Towards a Personalized and Dynamic CRT-D

Summary

Background: In spite of cardiac resynchronization therapy (CRT) benefits, 25 – 30% of patients are still non responders. One of the possible reasons could be the non optimal atrioventricular (AV) and interventricular (VV) intervals settings. Our aim was to exploit a numerical model of cardiovascular system for AV and VV intervals optimization in CRT.

Methods: A numerical model of the cardiovascular system CRT-dedicated was previously developed. Echocardiographic parameters, Systemic aortic pressure and ECG were collected in 20 consecutive patients before and after CRT. Patient data were simulated by the model that was used to optimize and set into the device the intervals at the baseline and at the follow up. The optimal AV and VV intervals were chosen to optimize the simulated selected variable/s on the base of both echocardiographic and electrocardiographic parameters.

Results: Intervals were different for each patient and in most cases, they changed at follow up. The model can well reproduce clinical data as verified with Bland Altman analysis and T-test (p > 0.05). Left ventricular remodeling was 38.7% and left ventricular ejection fraction increasing was 11% against the 15% and 6% reported in literature, respectively.

Conclusions: The developed numerical model could reproduce patients conditions at the baseline and at the follow up including the CRT effects. The model could be used to optimize AV and VV intervals at the baseline and at the follow up realizing a personalized and dynamic CRT. A patient tailored CRT could improve patients outcome in comparison to literature data.

Keywords

Cardiac resynchronization therapy - cardiovascular modeling - lumped parameter models - AV and VV optimization

• References

• 1 Dickstein K, Vardas PE, Auricchio A, Daubert JC, Linde C, McMurray J, Ponikowski P, Priori SG, Sutton R, van Veldhuisen DJ. 2010 Focused Update of ESC Guidelines on device therapy in heart failure. An update of the 2008 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure and the 2007 ESC guidelines for cardiac and resynchronization therapy. European Heart Journal 2010; 31: 2677-2687.
• 2 Bilchick KC, Kamath K, Dimarco JP, Stukenborg GJ. Bundle-Branch Block Morphology and Other Predictors of Outcome After Cardiac Resynchronization Therapy in Medicare Patients. Circulation 2010; 16 122 (20) 2022-2030.
• 3 Yu C, Abraham W, Bax J, Chung E, Fedewa M, Ghio S, Leclercq C, LeÓn A, Merlino J. Nihoyannopoulos. Predictors of response to cardiac resynchronization therapy (PROSPECT) - study design. American Heart Journal 2005; 149 (04) 600-605.
• 4 Forleo GB, Della Rocca DG, Papavasileiou LP, Di Molfetta A, Santini L, Romeo F. Left ventricular pacing with a new quadripolar transvenous lead for CRT: early results of a prospective comparison with conventional implant outcomes. Heart Rhythm 2011; 8 (01) 31-37.
• 5 Kamdar R, Frain E, Warburton F, Richmond L, Mullan V, Berriman T, Thomas G, Tenkorang J, Dhinoja M, Earley M, Sporton S, Schilling R. A prospective comparison of echocardiography and device algorithms for atrioventricular and interventricular interval optimization in cardiac resynchronization therapy. Europace 2010; 12 (01) 84-91.
• 6 van Gelder BM, Bracke FA, Meijer A, Lakerveld LJM, Pijls NHL. Effect of Optimizing the VV Interval on Left Ventricular Contractility in Cardiac Resynchronization Therapy. Am J Cardiol 2004; 93: 1500-1503.
• 7 Whinnett ZL, Nott G, Davies JE, Willson K, Manisty CH, Kanagaratnam P, Peters NS, Davies DW, Hughes AD, Mayet J, Francis DP. Maximizing Efficiency of Alternation Algorithms for Hemodynamic Optimization of the AV Delay of Cardiac Resynchronization Therapy. Pacing Clin Electrophysiol 2011; 34 (02) 217-225.
• 8 Gras D, Gupta MS, Boulogne E, Guzzo L, Abraham WT. Optimization of AV and VV delays in the real-word CRT patient population: an international survey on current clinical practice. Pacing Clin Electrophysiol 2009; 32 (01) S236-239.
• 9 Singh JP, Abraham WT. Enhancing the Response to Cardiac Resynchronization Therapy. J Am Coll Card 2010; 55 (06) 576-578.
• 10 Abraham WT, Gras D, Yu CM, Guzzo L, Gupta MS. 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. Am Heart J 2010; 159 (06) 944-948.
• 11 Baker J, Mc Kenzie J, Beau S. et al. Acute Evaluation of programmer-guided AV/PV and VV Delay optimization comparing an IEGM method and echocardiogram for cardiac resynchronization therapy in heart failure patients and dual-chamber ICD implants.Journal of Cardiovascular Electrophysiology. 2007; 2 (18) 185-191.
• 12 Stein KM, Ellenbogen KA, Gold MR. et al. SmartDelay Determined AV Optimization: A Comparison of AV Delay Methods Used in Cardiac Resynchronization Therapy (SMART-AV): Rationale and Design. Pacing Clin Electrophysiol 2010; 33 (01) 54-63.
• 13 Ferrari G, De Lazzari C, Mimmo R, Tosti G, Ambrosi D. A modular numerical model of the cardiovascular system for studying and training in the field of cardiovascular physiopathology. Jour Biomed Eng 1992; 14: 91-107.
• 14 Ferrari G, Kozarski M, Gu YJ, De Lazzari C, Di Molfetta A, Palko KJ, Zielinski K, GÓrczynska K, Darowski M, Rakhorst G. Application of a user friendly comprehensive circulatory model for hemodynamic and ventricular variables estimate. Int J Art Organs 2008; 31 (12) 1043-1054.
• 15 Di Molfetta A, Santini L, Forleo GB, Cesario M, Tota C, Sgueglia M, Sergi D, Ferrari G, Romeo F. Use of a comprehensive numerical model to improve biventricular pacemaker temporization in patients affected by heart failure undergoing to CRT-D therapy. Med Biol Eng Comput 2010; 48 (08) 755-764.
• 16 Korakianitis T, Shi Y. A concentrated parameter model for the human cardiovascular system including heart valve dynamics and atrioventricular interaction. Med Eng Phys 2006; 28: 613-628.
• 17 Sagawa K, Maughan L, Suga H, Sunagawa H. Cardiac contraction and the Pressure-Volume relationships. New York: Oxford University Press; 1988
• 18 Shanks M, Antoni ML, Hoke U, Bertini M, Ng AC, Auger D, Marsan NA, van Erven L, Holman ER, Schalij MJ, Bax JJ, Delgado V. The effect of cardiac resynchronization therapy on left ventricular diastolic function assessed with speckle tracking echocardiography. Eur J Heart Fail 2011; 13 (010) 1133-1139.
• 19 Pyxara SA, Pinamonti B, Barbati G, Santangelo S, Valentincic M, Cettolo F, Secoli G, Magnani S, Merlo M, Lo Giudice F, Perkan A, Sinagra G. Echocardiographic evaluation of systolic and mean pulmonary artery pressure in the follow up of patients with pulmonary hypertension. Eur J Echocardiogr 2011; 12 (09) 696-701.
• 20 Ypenburg C, van Bommel RJ, Borleffs CJW, Bleeker GB, Boersma E, Schalij M, Bax JJ. Long-Term Prognosis After Cardiac Resynchronization Therapy Is Related to the Extent of Left Ventricular Reverse Remodeling at Midterm Follow-Up. J Am Coll Cardiol 2009; 53: 483-490.
• 21 Corino VD, Belletti S, Terranova P, Lombardi F, Mainardi LT. Heart Rate and systolic blood pressure in patients with persistent atrial fibrillation. A linguistic analysis. Methods Inf Med 2010; 49 (05) 516-520.
• 22 Rantner LJ, Stühlinger MC, Nowak CN, Spuller K, Etsadashvili K, Stühlinger X, Berger T, Dichtl W, Gothe RM, Fischer G, Hintringer F. Localizing the accessory pathway in ventricular preexcitation patients using a score based algorithm. Methods Inf Med 2012; 51 (01) 3-12.