© 2008 European Society of Cardiology
Cardiac resynchronization therapy in the intensive care setting; the promise and peril of using implantable devices off label
Karolinska Institutet, Department of Cardiology, Karolinska University Hospital Stockholm, Sweden
Saint Louis University School of Medicine St. Louis, MO, USA
Corresponding author. Karolinska University Hospital, Department of Cardiology, 17176 Stockholm, Sweden. Tel.: +46 8 51772639, +46 70 4848355(mobile); fax: +46 8 311044. E-mail address: frieder.braunschweig{at}karolinska.se
Received February 3, 2008; Though the deleterious impact of ventricular conduction abnormalities on cardiac performance has been recognized for a long time, it was not until recently that electromechanical dyssynchrony has been seen as a potential target amenable to specific treatment. Cardiac resynchronization therapy (CRT) has been established as an effective treatment for patients with moderate-to-severe symptomatic heart failure, decreased left ventricular (LV) function and a wide QRS [1-3]. In these patients, CRT enhances LV performance, exercise capacity and quality of life and is associated with improved survival. As a consequence, CRT-implantation is recommended for selected patients with heart failure [4]. Notably, trial evidence for CRT efficacy has been limited to patients in chronic heart failure who are in reasonably stable condition and treated with optimal background pharmacological therapy. Clinical trials have excluded patients on intravenous inotropic support, and those with other severe organ failure or a limited predicted survival. However, a number of invasive or echocardiographic studies have shown that biventricular stimulation acutely improves haemodynamic function measured as cardiac index, filling pressures, stroke work and dp/dt [5,6]. These findings suggest that CRT might produce a significant acute benefit in a situation of refractory haemodynamic compromise.
In this current issue of the European Journal of Heart Failure, Milliez and co-workers present results from "rescue" CRT implantation in 20 patients with catecholamine-dependent refractory heart failure [7]. The procedure was performed in a desperate clinical situation after "end of the road" conventional intensive care medicine had been administered: several attempts at progressive catecholamine weaning in the setting of contraindications to treatment with a cardiac assist device or heart transplantation. In this series, eight patients had a QRS interval of more than 160 ms and the remaining 12 had a QRS duration between 130 and 160 ms and fulfilled 2 of 3 echocardiographic asynchrony criteria suggesting a potential benefit of electromechanical resynchronization.
The short-term results are impressive. All patients were successfully weaned from catecholamine support, mostly within 2 days post-implantation and the systemic blood pressure increased markedly. Concordant with the haemodynamic response, a sharp fall in natriuretic peptides and an increase in urine output were observed. Subsequently, patients were discharged from hospital and standard drug treatment was successfully reinitiated. During longer-term follow-up 17, 16 and 11 patients were alive after 3, 6 and 18 months respectively, and 11 patients improved to NYHA class II. These results compare favourably with the expected outcome in NYHA-class IV patients on inotropic support [8] and confirm other case series evaluating CRT in a similar context [9-11].
Due to the uncontrolled and retrospective study design, the true contribution of CRT beyond the effect of concurrent interventions or spontaneous improvement remains unclear. Of note, despite the positive clinical course, there was only a 3% change in LV ejection fraction after 3 months which is of uncertain clinical relevance and within the error margin of echocardiographic measurement. Unfortunately, no further data supporting the occurrence of reverse remodelling, such as LV volumes or NT-proBNP, are provided. The article also highlights the need to strongly consider the adoption of current guidelines for the implantation of resynchronization devices: patients in this series had QRS widening and at least two HF hospitalisations in the 15 months prior to CRT implantation. Conceivably, in some patients further disease progression to inotrope-dependent heart failure could have been delayed by a timely intervention.
Nevertheless, the clinical value of "rescue-CRT" in the ICU setting may now warrant systematic evaluation in controlled studies. Despite potential methodological problems, this population can indeed be studied as we have learned from various recent trials [8,12]. Potential drawbacks of "rescue-CRT" include an increased procedural risk by operating on critically ill patients and, considering the fact that nine patients died during early follow-up in the study by Milliez et al., an overall limited long-term prognosis. With these factors in mind, the cost effectiveness of CRT therapy in a high risk population, especially if combined with defibrillator therapy, will need to be critically analyzed.
Finally, the present article raises a more generic concern about the off-label use of devices. Given the invasiveness of many device procedures and the attendant costs, the cardiology community should find ways to carefully and systematically evaluate new indications. We simply do not know at this juncture if multiple other investigators have attempted to use CRT to wean patients from inotropic drugs; negative experiences are far less likely to find their way into the medical literature than reports suggesting benefit.
In summary, the authors are to be congratulated for pushing the boundary of current CRT indications and reporting their findings. Clearly, any reasonable attempt to salvage inotrope-dependent patients fills a clinical need. However, since acute haemodynamic response does not correlate with long term outcomes, success cannot be measured by survival to hospital discharge or even short-term survival. Whether clinicians should favourably interpret the data in the present report and consider CRT as a viable intervention of last resort is far from clear. Until a properly designed randomised study is performed, caution is advised. Only through prospective analysis will we be able to clarify if this approach brings great promise or added peril to patients near the end-stage of heart failure.
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