Philipp Bengel1, Shakil Ahmad1,2, Samuel Sossalla3,4. 1. Clinic for Cardiology and Pneumology/Heart Center, University Medical Center Goettingen, DZHK (German Centre for Cardiovascular Research), Goettingen, Germany. 2. Department for Internal Medicine II, Cardiology, Pneumology, Intensive Care, University Hospital Regensburg, Regensburg, Germany. 3. Clinic for Cardiology and Pneumology/Heart Center, University Medical Center Goettingen, DZHK (German Centre for Cardiovascular Research), Goettingen, Germany. ssossalla@med.uni-goettingen.de. 4. Department for Internal Medicine II, Cardiology, Pneumology, Intensive Care, University Hospital Regensburg, Regensburg, Germany. ssossalla@med.uni-goettingen.de.
Abstract
PURPOSE OF REVIEW: Over the last years, evidence is accumulating that enhanced late sodium current (INaL) in cardiac pathologies has fundamental consequences for cellular electrophysiology. This review discusses the underlying mechanisms of INaL-induced arrhythmias and the significance of INaL-inhibition as a possible therapeutic approach. RECENT FINDINGS: Inhibition of enhanced INaL, e.g., by ranolazine, was shown to reverse these effects in different myocardial diseases including heart failure. The antianginal drug ranolazine has already been examined in larger clinical trials with promising antiarrhythmic actions. Enhanced INaL was found to be present in several cardiac pathologies like ischemia, long QT syndromes, hypertrophic cardiomyopathy, and heart failure. In settings of enhanced INaL, a sodium-dependent calcium overload leads to severe impairment of excitation-contraction coupling and therefore has a high proarrhythmogenic potential. Experimental data showed that inhibition of INaL has a high antiarrhythmic potential which could be confirmed in further clinical trials.
PURPOSE OF REVIEW: Over the last years, evidence is accumulating that enhanced late sodium current (INaL) in cardiac pathologies has fundamental consequences for cellular electrophysiology. This review discusses the underlying mechanisms of INaL-induced arrhythmias and the significance of INaL-inhibition as a possible therapeutic approach. RECENT FINDINGS: Inhibition of enhanced INaL, e.g., by ranolazine, was shown to reverse these effects in different myocardial diseases including heart failure. The antianginal drug ranolazine has already been examined in larger clinical trials with promising antiarrhythmic actions. Enhanced INaL was found to be present in several cardiac pathologies like ischemia, long QT syndromes, hypertrophic cardiomyopathy, and heart failure. In settings of enhanced INaL, a sodium-dependent calcium overload leads to severe impairment of excitation-contraction coupling and therefore has a high proarrhythmogenic potential. Experimental data showed that inhibition of INaL has a high antiarrhythmic potential which could be confirmed in further clinical trials.
Entities:
Keywords:
Arrhythmia; Heart failure; Late sodium current; Ranolazine; Remodeling
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