible arrhythmias were the categories of VF cardiac arrest, Syncopal VT, and Symptomatic VT, below. METHODS AND RESULTS: Of 5989 patients screened, 4595 were registered and 1016 were randomized. Mortality follow-up through 1996 was obtained on the 4219 Registry patients enrolled before 1997 through the National Death Index. Crude mortality rates (mean+/-SD, follow-up, 16.9+/-11.5 months) were: VF cardiac arrest, 17.0% (n=1399, 238 deaths); Syncopal VT, 21.2% (n=598, 127 deaths); Symptomatic VT, 15.8% (n=1065, 168 deaths); Stable (asymptomatic) VT, 19.7% (n=497, 98 deaths); VT/VF with transient/correctable cause, 17.8% (n=270, 48 deaths); and Unexplained syncope, 12.3% (n=390, 48 deaths). CONCLUSIONS: Patients with seemingly lower-risk or unknown-risk VAs (asymptomatic VT, and VT/VF associated with a transient factor) have a (high) mortality similar to that of higher-risk, AVID-eligible VAs. The similar (and poor) prognosis of most patients with VT/VF suggests the need for reevaluation of a priori risk grouping and raises the question of the appropriate arrhythmia therapy for a broad range of patients.

Prolongation of ventricular depolarization. ECG manifestation of mexiletine toxicity.

Mexiletine is a type 1B antiarrhythmic drug similar to lidocaine. Prolongation of ventricular depolarization has not been previously reported with the usual oral dosage of mexiletine. We describe a patient with renal failure and heart failure on low-dose oral therapy who developed mexiletine toxicity, which was manifested by ECG prolongation of ventricular depolarization. This was confirmed by elevated plasma concentration of mexiletine. This case illustrates that contrary to the usual belief, mexiletine pharmacokinetics are altered by renal failure. It is important to monitor mexiletine therapy by plasma levels in patients with impaired renal function to avoid mexiletine toxicity.

Comparative study of protease inhibitors on coagulation abnormalities in canine pancreatitis.

Coagulation abnormalities induced by pancreatitis were studied in 36 dogs. The 12 dogs in group I underwent a duodenotomy alone. The six dogs in groups II, III, IV, and V had pancreatitis induced by bile injection (1 cc/kg) into the pancreatic duct. Twenty minutes after bile-induced pancreatitis, group III was given 1.0 mg/kg aprotinin (trasylol), group IV was given 10 mg/kg S-2441, a new synthetic protease inhibitor, and group V was given 0.5 mg/kg alpha 2-antitrypsin by intravenous infusion over 10 min. Blood was drawn for amylase, protime (PT), partial thromboplastin time (PTT), fibrinogen, and platelets, in addition to markers of hypercoagulation, fibrinopeptide A, and antithrombin III, and markers of fibrinolysis, B beta 15-42 immunoreactive peptide (IP), and alpha 2-antiplasmin at baseline, 1/2, 1, 3, 6, 24, 48, and 72 hr after duodenotomy or bile injection. There was no significant difference in PT, platelets, antithrombin III, and fibrinopeptide A among the five groups. With the induction of pancreatitis (group II), serum amylase was significantly elevated but fibrinogen only became elevated at 24 hr and PTT at 48 hr. The increase in B beta 15-42 IP seen 30 min after induction of pancreatitis and the decrease in alpha 2-antiplasmin were blunted by aprotinin, alpha 1-antitrypsin, and S-2441, but inhibition of the rise in amylase and B beta 15-42 IP only reached significance with S-2441 (P less than 0.05). Pancreatitis-induced fibrinolysis was inhibited by S-2441 suggesting that synthetic protease inhibitors may play a therapeutic role in pancreatitis.