Cardiac Resynchronization Therapy - Evolving Strategies to Enhance Response

Abstract

Abstract
Cardiac resynchronization therapy (CRT) has gained widespread acceptance as a safe and effective therapeutic strategy for congestive heart failure (CHF) refractory to optimal medical therapy. The use of implantable devices has substantially altered the natural history of systolic heart failure. These devices exert their physiological impact through ventricular remodeling, associated with a reduction in left ventricular (LV) volumes and an improvement in ejection fraction (EF). Several prospective randomized studies have shown that this in turn translates into long-term clinical benefits such as improved quality of life, increased functional capacity, and reduction in hospitalization for heart failure and overall mortality. Despite these obvious benefits, there remain more than a few unresolved concerns, the most important being that up to one-third of patients treated with CRT do not derive any detectable benefit. There are several determinants of successful delivery and response to CRT, including selecting the appropriate patient, patient-specific optimal LV pacing lead placement, and appropriate post-implant device care and follow-up. This article highlights the importance of collectively working on all of these aspects of CRT to enhance and maximize response.

Keywords
Cardiac resynchronization therapy, heart failure, biventricular pacemaker, cardiomyopathy

Disclosure: The author has received research grants and lecture and consulting fees from Biotronik, Boston Scientific, Medtronic, Sorin Group, and St Jude Medical.
Received: January 21, 2010 Accepted: February 10, 2010 Citation: US Cardiology, 2010;7(1):61├óÔé¼ÔÇ£6
Correspondence: Jagmeet P Singh, MD, DPhil, Director, Cardiac Resynchronization Therapy Program, Cardiac Arrhythmia Service, Massachusetts General Hospital Heart Center, Harvard Medical School, Boston, MA 02114. E: jsingh@partners.org

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Cardiac resynchronization therapy (CRT) has achieved widespread approval as a safe and efficient therapeutic strategy for medically refractory congestive heart failure (CHF). The standard indications for CRT include patients with advanced heart failure and evidence of systolic dysfunction (ejection fraction [EF] ├óÔÇ░┬ñ35%), conduction tissue disease (QRS duration ├óÔÇ░─ä120ms), and marked cardiac symptoms (New York Heart Association [NYHA] class III and IV), despite optimal medical therapy.1 CRT and CRT with defibrillator therapy (CRT-D) involve placement of right atrial (RA), right ventricular (RV), and left ventricular (LV) leads, and exert their physiological impact via synchronizing ventricular contraction. This in turn results in improved pumping efficiency, improved LV filling, and a reduction in the extent of mitral regurgitation.2,3 These implantable devices have substantially altered the natural history of patients with heart failure and exert their physiological impact through ventricular remodeling, which occurs over time with a reduction in LV volumes and improvement in EF.

Several prospective randomized studies have shown that this in turn translates into longterm clinical benefits such as improved quality of life, increased functional capacity, reduction in hospitalization for heart failure, and reduction in overall mortality.1,4Despite these palpable benefits, there remain more than a few unresolved concerns, the most important being that up to one-third of patients treated with CRT do not derive any detectable benefit.5 Given the high prevalence, morbidity, and mortality of CHF and the substantial price tag to society both from CHF as a disease and from CRT as a therapy, the importance of maximizing the response of all patients to CRT is evidently immense. There are several determinants of successful delivery and response to device therapy, which include selecting the appropriate patient, patient-specific appropriate LV lead placement, and optimal post-implant device care and follow-up. This article highlights the importance of collectively working on all of these fronts to enhance the response to CRT.

Patient Selection Surface Electrocardiogram and Mechanical Dyssynchrony
After meeting the criteria of compromised LV function and medically refractory heart failure (NYHA >3), patient selection is still driven by the presence of a wide QRS on the surface electrocardiogram (ECG). It is noteworthy that ECG evidence of an intra-ventricular conduction defect, although a surrogate for ventricular dyssynchrony, is not predictive of acute and long-term response to CRT.

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References
  1. Cleland JG, Daubert JC, Erdmann E, et al., The effect of cardiac resynchronization on morbidity and mortality in heart failure, N Engl J Med, 2005;352:1539├óÔé¼ÔÇ£49.
  2. Auricchio A, Stellbrink C, Butter C, et al., Clinical efficacy of cardiac resynchronization therapy using left ventricular pacing in heart failure patients stratified by severity of ventricular conduction delay, J Am Coll Cardiol, 2003;42: 2109├óÔé¼ÔÇ£16.
  3. Breithardt OA, Sinha AM, Schwammenthal E, et al., Acute effects of cardiac resynchronization therapy on functional mitral regurgitation in advanced systolic heart failure, J Am Coll Cardiol, 2003;41:765├óÔé¼ÔÇ£70. Erratum: J Am Coll Cardiol, 2003;41(10):1852.
  4. Bristow MR, Saxon LA, Boehmer J, et al., Cardiacresynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure, N Engl J Med, 2004;350:2140├óÔé¼ÔÇ£50.
  5. Abraham WT, Fisher WG, Smith AL, et al., Cardiac resynchronization in chronic heart failure, N Engl J Med, 2002;346:1845├óÔé¼ÔÇ£53.
  6. Auricchio A, Abraham WT, Cardiac resynchronization therapy: current state of the art: cost versus benefit, Circulation, 2004;109:300├óÔé¼ÔÇ£7.
  7. Bax JJ, Bleeker GB, Marwick TH, et al., Left ventricular dyssynchrony predicts response and prognosis after cardiac resynchronization therapy, J Am Coll Cardiol, 2004;44:1834├óÔé¼ÔÇ£40.
  8. Molhoek SG, Vane L, Bootsma M, et al., QRS duration and shortening to predict clinical response to cardiac resynchronization therapy in patients with end-stage heart failure, Pacing Clin Electrophysiol, 2004;27:308├óÔé¼ÔÇ£13.
  9. Auricchio A, Fantoni C, Regoli F, et al., Characterization of left ventricular activation in patients with heart failure and left bundle-branch block, Circulation, 2004;109:1133├óÔé¼ÔÇ£9.
  10. Peichl P, Kautzner J, Cihak R, Bytesnik J, The spectrum of inter- and intraventricular conduction abnormalities in patients eligible for cardiac resynchronization therapy, Pacing Clin Electrophysiol, 2004;27:1105├óÔé¼ÔÇ£12.
  11. Wokhlu A, Rea RF, Asirvatham SJ, et al., Upgrade and de novo cardiac resynchronization therapy: impact of paced or intrinsic QRS morphology on outcomes and survival, Heart Rhythm, 2009;6:1439├óÔé¼ÔÇ£47.
  12. Varma N, Left ventricular conduction delays and relation to QRS configuration in patients with left ventricular dysfunction, Am J Cardiol, 2009;103:1578├óÔé¼ÔÇ£85.
  13. Beshai JF, Grimm RA, Nagueh SF, et al., Cardiacresynchronization therapy in heart failure with narrow QRS complexes, N Engl J Med, 2007;357:2461├óÔé¼ÔÇ£71.
  14. Chung ES, Leon AR, Tavazzi L, et al., Results of the Predictors of Response to CRT (PROSPECT) trial, Circulation, 2008;117:2608├óÔé¼ÔÇ£16.
  15. Tournoux FB, Manzke R, Chan RC, et al., Integrating functional and anatomical information to facilitate cardiac resynchronization therapy, Pacing Clin Electrophysiol, 2007;30:1021├óÔé¼ÔÇ£2.
  16. Tournoux F, Chan RC, Manzke R, et al., Integrating functional and anatomical information to guide cardiac resynchronization therapy, Eur J Heart Fail, 2010;12:52├óÔé¼ÔÇ£7.
  17. Bleeker GB, Schalij MJ, Van Der Wall EE, Bax JJ, Posterolateral scar tissue resulting in non-response to cardiac resynchronization therapy, J Cardiovasc Electrophysiol, 2006;17:899├óÔé¼ÔÇ£901.
  18. Murphy RT, Sigurdsson G, Mulamalla S, et al., Tissue synchronization imaging and optimal left ventricular pacing site in cardiac resynchronization therapy, Am J Cardiol, 2006;97:1615├óÔé¼ÔÇ£21.
  19. Truong QA, Hoffmann U, Singh JP, Potential uses of computed tomography for management of heart failure patients with dyssynchrony, Crit Pathw Cardiol, 2008;7:185├óÔé¼ÔÇ£90.
  20. Truong QA, Singh JP, Cannon CP, et al., Quantitative analysis of intraventricular dyssynchrony using wall thickness by multidetector computed tomography, JACC Cardiovasc Imaging, 2008;1:772├óÔé¼ÔÇ£81.
  21. Singh JP, Houser S, Heist EK, Ruskin JN, The coronary venous anatomy: a segmental approach to aid cardiac resynchronization therapy, J Am Coll Cardiol, 2005;46:68├óÔé¼ÔÇ£74.
  22. Blendea D, Shah RV, Auricchio A, et al., Variability of coronary venous anatomy in patients undergoing cardiac resynchronization therapy: a high-speed rotational venography study, Heart Rhythm, 2007;4:1155├óÔé¼ÔÇ£62.
  23. Fung JW, Yu CM, Yip G, et al., Variable left ventricular activation pattern in patients with heart failure and left bundle branch block, Heart, 2004;90:17├óÔé¼ÔÇ£19.
  24. Singh JP, Fan D, Heist EK, et al., Left ventricular lead electrical delay predicts response to cardiac resynchronization therapy, Heart Rhythm, 2006;3:1285├óÔé¼ÔÇ£92.
  25. Heist EK, Fan D, Mela T, et al., Radiographic left ventricularright ventricular interlead distance predicts the acute hemodynamic response to cardiac resynchronization therapy, Am J Cardiol, 2005;96:685├óÔé¼ÔÇ£90.
  26. Singh JP, Heist EK, Ruskin JN, Harthorne JW, ├óÔé¼┼øDialing-in├óÔé¼┼Ñ cardiac resynchronization therapy: overcoming constraints of the coronary venous anatomy, J Interv Card Electrophysiol, 2006;17:51├óÔé¼ÔÇ£8.
  27. Arzola-Castaner D, Taub C, Kevin Heist E, et al., Left ventricular lead proximity to an akinetic segment and impact on outcome of cardiac resynchronization therapy, J Cardiovasc Electrophysiol, 2006;17:623├óÔé¼ÔÇ£7.
  28. Leon AR, Abraham WT, Brozena S, et al., Cardiac resynchronization with sequential biventricular pacing for the treatment of moderate-to-severe heart failure, J Am Coll Cardiol, 2005;46:2298├óÔé¼ÔÇ£2304.
  29. Kerlan JE, Sawhney NS, Waggoner AD, et al., Prospective comparison of echocardiographic atrioventricular delay optimization methods for cardiac resynchronization therapy, Heart Rhythm, 2006;3:148├óÔé¼ÔÇ£54.
  30. Sawhney NS, Waggoner AD, Garhwal S, et al., Randomized prospective trial of atrioventricular delay programming for cardiac resynchronization therapy, Heart Rhythm, 2004;1: 562├óÔé¼ÔÇ£7.
  31. Waggoner AD, Rovner A, de las Fuentes L, et al., Clinical outcomes after cardiac resynchronization therapy: importance of left ventricular diastolic function and origin of heart failure, J Am Soc Echocardiogr, 2006;19:307├óÔé¼ÔÇ£13.
  32. Ritzema J, Melton IC, Richards AM, et al., Direct left atrial pressure monitoring in ambulatory heart failure patients: initial experience with a new permanent implantable device, Circulation, 2007;116:2952├óÔé¼ÔÇ£9.
  33. Moss AJ, Hall WJ, Cannom DS, et al., Cardiacresynchronization therapy for the prevention of heart-failure events, N Engl J Med, 2009;361:1329├óÔé¼ÔÇ£38.
  34. St John Sutton M, Ghio S, Plappert T, et al., Cardiac resynchronization induces major structural and functional reverse remodeling in patients with New York Heart Association