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Aims: The implantable cardiac defibrillator/cardiac resynchronization therapy with defibrillator-based HeartLogic™ algorithm has recently been developed for early detection of impending decompensation in heart failure (HF) patients; but whether this novel algorithm can reduce HF hospitalizations has not been evaluated. We investigated if activation of the HeartLogic algorithm reduces the number of hospital admissions for decompensated HF in a 1 year post-activation period as compared with a 1 year pre-activation period., Methods and Results: Heart failure patients with an implantable cardiac defibrillator/cardiac resynchronization therapy with defibrillator with the ability to activate HeartLogic and willingness to have remote device monitoring were included in this multicentre non-blinded single-arm trial with historical comparison. After a HeartLogic alert, the presence of HF symptoms and signs was evaluated. If there were two or more symptoms and signs apart from the HeartLogic alert, lifestyle advices were given and/or medication was adjusted. After activation of the algorithm, patients were followed for 1 year. HF events occurring in the 1 year prior to activation and in the 1 year after activation were compared. Of the 74 eligible patients (67.2 ± 10.3 years, 84% male), 68 patients completed the 1 year follow-up period. The total number of HF hospitalizations reduced from 27 in the pre-activation period to 7 in the post-activation period (P = 0.003). The number of patients hospitalized for HF declined from 21 to 7 (P = 0.005), and the hospitalization length of stay diminished from average 16 to 7 days (P = 0.079). Subgroup analysis showed similar results (P = 0.888) for patients receiving cardiac resynchronization therapy during the pre-activation period or not receiving cardiac resynchronization therapy, meaning that the effect of hospitalizations cannot solely be attributed to reverse remodelling. Subanalysis of a single-centre Belgian subpopulation showed important reductions in overall health economic costs (P = 0.025)., Conclusion: Activation of the HeartLogic algorithm enables remote monitoring of HF patients, coincides with a significant reduction in hospitalizations for decompensated HF, and results in health economic benefits., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Noninducibility of ventricular tachycardia (VT) with an equal or longer cycle length (CL) than that of the clinical VT is considered the minimum ablation endpoint in patients with structural heart disease. Because their clinical relevance remains unclear, fast nonclinical VTs are often not targeted. However, an accepted definition for fast VT is lacking. The shortest possible CL of a monomorphic reentrant VT is determined by the ventricular refractory period (VRP)., Objective: The purpose of this study was to propose a patient-specific definition for fast VT based on the individual VRP (fVT VRP ) and assess the prognostic significance of persistent inducibility after ablation of fVT VRP for VT recurrence., Methods: Of 191 patients with previous myocardial infarction or with nonischemic cardiomyopathy undergoing VT ablation, 70 (age 63 ± 13 years; 64% ischemic) remained inducible for a nonclinical VT and composed the study population. FVT VRP was defined as any VT with CL ≤VRP 400 + 30 ms. Patients were followed for VT recurrence., Results: After ablation, 30 patients (43%) remained inducible exclusively for fVT VRP and 40 (57%) for any slower VT. Patients with only fVT VRP had 3-year VT-free survival of 64% (95% confidence interval [CI] 46%-82%) compared to 27% (95% CI 14%-48%) for patients with any slower remaining VT (P = .013). Inducibility of only fVT VRP was independently associated with lower VT recurrence (hazard ratio 0.38; 95% CI 0.19-0.86; P = .019). Among 36 patients inducible for any fVT VRP , only 1 had recurrence with fVT VRP ., Conclusion: In patients with structural heart disease, inducibility of exclusively fVT VRP after ablation is associated with low VT recurrence., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Individualized estimation of prognosis after cardiac resynchronization therapy (CRT) remains challenging. Our aim was to develop a multiparametric prognostic risk score (CRT-SCORE) that could be used for patient-specific clinical shared decision making about CRT implantation. The CRT-SCORE was derived from an ongoing CRT registry, including 1,053 consecutive patients (age 67 ± 10 years, 76% male). Using preimplantation variables, 100 multiple imputed datasets were generated for model calibration. Based on multivariate Cox regression models, cross-validated linear prognostic scores were calculated, as well as survival fractions at 1 and 5 years. Specifically, the CRT-SCORE was calculated using atrioventricular junction ablation, age, gender, etiology, New York Heart Association class, diabetes, hemoglobin level, renal function, left bundle branch block, QRS duration, atrial fibrillation, left ventricular systolic and diastolic functions, and mitral regurgitation, and showed a good discriminative ability (areas under the curve 0.773 at 1 year and 0.748 at 5 years). During the long-term follow-up (median 60 months, interquartile range 31 to 85), all-cause mortality was observed in 494 (47%) patients. Based on the distribution of the CRT-SCORE, lower- and higher-risk patient groups were identified. Estimated mean survival rates of 98% at 1 year and 92% at 5 years were observed in the lowest 5% risk group (L5 CRT-SCORE: -4.42 to -1.60), whereas the highest 5% risk group (H5 CRT-SCORE: 1.44 to 2.89) showed poor survival rates: 78% at 1 year and 22% at 5 years. In conclusion, the CRT-SCORE allows accurate prediction of 1- and 5-year survival rates after CRT using readily available and CRT-specific clinical, electrocardiographic, and echocardiographic parameters. The model may assist clinicians in counseling patients and in decision making., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Myocardial scar is known to be associated with limited left ventricular (LV) reverse remodeling after cardiac resynchronization therapy (CRT). However, the impact of diffuse myocardial interstitial fibrosis, as assessed with myocardial T 1 mapping cardiac magnetic resonance (CMR), has not been studied in patients with CRT. Therefore, we aimed at evaluating the association between diffuse myocardial interstitial fibrosis, in nonischemic cardiomyopathy patients, and LV reverse remodeling after CRT. A total of 40 patients (61 ± 11 years) with nonischemic cardiomyopathy who underwent CMR before CRT implantation were included. Myocardial T 1 mapping was performed using an inversion-recovery Look-Locker sequence after gadolinium injection. Myocardial contrast-enhanced T 1 time values were assessed from segments without delayed contrast enhancement and normalized for heart rate. At 6-month follow-up, LV reverse remodeling was assessed by the reduction in LV end-systolic volume. Before CRT implantation, mean myocardial contrast-enhanced T 1 time was 351 ± 46 ms. At 6-month follow-up, LV end-systolic volume decreased by 24 ± 21%. Myocardial contrast-enhanced T 1 time showed a significant correlation with LV reverse remodeling (r = 0.5, p = 0.001) together with hemoglobin level, renal function, LV dyssynchrony, and presence of delayed contrast enhancement. Multivariate regression analysis identified myocardial contrast-enhanced T 1 time (β -0.160, p = 0.022), LV dyssynchrony (β -0.267, p = 0.002), and renal function (β -0.334, p = 0.021) as independent associates of LV reverse remodeling. In conclusion, in nonischemic cardiomyopathy, diffuse interstitial myocardial fibrosis quantified with T 1 mapping CMR is independently associated with LV reverse remodeling after CRT and might, therefore, be used to optimize patient selection., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Super-response to cardiac resynchronization therapy (CRT) is associated with significant left ventricular (LV) reverse remodeling and improved clinical outcome. The study aimed to: (1) evaluate whether LV reverse remodeling remains sustained during long-term follow-up in super-responders and (2) analyze the association between the course of LV reverse remodeling and ventricular arrhythmias. Of all, primary prevention super-responders to CRT were selected. Super-response was defined as LV end-systolic volume reduction of ≥30% 6 months after device implantation. Cox regression analysis was performed to investigate the association of LV ejection fraction (LVEF) as time-dependent variable with implantable-cardioverter defibrillator (ICD) therapy and mortality. A total of 171 super-responders to CRT-defibrillator were included (mean age 67 ± 9 years; 66% men; 37% ischemic heart disease). Here of 129 patients received at least 1 echocardiographic evaluation after a median follow-up of 62 months (25th to 75th percentile, 38 to 87). LV end-diastolic volume, LV end-systolic volume, and LVEF after 6-month follow-up were comparable with those after 62-month follow-up (p = 0.90, p = 0.37, and p = 0.55, respectively). Changes in LVEF during follow-up in super-responders were independently associated with appropriate ICD therapy (hazard ratio 0.94, 95% CI 0.90 to 0.98; p = 0.005) and all-cause mortality (hazard ratio 0.95, 95% CI 0.91 to 1.00; p = 0.04). A 5% increase in LVEF was associated with a 1.37 times lower risk of appropriate ICD therapy and a 1.30 times lower risk of mortality. In conclusion, LV reverse remodeling in super-responders to CRT remains sustained during long-term follow-up. Changes in LVEF during follow-up were associated with mortality and ICD therapy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background and Objectives: Cardiac resynchronization therapy (CRT) is a well established heart failure treatment that has shown to improve renal function. However, landmark CRT trials excluded patients with severe renal dysfunction. Therefore, this study evaluated the effect of CRT on renal function and long-term prognosis in patients with stage 4 CKD., Design, Setting, Participants, & Measurements: This study evaluated 73 consecutive CRT patients (71±10 years) with stage 4 CKD who underwent echocardiographic and renal function evaluation at baseline and 6-month follow-up between 2000 and 2012. As a control group, 18 patients with stage 4 CKD who received an implantable cardioverter defibrillator (ICD) were selected. CRT recipients with ≥15% reduction in left ventricular end-systolic volume at 6-month follow-up were classified as CRT responders. During long-term follow-up (median, 33 months), appropriate defibrillator therapy, heart failure hospitalizations, and all-cause mortality (combined end point) were recorded., Results: At 6-month follow-up, a significant reduction in left ventricular end-systolic volume was observed in CRT patients compared with patients with ICD (from 159±78 to 145±78 ml in CRT patients and from 126±54 to 119±49 ml in ICD patients; P=0.05), and CRT response was observed in 22 patients (30%). Compared with ICD patients, eGFR improved among CRT patients (from 25±4 to 30±9 ml/min per 1.73 m(2); interaction time and group, P=0.04) and was more pronounced among CRT responders (25±3 to 34±9 ml/min per 1.73 m(2); P<0.001). The combined end point was observed in 17 ICD and 62 CRT patients. CRT patients showed superior survival compared with ICD patients (log-rank P=0.03). More importantly, CRT response was independently associated with improved survival free from the combined end point (hazard ratio, 0.51; 95% confidence interval, 0.27 to 0.98; P=0.04) after adjustment for clinical and echocardiographic parameters., Conclusions: Response to CRT occurs in approximately 30% of patients with stage 4 CKD, which is less than in the average CRT population. CRT was associated with better clinical outcome, and particularly, CRT response was associated with improvement in eGFR and better long-term prognosis., (Copyright © 2015 by the American Society of Nephrology.)

Background: Transvenous left ventricular (LV) lead placement for cardiac resynchronization therapy-defibrillator (CRT-D) delivery is unsuccessful in 8% to 10% of cases. These patients might benefit from an epicardial lead. However, data on long-term epicardial lead performance are scarce. Furthermore, extracting an epicardial lead requires a rethoracotomy., Objective: The purpose of this study was to determine data on almost a decade of experience with epicardial leads and investigate the safety of partially leaving this lead in place after device infection., Methods: All adult patients receiving an epicardial lead (Medtronic CapSure Epi, model 4968) for CRT-D in the Leiden University Medical Center were included. Leads were implanted during a standalone procedure or in combination with other cardiothoracic procedures. Electrical lead parameters were assessed at implantation and every 6 months thereafter. In case of device infection the epicardial lead was cut off parasternal, just outside the thoracic cavity, leaving the distal part of the lead in place., Results: Two-hundred sixteen patients were included with a median follow-up of 3 years (25th-75th percentile 1.0-5.5). LV pacing threshold decreased within 6 months after implantation [1.1 V (95% confidence interval [CI] 0.9-1.2) vs 0.8 V (95% CI 0.7-0.9), P = .01] and stabilized thereafter. Mean LV electrogram was 15.2 ± 7.5 mV, and average lead impedance was 633.5 ± 174.0 Ω. Five-year cumulative incidence was 1.6% for lead failure and 9.6% for device infection. The retained epicardial lead caused skin erosion in 3 patients and fistula formation in 1., Conclusion: This study demonstrates that epicardial LV leads have an excellent long-term performance. Partially retaining the lead after device infection was associated with a risk of reinfection with limited long-term clinical implications for the patient., (Copyright © 2015. Published by Elsevier Inc.)

Aims: Mortality and ventricular arrhythmias are reduced in patients responding to cardiac resynchronization therapy (CRT). This response is accompanied by improvement in LVEF, and some patients even outgrow original eligibility criteria for implantable cardioverter-defibrillator (ICD) implantation. It is however unclear if these patients still benefit from ICD treatment. The current study aimed to evaluate if the incidence of ICD therapy is related to the extent of CRT response., Methods and Results: All patients who underwent primary prevention CRT-defibrillator implantation were included. They were divided into subgroups according to the reduction in LV end-systolic volume (LVESV) 6 months after implantation. Pre-defined subgroups were: negative responders (increased LVESV), non-responders (decreased LVESV 0-14%), responders (decreased LVESV 15-29%), and super-responders (decreased LVESV ≥30%). During a median follow-up of 57 months (25th-75th percentile 39-84), 512 patients were studied [101 (20%) negative responders, 101 (20%) non-responders, 149 (29%) responders, and 161 (31%) super-responders]. In the first year of follow-up super-responders received significantly less appropriate ICD therapy (3% vs. 12%; P < 0.001). The 5-year cumulative incidence of appropriate ICD therapy was 31% [95% confidence interval (CI) 19-43] in negative responders, 39% (95% CI 25-53) in non-responders, 34% (95% CI 25-43) in responders, and 27% (95% CI 18-35) in super-responders, respectively (p = 0.13)., Conclusions: The extent of CRT response was associated with a parallel reduction of appropriate device therapy during the first year of follow-up. Thereafter, no association was observed. Furthermore, 23% of super-responders were treated for potentially life-threatening arrhythmias and benefit from ICD treatment., (© 2014 The Authors. European Journal of Heart Failure © 2014 European Society of Cardiology.)

Background: Limited data are available on efficacy, safety, and long-term prognosis after cardiac resynchronization therapy (CRT) in elderly patients. We aimed at evaluating the effect of CRT, device-related adverse events, and long-term outcome after CRT among elderly patients., Methods and Results: A total of 798 CRT recipients (208 elderly: age, ≥75 years; 590 nonelderly: age, <75 years) underwent clinical and echocardiographic evaluation at baseline and 6-month follow-up. Elderly patients had similar improvements in clinical symptoms, left ventricular function, and left ventricular reverse remodeling as their counterparts. Similar rates of device-related in-hospital (within 24 hours; P=0.552), early (within 30 days; P=0.984), and long-term adverse events (entire follow-up; hazard ratio, 0.90; P=0.620) were observed between groups. During long-term follow-up (median, 38.6 months; interquartile range, 22.5-61.8 months), all-cause mortality rate was significantly higher among the elderly patients. However, the differences in cumulative event rates started after 4 years of follow-up (P=0.013), and the cause of death was mainly noncardiac (29% in the elderly versus 19% in nonelderly; P<0.001). Diabetes mellitus (hazard ratio, 2.322; P=0.019), impaired renal function (hazard ratio, 0.975; P=0.006), and reduced 6-minute walk distance (hazard ratio, 0.996; P<0.019) were independently associated with all-cause mortality in elderly patients., Conclusions: CRT efficacy and device-related adverse events in elderly patients were comparable with that of nonelderly patients. However, after 4 years of follow-up, elderly patients showed worse survival and the cause of death was mainly noncardiac. Diabetes mellitus, impaired renal function, and reduced 6-minute walk distance were independently associated with all-cause mortality of elderly patients., (© 2014 American Heart Association, Inc.)

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 © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: The relationship between changes in N-terminal pro-brain natriuretic peptide (NT-proBNP) and echocardiographic or clinical definitions of response to cardiac resynchronization therapy (CRT) has not been evaluated. The aims of the present evaluation were to assess: (1) the relationship between changes in NT-proBNP after 6 months of CRT and clinical and echocardiographic responses; (2) the association between NT-proBNP changes and long-term outcome., Methods: In 170 patients treated with CRT (age 61 ± 11 years, 75% male), clinical and echocardiographic parameters and circulating NT-proBNP levels were assessed at baseline and 6 months after CRT. At 6 months follow-up, improvement in New York Heart Association class ≥ 1 point, decrease in left ventricular end-systolic volume ≥ 15%, and decrease in NT-proBNP ≥ 15% defined clinical, echocardiographic, and neurohormonal CRT response, respectively. All-cause mortality data were collected and related to neurohormonal response., Results: Neurohormonal, echocardiographic, and clinical response rates were 54%, 58%, and 66%, respectively. The majority of patients (71%) showing echocardiographic response had NT-proBNP reduction ≥ 15%. In contrast, only 58% of patients who showed clinical response also had NT-proBNP reduction ≥ 15%. During a median follow-up of 32 months, 40 patients died. Patients with neurohormonal response demonstrated a superior long-term outcome compared to patients without neurohormonal response (log-rank P = 0.02)., Conclusions: NT-proBNP reduction ≥ 15% showed better agreement with echocardiographic response compared to clinical response. Neurohormonal response was associated with superior long-term outcome compared to insufficient reduction in NT-proBNP levels., (©2013, The Authors. Journal compilation ©2013 Wiley Periodicals, Inc.)

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.

Objectives: Right ventricular (RV) function is an important prognostic marker in heart failure. However, its impact on all-cause mortality following cardiac resynchronisation therapy (CRT) independent of confounding factors has not been evaluated. Furthermore, evidence concerning the effect of CRT on RV function is limited. The study's aims were to: (1) assess the prognostic importance of RV function among CRT recipients, and (2) characterise RV functional change following CRT and its determinants., Design: Retrospective observational study., Setting: Single tertiary centre., Patients: A total of 848 CRT recipients (median age 65 years, 78% male, 60% ischaemic) underwent echocardiography before and 6 months after CRT. RV function was evaluated using tricuspid annular plane systolic excursion (TAPSE), with a ≤14 mm threshold indicating severe RV impairment. The primary endpoint was long-term all-cause mortality., Results: Significant baseline RV dysfunction was observed in 286 (34%) individuals. After a median 44 months, 288 deaths occurred. RV impairment was associated with a greater incidence of all-cause mortality (log-rank p<0.001). Independent predictors of this endpoint were functional class, ischaemic aetiology, diabetes, atrial fibrillation, renal dysfunction, bigger left ventricular (LV) end-systolic volume, less LV dyssynchrony and reduced TAPSE. Importantly, TAPSE added prognostic value to these recognised prognostic parameters (likelihood-ratio test p<0.001). Furthermore, improvement in RV function after CRT was independent of the improvement in LV systolic function but significantly associated with the improvement in LV diastolic function. Importantly, a favourable RV functional response to CRT was associated with superior survival., Conclusions: RV function is an independent predictor of long-term outcome following CRT.

Objective: The influence of diabetes on cardiac resynchronization therapy (CRT) remains unclear. The aims of the current study were to 1) assess the changes in left ventricular (LV) systolic and diastolic function and 2) evaluate long-term prognosis in CRT recipients with diabetes., Research Design and Methods: A total of 710 CRT recipients (171 with diabetes) were included from an ongoing registry. Echocardiographic evaluation, including LV systolic and diastolic function assessment, was performed at baseline and 6-month follow-up. Response to CRT was defined as a reduction of ≥15% in LV end-systolic volume (LVESV) at the 6-month follow-up. During long-term follow-up (median = 38 months), all-cause mortality (primary end point) and cardiac death or heart failure hospitalization (secondary end point) were recorded., Results: At the 6-month follow-up, significant LV reverse remodeling was observed both in diabetic and non-diabetic patients. However, the response to CRT occurred more frequently in non-diabetic patients than in diabetic patients (57 vs. 45%, P < 0.05). Furthermore, a significant improvement in LV diastolic function was observed both in diabetic and non-diabetic patients, but was more pronounced in non-diabetic patients. The determinants of the response to CRT among diabetic patients were LV dyssynchrony, ischemic cardiomyopathy, and insulin use. Both primary and secondary end points were more frequent in diabetic patients (P < 0.001). Particularly, diabetes was independently associated with all-cause mortality together with ischemic cardiomyopathy, renal function, LVESV, LV dyssynchrony, and LV diastolic dysfunction., Conclusions: Heart failure patients with diabetes exhibit significant improvements in LV systolic and diastolic function after CRT, although they are less pronounced than in non-diabetic patients. Diabetes was independently associated with all-cause mortality.

Aims: The aims of this study were: (i) to characterize consecutive cardiac resynchronization therapy (CRT) recipients with right bundle branch block (RBBB) in comparison with left bundle branch block (LBBB) and (ii) to identify independent predictors of long-term outcome among CRT recipients with RBBB. The presence of RBBB has been associated with poorer prognosis after CRT compared with LBBB; however, little is known about the differences in cardiac mechanics between RBBB and LBBB patients. Furthermore, predictors of favourable outcome after CRT in patients with RBBB have not been identified., Methods and Results: Five hundred and sixty-one consecutive CRT recipients (89 with RBBB and 472 with LBBB) underwent echocardiography before and 6 months after CRT to determine left ventricular (LV) size and function, and interventricular and LV dyssynchrony (as measured by tissue Doppler imaging). Long-term follow-up to identify a composite endpoint of all-cause mortality or heart failure hospitalization was available. Right bundle branch block patients exhibited a higher prevalence of male gender, ischaemic heart disease, atrial fibrillation, and lower exercise capacity when compared with LBBB patients, despite smaller LV volumes. In addition, the extent of both interventricular and LV dyssynchrony was less in RBBB patients. Six months after CRT, RBBB patients also showed limited LV reverse remodelling. At long-term follow-up, LV dyssynchrony and mitral regurgitation were identified as independent predictors of all-cause mortality or heart failure hospitalization among RBBB patients., Conclusion: Left ventricular dyssynchrony may be an important determinant of outcome following CRT in patients with RBBB and may help in the selection of CRT candidates.

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.

'Multimodality' imaging--the side-by-side interpretation of data obtained from various noninvasive imaging techniques, such as echocardiography, radionuclide techniques, multidetector CT (MDCT), and MRI--allows anatomical, morphological, and functional data to be combined, increases diagnostic accuracy, and improves the efficacy of cardiovascular interventions and clinical outcomes. During the past decade, advances in software and hardware have allowed co-registration of various imaging modalities, resulting in cardiac 'hybrid' or 'fusion' imaging. In this Review, we discuss the roles of both multimodality and hybrid imaging in three broad areas of cardiology--coronary artery disease (CAD), heart failure, and valvular heart disease. In the evaluation of CAD, integration of either single-photon emission computed tomography (SPECT) or PET with CT coronary angiography provides both morphological and functional data in a single procedure. Accordingly, the functional consequences (myocardial hypoperfusion on SPECT or PET) of anatomical pathology (coronary anatomy on MDCT or MRI) can be assessed. Co-registration of PET and MRI data sets to provide cellular and molecular information on plaque composition and stability is now possible. Furthermore, novel imaging modalities have been implemented to guide electrophysiological and transcatheter-based procedures, such as cardiac resynchronization therapy (an established treatment for patients with heart failure), and transcatheter valve repair or replacement procedures.

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 improves clinical symptoms and prognosis of heart failure patients. However, it has been shown that up to 40% of patients do not respond to this therapy. Three main determinants of cardiac resynchronization therapy response have been identified: left ventricular dyssynchrony, left ventricular lead position, and extent and location of myocardial scar tissue. Two-dimensional echocardiography is the first imaging technique to evaluate patients who may be candidates for cardiac resynchronization therapy. However, a multimodality approach based on 3-dimensional imaging techniques may provide a more comprehensive evaluation of these patients by combining the assessment of the aforementioned pathophysiological determinants of cardiac resynchronization therapy response., (Copyright © 2011 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.)

Aims: Changes in left ventricular (LV) diastolic function after cardiac resynchronization therapy (CRT) in relation to LV reverse remodelling and heart failure aetiology have not been extensively characterized. The aims of the study were to evaluate changes in LV diastolic function with speckle-tracking echocardiography in relation to: (i) cardiac resynchronization therapy response (LV remodelling) and (ii) heart failure aetiology., Methods and Results: A total of 192 heart failure patients undergoing CRT implantation were evaluated. Speckle-tracking echocardiography was performed before and 6 months after implantation and reliable analysis was obtained in 188 patients. Left ventricular diastolic function was assessed by measuring diastolic strain rate during the isovolumic relaxation period (SR(IVR)) and by calculating the ratio of peak transmitral E-wave to SR(IVR) (E/SR(IVR)). Changes in LV diastolic parameters were evaluated in responders and non-responders and in patients with ischaemic and non-ischaemic cardiomyopathy. Response to CRT was defined as ≥15% reduction in LV end-systolic volume at 6 months follow-up. One-hundred and nine patients (58%) were defined as responders. Significant improvements in LV diastolic performance were observed in responders with improvement in SR(IVR) (from 0.14 ± 0.08 to 0.18 ± 0.12 s(-1), P= 0.001) and E/SR(IVR) (from 834 ± 840 to 641 ± 612, P= 0.04). In addition, LV relaxation improved in patients with non-ischaemic aetiology (SR(IVR): from 0.15 ± 0.08 to 0.19 ± 0.13 s(-1), P= 0.004). In contrast, LV relaxation did not improve in non-responders and in patients with ischaemic heart disease., Conclusions: Novel diastolic strain rate indices are useful for evaluating changes in LV diastolic function after CRT. Improvement in diastolic function was only observed in responders to CRT and patients with non-ischaemic aetiology.

Triplane tissue synchronization imaging (TSI) and real-time 3-dimensional echocardiography (RT3DE) provide different characterizations of left ventricular (LV) mechanics and dyssynchrony. Triplane TSI assesses differences in time to peak systolic segmental myocardial tissue velocities, whereas RT3DE evaluates differences in time to minimum end-systolic regional volumes. Whether an approach using the 2 3D techniques predicts better significant reverse remodeling after cardiac resynchronization therapy (CRT) remains unknown. In 166 patients (mean age 66 ± 9 years, 78% men) treated with CRT, baseline LV dyssynchrony was assessed using RT3DE and triplane TSI. LV dyssynchrony was defined by a systolic dyssynchrony index ≥6.4% when assessed with RT3DE and SD of time to peak velocity of 12 segments (Ts-SD-12) ≥33 ms with triplane TSI. CRT response was defined by ≥15% decrease in LV end-systolic volume at 6-month follow-up. Mean LV dyssynchrony using Ts-SD-12 was 48 ± 26 ms and mean systolic dyssynchrony index was 8.51 ± 3.81%. Response to CRT was observed in 86.3% of patients showing LV dyssynchrony with the 2 methods. In contrast, 97% of patients who did not show significant LV dyssynchrony with any of the techniques were nonresponders (p <0.001). Importantly, systolic dyssynchrony index and LV dyssynchrony using Ts-SD-12 were independent predictors of response to CRT (p <0.001 for each technique). Assessment of LV dyssynchrony with the 2 techniques showed incremental value for prediction of significant LV reverse remodeling over its assessment with only 1 technique (chi-square 90.18, p <0.001). In conclusion, the combined use of 2 different 3D techniques to assess LV dyssynchrony permits accurate prediction of response to CRT., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The number of patients with congenital heart disease (CHD) has significantly increased over the last decades. The CHD population has a high prevalence of heart failure during late follow-up and this is a major cause of mortality. Cardiac resynchronization therapy (CRT) may be a promising therapy to improve the clinical outcome of CHD and paediatric patients with heart failure. However, the CHD and paediatric population is a highly heterogeneous group with different anatomical substrates that may influence the effects of CRT. Echocardiography is the mainstay imaging modality to evaluate CHD and paediatric patients with heart failure and novel echocardiographic tools permit a comprehensive assessment of cardiac dyssynchrony that may help selecting candidates for CRT. This article reviews the role of CRT in the CHD and paediatric population with heart failure. The current inclusion criteria for CRT as well as the outcomes of different anatomical subgroups are evaluated. Finally, echocardiographic assessment of mechanical dyssynchrony in the CHD and paediatric population and its role in predicting response to CRT is comprehensively discussed.

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.

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.)

Cost-effectiveness estimates can help optimize use of available financial resources and this is especially relevant for implementation of cardiac resynchronization therapy (CRT), given the high upfront costs and the timescale of expected benefits. All available cost-effectiveness estimates for devices with (CRT-P) or without (CRT-D) a defibrillator are based on results of randomized trials of selected patients, with a relatively brief follow-up. Extrapolation suggests that the cost effectiveness of CRT may become more favourable as time horizons increase. Using a lifetime time horizon and comparison with optimal medical therapy, the cost effectiveness of both CRT-P and CRT-D appears to meet the $50 000/QALY benchmark commonly used for health-care interventions in the USA, as well as similar thresholds used in Europe. The absence of direct comparisons of the efficacy/effectiveness of CRT-P and CRT-D hampers cost-effectiveness comparisons, and so clinical judgment in the context of current evidence supporting the benefits of cardioverter-defibrillators may provide a rational basis for choosing between CRT-P and CRT-D. Efforts are currently being dedicated to improve CRT response rates by improved patient selection and, reasonably, any improvement in this field will translate into improved effectiveness, and therefore into improved cost effectiveness. The extended longevity of CRT devices will also positively impact cost-effectiveness estimates.

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.)

Purpose: The aim of the current study was to evaluate the relationship between the site of latest mechanical activation as assessed with gated myocardial perfusion SPECT (GMPS), left ventricular (LV) lead position and response to cardiac resynchronization therapy (CRT)., Methods: The patient population consisted of consecutive patients with advanced heart failure in whom CRT was currently indicated. Before implantation, 2-D echocardiography and GMPS were performed. The echocardiography was performed to assess LV end-systolic volume (LVESV), LV end-diastolic volume (LVEDV) and LV ejection fraction (LVEF). The site of latest mechanical activation was assessed by phase analysis of GMPS studies and related to LV lead position on fluoroscopy. Echocardiography was repeated after 6 months of CRT. CRT response was defined as a decrease of ≥15% in LVESV., Results: Enrolled in the study were 90 patients (72% men, 67±10 years) with advanced heart failure. In 52 patients (58%), the LV lead was positioned at the site of latest mechanical activation (concordant), and in 38 patients (42%) the LV lead was positioned outside the site of latest mechanical activation (discordant). CRT response was significantly more often documented in patients with a concordant LV lead position than in patients with a discordant LV lead position (79% vs. 26%, p<0.01). After 6 months, patients with a concordant LV lead position showed significant improvement in LVEF, LVESV and LVEDV (p<0.05), whereas patients with a discordant LV lead position showed no significant improvement in these variables., Conclusion: Patients with a concordant LV lead position showed significant improvement in LV volumes and LV systolic function, whereas patients with a discordant LV lead position showed no significant improvements.

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., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier 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.

Background The Seattle Heart Failure Model (SHFM) provides accurate estimates of survival in heart failure (HF) patients. The model is, however, not developed for HF patients with cardiac resynchronization therapy (CRT). The aim of this study was to assess the prognostic value of SHFM combined with QRS morphology and CRT-related change in QRS duration in implantable cardioverter defibrillator (ICD) and CRT defibrillator (CRT-D) recipients. Methods All patients who underwent prophylactic ICD implantation at the Leiden University Medical Center since 1996 were included. Baseline SHFM, QRS morphology, and duration before and after device implantation were determined. The regression coefficients of the QRS characteristics derived from a Cox regression analysis were implemented in the SHFM. SHFM-estimated survival was compared with Kaplan-Meier observed survival. Results The current study includes 1,834 defibrillator recipients (63 ± 11 years; 79% male; 53% CRT-D). In 585 (60%) CRT-D recipients a left bundle branch block was present, the mean QRS duration was 147 ± 31 ms before and 151 ± 27 ms after device implantation. After a median follow-up of 4.4 years (25th-75th percentile 2.7-6.4 years), 285 (29%) CRT-D recipients had died. CRT-related decrease in QRS duration adjusted for QRS morphology was associated with improved survival (hazard ratio 1.05/10 ms; 95% confidence interval [CI]: 1.01-1.09; P = 0.02). The estimated 5-year survival of CRT-D recipients after implementation of the QRS characteristic was 70%, and comparable with the observed 5-year survival of 68% (95% CI: 65-72). Conclusion Implementation of native QRS morphology and change in QRS duration due to CRT in the SHFM improves the prognostic value of this model in HF patients with CRT-D. [ABSTRACT FROM AUTHOR]

Background Large randomized trials demonstrated the beneficial effect of implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy–defibrillator (CRT-D) treatments in selected patients. Data on long-term follow-up of patients outside the setting of clinical trials are scarce. Objective The aim of this study was to evaluate the long-term outcome of ICD and CRT-D recipients. Methods All patients who underwent ICD (n = 1729 [57%]) or CRT-D (n = 1326 [43%]) implantation at the Leiden University Medical Center since 1996 were evaluated. Follow-up visits were performed every 3–6 months, and events were registered. Cumulative incidence curves of device therapy and device-related complications were adjusted for the competing risk of all-cause mortality. Results After a median follow-up of 5.1 years (25th–75th percentile 3.1–7.8 years), 842 patients (28%) died. The cumulative incidence of all-cause mortality was 49% (95% confidence interval [CI] 45%–54%) in ICD recipients after 12 years of follow-up and 55% (95% CI 52%–58%) in CRT-D recipients after 8 years of follow-up. A total of 1081 patients (35%) received appropriate defibrillator therapy. The cumulative incidence of appropriate therapy in ICD patients was 58% (95% CI 54%–62%) after 12 years of follow-up and 39% (95% CI 35%–43%) in CRT-D patients after 8 years of follow-up. Twelve-year cumulative incidences of adverse events were 20% (95% CI 18%–22%) for inappropriate shock, 6% (95% CI 5%–8%) for device-related infection, and 17% (95% CI 14%–21%) for lead failure. Conclusion After long-term follow-up of ICD (12 years) and CRT-D (8 years) recipients, 49% of ICD recipients and 55% of CRT-D recipients had died. Appropriate ICD therapy was received by the majority (58%) of ICD recipients and by almost 40% of CRT-D recipients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM PUBLISHER]

Background: Cardiac device infections (CDIs) are a serious complication associated with the implantation of cardiac rhythm devices. However, the effect of CDI on the subsequent risk of mortality is unknown. Objective: To assess the prognostic importance of CDI in recipients of implantable cardioverter-defibrillator and cardiac resynchronization therapy – defibrillator. Methods: All patients who received their initial implantable cardioverter-defibrillator/cardiac resynchronization therapy – defibrillator between January 2000 and September 2009 were included. During follow-up, the occurrence of CDI and all-cause mortality were noted. The prognostic importance of the first CDI on mortality was assessed by modeling CDI as a time-dependent covariate in the Cox proportional hazards model. Results: A total of 2476 patients (79% men; mean age 62 ± 13 years) were included in this analysis. During follow-up, CDI occurred in 64 (2.6%) patients. The 1-year mortality following first CDI was 16.9% (95% confidence interval 6.7%–27.1%). Experiencing the first CDI was associated with a 1.9-fold (hazard ratio 1.87; 95% confidence interval 1.07–3.26) increased risk of mortality compared to patients who did not experience CDI. After controlling for possible confounders, this increased to a 2.4-fold (hazard ratio 2.40; 95% confidence interval 1.35–4.28) increased risk of mortality. Conclusions: In a large cohort of patients who receive implantable cardioverter-defibrillator/cardiac resynchronization therapy – defibrillator after their initial implant, the 3-year incidence of CDI was 2.6%. The occurrence of CDI was associated with substantial 1-year mortality, and patients experiencing CDI had a more than 2-fold increased risk of mortality compared with patients who remained free from CDI. [Copyright &y& Elsevier]

The article presents a study on the effect of myocardial ultrasound reflectivity on cardiac resynchronization therapy (CRT) response. It says that one important aspect for the response of CRT is left ventricular (LV) fibrosis due to the benefits of CRT. Methods used include standard echocardiography, mechanical dyssynchrony, and CRT implantation to 184 heart failure patients. Results show the importance of assessment of myocardial ultrasound reflectivity to predict the CRT response of patients.

The authors discuss an incremental value of assessing left ventricular (LV) twist mechanics in patients with heart failure (HF) and its potential usefulness in characterizing response to cardiac resynchronization therapy (CRT) and reversal of LV remodeling at 6 months follow-up. They also underscore a critical relationship between LV lead position and changes in LV twist after CRT, and suggest that the reversal of LV remodeling in HF patients following CRT primarily results from restoration of the global sequence of LV twist mechanics. [Copyright &y& Elsevier]

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). [ABSTRACT FROM PUBLISHER]

Cardiac pacing is the only effective treatment for patients with sick sinus syndrome and atrioventricular conduction disorders. In cardiac pacing, the endocardial pacing lead is typically positioned at the right ventricular (RV) apex. At the same time, there is increasing indirect evidence, derived from large pacing mode selection trials and observational studies, that conventional RV apical pacing may have detrimental effects on cardiac structure and left ventricular function, which are associated with the development of heart failure. These detrimental effects may be related to the abnormal electrical and mechanical activation pattern of the ventricles (or ventricular dyssynchrony) caused by RV apical pacing. Still, it remains uncertain if the deterioration of left ventricular function as noted in a proportion of patients receiving RV apical pacing is directly related to acutely induced left ventricular dyssynchrony. The upgrade from RV pacing to cardiac resynchronization therapy may partially reverse the deleterious effects of RV pacing. It has even been suggested that selected patients with a conventional pacemaker indication should receive cardiac resynchronization therapy to avoid the deleterious effects. This review will provide a contemporary overview of the available evidence on the detrimental effects of RV apical pacing. Furthermore, the available alternatives for patients with a standard pacemaker indication will be discussed. In particular, the role of cardiac resynchronization therapy and alternative RV pacing sites in these patients will be reviewed. [Copyright &y& Elsevier]

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]

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 re- sponders. 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 (onloff 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. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the value of real-time three-dimensional echocardiography (RT3DE) to predict acute response to cardiac resynchronization therapy (CRT). Methods: Sixty consecutive heart failure patients scheduled for CRT were included. RT3DE was performed before and within 48 hours after pacemaker implantation to calculate both left ventricular (LV) volumes and LV dyssynchrony. LV dyssynchrony was defined as the standard deviation of the time taken to reach the minimum systolic volume for 16 LV segments (referred to as the systolic dyssynchrony index, SDI). Patients were subsequently divided into acute responders or nonresponders, based on a reduction ≥ 15% in LV end-systolic volume immediately after CRT. Results: Four patients (7%) were excluded from further analysis because of either suboptimal apical acquisitions or significant translation artifacts. Out of the remaining 56 patients, 35 patients (63%) were classified as acute responders. Baseline characteristics were similar between responders and nonresponders, except for the SDI, which was larger in responders. Moreover, responders demonstrated a significant reduction of SDI immediately after CRT (from 9.7 ± 4.1% to 3.6 ± 1.8%, P < 0.0001), whereas SDI did not change in nonresponders (3.4 ± 1.8% vs 3.1 ± 1.1%, NS). ROC curve analysis revealed that a cut-off value for SDI of 5.6% yielded a sensitivity of 88% with a specificity of 86% to predict acute echocardiographic response to CRT (AUC 0.96). Conclusion: RT3DE is highly predictive for acute response to CRT (sensitivity 88% and specificity 86%). In addition, RT3DE allows assessment of changes in LV volumes and LV ejection fraction before and after CRT implantation. [ABSTRACT FROM AUTHOR]

We report the case of a 13-year-old girl with congenitally corrected transposition of the great arteries. Since the implantation of a conventional pacemaker for acquired complete atrioventricular block, the patient experienced increased heart failure symptoms. Using triplane tissue Doppler imaging, significant intraventricular dyssynchrony induced by unilateral pacing and associated with diminished exercise capacity was demonstrated. A biventricular pacemaker was successfully implanted transvenously, leading to synchronous activation of the systemic ventricle and improved exercise capacity. [ABSTRACT FROM AUTHOR]