Impact of mechanical activation, scar, and electrical timing on cardiac resynchronization therapy response and clinical outcomes.

OBJECTIVES Using cardiac magnetic resonance (CMR), we sought to evaluate the relative influences of mechanical, electrical, and scar properties at the left ventricular lead position (LVLP) on cardiac resynchronization therapy (CRT) response and clinical events. BACKGROUND CMR cine displacement encoding with stimulated echoes (DENSE) provides high-quality strain for overall dyssynchrony (circumferential uniformity ratio estimate [CURE] 0 to 1) and timing of onset of circumferential contraction at the LVLP. CMR DENSE, late gadolinium enhancement, and electrical timing together could improve upon other imaging modalities for evaluating the optimal LVLP. METHODS Patients had complete CMR studies and echocardiography before CRT. CRT response was defined as a 15% reduction in left ventricular end-systolic volume. Electrical activation was assessed as the time from QRS onset to LVLP electrogram (QLV). Patients were then followed for clinical events. RESULTS In 75 patients, multivariable logistic modeling accurately identified the 40 patients (53%) with CRT response (area under the curve: 0.95 [p < 0.0001]) based on CURE (odds ratio [OR]: 2.59/0.1 decrease), delayed circumferential contraction onset at LVLP (OR: 6.55), absent LVLP scar (OR: 14.9), and QLV (OR: 1.31/10 ms increase). The 33% of patients with CURE <0.70, absence of LVLP scar, and delayed LVLP contraction onset had a 100% response rate, whereas those with CURE ≥0.70 had a 0% CRT response rate and a 12-fold increased risk of death; the remaining patients had a mixed response profile. CONCLUSIONS Mechanical, electrical, and scar properties at the LVLP together with CMR mechanical dyssynchrony are strongly associated with echocardiographic CRT response and clinical events after CRT. Modeling these findings holds promise for improving CRT outcomes.

[1]  Christine H. Lorenz,et al.  Motion-guided segmentation for cine DENSE MRI , 2009, Medical Image Anal..

[2]  Craig H Meyer,et al.  Imaging three‐dimensional myocardial mechanics using navigator‐gated volumetric spiral cine DENSE MRI , 2010, Magnetic resonance in medicine.

[3]  Jagmeet P. Singh,et al.  Left ventricular lead electrical delay predicts response to cardiac resynchronization therapy. , 2006, Heart rhythm.

[4]  D. Kass,et al.  Physiology of biventricular pacing , 2007, Current cardiology reports.

[5]  H. Jensen,et al.  Left Ventricular Lead Performance in Cardiac Resynchronization Therapy: Impact of Lead Localization and Complications , 2005, Pacing and clinical electrophysiology : PACE.

[6]  Daniel B. Mark,et al.  TUTORIAL IN BIOSTATISTICS MULTIVARIABLE PROGNOSTIC MODELS: ISSUES IN DEVELOPING MODELS, EVALUATING ASSUMPTIONS AND ADEQUACY, AND MEASURING AND REDUCING ERRORS , 1996 .

[7]  S. Saba,et al.  Dyssynchrony by speckle-tracking echocardiography and response to cardiac resynchronization therapy: results of the Speckle Tracking and Resynchronization (STAR) study , 2010, European heart journal.

[8]  Christopher M Kramer,et al.  Myocardial tissue tracking with two-dimensional cine displacement-encoded MR imaging: development and initial evaluation. , 2004, Radiology.

[9]  S. Saba,et al.  Echocardiography-Guided Left Ventricular Lead Placement for Cardiac Resynchronization TherapyClinical Perspective , 2013 .

[10]  Katherine C. Wu,et al.  Cardiac magnetic resonance assessment of dyssynchrony and myocardial scar predicts function class improvement following cardiac resynchronization therapy. , 2008, JACC. Cardiovascular imaging.

[11]  Kenneth A. Ellenbogen,et al.  The relationship between ventricular electrical delay and left ventricular remodelling with cardiac resynchronization therapy , 2011, European heart journal.

[12]  F. Harrell,et al.  Prognostic/Clinical Prediction Models: Multivariable Prognostic Models: Issues in Developing Models, Evaluating Assumptions and Adequacy, and Measuring and Reducing Errors , 2005 .

[13]  Jeroen J. Bax,et al.  Effect of Posterolateral Scar Tissue on Clinical and Echocardiographic Improvement After Cardiac Resynchronization Therapy , 2006, Circulation.

[14]  Mark A Hlatky,et al.  2012 ACCF/AHA/HRS focused update incorporated into the ACCF/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. , 2013, Circulation.

[15]  David Begley,et al.  Targeted left ventricular lead placement to guide cardiac resynchronization therapy: the TARGET study: a randomized, controlled trial. , 2012, Journal of the American College of Cardiology.

[16]  Charles Antzelevitch,et al.  Effect of Epicardial or Biventricular Pacing to Prolong QT Interval and Increase Transmural Dispersion of Repolarization: Does Resynchronization Therapy Pose a Risk for Patients Predisposed to Long QT or Torsade de Pointes? , 2003, Circulation.

[17]  Shunichi Homma,et al.  Parameterization of Left Ventricular Wall Motion for Detection of Regional Ischemia , 2005, Annals of Biomedical Engineering.

[18]  J. Holmes,et al.  Postprocedure Mapping of Cardiac Resynchronization Lead Position Using Standard Fluoroscopy Systems: Implications for the Nonresponder with Scar , 2014, Pacing and clinical electrophysiology : PACE.

[19]  M. Link,et al.  2012 ACCF/AHA/HRS focused update of the 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. , 2012, The Journal of thoracic and cardiovascular surgery.

[20]  Jeroen J. Bax,et al.  Combined longitudinal and radial dyssynchrony predicts ventricular response after resynchronization therapy. , 2007, Journal of the American College of Cardiology.

[21]  Jeroen J. Bax,et al.  Optimal left ventricular lead position predicts reverse remodeling and survival after cardiac resynchronization therapy. , 2008, Journal of the American College of Cardiology.

[22]  Aaron T. Hess,et al.  Tracking Myocardial Motion From Cine DENSE Images Using Spatiotemporal Phase Unwrapping and Temporal Fitting , 2007, IEEE Transactions on Medical Imaging.

[23]  H. Wen,et al.  Systolic myocardial dysfunction in patients with type 2 diabetes mellitus: identification at MR imaging with cine displacement encoding with stimulated echoes. , 2012, Radiology.

[24]  Michael Salerno,et al.  MR cine DENSE dyssynchrony parameters for the evaluation of heart failure: comparison with myocardial tissue tagging. , 2012, JACC. Cardiovascular imaging.

[25]  Maria Drangova,et al.  Delayed enhancement magnetic resonance imaging predicts response to cardiac resynchronization therapy in patients with intraventricular dyssynchrony. , 2006, Journal of the American College of Cardiology.

[26]  John Gorcsan,et al.  Echocardiography-Guided Left Ventricular Lead Placement for Cardiac Resynchronization Therapy: Results of the Speckle Tracking Assisted Resynchronization Therapy for Electrode Region Trial , 2013, Circulation. Heart failure.

[27]  D. Exner,et al.  Association between QRS duration and outcome with cardiac resynchronization therapy: a systematic review and meta-analysis. , 2013, Journal of electrocardiology.

[28]  H. Halperin,et al.  Systolic Improvement and Mechanical Resynchronization Does Not Require Electrical Synchrony in the Dilated Failing Heart With Left Bundle-Branch Block , 2002, Circulation.