Tetsuari Onishi

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.

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.

Mechanistic Features Associated With Improvement in Mitral Regurgitation After Cardiac Resynchronization Therapy and Their Relation to Long-Term Patient Outcome

Background—Mechanisms of mitral regurgitation (MR) reduction with cardiac resynchronization therapy (CRT) are complex, and their association with long-term outcome is unclear. We sought to elucidate mechanistic features of reduction in MR with CRT, which impact long-term patient survival. Methods and Results—A prospective longitudinal study of 277 patients with heart failure with QRS width ≥120 ms and ejection fraction ⩽35% for CRT was performed. Quantitative echocardiography, including dyssynchrony analysis, was performed at baseline. MR was quantified by color Doppler before and 6 months after CRT. Predefined end points of death, transplant, or left ventricular assist device were tracked during 4 years. There were 114 (48%) patients with CRT with significant MR (≥moderate) at baseline; of whom 48 (42%) patients had MR improvement, and 24 (19%) patients had MR worsening after CRT. The 66 events (47 deaths, 10 transplantations, and 9 left ventricular assist devices) were strongly associated with significant MR after CRT (hazard ratio, 3.58; 95% confidence interval, 2.18–5.87; P<0.0001). Three echocardiographic features were independently associated with amelioration of significant MR after CRT by multivariable analysis: anteroseptal to posterior wall radial strain dyssynchrony >200 ms, lack of severe left ventricular dilatation (end-systolic dimension index <29 mm/m2), and lack of echocardiographic scar at papillary muscle insertion sites (all P<0.05) and, when combined, were additively associated with long-term survival (P=0.0001). Conclusions—Significant MR after CRT was strongly associated with less favorable long-term survival. Echocardiographic mechanistic features were identified that were associated with improvement in MR after CRT and favorable long-term survival.

Usefulness of Echocardiographically Guided Left Ventricular Lead Placement for Cardiac Resynchronization Therapy in Patients With Intermediate QRS Width and Non–Left Bundle Branch Block Morphology

The current guidelines most strongly support cardiac resynchronization therapy (CRT) for patients with heart failure with a QRS width of ≥150 ms and left bundle branch block (LBBB). Our objective was to assess the potential benefit of echocardiographically guided left ventricular (LV) lead positioning for patients with a QRS width <150 ms or non-LBBB as a substudy of the Speckle Tracking Assisted Resynchronization Therapy for Electrode Region (STARTER) prospective, randomized controlled trial. The STARTER trial randomized 187 patients with heart failure, a QRS of ≥120 ms, and ejection fraction of ≤35% to LV lead guided to the site of latest mechanical activation by speckle tracking radial strain versus routine implantation. The predefined primary end point was heart failure hospitalization or death within 2 years. This substudy included 151 CRT patients with matching echocardiographic and LV lead position data and complete follow-up data. Patients with a QRS width of 120 to 149 ms or non-LBBB and LV lead concordant or adjacent to the site of latest mechanical activation had favorable outcomes after CRT similar to those with LBBB or a QRS width of ≥150 ms. In contrast, patients with a QRS of 120 to 149 ms or non-LBBB and remote LV leads had unfavorable outcomes (hazard ratio 5.45, 95% confidence interval 2.36 to 12.6, p <0.001, and hazard ratio 4.92, 95% confidence interval 2.12 to 11.39, p <0.001, respectively, with significant interaction after adjusting for baseline variables, p = 0.038 and p = 0.008). In conclusion, LV lead positioning with respect to the echocardiographic site of latest activation was significantly associated with more favorable clinical outcomes in patients with a QRS duration <150 ms and/or non-LBBB. Additional prospective study is warranted.

Mechanistic Features Associated with Improvement in Mitral Regurgitation Following Cardiac Resynchronization Therapy and Their Relation to Long Term Patient Outcome

Background—Mechanisms of mitral regurgitation (MR) reduction with cardiac resynchronization therapy (CRT) are complex, and their association with long-term outcome is unclear. We sought to elucidate mechanistic features of reduction in MR with CRT, which impact long-term patient survival. Methods and Results—A prospective longitudinal study of 277 patients with heart failure with QRS width ≥120 ms and ejection fraction ⩽35% for CRT was performed. Quantitative echocardiography, including dyssynchrony analysis, was performed at baseline. MR was quantified by color Doppler before and 6 months after CRT. Predefined end points of death, transplant, or left ventricular assist device were tracked during 4 years. There were 114 (48%) patients with CRT with significant MR (≥moderate) at baseline; of whom 48 (42%) patients had MR improvement, and 24 (19%) patients had MR worsening after CRT. The 66 events (47 deaths, 10 transplantations, and 9 left ventricular assist devices) were strongly associated with significant MR after CRT (hazard ratio, 3.58; 95% confidence interval, 2.18–5.87; P<0.0001). Three echocardiographic features were independently associated with amelioration of significant MR after CRT by multivariable analysis: anteroseptal to posterior wall radial strain dyssynchrony >200 ms, lack of severe left ventricular dilatation (end-systolic dimension index <29 mm/m2), and lack of echocardiographic scar at papillary muscle insertion sites (all P<0.05) and, when combined, were additively associated with long-term survival (P=0.0001). Conclusions—Significant MR after CRT was strongly associated with less favorable long-term survival. Echocardiographic mechanistic features were identified that were associated with improvement in MR after CRT and favorable long-term survival.

Characterization of Right Ventricular Remodeling in Pulmonary Hypertension Associated With Patient Outcomes by 3-Dimensional Wall Motion Tracking Echocardiography

Background—Adverse right ventricular (RV) remodeling has significant prognostic and therapeutic implications to patients with pulmonary hypertension (PH). However, differentiating RV adaption from adverse remodeling associated with poor outcomes is difficult. We hypothesized that novel 3-dimensional (3D) wall motion tracking echocardiography can differentiate morphological features of RV adaption from adverse remodeling heralding an unfavorable short-term prognosis in patients with PH. Methods and Results—We studied 112 subjects: 92 patients with PH and 20 normal controls with 3D wall motion tracking for RV end-systolic volume index (ESVi), RV ejection fraction (EF), and RV global area strain. Patients with PH also had invasive hemodynamic measurements. Pressure–volume relations classified patients with PH into 3 groups, such as RV adapted, RV adapted–remodeled, and RV adverse–remodeled. The predefined combined end point was PH-related hospitalization, death, or lung surgery (lung transplantation or pulmonary endarterectomy) during 6 months. The 92 patients with PH had significantly larger RV volumes, lower RVEF and global area strain than normal controls as expected. Patients with PH classified as RV adapted (ESVi, ⩽72 mL/m2) had a more favorable clinical outcome than those classified as RV adapted–remodeled (ESVi, 73–113 mL/m2) or RV adverse–remodeled (ESVi, ≥114 mL/m2): hazard ratio, 0.15; 95% confidence intervals, 0.07 to 0.39; P<0.0001. RV adverse–remodeled patients (ESVi, ≥114 mL/m2) had worse short-term outcome than the RV adapted–remodeled patients: hazard ratio, 2.2; 95% confidence interval, 0.91 to 5.39; P=0.04. Conclusions—Quantitative 3D echocardiography in patients with PH demonstrated morphological subsets of RV adaption and remodeling associated with clinical outcomes.

The Contemporary Role of Echocardiography in Improving Patient Response to Cardiac Resynchronization Therapy

Cardiac resynchronization therapy (CRT) is an important therapy for heart failure patients with widened electrocardiographic QRS complexes and depressed ejection fractions, however, approximately one-third do not respond. This article presents a practical contemporary approach to the utility of echocardiography to improve CRT patient response by assessing mechanical dyssynchrony, optimizing left ventricular lead positioning, and performing appropriate echo-Doppler optimization, along with future potential roles. Specifically, recent long-term outcome data are presented that demonstrates that baseline dyssynchrony is a powerful marker associated with CRT response, in particular for patients with narrower QRS duration or non left bundle branch block morphology. Advances in speckle tracking echocardiography to tailor delivery of CRT by guiding LV lead position is discussed, including data from randomized clinical trials supporting targeting the LV lead toward the site of latest activation. In addition, an update on the current role of Doppler echocardiographic device optimization after CRT implantation is reviewed.

Echocardiography-Guided Left Ventricular Lead Placement for Cardiac Resynchronization Therapy

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.

A SIMPLIFIED FORMULA FOR ESTIMATION OF EJECTION FRACTION FROM SPECKLE TRACKING ECHOCARDIOGRAPHIC GLOBAL STRAIN: COMPARISON WITH CARDIAC MAGNETIC RESONANCE

Global strain by speckle tracking echocardiography (STE) is emerging as a reproducible quantitative means to assess left ventricular function. Our aim was to determine a simplified formula to estimate ejection fraction (EF), using cardiac magnetic resonance (CMR) for comparison. We studied 80

HE UTILITY OF A NOVEL OFF-LINE APPROACH TO QUANTIFY DYSSYNCHRONY FROM ROUTINE CARDIAC MAGNETIC RESONANCE IMAGES: COMPARISON WITH ECHOCARDIOGRAPHIC SPECKLE TRACKING

Methods: We studied 50 consecutive pts who had both CMR and echo with a wide range of QRS width and ejection fractions (EF). Mid-LV short axis CMR images were analyzed from routine DICOM data sets using a novel software program (Image-Arena VA, TomTec, Corp) and compared with similar short axis echo images for speckle tracking radial strain (TomTec, Corp). Radial dyssynchrony was deined as the time difference between the anteroseptal and posterior wall peak strain.