American Journal of Cardiovascular Drugs

, Volume 2, Issue 4, pp 219–226 | Cite as

Cardiac Resynchronization Therapy in Patients with Chronic Heart Failure

Pathophysiology and Current Experience
  • Karlheinz Seidl
  • Monika Rameken
  • Margit Vater
  • Jochen Senges
Leading Article


Congestive heart failure afflicts 2 to 4 million people in the US and nearly 15 million people worldwide. Accepted goals of heart failure treatment include: (i) improvement of symptoms; (ii) prevention of disease progression; and (iii) reduction in morbidity and mortality. Complex pharmacological therapies achieve these goals, but not in all patients with heart failure. Cardiac resynchronization therapy (CRT) represents a new therapeutic approach in patients with chronic heart failure. CRT is only applicable to a subgroup of patients with ventricular conduction system delay, characterized by prolonged QRS duration. Bundle branch block impacts 20 to 30% of patients with New York Heart Association (NYHA) functional class III–IV heart failure and consists predominantly of left bundle branch block. When left ventricular (LV) conduction delay is superimposed upon ventricular dysfunction, it appears to be a marker of disease severity. These conduction abnormalities have deleterious effects both on systolic function and LV filling, and they can induce or enhance mitral functional regurgitation. CRT attempts to correct the deleterious effect of dysynchrony by increasing LV filling time, decreasing septal dyskinesis and reducing mitral regurgitation. Several observational studies and randomized, controlled trials have shown the benefit of CRT in a subgroup of patients with heart failure, with conduction delays. Improvements were found in the mean distance walked in 6 minutes, quality of life (QOL), NYHA functional class, in peak oxygen uptake (V̇O2), total exercise time, reduction of hospitalization, LV function and reduction of the LV end-diastolic diameter. These studies support the therapeutic value of ventricular resynchronization in patients with severe heart failure, who have intraventricular conduction delay but who do not have a standard indication for the implantation of a pacemaker. In respect to these study results, possible indications for a biventricular pacing device at this time are as follows: NYHA functional class III, LV ejection fraction <35%, sinus rhythm, QRS duration >150 msec and drug refractory despite individual optimal heart failure therapy. CRT significantly improved symptoms, exercise tolerance and QOL in most patients. However, further studies are needed to assess long-term clinical effects and prognosis, as well as economic benefit of this therapeutic approach.


  1. 1.
    Eriksson H. Heart failure: a growing public health problem. J Intern Med 1995; 237: 135–41PubMedCrossRefGoogle Scholar
  2. 2.
    Ho KKL, Pinsky JL, Kannel WB, et al. The epidemiology of heart failure: the Framingham study. J Am Coll Cardiol 1993; 22 Suppl. A: 6A–13APubMedCrossRefGoogle Scholar
  3. 3.
    Kannel WB, Belanger AJ. Epidemiology of heart failure. Am Heart J 1991; 121: 951–7PubMedCrossRefGoogle Scholar
  4. 4.
    Cowie MR, Mostered A, Wood DA, et al. The epidemiology of heart failure. Eur Heart J 1997; 18:208–25PubMedCrossRefGoogle Scholar
  5. 5.
    The Solvd Investigators. Effect of enalapril on survival in patients with reduced LV ejection fractions and congestive heart failure. N Engl J Med 1991; 325: 293–302CrossRefGoogle Scholar
  6. 6.
    The Consensus Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure: results of the cooperative north Scandinavian enalapril survival study. N Engl J Med 1987; 316: 1429–35CrossRefGoogle Scholar
  7. 7.
    Pfeffer MA, Braunwald E, Moye LA, et al. Effects of Captopril on mortality and morbidity in patients with LV dysfunction after myocardial infarction: results of the survival and ventricular enlargement study. N Engl J Med 1992; 327: 669–77PubMedCrossRefGoogle Scholar
  8. 8.
    The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators. Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. Lancet 1993; II: 821–7Google Scholar
  9. 9.
    Kober L, Torp Pedersen C, Carlsen JE, et al. A clinical trial of the angiotensin-converting-enzyme inhibitor trandolapril in patients with severe LV dysfunction after myocardial infarction. N Engl J Med 1995; 333: 1670–6PubMedCrossRefGoogle Scholar
  10. 10.
    The CIBIS II Study Group. The cardiac insufficiency bisoprolol study II (CIBIS II): a randomized trial. Lancet 1999; 353: 9–13CrossRefGoogle Scholar
  11. 11.
    The MERIT-HF Study Group. Effect of metoprolol CR/XL in chronic heart failure: metoprolol CR/XL randomized intervention trial in congestive heart failure (MERIT-HF). Lancet 1999; 353: 2001–7CrossRefGoogle Scholar
  12. 12.
    Pitt B, Zannad F, Remme WJ, et al. The effect of Spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med 1999; 341: 709–17PubMedCrossRefGoogle Scholar
  13. 13.
    The Digitals Investigative Group. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med 1997; 336: 525–33CrossRefGoogle Scholar
  14. 14.
    Hochleitner M, Hortnagl H, Choi-Keung NG, et al. Usefulness of physiologic dual-chamber pacing in drug-resistant idiopathic dilated cardiomyopathy. Am J Cardiol 1990; 66: 198–202PubMedCrossRefGoogle Scholar
  15. 15.
    Linde C, Gadler F, Edner M, et al. Results of atrioventricular synchronous pacing with optimized delay in patients with severe congestive heart failure. Am J Cardiol 1995; 75: 919–23PubMedCrossRefGoogle Scholar
  16. 16.
    Gold MR, Feliciano Z, Gottlieb SS, et al. Dual-chamber pacing with a short atrioventricular delay in congestive heart failure: a randomized study. J Am Coll Cardiol 1995; 26: 967–73PubMedCrossRefGoogle Scholar
  17. 17.
    Brecker SJD, Xiao HB, Sparrow J, et al. Effects of dual-chamber pacing with short atrioventricular delay in dilated cardiomyopathy. Lancet 1992; 340: 1308–12PubMedCrossRefGoogle Scholar
  18. 18.
    Bakker P, Meiburg H, de Jonge N, et al. Beneficial effects of biventricular pacing in congestive heart failure [abstract]. PACE 1994; 17: 820Google Scholar
  19. 19.
    Cazeau S, Ritter P, Bakdach S, et al. Four chamber pacing in dilated cardiomyopathy. PACE 1994; 17(11 Pt 2): 1974–9PubMedCrossRefGoogle Scholar
  20. 20.
    Wilensky RL, Yudelman P, Cohen AL, et al. Serial electrocardiographic changes in idiopathic dilated cardiomyopathy confirmed at necropsy. Am J Cardiol 1998; 62: 276–83CrossRefGoogle Scholar
  21. 21.
    Aaronson KD, Schwartz S, Chen TM, et al. Development and prospective validation of a clinical index to predict survival in ambulatory patients referred for cardiac transplant evaluation. Circulation 1997; 95: 2660–7PubMedCrossRefGoogle Scholar
  22. 22.
    Xiao HB, Brecker SJD, Gibson DG. Effects of abnormal activation on the time course of the LV pressure pulse in dilated cardiomyopathy. Br Heart J 1992; 68: 403–7PubMedCrossRefGoogle Scholar
  23. 23.
    Venkateshawar K, Gottpary K, Kreha P, et al., for the VEST investigators. The resting electrocardiogram provides a sensitive and inexpensive marker of prognosis to patients with chronic congestive heart failure [abstract]. J Am Coll Cardiol 1999; 33: 145AGoogle Scholar
  24. 24.
    Xiao H, Roy C, Pujimoto S, et al. Natural history of abnormal conduction and its relation to prognosis in patients with dilated cardiomyopathy. Am J Cardiol 1996; 57: 163–70Google Scholar
  25. 25.
    Nishimura RA, Hayes DL, Koince Jr DR, et al. Mechanism of hemodynamic improvement by dual-chamber pacing for active LV dysfunction: an acute doppler and catheterisation study. J Am Coll Cardiol 1995; 25: 281–8PubMedCrossRefGoogle Scholar
  26. 26.
    Shinbane JS, Chu E, DeMarco T, et al. Evaluation of acute dual-chamber pacing with a range of atrioventricular delays on cardiac performance in refractory heart failure. J Am Coll Cardiol 1997; 30: 1295–300PubMedCrossRefGoogle Scholar
  27. 27.
    Grines C, Bashore T, Boudoulas H, et al. Functional abnormalities in isolated left bundle branch block: the effect of interventricular asynchrony. Circulation 1989; 79: 845–53PubMedCrossRefGoogle Scholar
  28. 28.
    Foster AH, Gold MR, McLaughlin JS. Acute hemodynamic effects of atriobiventricular pacing in humans. Ann Thorac Surg 1995; 59: 294–300PubMedCrossRefGoogle Scholar
  29. 29.
    Xiao Lee C, Gibson D. Effects of left bundle branch block on diastolic function in dilated cardiomyopathy. Br Heart J 1991; 66: 443–7CrossRefGoogle Scholar
  30. 30.
    Leclercq C, Cazeau S, Le Breton H, et al. Acute hemodynamic effects of biventricular DDD pacing in patients with end-stage heart failure. J Am Coll Cardiol 1998; 32(7): 1825–31PubMedCrossRefGoogle Scholar
  31. 31.
    Blanc JJ, Etienne Y, Gilard M, et al. Evaluation of different ventricular pacing sites in patients with severe heart failure: results of an acute hemodynamic study. Circulation 1997; 96(10): 3273–7PubMedCrossRefGoogle Scholar
  32. 32.
    Auricchio A, Stellbrink C, Sack S, et al. The pacing therapies for congestive heart failure (PATH-CHF) study: rationale, design, and endpoints of a prospective randomized multicenter study. Am J Cardiol 1999; 83: 130D–5DPubMedCrossRefGoogle Scholar
  33. 33.
    Auricchio A, Ding J, Kramer A. Comparison of LV pacing sites for heart failure patients [abstract]. Circulation 1998; 98(I): 302Google Scholar
  34. 34.
    Auricchio A, Stellbrink C, Block M, et al. Effect of pacing chamber and atrioventricular delay on acute systolic function of paced patients with congestive heart failure. Circulation 1999; 99: 2993–3001PubMedCrossRefGoogle Scholar
  35. 35.
    Kass DS, Chen CH, Curry C, et al. Improved LV mechanics from acute VDD pacing in patients with dilated cardiomyopathy and ventricular conduction delay. Circulation 1999; 99: 1567–73PubMedCrossRefGoogle Scholar
  36. 36.
    Saxon LA, Kerwin WF, Cahalan MK, et al. Acute effects of intraoperative multisite ventricular pacing on LV function and activation/contraction sequence in patients with depressed ventricular function. J Cardiovasc Electrophysiol 1989; 9: 13–21CrossRefGoogle Scholar
  37. 37.
    Butter C, Auricchio A, Stellbrink C, et al. Effects of resynchronization therapy stimulation site on the systolic function of heart failure patients. Circulation 2001; 104: 3026–9PubMedCrossRefGoogle Scholar
  38. 38.
    Daubert JC, Ritter P, Le Breton H, et al. Permanent LV pacing with transvenous leads into the coronary veins. Pacing Clin Electrophysiol 1998; 21(1 Pt 2): 239–45PubMedCrossRefGoogle Scholar
  39. 39.
    Gras D, Mabo P, Tang T, et al. Multi-site pacing as a Suppl.emental treatment of congestive heart failure: preliminary results of the Medtronic Inc InSync Study. Pacing Clin Electrophysiol 1998; 21(II): 2249–55PubMedCrossRefGoogle Scholar
  40. 40.
    Kuhlkamp V. Initial experience with an implantable cardioverter-defibrillator incorporating cardiac resynchronization therapy. J Am Coll Cardiol 2002 Mar; 39(5): 790–7PubMedCrossRefGoogle Scholar
  41. 41.
    St John Sutton M, Plappert T, Abraham WT. Echocardiographic predictors of functional class changes during cardiac resynchronization therapy: results of the MIRACLE trial. J Am Coll Cardiol 2002; 39(5 Suppl. A): 107ACrossRefGoogle Scholar
  42. 42.
    Cazeau S, Leclercq C, Lavergne T, et al. Effects of multisite biventricular pacing in patients with heart failure and intraventricular conduction delay. N Engl J Med 2001; 344(12): 873–80PubMedCrossRefGoogle Scholar
  43. 43.
    Abraham WT, Fisher W, Smith A, et al. Long-term improvement in functional status, quality of life and exercise capacity with cardiac resynchronization therapy: the MIRCALE trial experience. J Am Coll Cardiol 2002; 39(5 Suppl. A): 159ACrossRefGoogle Scholar
  44. 44.
    Bristow M, Feldman A, Saxon L. Heart failure management using implantable devices for ventricular resynchronization: comparison of medical therapy, pacing and defibrillation in chronic heart failure (Companion) tirai. J Cardiac Failure 2000; 6(3): 276–85CrossRefGoogle Scholar
  45. 45.
    The Antiarrhythmics vs Implantable Defibrillators (AVID) Investigators. A comparison of antiarrhythmic-drug therapy with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias. N Engl J Med 1997; 337: 1576–83CrossRefGoogle Scholar
  46. 46.
    Guarnieri T, Levine JH, Griffith LS, et al. When ‘sudden cardiac death’ is not so sudden: lessons learned from the automatic implantable defibrillator. Am Heart J 1988; 115(1 Pt 1): 205–7PubMedCrossRefGoogle Scholar
  47. 47.
    Kim SG. Implantable defibrillator therapy; does it really prolong life? How can we prove it?. Am J Cardiol 1993; 71: 1213–8PubMedCrossRefGoogle Scholar
  48. 48.
    Stellbrink C, Auricchio A, Butter C. Pacing therapies in congestive heart failure II study. et al. Am J Cardiol 2000; 86(9 Suppl. 1): K138–43CrossRefGoogle Scholar
  49. 49.
    Stellbrink C, Auricchio A, Diem B, et al. Potential benefit of biventricular pacing in patients with congestive heart failure and ventricular tachyarrhythmia. Am J Cardiol 1999; 83: 143D–50DPubMedCrossRefGoogle Scholar
  50. 50.
    Higgins SL, Yong P, Sheck D, et al. Biventricular pacing diminishes the need for implantable cardioverter defibrillator therapy. J Am Coll Cardiol 2000; 36(3): 824–7PubMedCrossRefGoogle Scholar
  51. 51.
    Walker S, Levy TM, Coats AJS, et al. Be-ventricular pacing in congestive cardiac failure: current experience and future directions. Eur Heart J 2000; 21: 884–9PubMedCrossRefGoogle Scholar
  52. 52.
    Hill MRS, Conners SP, Hassa A, et al. Coronary venous vasculature in congestive heart failure patients: opportunities for LV pacing [abstract]. Europace 2000; 1: D238Google Scholar
  53. 53.
    Sogaard P, Kin Y, Jensen HK, et al. Impact of electrode positioning in biventricular pacing on LV synchrony and function: a 3-dimensional transthoracic second harmonic echocardiographic study with tissue Doppler imaging [abstract]. Europace 2000; 1: D238Google Scholar

Copyright information

© Adis International Limited 2002

Authors and Affiliations

  • Karlheinz Seidl
    • 1
  • Monika Rameken
    • 1
  • Margit Vater
    • 1
  • Jochen Senges
    • 1
  1. 1.Department of CardiologyHeart CentreLudwigshafenGermany

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