title: Measurement precision in the optimization of cardiac resynchronization therapy.
abstract: BACKGROUND
  Cardiac resynchronization therapy improves morbidity and mortality in appropriately selected patients. Whether atrioventricular (AV) and interventricular (VV) pacing interval optimization confers further clinical improvement remains unclear. A variety of techniques are used to estimate optimum AV/VV intervals; however, the precision of their estimates and the ramifications of an imprecise estimate have not been characterized previously.
  
  
  RESULTS
  An objective methodology for quantifying the precision of estimated optimum AV/VV intervals was developed, allowing physiologic effects to be distinguished from measurement variability. Optimization using multiple conventional techniques was conducted in individual sessions with 20 patients. Measures of stroke volume and dyssynchrony were obtained using impedance cardiography and echocardiographic methods, specifically, aortic velocity-time integral, mitral velocity-time integral, A-wave truncation, and septal-posterior wall motion delay. Echocardiographic methods yielded statistically insignificant data in the majority of patients (62%-82%). In contrast, impedance cardiography yielded statistically significant results in 84% and 75% of patients for AV and VV interval optimization, respectively. Individual cases demonstrated that accepting a plausible but statistically insignificant estimated optimum AV or VV interval can result in worse cardiac function than default values.
  
  
  CONCLUSIONS
  Consideration of statistical significance is critical for validating clinical optimization data in individual patients and for comparing competing optimization techniques. Accepting an estimated optimum without knowledge of its precision can result in worse cardiac function than default settings and a misinterpretation of observed changes over time. In this study, only impedance cardiography yielded statistically significant AV and VV interval optimization data in the majority of patients.
authors.affiliation: Division of Cardiovascular Medicine and Center for Biomedical Informatics Research, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Turcott
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Witteles
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Wang
authors.forename: Randall H
authors.initials: RH
authors.lastname: Vagelos
authors.forename: Michael B
authors.initials: MB
authors.lastname: Fowler
authors.forename: Euan A
authors.initials: EA
authors.lastname: Ashley
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001283:Atrioventricular Node / Q000503:physiopathology*; D002304:Cardiac Pacing, Artificial / Q000379:methods*; D002307:Cardiography, Impedance; D017147:Defibrillators, Implantable; D015150:Echocardiography, Doppler; D004554:Electric Countershock / Q000379:methods*; D005260:Female; D006333:Heart Failure / Q000175:diagnosis / Q000503:physiopathology* / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010138:Pacemaker, Artificial; D011930:Reaction Time / Q000502:physiology; D015203:Reproducibility of Results; D013318:Stroke Volume / Q000502:physiology