Echocardiography-guided left ventricular (LV) lead placement at the site of latest mechanical activation improves heart failure outcomes in patients receiving a cardiac resynchronization therapy defibrillator (CRT-D). In this study, we test the hypothesis that a strategy of echocardiography-guided LV lead placement improves patient survival rate free from appropriate CRT-D therapy for ventricular arrhythmias. Patients enrolled in the prospective, randomized Speckle Tracking Assisted Resynchronization Therapy for Electrode Region trial and treated with a CRT-D device (108 with the echo-guided strategy and 75 with the routine strategy) were followed to the end point of death or first appropriate CRT-D therapy. Over a follow-up period of 3.7 ± 2.1 years, 62 patients (33%) died and 40 (22%) received appropriate CRT-D therapy. Compared with the routine group, patients in the echo-guided group had improved CRT-D therapy-free survival rate (hazard ratio = 0.64, 95% confidence interval = 0.42 to 0.98, p = 0.038). Patients randomized to the echo-guided LV lead placement were more likely to resynchronize their LV compared with the routine group (72% vs 48%, respectively, p = 0.006). Patients whose LV did resynchronize after CRT-D had improved therapy-free survival rate compared with those whose LV did not resynchronize (hazard ratio = 0.49, 95% confidence interval = 0.28 to 0.86, p = 0.012). In conclusion, a strategy of echo-guided LV lead placement improved the patient survival rate free from defibrillator therapy in CRT-D recipients.
The Speckle Tracking Assisted Resynchronization Therapy for Electrode Region (STARTER) was a prospective, single-center, double-blinded, randomized trial comparing transvenous left ventricular (LV) lead positioning using speckle tracking echocardiographic guidance with a routine approach without imaging guidance. STARTER demonstrated the superiority of the echo-guided approach for the primary end point of death or first heart failure hospitalization. In the present analysis, we investigated the effect of LV lead implantation strategy on the cardiac resynchronization therapy defibrillator (CRT-D) therapy-free survival rates in the STARTER population.
Methods
STARTER was a prospective, single-center, double-blinded, randomized trial comparing speckle tracking echo-guided LV lead positioning with a routine approach without imaging guidance. One hundred and eighty-seven patients were enrolled in STARTER and implanted with a CRT device at the University of Pittsburgh Medical Center between June 2005 and March 2011, including 110 patients in the echo-guided arm and 77 patients in the routine arm of the study. Details of the study are published elsewhere. Briefly, STARTER enrolled patients who were at least 18 years of age with New York Heart Association heart failure classes II to IV symptoms on optimal medical therapy and a baseline left ventricular ejection fraction (LVEF) ≤35% and QRS duration ≥120 ms. All patients received CRT-D, except for 4 patients (2 in each study arm) who received CRT pacemakers. The present analysis is therefore based on the 183 patients with CRT-D, including the 108 in the echo-guided arm and the 75 in the routine arm.
As previously detailed, all echocardiographic studies (GE Vivid 7 system, Horten, Norway) were analyzed by the core lab at the University of Pittsburgh Medical Center Presbyterian. LV volumes were assessed by biplane Simpson rule using manual tracing of digital images. For speckle tracking radial strain, digital grayscale 2-dimensional cine loop images were acquired at end-expiratory apnea from basal and mid-LV short-axis views with frame rates of 60 to 90 Hz for off-line analysis (GE EchoPac BT08-BT11, Fairfield, Connecticut). The times to peak strain from 8 free-wall segments (4 from each view) were determined from a minimum of 3 consecutive beats and averaged. The site of latest activation was determined as the segment with the latest peak strain. Dyssynchrony was determined as the time difference between peak strain in the anteroseptal segment and the peak strain in the posterior wall, as previously described.
Polar maps using a 16-segment model of the time to peak strain in the LV were constructed, and LV lead position as determined by fluoroscopic cine loops in the orthogonal planes obtained at the time of device implantation was superimposed on this map. Exact concordance was defined as when the LV lead was positioned in the exact segment with the latest mechanical activation. Adjacent segments were defined as those segments immediately adjacent to the latest activation site, including touching diagonally, using the 10 free-wall segments of the 16-segment model.
LV volumes and LVEF were obtained from follow-up echocardiograms obtained 6 to 12 months after CRT implant. Dyssynchrony after CRT was determined by speckle tracking as before CRT. Resynchronization was defined as a 50% decrease in the radial dyssynchrony (difference in time to peak anteroseptal to posterior wall strain) from before to after CRT, providing that the patient manifested at least 95 ms dyssynchrony measure at baseline. For this analysis, the predefined end points were death or appropriate CRT-D therapy for ventricular arrhythmias. Patients were censored at the time of first appropriate device therapy. All device electrograms were adjudicated by an electrophysiologist at the time of any device therapy. Only therapies delivered for ventricular arrhythmias were used in this analysis.
All continuous variables are expressed as mean ± SD and were compared using the Student t test or analysis of variance, as appropriate. Discrete variables are expressed as number of events and percentages and compared using the chi-square test. Time to events was calculated according to the Kaplan-Meier method and compared using the log-rank test. Hazard ratios (HRs) were generated using Cox regression. All analyses were conducted using SPSS software version 19 (IBM, Inc., Armonk, New York). p Values ≤0.05 were considered statistically significant.
Results
As previously described, STARTER enrolled patients with a mean age of 66 ± 12 years, predominantly men (73%) with a low LVEF of 26% ± 7% and ischemic cardiomyopathy in the majority (62%), and a QRS duration of 159 ± 27 ms. Twelve percent of the patients had a history of sustained ventricular arrhythmias before CRT-D implantation. At enrollment, patients belonged to the New York Heart Association’s heart failure classes II (13%), III (71%), and IV (16%), and most were on optimal pharmacological therapy at the time of CRT-D implantation, with 88% of the subjects receiving β blockers and 82% receiving angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Within the overall cohort, 44 patients had persistent atrial arrhythmias and 40 patients underwent CRT-D because of chronic right ventricular pacing. All these parameters were balanced between the echocardiography-guided and the routine LV lead placement groups.
During a mean follow-up of 3.7 ± 2.1 years (median 3.7), 62 patients (33%) died, 40 (22%) received appropriate CRT-D therapy, and 10 (5%) were hospitalized for ventricular arrhythmias. Table 1 lists the baseline clinical characteristics of patients who died or received CRT-D therapy for ventricular arrhythmias during follow-up. Patients who died or received CRT-D therapy were more likely to have ischemic heart disease, lower LVEF, and worse heart failure class than patients who lived without CRT-D therapy.
