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The non-responders in cardiac resynchronisation therapy: do we have solutions?

  • Patients' selection by imaging, presented by M Glikson (Ramat Gan, IL)
  • Role of catheter ablation in case of arrythmias and incomplete biventricular capture, presented by J Kautzner (Prague, CZ) - Slides
  • Left ventricular lead implantation positioning, presented by C Leclercq (Rennes, FR) - Slides
  • What after cardiac resynchronisation therapy failure? Presented by M R Cowie (London, GB) - Slides
Non-Invasive Imaging

Non-responders to cardiac resynchronization therapy: which therapeutic options should be considered?
Cardiac resynchronization therapy (CRT) is considered a breakthrough in the treatment of congestive heart failure (CHF) and has been shown to markedly improve morbidity and mortality in patients who respond to this therapy. The latest recommendation of the ESC on its use, the 2010 focused update, recommends considering its use on patients with all degrees of CHF as long as they have a reasonable functional status and life expectancy, an ejection fraction < 35%, and a QRS width > 120 ms; in patients with mild heart failure, a QRS width > 150 ms is required. Unfortunately, at best about 60% of patients benefit from CRT (“responders”), and it has been impossible so far to accurately predict who responds and who not. Initial enthusiasm for echocardiographic parameters was severely frustrated by the large, multicenter PROSPECT trial in which blinded echo core-lab readings revealed large inter-observer variabilities and low predictive accuracies of these parameters.

Patients' selection by imaging

Michael Glikson (Tel Hashomer, Israel) reviewed this history and pointed out that CRT response is determined by a triad of pre-existing left ventricular dyssynchrony (mechanical discoordination), placement of pacing electrodes in a region of delayed contraction and absence or presence of myocardial scar in the paced region. Only if all three components are propitious can a success be expected. Newer echo techniques like assessment of regional mechanics (strain), rather than tissue velocities, cross-correlation, 3D imaging, and others may yet improve prediction of CRT response. Better selection of pacing sites (e.g., by cardiac CT imaging of the cardiac veins) and exclusion of candidates with large myocardial scars (e.g., by magnetic resonance imaging) are now feasible. All of these have been shown in unblinded studies to improve response rates, but rigorous large-scale, multicentric studies are lacking to date.

Role of catheter ablation in case of arrythmias and incomplete biventricular capture

In the following talk, Josef Kautzner (Prague, Czech Republic) explored therapeutic options in those cases where CRT fails because of unfavorable arrhythmias, which can be atrial arrhythmias precluding left ventricular capture (even in the presence of ventricular rate control), CRT-triggered ventricular tachycardias, and frequent ventricular premature beats (VPB). All of these arrhythmias are now amenable to catheter-based therapies. For example, in patients with persistent or permanent atrial fibrillation, atrioventricular node ablation can restore ventricular capture by the CRT device and improve CRT success and heart failure symptoms, although rigorous data on mortality are lacking. CRT may also induce frequent ventricular tachycardias (“arrhythmic storm”), which can be ablated by catheter. Finally, frequent VPB jeopardizing the effect of CRT may also be treated by catheter ablation, if their origin can be defined.

Left ventricular lead implantation positioning

Christophe Leclercq (Rennes, France) focussed on the possibilities of improving suboptimal left ventricular lead positioning. He reminded us that the posterolateral region is not always the most mechanically delayed region, and that too apical positions may be detrimental. The yet unpublished randomized TARGET trial seems to point to a symptomatic benefit from echo-guided selection of the pacing site based on regional strain. Further, even when a lead has already been placed in an apparently unfavorable position, implanting an additional lead in a better location should be considered; a randomized trial of this strategy under Leclercq’s leadership is ongoing. The future may bring multipolar leads and even leadless, implantable pacing devices.

What after cardiac resynchronisation therapy failure?

In the final presentation, Martin Cowie (London, UK) reviewed the options in end-stage CHF if CRT has failed. First, of course, correctable causes of failure should be sought and corrected, e.g. atrial arrhythmias, for which previous speakers had outlined possible therapies. Second, medical therapy must be optimised, including uptitration to the guideline-recommended high doses of angiotensin-converting enzyme (ACE) inhibitors and beta-blockers, addition of an aldosterone blocker, and adequate diuretic doses. Anaemia is a correctable frequent occurrence in CHF. After this, there are a few further options to consider. Digoxin, although now unfashionable, has the weight of large randomized DIG trial evidence for symptomatic improvement, although medical co-therapy was different from today’s practice of the time of this trial. Furthermore, the combination of hydralazine and nitrates has been found beneficial (both in terms of morbidity and mortality) in several large trials, even as an addition to modern drug therapy as outlined above, and should be tried with uptitration and close observation for symptomatic hypotension or lupus-like symptoms. Implantable hemodynamic monitors, a technical innovation, may have considerable impact on the management of severe CHF allowing the prediction of clinical deterioration at an early stage (e.g., by increases in pulmonary pressures) and thus allowing an acute drug intervention to avoid decompensation. Finally, for a small group of patients, cardiac transplantation or assist devices may be appropriate and such options should be evaluated early on. However, good palliative care is all that can be offered once the disease progresses to end-stage in spite of optimised therapy and exclusion of potentially reversible pathologies.




The non-responders in cardiac resynchronisation therapy: do we have solutions?

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.