Assessment of Systolic Dyssynchrony for Cardiac Resynchronization Therapy Is Not Clinically Useful

Abstract

C ardiac resynchronization therapy (CRT) is an effective treatment in patients with medically refractory heart failure. Several clinical trials have shown improvement in both left ventricular (LV) function and symptoms with CRT compared with controls, 1-4 with the 2 largest trials showing a reduction in rates of hospitalization and death. 5,6 On the basis of data from these studies, most international guidelines agree on the standard indications for CRT: impaired functional status with New York Heart Association functional class III or IV, LV ejection fraction (LVEF) Յ35%, and prolonged QRS duration Ն120 ms in the setting of optimal medical therapy. 7-9 However, not all patients experienced improvement in symptoms or LV function, and numerous studies have focused on improving the selection criteria for CRT in the hopes of excluding these "nonresponders." [1][2][3][4] One of the most frequently studied modalities for patient selection is echocardiographic measurement of LV systolic dyssynchrony based on the supposition that there is a threshold for mechanical dyssynchrony below which there is no therapeutic benefit. Despite these studies, we argue that current echocardiographic methods of measuring dyssynchrony should not be used to exclude patients who are otherwise candidates for CRT. Conversely, in patients with narrow QRS, echocardiographic evidence of dyssynchrony is insufficient to warrant CRT on the basis of current data. Response by Delgado and Bax on p 663There are important unresolved issues regarding the use of mechanical dyssynchrony measurements for determining CRT eligibility in an individual patient. Let us examine the case of a 60-year-old man with ischemic cardiomyopathy, recurrent hospitalizations, and New York Heart Association functional class III despite an excellent heart failure drug regimen. He inquires about additional therapy to help improve his symptoms and keep him out of the hospital. His LVEF is 30% by echocardiogram, and the ECG shows a QRS duration of 150 ms in a left bundle-branch block configuration. Current guidelines clearly state that this patient qualifies for CRT. However, proponents of mechanical dyssynchrony would require additional evaluation before referring him for CRT. If evaluation for mechanical dyssynchrony is undertaken, many issues are unresolved, including the value of measuring intraventricular and/or interventricular dyssynchrony, the best modality to use for intraventricular dyssynchrony, and the threshold values that define the presence of mechanical dyssynchrony. Most importantly, if mechanical dyssynchrony is not demonstrated, is the weight of this evidence sufficient to advise against CRT implantation in the patient, contrary to guidelines?After reviewing the available data, we will present the case that current measures of mechanical dyssynchrony do not add clinical utility in selecting patients for CRT beyond current guidelines. Key issues to be addressed include the following: (1) defining "response" to CRT; (2) the clinical relevance of employing echo...

Constrained manifold learning for the characterization of pathological deviations from normality

“…In particular, we would like to apply these considerations to cardiac resynchronization therapy (CRT) studies, supported by the following paradigm: CRT targets the correction of the dyssynchrony in the motion of the cardiac chambers, leading to improvements in the cardiac function, the patient condition, and ventricular size (StJohnSutton et al, 2003); however, CRT patient selection still discards mechanical dyssynchrony as a selection criteria (Dickstein et al, 2010). There are several reasons for this: there is currently no consensus regarding the accurate characterization of mechanical dyssynchrony, its link with CRT outcome, and the way to include it within the patient selection process (Fornwalt et al, 2009;Fornwalt, 2011;Delgado and Bax, 2011;Sung and Foster, 2011).…”

Temporal diffeomorphic free-form deformation: Application to motion and strain estimation from 3D echocardiography

“…This is a pre-print version The final version can be downloaded from http://www.sciencedirect.com/ between mechanical dyssynchrony and response to CRT is still a controversial issue (Delgado and Bax (2011);Sung and Foster (2011)), particularly limited if a single parameter (measured strain) is considered in the analysis. Comparing the measured strain to the deformation patterns of specific mechanisms involved in CRT response may be a more relevant strategy (Parsai et al (2009)) and this could be achieved with the use of 3D strain analysis by using such a tool as the one we present.…”

Quantitative assessment of left ventricular mechanical dyssynchrony using cine cardiovascular magnetic resonance imaging: Inter-study reproducibility

“…2 Numerous echocardiographic dyssynchrony parameters have been evaluated with the aim to directly quantify LV mechanical dyssynchrony; 3 however, none led to a significant optimisation of CRT response. 2,4,5 Since CRT specifically targets cardiac dyssynchrony, a direct, robust and reproducible quantification of LV mechanical dyssynchrony with superiority over current clinical parameters is crucial. Inter-study reproducibility is a key requirement when repeated examinations are required.…”

“…While numerous echocardiographic dyssynchrony parameters have been proposed, 3 none of these succeeded in improving patient selection for CRT. 2,4,5 More recently, dyssynchrony measures based on cardiovascular magnetic resonance (CMR) imaging have been developed, most of them based on CMR myocardial tagging 6,7 or displacement encoding with stimulated echoes (DENSE). 8 Studies applying these measures in smaller cohorts showed promising results regarding the prediction of CRT response.…”