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OUR MISSION: TO REDUCE THE BURDEN OF CARDIOVASCULAR DISEASE
Dr. Frits Prinzen,
Dr. Tomaselli presented data from a series of studied performed in the established canine model of LBBB and heart failure (“dyssynchronous heart failure”, DHF). DHF is induced by 3-6 weeks of rapid pacing while CRT is mimicked by using rapid biventricular pacing. He showed that DHF leads to a wide range of changes in the genome, transcriptome, proteome and physiome. Part of these changes appear to be related to the presence of heart failure, others appear to be caused be regional differences in mechanical load, because several ion channels are expressed differently in early and late-activated regions. Also, application of CRT leads to disappearance of the regional differences and some of the global changes. Recent data showed that in DHF abnormalities in calcium handling even include regionally different destruction of the sarcoplasmic reticulum and uncoupling of ryanodine receptors, abnormalities that were most pronounced in the late activated LV lateral wall and disappeared upon CRT. Other findings are that the down regulation of beta-asrenergic receptors in the DHF model is uniform, but recovers substantially upon CRT. At another level, a wide range of changes in mitochondrial metabolism, such as oxydative metabolism, occur in DHF which recover during CRT.
Dr. Auricchio presented his work on electrical mapping in LBBB patients, CRT candidates using CARTO and Ensite mapping. Of particular interest is the separation in the population between ~30% of patients with hardly any delay in transseptaal conduction, wheteher the majority of these patients exhibit a disproportionately long transseptaal conduction time. There is evidence that this delay is at least part of the substrate for CRT. The slow transseptaal conduction appears to be connected with the U-shaped pattern of activation (from apex over the LV apex towards the LV free wall, which has been shown by non-contact endocardial and epicardial mapping techniques by several investigators
Dr. Derval discussed the problem that the amount of shortening of the QRS complex does not always correlate with the clinical benefit of CRT., but that pacing site DOES seem to be important. He presented a small study where measurement of LVdP/dtmax was combined with endocardial non-contact mapping, indicating that reduction in LV activation time does not perfectly correlate with acute hemodynamic response. A promising new approach is noninvasive electrocardiographic imaging, which uses body surface mapping in combination with imaging of the anatomy and position of the heart in the chest.
Dr. Merkely started to remember the audience that lead-related complications are still a major issue in pacemaker therapies. He then mentioned several options to reduce these problems. Better, multi-modality imaging can improve evaluation of the anatomy of the coronary sinus. This may help to chose the most suited tools, such as guiding catheters and the lead with the most appropriate lead-fixation capability, and chose the most appropriate site for optimal lead implantation. Some LV pacing leads have a design that helps to secure the lead in a more basal position. Dr. Merkely and colleagues have successfully employed a stent to stabilize lead position in the coronary vein. Another problem with LV pacing is phrenic nerve stimulation. The novel quadrupolar leads can solve this problem for a great deal by creating variable stimulation configurations withour repositioning the lead. The option to use the quadrupolar leads for multisite pacing needs to be investigated in more depth. Precise and complicated lead positioning may require long X-ray radiation times. Novel electromagnetic navigation systems are promising in this regard. Dr Merkely further mentioned imaging of scar location for better lead positioning and the novel approach of transseptaal LV endocardial pacing. Finally, interesting observations have been made that direct His bundle pacing can significantly narrow the QRS complex of LBBB patients, suggesting very proximal block.
From bench to practice: cardiac resynchronisation therapy
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