- Email: [email protected]
Characterization of the optimal left ventricular pacing region in dyssynchronous heart failure: Implications for biventricular cardiac resynchronization
S86 *Paulus Kirchhof, MD, *Larissa Fabritz, MD, Melanie Zwiener, PhD, Henning Witt, PhD, *Michael Scha¨fers, MD, Patricia Ruiz, PhD, *Thomas Wichter, MD and *Bodo Levkau, MD. University Hospital Mu¨nster, Mu¨nster, Germany, Max Planck Institute for Molecular Genetics, Berlin, Germany, Max Planck Institute for Molecular Genetics, Germany and University of Essen, Germany. Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited arrhythmogenic disorder characterized by spontaneous ventricular tachycardias and dilatation and dysfunction of the right ventricle. Mutations in proteins that form mechanical connections between myocytes, i.e. in plakophilin, desmoplakin, and plakoglobin (Naxos disease), have been associated with ARVC and cause haplo-insufficiency (less functional protein). To study the functional relevance of plakoglobin for ARVC, we studied mice with heterozygous deletion of the plakoglobin gene (plako-/⫹) and corresponding reduced cardiac plakoglobin expression (JCB 82:8-15,1999) and their wild type littermates (WT). Forty weeks (wk) old plako-/⫹ mice had enlarged right ventricles on echocardiography (15 MHz transducer, examination following NIH study on ARVC protocol adapted to mice, RV short axis diameter plako-/⫹ 1.81⫾0.15mm vs. WT 1.25⫾0.06mm, area plako-/⫹ 4.9⫾0.4mm2 vs. WT 2.2⫾0.3mm2, RV area long axis area plako-/⫹ 6.6⫾0.5mm2 vs. WT 4.4⫾0.3 mm2, all p⬍0.01, 11 plako-/⫹ and n⫽9 WT) and on mouse 18C-FDG PET. Left ventricular size and function were not altered in plako-/⫹ mice. In isolated, Langendorff-perfused hearts, orciprenaline (1.6M) provoked spontaneous ventricular tachycardias in 40wk old plako-/⫹ mouse hearts (9/13 plako-/⫹ vs. 1/7 WT, p⬍0.01, Figure), but not in 12wk old mouse hearts (2/10 plako-/⫹ vs. 3/10 WT). RV activation times were not different between genotypes. Monophasic action potential data will be reported. Conclusions: Heterozygous plakoglobin deficiency provokes ARVC with selective right ventricular enlargement and catecholamine-induced ventricular tachycardias. Plakoglobin-/⫹ mice are a model to study arrhythmia mechanisms in ARVC.
AB43-2 CHARACTERIZATION OF THE OPTIMAL LEFT VENTRICULAR PACING REGION IN DYSSYNCHRONOUS HEART FAILURE: IMPLICATIONS FOR BIVENTRICULAR CARDIAC RESYNCHRONIZATION Robert H. Helm, MD, Melissa J. Byrne, PhD, Samantapudi K. Daya, MD, James Chen, Richard Tunin, MS, Menekhem M. Zviman, PhD, Henry R. Halperin, MD, Ronald Berger, MD, PhD, David A. Kass, MD and Albert C. Lardo, PhD. Johns Hopkins Medical Institute, Baltimore, MD. Background: We recently characterized the full 3-D geographic distribution of efficacious left ventricular (LV) pacing sites during biventricular pacing (BiV) in a model of dyssynchronous contraction (DC) without heart failure (HF). Whether the superimposed effect of HF in this model changes the spatial distribution of these sites and the corresponding degree of mechanical synchrony, however, remains unknown. Methods: HF and DC was induced in 5 dogs by tachypacing (210 min-1 x 3 weeks) and ablation of the left bundle branch, respectively. An epicardial, elastic sock fitted with 128 electrodes was interfaced with a computercontrolled stimulation system enabling random testing of various LV stimulation sites (N⬃90) during BiV. dP/dtmax was recorded and 3-D function maps generated. Tagged-MRIs were also acquired and an index of
Heart Rhythm, Vol 2, No 5, May Supplement 2005 mechanical synchrony (CURE, Circ, 2002;106:1760) was generated for each LV site tested and superimposed on dP/dt maps (Fig). Results: The maximal BiV dP/dtmax response was ⫹21⫾4% over dyssynchronous baseline. Areas representing ⱖ70, 80, and 90% of this maximal response comprised 37⫾5, 19⫾4,and 9⫾2% of the total LV surface area. The ⱖ70% max response area originated 38⫾5° from the anterior interventricular junction, traversed 77⫾10° of the mid-LV surface, was centered over the anteriolateral wall, and stretched evenly from apex-to-base. Pacing within the ⱖ70% response region was associated with improved mechanical synchrony as determined by MRI (CURE ⫽ 0.89⫾0.04 verses 0.56⫾0.15 outside the region). Conclusion: The optimal LV stimulation region and mechanical synchrony can be quantified using MRI in a model of dyssynchronous heart failure. These data have implications for optimizing LV lead placement in candidates for BiV, especially those with variant coronary sinus anatomy.
AB43-3 THE TRANSMURAL LOCATION OF EARLIEST ACTIVATION FOLLOWING A DEFIBRILLATION SHOCK IS SPECIES DEPENDENT Xianhong Fang, MD, Gregory P. Walcott, MD, Jian Huang, MD, PhD, Sharon Melnick, Cheryl R. Killingsworth, DVM, PhD, William M. Smith, PhD and Raymond E. Ideker, MD, PhD. University of Alabama at Birmingham, Birmingham, AL. Background: Electrical and optical mapping studies have found that earliest activation following a shock of near defibrillation threshold (DFT) strength is not recorded until tens of msec after the shock. One possible explanation for this quiescent period is that activation is confined to Purkinje fibers during this time. The Purkinje distribution is limited to the endocardium in dogs but extends almost to the epicardium in pigs. Therefore, if activation occurs in Purkinje fibers during the quiescent period, the site of earliest recorded activation in the working myocardium following the shock should be near the endocardium in dogs but near the epicardium in pigs. Methods: In 6 pigs and 5 dogs, 84-90 plunge needles each containing 6 (LV) or 4 (RV) electrodes 2 mm apart were inserted in the ventricular freewalls. Shocks of DFT strength and 10% or 20% below the DFT were given from electrodes in the RV and SVC. The potentials created by the shocks as well as the site of earliest postshock activation were recorded for failed and type B successful shocks. The locations of the recording electrodes were determined by manual digitization. The shock potential gradient (VV) was calculated from the shock potentials and electrode locations. Results: The mean time from the shock until earliest recorded postshock activation was 48⫾13 ms in dogs and 52⫾12 ms in pigs (P⫽NS). Earliest activation in dogs was within the endocardial half of the LV wall in 79% of the shock episodes and in the epicardial half in 21% of episodes, while in pigs it was in the endocardial half in 16% and in the epicardial half in 84%(P⬍0.05). The distribution of VV along the 6 electrodes of the needle recording earliest postshock activation was similar in both species; VV in the endocardial half of the wall was significantly greater than in the epicardial half. Conclusion: The earliest site of postshock activation is near the endocardium in dogs but near the epicardium in pigs. This difference is not due to
AB43-2 CHARACTERIZATION OF THE OPTIMAL LEFT VENTRICULAR PACING REGION IN DYSSYNCHRONOUS HEART FAILURE: IMPLICATIONS FOR BIVENTRICULAR CARDIAC RESYNCHRONIZATION Robert H. Helm, MD, Melissa J. Byrne, PhD, Samantapudi K. Daya, MD, James Chen, Richard Tunin, MS, Menekhem M. Zviman, PhD, Henry R. Halperin, MD, Ronald Berger, MD, PhD, David A. Kass, MD and Albert C. Lardo, PhD. Johns Hopkins Medical Institute, Baltimore, MD. Background: We recently characterized the full 3-D geographic distribution of efficacious left ventricular (LV) pacing sites during biventricular pacing (BiV) in a model of dyssynchronous contraction (DC) without heart failure (HF). Whether the superimposed effect of HF in this model changes the spatial distribution of these sites and the corresponding degree of mechanical synchrony, however, remains unknown. Methods: HF and DC was induced in 5 dogs by tachypacing (210 min-1 x 3 weeks) and ablation of the left bundle branch, respectively. An epicardial, elastic sock fitted with 128 electrodes was interfaced with a computercontrolled stimulation system enabling random testing of various LV stimulation sites (N⬃90) during BiV. dP/dtmax was recorded and 3-D function maps generated. Tagged-MRIs were also acquired and an index of
Heart Rhythm, Vol 2, No 5, May Supplement 2005 mechanical synchrony (CURE, Circ, 2002;106:1760) was generated for each LV site tested and superimposed on dP/dt maps (Fig). Results: The maximal BiV dP/dtmax response was ⫹21⫾4% over dyssynchronous baseline. Areas representing ⱖ70, 80, and 90% of this maximal response comprised 37⫾5, 19⫾4,and 9⫾2% of the total LV surface area. The ⱖ70% max response area originated 38⫾5° from the anterior interventricular junction, traversed 77⫾10° of the mid-LV surface, was centered over the anteriolateral wall, and stretched evenly from apex-to-base. Pacing within the ⱖ70% response region was associated with improved mechanical synchrony as determined by MRI (CURE ⫽ 0.89⫾0.04 verses 0.56⫾0.15 outside the region). Conclusion: The optimal LV stimulation region and mechanical synchrony can be quantified using MRI in a model of dyssynchronous heart failure. These data have implications for optimizing LV lead placement in candidates for BiV, especially those with variant coronary sinus anatomy.
AB43-3 THE TRANSMURAL LOCATION OF EARLIEST ACTIVATION FOLLOWING A DEFIBRILLATION SHOCK IS SPECIES DEPENDENT Xianhong Fang, MD, Gregory P. Walcott, MD, Jian Huang, MD, PhD, Sharon Melnick, Cheryl R. Killingsworth, DVM, PhD, William M. Smith, PhD and Raymond E. Ideker, MD, PhD. University of Alabama at Birmingham, Birmingham, AL. Background: Electrical and optical mapping studies have found that earliest activation following a shock of near defibrillation threshold (DFT) strength is not recorded until tens of msec after the shock. One possible explanation for this quiescent period is that activation is confined to Purkinje fibers during this time. The Purkinje distribution is limited to the endocardium in dogs but extends almost to the epicardium in pigs. Therefore, if activation occurs in Purkinje fibers during the quiescent period, the site of earliest recorded activation in the working myocardium following the shock should be near the endocardium in dogs but near the epicardium in pigs. Methods: In 6 pigs and 5 dogs, 84-90 plunge needles each containing 6 (LV) or 4 (RV) electrodes 2 mm apart were inserted in the ventricular freewalls. Shocks of DFT strength and 10% or 20% below the DFT were given from electrodes in the RV and SVC. The potentials created by the shocks as well as the site of earliest postshock activation were recorded for failed and type B successful shocks. The locations of the recording electrodes were determined by manual digitization. The shock potential gradient (VV) was calculated from the shock potentials and electrode locations. Results: The mean time from the shock until earliest recorded postshock activation was 48⫾13 ms in dogs and 52⫾12 ms in pigs (P⫽NS). Earliest activation in dogs was within the endocardial half of the LV wall in 79% of the shock episodes and in the epicardial half in 21% of episodes, while in pigs it was in the endocardial half in 16% and in the epicardial half in 84%(P⬍0.05). The distribution of VV along the 6 electrodes of the needle recording earliest postshock activation was similar in both species; VV in the endocardial half of the wall was significantly greater than in the epicardial half. Conclusion: The earliest site of postshock activation is near the endocardium in dogs but near the epicardium in pigs. This difference is not due to