Gabe B. Bleeker

Effect of Posterolateral Scar Tissue on Clinical and Echocardiographic Improvement After Cardiac Resynchronization Therapy

Background— Currently, one third of patients treated with cardiac resynchronization therapy (CRT) do not respond. Nonresponse to CRT may be explained by the presence of scar tissue in the posterolateral left ventricular (LV) segments, which may result in ineffective LV pacing and inadequate LV resynchronization. In the present study, the relationship between transmural posterolateral scar tissue and response to CRT was evaluated. Methods and Results— Forty consecutive patients with end-stage heart failure (NYHA class III/IV), LV ejection fraction ≤35%, QRS duration >120 ms, left bundle-branch block, and chronic coronary artery disease were included. The localization and transmurality of scar tissue were evaluated with contrast-enhanced MRI. Next, LV dyssynchrony was assessed at baseline and immediately after implantation with tissue Doppler imaging. Clinical parameters, LV volumes, and LV ejection fraction were assessed at baseline and at a 6-month follow-up. Fourteen patients (35%) had a transmural (>50% of LV wall thickness) posterolateral scar. In contrast to patients without posterolateral scar tissue, these patients showed a low response rate (14% versus 81%; P<0.05) and did not show improvement in clinical or echocardiographic parameters. In addition, LV dyssynchrony remained unchanged after CRT implantation (84±46 versus 78±41 ms; P=NS). Patients without posterolateral scar tissue and severe baseline dyssynchrony (≥65 ms) showed an excellent response rate of 95% compared with patients with a posterolateral scar and/or absent LV dyssynchrony (11%). Conclusions— CRT does not reduce LV dyssynchrony in patients with transmural scar tissue in the posterolateral LV segments, resulting in clinical and echocardiographic nonresponse to CRT.

Optimal Left Ventricular Lead Position Predicts Reverse Remodeling and Survival After Cardiac Resynchronization Therapy

OBJECTIVES The aim of the current study was to evaluate echocardiographic parameters after 6 months of cardiac resynchronization therapy (CRT) as well as long-term outcome in patients with the left ventricular (LV) lead positioned at the site of latest activation (concordant LV lead position) as compared with that seen in patients with a discordant LV lead position. BACKGROUND A nonoptimal LV pacing lead position may be a potential cause for nonresponse to CRT. METHODS The site of latest mechanical activation was determined by speckle tracking radial strain analysis and related to the LV lead position on chest X-ray in 244 CRT candidates. Echocardiographic evaluation was performed after 6 months. Long-term follow-up included all-cause mortality and hospitalizations for heart failure. RESULTS Significant LV reverse remodeling (reduction in LV end-systolic volume from 189 +/- 83 ml to 134 +/- 71 ml, p < 0.001) was noted in the group of patients with a concordant LV lead position (n = 153, 63%), whereas patients with a discordant lead position showed no significant improvements. In addition, during long-term follow-up (32 +/- 16 months), less events (combined for heart failure hospitalizations and death) were reported in patients with a concordant LV lead position. Moreover, a concordant LV lead position appeared to be an independent predictor of hospitalization-free survival after long-term CRT (hazard ratio: 0.22, p = 0.004). CONCLUSIONS Pacing at the site of latest mechanical activation, as determined by speckle tracking radial strain analysis, resulted in superior echocardiographic response after 6 months of CRT and better prognosis during long-term follow-up.

Assessment of left ventricular dyssynchrony by speckle tracking strain imaging comparison between longitudinal, circumferential, and radial strain in cardiac resynchronization therapy.

OBJECTIVES The objective of this study was to assess the usefulness of each type of strain for left ventricular (LV) dyssynchrony assessment and its predictive value for a positive response after cardiac resynchronization therapy (CRT). Furthermore, changes in extent of LV dyssynchrony for each type of strain were evaluated during follow-up. BACKGROUND Different echocardiographic techniques have been proposed for assessment of LV dyssynchrony. The novel 2-dimensional (2D) speckle tracking strain analysis technique can provide information on radial strain (RS), circumferential strain (CS), and longitudinal strain (LS). METHODS In 161 patients, 2D echocardiography was performed at baseline and after 6 months of CRT. Extent of LV dyssynchrony was calculated for each type of strain. Response to CRT was defined as a decrease in LV end-systolic volume >/=15% at follow-up. RESULTS At follow-up, 88 patients (55%) were classified as responders. Differences in baseline LV dyssynchrony between responders and nonresponders were noted only for RS (251 +/- 138 ms vs. 94 +/- 65 ms; p < 0.001), whereas no differences were noted for CS and LS. A cut-off value of radial dyssynchrony >/=130 ms was able to predict response to CRT with a sensitivity of 83% and a specificity of 80%. In addition, a significant decrease in extent of LV dyssynchrony measured with RS (from 251 +/- 138 ms to 98 +/- 92 ms; p < 0.001) was demonstrated only in responders. CONCLUSIONS Speckle tracking radial strain analysis constitutes the best method to identify potential responders to CRT. Reduction in LV dyssynchrony after CRT was only noted in responders.

Long-term prognosis after cardiac resynchronization therapy is related to the extent of left ventricular reverse remodeling at midterm follow-up.

OBJECTIVES The aim of the current study was to evaluate the relation between the extent of left ventricular (LV) reverse remodeling and clinical/echocardiographic improvement after 6 months of cardiac resynchronization therapy (CRT) as well as long-term outcome. BACKGROUND Despite the current selection criteria, individual response to CRT varies significantly. Furthermore, it has been suggested that reduction in left ventricular end-systolic volume (LVESV) after CRT is related to outcome. METHODS A total of 302 CRT candidates were included. Clinical status and echocardiographic evaluation were performed before implantation and after 6 months of CRT. Long-term follow-up included all-cause mortality and hospitalizations for heart failure. RESULTS Based on different extents of LV reverse remodeling, 22% of patients were classified as super-responders (decrease in LVESV > or =30%), 35% as responders (decrease in LVESV 15% to 29%), 21% as nonresponders (decrease in LVESV 0% to 14%), and 22% negative responders (increase in LVESV). More extensive LV reverse remodeling resulted in more clinical improvement, with a larger increase in LV function and more reduction in mitral regurgitation. In addition, more LV reverse remodeling resulted in less heart failure hospitalizations and lower mortality during long-term follow-up (22 +/- 11 months); 1- and 2-year hospitalization-free survival rates were 90% and 70% in the negative responder group compared with 98% and 96% in the super-responder group (log-rank p value <0.001). CONCLUSIONS The extent of LV reverse remodeling at midterm follow-up is predictive for long-term outcome in CRT patients.

Can LV Dyssynchrony as Assessed with Phase Analysis on Gated Myocardial Perfusion SPECT Predict Response to CRT

Cardiac resynchronization therapy (CRT) is now a well-recognized therapeutic option for patients with end-stage heart failure. However, not all patients respond to CRT, and, therefore, preimplantation identification of responders is desirable. The aim of the present study was to investigate whether the degree of left ventricular (LV) dyssynchrony, as assessed with phase analysis from gated myocardial perfusion SPECT (GMPS), can predict which patients will respond to CRT. Methods: Forty-two patients with severe heart failure, depressed LV ejection fraction, and wide QRS complex were prospectively included for implantation of a CRT device and underwent GMPS and 2-dimensional echocardiography as part of the clinical protocol. Clinical status was evaluated using the New York Heart Association (NYHA) classification, 6-min walk test, and quality-of-life score. The histogram bandwidth and phase SD (parameters indicating LV dyssynchrony) were assessed from GMPS, and the clinical status and echocardiographic variables were reassessed at 6-mo follow-up. Results: Responders (71%) and nonresponders (29%) had comparable baseline characteristics, except for histogram bandwidth (175° ± 63° vs. 117° ± 51° [P < 0.01]) and phase SD (56.3° ± 19.9° vs. 37°.1 ± 14.4° [P < 0.01]), which were significantly larger in responders compared with nonresponders. Moreover, receiver-operating-characteristic curve analysis demonstrated an optimal cutoff value of 135° for histogram bandwidth (sensitivity and specificity of 70%) and of 43° for phase SD (sensitivity and specificity of 74%) for the prediction of response to CRT. Conclusion: Response to CRT is related to the presence of LV dyssynchrony assessed by phase analysis with GMPS. A cutoff value of 135° for histogram bandwidth and of 43° for phase SD could be used to predict response to CRT. Larger prospective studies are warranted to confirm the present findings.

Left Ventricular Resynchronization Is Mandatory for Response to Cardiac Resynchronization Therapy: Analysis in Patients With Echocardiographic Evidence of Left Ventricular Dyssynchrony at Baseline

Background— Recent studies have demonstrated that a positive response to cardiac resynchronization therapy (CRT) is related to the presence of preimplantation left ventricular (LV) dyssynchrony. The time course and the extent of LV resynchronization after CRT implantation and their relationship to response are currently unknown. Methods and Results— One hundred consecutive patients scheduled for implantation of a CRT device were prospectively included if they met the following criteria: New York Heart Association class III to IV, LV ejection fraction ≤35%, QRS duration >120 ms, and LV dyssynchrony (≥65 ms) on color-coded tissue Doppler imaging. Immediately after CRT implantation, LV dyssynchrony was reduced from 114±36 to 40±33 ms (P<0.001), which persisted at the 6-month follow-up (35±31 ms; P<0.001 versus baseline; P=0.14 versus immediately after implantation). At the 6-month follow-up, 85% of patients were classified as responders to CRT (defined as >10% reduction in LV end-systolic volume). Immediately after implantation, the responders to CRT demonstrated a significant reduction in LV dyssynchrony from 115±37 to 32±23 ms (P<0.001). The nonresponders, however, did not show a significant reduction in LV dyssynchrony (106±29 versus 79±44 ms; P=0.08). If the extent of acute LV resynchronization was <20%, response to CRT at the 6-month follow-up was never observed. Conversely, 93% of patients with LV resynchronization ≥20% responded to CRT. Conclusions— LV resynchronization after CRT is an acute phenomenon and predicts response to CRT at 6-month follow-up in patients with echocardiographic evidence of LV dyssynchrony at baseline.

Hemodynamic Effects of Long-Term Cardiac Resynchronization Therapy Analysis by Pressure-Volume Loops

Background— Acute hemodynamic effects of cardiac resynchronization therapy (CRT) were reported previously, but detailed invasive studies showing hemodynamic consequences of long-term CRT are not available. Methods and Results— We studied 22 patients scheduled for implantation of a CRT device based on conventional criteria (New York Heart Association class III or IV, left ventricular [LV] ejection fraction <35%, left bundle-branch block, and QRS duration >120 ms). During diagnostic catheterization before CRT, we acquired pressure-volume loops using conductance catheters during atrial pacing at 80, 100, 120, and 140 bpm. Studies were repeated during biventricular pacing at the same heart rates after 6 months of CRT. Our data show a significant clinical benefit of CRT (New York Heart Association class change from 3.1±0.5 to 2.1±0.8; quality-of-life score change from 44±12 to 31±16; and 6-minute hall-walk distance increased from 260±149 to 396±129 m; all P<0.001), improved LV ejection fraction (from 29±10% to 40±13%, P<0.01), decreased end-diastolic pressure (from 18±8 to 13±6 mm Hg, P<0.05), and reverse remodeling (end-diastolic volume decreased from 257±67 to 205±54 mL, P<0.01). Previously reported acute improvements in LV function remained present at 6 months: dP/dtmax increased 18%, −dP/dtmin increased 13%, and stroke work increased 34% (all P<0.01). Effects of increased heart rate were improved toward more physiological responses for LV ejection fraction, cardiac output, and dP/dtmax. Moreover, our study showed improved ventricular-arterial coupling (69% increase, P<0.01) and improved mechanical efficiency (44% increase, P<0.01). Conclusions— Hemodynamic improvements with CRT, previously shown in acute invasive studies, are maintained chronically. In addition, ventricular-arterial coupling, mechanical efficiency, and chronotropic responses are improved after 6 months of CRT. These findings may help to explain the improved functional status and exercise tolerance in patients treated with CRT.

Real‐Time Three‐Dimensional Echocardiography Permits Quantification of Left Ventricular Mechanical Dyssynchrony and Predicts Acute Response to Cardiac Resynchronization Therapy

Objective: To evaluate the value of real‐time three‐dimensional echocardiography (RT3DE) to predict acute response to cardiac resynchronization therapy (CRT).

Mechanism of improvement in mitral regurgitation after cardiac resynchronization therapy

AIMS The aim of the current study was to evaluate the relationship between the presence of left ventricular (LV) dyssynchrony at baseline and acute vs. late improvement in mitral regurgitation (MR) after cardiac resynchronization therapy (CRT). METHODS AND RESULTS Sixty eight patients consecutive (LV ejection fraction 23 +/- 8%) with at least moderate MR (>or=grade 2+) were included. Echocardiography was performed at baseline, 1 day after CRT initiation and at 6 months follow-up. Speckle tracking radial strain was used to assess LV dyssynchrony at baseline. The majority of patients improved in MR after CRT, with 43% improving immediately after CRT, and 20% improving late (after 6 months) after CRT. Early and late responders had similar extent of LV dyssynchrony (209 +/- 115 ms vs. 190 +/- 118 ms, P = NS); however, the site of latest activation in early responders was mostly inferior or posterior (adjacent to the posterior papillary muscle), whereas the lateral wall was the latest activated segment in late responders. CONCLUSION Current data suggest that the presence of baseline LV dyssynchrony is related to improvement in MR after CRT. LV dyssynchrony involving the posterior papillary muscle may lead to an immediate reduction in MR, whereas LV dyssynchrony in the lateral wall resulted in late response to CRT.

Real-Time Three-Dimensional Echocardiography as a Novel Approach to Quantify Left Ventricular Dyssynchrony: A Comparison Study with Phase Analysis of Gated Myocardial Perfusion Single Photon Emission Computed Tomography

BACKGROUND Different imaging modalities have been explored for assessment of left ventricular (LV) dyssynchrony. Gated myocardial perfusion single photon emission computed tomography (GMPS) with phase analysis is a reliable technique to quantify LV dyssynchrony and predict response to cardiac resynchronization therapy. OBJECTIVE Real-time 3-dimensional echocardiography (RT3DE) is a novel imaging technique that provides a LV systolic dyssynchrony index, based on regional volumetric changes as a function of time and calculated as the SD of time to minimum systolic volume of 16 standard myocardial segments expressed in percentage of cardiac cycle. The aim of this study was to compare LV dyssynchrony evaluated with GMPS with LV dyssynchrony assessed with RT3DE. METHODS The study population consisted of 40 patients with heart failure who underwent both GMPS and RT3DE. RESULTS Good correlations between LV dyssynchrony assessed with RT3DE and GMPS were demonstrated (r = 0.76 for histogram bandwidth, r = 0.80 for phase SD, P < .0001). Patients with substantial LV dyssynchrony on GMPS (defined as > or = 135 degrees for histogram bandwidth and > or = 43 degrees for phase SD) had significantly higher LV systolic dyssynchrony index than patients without substantial LV dyssynchrony. CONCLUSIONS The good correlations between LV dyssynchrony assessed with GMPS and with RT3DE provide further support for the use of RT3DE for reliable assessment of LV dyssynchrony.