Optimization of Lead Placement in the Right Ventricle During Cardiac Resynchronization Therapy. A Simulation Study

[EN] Patients suffering from heart failure and left bundle branch block show electrical ventricular dyssynchrony causing an abnormal blood pumping. Cardiac resynchronization therapy (CRT) is recommended for these patients. Patients with positive therapy response normally present QRS shortening and an increased left ventricle (LV) ejection fraction. However, around one third do not respond favorably. Therefore, optimal location of pacing leads, timing delays between leads and/or choosing related biomarkers is crucial to achieve the best possible degree of ventricular synchrony during CRT application. In this study, computational modeling is used to predict the optimal location and delay of pacing leads to improve CRT response. We use a 3D electrophysiological computational model of the heart and torso to get insight into the changes in the activation patterns obtained when the heart is paced from different regions and for different atrioventricular and interventricular delays. The model represents a heart with left bundle branch block and heart failure, and allows a detailed and accurate analysis of the electrical changes observed simultaneously in the myocardium and in the QRS complex computed in the precordial leads. Computational simulations were performed using a modified version of the O'Hara et al. action potential model, the most recent mathematical model developed for human ventricular electrophysiology. The optimal location for the pacing leads was determined by QRS maximal reduction. Additionally, the influence of Purkinje system on CRT response was assessed and correlation analysis between several parameters of the QRS was made. Simulation results showed that the right ventricle (RV) upper septum near the outflow tract is an alternative location to the RV apical lead. Furthermore, LV endocardial pacing provided better results as compared to epicardial stimulation. Finally, the time to reach the 90% of the QRS area was a good predictor of the instant at which 90% of the ventricular tissue was activated. Thus, the time to reach the 90% of the QRS area is suggested as an additional index to assess CRT effectiveness to improve biventricular synchrony.This work was supported by the Secretaría de Educación Superior, Ciencia, Tecnología e Innovación (SENESCYT) of Ecuador CIBAE-023-2014, the Plan Estatal de Investigación Científica y Técnica y de Innovación 2013 2016 from the Ministerio de Economía, Industria y Competitividad of Spain and Fondo Europeo de Desarrollo Regional (FEDER) DPI2016-75799-R (AEI/FEDER, UE), and by Dirección General de Política Científica de la Generalitat Valenciana (PROMETEU 2016/088).Carpio-Garay, EF.; Gómez García, JF.; Sebastian, R.; López-Pérez, AD.; Castellanos, E.; Almendral, J.; Ferrero De Loma-Osorio, JM.... (2019). Optimization of Lead Placement in the Right Ventricle During Cardiac Resynchronization Therapy. A Simulation Study. Frontiers in Physiology. 10:1-17. https://doi.org/10.3389/fphys.2019.00074S11710Abraham, W. T., Fisher, W. G., Smith, A. L., Delurgio, D. B., Leon, A. R., Loh, E., … Messenger, J. (2002). Cardiac Resynchronization in Chronic Heart Failure. New England Journal of Medicine, 346(24), 1845-1853. doi:10.1056/nejmoa013168Abraham, W. T., Gras, D., Yu, C. M., Guzzo, L., & Gupta, M. S. (2010). Rationale and design of a randomized clinical trial to assess the safety and efficacy of frequent optimization of cardiac resynchronization therapy: The Frequent Optimization Study Using the QuickOpt Method (FREEDOM) trial. American Heart Journal, 159(6), 944-948.e1. doi:10.1016/j.ahj.2010.02.034Ai, X., & Pogwizd, S. M. (2005). Connexin 43 Downregulation and Dephosphorylation in Nonischemic Heart Failure Is Associated With Enhanced Colocalized Protein Phosphatase Type 2A. Circulation Research, 96(1), 54-63. doi:10.1161/01.res.0000152325.07495.5aAkar, F. G., Nass, R. D., Hahn, S., Cingolani, E., Shah, M., Hesketh, G. G., … Tomaselli, G. F. (2007). Dynamic changes in conduction velocity and gap junction properties during development of pacing-induced heart failure. American Journal of Physiology-Heart and Circulatory Physiology, 293(2), H1223-H1230. doi:10.1152/ajpheart.00079.2007ARBELO, E., TOLOSANA, J. M., TRUCCO, E., PENELA, D., BORRÀS, R., DOLTRA, A., … MONT, L. (2013). Fusion-Optimized Intervals (FOI): A New Method to Achieve the Narrowest QRS for Optimization of the AV and VV Intervals in Patients Undergoing Cardiac Resynchronization Therapy. Journal of Cardiovascular Electrophysiology, 25(3), 283-292. doi:10.1111/jce.12322Auricchio, A., Fantoni, C., Regoli, F., Carbucicchio, C., Goette, A., Geller, C., … Klein, H. (2004). Characterization of Left Ventricular Activation in Patients With Heart Failure and Left Bundle-Branch Block. Circulation, 109(9), 1133-1139. doi:10.1161/01.cir.0000118502.91105.f6Auricchio, A., Klein, H., Tockman, B., Sack, S., Stellbrink, C., Neuzner, J., … Spinelli, J. (1999). Transvenous biventricular pacing for heart failure: can the obstacles be overcome? The American Journal of Cardiology, 83(5), 136-142. doi:10.1016/s0002-9149(98)01015-7Barber, F., García-Fernández, I., Lozano, M., & Sebastian, R. (2018). Automatic estimation of Purkinje-Myocardial junction hot-spots from noisy endocardial samples: A simulation study. International Journal for Numerical Methods in Biomedical Engineering, 34(7), e2988. doi:10.1002/cnm.2988Barold, S. S., Ilercil, A., & Herweg, B. (2008). Echocardiographic optimization of the atrioventricular and interventricular intervals during cardiac resynchronization. Europace, 10(Supplement 3), iii88-iii95. doi:10.1093/europace/eun220Bertaglia, E., Migliore, F., Baritussio, A., De Simone, A., Reggiani, A., Pecora, D., … Stabile, G. (2017). Stricter criteria for left bundle branch block diagnosis do not improve response to CRT. Pacing and Clinical Electrophysiology, 40(7), 850-856. doi:10.1111/pace.13104Bertini, M., Ziacchi, M., Biffi, M., Martignani, C., Saporito, D., Valzania, C., … Boriani, G. (2008). Interventricular Delay Interval Optimization in Cardiac Resynchronization Therapy Guided by Echocardiography Versus Guided by Electrocardiographic QRS Interval Width. The American Journal of Cardiology, 102(10), 1373-1377. doi:10.1016/j.amjcard.2008.07.015BLEEKER, G. B., SCHALIJ, M. J., MOLHOEK, S. G., VERWEY, H. F., HOLMAN, E. R., BOERSMA, E., … BAX, J. J. (2004). Relationship Between QRS Duration and Left Ventricular Dyssynchrony in Patients with End-Stage Heart Failure. Journal of Cardiovascular Electrophysiology, 15(5), 544-549. doi:10.1046/j.1540-8167.2004.03604.xBonakdar, H. R., Jorat, M. V., Fazelifar, A. F., Alizadeh, A., Givtaj, N., Sameie, N., … Haghjoo, M. (2009). Prediction of response to cardiac resynchronization therapy using simple electrocardiographic and echocardiographic tools. Europace, 11(10), 1330-1337. doi:10.1093/europace/eup258Bordachar, P., Derval, N., Ploux, S., Garrigue, S., Ritter, P., Haissaguerre, M., & Jaïs, P. (2010). Left Ventricular Endocardial Stimulation for Severe Heart Failure. Journal of the American College of Cardiology, 56(10), 747-753. doi:10.1016/j.jacc.2010.04.038Boukens, B. J., Rivaud, M. R., Rentschler, S., & Coronel, R. (2014). Misinterpretation of the mouse ECG: ‘musing the waves ofMus musculus’. The Journal of Physiology, 592(21), 4613-4626. doi:10.1113/jphysiol.2014.279380Bradley, C. P., Pullan, A. J., & Hunter, P. J. (1997). Geometric modeling of the human torso using cubic hermite elements. Annals of Biomedical Engineering, 25(1), 96-111. doi:10.1007/bf027385422013 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy. (2013). European Heart Journal, 34(29), 2281-2329. doi:10.1093/eurheartj/eht150Brugada, J., Brachmann, J., Delnoy, P. P., Padeletti, L., Reynolds, D., Ritter, P., … Singh, J. P. (2014). Automatic Optimization of Cardiac Resynchronization Therapy Using SonR—Rationale and Design of the Clinical Trial of the SonRtip Lead and Automatic AV-VV Optimization Algorithm in the Paradym RF SonR CRT-D (RESPOND CRT) Trial. American Heart Journal, 167(4), 429-436. doi:10.1016/j.ahj.2013.12.007Cano, O., Osca, J., Sancho-Tello, M.-J., Sánchez, J. M., Ortiz, V., Castro, J. E., … Olagüe, J. (2010). Comparison of Effectiveness of Right Ventricular Septal Pacing Versus Right Ventricular Apical Pacing. The American Journal of Cardiology, 105(10), 1426-1432. doi:10.1016/j.amjcard.2010.01.004Cazeau, S., Leclercq, C., Lavergne, T., Walker, S., Varma, C., Linde, C., … Daubert, J.-C. (2001). Effects of Multisite Biventricular Pacing in Patients with Heart Failure and Intraventricular Conduction Delay. New England Journal of Medicine, 344(12), 873-880. doi:10.1056/nejm200103223441202Chung, E. S., Leon, A. R., Tavazzi, L., Sun, J.-P., Nihoyannopoulos, P., Merlino, J., … Murillo, J. (2008). Results of the Predictors of Response to CRT (PROSPECT) Trial. Circulation, 117(20), 2608-2616. doi:10.1161/circulationaha.107.743120ClelandJ. G. F. DaubertJ.-C. ErdmannE. FreemantleN. GrasD. KappenbergerL. The Effect of Cardiac Resynchronization on Morbidity and Mortality in Heart Failure.2005Coppola, G., Ciaramitaro, G., Stabile, G., DOnofrio, A., Palmisano, P., Carità, P., … Corrado, E. (2016). Magnitude of QRS duration reduction after biventricular pacing identifies responders to cardiac resynchronization therapy. International Journal of Cardiology, 221, 450-455. doi:10.1016/j.ijcard.2016.06.203Coronel, R., Wilders, R., Verkerk, A. O., Wiegerinck, R. F., Benoist, D., & Bernus, O. (2013). Electrophysiological changes in heart failure and their implications for arrhythmogenesis. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1832(12), 2432-2441. doi:10.1016/j.bbadis.2013.04.002Crozier, A., Blazevic, B., Lamata, P., Plank, G., Ginks, M., Duckett, S., … Niederer, S. A. (2016). The relative role of patient physiology and device optimisation in cardiac resynchronisation therapy: A computational modelling study. Journal of Molecular and Cellular Cardiology, 96, 93-100. doi:10.1016/j.yjmcc.2015.10.026Da Costa, A., Gabriel, L., Romeyer-Bouchard, C., Géraldine, B., Gate-Martinet, A., Laurence, B., … Isaaz, K. (2013). Focus on right ventricular outflow tract septal pacing. Archives of Cardiovascular Diseases, 106(6-7), 394-403. doi:10.1016/j.acvd.2012.08.005De Pooter, J., El Haddad, M., Timmers, L., Van Heuverswyn, F., Jordaens, L., Duytschaever, M., & Stroobandt, R. (2015). Different Methods to Measure QRS Duration in CRT Patients: Impact on the Predictive Value of QRS Duration Parameters. Annals of Noninvasive Electrocardiology, 21(3), 305-315. doi:10.1111/anec.12313Derval, N., Steendijk, P., Gula, L. J., Deplagne, A., Laborderie, J., Sacher, F., … Jaïs, P. (2010). Optimizing Hemodynamics in Heart Failure Patients by Systematic Screening of Left Ventricular Pacing Sites. Journal of the American College of Cardiology, 55(6), 566-575. doi:10.1016/j.jacc.2009.08.045DeskR. WilliamsL. HealthK. Characteristics and Distribution of M Cells in Arterially.1998Dou, J., Xia, L., Deng, D., Zang, Y., Shou, G., Bustos, C., … Crozier, S. (2012). A Study of Mechanical Optimization Strategy for Cardiac Resynchronization Therapy Based on an Electromechanical Model. Computational and Mathematical Methods in Medicine, 2012, 1-13. doi:10.1155/2012/948781DURRER, D., VAN DAM, R. T., FREUD, G. E., JANSE, M. J., MEIJLER, F. L., & ARZBAECHER, R. C. (1970). Total Excitation of the Isolated Human Heart. Circulation, 41(6), 899-912. doi:10.1161/01.cir.41.6.899Dutta, S., Mincholé, A., Quinn, T. A., & Rodriguez, B. (2017). Electrophysiological properties of computational human ventricular cell action potential models under acute ischemic conditions. Progress in Biophysics and Molecular Biology, 129, 40-52. doi:10.1016/j.pbiomolbio.2017.02.007Elhakam Elzoghby, I. A., Attia, I., Azab, A. E., & Hammouda, M. (2017). Impact of Cardiac Resynchronization Therapy on Heart Failure Patients: Experience from One Center. Archives of Medicine, 09(04). doi:10.21767/1989-5216.1000232Ferrer, A., Sebastián, R., Sánchez-Quintana, D., Rodríguez, J. F., Godoy, E. J., Martínez, L., & Saiz, J. (2015). Detailed Anatomical and Electrophysiological Models of Human Atria and Torso for the Simulation of Atrial Activation. PLOS ONE, 10(11), e0141573. doi:10.1371/journal.pone.0141573FLEVARI, P., LEFTHERIOTIS, D., FOUNTOULAKI, K., PANOU, F., RIGOPOULOS, A. G., PARASKEVAIDIS, I., & KREMASTINOS, D. T. (2009). Long-Term Nonoutflow Septal Versus Apical Right Ventricular Pacing: Relation to Left Ventricular Dyssynchrony. Pacing and Clinical Electrophysiology, 32(3), 354-362. doi:10.1111/j.1540-8159.2008.02244.xGRAS, D., GUPTA, M. S., BOULOGNE, E., GUZZO, L., & ABRAHAM, W. T. (2009). Optimization of AV and VV Delays in the Real-World CRT Patient Population: An International Survey on Current Clinical Practice. Pacing and Clinical Electrophysiology, 32, S236-S239. doi:10.1111/j.1540-8159.2008.02294.xGreenbaum, R. A., Ho, S. Y., Gibson, D. G., Becker, A. E., & Anderson, R. H. (1981). Left ventricular fibre architecture in man. Heart, 45(3), 248-263. doi:10.1136/hrt.45.3.248Guo, T., Li, R., Zhang, L., Luo, Z., Zhao, L., Yang, J., … Hua, B. (2015). Biventricular Pacing With Ventricular Fusion by Intrinsic Activation in Cardiac Resynchronization Therapy. International Heart Journal, 56(3), 293-297. doi:10.1536/ihj.14-260Gurev, V., Constantino, J., Rice, J. J., & Trayanova, N. A. (2010). Distribution of Electromechanical Delay in the Heart: Insights from a Three-Dimensional Electromechanical Model. Biophysical Journal, 99(3), 745-754. doi:10.1016/j.bpj.2010.05.028Heidenreich, E. A., Ferrero, J. M., Doblaré, M., & Rodríguez, J. F. (2010). Adaptive Macro Finite Elements for the Numerical Solution of Monodomain Equations in Cardiac Electrophysiology. Annals of Biomedical Engineering, 38(7), 2331-2345. doi:10.1007/s10439-010-9997-2Huang, W., Su, L., Wu, S., Xu, L., Xiao, F., Zhou, X., & Ellenbogen, K. A. (2017). A Novel Pacing Strategy With Low and Stable Output: Pacing the Left Bundle Branch Immediately Beyond the Conduction Block. Canadian Journal of Cardiology, 33(12), 1736.e1-1736.e3. doi:10.1016/j.cjca.2017.09.013Keller, D. U. J., Weber, F. M., Seemann, G., & Dössel, O. (2010). Ranking the Influence of Tissue Conductivities on Forward-Calculated ECGs. IEEE Transactions on Biomedical Engineering, 57(7), 1568-1576. doi:10.1109/tbme.2010.2046485Krum, H., Lemke, B., Birnie, D., Lee, K. L.-F., Aonuma, K., Starling, R. C., … Martin, D. (2012). A novel algorithm for individualized cardiac resynchronization therapy: Rationale and design of the adaptive cardiac resynchronization therapy trial. American Heart Journal, 163(5), 747-752.e1. doi:10.1016/j.ahj.2012.02.007Leclercq, C., Sadoul, N., Mont, L., Defaye, P., Osca, J., Mouton, E., … Fernandez-Lozano, I. (2015). Comparison of right ventricular septal pacing and right ventricular apical pacing in patients receiving cardiac resynchronization therapy defibrillators: the SEPTAL CRT Study. European Heart Journal, 37(5), 473-483. doi:10.1093/eurheartj/ehv422LEE, A. W. C., CROZIER, A., HYDE, E. R., LAMATA, P., TRUONG, M., SOHAL, M., … NIEDERER, S. (2017). Biophysical Modeling to Determine the Optimization of Left Ventricular Pacing Site and AV/VV Delays in the Acute and Chronic Phase of Cardiac Resynchronization Therapy. Journal of Cardiovascular Electrophysiology, 28(2), 208-215. doi:10.1111/jce.13134Lee, A. W. C., Costa, C. M., Strocchi, M., Rinaldi, C. A., & Niederer, S. A. (2018). Computational Modeling for Cardiac Resynchronization Therapy. Journal of Cardiovascular Translational Research, 11(2), 92-108. doi:10.1007/s12265-017-9779-4Lee, H., Park, J.-H., Seo, I., Park, S.-H., & Kim, S. (2014). Improved application of the electrophoretic tissue clearing technology, CLARITY, to intact solid organs including brain, pancreas, liver, kidney, lung, and intestine. BMC Developmental Biology, 14(1). doi:10.1186/s12861-014-0048-3Linde, C., Ellenbogen, K., & McAlister, F. A. (2012). Cardiac resynchronization therapy (CRT): Clinical trials, guidelines, and target populations. Heart Rhythm, 9(8), S3-S13. doi:10.1016/j.hrthm.2012.04.026Lopez-Perez, A., Sebastian, R., & Ferrero, J. M. (2015). Three-dimensional cardiac computational modelling: methods, features and applications. BioMedical Engineering OnLine, 14(1). doi:10.1186/s12938-015-0033-5Mafi Rad, M., Blaauw, Y., Dinh, T., Pison, L., Crijns, H. J., Prinzen, F. W., & Vernooy, K. (2014). Different regions of latest electrical activation during left bundle-branch block and right ventricular pacing in cardiac resynchronization therapy patients determined by coronary venous electro-anatomic mapping. European Journal of Heart Failure, 16(11), 1214-1222. doi:10.1002/ejhf.178Miri, R., Graf, I. M., & Dossel, O. (2009). Efficiency of Timing Delays and Electrode Positions in Optimization of Biventricular Pacing: A Simulation Study. IEEE Transactions on Biomedical Engineering, 56(11), 2573-2582. doi:10.1109/tbme.2009.2027692Miri, R., Reumann, M., Farina, D., & Dössel, O. (2009). Concurrent optimization of timing delays and electrode positioning in biventricular pacing based on a computer heart model assuming 17 left ventricular segments. Biomedizinische Technik/Biomedical Engineering, 54(2), 55-65. doi:10.1515/bmt.2009.013Miri, R., Reumann, M., Keller, D. U. J., Farina, D., & Dossel, O. (2008). Comparison of the electrophysiologically based optimization methods with different pacing parameters in patient undergoing resynchronization treatment. 2008 30th Annual International Conference of the IEEE Engineering in Medicine and Biology Society. doi:10.1109/iembs.2008.4649513MOLHOEK, S. G., BAX, J. J., BOERSMA, E., ERVEN, L. V., BOOTSMA, M., STEENDIJK, P., … SCHALIJ, M. J. (2004). QRS Duration and Shortening to Predict Clinical Response to Cardiac Resynchronization Therapy in Patients with End‐Stage Heart Failure. Pacing and Clinical Electrophysiology, 27(3), 308-313. doi:10.1111/j.1540-8159.2004.00433.xMora, M. T., Ferrero, J. M., Romero, L., & Trenor, B. (2017). Sensitivity analysis revealing the effect of modulating ionic mechanisms on calcium dynamics in simulated human heart failure. PLOS ONE, 12(11), e0187739. doi:10.1371/journal.pone.0187739MUTO, C., OTTAVIANO, L., CANCIELLO, M., CARRERAS, G., CALVANESE, R., ASCIONE, L., … TUCCILLO, B. (2007). Effect of Pacing the Right Ventricular Mid-Septum Tract in Patients with Permanent Atrial Fibrillation and Low Ejection Fraction. Journal of Cardiovascular Electrophysiology, 18(10), 1032-1036. doi:10.1111/j.1540-8167.2007.00914.xO’Hara, T., Virág, L., Varró, A., & Rudy, Y. (2011). Simulation of the Undiseased Human Cardiac Ventricular Action Potential: Model Formulation and Experimental Validation. PLoS Computational Biology, 7(5), e1002061. doi:10.1371/journal.pcbi.1002061Passini, E., Mincholé, A., Coppini, R., Cerbai, E., Rodriguez, B., Severi, S., & Bueno-Orovio, A. (2016). Mechanisms of pro-arrhythmic abnormalities in ventricular repolarisation and anti-arrhythmic therapies in human hypertrophic cardiomyopathy. Journal of Molecular and Cellular Cardiology, 96, 72-81. doi:10.1016/j.yjmcc.2015.09.003Pitzalis, M. V., Iacoviello, M., Romito, R., Massari, F., Rizzon, B., Luzzi, G., … Rizzon, P. (2002). Cardiac resynchronization therapy tailored by echocardiographic evaluation of ventricular asynchrony. Journal of the American College of Cardiology, 40(9), 1615-1622. doi:10.1016/s0735-1097(02)02337-9Pluijmert, M., Bovendeerd, P. H. M., Lumens, J., Vernooy, K., Prinzen, F. W., & Delhaas, T. (2016). New insights from a computational model on the relation between pacing site and CRT response. EP Europace, 18(suppl_4), iv94-iv103. doi:10.1093/europace/euw355Potse, M., Dube, B., Richer, J., Vinet, A., & Gulrajani, R. M. (2006). A Comparison of Monodomain and Bidomain Reaction-Diffusion Models for Action Potential Propagation in the Human Heart. IEEE Transactions on Biomedical Engineering, 53(12), 2425-2435. doi:10.1109/tbme.2006.880875Potse, M., Krause, D., Bacharova, L., Krause, R., Prinzen, F. W., & Auricchio, A. (2012). Similarities and differences between electrocardiogram signs of left bundle-branch block and left-ventricular uncoupling. Europace, 14(suppl 5), v33-v39. doi:10.1093/europace/eus272Prassl, A. J., Kickinger, F., Ahammer, H., Grau, V., Schneider, J. E., Hofer, E., … Plank, G. (2009). Automatically Generated, Anatomically Accurate Meshes for Cardiac Electrophysiology Problems. IEEE Transactions on Biomedical Engineering, 56(5), 1318-1330. doi:10.1109/tbme.2009.2014243PRINZEN, F. W., & PESCHAR, M. (2002). Relation Between the Pacing Induced Sequence of Activation and Left Ventricular Pump Function in Animals. Pacing and Clinical Electrophysiology, 25(4), 484-498. doi:10.1046/j.1460-9592.2002.00484.xVan Deursen, C., van Geldorp, I. E., Rademakers, L. M., van Hunnik, A., Kuiper, M., Klersy, C., … Prinzen, F. W. (2009). Left Ventricular Endocardial Pacing Improves Resynchronization Therapy in Canine Left Bundle-Branch Hearts. Circulation: Arrhythmia and Electrophysiology, 2(5), 580-587. doi:10.1161/circep.108.846022Prinzen, F. W., Vernooy, K., Lumens, J., & Auricchio, A. (2017). Physiology of Cardiac Pacing and Resynchronization. Clinical Cardiac Pacing, Defibrillation and Resynchronization Therapy, 213-248. doi:10.1016/b978-0-323-37804-8.00007-9Rickard, J., Karim, M., Baranowski, B., Cantillon, D., Spragg, D., Tang, W. H. W., … Varma, N. (2017). Effect of PR interval prolongation on long-term outcomes in patients with left bundle branch block vs non–left bundle branch block morphologies undergoing cardiac resynchronization therapy. Heart Rhythm, 14(10), 1523-1528. doi:10.1016/j.hrthm.2017.05.028Romero, D., Sebastian, R., Bijnens, B. H., Zimmerman, V., Boyle, P. M., Vigmond, E. J., & Frangi, A. F. (2010). Effects of the Purkinje

Effects of cavitation bubble interaction with temporally separated fs-laser pulses

We present a time-resolved photographic analysis of the pulse-to-pulse interaction. In particular, we studied the influence of the cavitation bubble induced by a fs-pulse on the optical focusing of the consecutive pulse and its cavitation bubble dynamics in dependence on temporal pulse separation in water. As a first result, by decreasing the temporal separation of laser pulses, there is a diminishment of the laser-induced optical breakdown (LIOB) efficiency in terms of energy conversion, caused by disturbed focusing into persisting gas bubbles at the focal volume. A LIOB at the focal spot is finally suppressed by impinging the expanding or collapsing cavitation bubble of the preceding pulse. These results could be additionally confirmed in porcine gelatin solution with various concentrations. Hence, the interaction between the laser and transparent ophthalmic tissue may be accompanied by a raised central laser energy transmission, which could be observed in case of a temporal pulse overlap. In conclusion, our experimental results are of particular importance for the optimization of the prospective ophthalmic surgical process with future generation fs-lasers

Improving the Diagnostic Performance of F-18-Fluorodeoxyglucose Positron-Emission Tomography/Computed Tomography in Prosthetic Heart Valve Endocarditis

Background: F-18-Fluorodeoxyglucose (FDG) positron-emission tomography/computed tomography (PET/CT) was recently introduced as a new tool for the diagnosis of prosthetic heart valve endocarditis (PVE). Previous studies reporting a modest diagnostic accuracy may have been hampered by unstandardized image acquisition and assessment, and several confounders, as well. The aim of this study was to improve the diagnostic performance of FDG PET/CT in patients in whom PVE was suspected by identifying and excluding possible confounders, using both visual and standardized quantitative assessments. Methods: In this multicenter study, 160 patients with a prosthetic heart valve (median age, 62 years [43-73]; 68% male; 82 mechanical valves; 62 biological; 9 transcatheter aortic valve replacements; 7 other) who underwent FDG PET/CT for suspicion of PVE, and 77 patients with a PV (median age, 73 years [65-77]; 71% male; 26 mechanical valves; 45 biological; 6 transcatheter aortic valve replacements) who underwent FDG PET/CT for other indications (negative control group), were retrospectively included. Their scans were reassessed by 2 independent observers blinded to all clinical data, both visually and quantitatively on available European Association of Nuclear Medicine Research Ltd-standardized reconstructions. Confounders were identified by use of a logistic regression model and subsequently excluded. Results: Visual assessment of FDG PET/CT had a sensitivity/specificity/positive predictive value/negative predictive value for PVE of 74%/91%/89%/78%, respectively. Low inflammatory activity (C-reactive protein <40 mg/L) at the time of imaging and use of surgical adhesives during prosthetic heart valve implantation were significant confounders, whereas recent valve implantation was not. After the exclusion of patients with significant confounders, diagnostic performance values of the visual assessment increased to 91%/95%/95%/91%. As a semiquantitative measure of FDG uptake, a European Association of Nuclear Medicine Research Ltd-standardized uptake value ratio of 2.0 was a 100% sensitive and 91% specific predictor of PVE. Conclusions: Both visual and quantitative assessments of FDG PET/CT have a high diagnostic accuracy in patients in whom PVE is suspected. FDG PET/CT should be implemented early in the diagnostic workup to prevent the negative confounding effects of low inflammatory activity (eg, attributable to prolonged antibiotic therapy). Recent valve implantation was not a significant predictor of false-positive interpretations, but surgical adhesives used during implantation were

Improving the diagnostic performance of 18F-fluorodeoxyglucose positron-emission tomography/computed tomography in prosthetic heart valve endocarditis

BACKGROUND: 18F-Fluorodeoxyglucose (FDG) positron-emission tomography/computed tomography (PET/CT) was recently introduced as a new tool for the diagnosis of prosthetic heart valve endocarditis (PVE). Previous studies reporting a modest diagnostic accuracy may have been hampered by unstandardized image acquisition and assessment, and several confounders, as well. The aim of this study was to improve the diagnostic performance of FDG PET/CT in patients in whom PVE was suspected by identifying and excluding possible confounders, using both visual and standardized quantitative assessments. METHODS: In this multicenter study, 160 patients with a prosthetic heart valve (median age, 62 years [43-73]; 68% male; 82 mechanical valves; 62 biological; 9 transcatheter aortic valve replacements; 7 other) who underwent FDG PET/CT for suspicion of PVE, and 77 patients with a PV (median age, 73 years [65-77]; 71% male; 26 mechanical valves; 45 biological; 6 transcatheter aortic valve replacements) who underwent FDG PET/CT for other indications (negative control group), were retrospectively included. Their scans were reassessed by 2 independent observers blinded to all clinical data, both visually and quantitatively on available European Association of Nuclear Medicine Research Ltd-standardized reconstructions. Confounders were identified by use of a logistic regression model and subsequently excluded. RESULTS: Visual assessment of FDG PET/CT had a sensitivity/specificity/positive predictive value/negative predictive value for PVE of 74%/91%/89%/78%, respectively. Low inflammatory activity (C-reactive protein <40 mg/L) at the time of imaging and use of surgical adhesives during prosthetic heart valve implantation were significant confounders, whereas recent valve implantation was not. After the exclusion of patients with significant confounders, diagnostic performance values of the visual assessment increased to 91%/95%/95%/91%. As a semiquantitative measure of FDG uptake, a European Association of Nuclear Medicine Research Ltd-standardized uptake value ratio of ≥2.0 was a 100% sensitive and 91% specific predictor of PVE. CONCLUSIONS: Both visual and quantitative assessments of FDG PET/CT have a high diagnostic accuracy in patients in whom PVE is suspected. FDG PET/CT should be implemented early in the diagnostic workup to prevent the negative confounding effects of low inflammatory activity (eg, attributable to prolonged antibiotic therapy). Recent valve implantation was not a significant predictor of false-positive interpretations, but surgical adhesives used during implantation were