Evan Adelstein

Echocardiography-Guided Left Ventricular Lead Placement for Cardiac Resynchronization Therapy Results of the Speckle Tracking Assisted Resynchronization Therapy for Electrode Region Trial

Background— Cardiac resynchronization therapy improves mortality and morbidity in patients with heart failure (HF) with wide QRS complex and diminished left ventricular (LV) function, but response is variable. Methods and Results— The Speckle Tracking Assisted Resynchronization Therapy for Electrode Region (STARTER) was a prospective, double-blind, randomized controlled trial testing the hypothesis that an incremental benefit to cardiac resynchronization therapy would be gained by echo-guided (EG) transvenous LV lead placement versus a routine fluoroscopic approach. EG LV lead placement was attempted at the site of latest time to peak radial strain by speckle tracking echocardiography. The prespecified primary end point was first HF hospitalization or death. Of 187 New York Heart Association class II to IV patients with HF (62% ischemic; ejection fraction 26±6%; QRS 159±27 ms), 110 were randomized to EG and 77 to routine strategies. Primary events included 30 deaths and 37 HF hospitalizations over 1.8 years. Using intention-to-treat, patients randomized to an EG strategy had a significantly more favorable event-free survival (hazard ratio, 0.48; 95% confidence interval, 0.28–0.82; P =0.006). Exact or adjacent concordance of LV lead with latest site could be achieved in 85% of the EG group and occurred fortuitously in 66% of controls ( P =0.010) and was associated with an improvement in event-free survival (hazard ratio, 0.40; 95% confidence interval, 0.22–0.71; P =0.002). Conclusions— A strategy of EG LV lead placement for cardiac resynchronization therapy improved patient outcomes by reducing the combined risk of death or HF hospitalizations and has implications for delivery of cardiac resynchronization therapy. Clinical Trial Registration— URL: . Unique identifier: [NCT00156390][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00156390&atom=%2Fcirchf%2F6%2F3%2F427.atomBackground—Cardiac resynchronization therapy improves mortality and morbidity in patients with heart failure (HF) with wide QRS complex and diminished left ventricular (LV) function, but response is variable. Methods and Results—The Speckle Tracking Assisted Resynchronization Therapy for Electrode Region (STARTER) was a prospective, double-blind, randomized controlled trial testing the hypothesis that an incremental benefit to cardiac resynchronization therapy would be gained by echo-guided (EG) transvenous LV lead placement versus a routine fluoroscopic approach. EG LV lead placement was attempted at the site of latest time to peak radial strain by speckle tracking echocardiography. The prespecified primary end point was first HF hospitalization or death. Of 187 New York Heart Association class II to IV patients with HF (62% ischemic; ejection fraction 26±6%; QRS 159±27 ms), 110 were randomized to EG and 77 to routine strategies. Primary events included 30 deaths and 37 HF hospitalizations over 1.8 years. Using intention-to-treat, patients randomized to an EG strategy had a significantly more favorable event-free survival (hazard ratio, 0.48; 95% confidence interval, 0.28–0.82; P=0.006). Exact or adjacent concordance of LV lead with latest site could be achieved in 85% of the EG group and occurred fortuitously in 66% of controls (P=0.010) and was associated with an improvement in event-free survival (hazard ratio, 0.40; 95% confidence interval, 0.22–0.71; P=0.002). Conclusions—A strategy of EG LV lead placement for cardiac resynchronization therapy improved patient outcomes by reducing the combined risk of death or HF hospitalizations and has implications for delivery of cardiac resynchronization therapy. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00156390.

Relationship of Echocardiographic Dyssynchrony to Long-Term Survival After Cardiac Resynchronization Therapy

Background— The ability of echocardiographic dyssynchrony to predict response to cardiac resynchronization therapy (CRT) has been unclear. Methods and Results— A prospective, longitudinal study was designed with predefined dyssynchrony indexes and outcome variables to test the hypothesis that baseline dyssynchrony is associated with long-term survival after CRT. We studied 229 consecutive class III to IV heart failure patients with ejection fraction ≤35% and QRS duration ≥120 milliseconds for CRT. Dyssynchrony before CRT was defined as tissue Doppler velocity opposing-wall delay ≥65 milliseconds, 12-site SD (Yu Index) ≥32 milliseconds, speckle tracking radial strain anteroseptal-to-posterior wall delay ≥130 milliseconds, or pulsed Doppler interventricular mechanical delay ≥40 milliseconds. Outcome was defined as freedom from death, heart transplantation, or left ventricular assist device implantation. Of 210 patients (89%) with dyssynchrony data available, there were 62 events: 47 deaths, 9 transplantations, and 6 left ventricular assist device implantations over 4 years. Event-free survival was associated with Yu Index (P=0.003), speckle tracking radial strain (P=0.003), and interventricular mechanical delay (P=0.019). When adjusted for confounding baseline variables of ischemic origin and QRS duration, Yu Index and radial strain dyssynchrony remained independently associated with outcome (P<0.05). Lack of radial dyssynchrony was particularly associated with unfavorable outcome in those with QRS duration of 120 to 150 milliseconds (P=0.002). Conclusions— The absence of echocardiographic dyssynchrony was associated with significantly less favorable event-free survival after CRT. Patients with narrower QRS duration who lacked dyssynchrony had the least favorable long-term outcome. These observations support the relationship of dyssynchrony and CRT response.

Impact of scar burden by single-photon emission computed tomography myocardial perfusion imaging on patient outcomes following cardiac resynchronization therapy.

AIMS Ischaemic heart disease negatively impacts response to cardiac resynchronization therapy (CRT), yet the impact of infarct scar burden on clinical outcomes and its interaction with mechanical dyssynchrony have not been well described. METHODS AND RESULTS We studied 620 NYHA classes III-IV heart failure patients with ejection fraction (EF) ≤ 35% and QRS duration ≥120 ms referred for CRT. Included were 190 ischaemic cardiomyopathy (ICM) CRT recipients with scar burden quantified by rest-redistribution Tl(201) myocardial perfusion imaging using a 17-segment (0 = normal to 4 = absence of uptake) summed rest score (SRS). Non-ICM (NICM) CRT recipients (n = 380) and 50 patients referred for CRT with unsuccessful LV lead implant comprised the comparison groups. Echocardiographic dyssynchrony analysis was performed in a subgroup of 150 patients. Follow-up left ventricular EF (LVEF) and volumes were examined at 7 ± 3 months in 143 patients. The outcome of death, cardiac transplant, or mechanical circulatory support was assessed in all. Over 2.1 ± 1.6 years, ICM patients had significantly worse survival and less LVEF improvement than NICM patients (P < 0.01). Ischaemic cardiomyopathy patients with low scar burden (SRS < 27) had favourable survival and LVEF improvement, similar to NICM patients. A high scar burden (SRS ≥ 27) was associated with reduced survival and lack of LV functional improvement (P ≤ 0.01), similar to those with unsuccessful LV lead implant, whereas baseline dyssynchrony was not predictive of outcome in these patients. CONCLUSION Extensive scar burden in ICM patients unfavourably affected clinical and LV functional outcomes after CRT, regardless of baseline dyssynchrony measures. Patients with ICM and lower scar burden had significantly better outcomes, similar to NICM patients.

Echocardiography-Guided Left Ventricular Lead Placement for Cardiac Resynchronization TherapyClinical Perspective

Background— Cardiac resynchronization therapy improves mortality and morbidity in patients with heart failure (HF) with wide QRS complex and diminished left ventricular (LV) function, but response is variable. Methods and Results— The Speckle Tracking Assisted Resynchronization Therapy for Electrode Region (STARTER) was a prospective, double-blind, randomized controlled trial testing the hypothesis that an incremental benefit to cardiac resynchronization therapy would be gained by echo-guided (EG) transvenous LV lead placement versus a routine fluoroscopic approach. EG LV lead placement was attempted at the site of latest time to peak radial strain by speckle tracking echocardiography. The prespecified primary end point was first HF hospitalization or death. Of 187 New York Heart Association class II to IV patients with HF (62% ischemic; ejection fraction 26±6%; QRS 159±27 ms), 110 were randomized to EG and 77 to routine strategies. Primary events included 30 deaths and 37 HF hospitalizations over 1.8 years. Using intention-to-treat, patients randomized to an EG strategy had a significantly more favorable event-free survival (hazard ratio, 0.48; 95% confidence interval, 0.28–0.82; P =0.006). Exact or adjacent concordance of LV lead with latest site could be achieved in 85% of the EG group and occurred fortuitously in 66% of controls ( P =0.010) and was associated with an improvement in event-free survival (hazard ratio, 0.40; 95% confidence interval, 0.22–0.71; P =0.002). Conclusions— A strategy of EG LV lead placement for cardiac resynchronization therapy improved patient outcomes by reducing the combined risk of death or HF hospitalizations and has implications for delivery of cardiac resynchronization therapy. Clinical Trial Registration— URL: . Unique identifier: [NCT00156390][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00156390&atom=%2Fcirchf%2F6%2F3%2F427.atomBackground—Cardiac resynchronization therapy improves mortality and morbidity in patients with heart failure (HF) with wide QRS complex and diminished left ventricular (LV) function, but response is variable. Methods and Results—The Speckle Tracking Assisted Resynchronization Therapy for Electrode Region (STARTER) was a prospective, double-blind, randomized controlled trial testing the hypothesis that an incremental benefit to cardiac resynchronization therapy would be gained by echo-guided (EG) transvenous LV lead placement versus a routine fluoroscopic approach. EG LV lead placement was attempted at the site of latest time to peak radial strain by speckle tracking echocardiography. The prespecified primary end point was first HF hospitalization or death. Of 187 New York Heart Association class II to IV patients with HF (62% ischemic; ejection fraction 26±6%; QRS 159±27 ms), 110 were randomized to EG and 77 to routine strategies. Primary events included 30 deaths and 37 HF hospitalizations over 1.8 years. Using intention-to-treat, patients randomized to an EG strategy had a significantly more favorable event-free survival (hazard ratio, 0.48; 95% confidence interval, 0.28–0.82; P=0.006). Exact or adjacent concordance of LV lead with latest site could be achieved in 85% of the EG group and occurred fortuitously in 66% of controls (P=0.010) and was associated with an improvement in event-free survival (hazard ratio, 0.40; 95% confidence interval, 0.22–0.71; P=0.002). Conclusions—A strategy of EG LV lead placement for cardiac resynchronization therapy improved patient outcomes by reducing the combined risk of death or HF hospitalizations and has implications for delivery of cardiac resynchronization therapy. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00156390.

Usefulness of Baseline Electrocardiographic QRS Complex Pattern to Predict Response to Cardiac Resynchronization

Cardiac resynchronization therapy (CRT) improves morbidity and mortality in patients with heart failure with QRS>120 ms, yet most patients studied in clinical trials manifested baseline left branch bundle block (LBBB). It is unclear whether benefits of CRT extend to patients with right branch bundle block (RBBB) or a paced QRS at baseline despite QRS>120 ms. Orthotopic heart transplantation- and ventricular assist device-free survival, symptomatic response, and echocardiographic response were evaluated in the 636 patients who underwent CRT at our institution from 2000 to 2007 in whom the baseline electrocardiogram showed LBBB (n=412; 65%), paced QRS (n=162; 26%), or RBBB (n=62; 10%). Mortality was assessed using the Social Security Death Index, and the medical record was analyzed for clinical data. A decrease in New York Heart Association class>or=0.5 after >or=6 months of CRT defined symptomatic response. Echocardiographic evidence of improved left ventricular function and reverse remodeling was evaluated after >or=6 months of CRT. Survival free from orthotopic heart transplantation and ventricular assist device placement was best in patients with LBBB and worst in those with RBBB, whereas patients with paced QRS had an intermediate prognosis (p=0.003). This finding remained significant after controlling for baseline differences among the 3 groups. Symptomatic response was observed most often in patients with LBBB (60%), occurred least often in patients with RBBB (14%), and was intermediate in patients with paced QRS (46%; p<0.001). Echocardiographic improvement showed a similar stepwise trend. In conclusion, patients with RBBB undergoing CRT had low rates of symptomatic and echocardiographic response, and their survival free from orthotopic heart transplantation or ventricular assist device placement was significantly worse than in patients with LBBB. Patients with conventionally paced QRS experienced an intermediate response.

The relationship of QRS morphology and mechanical dyssynchrony to long-term outcome following cardiac resynchronization therapy

AIMS Because benefits of cardiac resynchronization therapy (CRT) appear to be less favourable in non-left bundle branch block (LBBB) patients, this prospective longitudinal study tested the hypothesis that QRS morphology and echocardiographic mechanical dyssynchrony were associated with long-term outcome after CRT. METHODS AND RESULTS Two-hundred and seventy-eight consecutive New York Heart Association class III and IV CRT patients with QRS ≥120 ms and ejection fraction ≤35% were studied. The pre-specified primary endpoint was death, heart transplant, or left ventricular assist device over 4 years. Dyssynchrony assessed before CRT included interventricular mechanical delay (IVMD) and speckle-tracking radial strain using pre-specified cut-offs for each. Of 254 with baseline quantitative echocardiographic data available, 128 had LBBB, 81 had intraventricular conduction delay (IVCD), and 45 had right bundle branch block (RBBB). Radial dyssynchrony was observed in 85% of the patients with LBBB, 59% with IVCD*, and 40% with RBBB* (*P < 0.01 vs. LBBB). Of 248 (98%) with follow-up, LBBB patients had a significantly more favourable long-term survival than non-LBBB patients. However, non-LBBB patients with dyssynchrony had a more favourable event-free survival than those without dyssynchrony: radial dyssynchrony hazard ratio 2.6, 95% confidence interval (CI) 1.47-4.53 (P = 0.0008) and IVMD hazard ratio 4.9, 95% CI 2.60-9.16 (P = 0.0007). Right bundle branch block patients who lacked dyssynchrony had the least favourable outcome. CONCLUSION Non-LBBB patients with dyssynchrony had a more favourable long-term survival than non-LBBB patients who lacked dyssynchrony. Mechanical dyssynchrony and QRS morphology are associated with outcome following CRT.

Comparative Mechanical Activation Mapping of RV Pacing to LBBB by 2D and 3D Speckle Tracking and Association With Response to Resynchronization Therapy

OBJECTIVES The goals of this study were to compare patterns of mechanical activation in patients with chronic right ventricular (RV) pacing with those with left bundle branch block (LBBB) using 2-dimensional and novel 3-dimensional speckle tracking, and to compare ejection fraction (EF) response and long-term survival after cardiac resynchronization therapy (CRT). BACKGROUND Several randomized CRT trials have excluded patients with chronic RV pacing, and current guidelines for CRT include patients with intrinsically widened QRS, typically LBBB. METHODS We studied 308 patients who were referred for CRT: 227 had LBBB, 81 were RV paced. Dyssynchrony was assessed by tissue Doppler, routine pulsed Doppler, and 2-dimensional speckle-tracking radial strain. 3D strain was assessed using speckle tracking from a pyramidal dataset in a subset of 57 patients for mechanical activation mapping. Survival after CRT was compared with survival in a group of 46 patients with attempted, but failed, CRT. RESULTS Patients with chronic RV pacing and LBBB had similar intraventricular dyssynchrony, with opposing wall delays by tissue Doppler of 82 +/- 45 ms versus 87 +/- 63 ms and anteroseptum-to-posterior delays by speckle tracking of 225 +/- 142 ms, versus 211 +/- 107 ms, respectively. RV-paced patients, however, had greater interventricular dyssynchrony: 44 +/- 24 ms versus 35 +/- 21 ms (p < 0.01), which correlated with their greater QRS duration (p < 0.001). Sites of latest mechanical activation were most often posterior or lateral in both groups, but RV-paced patients had sites of earliest activation more often from the inferior-septum and apex (p < 0.05). EF response was similar in RV-paced and LBBB groups, and survival free from transplantation or mechanical support after CRT was similarly favorable as compared with failed CRT patients over 5 years (p < 0.01). CONCLUSIONS RV-paced patients, when compared with LBBB patients, had similar dyssynchronous patterns of mechanical activation and greater interventricular dyssynchrony. Importantly, RV-paced patients had similar EF response and long-term outcome as those with LBBB, which supports their candidacy for CRT.

A prospective pilot study to evaluate the relationship between acute change in left ventricular synchrony after cardiac resynchronization therapy and patient outcome using a single-injection gated SPECT protocol.

Background— There are ongoing efforts to optimize patient selection criteria for cardiac resynchronization therapy (CRT). In this regard, the relationship between acute change in left ventricular synchrony (LV) after CRT and patient outcome remains undefined. Methods and Results— A novel protocol was designed to evaluate acute change in left LV synchrony after CRT using phase analysis of standard gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging with a single injection of radiotracer and prospectively applied to 44 patients undergoing CRT. Immediately after CRT, 18 (41%), 11 (25%), and 15 (34%) patients had an improvement, no change, or a worsening in LV synchrony. An algorithm incorporating the presence of baseline dyssynchrony, myocardial scar burden, and lead concordance predicted acute improvement or no change in LV synchrony with 72% sensitivity, 93% specificity, 96% positive predictive value, and 64% negative predictive value and had 96% negative predictive value for acute deterioration in synchrony. Over a follow-up period of 9.6±6.8 months, patients who had an acute deterioration in synchrony after CRT had a higher composite event rate of death, heart failure hospitalizations, appropriate defibrillator discharges, and CRT device deactivation for worsening heart failure symptoms, compared with patients who had an improvement or no change [hazard ratio, 4.6 (1.3 to 16.0); log rank test; P=0.003]. Conclusions— In this single-center pilot study, phase analysis of gated SPECT was successfully used to predict acute change in LV synchrony and patient outcome after CRT.

Fluoroscopic Screening of Asymptomatic Patients Implanted With the Recalled Riata Lead Family

Background— The Food and Drug Administration recently issued a class I recall of the St. Jude Medical Riata implantable cardioverter-defibrillator lead presumably because of increased risk of electric failure and mechanical separation via inside-out abrasion. We sought to examine the incidence and time dependence of inside-out abrasion in asymptomatic patients implanted with the Riata lead. Methods and Results— Asymptomatic patients implanted with the Riata lead at our institution were offered voluntary fluoroscopic screening in 3 views. Electric testing of the Riata lead with provocative isometric muscle contraction was performed at the time of fluoroscopic screening. Of the 245 patients undergoing fluoroscopic screening, 53 (21.6%) patients showed clear evidence of lead separation. Of these externalized leads, 0%, 13%, and 26% had a dwell time of <3 years, 3 to 5 years, and >5 years, respectively (P=0.037). Externalized leads had a significantly pronounced decrease in R-wave amplitude (−1.7±2.9 mV versus +0.35±2.5 mV; P<0.001), and more patients with externalized leads had ≥25% decrease in R-wave amplitude from baseline (28.0% versus 8.1%; P=0.018). One patient with externalization exhibited new noise on near-field electrogram. Conclusions— The Riata lead exhibits time-dependent high rates of cable externalization exceeding 20% at >5 years of dwell time. Externalized leads are associated with a more pronounced decrease in R-wave amplitude, which may be an early marker of future electric failure. The use of fluoroscopic and electric screening of asymptomatic patients with the Riata lead remains controversial in the management of patients affected by the recent Food and Drug Administration recall.

Usefulness of Echocardiographic Dyssynchrony in Patients With Borderline QRS Duration to Assist With Selection for Cardiac Resynchronization Therapy

OBJECTIVES To test the hypothesis that echocardiographic dyssynchrony may assist in the selection of patients with borderline QRS duration for cardiac resynchronization therapy (CRT). BACKGROUND Although echocardiographic dyssynchrony is currently not recommended to select patients with QRS duration widening for CRT, its utility in patients with borderline QRS widening is unclear. METHODS Of 221 consecutive heart failure patients with an ejection fraction (EF) < or =35% referred for CRT, 86 had a borderline QRS duration of 100 to 130 ms (115 +/- 8 ms) and 135 patients had wide QRS >130 ms (168 +/- 26 ms). Dyssynchrony was assessed using interventricular mechanical delay, tissue Doppler imaging longitudinal velocity opposing wall delay, and speckle tracking radial strain for septal to posterior wall delay. Response to CRT was defined as > or =15% increase in EF, and reverse remodeling as > or =10% decrease in end-systolic volume. RESULTS There were 201 patients with baseline quantitative echocardiographic data available, and 187 with follow-up data available 8 +/- 5 months after CRT. A smaller proportion of borderline QRS duration patients (53%) were EF responders compared with 75% with widened QRS (p < 0.05). Interventricular mechanical delay > or =40 ms and opposing wall delay > or =65 ms were predictive of EF response in the wide QRS duration group, but not the borderline QRS duration group. Speckle tracking radial dyssynchrony > or =130 ms, however, was predictive of EF response in both wide QRS interval patients (88% sensitivity, 74% specificity) and borderline QRS interval patients (79% sensitivity, 82% specificity) and associated reverse remodeling with reduction in end-systolic volume (p < 0.0005). CONCLUSIONS Radial dyssynchrony by speckle tracking strain was associated with EF and reverse remodeling response to CRT in patients with borderline QRS duration and has the potential to assist with patient selection.