Individualised approaches key to success in resynchronisation therapy non-responders

Non-responsiveness after cardiac resynchronisation therapy (CRT) occurs in 43% of patients, indicating the importance of improved outcomes in the future. A variety of root causes and potential resolution strategies were presented, all of them emphasising the importance of individualised treatment approaches [1].

Prof. Jagmeet Singh (Massachusetts General Hospital, USA) presented treatment strategies for patients not responding to CRT [1]. Response can be assessed using hard measurements, remodelling, soft clinical measurements, and composite scores. As much as 43% of CRT patients are classified as non- or negative-responders after 6 months. However, responding is a continuum and a clear classification is often difficult. For example, 30-40% of patients can be mild responders and non-responsive in some way.

Determinants of CRT response include patient selection, lead implantation, device programming, and follow-up. For example, CRT in heart failure with narrow QRS complex increased mortality [2]. The considerable variability in electrical activation sequence as shown in endocardial maps may explain the variability in CRT response and argue against the one-size-fits-all ‘anatomical lead positioning’ strategy [3]. Furthermore, non-responsiveness is often multifactorial, with some of the factors not being directly related to CRT (e.g. suboptimal medication, comorbidities).

Individualised care using an integrated approach including heart failure, cardiac arrhythmia, and echocardiography services has been shown to significantly reduce the risk of mortality (see Figure). Optimisation of the devices, such as sound standard programming and use of automatic algorithms (e.g. AdaptivCRT, SMART-CRT, Respond-CRT, Synch-AV), also showed improved outcomes.

Figure: Improvement of event-free survival by multi-disciplinary CRT clinic versus conventional follow-up [4]



CRT, cardiac resynchronisation therapy; FU, follow-up.

Lead location has also been shown to contribute to clinical benefit. Apical left ventricular lead locations were associated with worse outcome irrespective of QRS morphology and electrical activation sequence, while targeting the most electrically delayed areas improved clinical outcome [5]. A study on multipoint pacing (NCT02006069) was recently stopped for futility, although multisite pacing was shown to be effective in some cases.

Prof. Singh summarised the importance of an individualised approach in CRT. Without selection of the right procedure for the individual at the beginning, non-responsiveness is likely. To gain relevant clinical benefit, treatment of non-responsiveness must also follow an individualised approach including medical optimisation, resolution of rhythm issues, AV optimisation, reassessment of lead location, and alternative pacing approaches.

1. 
   
   1. Singh J. How to treat cardiac resynchronisation therapy non-responders? EHRA 2021 Congress, 23-25 April.
   2. Ruschitzka F, et al. N Engl J Med 2013;369:1395-1405.
   3. Singh JP, et al. J Am Coll Cardiol EP 2020; in press.
   4. Altman R, et al. Eur. Heart J. 2012;33(17):2181-2188.
   5. Singh JP, et al. Circulation 2011:123:1159-1166.

 

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Posted on 16 June 202125 June 2021