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A posteriori confounders to the Bayesian meta-analysis of resynchronisation and implantable defibrillator therapy
- Michael Y. Henein, Robin Chung, Research Fellow, Royal Brompton Hospital, London SW3 6NP (23 October 2007)
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ICDs in Heart Failure
- Mahmood Ahmad, Mehboob Ahmad Rehan (2 November 2007)
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Michael Y. Henein, Consultant Cardiologist West Middlesex University Hospitals NHS Trust, Twickenham TW7 6AF, Robin Chung, Research Fellow, Royal Brompton Hospital, London SW3 6NP
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Lam and Owen (1) report an insightful and welcome Bayesian meta- analysis of permutations of cardiac resynchronisation (CRT) and implantable cardiac defibrillator (ICD) therapy. The authors conclude that the current evidence base is insufficient to demonstrate superiority of combined CRT+ICD (CRT-D) versus CRT alone (CRT-P) in patients with heart failure due to left ventricular dysfunction. There are several confounding factors that may contribute to the current state of affairs: the non-responder rate, arrhythmogenicity, effect of raised filling pressures, and continued optimisation of medical therapy. Despite the significant healthcare burden posed by chronic heart failure, only 3% of cardiomyopathy patients and 1% of heart failure patients discharged from hospital meet the eligibility criteria for CRT (2) from the trials forming the current evidence base. Although CRT has been shown to improve morbidity and decrease mortality, the significant non-responder rate of 30- 40% (3, 4) is but one contributing factor to Lam and Owen’s findings. Combined CRT and ICD therapy may have been prescribed in patients without an arrhythmogenic substrate for pulseless ventricular tachyarrhythmia or fibrillation, but likewise raised left atrial pressure may also contribute significantly to mortality by compromising subendocardial blood flow and hence provoking a substrate for arrhythmia, irrespective of the aetiology of ventricular disease. The causes of death in heart failure may be distinguished by time course as well as aetiology: sudden cardiac death due to arrhythmia or progressive intractable pump failure due to irreversible myocardial damage. The former is easily detectable and monitored via device interrogation, but even in ICD patients defibrillator discharge is not recorded in two thirds (5). Progressive pump failure may be assessed using Doppler echocardiographic criteria of raised left ventricular end diastolic pressure and left atrial pressure. Moreover, the distinction between sudden cardiac death and frank pump failure is by no means absolute, and so mode of death may be neither bi-modal nor mutually exclusive in this particular group of patients. Controversies in the aetiology of left bundle branch block may also complicate the rôle of ICD and CRT. Inclusion criteria for ICD therapy and for CRT uniformly stipulate symptomatic impaired left ventricular systolic function. ICD criterion stipulate additional evidence of arrhythmia, whereas indications for CRT stipulate dyssynchrony (NYHA class III/IV and left bundle branch block morphology with QRS duration > 150 ms or > 120 ms with evidence of mechanical dyssnchrony) comprising a broader and heterogeneous group of patients. The typical characterisation of left bundle branch block as delayed conduction may be reductionist. The presence of prolonged PR interval and left bundle branch block in dilated cardiomyopathy on 12-lead surface electrocardiogram may in fact represent bilateral bundle branch block due to latent activation by delayed early potentials and prolonged late potentials (6). Furthermore, QRS duration alone does not define the risk for sudden cardiac death, but incremental increase in QRS duration over time identifies high-risk patients (7). Finally, variations in primary medical management of chronic heart failure may also play a confounding role in mortality outcomes. The EuroHeart failure survey (8) reported that less than 50% of patients on drug therapy were on β-blocker therapy, though 80% were on an ACE- inhibitor. Similarly upon entry to the CARE-HF study (3), 95% of patients were receiving ACE-inhibitor or angiotensin receptor blocker therapy, but only 39% had achieved at least half target dose (9). Patients may be unwilling or unable to tolerate ‘optimal’ doses of medical therapy prior to CRT referral, but indeed they may be benefiting from continued pharmacological optimisation after CRT owing to the synergistic effect of pacing and medical therapy. Even without CRT successful medical therapy optimization may reduce left atrial pressure and remove its risk for mortality. Lam and Owen concluded that combined therapy did not demonstrate a significant difference with respect to either of the other two. Their findings suggest that inclusion criteria for such expensive therapy are not stringent enough based on current evidence for arrhythmia and partial recovery of ventricular function with medical therapy Robin Chung, Research Fellow, Royal Brompton Hospital Michael Y. Henein, Consultant Cardiologist, West Middlesex University Hospitals NHS Trust, michaelhenein@nhs.net References: 1. Lam SK, Owen A. Combined resynchronisation and implantable defibrillator therapy in left ventricular dysfunction: Bayesian network meta-analysis of randomised controlled trials. BMJ 2007 Oct 11 epub. 2. McAlister FA, Tu JV, Newman A, Lee D, Kimber S, Cujec B, et al. How many patients with heart failure are eligible for cardiac resynchronization? Insights from 2 prospective cohorts. Eur Heart J 2006;27:323-9. 3. Cleland JG, Daubert JC, Erdmann E, Freemantle N, Gras D, Kappenberger L, Tavazzi L; Cardiac Resynchronization-Heart Failure (CARE- HF) Study Investigators. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med. 2005 Apr 14;352(15):1539-49 4. McAlister FA, Ezekowitz J, Hooton N, Vandermeer B, Dryden DM, Spooner C, et al. The role of cardiac resynchronization therapy in patients with left ventricular systolic dysfunction: a systematic review. JAMA 2007;297:2502-14. 5. Ezekowitz J, Dryden DM, Hooton N, Vandermeer B, Friesen C, Spooner C, et al. Implantable cardioverter defibrillators for adults with left ventricular systolic dysfunction: a systematic review. Ann Intern Med 2007;147:251-62. 6. Xiao HB, Roy C, Gibson DG. Nature of ventricular activation in patients with dilated cardiomyopathy: evidence for bilateral bundle branch block. British Heart Journal 1994;72:167-174. 7. Shamim W, Yousufuddin M, Cicoria M, Gibson DG, Coats AJ, Henein MY. Incremental changes in QRS duration in serial ECGs over time identify high risk elderly patients with heart failure. Heart. 2002 Jul;88(1):47- 51. 8. Komajda M, Follath F, Swedberg K, Cleland J, Aguilar JC, Cohen- Solal A, Dietz R, Gavazzi A, Van Gilst WH, Hobbs R, Korewicki J, Madeira HC, Moiseyev VS, Preda I, Widimsky J, Freemantle N, Eastaugh J, Mason J; Study Group on Diagnosis of the Working Group on Heart Failure of the European Society of Cardiology. The EuroHeart Failure Survey programme--a survey on the quality of care among patients with heart failure in Europe. Part 2: treatment. Eur Heart J. 2003 Mar;24(5):464-74. 9. Cleland JG, Daubert JC, Erdmann E, Freemantle N, Gras D, Kappenberger L, Klein W, Tavazzi L; CARE-HF study Steering Committee and Investigators.Baseline characteristics of patients recruited into the CARE -HF study. Eur J Heart Fail. 2005 Mar 2;7(2):205-14 (Table 5). Competing interests: None declared |
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Mahmood Ahmad, ST3-LAT Medway Maritime Hospital, Gillingham, Kent, ME7 5NY, Mehboob Ahmad Rehan
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Guidelines for the treatment of chronic heart failure from the European Society of Cardiology Guidelines in 2005 only recommend ICDs for patients who have survived VF arrests or have sustained Ventricular tachycardia associated with compromise. (IA evidence). They have not recommended extending it into the general population because of its increased morbidity because ICD-implantation and low cost-effectiveness. [1] [1] Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005) The Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology European Heart Journal 2005 26(11):1115-1140 Competing interests: None declared |
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