The following are key points to remember from this clinical update on avoiding nonresponders to cardiac resynchronization therapy (CRT):

1. About one third of patients who undergo implantation of a CRT device do not improve their heart failure symptoms.
2. CRT efficacy across clinical trials has been expressed through a variety of endpoints: functional assessment, hard outcomes, remodeling, and clinical composite measures. The nonresponse rates are generally lowest when functional measures are used as endpoints and highest when remodeling is considered.
3. Current dyssynchrony imaging techniques are not recommended as a selection criterion for CRT.
4. Ischemic etiology, male gender, New York Heart Association functional class IV, severe mitral regurgitation, marked left atrial dilatation, and a short interventricular mechanical delay have been associated with worse clinical and echocardiographic outcomes.
5. The value of CRT in patients with atrial fibrillation (AF) is not well borne out. Only a single randomized trial prospectively stratified population by presence versus absence of AF. In the subgroup of patients with AF, CRT conferred no measurable benefit. Atrioventricular (AV) nodal ablation may be considered in patients with AF and reduced left ventricular ejection fraction, especially when nearly 100% biventricular pacing is not otherwise achievable.
6. The value of left ventricular endocardial pacing and multisite pacing is being evaluated in clinical trials.
7. One hundred percent biventricular stimulation is desired in all patients with CRT. While the CRT device measures the percentage of biventricular stimulation, this assessment is limited by its underappreciation of fusion and pseudofusion complexes. The consistency of BiV capture can be verified using 24-hour ambulatory and/or exercise electrocardiograms.
8. A tall R wave in V1 is nearly always present in association with effective CRT. Short-paced QRS are associated with the best response to CRT.
9. Empiric programming of a 100–120 milliseconds sensed AV delay and simultaneous BiV stimulation is noninferior to programming based on echocardiographic parameters. Echocardiographic optimization is, however, advised in cases of CRT nonresponse.
10. The In-TIME trial showed that, compared with in-office monitoring, remote device monitoring was associated with a significant decrease in the rate of worsened clinical composite score and death from all causes.
11. In a large retrospective analysis of CRT recipients, 11.5% had a <90% BiV stimulation, caused by either atrial tachyarrhythmia or by frequent ventricular extrasystoles. Arrhythmia suppression, either with ablation or antiarrhythmic medication, may prevent nonresponse to CRT.

Keywords: Arrhythmias, Cardiac, Atrioventricular Node, Cardiac Resynchronization Therapy, Echocardiography, Electrocardiography, Heart Failure, Mitral Valve Insufficiency, Pacemaker, Artificial, Stroke Volume, Tachycardia, Ventricular Function, Left, Ventricular Premature Complexes

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