Advertisement

Heart Failure Reviews

, Volume 17, Issue 1, pp 97–105 | Cite as

Cardiac resynchronization therapy: the issue of non-response

  • Luigi Padeletti
  • Alessandro Paoletti Perini
  • Edoardo Gronda
Article

Abstract

Cardiac resynchronization therapy reduces mortality and morbidity in heart failure patients with wide QRS and severe impairment of left ventricular systolic function, who are symptomatic despite optimal medical therapy. However, a high percentage of patients fail to show clinical or echocardiographic response to this treatment. Beyond current selection criteria, other elements, such as QRS duration and morphology, concomitant medical therapy, degree of right ventricle dysfunction, myocardial viability, presence of left ventricular dyssynchrony, and associated renal dysfunction, play a crucial role in modulating the response to cardiac resynchronization. Consequently, they should be part of the standard pre-implant evaluation, as they could be used to identify patients who are very unlikely to be responders.

Keywords

Cardiac resynchronization therapy Non-responders QRS morphology Myocardial dyssynchrony Myocardial viability Right ventricular dysfunction Renal dysfunction 

References

  1. 1.
    Cleland JGF, Daubert JC, Erdmann E et al (2005) The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Eng J Med 352:1539–1549CrossRefGoogle Scholar
  2. 2.
    Bristow MR, Saxon LA, Boehmer J et al (2004) Cardiac-resynchronization therapy with or without implantable defibrillator in advanced chronic heart failure. N Eng J Med 350:2140–2150CrossRefGoogle Scholar
  3. 3.
    Abraham WT, Fisher WJ, Smith Al et al (2002) Cardiac resynchronization in chronic heart failure. N Eng J Med 346:1845–1853CrossRefGoogle Scholar
  4. 4.
    Cazeau S, Leclercq C, Lavergne T et al (2001) Effects of multisite biventricular pacing in patients with heart failure and intraventricular conduction delay. N Eng J Med 344:873–880CrossRefGoogle Scholar
  5. 5.
    Cleland JGF, Baubert JC, Erdmann E et al (2006) Longer-term effect of cardiac resynchronization therapy on mortality in heart failure [the CArdiac REsynchronization-Heart Failure (CARE-HF) trial extension phase]. Eur Heart J 27:1928–1931PubMedCrossRefGoogle Scholar
  6. 6.
    Jessup M, Abraham WT, Casey DE et al (2009) 2009 Focused update: ACCF/AHA guidelines for the diagnosis and management of heart failure in adults. A report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines. Developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation 119:1977–2016PubMedCrossRefGoogle Scholar
  7. 7.
    Vardas PE, Auricchio A, Blanc JJ et al (2007) Guidelines for cardiac pacing and cardiac resynchronization therapy. The Task Force for Cardiac Pacing and Cardiac Resynchronization Therapy of the European Society of Cardiology. Developed in collaboration with the European Heart Rhythm Association. Eur Heart J 28:2256–2295PubMedCrossRefGoogle Scholar
  8. 8.
    Dickstein K, Vardas PE, Auricchio A et al (2010) 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. Developed with the special contribution of the Heart Failure Association and the European Heart Rhythm Association. Eur Heart J 31:2677–2687PubMedCrossRefGoogle Scholar
  9. 9.
    Bax JJ, Gorcsan J III (2009) Echocardiographic and noninvasive imaging in cardiac resynchronization therapy. J Am Coll Cardiol 53:1933–1943PubMedCrossRefGoogle Scholar
  10. 10.
    Yu CM, Sanderson JE, Gorcsan J III (2010) Echocardiography, dyssynchrony, and the response to cardiac resynchronization therapy. Eur Heart J 31:2326–2339PubMedCrossRefGoogle Scholar
  11. 11.
    Fornwalt BK, Sprague WW, BeDell P et al (2010) Agreement is poor among current criteria used to define response to cardiac resynchronization therapy. Circulation 121:1985–1991PubMedCrossRefGoogle Scholar
  12. 12.
    Yu CM, Bleeker JB, Fung JW et al (2005) Left ventricular reverse remodelling but not clinical improvement predicts long-term survival after cardiac resynchronization therapy. Circulation 112:1580–1586PubMedCrossRefGoogle Scholar
  13. 13.
    White HD, Norris RM, Brown MA et al (1987) Left-ventricular end-systolic volume as the major determinant of survival after recovery from myocardial infarction. Circulation 76:44–51PubMedCrossRefGoogle Scholar
  14. 14.
    Ypenburg C, Bommel RJ, Borleffs CJ et al (2009) Long-term prognosis after cardiac resynchronization therapy is related to the extent of left ventricular reverse remodelling at midterm follow-up. J Am Coll Cardiol 53:483–490PubMedCrossRefGoogle Scholar
  15. 15.
    Foley PW, Leyva F, Frenneaux MP (2009) What is treatment success in cardiac resynchronization therapy? Europace Suppl 5:v58–v65Google Scholar
  16. 16.
    Chung ES, Leon AR, Tavazzi L et al (2008) Results of the Predictors Response to CRT (PROSPECT) trial. Circulation 117:2608–2616PubMedCrossRefGoogle Scholar
  17. 17.
    Shamim W, Francis DP, Yousufuddin M et al (1999) Intraventricular conduction delay: a prognostic marker in chronic heart failure. Int J Cardiol 70:171–178PubMedCrossRefGoogle Scholar
  18. 18.
    Gottipaty V et al. for the VEST Investigators. (1999) The resting electrocardiogram provides a sensitive and inexpensive marker of prognosis in patients with chronic congestive heart failure (abstr). J Am Coll Cardiol 33, 145Google Scholar
  19. 19.
    Linde C, Abraham WT, Gold MR et al (2008) Randomized trial of cardiac resynchronization in mildly symptomatic heart failure patients and in asymptomatic patients with left ventricular dysfunction and previous heart failure symptoms. J Am Coll Cardiol 52:1834–1843PubMedCrossRefGoogle Scholar
  20. 20.
    Moss AJ et al (2009) Cardiac-resynchronization therapy for the prevention of heart-failure events. N Engl J Med 361:1329–1338PubMedCrossRefGoogle Scholar
  21. 21.
    Baldasseroni S, Opasich C, Gorini M et al (2002) Left-bundle-branch block is associated with increase 1-year sudden and total mortality rate in 5517 outpatients with congestive heart failure: A report from the Italian Network on Congestive Heart Failure. Am Heart J 143:398–405PubMedCrossRefGoogle Scholar
  22. 22.
    De Guillebon M, Thambo JB, Ploux S et al (2010) Reliability and reproducibility of QRS duration in the selection of candidates for cardiac resynchronization therapy. J Cardiovasc Electrophysiol 21:890–892PubMedGoogle Scholar
  23. 23.
    Mirvis DM, Goldberger AL (2005) Electrocardiography. In: Zipes DP, Libby P, Bonow RO, Braunwald E (eds) Braunwald’s Heart Disease. A textbook of cardiovascular medicine, 7th edn. Elsevier Saunders, Philadelphia, Pennsylvania, pp 127–128Google Scholar
  24. 24.
    Zannad F, Huvelle E, Dickstein K et al (2007) Left bundle branch block as a risk factor for progression to heart failure. Europ J Heart Fail 9:7–14CrossRefGoogle Scholar
  25. 25.
    Underwood SR, Walton S, Laming PJ et al (1984) Patterns of ventricular contraction in patients with conduction abnormality studied by radionuclide angiocardiography. Br Heart J 51:568–574PubMedCrossRefGoogle Scholar
  26. 26.
    Grines CL, Bashore TM, Boudoulas H et al (1989) Functional abnormalities in isolated left bundle branch block. The effect of interventricular asynchrony. Circulation 79:845–853PubMedCrossRefGoogle Scholar
  27. 27.
    Nelson GS, Curry CW, Bradley TW et al (2000) Predictors of systolic augmentation from left ventricular preexcitation in patients with dilated cardiomyopathy and intraventricular conduction delay. Circulation 101:2703–2709PubMedGoogle Scholar
  28. 28.
    Bleeker GB, Schalij MJ, Molhoek SG et al (2004) Relationship between QRS duration and left ventricular dyssynchrony in patients with end-stage heart failure. J Cardiovasc Electrophysiol 15:544–549PubMedCrossRefGoogle Scholar
  29. 29.
    Porciani MC, Cappelli F, Perrotta L et al (2010) Has mechanical dyssynchrony still a role in predicting cardiac resynchronization therapy response? Echocardiography 27:831–838PubMedCrossRefGoogle Scholar
  30. 30.
    Baldasseroni S, Gentile A, Gorini M et al (2003) Intraventricular conduction defects in patients with congestive heart failure: left but not right bundle branch block is an independent predictor of prognosis. A report from the Italian Network on Congestive Heart Failure (IN-CHF database). Ital Heart J 4:607–613PubMedCrossRefGoogle Scholar
  31. 31.
    Gervais R, Leclercq C, Shankar A et al (2009) Surface electrocardiogram to predict outcome in candidates for cardiac resynchronization therapy: a sub-analysis of the CARE-HF trial. Eur J Heart Fail 11:699–705PubMedCrossRefGoogle Scholar
  32. 32.
    Barsheshet A, Leor J, Goldbourt U et al (2008) Effect of bundle branch block patterns on mortality in hospitalized patients with heart failure. Am J Cardiol 101:1303–1308PubMedCrossRefGoogle Scholar
  33. 33.
    Barsheshet A, Goldenberg I, Garty M et al (2011) Relation of bundle branch block to long-term (four-year) mortality in hospitalized patients with systolic heart failure. Am J Cardiol 107:540–544PubMedCrossRefGoogle Scholar
  34. 34.
    Adelstein EC, Saba S (2009) Usefulness of baseline electrocardiographic QRS complex pattern to predict response to cardiac resynchronization therapy. Am J Cardiol 103:238–242PubMedCrossRefGoogle Scholar
  35. 35.
    Chandra R, Zolty R, Palma E (2010) A left hemiblock improves cardiac resynchronization therapy outcomes in patients with a right bundle branch block. Clin Cardiol 33:89–93PubMedCrossRefGoogle Scholar
  36. 36.
    Egoavil CA, Ho RT, Greenspon AJ, Pavri BB (2005) Cardiac resynchronization therapy in patients with right bundle branch block: Analysis of pooled data from the MIRACLE and Contak CD trials. Heart Rhythm 2:611–615PubMedCrossRefGoogle Scholar
  37. 37.
    Bilchick KC, Kamath S, DiMarco JP, Stukenborg GJ (2010) Bundle-branch morphology an dother predictors of outcome after cardiac resynchronization therapy in Medicare patients. Circulation 122:2022–2030PubMedCrossRefGoogle Scholar
  38. 38.
    Byrne MJ, Helm RH, Daya S et al (2007) Diminshed left ventricular dyssynchrony and impact of resynchronization in failing hearts with right versus left bundle branch block. J Am Coll Cardiol 50:1484–1490PubMedCrossRefGoogle Scholar
  39. 39.
    Fantoni C, Kawabata M, Massaro R et al (2005) Right and left ventricular activation sequence in patients with heart failure and right bundle branch block: a detailed analysis using three-dimensional non-fluoroscopic electroanatomic mapping system. J Cardiovasc Electrophysiol 16:112–119PubMedCrossRefGoogle Scholar
  40. 40.
    Heywood JT, Fonarow GC, Yancy CW et al (2010) Comparison of medical therapy dosing in outpatients cared for in cardiology practices with heart failure and reduced ejection fraction with and without device therapy: a report from IMPROVE-HF. Circ Heart Fail 3:596–605PubMedCrossRefGoogle Scholar
  41. 41.
    Adlbrecht C, Hülsmann M, Gwechenberger M et al (2009) Outcome after device implantation in chronic heart failure is dependent on concomitant medical treatment. Eur J Clin Invest 39:1073–1081PubMedCrossRefGoogle Scholar
  42. 42.
    Voigt A, Shalaby A, Adelstein E, Saba S (2010) Beta-blockers utilization and outcomes in patients receiving cardiac resynchronization therapy. Clin Cardiol 33:E1–E5PubMedCrossRefGoogle Scholar
  43. 43.
    Komajda M, Hanon O, Hochadel M et al (2009) Contemporary management of octogenarians hospitalized for heartfailure in Europe: Euro Heart Survay II. Eur Heart J 30:478–486PubMedCrossRefGoogle Scholar
  44. 44.
    Boriani G, Gasparini M, Landolina M et al (2009) Effectiveness of cardiac resynchronization therapy in heart failure patients with valvular heart disease: comparision with patients affected by ischaemic heart disease or dilated cardiomyopathy. The InSync/InSync ICD Registry. Eur Heart J 30:2275–2283PubMedCrossRefGoogle Scholar
  45. 45.
    Haddad F, Doyle R, Murphy DJ, Hunt SA (2008) Right ventricular function in cardiovascular disease. Part II: pathophysiology, clinical importance, and management of right ventricular failure. Circulation 117:1717–1731PubMedCrossRefGoogle Scholar
  46. 46.
    Polak JF, Holman BL, Wynne J, Colucci WS (1983) Right ventricular ejection fraction: an indicator of increased mortality in patients with congestive heart failure associated with coronary artery disease. J Am Coll Cardiol 2:217–224PubMedCrossRefGoogle Scholar
  47. 47.
    Di Salvo TG, Mathier M, Semigran MJ, Dec GW (1995) Preserved right ventricular ejection fraction predicts exercise capacity and survival in advanced heart failure. J Am Coll Cardiol 25:1143–1153PubMedCrossRefGoogle Scholar
  48. 48.
    De Groote P, Millaire A, Foucher-Hossein C et al (1998) Right ventricular ejection fraction is an independent predictor of survival in patients with moderate heart failure. J Am Coll Cardiol 32:948–954PubMedCrossRefGoogle Scholar
  49. 49.
    Ghio S, Gavazzi A, Campana C et al (2001) Independent and additive prognostic value of right ventricular systolic function and pulmonary artery pressure in patients with chronic heart failure. J Am Coll Cardiol 37:183–188PubMedCrossRefGoogle Scholar
  50. 50.
    Field ME, Solomo SD, Lewis EF et al (2006) Right ventricular dysfunction and adverse outcome in patients with advanced heart failure. J Card Fail 12:616–620PubMedCrossRefGoogle Scholar
  51. 51.
    Scuteri L, Rordorf R, Marsan NA et al (2009) Relevance of echocardiographic evaluation of right ventricular function in patients undergoing cardiac resynchronization therapy. Pacing Clin Electrophysiol 32:1040–1049PubMedCrossRefGoogle Scholar
  52. 52.
    Ogunyankin KO, Puthumana JJ (2010) Effect of cardiac resynchronization therapy on right ventricular function. Curr Opin Cardiol 22:464–468CrossRefGoogle Scholar
  53. 53.
    Haddad F, Hunt SA, Rosenthal DN, Murphy DJ (2008) Right ventricular function in cardiovascular disease, part I: Anatomy, physiology, aging, and functional assessment of the right ventricle. Circulation 117:1436–1448PubMedCrossRefGoogle Scholar
  54. 54.
    Tei C, Dujardin KS, Hodge DO et al (1996) Doppler echocardiographic index for assessment of global right ventricular function. J Am Soc Echocardiogr 9:838–847PubMedCrossRefGoogle Scholar
  55. 55.
    Ghio S, Recusani F, Klersy C et al (2000) Prognostic usefulness of tricuspid annular plane systolic excursion in patients with congestive heart failure secondary to idiopathic or ischemic dilated cardiomiopathy. Am J Cardiol 85:837–842PubMedCrossRefGoogle Scholar
  56. 56.
    Ghio S, Freemantle N, Scelsi L et al (2009) Long-term left ventricular reverse remodelling with cardiac resynchronization therapy: results from the CARE-HF trial. Eur J Heart Fail 11:480–488PubMedCrossRefGoogle Scholar
  57. 57.
    Bleeker GB, Kaandorp TA, Lamb HJ et al (2006) Effect of posterolateral scar tissue on clinical and echocardiographic improvement after cardiac resynchronization therapy. Circulation 113:969–976PubMedCrossRefGoogle Scholar
  58. 58.
    Ypenburg C, Roes SD, Bleeker GB et al (2007) Effect of total scar burden on contrast-enhanced magnetic resonance imaging on response to cardiac resynchronization therapy. Am J Cardiol 99:657–660PubMedCrossRefGoogle Scholar
  59. 59.
    Mele D, Agricola E, Galderisi M et al (2009) Echocardiographic myocardial scar burden predicts response to cardiac resynchronization therapy in ischemic heart failure. J Am Soc Echocardiogr 22:702–708PubMedCrossRefGoogle Scholar
  60. 60.
    Da Costa A, Thévenin J, Roche F et al (2006) Prospective validation of stress echocardiography as an identifier of cardiac resynchronization therapy. Heart Rhythm 3:406–413PubMedCrossRefGoogle Scholar
  61. 61.
    Sénéschal M, Lancellotti P, Garceau P et al (2010) Usefulness and limitation of dobutamine stress echocardiography to predict acute response to cardiac resynchronization therapy. Echocardiography 27:50–57CrossRefGoogle Scholar
  62. 62.
    Sénéschal M, Lancellotti P, Magne J et al (2010) Contractile reserve assessed using dobutamine echocardiography predicts left ventricular reverse remodelling after cardiac resynchronization therapy: prospective validation in patients with left ventricular dyssynchrony. Echocardiography 27:668–676CrossRefGoogle Scholar
  63. 63.
    Bax JJ, Bleeker GB, Marwick TH et al (2004) Left ventricular dyssynchrony predicts response and prognosis after cardiac resynchronization therapy. J Am Coll Cardiol 44:1834–1840PubMedCrossRefGoogle Scholar
  64. 64.
    Van Bommel RJ, Ypenburg C, Borleffs CJW et al (2010) Value of tissue Doppler echocardiography in predicting response to cardiac resynchronization therapy in patients with heart failure. Am J Cardiol 105:1153–1158PubMedCrossRefGoogle Scholar
  65. 65.
    Bleeker GB, Sjoerd AM, Holman ER et al (2007) Left ventricular resynchronization is mandatory for response to cardiac resynchronization therapy. Analysis in patients with echocardiographic evidence of left ventricular dyssynchrony at baseline. Circulation 116:1440–1448PubMedCrossRefGoogle Scholar
  66. 66.
    Gorcsan J 3rd, Tanabe M, Bleeker GB et al (2007) Combined longitudinal and radial dyssynchrony predicts ventricular response after resynchronization therapy. J Am Coll Cardiol 50:1476–1483PubMedCrossRefGoogle Scholar
  67. 67.
    Tanaka H, Nesser HJ, Buck T et al (2010) Dyssynchrony by speckle-tracking echocardiography and response to cardiac resynchronization therapy: results of the Speckle Tracking and Resynchronization (STAR) study. Eur Heart J 31:1690–1700PubMedCrossRefGoogle Scholar
  68. 68.
    Taylor AJ, Elsik M, Broughton A et al (2010) Combined dyssynchrony and scar imaging with cardiac magnetic resonance imaging predicts clinical response and long-term prognosis following cardiac resynchronization therapy. Europace 12:708–713PubMedCrossRefGoogle Scholar
  69. 69.
    Bax JJ, Bleeker GB, Marwick TH et al (2004) Left ventricular dyssynchrony predicts response and prognosis after cardiac resynchronization therapy. J Am Coll Cardiol 44:1834–1840PubMedCrossRefGoogle Scholar
  70. 70.
    Chalil S, Stegemann B, Muhyaldeen S et al (2007) Intraventricular dyssynchrony predicts mortality and morbidity following cardiac resynchronization therapy: a study using cardiovascular magnetic resonance tissue synchronization imaging. J Am Coll Cardiol 50:243–252PubMedCrossRefGoogle Scholar
  71. 71.
    Hillege HL, Nitsch D, Pfeffer MA et al (2006) Renal function as a predictor of outcome in a broad spectrum of patients with heart failure. Circulation 113:671–678PubMedCrossRefGoogle Scholar
  72. 72.
    Coresh J, Astor BC, Greene T, Eknoyan G, Levey AS (2003) Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey. Am J Kidney Dis 41:1–12PubMedCrossRefGoogle Scholar
  73. 73.
    Foley RN, Parfrey PS, Sarnak MJ (1998) Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis 32:S112–S119PubMedCrossRefGoogle Scholar
  74. 74.
    Ronco C, Happio M, House A, Anavekar N, Bellomo R (2008) Cardiorenal sindrome. J Am Coll Cardiol 52:1527–1539PubMedCrossRefGoogle Scholar
  75. 75.
    Go AS, Chertow GM, Fan D, McCulloch CE, HSU CY (2004) Chronic kidney disease and the risks of death, cardiovascular events and hospitalization. N Engl J Med 351:1296–1305PubMedCrossRefGoogle Scholar
  76. 76.
    Manjunath G, Tighouart H, Hibrahim H et al (2003) Level of kidney function as a risk factor for cardiovascular outcomes in the community. J Am Coll Cardiol 41:47–55PubMedCrossRefGoogle Scholar
  77. 77.
    Logar CM, Herzog CA, Beddhu S (2003) Diagnosis and therapy of coronary artery disease in renal failure, end-stage renal disease, and renal transplant populations. Am J Med Sci 325:214–227PubMedCrossRefGoogle Scholar
  78. 78.
    McAlister FA, Ezekowitz J, Tonelli M, Armstrong PW (2004) Renal insufficiency and heart failure. Prognostic and therapeutics implications from a prospective cohort study. Circulation 109:1004–1009PubMedCrossRefGoogle Scholar
  79. 79.
    Goldenberg I, Moss AJ, Mcnitt S et al (2006) Relations among renal function, risk of sudden cardiac death and benefit of the implanted cardiac defibrillator in patients with ischemic LV dysfunction. Am J Cardiol 98:485–490PubMedCrossRefGoogle Scholar
  80. 80.
    Adelstein EC, Shalaby A, Saba S (2010) Response to cardiac resynchronization therapy in patients with heart failure and renal insufficiency. Pacing Clin Electrophysiol 33:850–859PubMedCrossRefGoogle Scholar
  81. 81.
    Fung JWH, Szeto CC, Chan JYS et al (2007) Prognostic value of renal function in patients with cardiac resynchronization therapy. Int J Cardiol 122:10–16PubMedCrossRefGoogle Scholar
  82. 82.
    Heywood JT, Fonarow GC, Yancy CW et al (2010) Influence of renal function on the use of guideline-recommended therapies for patients with heart failure. Am J Cardiol 105:1140–1146PubMedCrossRefGoogle Scholar
  83. 83.
    Sakhuja R, Keebler M, Lai TS et al (2009) Meta-analysis of mortality in dialysis patients with an implantable cardioverter defibrillator. Am J Cardiol 103:735–741PubMedCrossRefGoogle Scholar
  84. 84.
    Saxon LA, Bristow MR, Bohemer J et al (2006) Predictors of sudden cardiac death and appropriate shock in the comparison of medical therapy, pacing and defibrillation in heart failure (COMPANION). Circulation 114:2766–2772PubMedCrossRefGoogle Scholar
  85. 85.
    Cuculich PS, Sanchez JM, Kerzner R et al (2007) Poor prognosis for patients with chronic kidney disease despite ICD therapy for the primary prevention of sudden death. Pacing Clin Electrophysiol 30:207–213PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Luigi Padeletti
    • 1
  • Alessandro Paoletti Perini
    • 1
  • Edoardo Gronda
    • 2
  1. 1.Istituto di Clinica Medica e CardiologiaUniversità degli Studi di FirenzeFlorenceItaly
  2. 2.FESC Gruppo Multimedica, IRCCS Sesto San GiovanniMilanItaly

Personalised recommendations