title: Impact of mechanical activation, scar, and electrical timing on cardiac resynchronization therapy response and clinical outcomes.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Medicine, Cardiovascular Division, University of Virginia Health System, Charlottesville, Virginia. Electronic address: bilchick@virginia.edu.
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Bilchick
authors.affiliation: Department of Medicine, Cardiovascular Division, University of Virginia Health System, Charlottesville, Virginia.
authors.forename: Sujith
authors.initials: S
authors.lastname: Kuruvilla
authors.affiliation: Department of Medicine, Cardiovascular Division, University of Virginia Health System, Charlottesville, Virginia.
authors.forename: Yasmin S
authors.initials: YS
authors.lastname: Hamirani
authors.affiliation: Department of Biomedical Engineering, University of Virginia Health System, Charlottesville, Virginia.
authors.forename: Raghav
authors.initials: R
authors.lastname: Ramachandran
authors.affiliation: Department of Biomedical Engineering, University of Virginia Health System, Charlottesville, Virginia.
authors.forename: Samantha A
authors.initials: SA
authors.lastname: Clarke
authors.affiliation: Department of Biomedical Engineering, University of Virginia Health System, Charlottesville, Virginia.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Parker
authors.affiliation: Department of Public Health Sciences, University of Virginia Health System, Charlottesville, Virginia.
authors.forename: George J
authors.initials: GJ
authors.lastname: Stukenborg
authors.affiliation: Department of Medicine, Cardiovascular Division, University of Virginia Health System, Charlottesville, Virginia.
authors.forename: Pamela
authors.initials: P
authors.lastname: Mason
authors.affiliation: Department of Medicine, Cardiovascular Division, University of Virginia Health System, Charlottesville, Virginia.
authors.forename: John D
authors.initials: JD
authors.lastname: Ferguson
authors.affiliation: Department of Medicine, Cardiovascular Division, University of Virginia Health System, Charlottesville, Virginia.
authors.forename: J Randall
authors.initials: JR
authors.lastname: Moorman
authors.affiliation: Department of Medicine, Cardiovascular Division, University of Virginia Health System, Charlottesville, Virginia.
authors.forename: Rohit
authors.initials: R
authors.lastname: Malhotra
authors.affiliation: Department of Medicine, Cardiovascular Division, University of Virginia Health System, Charlottesville, Virginia.
authors.forename: J Michael
authors.initials: JM
authors.lastname: Mangrum
authors.affiliation: Department of Medicine, Cardiovascular Division, University of Virginia Health System, Charlottesville, Virginia.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Darby
authors.affiliation: Department of Medicine, Cardiovascular Division, University of Virginia Health System, Charlottesville, Virginia.
authors.forename: John
authors.initials: J
authors.lastname: Dimarco
authors.affiliation: Department of Medicine, Cardiovascular Division, University of Virginia Health System, Charlottesville, Virginia; Department of Biomedical Engineering, University of Virginia Health System, Charlottesville, Virginia.
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Holmes
authors.affiliation: Department of Medicine, Cardiovascular Division, University of Virginia Health System, Charlottesville, Virginia; Department of Biomedical Engineering, University of Virginia Health System, Charlottesville, Virginia; Department of Radiology and Medical Imaging, University of Virginia Health System, Charlottesville, Virginia.
authors.forename: Michael
authors.initials: M
authors.lastname: Salerno
authors.affiliation: Department of Medicine, Cardiovascular Division, University of Virginia Health System, Charlottesville, Virginia; Department of Radiology and Medical Imaging, University of Virginia Health System, Charlottesville, Virginia.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Kramer
authors.affiliation: Department of Biomedical Engineering, University of Virginia Health System, Charlottesville, Virginia; Department of Radiology and Medical Imaging, University of Virginia Health System, Charlottesville, Virginia.
authors.forename: Frederick H
authors.initials: FH
authors.lastname: Epstein
mesh_terms: D000368:Aged; D058406:Cardiac Resynchronization Therapy / Q000379:methods*; D004452:Echocardiography; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D006329:Heart Conduction System / Q000503:physiopathology*; D006333:Heart Failure / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D008875:Middle Aged; D013318:Stroke Volume; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000502:physiology*; D020257:Ventricular Remodeling
keywords: cardiac magnetic resonance; cardiac resynchronization therapy; heart failure; myocardial infarction; ventricular tachycardia