Electrophysiology and Pacing Unit
IRCCS Istituto Clinico Humanitas
Rozzano-Milano
Italy
Tel: +39 0 282244622
Fax: +39 0 282244693
E-mail address
: maurizio.gasparini{at}humanitas.it
Medizinischen Klinik und Poliklinik C
Kardiologie/Angiologie
Universitätsklinikum Münster
D-48129 Münster
Germany
Tel: +49 251 83 4 7617
Fax: +49 251 83 4 7864
E-mail address: g.breithardt{at}uni-muenster.de
We read with great interest the recently published ESC Guidelines on the diagnosis and treatment of heart failure.1 Particularly noteworthy were the recommendations that up-dated the indications for implantable cardioverter defibrillators (ICD) in heart failure patients (p. 1132). The three specific recommendations took into account the recently released clinical evidence of ICD benefit on overall survival in heart failure patients, thus founding the basis for making ICD therapy an important tool in managing such patients. The third point, essentially a newly formulated recommendation based on the recently produced clinical evidence primarily derived from MADIT II and SCD-Heft, the two largest randomized, controlled multi-centre ICD trials,2,3 reads as follows: ICD implantation is reasonable in selected patients with LVEF<3035%, not within 40 days of a myocardial infarction, on optimal background therapy including ACE-inhibitor, ARB, beta-blocker, and an aldosterone antagonist, where appropriate, to reduce sudden death (Class of recommendation I, level of evidence A) [references 90,96,97].
Although we generally applaud the task force and the authors for officially recognizing ICD as a Class I indication for heart failure patients, we respectfully question their phrase, to reduce sudden death, as this is frankly an incorrect interpretation of the very trials they cite in support of their recommendation.
First, we would like to draw your attention to the fact that the cited trials were powered and designed to evaluate as primary endpoint death from any causenot sudden death. MADIT II and SCD-HeFT showed that ICDs improved survival from death for any cause (hazard ratio MADIT II: 0.69, CI 0.510.93, P=0.016; SCD-HeFT: 0.77, CI 0.620.96, P=0.007).2,3 Neither MADIT II nor SCD-HeFT provide any mention whatsoever of the effects of ICD on sudden death. Secondly, the phrase specifying that ICD should not be implanted within 40 days of a myocardial infarction is based on the negative results of the DINAMIT trial, which surprisingly is not cited here.4 Although this statement is absolutely correct with regard to the primary outcome of the trial (all-cause mortality), it is completely incorrect if sudden death is considered (as done in these guidelines). In fact, DINAMIT showed that ICD therapy significantly reduced sudden death after recent acute myocardial infarct (hazard ratio for risk of sudden death 0.42, CI 0.220.83, P=0.009). Nonetheless, the significant reduction of sudden death obtained in this trial was not sufficient to overcome the unfavourable impact of non-sudden deaths in the ICD arm, resulting in an overall neutral outcome. The experience of the DINAMIT trial4 clearly pointed out the importance, especially in a heart failure population, of considering total mortality as primary outcome, avoiding the pitfalls of considering only sudden death reduction.
On the basis of the abovementioned considerations, it becomes clear that the third recommendation should be corrected by deleting the phrase sudden death and replacing it by total mortality.
We feel strongly about correcting this error, not only because it is a misinterpretation of the pertinent trial outcomes, but more importantly, because it implicitly underestimates the importance of ICD therapy in the heart failure population, as demonstrated by these landmark studies.
Thank you for your consideration.
References
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