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Objectives: The aim of this study was to explore the association between mechanical dyssynchrony of the left ventricle before cardiac resynchronization therapy (CRT) and improvement of mitral regurgitation (MR) after CRT., Background: MR is very frequent among patients with dilated cardiomyopathy and conduction delay., Methods: Echocardiograms (pre-CRT and 12 ± 3.8 months thereafter) of 314 patients with dilated cardiomyopathy and any degree of MR, who underwent CRT device implantation according to guidelines, were analyzed. Left ventricular (LV) mechanical dyssynchrony was assessed by apical rocking (ApRock) and septal flash (SF), while MR severity was graded from I to IV on the basis of vena contracta width, regurgitation jet size, and proximal isovelocity surface area., Results: At baseline, 30% of patients presented with severe MR (grade III or IV). In 62% of patients, MR decreased after CRT, and these patients more frequently had left bundle branch block, had more severe MR, had more dilated left ventricles, had lower ejection fractions, and more often had ApRock and SF. Reverse remodeling was more frequent among patients with MR reduction (ΔLV end-systolic volume -35.5% ± 27.2% vs -4.1% ± 33.2%; P < 0.001). In a multivariable logistic stepwise regression, only ApRock (odds ratio [OR]: 3.8; 95% CI: 1.7-8.5; P = 0.001), SF (OR: 3.6; 95% CI: 1.6-7.9; P = 0.002), and baseline MR (OR: 1.4; 95% CI: 1.0-1.9; P = 0.046) remained significantly associated with MR reduction., Conclusions: ApRock, SF, and severity of MR at baseline are strongly associated with MR reduction after CRT, while LV reverse remodeling is its underlying mechanism. Therefore, in patients with heart failure with LV dyssynchrony on optimal medical treatment, CRT should be the primary treatment attempt for relevant MR., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Setting up a randomized trial to assess the association of mechanical dyssynchrony (MD) and the success of cardiac resynchronization therapy (CRT) in heart failure with a wide QRS complex is ethically challenging. We therefore investigated this association in a retrospective cohort study observing different treatment strategies which were chosen based on the availability of health care resources. The survival of 500 patients from six Western European centers treated with CRT was compared to their 137 Eastern European counterparts not treated with CRT, with regard to the presence of MD. MD was visually assessed and was defined as the presence of apical rocking and/or septal flash. Patients were followed for a mean of 26 ± 8 months for the occurrence of death of any cause. As compared with medical therapy alone, CRT was associated with a more favorable survival (hazard ratio (HR), 0.53; 95% confidence interval (CI) 0.35-0.79; P = 0.002). Patients with MD treated by CRT had better survival than patients belonging to all other groups-they showed 72%, 66% and 56% reduction in all-cause mortality, respectively, compared to patients with MD not treated by CRT (HR 0.28; 95% CI 0.17-0.44), patients without MD treated by CRT (HR 0.34; 95% CI 0.22-0.52) and patients without MD not treated by CRT (HR 0.44; 95% CI 0.25-0.76). Patients with wide QRS complex who are treated with CRT have a significantly better survival when MD is present.

Aims: Investigating the acute impact of cardiac resynchronization therapy (CRT) on regional myocardial work distribution in the left ventricle (LV) and to which extent it is related to long-term reverse remodelling., Methods and Results: One hundred and thirty heart failure patients, referred for CRT implantation, were recruited in our prospective multicentre study. Regional myocardial work was calculated from non-invasive segmental stress-strain loop area before and immediately after CRT. The magnitude of volumetric reverse remodelling was determined from the change in LV end-systolic volume, 11 ± 2 months after implantation. CRT caused acute redistribution of myocardial work across the LV, with an increase in septal work, and decrease in LV lateral wall work (all P < 0.05). Amongst all LV walls, the acute change in work in the septum and lateral wall of the four-chamber view correlated best and significantly with volumetric reverse remodelling (r = 0.62, P < 0.0001), with largest change seen in patients with most volumetric reverse remodelling. In multivariate linear regression analysis, including conventional parameters, such as pre-implant QRS morphology and duration, LV ejection fraction, ischaemic origin of cardiomyopathy, and the redistribution of work across the septal and lateral walls, the latter appeared as the strongest determinant of volumetric reverse remodelling after CRT (model R2 = 0.414, P < 0.0001)., Conclusion: The acute redistribution of regional myocardial work between the septal and lateral wall of the LV is an important determinant of reverse remodelling after CRT implantation. Our data suggest that the treatment of the loading imbalance should, therefore, be the main aim of CRT., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Aim: To determine if incorporation of assessment of mechanical dyssynchrony could improve the prognostic value of patient selection based on current guidelines., Methods and Results: Echocardiography was performed in 1060 patients before and 12 ± 6 months after cardiac resynchronization therapy (CRT) implantation. Mechanical dyssynchrony, defined as the presence of apical rocking or septal flash was visually assessed at the baseline examination. Response was defined as ≥15% reduction in left ventricular end-systolic volume at follow-up. Patients were followed for a median of 59 months (interquartile range 37-86 months) for the occurrence of death of any cause. Applying the latest European guidelines retrospectively, 63.4% of the patients had been implanted with a Class I recommendation, 18.2% with Class IIa, 9.4% with Class IIb, and in 9% no clear therapy recommendation was present. Response rates were 65% in Class I, 50% in IIa, 38% in IIb patients, and 40% in patients without a clear guideline-based recommendation. Assessment of mechanical dyssynchrony improved response rates to 77% in Class I, 75% in IIa, 62% in IIb, and 69% in patients without a guideline-based recommendation. Non-significant difference in survival among guideline recommendation classes was found (Log-rank P = 0.2). Presence of mechanical dyssynchrony predicted long-term outcome better than guideline Classes I, IIa, IIb (Log-rank P < 0.0001, 0.006, 0.004, respectively) and in patients with no guideline recommendation (P = 0.02). Comparable results were observed using the latest American Guidelines., Conclusion: Our data suggest that current guideline criteria for CRT candidate selection could be improved by incorporating assessment of mechanical asynchrony.

Aims: The interaction between asynchronous regional myocardial activation and left ventricular (LV) wall remodelling has not been well established. We investigated the relationship between time of onset of longitudinal shortening (Tonset), regional myocardial work, and segmental LV wall thickness (SWT) in patients treated with cardiac resynchronization therapy (CRT)., Methods and Results: We analysed 26 patients with sinus rhythm, non-ischaemic cardiomyopathy (63 ± 9 years, 69% male, QRS duration 174 ± 18 ms) and positive response to CRT (15% reduction in end-systolic volume). Longitudinal strain was obtained by 2D speckle-tracking echocardiography before and after [14.5 (7-29) months] CRT. Tonset and SWT were measured in 18 segments per LV. Segmental myocardial work was calculated from non-invasive segmental stress-strain loop area. Before CRT, Tonset was the shortest in septal and anteroseptal and the longest in lateral and posterior walls (P < 0.001) and not different after CRT (P = 0.733). Before CRT, septal and anteroseptal walls were significantly thinner than lateral and posterior. After CRT, reverse remodelling increased thickness in septal and anteroseptal and thinned lateral and posterior segments (P < 0.001). Before CRT, non-uniformity in work distribution with reduced work in septal and anteroseptal and increased work in lateral and posterior walls (P < 0.001) was observed. After CRT, distribution of myocardial work was uniform (P = 0.215)., Conclusion: Dys-synchronous myocardial shortening is related to thinning of early and thickening of late activated segments in heart failure with conduction delay. Correction of dys-synchrony leads to regression of inhomogeneity towards more evenly distributed wall thickness. Regional differences in myocardial work load that are homogenized by successful CRT are considered as the underlying pathophysiological mechanism.

Background: New echocardiographic parameters (apical rocking [AR], septal flash [SF]) are intended to detect patterns specific to responders to cardiac resynchronization therapy (CRT). The patterns are visually recognized and qualitatively described, requiring experience and training. Speckle-tracking echocardiography can reflect SF and AR by using newly developed, dedicated parameters, such as start systolic index (SSI) and peak longitudinal displacement (PLD). The aim of this study was to investigate whether SSI and PLD can identify potential CRT responders., Methods: In 125 patients, echocardiograms from before and 9 ± 3 months after CRT were retrospectively analyzed with dedicated EchoPAC prerelease software. From speckle-tracking baseline images, color-coded bull's-eye displays of SSI and PLD were generated. Cutoff values for both parameters were derived from 25 randomly selected patients and applied to the remaining 100 patients to identify CRT response, defined as a decrease in end-systolic volume of ≥15% during follow-up. The performance of SSI and PLD was compared with the visual assessment of AR and SF by expert and novice readers., Results: Expert readers detected 77 patients with AR, identifying CRT responders with sensitivity and specificity of 85 ± 2% and 82 ± 2%, respectively. Novice readers reached 74 ± 7% sensitivity and 55 ± 11% specificity, while the sensitivity and specificity of the quantitative analysis were 72 ± 3% and 84 ± 4% for SSI and 80 ± 1% and 75 ± 2% for PLD, respectively., Conclusions: New speckle-tracking-based quantitative assessment of mechanical dyssynchrony by SSI and PLD performs comparably in identifying CRT responders as visual analysis by expert readers and performs significantly better than novice readers., (Copyright © 2016 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Aims: Apical rocking (ApRock) and septal flash (SF) are often observed phenomena in asynchronously contracting ventricles. We investigated the relationship of visually assessed ApRock and SF, reverse remodelling, and long-term survival in cardiac resynchronization therapy (CRT) candidates., Methods and Results: A total of 1060 patients eligible for CRT underwent echocardiographic examinations before and 12 ± 6 months after device implantation. Three blinded physicians were asked to visually assess the presence of ApRock and SF before device implantation and also their correction by CRT 12 ± 6 months post-implantation. Patients with a left ventricular (LV) end-systolic volume decrease of ≥15% during the first year of follow-up were regarded as responders. Patients were followed for a median period of 46 months (interquartile range: 27-65 months) for the occurrence of death of any cause. If corrected by CRT, visually assessed ApRock and SF were associated with reverse remodelling with a sensitivity of 84 and 79%, specificity of 79 and 74%, and accuracy of 82 and 77%, respectively. ApRock (hazard ratio [HR] 0.40, 95% confidence interval [CI] 0.30-0.53, P < 0.0001) and SF (HR 0.45 [CI 0.34-0.61], P < 0.001) were independently associated with lower all-cause mortality after CRT and had an incremental value over clinical variables and QRS width for identifying CRT responders. Both the absence of ApRock/SF and unsuccessful correction of ApRock/SF despite CRT were associated with a high risk for non-response and an unfavourable long-term survival., Conclusion: A specific LV mechanical dyssynchrony pattern, characterized by ApRock and SF, is associated with a more favourable long-term survival after CRT. Both parameters are also indicators of an effective therapy., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Aims  Investigating the acute impact of cardiac resynchronization therapy (CRT) on regional myocardial work distribution in the left ventricle (LV) and to which extent it is related to long-term reverse remodelling. Methods and results  One hundred and thirty heart failure patients, referred for CRT implantation, were recruited in our prospective multicentre study. Regional myocardial work was calculated from non-invasive segmental stress–strain loop area before and immediately after CRT. The magnitude of volumetric reverse remodelling was determined from the change in LV end-systolic volume, 11 ± 2 months after implantation. CRT caused acute redistribution of myocardial work across the LV, with an increase in septal work, and decrease in LV lateral wall work (all P  < 0.05). Amongst all LV walls, the acute change in work in the septum and lateral wall of the four-chamber view correlated best and significantly with volumetric reverse remodelling (r  = 0.62, P  < 0.0001), with largest change seen in patients with most volumetric reverse remodelling. In multivariate linear regression analysis, including conventional parameters, such as pre-implant QRS morphology and duration, LV ejection fraction, ischaemic origin of cardiomyopathy, and the redistribution of work across the septal and lateral walls, the latter appeared as the strongest determinant of volumetric reverse remodelling after CRT (model R 2 = 0.414, P  < 0.0001). Conclusion  The acute redistribution of regional myocardial work between the septal and lateral wall of the LV is an important determinant of reverse remodelling after CRT implantation. Our data suggest that the treatment of the loading imbalance should, therefore, be the main aim of CRT. [ABSTRACT FROM AUTHOR]

Aims Observation of better outcome in women after cardiac resynchronization therapy (CRT) has led to controversies about a potential sex-specific response. In this study, we investigated to which extent this sex-specific difference in CRT outcome could be explained by differences in baseline characteristics between both sexes. Methods and results We retrospectively analysed data from a multicentre registry of 1058 patients who received CRT. Patients were examined by echocardiography before and 12 ± 6 months after implantation. Response was defined as ≥15% reduction of left ventricular end-systolic volume at follow-up. Patient's characteristics at baseline, including New York Heart Association class, ejection fraction, QRS width and morphology, ischaemic aetiology of cardiomyopathy (ICM), number of scarred segments, age at implantation, atrial fibrillation, and mechanical dyssynchrony (Dyss) were analysed. Patients were followed for a median duration of 59 months. Primary end point was all-cause mortality. Women (24% of the population) had less ICM (23% vs. 49%, P  <   0.0001), less scarred segments (0.4 ± 1.3 vs. 1.0 ± 2.1, P  <   0.0001), more left bundle branch block (LBBB; 87% vs. 80%, P  =   0.01), and more Dyss at baseline (78% vs. 57%, P  <   0.0001). Without matching baseline differences, women showed better survival (log rank P  <   0.0001). After matching, survival was similar (log rank P  =   0.58). In multivariable analysis, female sex was no independent predictor of neither volumetric response (P  =   0.06) nor survival (P  =   0.31). Conclusion Our data suggest that the repeatedly observed better outcome in women after CRT is mainly due to the lower rate ICM and smaller scars. When comparing patients with similar baseline characteristics, the response of both sexes to CRT is similar. [ABSTRACT FROM AUTHOR]

Background: Psychological distress is common in patients with cardiovascular disease and negatively impacts outcome. Hypothesis: Psychological distress is high in acute high risk cardiac patients eligible for a WCD, and associated with low quality of life. Distress is aggravated by WCD. Methods: Consecutive patients eligible for a WCD were included in the prospective, multicenter “Cologne Registry of External Defibrillator” registry. Quality of life (Short Form-12), depressive symptoms (Beck-Depression Inventory II) and anxiety (State Trait Anxiety Inventory) were assessed at enrollment and 6-weeks, and associations with WCD prescription were analyzed. Results: 123 patients (mean [SD] age 59 [± 14] years, 75% male) were included, 85 (69%) of whom received a WCD. At enrollment 21% showed clinically significant depressive symptoms and 52% anxiety symptoms, respectively. At 6 weeks, depressive and anxious symptoms significantly decreased to 7% and 25%, respectively. Depressive symptoms at enrollment and changes at 6 weeks showed significant associations with health-related quality of life, whereas anxious symptoms did not. There was a trend for better improvement of depression scores in patients with WCD (mean [SD] change in score points: -4.1 [6.1] vs -1.8 [3.9]; p = 0.09), whereas change of the anxiousness score was not different (-4.6 [9.5]) vs -3.7 [9.1], p = 0.68). Conclusion: In patients eligible for a WCD, depressive and anxiety symptoms were initially common and depressive symptoms showed a strong association with reduced health-related quality of life contributing to their clinical relevance. WCD recipients showed at least similar improvement of depression and anxiety at 6 weeks when compared to non recipients. [ABSTRACT FROM AUTHOR]

Aim To determine if incorporation of assessment of mechanical dyssynchrony could improve the prognostic value of patient selection based on current guidelines. Methods and results Echocardiography was performed in 1060 patients before and 12 ± 6 months after cardiac resynchronization therapy (CRT) implantation. Mechanical dyssynchrony, defined as the presence of apical rocking or septal flash was visually assessed at the baseline examination. Response was defined as ≥15% reduction in left ventricular end-systolic volume at follow-up. Patients were followed for a median of 59 months (interquartile range 37–86 months) for the occurrence of death of any cause. Applying the latest European guidelines retrospectively, 63.4% of the patients had been implanted with a Class I recommendation, 18.2% with Class IIa, 9.4% with Class IIb, and in 9% no clear therapy recommendation was present. Response rates were 65% in Class I, 50% in IIa, 38% in IIb patients, and 40% in patients without a clear guideline-based recommendation. Assessment of mechanical dyssynchrony improved response rates to 77% in Class I, 75% in IIa, 62% in IIb, and 69% in patients without a guideline-based recommendation. Non-significant difference in survival among guideline recommendation classes was found (Log-rank P  = 0.2). Presence of mechanical dyssynchrony predicted long-term outcome better than guideline Classes I, IIa, IIb (Log-rank P  <   0.0001, 0.006, 0.004, respectively) and in patients with no guideline recommendation (P  = 0.02). Comparable results were observed using the latest American Guidelines. Conclusion Our data suggest that current guideline criteria for CRT candidate selection could be improved by incorporating assessment of mechanical asynchrony. [ABSTRACT FROM AUTHOR]

Aims The interaction between asynchronous regional myocardial activation and left ventricular (LV) wall remodelling has not been well established. We investigated the relationship between time of onset of longitudinal shortening (T onset), regional myocardial work, and segmental LV wall thickness (SWT) in patients treated with cardiac resynchronization therapy (CRT). Methods and results We analysed 26 patients with sinus rhythm, non-ischaemic cardiomyopathy (63 ± 9 years, 69% male, QRS duration 174 ± 18 ms) and positive response to CRT (15% reduction in end-systolic volume). Longitudinal strain was obtained by 2D speckle-tracking echocardiography before and after [14.5 (7–29) months] CRT. T onset and SWT were measured in 18 segments per LV. Segmental myocardial work was calculated from non-invasive segmental stress–strain loop area. Before CRT, T onset was the shortest in septal and anteroseptal and the longest in lateral and posterior walls (P  < 0.001) and not different after CRT (P  = 0.733). Before CRT, septal and anteroseptal walls were significantly thinner than lateral and posterior. After CRT, reverse remodelling increased thickness in septal and anteroseptal and thinned lateral and posterior segments (P  < 0.001). Before CRT, non-uniformity in work distribution with reduced work in septal and anteroseptal and increased work in lateral and posterior walls (P  < 0.001) was observed. After CRT, distribution of myocardial work was uniform (P  = 0.215). Conclusion Dys-synchronous myocardial shortening is related to thinning of early and thickening of late activated segments in heart failure with conduction delay. Correction of dys-synchrony leads to regression of inhomogeneity towards more evenly distributed wall thickness. Regional differences in myocardial work load that are homogenized by successful CRT are considered as the underlying pathophysiological mechanism. [ABSTRACT FROM AUTHOR]