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Antiarrhythmic drug therapy in CHF guided by sicilian gambit
The 2nd Annual Scientific Meeting
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Oct. 16 (Fri.) 9:50-11:50 PS I - 5 Antiarrhythmic Drug Therapy in CHF Guided by Sicilian Gambit
Satoshi Ogawa
(Keio University)
Conventional empirical antiarrhythmic therapy carries a substantial risk of worsening arrhythmias and heart failure leading to sudden death in patients with congestive heart failure (CHF). Target-based selection of antiarrhythmic drugs proposed by Sicilian Gambit allows more rational approach to patients with severely depressed left ventricular function. Apart from the issue of sudden death prevention in CHF, atrial fibrillation (AF) is one of the most important arrhythmias which require antiarrhythmic therapy without such potential complications. When selecting drugs, duration of AF should be considered in terms of atrial remodeling. In the early stage of AF, shortening of atrial refractory periods due to atrial electrical remodeling appears to play a crucial role and thus drugs that prolong atrial refractory periods by modifying atrial K channels may be a drug of choice. Na channel blockers with slow to intermediate kinetics are also known to prolong atrial refratory periods, but their use is limited because of their potent negative inotropic action. Ca channel blockers have been suggested to prevent atrial remodeling. In the late stage of AF, atrial dilatation secondary to AF persistence results in structural remodeling, such as fibrosis, myocardial disarray or abnormal gap junction function, then modification of atrial conduction by Na channel blockers may become a therapeutic choice. Thus, K channel blockers with no action on conduction are expected to be less effective in this setting. Furthermore, K channel blockers are known to be of limited values for terminating AF due to their reverse use-dependent blocking properties, and Na channel blockers are recommended for this purpose. Sicilian Gambit has provided a list of antiarrhythmic agents summarizing the action of drugs on membrane channels, receptors, and pumps as well as on ECG parameters and left ventricular function. Using this table, one can easily get the idea which drugs can be prescribed in an individual patient to suppress specific target molecules. For example, for the prevention of AF recurrence after cardioversion drugs that suppress K channels including amiodarone (potent), procainamide, quinidine, disopyramide, pirmenol, cibenzoline and bepridil, can be considered. Among these, drugs that have Na channel blocking actions of slow kinetic properties, such as disopyramide, pirmenol and cibenzoline, are excluded in patients with severely depressed LV function. Finally, most appropriate drugs can be selected by further taking drug metabolism vs. liver / kidney function, serum electrolytes, drugs being administered concomitantly, and associated diseases, into considerations. The Japanese committee for antiarrhythmic drug therapy is now in its final process to deliver an computer assisted practical guideline (CD-ROM) based on the above mentioned concept of Sicilian Gambit.
JHFS
27
•
Oct. 16 (Fri.) 9:50-11:50 PS I - 5 Antiarrhythmic Drug Therapy in CHF Guided by Sicilian Gambit
Satoshi Ogawa
(Keio University)
Conventional empirical antiarrhythmic therapy carries a substantial risk of worsening arrhythmias and heart failure leading to sudden death in patients with congestive heart failure (CHF). Target-based selection of antiarrhythmic drugs proposed by Sicilian Gambit allows more rational approach to patients with severely depressed left ventricular function. Apart from the issue of sudden death prevention in CHF, atrial fibrillation (AF) is one of the most important arrhythmias which require antiarrhythmic therapy without such potential complications. When selecting drugs, duration of AF should be considered in terms of atrial remodeling. In the early stage of AF, shortening of atrial refractory periods due to atrial electrical remodeling appears to play a crucial role and thus drugs that prolong atrial refractory periods by modifying atrial K channels may be a drug of choice. Na channel blockers with slow to intermediate kinetics are also known to prolong atrial refratory periods, but their use is limited because of their potent negative inotropic action. Ca channel blockers have been suggested to prevent atrial remodeling. In the late stage of AF, atrial dilatation secondary to AF persistence results in structural remodeling, such as fibrosis, myocardial disarray or abnormal gap junction function, then modification of atrial conduction by Na channel blockers may become a therapeutic choice. Thus, K channel blockers with no action on conduction are expected to be less effective in this setting. Furthermore, K channel blockers are known to be of limited values for terminating AF due to their reverse use-dependent blocking properties, and Na channel blockers are recommended for this purpose. Sicilian Gambit has provided a list of antiarrhythmic agents summarizing the action of drugs on membrane channels, receptors, and pumps as well as on ECG parameters and left ventricular function. Using this table, one can easily get the idea which drugs can be prescribed in an individual patient to suppress specific target molecules. For example, for the prevention of AF recurrence after cardioversion drugs that suppress K channels including amiodarone (potent), procainamide, quinidine, disopyramide, pirmenol, cibenzoline and bepridil, can be considered. Among these, drugs that have Na channel blocking actions of slow kinetic properties, such as disopyramide, pirmenol and cibenzoline, are excluded in patients with severely depressed LV function. Finally, most appropriate drugs can be selected by further taking drug metabolism vs. liver / kidney function, serum electrolytes, drugs being administered concomitantly, and associated diseases, into considerations. The Japanese committee for antiarrhythmic drug therapy is now in its final process to deliver an computer assisted practical guideline (CD-ROM) based on the above mentioned concept of Sicilian Gambit.
JHFS
27