Paula Münkler1,2, Niklas Klatt1, Katharina Scherschel1,2,3,4, Pawel Kuklik1,5, Christiane Jungen1,2,6, Ersin Cavus1, Christian Eickholt1,5, Jan Christoph7, Marc D Lemoine1,2, Torsten Christ2,8, Stephan Willems1,2,5, René Riedel1,9,10, Paulus Kirchhof1,2,11, Christian Meyer1,2,3,4. 1. Department of Cardiology, University Heart and Vascular Center Hamburg, University Hospital Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany. 2. DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, Berlin, Germany. 3. Division of Cardiology, Angiology and Intensive Care, Cardiac Neuro- and Electrophysiology Research Consortium (cNEP), EKV Düsseldorf, Düsseldorf, Germany. 4. Cardiac Neuro- and Electrophysiology Research Consortium (cNEP), Medical Faculty, Heinrich Heine University Düsseldorf, Kirchfeldstraße 40, 40217, Düsseldorf, Germany. 5. Department of Cardiology, Asklepios Hospital St Georg, Lohmühlenstraße 5, 20099, Hamburg, Germany. 6. Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands. 7. Cardiovascular Research Institute University of California, San Francisco, 555 Mission Bay Blvd South, 352S, San Francisco, CA, USA. 8. Institute of Experimental Pharmacology and Toxicology, University Medical Centre, Martinistraße 52, 20246 Hamburg, Germany. 9. Max Planck Institute for Evolutionary Biology, Plön, Germany. 10. German Rheumatism Research Centre Berlin-an Institute of the Leibniz Association, Berlin, Germany. 11. Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, UK.
Abstract
AIMS: Cardiac arrhythmia originating from the papillary muscle (PM) can trigger ventricular fibrillation (VF) and cause sudden cardiac death even in the absence of structural heart disease. Most premature ventricular contractions, however, are benign and hitherto difficult to distinguish from a potentially fatal arrhythmia. Altered repolarization characteristics are associated with electrical instability, but electrophysiological changes which precede degeneration into VF are still not fully understood. METHODS AND RESULTS: Ventricular arrhythmia (VA) was induced by aconitine injection into PMs of healthy sheep. To investigate mechanisms of degeneration of stable VA into VF in structurally healthy hearts, endocardial high-density and epicardial mapping was performed during sinus rhythm (SR) and VA. The electrical restitution curve, modelling the relation of diastolic interval and activation recovery interval (a surrogate parameter for action potential duration), is steeper in VA than in non-arrhythmia (ventricular pacing and SR). Steeper restitution curves reflect electrical instability and propensity to degenerate into VF. Importantly, we find the parameter repolarization time in relation to cycle length (RT/CL) to differentiate self-limiting from degenerating arrhythmia with high specificity and sensitivity. CONCLUSION: RT/CL may serve as a simple index to aid differentiation between self-limiting and electrically instable arrhythmia with the propensity to degenerate to VF. RT/CL is independent of cycle length and could easily be measured to identify electrical instability in patients.
AIMS: Cardiac arrhythmia originating from the papillary muscle (PM) can trigger ventricular fibrillation (VF) and cause sudden cardiac death even in the absence of structural heart disease. Most premature ventricular contractions, however, are benign and hitherto difficult to distinguish from a potentially fatal arrhythmia. Altered repolarization characteristics are associated with electrical instability, but electrophysiological changes which precede degeneration into VF are still not fully understood. METHODS AND RESULTS: Ventricular arrhythmia (VA) was induced by aconitine injection into PMs of healthy sheep. To investigate mechanisms of degeneration of stable VA into VF in structurally healthy hearts, endocardial high-density and epicardial mapping was performed during sinus rhythm (SR) and VA. The electrical restitution curve, modelling the relation of diastolic interval and activation recovery interval (a surrogate parameter for action potential duration), is steeper in VA than in non-arrhythmia (ventricular pacing and SR). Steeper restitution curves reflect electrical instability and propensity to degenerate into VF. Importantly, we find the parameter repolarization time in relation to cycle length (RT/CL) to differentiate self-limiting from degenerating arrhythmia with high specificity and sensitivity. CONCLUSION: RT/CL may serve as a simple index to aid differentiation between self-limiting and electrically instable arrhythmia with the propensity to degenerate to VF. RT/CL is independent of cycle length and could easily be measured to identify electrical instability in patients.