Hemodynamic effects of intravenous sematilide in patients with congestive heart failure: a class III antiarrhythmic agent without cardiodepressant effects.
OBJECTIVE
This study sought to evaluate the hemodynamic effects of intravenous sematilide hydrochloride, a selective class III antiarrhythmic agent, in patients with heart failure and left ventricular systolic dysfunction.


BACKGROUND
Class I antiarrhythmic agents, which primarily slow conduction, can depress ventricular function, particularly in patients with heart failure. In contrast, pure class III agents, which selectively prolong repolarization, do not adversely affect hemodynamic variables in animal models, but there are no data evaluating their hemodynamic effects in humans.


METHODS
In 39 patients with congestive heart failure and a left ventricular ejection fraction < 40%, hemodynamic and electrocardiographic measurements were obtained at baseline, after a loading dose and during a maintenance infusion of intravenous sematilide using either a low (0.75 then 0.3 mg/min) or high dose (1.5 then 0.6 mg/min) regimen. The study had an 80% power to detect clinically meaningful differences in hemodynamic variables.


RESULTS
Both low (n = 20) and high (n = 19) dose sematilide infusions produced dose-dependent increases in QT interval (5 +/- 8% [mean +/- SD] and 18 +/- 10%, respectively) and corrected QT interval (4 +/- 8% and 14 +/- 10%), and high dose sematilide decreased heart rate by 7 +/- 10% (all p < 0.025 vs. baseline). Neither dose regimen had a statistically significant effect on any other hemodynamic variable, including mean arterial, right atrial, pulmonary artery and pulmonary capillary wedge pressures; cardiac index, stroke volume, systemic and pulmonary vascular resistances; and left ventricular stroke work index. Sematilide showed no adverse hemodynamic effects in patients with left ventricular ejection fraction < or = 25% or > 25% and in patients with cardiac index < 2 or > or = 2 liters/min per m2. Sustained polymorphic ventricular tachycardia (n = 1) and excessive QT prolongation (n = 4) were seen during the high dose.


CONCLUSIONS
Sematilide, in the doses administered, prolonged repolarization but did not alter hemodynamic variables in patients with heart failure. These data suggest that class III antiarrhythmic agents, which selectively prolong repolarization, are not cardiodepressant but may be proarrhythmic in humans, especially at high doses.
Stambler
B S
BS
Division of Cardiology, Medical College of Virginia, Richmond, USA.
Gottlieb
S S
SS
Singh
B N
BN
Ramanathan
K B
KB
Ogilby
J D
JD
Ellenbogen
K A
KA
D000328:Adult; D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011342:Procainamide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
D000889:Anti-Arrhythmia Agents; C062818:sematilide; D011342:Procainamide