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Purpose To assess long-term geometric changes of the mitral valve apparatus using cardiac CT in individuals who underwent cardiac resynchronization therapy (CRT). Materials and Methods Participants from a randomized controlled trial with cardiac CT examinations before CRT implantation and at 6 months follow-up (Clinicaltrials.gov identifier NCT01323686) were invited to undergo an additional long-term follow-up cardiac CT examination. The geometry of the mitral valve apparatus, including mitral valve annulus area, A2 leaflet angle, tenting height, and interpapillary muscle distances, were assessed. Geometric changes at the long-term follow-up examination were reported as mean differences (95% CI), and the Pearson correlation test was used to assess correlation between statistically significant geometric changes and left ventricular (LV) volumes and function. Results Thirty participants (mean age, 68 years ± 9 [SD]; 25 male participants) underwent cardiac CT imaging after a median long-term follow-up of 9.0 years (IQR, 8.4-9.4). There were reductions in end-systolic A2 leaflet angle (-4° [95% CI: -7, -2]), end-systolic tenting height (-1 mm [95% CI: -2, -1]), and end-systolic and end-diastolic interpapillary muscle distances (-4 mm [95% CI: -6, -2]) compared with pre-CRT implantation values. The mitral valve annulus area remained unchanged. LV end-diastolic and end-systolic volumes decreased (-68 mL [95% CI: -99, -37] and -67 mL [95% CI: -96, -39], respectively), and LV ejection fraction increased (13% [95% CI: 7, 19]) at the long-term follow-up examination. Changes in interpapillary muscle distances showed moderate to strong correlations with LV volumes ( r = 0.42-0.72; P < .05), while A2 leaflet angle and tenting height were not correlated to LV volumes or function. Conclusion Among the various geometric changes in the mitral valve apparatus after long-term CRT, the reduction in interpapillary muscle distances correlated with LV volumes while the reduced A2 leaflet angle and tenting height did not correlate with LV volumes. Keywords: Mitral Valve Apparatus, Cardiac Resynchronization Therapy, Cardiac CT Supplemental material is available for this article. © RSNA, 2024.

Implantable devices form an integral part of the management of patients with heart failure (HF) and provide adjunctive therapies in addition to cornerstone drug treatment. Although the number of these devices is growing, only few are supported by robust evidence. Current devices aim to improve haemodynamics, improve reverse remodelling, or provide electrical therapy. A number of these devices have guideline recommendations and some have been shown to improve outcomes such as cardiac resynchronization therapy, implantable cardioverter-defibrillators and long-term mechanical support. For others, more evidence is still needed before large-scale implementation can be strongly advised. Of note, devices and drugs can work synergistically in HF as improved disease control with devices can allow for further optimization of drug therapy. Therefore, some devices might already be considered early in the disease trajectory of HF patients, while others might only be reserved for advanced HF. As such, device therapy should be integrated into HF care programmes. Unfortunately, implementation of devices, including those with the greatest evidence, in clinical care pathways is still suboptimal. This clinical consensus document of the Heart Failure Association (HFA) and European Heart Rhythm Association (EHRA) of the European Society of Cardiology (ESC) describes the physiological rationale behind device-provided therapy and also device-guided management, offers an overview of current implantable device options recommended by the guidelines and proposes a new integrated model of device therapy as a part of HF care., (© 2024 European Society of Cardiology.)

Cardiac resynchronization therapy (CRT) is an effective therapy in selected patients with advanced heart failure that reduces all-cause mortality at short-term follow-up. However, data regarding long-term mortality after CRT implantation are scarce, with no separate analysis available of the covariates associated with respectively short-term and long-term outcomes. Accordingly, the present study evaluated the risk factors associated with short-term (2-year follow-up) versus long-term (10-year follow-up) mortality after CRT implantation. Patients who underwent CRT implantation and had echocardiographic evaluation before implantation were included in the present study. The primary end point was all-cause mortality, and independent associates of short-term (2-year follow-up) and long-term (10-year follow-up) mortality were compared. In total, 894 patients (mean age 66 ± 10 years, 76% males) who underwent CRT implantation were included in the present study. The cumulative overall survival rates for the total population were 91%, 71%, and 45% at 2-, 5- and 10-year follow-up, respectively. Multivariable Cox regression analysis showed that short-term mortality was associated with both clinical and echocardiographic variables at the moment of CRT implantation; whereas long-term mortality was predominantly associated with baseline clinical parameters and was less strongly associated with baseline echocardiographic parameters. In conclusion, at long-term (10-year) follow-up, a significant proportion (45%) of patients with advanced heart failure who underwent CRT implantation were still alive. Importantly, the risk assessment for short-term (2-year follow-up) and long-term (10-year follow-up) mortality differ considerably, which may influence clinical decision making., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aims: Tricuspid regurgitation (TR) is common in patients with heart failure (HF) and is associated with worse outcome. This study investigated the effect of cardiac resynchronization therapy (CRT) on TR severity and long-term outcome., Methods and Results: Tricuspid regurgitation severity was assessed at baseline and 6 months after CRT implantation, using a multiparametric approach. Patients were divided into four groups: (i) no or mild TR without progression; (ii) no or mild TR with progression to significant (moderate-severe) TR; (iii) significant TR with improvement to no or mild TR; and (iv) significant TR without improvement. The primary endpoint was all-cause mortality. A total of 852 patients (mean age 65 ± 11 years, 77% male) were included. At baseline, 184 (22%) patients had significant TR, with 75 (41%) showing significant improvement at 6-month follow-up. After a median follow-up of 92 (50-137) months, 494 (58%) patients died. Patients with significant TR showing improvement at follow-up had better outcomes than those showing no improvement (P = 0.016). On multivariable analysis, no or mild TR progressing to significant TR [hazard ratio (HR) 1.745; 95% confidence interval (CI): 1.287-2.366; P < 0.001] and significant TR without improvement (HR 1.572; 95% CI: 1.198-2.063; P = 0.001) were independently associated with all-cause mortality, whereas significant TR with improvement at follow-up was not (HR: 1.153; 95% CI: 0.814-1.633; P = 0.424)., Conclusion: Improvement of significant TR after CRT is observed in a substantial proportion of patients, highlighting the potential benefit of CRT for patients with HF having significant TR. Significant TR at 6 months after CRT is independently associated with increased long-term mortality., Competing Interests: Conflict of interest: The Department of Cardiology, Heart Lung Center, Leiden University Medical Centre received research grants from Abbott Vascular, Bayer, Biotronik, Bioventrix, Boston Scientific, Edwards Lifesciences, GE Healthcare, Ionis, and Medtronic. J.J.B. received speaker fees from Abbott Vascular. N.A.M. received speaker fees from Abbott Vascular and GE Healthcare. V.D. received speaker fees from Abbott Vascular, Edwards Lifesciences, MSD, and GE Healthcare. All remaining authors have declared no conflicts of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Chronic pressure overload and right ventricular (RV) dysfunction can lead to RV-pulmonary artery (PA) uncoupling in patients with heart failure. The evolution and prognostic values of RV-PA coupling assessed by echocardiography in patients undergoing cardiac resynchronization therapy (CRT) have not been thoroughly investigated. The aim of this study was to evaluate the evolution and prognostic value of tricuspid annular plane systolic excursion (TAPSE)/pulmonary artery systolic pressure (PASP) ratio in CRT recipients., Methods and Results: The RV-PA coupling was measured non-invasively with echocardiography using the TAPSE/PASP ratio at baseline and 6 month follow-up in CRT recipients. The cut-off value for TAPSE/PASP uncoupling was derived from spline curve analysis (i.e. <0.45 mm/mmHg). The primary endpoint was all-cause mortality. A total of 807 patients (age 66 ± 11 years, 76% men) were analysed. During a median follow-up of 97 (54-143) months, 483 (60%) patients died. Survival rates at 3 and 5 year follow-up were significantly lower for patients with a TAPSE/PASP ratio <0.45 mm/mmHg (76% and 58%, respectively), compared with those with a TAPSE/PASP ratio ≥0.45 mm/mmHg (91% and 82%, respectively) (P < 0.001). On multivariable analysis, TAPSE/PASP ratio <0.45 mm/mmHg (hazard ratio 1.437; 95% confidence interval: 1.145-1.805; P = 0.002) was independently associated with all-cause mortality, whereas TAPSE <17 mm (hazard ratio 1.237; 95% confidence interval: 0.990-1.546; P = 0.061) was not. In addition, no improvement of the TAPSE/PASP ratio after CRT implantation was independently associated with worse survival., Conclusions: The TAPSE/PASP ratio at baseline is independently associated with long-term outcomes in CRT recipients. The baseline TAPSE/PASP ratio has incremental value over TAPSE, which does not take account of RV afterload. A lack of improvement in the TAPSE/PASP ratio after CRT implantation is associated with worse survival., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Left ventricular (LV) dilatation may limit LV reverse remodeling after cardiac resynchronization therapy (CRT)., Objective: The purpose of this study was to evaluate the impact of baseline LV volumes on LV reverse remodeling after CRT and whether this is associated with improved survival., Methods: Patients were stratified into quintiles according to baseline LV end-diastolic volume indexed for body surface area (LVEDVi). LV reverse remodeling was defined as ≥15% reduction in LV end-systolic volume at 6-month follow-up after CRT. Independent associates of LV remodeling were assessed and long-term mortality rates were compared between patients with and without LV reverse remodeling (across LVEDVi quintiles)., Results: A total of 864 patients were included (mean age 66 ± 10 years; 657 patients (76%) were male), of whom 101 (12%) were in quintile 1 (<65 mL/m 2 ), 272 (32%) in quintile 2 (65-95 mL/m 2 ), 247 (29%) in quintile 3 (95-125 mL/m 2 ), 151 (18%) in quintile 4 (125-155 mL/m 2 ), and 93 (11%) in quintile 5 (>155 mL/m 2 ). Patients with larger baseline LVEDVi had worse survival after CRT (log-rank, P = .019). The cumulative 10-year survival was significantly better in patients with vs without LV reverse remodeling (48.7% vs 33.9%; P < .001). Significant LV reverse remodeling was observed in all LVEDVi quintiles. In addition, patients with LV reverse remodeling had superior survival than did patients without LV reverse remodeling, regardless of baseline LVEDVi quintile (log-rank, P < .05 for all)., Conclusion: Many patients with larger baseline LV volumes still show significant LV reverse remodeling after CRT and had superior survival (regardless of baseline LV volumes) than did patients without LV reverse remodeling. Therefore, CRT should not be denied on the basis of severe LV dilatation., (Copyright © 2022 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Aims: Left atrial (LA) function is a marker of prognosis in patients with heart failure. The prognostic implications of an improvement in LA function in addition to an improvement in left ventricular (LV) function after cardiac resynchronization therapy (CRT) implantation are unknown. This study aimed to evaluate the prognostic value of a significant change in LA reservoir strain (RS) and/or LV global longitudinal strain (GLS) after initiation of CRT., Methods and Results: LARS and LVGLS were measured with speckle-tracking echocardiography. Significant improvement in LARS and LVGLS was defined as a percentage change of +5% and +20% at 6 months after CRT implantation, respectively. Patients were divided into three groups: no significant reverse remodelling (no improvement in LARS and LVGLS), incomplete reverse remodelling (improvement in LARS or LVGLS), and complete reverse remodelling (improvement in LARS and LVGLS). The primary endpoint was all-cause mortality. A total of 923 patients (mean age 65 ± 10 years, 77% male) were included, of which 221 (24%) had complete reverse remodelling, 414 (45%) incomplete reverse remodelling, and 288 (31%) no significant reverse remodelling. Five-years' mortality was 24%, 29%, and 36% for patients with complete, incomplete, and no significant reverse remodelling, respectively (P < 0.001). On multivariable analysis, complete reverse remodelling (hazard ratio 0.477; 95% confidence interval: 0.362-0.628; P < 0.001) was associated with the lowest risk of mortality., Conclusions: Patients with complete reverse remodelling have a lower mortality risk than those showing incomplete or no significant reverse remodelling. The use of integrated LA and LV deformation imaging may improve risk-stratification of CRT recipients., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2022. For permissions, please email: journals.permissions@oup.com.)

Background: Cardiac resynchronization therapy (CRT) candidates often present with significant mitral and tricuspid regurgitation, pulmonary hypertension and right ventricular dysfunction when referred for device implantation. This study investigated the prognostic value of a novel cardiac staging system, based on the extent of cardiac remodeling prior to implantation., Methods: Data were collected from an ongoing registry of CRT recipients. Patients were divided into 4 groups according to the extent of cardiac remodeling: group 1: left ventricular systolic dysfunction, group 2: left atrial dilatation and/or significant mitral regurgitation, group 3: pulmonary arterial hypertension and/or significant tricuspid regurgitation and group 4: right ventricular systolic impairment. Patients were followed up for the occurrence of all-cause mortality., Results: A total of 844 patients (age 65 ± 10 years, 77% men) were included. Of the overall population, 145 (17%) patients were in group 1, 161 (19%) in group 2, 157 (19%) in group 3 and 381 (45%) in group 4. After a median follow-up of 95 (51-145) months, 517 (61%) patients died. Patients in groups 2, 3 and 4 had significantly higher mortality rates than those in group 1 (p = 0.025, p < 0.001 and p < 0.001, respectively). On multivariable analysis, groups 3 (HR 1.415; 95% CI 1.024-1.957; p = 0.032) and 4 (HR 1.599; 95% CI 1.204-2.123; p = 0.001) were independently associated with all-cause mortality., Conclusions: Most CRT candidates already present with extensive cardiac remodeling at the time of referral. Detection of the extent of cardiac remodeling before CRT implantation results in improved risk-stratification, and underscores the need for early referral., (Copyright © 2022. Published by Elsevier B.V.)

Cardiac resynchronization therapy (CRT) is one of the most effective therapies for heart failure with reduced ejection fraction and leads to improved quality of life, reductions in heart failure hospitalization rates and all-cause mortality. Nevertheless, up to two-thirds of eligible patients are not referred for CRT. Furthermore, post-implantation follow-up is often fragmented and suboptimal, hampering the potential maximal treatment effect. This joint position statement from three European Society of Cardiology Associations, Heart Failure Association (HFA), European Heart Rhythm Association (EHRA) and European Association of Cardiovascular Imaging (EACVI), focuses on optimized implementation of CRT. We offer theoretical and practical strategies to achieve more comprehensive CRT referral and post-procedural care by focusing on four actionable domains: (i) overcoming CRT under-utilization, (ii) better understanding of pre-implant characteristics, (iii) abandoning the term 'non-response' and replacing this by the concept of disease modification, and (iv) implementing a dedicated post-implant CRT care pathway., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Cardiac resynchronization therapy (CRT) is one of the most effective therapies for heart failure with reduced ejection fraction and leads to improved quality of life, reductions in heart failure hospitalization rates and all-cause mortality. Nevertheless, up to two-thirds of eligible patients are not referred for CRT. Furthermore, post-implantation follow-up is often fragmented and suboptimal, hampering the potential maximal treatment effect. This joint position statement from three European Society of Cardiology Associations, Heart Failure Association (HFA), European Heart Rhythm Association (EHRA) and European Association of Cardiovascular Imaging (EACVI), focuses on optimized implementation of CRT. We offer theoretical and practical strategies to achieve more comprehensive CRT referral and post-procedural care by focusing on four actionable domains: (i) overcoming CRT under-utilization, (ii) better understanding of pre-implant characteristics, (iii) abandoning the term 'non-response' and replacing this by the concept of disease modification, and (iv) implementing a dedicated post-implant CRT care pathway., (© the Author(s) 2020. This article has been co-published with permission in European Journal of Heart Failure (published by John Wiley & Sons Ltd on behalf of European Society of Cardiology) and EP Europace.)

Aims: Cardiac resynchronization therapy (CRT) restores mechanical efficiency to the failing left ventricular (LV) by resynchronization of contraction. Global, LV myocardial work efficiency (GLVMWE) can be quantified non-invasively with echocardiography. The prognostic implication of GLVMWE remains unexplored, and we therefore related GLVMWE before CRT to long-term prognosis., Methods and Results: Data were analysed from an ongoing registry of patients with Class I indications for CRT. GLVMWE was defined as the ratio of constructive work in all LV segments, divided by the sum of constructive and wasted work in all LV segments, as a percentage. It was derived from speckle tracking strain echocardiography and non-invasive blood pressure measurements, taken pre-CRT. Patients were dichotomized according to baseline, median GLVMWE [75%; interquartile range (IQR) 66-81%]. A total of 153 patients (66 ± 10 years, 72% male, 48% ischaemic heart disease) were analysed. After a median follow-up of 57 months (IQR 28-76 months), 31% of patients died. CRT recipients with less efficient baseline energetics (GLVMWE <75%) demonstrated lower event rates than patients with more efficient baseline energetics (GLVMWE ≥75%) (log-rank test, P = 0.029). On multivariable analysis, global LV wasted work ratio <75% pre-CRT was independently associated with a decreased risk of all-cause mortality (hazard ratio 0.48, 95% confidence interval 0.25-0.92; P = 0.027), suggesting that the potential for improvement in LV efficiency is important for CRT benefit., Conclusion: GLVMWE can be derived non-invasively from speckle tracking strain echocardiography and non-invasive blood pressure recordings. A lower GLVMWE before CRT is independently associated with improved long-term outcome., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Aims: Cardiac resynchronization therapy (CRT) can reduce left ventricular end-systolic volume (LVESV), and a decrease of ≥15% is defined as a response. CRT can also improve LV global longitudinal strain (GLS). Changes in LVESV and LV GLS are individually associated with outcome post-CRT. We investigated LVESV and LV GLS changes and prognostic implications of improvement in LVESV and/or LV GLS, compared with no improvement in either parameter., Methods and Results: Baseline and 6-month echocardiograms were analysed from CRT recipients with heart failure. LV reverse remodelling was defined as a ≥15% reduction in LVESV at 6 months post-CRT. A ≥5% absolute improvement in LV GLS was defined as a change in LV GLS. A total of 1185 patients were included (mean age 65 ± 10 years, 73% male), and those with an improvement in LVESV and LV GLS (n = 131, 11.1%) had significantly lower mortality compared with other groups. On multivariable analysis, an improvement in both LVESV and LV GLS [hazard ratio (HR): 0.47; 95% confidence interval (CI): 0.31-0.71; P < 0.001] or an improvement in either LVESV or LV GLS (HR: 0.57; 95% CI: 0.47-0.71; P < 0.001) were independently associated with better prognosis, compared with no improvement in either parameter., Conclusion: Either a reduction in LVESV and/or an improvement in LV GLS at 6 months post-CRT are independently associated with improved long-term prognosis, compared with no change in both LVESV and LV GLS. This supports the use of LV GLS as a meaningful parameter in defining CRT response., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Functional mitral regurgitation (FMR) is common in heart failure (HF), and negatively impacts prognosis. Cardiac resynchronization therapy (CRT) can improve FMR, but the long-term changes in and impact of FMR after CRT are still unclear. The present study investigated the prevalence, evolution and impact on mortality of FMR before and after CRT in patients with HF. A total of 1,313 patients (66 ± 11 years, 77% male, 59% ischemic heart disease) treated with CRT were evaluated. Patients were divided into 4 groups of FMR according to the evolution at 6 months after CRT: no or mild FMR at baseline which remained unchanged at 6 months (grade 0-1 FMR unchanged, n = 609 [51%]), no or mild FMR which worsened to moderate to severe (grade 0-1 FMR worsened, n = 66 [6%)]), moderate to severe FMR which improved to no or mild (grade 2-4 improved, n = 209 [18%]), and moderate to severe FMR which remained unchanged (grade 2-4 unchanged, n = 309 [26%]). Over a mean follow-up of 51 ± 38 months, 297 (25%) patients died. Those with baseline FMR grade 0-1 which remained unchanged at 6-month follow-up, as well as baseline FMR grade 2-4 which improved, had lower mortality rates than patients with 6-month FMR grade 2-4 regardless of baseline FMR grade (p <0.001). Baseline FMR grade 2-4 that remained unchanged at 6-month follow-up was associated with increased mortality, independent of the clinical and left ventricular volumetric responses to CRT (hazard ratio, 1.77; 95% confidence interval, 1.41-2.22, p <0.001). In conclusion, moderate to severe FMR at baseline which remains unchanged at 6 months after CRT implantation is strongly associated with long-term mortality in patients with HF., (Copyright © 2018. Published by Elsevier Inc.)

Background: Functional mitral regurgitation (FMR) and atrial fibrillation (AF) are frequent heart failure (HF) complications. Cardiac resynchronization therapy (CRT) can improve FMR; however, little is known about the influence of AF on FMR improvement., Objective: The purpose of this study was to investigate the mechanisms and impact of baseline AF on FMR improvement after CRT., Methods: CRT recipients with HF, AF, or sinus rhythm (SR) at baseline with moderate or severe FMR, were included from an ongoing registry. Left atrial (LA), mitral annular (MA), and left ventricular (LV) dimensions were evaluated echocardiographically. FMR improvement was defined as ≥1 grade decrease from baseline to 6-month follow-up. Clinical and echocardiographic measurements were performed at baseline and 6-month follow-up., Results: A total of 419 patients (age 66 ± 8 years; 73% male) were analyzed. At 6-month follow-up, FMR improved in 145 patients (45.6%) with SR vs 31 of AF patients (30.7%) (P = .011). Despite similar LV reverse remodeling at 6 months after CRT (LV end-systolic volume decreased by 32.1 ± 43.2 mL in the SR group and by 27.7 ± 6.3 mL in those with AF; P = .353), patients with SR exhibited smaller LA volumes (63.0 ± 26.5 mL vs 103.1 ± 41.0 mL; P <.001) and MA diameters (42.3 ± 5.6 mm vs 46.1 ± 5.8 mm; P <.001) compared to AF patients., Conclusion: FMR improvement is more common in CRT recipients in SR vs AF, despite a similar degree of LV remodeling. LA volume and MA diameter are greater in the AF group, causing the negative impact of AF on FMR improvement in CRT, as well as indicating a potential therapeutic target (ie, AF rhythm control)., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: In heart failure (HF) patients, left ventricular mechanical dispersion (LVMD) reflects heterogeneous mechanical activation of the left ventricle. In HF patients, LVMD can be reduced after CRT. Whether lesser LVMD is associated with improved outcome is unknown., Objective: The purpose of this study was to relate LVMD to long-term prognosis in a large cohort of HF patients after 6 months of cardiac resynchronization therapy (CRT)., Methods: Clinical, echocardiographic, and ventricular arrhythmia (VA) data were analyzed from an ongoing registry of HF recipients of CRT. Baseline (before CRT) and 6-month echocardiograms were evaluated. LVMD was calculated as the standard deviation of the time from onset of the QRS complex to the peak longitudinal strain in a 17-segment model. Patients were divided into 2 groups according to the median LVMD (84 ms) at 6 months post-CRT., Results: Of 1185 patients (mean age 65 ± 10 years; 76% male), 343 (29%) died during a mean follow-up of 55 ± 36 months. Baseline LVMD was not associated with all-cause mortality and VA at follow-up. In contrast, patients with less LVMD (≤84 ms) at 6 months post-CRT had lower event rates (VA and mortality) compared to those with LVMD >84 ms. On multivariable analysis, greater LVMD at 6 months after CRT was independently associated with an increased risk of mortality (hazard ratio 1.002; P = .037) and VA (hazard ratio 1.003; P = .026)., Conclusion: Larger LVMD at 6 months after CRT is independently associated with all-cause mortality and VA. LVMD may be valuable in identifying patients who remain at high mortality risk after CRT implantation., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Myocardial fibrosis (macroscopic scar or diffuse reactive fibrosis) is one of the determinants of impaired left ventricular (LV) global longitudinal strain (GLS) in heart failure (HF) patients., Objective: The purpose of this study was to evaluate the prognostic value of LV GLS in HF patients treated with cardiac resynchronization therapy (CRT)., Methods: The study included 829 HF patients (mean age 64.6 ± 10.4 years; 72% men) treated with CRT. Before CRT implantation, LV GLS was assessed using 2-dimensional speckle tracking echocardiography. The primary endpoint was the combination of all-cause mortality, heart transplantation, and LV assist device implantation. The secondary endpoint was the occurrence of ventricular arrhythmias or appropriate implantable defibrillator device therapies., Results: During follow-up, 332 patients reached the primary endpoint, and 233 presented with the secondary endpoint. Patients were divided according to LV GLS quartiles. Patients with the most impaired LV GLS quartile had a 2-fold higher risk of reaching the combined endpoint compared with patients in the best LV GLS quartile (hazard ratio [HR] 2.088; 95% confidence interval [CI] 1.555-2.804; P <.001). LV GLS was significantly associated with the combined endpoint (HR 1.075; 95% CI 1.020-1.133; P = .007) after adjusting for clinical, electrocardiographic, and echocardiographic characteristics. Although patients in the most impaired LV GLS quartile showed higher event rates for the secondary endpoint compared with the other groups, LV GLS was not independently associated with the secondary endpoint (HR 1.047; 95% CI 0.989-1.107; P = .115)., Conclusion: In this large cohort of CRT patients, baseline LV GLS was independently associated with the combined endpoint., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Systolic dyssynchrony index (SDI) using three-dimensional echocardiography (3DE) was shown to be a reliable measure of left ventricular (LV) dyssynchrony. However, the prognostic value of SDI on long-term outcomes after cardiac resynchronization therapy (CRT) remains unknown., Methods and Results: A total of 414 patients (mean age 67 ± 10 years, 60% ischemic etiology) with 3DE evaluation before CRT implantation were included. SDI was evaluated as continuous value and in quartiles. The study endpoint was combined all-cause mortality, heart transplantation, and LV assist device implantation. At baseline, median SDI was 8.0% (IQR 5.6-11.3%). During a median follow-up of 45 months (IQR 25-59 months), the endpoint was observed in 94 (23%) patients. SDI was independently associated with the endpoint together with ischemic etiology, diabetes, and renal function (HR 0.914, P = 0.003) after adjustment for age, atrial fibrillation, hemoglobin level, NYHA functional class, and posterolateral LV lead position. Patients from the 1st, 2nd, and 3rd SDI quartiles showed similar survival and superior as compared to the 4th quartile with the lowest SDI values (≤5.5%; χ²: 30.4, log-rank P < 0.001). From receiver operating characteristic curve analysis, the optimal SDI cut-off value associated with the endpoint was >6.8% (area under the curve 0.634). Finally, a subgroup analysis (293 patients) demonstrated that a more pronounced reduction in SDI immediately after CRT (resynchronization) was independently associated with superior survival (HR 0.461, P = 0.011) after adjustment for prognostic relevant parameters., Conclusion: SDI is independently associated with long-term prognosis after CRT and might therefore be important to optimize risk-stratification in these patients., (© 2018 Wiley Periodicals, Inc.)

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.)

Aims: Assessment of left ventricular (LV) volumes and ejection fraction (LVEF) with cardiac imaging is important in the selection of patients for cardiac resynchronization therapy (CRT). Several observational studies have explored the role of imaging-derived LV dyssynchrony parameters to predict the response to CRT, but have yielded inconsistent results, precluding the inclusion of imaging-derived LV dyssynchrony parameters in current guidelines for selection of patients for CRT., Methods: The EuroCRT is a large European multicentre prospective observational study led by the European Association of Cardiovascular Imaging. We aim to explore if combing the value of cardiac magnetic resonance (CMR) and echocardiography could be beneficial for selecting heart failure patients for CRT in terms of improvement in long-term survival, clinical symptoms, LV function, and volumes. Speckle tracking echocardiography will be used to assess LV dyssynchrony and wasted cardiac work whereas myocardial scar will be assessed with late gadolinium contrast enhanced CMR. All data will be measured in core laboratories. The study will be conducted in European centres with known expertise in both CRT and multimodality cardiac imaging., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

Aims: To evaluate the impact of the interaction of QRS duration and morphology on left ventricular (LV) reverse remodelling and LV functional improvement in heart failure (HF) patients treated with cardiac resynchronization therapy (CRT)., Methods and Results: From an ongoing registry of HF patients treated with CRT according to contemporary guidelines, demographic, clinical, electrocardiographic (ECG) and echocardiographic characteristics were analysed. Patients were divided according to QRS duration and morphology: <150 ms vs. ≥150 ms and left bundle branch block (LBBB) vs. non-LBBB, respectively. Echocardiographic measurements were performed at baseline and at 6 months' follow-up. The effect of the interaction between QRS duration and morphology on LV reverse remodelling and LV ejection fraction (LVEF) was analysed using linear, mixed models. Of 1467 patients (mean age 65 ± 10 years, 77% male), 884 (60%) had a QRS ≥150 ms and 814 (55%) showed LBBB. The group with QRS ≥150 ms demonstrated larger LV reverse remodelling (mean reduction in LV end-systolic volume 34.3 mL vs. 14.8 mL; P < 0.001) and improvement in LVEF (mean increase 6.8% vs. 5.2%; P < 0.001) compared with their counterparts. Similarly, patients with LBBB QRS morphology showed greater LV reverse remodelling (mean reduction in LV end-systolic volume 30.8 mL vs. 17.4 mL; P < 0.001) and improvement in LVEF (mean increase 6.9% vs. 3.7%; P < 0.001) than those with non-LBBB QRS morphology., Conclusions: Left ventricular reverse remodelling and LV functional improvement are greater among HF patients with LBBB morphology and increasing QRS duration who receive CRT., (© 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.)

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.)

Aim: Left ventricular (LV) global longitudinal strain (GLS) reflects LV systolic function and correlates inversely with the extent of LV myocardial scar and fibrosis. The present subanalysis of the Echocardiography Guided CRT trial investigated the prognostic value of LV GLS in patients with narrow QRS complex., Methods and Results: Left ventricular (LV) global longitudinal strain (GLS) was measured on the apical 2-, 4- and 3-chamber views using speckle tracking analysis. Measurement of baseline LV GLS was feasible in 755 patients (374 with cardiac resynchronization therapy (CRT)-ON and 381 with CRT-OFF). The median value of LV GLS in the overall population was 7.9%, interquartile range 6.2-10.1%. After a mean follow-up period of 19.4 months, 95 patients in the CRT-OFF group and 111 in the CRT-ON group reached the combined primary endpoint of all-cause mortality and heart failure hospitalization. Each 1% absolute unit decrease in LV GLS was independently associated with 11% increase in the risk to reach the primary endpoint (Hazard ratio 1.11; 95% confidence interval 95% 1.04-1.17, P < 0.001), after adjusting for ischaemic cardiomyopathy and randomization treatment among other clinically relevant variables. When categorizing patients according to quartiles of LV GLS, the primary endpoint occurred more frequently in patients in the lowest quartile (<6.2%) treated with CRT-ON vs. CRT-OFF (45.6% vs. 28.7%, P = 0.009) whereas, no differences were observed in patients with LV GLS ≥6.2% treated with CRT-OFF vs. CRT-ON (23.7% vs. 24.5%, respectively; P  = 0.62)., Conclusion: Low LV GLS is associated with poor outcome in heart failure patients with QRS width <130 ms, independent of randomization to CRT or not. Importantly, in the group of patients with the lowest LV GLS quartile, CRT may have a detrimental effect on clinical outcomes., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For Permissions, please email: journals.permissions@oup.com.)

Purpose of Review: This article summarizes the most recent imaging techniques to assess left ventricular mechanical dyssynchrony and discusses their value to predict response to cardiac resynchronization therapy (CRT) together with assessment of myocardial scar and cardiac venous anatomy., Recent Findings: Left ventricular mechanical dyssynchrony has been associated with prognosis of heart failure patients and has been shown to influence the efficacy of CRT. Although current guidelines do not recommend the assessment of left ventricular mechanical dyssynchrony to select heart failure patients for CRT, technological advances in echocardiography, cardiac magnetic resonance, nuclear imaging and computed tomography have provided powerful tools to characterize left ventricular mechanical dyssynchrony and predict response to CRT. Most important, these imaging techniques permit integration of additional information that is relevant for the efficacy of CRT, such as the extent and location of myocardial scar and the anatomy of the coronary sinus and tributaries where the left ventricular pacing lead may be positioned., Summary: Left ventricular mechanical dyssynchrony is an important parameter to select heart failure patients who are candidates for CRT. The integration of this parameter together with extent and location of myocardial scar and cardiac venous anatomy is a key to optimize the efficacy of CRT.

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: 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: 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.

Background: Optimization of atrioventricular (AV) and ventriculoventricular (VV) delays of cardiac resynchronization therapy (CRT) devices maximizes left ventricular filling and stroke volume. However, the incremental value of these optimizations over empiric device programming remains unclear. The objective of this analysis was to perform a systematic review and meta-analysis of the effects of AV and VV delay optimization on clinical and echocardiographic end points of patients with heart failure treated with CRT., Methods: A standardized search strategy was performed and identified 12 trials comparing AV and/or VV delay optimization and conventional CRT device programming and their effects on various clinical and echocardiographic outcomes. Pooled odds ratios were analyzed using random-effect meta-analysis with Mantel-Haenszel method., Results: Combined data from a total of 4,356 patients with heart failure treated with CRT showed no differences in clinical or echocardiographic outcomes between patients who underwent AV and/or VV delay optimization and patients who underwent empiric device programming (Mantel-Haenszel odds ratio 0.86 [95% CI 0.68-1.09], P value for overall effect = .21 by intention-to-treat analysis)., Conclusion: The current literature suggests that routine AV and/or VV delay optimization has a neutral effect on clinical and echocardiographic outcomes based on pooled data from randomized and nonrandomized studies. Standardization of patient selection and optimization timing and method may help to further define the role of CRT device optimization., (Copyright © 2013 Mosby, Inc. All rights reserved.)

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.)