Management of recurrent ventricular tachyarrhythmias associated with Q-T prolongation

Eleven patients with acquired prolongation of the Q-Tc interval and recurrent ventricular tachyarrhythmias were studied. Five patients required 5 to 44 direct current shocks to correct prolonged ventricular tachyarrhythmias, and five were given at least two antiarrhythmic agents in an attempt to control the arrhythmias. In 4 of the 11 patients, when thioridazine, diuretic drugs and antiarrhythmic agents were withdrawn and hypokalemia or hypocalcemia corrected, ventricular tachyarrhythmias did not recur. The Q-Tc interval normalized in 2 to 3 days. Ventricular tachyarrhythmias were recurrent in the remaining seven patients, despite withdrawal of the drugs that caused the Q-Tc prolongation, attempted correction of hypokalemia when present and the administration of antiarrhythmic agents to four of the seven. All antiarrhythmic agents were then withdrawn in this group.

Immediately on the establishment of overdrive ventricular or atrioventricular sequential pacing in these patients, ventricular tachyarrhythmias were abolished. No breakthrough ventricular tachyarrhythmias occurred during temporary pacing. Temporary pacing was required for an average of 10 days and the Q-Tc interval normalized an average of 5 days from the onset of pacing. Three patients required a permanent pacemaker, one because of chronic complete heart block, one because of the sick sinus syndrome, and one because of frequent ventricular ectopic complexes complicating ischemic heart disease. All 11 patients survived their period of hospitalization.     

Targeting Nitric Oxide With Drug Therapy

Increasing knowledge of the role of nitric oxide (NO) in physiology and disease has stimulated efforts to target the NO pathway pharmacologically. These therapeutic strategies include NO donors that directly or indirectly release NO and agents that increase NO bioactivity. Traditional organic nitrates such as nitroglycerin, which indirectly release NO, were believed to have limited long-term efficacy and tolerability, chiefly because of nitrate tolerance. Recent studies, however, suggest more effective ways of using these agents and new applications for them. Nicorandil, a hybrid organic nitrate that also activates potassium channels, has demonstrated significant benefits in acute coronary syndromes. Other nitrates are being investigated for use in neurodegenerative diseases. Direct NO donors include NO gas, which is useful in respiratory disorders, and the more recent classes of diazeniumdiolates, sydnonimines, and S-nitrosothiols. Preliminary data suggest that these agents may be effective as anti-atherosclerotic agents as well as in other disease states. In addition, hybrid agents that consist of an NO donor coupled with a parent anti-inflammatory drug, including nonsteroidal anti-inflammatory drugs, have demonstrated enhanced efficacy and tolerability compared with the anti-inflammatory parent drug alone in diverse experimental models. Established drugs that enhance NO bioactivity include antihypertensive agents, particularly angiotensin-converting enzyme inhibitors, calcium channel blockers, and newer vasodilating β-blockers. In addition, 3-methylglutaryl coenzyme A reductase inhibitors (statins) promote NO bioactivity, both through and independent of lipid lowering. The NO-promoting actions of these established drugs provide some insight into their known benefits and suggest possible therapeutic potential.