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Background: Clinical or echocardiographic mid-term responses to cardiac resynchronization therapy (CRT) may have a different influence on a long-term prognosis of heart failure patients treated with CRT. The aim of the evaluation was to establish which definition of response to CRT, clinical or echocardiographic, best predicts long-term prognosis., Methods and Results: A total of 679 heart failure patients treated with CRT were included. All the patients underwent a complete history and physical examination and transthoracic echocardiogram prior to CRT implantation and at 6-month follow-up. The clinical and echocardiographic responses to CRT were defined based on clinical improvement (≥1 NYHA class) and LV reverse remodelling (reduction in LV end-systolic volume ≥15%) at 6-month follow-up, respectively. All the patients were prospectively followed up for the occurrence of death. The mean age was 65 ± 11 years and 79% of the patients were male. At 6-month follow-up, 510 (77%) patients showed clinical response to CRT and 412 (62%) patients showed echocardiographic response to CRT. During a mean follow-up of 37 ± 22 months, 140 (21%) patients died. Clinical and echocardiographic responses to CRT were both significantly related to all-cause mortality on univariable analysis. However, on multivariable Cox-regression analysis only echocardiographic response to CRT was independently associated with superior survival (hazard ratio: 0.38; 95% CI: 0.27-0.50; P < 0.001)., Conclusion: In a large population of heart failure patients treated with CRT, the reduction in LV end-systolic volume at the mid-term follow-up demonstrated to be a better predictor of long-term survival than improvement in the clinical status.

Aims: To evaluate the effects of cardiac resynchronization therapy (CRT) on long-term survival of patients without baseline left ventricular (LV) mechanical dyssynchrony., Methods and Results: A total of 290 heart failure patients (age 67 ± 10 years, 77% males) without significant baseline LV dyssynchrony (<60 ms as assessed with tissue Doppler imaging) were treated with CRT. Patients were divided according to the median LV dyssynchrony measured after 48 h of CRT into two groups. All-cause mortality was compared between the subgroups. In addition, the all-cause mortality rates of these subgroups were compared with the all-cause mortality of 290 heart failure patients treated with CRT who showed significant LV dyssynchrony (≥60 ms) at baseline. In the group of patients without significant LV dyssynchrony, median LV dyssynchrony increased from 22 ms (inter-quartile range 16-34 ms) at baseline to 40 ms (24-56 ms) 48 h after CRT. The cumulative mortality rates at 1-, 2-, and 3-year follow-up of patients with LV dyssynchrony ≥40 ms 48 h after CRT implantation were significantly higher when compared with patients with LV dyssynchrony <40 ms (10, 17, and 23 vs. 3, 8, and 10%, respectively; log-rank P< 0.001). Finally, the cumulative mortality rates at 1-, 2-, and 3-year follow-up of patients with baseline LV dyssynchrony were 3, 8, and 11%, respectively (log-rank P= 0.375 vs. patients with LV dyssynchrony <40 ms). Induction of LV dyssynchrony after CRT was an independent predictor of mortality (hazard ratio: 1.247; P= 0.009)., Conclusion: In patients without significant LV dyssynchrony, the induction of LV dyssynchrony after CRT may be related to a less favourable long-term outcome.

Objectives: The purpose of this study was to evaluate the impact of upgrading implantable cardioverter-defibrillator (ICD) therapy to cardiac resynchronization therapy (CRT) combined with defibrillator (CRT-D) on the occurrence of ventricular arrhythmia (VA) and appropriate ICD therapies., Background: CRT has been shown to improve left ventricular (LV) systolic function and induce reverse LV remodeling. In addition, it has been hypothesized that CRT may reduce the incidence of VA., Methods: Heart failure patients receiving an upgrade from ICD to CRT-D were evaluated. Patients were considered responders to CRT if LV end-systolic volume reduced ≥15% at 6 months of follow-up. Episodes of VA, triggering device therapy (anti-tachycardia pacing and shocks) were recorded before and after upgrade for the overall population. In addition, these outcomes were compared between CRT responders and nonresponders during the follow-up period after CRT response was assessed., Results: One hundred fifteen patients (93 males [81%], age 65 ± 12 years) were evaluated during a mean follow-up of 54 ± 34 months before CRT-D upgrade and 37 ± 27 months after upgrade. In CRT responders (n = 70), the frequency of VA requiring appropriate device therapy demonstrated a trend toward a decrease from 0.51 ± 0.79 to 0.30 ± 0.59 per patient per year after CRT-D upgrade (p = 0.052). In CRT nonresponders (n = 45), the frequency of VA requiring appropriate device therapy significantly increased from 0.40 ± 0.69 to 1.21 ± 2.53 per patient per year after CRT-D upgrade (p = 0.014)., Conclusions: After upgrade from ICD to CRT-D, nonresponders to CRT showed a significant increase in VA burden requiring appropriate device therapy., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Cardiac resynchronization therapy (CRT) is an established treatment of patients with heart failure. Several baseline characteristics can influence the CRT outcomes, and little is known about the effect of gender. The aim of the present study was to elucidate the gender-related differences in long-term survival after CRT. A total of 578 consecutive patients with heart failure underwent CRT. At baseline and 6 months after CRT, the clinical and echocardiographic parameters were obtained. All-cause mortality was compared between the men and women. The study population included 431 men (67 ± 9 years) and 147 women (65 ± 11 years). No differences in the clinical and echocardiographic characteristics were observed between the men and women, except for left bundle branch block and a nonischemic etiology of heart failure, which were more frequent in women (81% vs 68% and 63% vs 33%, respectively; p <0.01), and atrial fibrillation, which was more prevalent in men (20% vs 10%, respectively; p = 0.01). During a mean follow-up of 34 ± 25 months, 197 patients died (158 men and 39 women). Kaplan-Meier analysis showed a significant difference in long-term survival between the women and men (p = 0.007). The 2-year all-cause mortality rate was 15% in men and 8% in women (p = 0.025). Cox proportional hazard analysis revealed female gender is an independent predictor of long-term survival, together with heart failure etiology and renal function. In particular, women with heart failure due to a nonischemic etiology showed the best long-term survival rate. In conclusion, female gender and nonischemic etiology were independently associated with better long-term survival after CRT., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Introduction: Cardiac resynchronization therapy (CRT) has emerged as a treatment option for patients with end-stage heart failure and a QRS duration ≥120 ms. Nonetheless, many patients with a prolonged QRS do not demonstrate left ventricular (LV) mechanical dyssynchrony, and discrepancies between electrical and mechanical dyssynchrony have been observed. In addition, several studies demonstrated that superior benefits after CRT could be achieved when the LV pacing lead was positioned at the most delayed myocardial segment., Methods: A total of 248 heart failure patients scheduled for CRT were included. In all patients, a 12-lead electrocardiogram and 2-dimensional echocardiogram were obtained. Patients were divided into 5 QRS configuration subgroups: narrow, left bundle-branch block, right bundle-branch block, intraventricular conduction delay, and right ventricular pacing. With speckle-tracking radial strain analysis, we evaluated time to peak radial strain. Next, the segments with the least and with the most mechanical activation delay were identified, and LV dyssynchrony was defined as the time delay between the two., Results: Mean QRS duration was 164 ± 31 ms. Mean LV dyssynchrony in all patients was 186 ± 122 ms. Site of latest activation was predominantly located in the lateral (27%), posterior (26%), and inferior (20%) segments. Furthermore, extent of LV dyssynchrony was comparable between QRS configuration subgroups. An unequal distribution of LV segments with the most mechanical delay was observed in the left bundle-branch block and right ventricular pacing subgroups (P < .001 for both), whereas in the narrow, right bundle-branch block, and intraventricular conduction delay subgroups, a more homogeneous distribution was noted. No differences in distribution pattern or in extent of LV dyssynchrony were observed between ischemic and nonischemic heart failure patients., Conclusion: The lateral, posterior, and inferior segments take up 73% of the total latest activated segments in heart failure patients eligible for CRT. Presence of LV dyssynchrony can be observed in all QRS configurations. The site of latest activation may be outside the lateral or posterior segment, making echocardiographic assessment of LV dyssynchrony and site of latest activation a valuable technique to optimize patient outcome after CRT., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Background: Lack of response to cardiac resynchronization therapy (CRT) ranges between 30% to 40% of heart failure (HF) patients. The present study aimed to evaluate the clinical and echocardiographic determinants of nonresponse to CRT., Methods: A total of 581 patients (66.4 ± 10.0 years, 77.9% male) with advanced HF scheduled for CRT implantation were included. Clinical and echocardiographic evaluations were performed at baseline and 6 months of follow-up. Nonresponse was defined as no improvement in the New York Heart Association functional class, death from worsening HF or heart transplantation, and <15% reduction in left ventricular (LV) end-systolic volume., Results: At 6 months of follow-up, 254 patients (44%) did not respond to CRT. The nonresponders were more frequently male (81.9% vs 74.3%, P = .030) and had ischemic cardiomyopathy (69.7% vs 53.2%, P < .001), shorter QRS duration (150.6 ± 29.9 milliseconds vs 156.0 ± 32.5 milliseconds, P = .041), worse New York Heart Association functional class (2.8 ± 0.6 vs 2.7 ± 0.6, P = .008) and shorter 6-minute walk distance (297.9 ± 110.7 m vs 331.8 ± 112.6 m, P = .001), larger left atrial volumes (44.9 ± 16.9 mL/m(2) vs 40.9 ± 17.6 mL/m(2), P = .006), less baseline LV dyssynchrony (56.2 ± 41.3 milliseconds vs 69.1 ± 39.9 milliseconds, P < .001), and, more frequently, anterior LV lead position (12.4% vs 4.0%, P = .007). At multivariate analysis, only the ischemic etiology of HF (odds ratio [OR] 2.264, P = .005), shorter 6-minute walk distance at baseline (OR 0.998, P = .030), less baseline LV dyssynchrony (OR 0.989, P < .001), and anterior LV lead position (OR 3.713, P < .010) remained independent predictors of nonresponse to CRT., Conclusions: Ischemic etiology of HF, shorter baseline 6-minute walk distance, less baseline LV dyssynchrony, and anterior LV lead position are independent determinants of nonresponse to CRT., (Copyright © 2011 Mosby, Inc. All rights reserved.)

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.

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.

Aims: Cardiac resynchronization therapy (CRT) improves cardiac function, heart failure symptoms, and prognosis in selected patients. Many baseline characteristics associated with heart failure may influence prognosis after CRT. The objective of this study was to evaluate the effect of several baseline characteristics in relation to long-term prognosis in heart failure patients treated with CRT., Methods and Results: A total of 716 consecutive heart failure patients treated with CRT were included in an observational registry. All available data, including clinical and echocardiographic measurements, were analysed in relation to two endpoints: all-cause mortality and a combined endpoint of all-cause mortality or major cardiovascular event. Outcome data were collected by chart review, device interrogation, and telephone contact. Mean follow-up was 25 ± 19 months. During follow-up, 141 patients (20%) died (primary endpoint). Most of these patients (61%) died due to worsening heart failure. A total of 214 patients (30%) reached the secondary endpoint. Larger left ventricular end-systolic volume, less distance covered in the 6 min walking test, poor renal function, more severe heart failure, male gender, presence of atrial fibrillation, no posterolateral left ventricular (LV) lead, and no LV dyssynchrony were associated with poor prognosis after CRT., Conclusion: In this large single-centre registry, several baseline clinical and echocardiographic characteristics were associated with prognosis after CRT. Worsening heart failure was the main cause of death in heart failure patients treated with CRT.

Cardiac resynchronization therapy (CRT) is considered a class I indication in treatment of patients with New York Heart Association (NYHA) functional class III and IV heart failure. However, only small numbers of patients in large clinical trials have been in NYHA functional class IV. Therefore, little is known about the effects of CRT in this group. Therefore, we evaluated the effects of CRT in patients with NYHA functional class IV heart failure. Of all patients referred for CRT implantation, 61 patients with symptoms according to NYHA functional class IV were included. All patients were evaluated before implantation and at 6-month follow-up for clinical changes according to the clinical composite score and changes in left ventricular (LV) volumes and function. In addition, survival was evaluated during long-term follow-up. At 6-month follow-up, 9 patients (15%) had died and 2 patients (3%) were admitted for worsening heart failure. The remaining 39 patients (64%) showed improvement according to the clinical composite score. Decreases in LV end-systolic volume (from 167 ± 88 to 147 ± 93 ml, p = 0.009) and LV end-diastolic volume (from 211 ± 100 to 199 ± 113 ml, p = 0.135) were observed, as was a significant increase in LV ejection fraction (from 22 ± 8% to 28 ± 9%, p <0.001). During a mean follow-up of 30 ± 26 months, 36 patients (59%) died, 27 (75%) from worsening heart failure. Respective 1- and 2-year mortality rates were 25% and 38%. In conclusion, CRT decreases LV volumes and improves cardiac function in patients with NYHA functional class IV heart failure. Nevertheless, (heart failure) mortality remains high in these patients., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: Although most patients who improve in clinical status after cardiac resynchronization therapy (CRT) also show a significant left ventricular (LV) reverse remodeling, some patients do not show echocardiographic improvement. The aim of the present study was to evaluate the degree of agreement between clinical and echocardiographic response to CRT in a large cohort of heart failure patients, and to evaluate the characteristics of patients with clinical response but without echocardiographic response., Methods: In 440 consecutive heart failure patients (mean age 66 ± 11 years, 81% men) treated with CRT, agreement between clinical and echocardiographic responses at 6 months of follow-up were evaluated. The combined clinical response was defined as: ≥1-point New York Heart Association functional class improvement or ≥15% increase in 6-minute walk test. Echocardiographic response was defined by a reduction in LV end-systolic volume (LVESV) ≥15%., Results: At 6 months of follow-up, clinical response was observed in 84% (n = 370) of the patients. Significant reduction in LVESV was noted in 63% (n = 276). The majority of patients who improved clinically did show LV reverse remodeling (72%, n = 268). Importantly, 28% (n = 102) of patients who improved clinically did not show significant LV reverse remodeling. The patients with clinical response but without echocardiographic response had more often ischemic heart failure as compared to patients with positive clinical and echocardiographic response (69.6% vs 57.5%; P = .021). Moreover, patients with such discordant responses had more narrow QRS complex (148 ± 31 vs 159 ± 31 milliseconds; P = .004), and showed less LV dyssynchrony than patients with concordant positive responses (90 ± 77 vs 171 ± 105 milliseconds; P < .001)., Conclusions: Although there is a good concordance between echocardiographic and clinical response to CRT, up to 28% of the population experienced clinical response without significant LV reverse remodeling. Subjects with such discrepant responses have more frequently ischemic heart failure and show more narrow QRS complex and less LV dyssynchrony than patients with both clinical and echocardiographic response., (Copyright © 2010 Mosby, Inc. All rights reserved.)

The analysis of left ventricular (LV) mechanics provides novel insights into the effects of cardiac resynchronization therapy (CRT) on LV performance. Currently, advances in speckle-tracking echocardiographic analysis have permitted the characterization of subendocardial and subepicardial LV twist. The aim of this study was to investigate the role of the acute changes in subendocardial and subepicardial LV twist for the prediction of midterm beneficial effects of CRT. A total of 84 patients with heart failure scheduled for CRT were recruited. All patients underwent echocardiography before and <48 hours after CRT implantation and at 6-month follow-up. The assessment of LV volumes, ejection fractions, and mechanical dyssynchrony (systolic dyssynchrony index) was performed with real-time 3-dimensional echocardiography. The assessment of subendocardial and subepicardial LV twist was performed with 2-dimensional speckle-tracking echocardiography. A favorable outcome was defined as the occurrence of a reduction > or =15% in LV end-systolic volume associated with an improvement of > or =1 New York Heart Association functional class at 6-month follow-up. At 6-month follow-up, 53% of the patients showed favorable outcomes. Ischemic cause of heart failure, baseline systolic dyssynchrony index, immediate improvement in the LV ejection fraction, immediate improvement in systolic dyssynchrony index, and immediate improvement in subendocardial and subepicardial LV twist were significantly related to favorable outcomes. However, in multivariate logistic regression analysis, only the immediate improvement of subepicardial LV twist was independently related to favorable outcomes (odds ratio 2.31, 95% confidence interval 1.29 to 4.15, p = 0.005). Furthermore, the immediate improvement of subepicardial LV twist had incremental value over established parameters. In conclusion, the immediate improvement of subepicardial LV twist (but not subendocardial LV twist) is independently related to favorable outcomes after CRT., (2010 Elsevier Inc. All rights reserved.)

Cardiac resynchronization therapy (CRT) is an effective treatment for patients with drug-refractory, chronic heart failure. Multiple single-center and multicenter studies have shown significant reductions in left ventricular (LV) volumes and an increase in LV systolic function. More importantly, CRT reduces mortality and morbidity during long-term follow-up. Current guidelines consider CRT as a Class I indication for heart failure patients in New York Heart Association (NYHA) functional class III to IV with depressed LV ejection fraction or=120 ms). However, the benefits of this therapy could possibly be extended to selected subgroups of patients who do not fulfill these criteria. These subgroups include patients with mildly symptomatic heart failure and patients with a narrow QRS complex (<120 ms). Results from recent multicenter controlled clinical trials including heart failure patients in NYHA functional class I to II or with a narrow QRS complex are equivocal. Although expanding CRT to patients with a narrow QRS complex seems currently not likely, the benefits of CRT in mildly symptomatic patients are more evident. Perhaps attenuation of disease progression will prove to be a successful new treatment strategy in heart failure patients in the future. In addition, multimodality cardiac imaging will allow optimizing responder rate in patients undergoing CRT according to current guidelines., (Copyright (c) 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Several studies have demonstrated a relation between left ventricular (LV) dyssynchrony and response to cardiac resynchronization therapy (CRT). Many methods of determining LV dyssynchrony have been proposed, including a value of 65 ms as assessed by tissue Doppler imaging. The aim of the present validation study was to prospectively test the predictive accuracy of the 65-ms cutoff for LV dyssynchrony in a large cohort of patients with heart failure undergoing CRT. The study included 361 patients who had undergone CRT. The clinical and echocardiographic parameters were assessed at baseline and at 6 months of follow-up. The clinical response was defined as an improvement of > or = 1 New York Heart Association class, and the echocardiographic response was defined as a reduction in LV end-systolic volume of > or = 15%. At 6 months of follow-up, 259 patients (72%) had a clinical response and 187 patients (52%) had an echocardiographic response. The patients with a response had more LV dyssynchrony than did those without a response (91 + or - 49 ms vs 50 + or - 44 ms for the clinical response and 101 + or - 46 ms vs 55 + or - 45 ms for the echocardiographic response). On multivariate analysis, LV dyssynchrony remained predictive of the response, independent of other characteristics. In conclusion, LV dyssynchrony of > or = 65 ms was an independent predictor of both the clinical and the echocardiographic response in patients with heart failure who underwent CRT in this validation study., (Copyright 2010 Elsevier Inc. All rights reserved.)

Background: Cardiac resynchronization therapy for heart failure with left bundle branch block reduces left ventricular (LV) conduction delay, contraction asynchrony, and LV end-systolic volume ("reverse remodeling"). Up to one third of patients do not improve, and the electric requirements for reverse remodeling are unclear. We hypothesized that reverse remodeling is predicted by the left bundle branch block ventricular activation sequence, the paced activation sequence, and interactions between these 2 conditions., Methods and Results: Twelve-lead ECGs during left bundle branch block and cardiac resynchronization therapy were analyzed in 202 consecutive patients (New York Heart Association class III to IV heart failure, ejection fraction < or =35%) for predictors of reverse remodeling (> or =10% reduction in end-systolic volume) at 6 months. Greater longest baseline LV activation time predicted increased odds of reverse remodeling (odds ratio [confidence interval]=1.30 [1.11, 1.52] per 10-ms increase), whereas higher QRS scores for LV scar predicted reduced reverse remodeling (odds ratio [confidence interval]=0.49 [0.27, 0.88] for each 1-point increase from 0 to 4; 0.92 [0.83, 1.01] for each 1-point increase >4). After cardiac resynchronization therapy, increasing R amplitudes in leads V(1) through V(2) (odds ratio [confidence interval]=2.76 [1.01, 7.51] for each 1x increase over [baseline Rx4.5]) and left-->right frontal axis shift (odds ratio [confidence interval]=2.00 [0.99, 4.02]), indicators of ventricular activation wavefront fusion, were positive predictors of reverse remodeling. Predicted probability of reverse remodeling ranged from <20% for patients with adverse predictors to 99% for those with positive predictors., Conclusions: Ventricular activation with the use of the ECG accurately predicts LV reverse remodeling during cardiac resynchronization therapy. Greater longest baseline LV activation time and smaller scar volume combined with wavefront fusion on the paced ECG, anticipate higher probability of reverse remodeling.

Background: Left ventricular (LV) fibrosis is important for the response to cardiac resynchronization therapy (CRT). Calibrated integrated backscatter derived by 2D echocardiography quantifies myocardial ultrasound reflectivity, which may provide a surrogate of LV fibrosis. The aim of the study was first, to investigate the relation of myocardial ultrasound reflectivity assessed with calibrated integrated backscatter on CRT response, and second, to explore the "myocardial ultrasound reflectivity-CRT response" relation in patients with ischemic and nonischemic heart failure (HF)., Methods and Results: One hundred fifty-nine patients with HF referred for CRT underwent an extensive echocardiographic evaluation at baseline and at 6-month follow-up. LV dyssynchrony was derived from speckle-tracking analysis. Calibrated integrated backscatter was obtained from the parasternal long-axis view. The mean value of calibrated integrated backscatter of the anteroseptal and posterior wall was used to estimate myocardial ultrasound reflectivity. CRT response was defined as reduction >/=15% of LV end-systolic volume. At baseline, LV dyssynchrony was significantly larger in responders as compared with nonresponders (188+/-96 ms versus 115+/-68 ms, P<0.001), and CRT responders showed less myocardial ultrasound reflectivity as compared with nonresponders (-20.8+/-3.0 dB versus -17.0+/-3.0 dB, P<0.001). In multivariable logistic regression analysis, independent predictors for CRT response were LV dyssynchrony, renal function, and myocardial ultrasound reflectivity. Importantly, myocardial ultrasound reflectivity provided an incremental value to CRT response (chi(2) change=40, P<0.001). Considering patients with ischemic HF, the only independent predictor of CRT response was myocardial ultrasound reflectivity, whereas in patients with nonischemic HF, independent predictors of LV reverse remodeling were myocardial ultrasound reflectivity, LV dyssynchrony, and renal function., Conclusions: Assessment of myocardial ultrasound reflectivity is important in the prediction of CRT response in ischemic and nonischemic patients.

Background: Whether sequential biventricular pacing provides substantial benefits over conventional simultaneous stimulation remains unclear, particularly regarding the differences between ischemic and non-ischemic patients. The purpose of this study was to evaluate the acute effect of interventricular pacing interval (V-V) optimization on left ventricular (LV) systolic performance and dyssynchrony in ischemic versus non-ischemic patients., Methods: Sixty-nine consecutive patients underwent cardiac resynchronization therapy. Within 3 days after implantation, V-V was optimized by measuring (every 20-millisecond interval) LV systolic performance (LV outflow-tract velocity-time-integral, LVOT VTI) and LV dyssynchrony (using tissue Doppler imaging). Optimal pacing configuration was the one achieving maximal increase in LVOT VTI., Results: Optimized sequential pacing provided a significant improvement in LVOT VTI compared to simultaneous stimulation (from 138 +/- 42 to 163 +/- 38 mm, P < .001) and was associated with a significant reduction in LV dyssynchrony (from 33 +/- 31 to 19 +/- 24 milliseconds, P < .001). The increase in LVOT VTI and LV ejection fraction after implantation was greater in non-ischemic as compared to ischemic patients (P < .001). However, V-V optimization yielded a larger improvement in LV systolic performance in ischemic patients (P = .03). Consequently, the 2 groups showed comparable response after V-V optimization. A significant correlation was observed between LV scar tissue and optimal V-V interval (r = 0.58, P < .001), with a larger extent of scar related to a larger level of LV preactivation, probably reflecting slow intra-LV conduction., Conclusions: Optimized sequential biventricular pacing further increased LV systolic performance as compared to simultaneous stimulation, particularly in ischemic patients where the presence of a large scar was correlated with a larger LV preactivation.

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.

Aims: Predictors of Response to Cardiac Resynchronization Therapy (CRT) (PROSPECT) was the first large-scale, multicentre clinical trial that evaluated the ability of several echocardiographic measures of mechanical dyssynchrony to predict response to CRT. Since response to CRT may be defined as a spectrum and likely influenced by many factors, this sub-analysis aimed to investigate the relationship between baseline characteristics and measures of response to CRT., Methods and Results: A total of 286 patients were grouped according to relative reduction in left ventricular end-systolic volume (LVESV) after 6 months of CRT: super-responders (reduction in LVESV > or =30%), responders (reduction in LVESV 15-29%), non-responders (reduction in LVESV 0-14%), and negative responders (increase in LVESV). In addition, three subgroups were formed according to clinical and/or echocardiographic response: +/+ responders (clinical improvement and a reduction in LVESV > or =15%), +/- responders (clinical improvement or a reduction in LVESV > or =15%), and -/- responders (no clinical improvement and no reduction in LVESV > or =15%). Differences in clinical and echocardiographic baseline characteristics between these subgroups were analysed. Super-responders were more frequently females, had non-ischaemic heart failure (HF), and had a wider QRS complex and more extensive mechanical dyssynchrony at baseline. Conversely, negative responders were more frequently in New York Heart Association class IV and had a history of ventricular tachycardia (VT). Combined positive responders after CRT (+/+ responders) had more non-ischaemic aetiology, more extensive mechanical dyssynchrony at baseline, and no history of VT., Conclusion: Sub-analysis of data from PROSPECT showed that gender, aetiology of HF, QRS duration, severity of HF, a history of VT, and the presence of baseline mechanical dyssynchrony influence clinical and/or LV reverse remodelling after CRT. Although integration of information about these characteristics would improve patient selection and counselling for CRT, further randomized controlled trials are necessary prior to changing the current guidelines regarding patient selection for CRT.

Objectives: This study explored the effects of cardiac resynchronization therapy (CRT) on left ventricular (LV) twist, particularly in relation to LV lead position., Background: LV twist is emerging as a comprehensive index of LV function., Methods: Eighty heart failure patients were included. Two-dimensional echocardiography was performed at baseline, immediately after CRT, and at 6-month follow-up. Speckle-tracking analysis was applied to assess LV twist. The LV lead was placed preferably in a (postero)lateral vein, and at fluoroscopy, the position was classified as basal, midventricular, or apical. Response to CRT was defined as reduction of LV end-systolic volume>or=15% at 6-month follow-up. A control group comprised 30 normal subjects., Results: Peak LV twist in heart failure patients was 4.8+/-2.6 degrees compared with 15.0+/-3.6 degrees in the control subjects (p<0.001). At 6-month follow-up, peak LV twist significantly improved only in responders (56%), from 4.3+/-2.4 degrees to 8.5+/-3.2 degrees (p<0.001). The strongest predictor of response to CRT was the improvement of peak LV twist immediately after CRT (odds ratio: 1.899, 95% confidence interval: 1.334 to 2.703, p<0.001). Furthermore, LV twist significantly improved in patients with an apical (from 4.3+/-3.1 degrees to 8.6+/-3.0 degrees, p=0.001) and midventricular (from 4.8+/-2.2 degrees to 6.4+/-3.9 degrees, p=0.038) but not with a basal (5.0+/-3.3 degrees vs. 4.1+/-3.2 degrees, p=0.28) LV lead position. Similarly, LV ejection fraction significantly increased in patients with an apical (from 26+/-7% to 37+/-7%, p<0.001) and midventricular (from 26+/-6% to 33+/-8%, p<0.001) but not with a basal (26+/-5% vs. 28+/-8%, p=0.30) LV lead position., Conclusions: An immediate improvement of LV twist after CRT predicts LV reverse remodeling at 6-month follow-up.

Left ventricular (LV) twist and untwisting rate are emerging as global and thorough parameters for assessment of LV function. This study explored differences of LV twist and untwisting rate in patients with acute myocardial infarction (AMI) and patients with ischemic and nonischemic chronic heart failure (HF). Fifty patients with AMI, 49 with ischemic HF, and 38 with nonischemic HF were studied. As a control group, 28 subjects without evidence of structural heart disease were included. Speckle-tracking analysis was applied to LV short-axis images at basal and apical levels. LV twist was defined as the net difference of apical and basal rotations at isochronal time points. The first time derivative of LV untwist was defined as the LV untwisting rate. Compared with control subjects, peak LV twist was decreased in patients with AMI and extremely decreased in those with HF (p <0.001, analysis of variance). A strong correlation (r = 0.87, p <0.001) was found between peak LV twist and LV ejection fraction in the overall study population. LV untwisting rate was progressively decreased in patients with AMI and HF compared with control subjects (p <0.001, analysis of variance). A moderate correlation (r = 0.56, p <0.001) was noted between peak LV untwisting rate and grade of diastolic dysfunction in the overall study population. In conclusion, LV twist and untwisting rate are strongly related to LV systolic and diastolic functions, respectively. Impairment of LV function observed in patients with AMI and HF is associated with a decrease of LV twist and untwisting rate.

Unlabelled: 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, r(2) = 0.48, SEE = 25.4, P < 0.01) and phase SD (r = 0.65, r(2) = 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 degrees +/- 23 degrees vs. 68 degrees +/- 21 degrees , P < 0.01) and a larger phase SD (26 degrees +/- 6 degrees vs. 18 degrees +/- 5 degrees , P < 0.01) than did nonresponders. Receiver-operating-characteristic curve analysis identified an optimal cutoff value of 72.5 degrees 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 degrees ., 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.

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.

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.

Interruption of short-term cardiac resynchronization therapy (CRT) has been shown to acutely worsen left ventricular (LV) function, mitral regurgitation, and LV dyssynchrony. The present study aims to assess whether LV reverse remodeling influences interruption of CRT, and, more practically, whether long-term continuous pacing is necessary in patients with reverse LV remodeling. A total of 135 recipients of CRT were selected after showing LV reverse remodeling defined as a decrease in LV end-systolic volume > or =15% after 6 months of CRT ("responders"). Echocardiography was performed at baseline and after 6 months with intermittent CRT on and off. LV dyssynchrony was determined using tissue Doppler imaging. During interruption of CRT, an acute deterioration in LV function, mitral regurgitation, and LV desynchronization were noted in responder patients. Of note, worsening of these echocardiographic measurements was observed, but they did not return to baseline values. For comparison, 100 nonresponder patients (without LV reverse remodeling) showed no significant echocardiographic changes during interruption. In conclusion, despite the presence of LV reverse remodeling, interruption of CRT resulted in worsening of LV function and desynchronization. Therefore, continuous long-term pacing is warranted to maintain the beneficial effects.

Background: In patients with heart failure cardiac resynchronization therapy (CRT) leads to reverse ventricular remodelling., Aim: To evaluate whether myocardial collagen metabolism in patients with heart failure is implicated in adverse ventricular remodelling and response to CRT., Methods: Collagen synthesis and degradation were assessed from the concentrations of aminoterminal propeptides of type I and type III collagen (PINP and PIIINP) and carboxyterminal telopeptide of type I collagen (ICTP), respectively, in serum of 64 patients with heart failure before and after 6 months of CRT. Forty-six patients (72%) showed a > 10% reduction in LV end-systolic volume at follow-up and were classified as responders to CRT, the other 18 patients (28%) were classified as non-responders., Results: Responders demonstrated a mean (+/-SEM) increase of serum PINP and PIIINP during follow-up, from 32.9+/-2.2 to 46.7+/-4.0 microg/L (p < 0.001) and from 4.59+/-0.24 to 5.13+/-0.36 microg/L (p < 0.05), respectively. In non-responders, serum PINP and PIIINP remained unchanged during follow-up. At baseline, responders had significantly lower serum PINP than non-responders (32.9+/-2.2 vs. 41.8+/-4.3 microg/L; p < 0.05). ICTP levels of responders at baseline tended to be higher than in non-responders (3.54+/-0.56 vs. 2.08+/-0.37 microg/L, p = ns), and in both groups ICTP levels did not change upon CRT., Conclusion: Reverse LV remodelling following CRT is associated with increased collagen synthesis rate in the first 6 months of follow-up.

Metabolic and mechanical stress in the failing heart activates the cardiac sympathetic afferent reflex (CSAR). It has been demonstrated that cardiac resynchronization therapy (CRT) acutely reduces MSNA in clinical responders. Mechanistically, this beneficial effect might be explained by acute deactivation of the CSAR. In addition to sympathoexcitation, CSAR inhibits the arterial baroreflex at the level of the nucleus tractus solitarii. Hence, in responders, CRT is likely to remove/reduce this inhibition. Therefore, we hypothesized that CRT acutely facilitates the arterial baroreflex. One day after implantation of a CRT device in 32 patients with chronic heart failure (LVEF; 27 +/- 6%), we measured noninvasive baroreflex sensitivity (BRS) and heart rate variability (HRV) in two conditions: CRT device switched on and switched off (on/off order randomized). BRS changes were correlated with the difference in unpaced/paced LVEF, a measure of acute mechanical response to CRT. CRT increased BRS by 35% from 2.96 to 3.79 ms/mmHg (P < 0.02) and increased HRV (standard deviation of the intervals between normal beats) from 18.5 to 24.0 ms (P < 0.01). The CRT-induced relative change in BRS correlated with the change in LVEF (r = 0.44; P < 0.01). In conclusion, CRT acutely increases BRS and HRV. This favorable response of the autonomic nervous system might be caused by CRT-induced CSAR deactivation. Follow-up studies should verify the mechanism of the acute response and the possible predictive value of an acute positive BRS response.

Background: Biventricular (BV) electrical wavefront fusion can induce improvement in left ventricular (LV) size and function during cardiac resynchronization therapy (CRT). Changes in BV wave propagation sequence and duration register in the QRS complex on the standard electrocardiogram. We developed a wave interference method for the characterization of BV fusion to predict LV reverse remodeling. Objective: To develop a simple electrocardiographic method for predicting reverse remodeling during CRT. Methods: QRS complexes during left bundle branch block (LBBB) and CRT were analyzed in 375 patients with ejection fraction ≤35% and New York Heart Association class III-IV (Leiden study: n = 226) as well as in patients with ejection fraction ≤40% and New York Heart Association class I-II (REVERSE trial: n = 149) for predictors of ≥10% reduction in left ventricular end-systolic volume at 6 months. CRT-induced changes in ventricular activation (QRS fusion contour), electrical asynchrony (QRS difference = BV-paced QRS – LBBB QRS, in milliseconds), and LBBB substrate (LV activation time and QRS score for LV scar) were quantified. Results: Multivariable predictors of reverse remodeling were as follows: (1) either of 2 BV fusion patterns: QRS normalization in leads V1 and V2 (n = 66 [18%]; odds ratio [OR] 3.71; 95% confidence interval [CI] 1.26–10.94) or a new or an increased R wave in leads V1-V2 (n = 267 [71%]; OR 1.55; 95% CI 0.65–3.65); (2) QRS difference ≤ −25 ms (OR 2.35; 95% CI 1.12–4.91); and (3) good substrate (low to moderate QRS score and LV activation time ≥110 ms; OR 2.94; 95% CI 1.68–5.14). Remodeling rates were 40% for poor substrate and persistent LBBB QRS complex (absent BV fusion; QRS type 3: n = 42 [11%]) and 97% for the best BV QRS fusion pattern and greater reduction in electrical asynchrony (larger QRS difference). Conclusion: Easily determined QRS complex attributes before and after CRT predict LV reverse remodeling. [Copyright &y& Elsevier]

Background—Functional mitral regurgitation (MR) is a common finding in heart failure patients with dilated cardiomyopathy and has important prognostic implications. However, the increased operative risk of these patients may result in low referral or high denial rate for mitral valve surgery. Cardiac resynchronization therapy (CRT) has been shown to have a favorable effect on MR. Aims of this study were to (1) evaluate CRT as a therapeutic option in heart failure patients with functional MR and high operative risk and (2) investigate the effect of MR improvement after CRT on prognosis. Methods and Results—A total of 98 consecutive patients with moderate-severe functional MR and high operative risk underwent CRT according to current guidelines. Echocardiography was performed at baseline and 6-month follow-up; severity of MR was graded according to a multiparametric approach. Significant improvement of MR was defined as a reduction ≥1 grade. All-cause mortality was assessed during follow-up (median 32 [range 6.0 to 116] months). Thirteen patients (13%) died before 6-months follow-up. In the remaining 85 patients, significant reduction in MR was observed in all evaluated parameters. In particular, 42 patients (49%) improved ≥1 grade of MR and were considered MR improvers. Survival was superior in MR improvers compared to MR nonimprovers (log rank P<0.001). Mitral regurgitation improvement was an independent prognostic factor for survival (hazard ratio 0.35, confidence interval 0.13 to 0.94; P=0.043). Conclusions—Cardiac resynchronization therapy is a potential therapeutic option in heart failure patients with moderate-severe functional MR and high risk for surgery. Improvement in MR results in superior survival after CRT. [ABSTRACT FROM AUTHOR]

Objectives: Aims of this study were to investigate the effect of renal function on left ventricular (LV) reverse remodeling and long-term outcome after cardiac resynchronization therapy (CRT), and to explore the relation between LV reverse remodeling and changes in renal function at 6-month follow-up. Background: Renal insufficiency is highly prevalent in heart failure patients, including patients eligible for CRT, and is associated with poor prognosis. Methods: The study comprised 490 patients undergoing CRT. Response to CRT was defined as a decrease in LV end-systolic volume ≥15% at 6-month follow-up. Primary end point during long-term follow-up was all-cause mortality. Results: At baseline, mean estimated glomerular filtration rate (eGFR) was 70 ± 28 ml/min/1.73 m2. At 6-month follow-up, 263 patients (54%) demonstrated response to CRT. Responders had an eGFR of 74 ± 26 ml/min/1.73 m2 versus 64 ± 28 ml/min/1.73 m2 in nonresponders (p < 0.001). During long-term follow-up, patients with an eGFR <60 ml/min/1.73 m2 had higher mortality than patients with an eGFR of 60 to 90 ml/min/1.73 m2 or an eGFR >90 ml/min/1.73 m2 (p < 0.001). Finally, responders to CRT had preservation of renal function (ΔeGFR −0.6), whereas nonresponders had a slight worsening in renal function (ΔeGFR −4.7, p < 0.05). Conclusions: Impaired renal function in CRT candidates is associated with nonresponse during 6-month follow-up. Additionally, patients with impaired renal function have worse long-term survival after CRT. Response to CRT results in preservation of renal function. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to assess the requirement for coronary sinus (CS) lead intervention after cardiac resynchronization therapy (CRT) and to evaluate the effectiveness of endovascular replacement. [ABSTRACT FROM PUBLISHER]

Background: Data on the occurrence and implications of new-onset atrial fibrillation (AF) following cardiac resynchronization therapy (CRT) are scarce. We studied the incidence of new onset AF in CRT-defibrillator (CRT-D) recipients. The influence of new-onset AF on echocardiographic response to CRT and the rate of adverse events also were evaluated. Objective: The purpose of this study was to assess the incidence and implications of new-onset AF following CRT. Methods: The study population consisted of 223 consecutive patients with no history of AF. New-onset AF was defined as atrial high-rate episodes >180 bpm for more than 10 minutes/day as detected by the device. Echocardiography was performed at baseline and after 6 months of biventricular pacing. Long-term events included implantable cardioverter-defibrillator therapy for ventricular arrhythmias, hospitalization for heart failure, and all-cause mortality. Results: Fifty-five (25%) patients developed new-onset AF during mean follow-up of 32 ± 16 months. When compared to the patients who maintained sinus rhythm during follow-up, patients who developed AF showed less left ventricular (LV) reverse remodeling (ΔLV end-systolic volume 37 ± 53 vs >19 ± 37 mL, P <.05) and less improvement in LV function (ΔLV ejection fraction 6.7% ± 8.9% vs 3.5% ± 10.3%, P <.05) . Importantly, patients who developed AF experienced more appropriate ICD shocks for ventricular arrhythmias, more inappropriate shocks, and more hospitalizations for heart failure. Conclusion: Recipients of CRT-D who develop new-onset AF show less echocardiographic response to CRT and more cardiac adverse events during long-term follow-up. [Copyright &y& Elsevier]

Background: Real-time 3-dimensional echocardiography (RT3DE) is a novel promising technique for the assessment of left ventricular (LV) dyssynchrony. Objective: This study sought to explore the value of RT3DE to assess LV and left atrium (LA) reverse remodeling and to predict response to cardiac resynchronization therapy (CRT). Methods: A total of 57 consecutive heart failure patients scheduled for CRT were included, and RT3DE was performed before and 6 months after implantation. LV dyssynchrony was defined as the standard deviation of the time to reach the minimum systolic volume for 16 LV segments, expressed in percentage of cardiac cycle (systolic dyssynchrony index, SDI). Patients were divided into responders or nonresponders, based on a reduction ≥15% in LV end-systolic volume after CRT. Results: Six patients (10%) were excluded from further analysis because of suboptimal images. Of the remaining 51 patients, 34 (67%) were classified as responders. Baseline characteristics were similar between responders and nonresponders, except for the SDI, which was larger in responders (9.7% ± 3.6% versus 5.1% ± 1.8%, P <.0001). ROC curve analysis revealed that a cutoff value for SDI of 6.4% yielded a sensitivity of 88% with a specificity of 85% to predict response to CRT. In responders, RT3DE also showed beneficial effects of CRT on LA: (1) significant LA reverse remodeling; (2) significant improvement in LA total emptying fraction and in LA conduit and reservoir function. Conclusion: RT3DE allows assessment of changes in LV and LA volumes and function after CRT, and it is highly predictive for response to CRT. [Copyright &y& Elsevier]

Objectives: This study sought to examine the changes in diastolic dyssynchrony with cardiac resynchronization therapy (CRT). Background: Little is known about the effect of CRT on diastolic dyssynchrony. Methods: Consecutive heart failure patients (n = 266, age 65.7 ± 10.0 years) underwent color-coded tissue Doppler imaging at baseline, 48 h, and 6 months after CRT. Systolic and diastolic dyssynchrony were defined as maximal time delay in peak systolic and early diastolic velocities, respectively, in 4 basal LV segments. CRT responders were defined as those with ≥15% decrease in LV end-systolic volume at 6 months. Results: Baseline LVEF was 25.2 ± 8.1%; 63.5% patients were CRT responders. Baseline incidence of systolic and diastolic dyssynchrony, and a combination of both was 46.2%, 51.9%, and 28.6%, respectively. Compared to nonresponders, responders had longer baseline systolic (79.2 ± 43.4 ms vs. 45.4 ± 30.4 ms; p < 0.001) and diastolic (78.5 ± 52.0 ms vs. 50.1 ± 38.2 ms; p < 0.001) delays. In follow-up, systolic delays (45.4 ± 31.6 ms at 48 h; 38.9 ± 26.2 ms at 6 months; p < 0.001) and diastolic delays (49.4 ± 36.3 ms at 48 h; 37.7 ± 26.0 ms at 6 months; p < 0.001) improved only in responders. Conclusions: At baseline: 1) diastolic dyssynchrony was more common than systolic dyssynchrony in HF patients; 2) nonresponders had less baseline diastolic dyssynchrony compared to responders. After CRT: 1) diastolic dyssynchrony improved only in responders. Further insight into the pathophysiology of diastolic dyssynchrony and its changes with CRT may provide incremental information on patient-specific treatments. [Copyright &y& Elsevier]