Cardiac Conduction and Microstructure in the Atrial Isthmus

Severe atrial conduction disturbances, namely atrial flutter and atrial fibrillation are associated with aging. In USA atrial fibrillation nowadays affects 6 % of the population elder than 65 years, a fraction rising steady with increasing life expectancy. Research on atrial conduction comprising functional and structural aspects associated ageing is therefore of particular interest. The lateral and posterior part of the lower right atrium is seen as critical substrate for the genesis of intermittent block of conduction. This region of interest (ROI) forms a network of cable-like muscle bundles comprising the terminal ramifications of the terminal crest, pectinate muscles and the tricuspidal valve vestibule. Recent studies on the tissue matrix in several regions of the atria suggest, that excitation spread at a sub-millimetre size scale may differ substantially from activation maps taken from clinical recordings at a coarser size scale. However clinical mapping systems capable of resolving activation sequences in the sub- millimetre range will not be available in the foreseeable future. Ultra-high resolution techniques, like the Cardiac Near Field (CNF) recording developed recently by our group, are ideally suited to study macro- as well as micro- propagation of the cardiac impulse in the ROI. CNF-analysis allows the determination of magnitude and direction of conduction velocity as well as the detection of complex discontinuities of conduction within an observation area of much less than 1 mm. From such high-resolution recordings taken simultaneously at 5 individual sites one can get details of conduction along an individual muscle fibre or specifically in zones where fibres branch or merge. Complex conduction caused by recurrent thin (some tens of microns) barriers formed by connective tissue can be detected by this new technique. The aim of the project is to study and compare mechanisms of macro- and micro-propagation in the ROI and to develop a structure-related computer model of this atrial zone with spatio-temporal resolution unknown until know. Four components of knowledge about the ROI are needed to reach this goal: 1. a detailed electro-anatomical map of signals reflecting magnitude and direction of local conduction velocity as well as an index of microstructural complexity 2. histological images revealing the course and the topology of conducting fibers, of connective tissue and of interstitial clefts. 3. methods of image processing to convert these images into microgrids of conduction parameters related to the histograph 4. methods to assemble these data to a structure related computer model. Validation of the virtual tissue model can be made by electrophysiological experiments and vice versa. Only a broad multidisciplinary view comprising histology, image analysis, measurement technique, signal processing, computer simulation and cardiac electrophysiology will let us achieve these goals. The scientists involved in this project will ensure this approach by cooperation established yet. The results should push forward the knowledge of microstructure related conduction disturbances, particularly in the Isthmus of the right atrium. A profound analysis of the signature of microstructure in CNF-signals will open new aspects of diagnostic tools of arrhythmia analysis for future minimal-invasive catheter techniques.

Severe atrial conduction disturbances, namely atrial flutter and atrial fibrillation are associated with aging. In USA atrial fibrillation nowadays affects 6 % of the population elder than 65 years, a fraction rising steady with increasing life expectancy. Research on atrial conduction comprising functional and structural aspects associated ageing is therefore of particular interest. The lateral and posterior part of the lower right atrium is seen as critical substrate for the genesis of intermittent block of conduction. This region of interest (ROI) forms a network of cable-like muscle bundles comprising the terminal ramifications of the terminal crest, pectinate muscles and the tricuspidal valve vestibule. Recent studies on the tissue matrix in several regions of the atria suggest, that excitation spread at a sub-millimetre size scale may differ substantially from activation maps taken from clinical recordings at a coarser size scale. However clinical mapping systems capable of resolving activation sequences in the sub- millimetre range will not be available in the foreseeable future. Ultra-high resolution techniques, like the Cardiac Near Field (CNF) recording developed recently by our group, are ideally suited to study macro- as well as micro- propagation of the cardiac impulse in the ROI. CNF-analysis allows the determination of magnitude and direction of conduction velocity as well as the detection of complex discontinuities of conduction within an observation area of much less than 1 mm. From such high-resolution recordings taken simultaneously at 5 individual sites one can get details of conduction along an individual muscle fibre or specifically in zones where fibres branch or merge. Complex conduction caused by recurrent thin (some tens of microns) barriers formed by connective tissue can be detected by this new technique. The aim of the project is to study and compare mechanisms of macro- and micro-propagation in the ROI and to develop a structure-related computer model of this atrial zone with spatio-temporal resolution unknown until know. Four components of knowledge about the ROI are needed to reach this goal: 1. a detailed electro-anatomical map of signals reflecting magnitude and direction of local conduction velocity as well as an index of microstructural complexity 2. histological images revealing the course and the topology of conducting fibers, of connective tissue and of interstitial clefts. 3. methods of image processing to convert these images into microgrids of conduction parameters related to the histograph 4. methods to assemble these data to a structure related computer model. Validation of the virtual tissue model can be made by electrophysiological experiments and vice versa. Only a broad multidisciplinary view comprising histology, image analysis, measurement technique, signal processing, computer simulation and cardiac electrophysiology will let us achieve these goals. The scientists involved in this project will ensure this approach by cooperation established yet. The results should push forward the knowledge of microstructure related conduction disturbances, particularly in the Isthmus of the right atrium. A profound analysis of the signature of microstructure in CNF-signals will open new aspects of diagnostic tools of arrhythmia analysis for future minimal-invasive catheter techniques.