Personalisation and Predictive Medicine in Cardiac Resynchronisation Therapy
Non-responder and Super-responder
The concept of non-responders14,15 was proposed in CRT therapy since there is a wide range of response to CRT and around 30 % of patients do not respond to CRT. There remains a lack of standard criteria to define non-responders, but LV reverse remodeling is considered to be an acceptable parameter with better predictive value for cardiovascular mortality compared with other criteria.16 Numerous studies aiming to predict CRT responders have been conducted, including clinical, electrical and imaging predictors at time points pre-, during and post-implantation.17 Potential parameters to facilitate patient selection have included QRS pattern and width, LV ejection fraction and dyssynchrony parameters. However, no parameters have been found to conclusively identify responders to CRT; a composite scoring system with several strong predictors may be needed. In addition, some patients demonstrate dramatic improvement after CRT, even approaching normal cardiac function; they are termed “superresponders”. 18 In these patients, a reduction of risk of ventricular arrhythmias has also been observed.19 Compared to non-responders, super-responders are understudied but the concept is clinically relevant for the secondary prevention of sudden death with CRTdefibrillator or CRT-pacemaker.20
Vulnerable Patients in Conventional Pacemaker Indications
Despite encouraging outcomes of CRT in bradycardia patients, LV dysfunction does not develop in all patients receiving RV pacing; a proportion of population may be resistant to pacinginduced systolic dyssynchrony.21,22 Therefore not every patient should be given CRT due to its high cost and relatively high complication rate. It is important to select vulnerable patients who are likely to develop systolic dyssynchrony when undergoing frequent ventricular pacing in bradycardia. Although it would be desirable to identify baseline predictors related to pacing-induced systolic dyssynchrony, there are a lack data to inform patient selection. The presence of RV pacing induced ventricular dyssynchrony may direct DDDR/CRT-Pacemaker device implant in patients with heart block and normal LVEF. The Efficacy of the Presence of Right Ventricular Apical Pacing Induced Ventricular Dyssynchrony as a Guiding Parameter for Biventricular Pacing in Patients with Bradycardia and Normal Ejection Fraction (ENHANCE) trial aims to address this crucial clinical issue.
Identification of Candidates Developing CRT-induced Proarrhythmia
Another emerging issue is that CRT-induced proarrhythmia, which might be related to the LV lead located within the epicardial scar.23 This is a rare but serious complication and is refractory to antiarrhythmic drugs. Switching off LV pacing presents a clinical dilemma since HF may deteriorate. Arrhythmia recurrence can be managed with catheter ablation but patients require a further intervention. An enhanced understanding of this complex clinical entity and early identification of patients developing CRT-induced proarrhythmia is important, and may amplify our knowledge of the potential complications of CRT.
Women and CRT
Clinical data have shown that women benefit more from CRT in comparison with men24; however, fewer women than men were enrolled in CRT clinical trials. Greater recruitment of female candidates may improve the non-responders rate.24 Although CRT is not recommended in narrow QRS patients,25 in a study of individual patient data, women demonstrated benefit from CRT-defibrillator at a shorter QRS duration compared to men,26 which highlights the importance of genderspecific medicine.