Hidekazu Tanaka

Echocardiographic Assessment of Myocardial Strain

Echocardiographic strain imaging, also known as deformation imaging, has been developed as a means to objectively quantify regional myocardial function. First introduced as post-processing of tissue Doppler imaging velocity converted to strain and strain rate, strain imaging has more recently also been derived from digital speckle tracking analysis. Strain imaging has been used to gain greater understanding into the pathophysiology of cardiac ischemia and infarction, primary diseases of the myocardium, and the effects of valvular disease on myocardial function, and to advance our understanding of diastolic function. Strain imaging has also been used to quantify abnormalities in the timing of mechanical activation for heart failure patients undergoing cardiac resynchronization pacing therapy. Further advances, such as 3-dimensional speckle tracking strain imaging, have emerged to provide even greater insight. Strain imaging has become established as a robust research tool and has great potential to play many roles in routine clinical practice to advance the care of the cardiovascular patient. This perspective reviews the physiology of myocardial strain, the technical features of strain imaging using tissue Doppler imaging and speckle tracking, their strengths and weaknesses, and the state-of-the-art present and potential future clinical applications.

Dyssynchrony by speckle-tracking echocardiography and response to cardiac resynchronization therapy: results of the Speckle Tracking and Resynchronization (STAR) study

Aims The Speckle Tracking and Resynchronization (STAR) study used a prospective multi-centre design to test the hypothesis that speckle-tracking echocardiography can predict response to cardiac resynchronization therapy (CRT). Methods and results We studied 132 consecutive CRT patients with class III and IV heart failure, ejection fraction (EF) ≤35%, and QRS ≥120 ms from three international centres. Baseline dyssynchrony was evaluated by four speckle tracking strain methods; radial, circumferential, transverse, and longitudinal (≥130 ms opposing wall delay for each). Pre-specified outcome variables were EF response and three serious long-term events: death, transplant, or left ventricular assist device. Of 120 patients (91%) with baseline dyssynchrony data, both short-axis radial strain and transverse strain from apical views were associated with favourable EF response 7 ± 4 months and long-term outcome over 3.5 years (P < 0.01). Radial strain had the highest sensitivity at 86% for predicting EF response with a specificity of 67%. Serious long-term unfavourable events occurred in 20 patients after CRT, and happened three times more frequently in those who lacked baseline radial or transverse dyssynchrony than in patients with dyssynchrony (P < 0.01). Patients who lacked both radial and transverse dyssynchrony had unfavourable clinical events occur in 53%, in contrast to events occurring in 12% if baseline dyssynchrony was present (P < 0.01). Circumferential and longitudinal strains predicted response when dyssynchrony was detected, but failed to identify dyssynchrony in one-third of patients who responded to CRT. Conclusion Dyssynchrony by speckle-tracking echocardiography using radial and transverse strains is associated with EF response and long-term outcome following CRT.

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.

Usefulness of three-dimensional speckle tracking strain to quantify dyssynchrony and the site of latest mechanical activation.

Previous methods to quantify dyssynchrony could not determine regional 3-dimensional (3-D) strain. We hypothesized that a novel 3-D speckle tracking strain imaging system can quantify left ventricular (LV) dyssynchrony and site of latest mechanical activation. We studied 64 subjects; 54 patients with heart failure were referred for cardiac resynchronization therapy (CRT) with an ejection fraction 25 +/- 6% and QRS interval 165 +/- 29 ms and 10 healthy volunteer controls. The 3-D speckle tracking system determined radial strain using a 16-segment model from a pyramidal 3-D dataset. Dyssynchrony was quantified as maximal opposing wall delay and SD in time to peak strain. The 3-D analysis was compared to standard 2-dimensional (2-D) strain datasets and site of 3-D latest mechanical activation, not possible by 2D was quantified. As expected, dyssynchrony in patients on CRT was significantly greater than in controls (maximal opposing wall delay 316 +/- 112 vs 59 +/- 12 ms and SD 124 +/- 48 vs 28 +/- 11 ms, p <0.001 vs normal). The 3-D opposing wall delay was closely correlated with 3-D 16-segment SD (r = 0.95) and 2-D mid-LV strain (r = 0.83) and SD (r = 0.85, all p values <0.001). The 3-D site of the latest mechanical activation was most commonly midposterior (26%), basal posterior (22%), midlateral (20%), and basal lateral (17%). Eleven patients studied after CRT demonstrated improvements in 3-D synchrony (300 +/- 124 to 94 +/- 37 ms) and ejection fraction (24 +/- 6% to 31 +/- 7%, p <0.05). In conclusion, 3-D speckle tracking can successfully quantify 3-D dyssynchrony and site the latest mechanical activation. This approach may play a clinical role in management of patients on CRT.

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.

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.

Echocardiographic Speckle Tracking Radial Strain Imaging to Assess Ventricular Dyssynchrony in a Pacing Model of Resynchronization Therapy

BACKGROUND Speckle tracking imaging is a promising new echocardiographic method to assess left ventricular (LV) mechanical dyssynchrony. Our aim was to assess a new speckle tracking regional strain algorithm by comparison with angle-corrected tissue Doppler (TD) in an animal model of left bundle branch block and cardiac resynchronization therapy. METHODS AND RESULTS Ten open-chest dogs had routine gray-scale and TD images of the mid-LV short-axis plane. Electrical activation was altered by pacing from right ventricular, LV free wall, and biventricular sites to create various degrees of mechanical dyssynchrony and alter regional function. Segmental time to peak strain, peak strain, and frame-by-frame strain were measured by angle-corrected TD, TD M-mode, and speckle tracking on the same digital cineloop. Of 240 possible paired TD and speckle tracking segments, data were available for 222 segments (93%); images with catheter artifacts were prospectively excluded. Comparative overall time to peak strain by each method correlated well: r = 0.96, bias = -6 +/- 20 ms. Of 80 possible paired M-mode TD and speckle tracking segments, strain data were available for 76 segments (95%). Comparative overall time to peak strain, peak strain, and frame-by-frame strain analysis in 1012 frames by each method correlated well: r = 0.98, bias of 1 +/- 14 ms; r = 0.82, bias of 3% +/- 7%; and r = 0.91, bias of 0% +/- 6%, respectively. CONCLUSION Regional strain analysis using echocardiographic speckle tracking radial strain strongly correlated with strain by angle-corrected TD imaging in an animal model of dyssynchrony. Speckle tracking radial strain has potential for clinical applications.

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.

Association of intraventricular mechanical dyssynchrony with response to cardiac resynchronization therapy in heart failure patients with a narrow QRS complex

Aims Current criteria for cardiac resynchronization therapy (CRT) are restricted to patients with a wide QRS complex (>120 ms). Overall, only 30% of heart failure patients demonstrate a wide QRS complex, leaving the majority of heart failure patients without this treatment option. However, patients with a narrow QRS complex exhibit left ventricular (LV) mechanical dyssynchrony, as assessed with echocardiography. To further elucidate the possible beneficial effect of CRT in heart failure patients with a narrow QRS complex, this two-centre, non-randomized observational study focused on different echocardiographic parameters of LV mechanical dyssynchrony reflecting atrioventricular, interventricular and intraventricular dyssynchrony, and the response to CRT in these patients. Methods and results A total of 123 consecutive heart failure patients with a narrow QRS complex (<120 ms) undergoing CRT was included at two centres. Several widely accepted measures of mechanical dyssynchrony were evaluated: LV filling ratio (LVFT/RR), LV pre-ejection time (LPEI), interventricular mechanical dyssynchrony (IVMD), opposing wall delay (OWD), and anteroseptal posterior wall delay with speckle tracking (ASPWD). Response to CRT was defined as a reduction ≥15% in left ventricular end-systolic volume at 6 months follow-up. Measures of dyssynchrony can frequently be observed in patients with a narrow QRS complex. Nonetheless, for LVFT/RR, LPEI, and IVMD, presence of predefined significant dyssynchrony is <20%. Significant intraventricular dyssynchrony is more widely observed in these patients. With receiver operator characteristic curve analyses, both OWD and ASPWD demonstrated usefulness in predicting response to CRT in narrow QRS patients with a cut-off value of 75 and 107 ms, respectively. Conclusion Mechanical dyssynchrony can be widely observed in heart failure patients with a narrow QRS complex. In particular, intraventricular measures of mechanical dyssynchrony may be useful in predicting LV reverse remodelling at 6 months follow-up in heart failure patients with a narrow QRS complex, but with more stringent cut-off values than currently used in ‘wide’ QRS patients.