Understanding Nonresponders of Cardiac Resynchronization Therapy—Current and Future Perspectives

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Abstract
Introduction: Cardiac resynchronization therapy (CRT) is now an established nonpharmacologic therapy for advanced heart failure with electromechanical delay. Despite compelling evidence of the benefits of CRT, one troubling issue is the lack of a favorable response in about one‐third of patients. Methods and Results: Currently, there is no unifying definition of responders, and published data were based on acute hemodynamic changes, chronic left ventricular reverse remodeling, as well as the intermediate or long‐term clinical response. The lack of improvement with CRT can be due to many factors including the placement of the left ventricular pacing lead in an inappropriate location, the absence of electrical conduction delay or mechanical dyssynchrony despite wide QRS complexes, and possibly failure to optimize the CRT settings after device implantation. In acute hemodynamic studies, placing the left ventricular leads at the free wall region has been suggested to generate the best pulse pressure and positive dp/dt. The degree of mechanical dyssynchrony has recently been assessed noninvasively in CRT patients by echocardiography and in particular by tissue Doppler imaging. These studies suggested that responders of left ventricular reverse remodeling or systolic function had more severe systolic dyssynchrony. However, further studies are needed to examine the clinical utility of these parameters when applied to the standardized anatomic or functional endpoints. Optimization of atrioventricular and interventricular pacing intervals may also reduce the number of nonresponders, though newer methods, especially interventricular pacing intervals, are still under clinical investigation. Conclusion: With the adjunctive use of imaging technology, physicians are able to characterize the response to CRT objectively, and cardiac imaging is an important clinical tool for determining more precisely the presence and degree of mechanical dyssynchrony.

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