Claudia Ypenburg

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.

Relative Merits of Left Ventricular Dyssynchrony, Left Ventricular Lead Position, and Myocardial Scar to Predict Long-Term Survival of Ischemic Heart Failure Patients Undergoing Cardiac Resynchronization Therapy

Background— The relative merits of left ventricular (LV) dyssynchrony, LV lead position, and myocardial scar to predict long-term outcome after cardiac resynchronization therapy remain unknown and were evaluated in the present study. Methods and Results— In 397 ischemic heart failure patients, 2-dimensional speckle tracking imaging was performed, with comprehensive assessment of LV radial dyssynchrony, identification of the segment with latest mechanical activation, and detection of myocardial scar in the segment where the LV lead was positioned. For LV dyssynchrony, a cutoff value of 130 milliseconds was used. Segments with <16.5% radial strain in the region of the LV pacing lead were considered to have extensive myocardial scar (>50% transmurality, validated in a subgroup with contrast-enhanced magnetic resonance imaging). The LV lead position was derived from chest x-ray. Long-term follow-up included all-cause mortality and hospitalizations for heart failure. Mean baseline LV radial dyssynchrony was 133±98 milliseconds. In 271 patients (68%), the LV lead was placed at the latest activated segment (concordant LV lead position), and the mean value of peak radial strain at the targeted segment was 18.9±12.6%. Larger LV radial dyssynchrony at baseline was an independent predictor of superior long-term survival (hazard ratio, 0.995; P=0.001), whereas a discordant LV lead position (hazard ratio, 2.086; P=0.001) and myocardial scar in the segment targeted by the LV lead (hazard ratio, 2.913; P<0.001) were independent predictors of worse outcome. Addition of these 3 parameters yielded incremental prognostic value over the combination of clinical parameters. Conclusions— Baseline LV radial dyssynchrony, discordant LV lead position, and myocardial scar in the region of the LV pacing lead were independent determinants of long-term prognosis in ischemic heart failure patients treated with cardiac resynchronization therapy. Larger baseline LV dyssynchrony predicted superior long-term survival, whereas discordant LV lead position and myocardial scar predicted worse outcome.

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.

Relation between global left ventricular longitudinal strain assessed with novel automated function imaging and biplane left ventricular ejection fraction in patients with coronary artery disease.

OBJECTIVE Automated function imaging (AFI) is a novel algorithm based on speckle-tracking imaging that can be used for assessment of global longitudinal strain of the left ventricle. The purpose of this study was to evaluate the relation between global longitudinal peak systolic strain average (GLPSS Avg) assessed by AFI and left ventricular ejection fraction (LVEF). METHODS The study population consisted of 222 consecutive patients with coronary artery disease (99 patients with acute ST-segment elevation myocardial infarction [STEMI] and 123 patients with advanced ischemic heart failure) and 20 age-matched controls. LVEF was calculated by Simpsons rule. The GLPSS Avg was obtained by AFI. RESULTS In the overall study group (65 +/- 10 years, 77% were men), mean GLPSS Avg was 11.1% +/- 4.8% and mean LVEF was 37% +/- 14%. Linear regression analysis showed a good correlation between GLPSS Avg and biplane LVEF for the overall study population (r = 0.83; P < .001). However, in patients with STEMI or heart failure the correlations were less strong (r = 0.42 and r = 0.62, both P < .001). CONCLUSION Systolic global longitudinal strain assessed by AFI was linearly related to biplane LVEF. In patients with STEMI or heart failure, less strong correlations were observed, suggesting that these 2 parameters reflect different aspects of systolic left ventricular function.

Magnetic resonance imaging and response to cardiac resynchronization therapy: relative merits of left ventricular dyssynchrony and scar tissue

AIM To assess the relative value of a novel measure of left ventricular (LV) dyssynchrony derived from magnetic resonance imaging (MRI) and the extent of scar tissue for prediction of response to cardiac resynchronization therapy (CRT). METHODS AND RESULTS Thirty-five heart failure patients scheduled for CRT were included. Left ventricular dyssynchrony was defined as the standard deviation of 16 segment time-to-maximum radial wall thickness (SDt-16) obtained from a cine-set of short-axis slices. Delayed-enhanced MRI was performed for scar analysis. Echocardiography was used to determine response to CRT (reduction > or =15% in LV end-systolic volume 6 months after implantation). At follow-up, 21 patients (60%) were classified as responders. On MRI, SDt-16 was significantly higher in responders compared with non-responders (median 97 vs. 60 ms, P < 0.001), whereas the total extent of scar was larger in non-responders (median 35% vs. 3% in responders, P < 0.001). At the logistic regression analysis, SDt-16 was directly associated (OR = 6.3, 95% CI 3.1-9.9, P < 0.001) and the total extent of scar was inversely associated (OR = 0.52, 95% CI 0.43-0.87, P < 0.001) with response to CRT. CONCLUSION Magnetic resonance imaging offers the unique opportunity to assess LV dyssynchrony and scar extent in a single session. Both these parameters are important predictors of echocardiographic response to 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.

Quantitative Gated SPECT–Derived Phase Analysis on Gated Myocardial Perfusion SPECT Detects Left Ventricular Dyssynchrony and Predicts Response to Cardiac Resynchronization Therapy

The significance of left ventricular (LV) dyssynchrony for the prediction of response to cardiac resynchronization therapy (CRT) has been demonstrated. Parameters reflecting LV dyssynchrony (phase SD, histogram bandwidth) can be derived from gated myocardial perfusion SPECT (GMPS) using phase analysis. The feasibility of LV dyssynchrony assessment with phase analysis on GMPS using Quantitative Gated SPECT (QGS) software has not been demonstrated in patients undergoing CRT. The aim of the present study was to validate the QGS algorithm for phase analysis on GMPS in a direct comparison with echocardiography using tissue Doppler imaging (TDI) for LV dyssynchrony assessment. Also, prediction of response to CRT using GMPS and phase analysis was evaluated. Methods: Patients (n = 40) with severe heart failure (New York Heart Association class III–IV), an LV ejection fraction of no more than 35%, and a QRS complex greater than or equal to 120 ms were evaluated for LV dyssynchrony using GMPS and echocardiography with TDI. At baseline and after 6 mo of CRT, clinical status, LV volumes, and LV ejection fraction were evaluated. Patients with functional improvement were classified as CRT responders. Results: Both histogram bandwidth (r = 0.69, r2 = 0.48, SEE = 25.4, P < 0.01) and phase SD (r = 0.65, r2 = 0.42, SEE = 26.8, P < 0.01) derived from GMPS correlated significantly with TDI for assessment of LV dyssynchrony. At baseline, CRT responders showed a significantly larger histogram bandwidth (94° ± 23° vs. 68° ± 21°, P < 0.01) and a larger phase SD (26° ± 6° vs. 18° ± 5°, P < 0.01) than did nonresponders. Receiver-operating-characteristic curve analysis identified an optimal cutoff value of 72.5° for histogram bandwidth to predict CRT response, yielding a sensitivity of 83% and a specificity of 81%. For phase SD, sensitivity and specificity similar to those for histogram bandwidth were obtained at a cutoff value of 19.6°. Conclusion: QGS phase analysis on GMPS correlated significantly with TDI for the assessment of LV dyssynchrony. Moreover, a high accuracy for prediction of response to CRT was obtained using either histogram bandwidth or phase SD.