Presence Of Mechanical Dyssynchrony Research Articles

The mechanistic interaction between mechanical dyssynchrony and filling pressure in cardiac resynchronization therapy candidates.

Both left ventricular (LV) mechanical dyssynchrony and filling pressure have been shown to be associated with outcome in heart failure patient treated with cardiac resynchronization therapy (CRT). To investigate the mechanistic link between mechanical dyssynchrony and filling pressure and to assess their combined prognostic value in CRT candidates. Left atrial pressure (LAP) estimation and quantification of mechanical dyssynchrony were retrospectively performed in 219 CRT patients using echocardiography. LAP was elevated (eLAP) in 49% of the population, normal (nLAP) in 40%, and indeterminate (iLAP) in 11%. CRT response was defined as %-decrease in LV end-systolic volume after 12±6 months CRT. Clinical endpoint was all-cause mortality during 4.8 years (interquartile range: 2.7-6.0 years). To investigate the mechanistic link between mechanical dyssynchrony and filling pressure, the CircAdapt computer model was used to simulate cardiac mechanics and hemodynamics in virtual hearts with LBBB and various causes of increased filling pressure. Patients with nLAP had more significant mechanical dyssynchrony than those with eLAP. The combined assessment of both parameters before CRT was significantly associated with reverse LV remodeling and post-CRT survival. Simulations revealed that mechanical dyssynchrony is attenuated by increased LV operational chamber stiffness, regardless of whether it is caused by passive or active factors, explaining the link between mechanical dyssynchrony and filling pressure. Our combined clinical-computational data demonstrate that in patients with LBBB, the presence of mechanical dyssynchrony indicates relatively normal LV compliance and low filling pressure, which may explain their strong association with positive outcomes after CRT.

Mechanical dyssynchrony and response to cardiac resynchronization therapy in heart failure patients with right ventricular pacing: a pre-specified subgroup analysis of the BUDAPEST CRT Upgrade trial

Abstract Introduction The BUDAPEST CRT Upgrade trial has established the strong clinical benefit of upgrading heart failure patients with a reduced left ventricular (LV) ejection fraction (HFrEF) and a high right ventricular pacing (RVP) burden to cardiac resynchronization therapy with defibrillator (CRT-D). Importantly, however, the CRT upgrade response is not homogeneous regarding LV reverse remodeling and associated clinical outcomes. The presence of mechanical dyssynchrony (MD) assessed by echocardiography has been linked to more CRT benefits; still, its change in response to CRT and added prognostic value in HFrEF patients with high RVP are scarcely investigated. Purpose Accordingly, we aimed to assess the prevalence, clinical characteristics, CRT response rate, and prognostic value of RVP-induced MD in the BUDAPEST CRT Upgrade cohort. Methods The multicentre, randomized, controlled trial enrolled 360 HFrEF patients with a pacemaker or implantable cardioverter defibrillator (ICD) and significant RVP (≥ 20%) who were randomly assigned to receive CRT-D upgrade or ICD in a 3:2 ratio. Protocol echocardiography was performed at baseline and at 12-month follow-up visits and was evaluated at a central core lab. Beyond LV end-diastolic (EDV) and end-systolic volumes (ESV), longitudinal strain-derived septal deformation patterns by speckle tracking were assessed to determine the presence of RVP-induced MD. The endpoints were volumetric non-response (defined by a relative decrease in LV ESV <15%) and the composite of volumetric non-response or HF hospitalization. Results The echocardiographic assessment was feasible in 325 patients at baseline; 133 (41%) patients presented with MD. Females were more likely to present with MD (female vs. male, 65% vs. 38%, p=0.003). MD patients had higher LV EDV (MD vs. no-MD, 248±78 vs. 219±78 mL, p=0.001) and LV ESV (190±67 vs. 165±64 mL, p<0.001) at baseline. In the CRT-D group, 126 (75%) patients were volumetric responders, and 41 (25%) were non-responders at 12 months. CRT patients with baseline MD were less likely to experience volumetric non-response (OR 0.35 [95% CI 0.15-0.82], p=0.015) or the composite endpoint (OR 0.37 [95% CI 0.17-0.77], p=0.008). Out of 57 CRT patients with baseline MD who had follow-up assessment available, 52 (91%) patients had a favorable change: the MD pattern disappeared. Patients with MD resolution at 12 months were less likely to experience volumetric non-response or the composite endpoint (OR 0.39 [95% CI 0.17-0.93], p=0.034; OR 0.38 [95% CI 0.16-0.86], p=0.021, respectively). CRT patients with resolved MD were less likely of ischemic etiology and had 100% posterior or lateral LV lead location. Conclusions The presence of RVP-induced MD and its resolution is associated with better clinical response in HFrEF patients undergoing CRT-D upgrade. MD assessment can refine patient selection algorithms of CRT.Figure 1

Echocardiographic mechanical dyssynchrony predicts long-term mortality in patients with cardiac resynchronisation therapy

Cardiac resynchronisation therapy (CRT) is an established treatment for patients with symptomatic heart failure with reduced left ventricular ejection fraction (LVEF ≤ 35%; HFrEF) and conduction disturbances (QRS duration ≥ 130 ms). The presence of mechanical dyssynchrony (MD) on echocardiography has been hypothesised to be of predictive value in determining indication for CRT. This study investigated the impact of MD (apical rocking [AR] and septal flash [SF]) on long-term survival in CRT recipients. HFrEF patients (n = 425; mean age 63.0 ± 10.6 years, 72.3% male, 60.7% non-ischaemic aetiology) with a guideline-derived indication for CRT underwent device implantation. MD markers were determined at baseline and after a mean follow-up of 11.5 ± 8.0 months; long-term survival was also determined. AR and/or SF were present in 307 (72.2%) participants at baseline. During post-CRT follow-up, AR and/or SF disappeared in 256 (83.4%) patients. Overall mean survival was 95.9 ± 52.9 months, longer in women than in men (109.1 ± 52.4 vs. 90.9 ± 52.4 months; p < 0.001) and in younger (< 60 years) versus older patients (110.6 ± 53.7 vs. 88.6 ± 51.1 months; p < 0.001). Patients with versus without MD markers at baseline generally survived for longer (106.2 ± 52.0 vs. 68.9 ± 45.4 months; p < 0.001), and survival was best in patients with resolved versus persisting MD (111.6 ± 51.2 vs. 79.7 ± 47.6 months p < 0.001). Age and MD at baseline were strong predictors of long-term survival in HFrEF patients undergoing CRT on multivariate analysis. Novel echocardiography MD parameters in HFrEF CRT recipients predicted long-term mediated better outcome, and survival improved further when AR and/or SF disappear after CRT implantation.Graphical abstract

Mechanical Dyssynchrony Combined with Septal Scarring Reliably Identifies Responders to Cardiac Resynchronization Therapy.

Background and aim: The presence of mechanical dyssynchrony on echocardiography is associated with reverse remodelling and decreased mortality after cardiac resynchronization therapy (CRT). Contrarily, myocardial scar reduces the effect of CRT. This study investigated how well a combined assessment of different markers of mechanical dyssynchrony and scarring identifies CRT responders. Methods: In a prospective multicentre study of 170 CRT recipients, septal flash (SF), apical rocking (ApRock), systolic stretch index (SSI), and lateral-to-septal (LW-S) work differences were assessed using echocardiography. Myocardial scarring was quantified using cardiac magnetic resonance imaging (CMR) or excluded based on a coronary angiogram and clinical history. The primary endpoint was a CRT response, defined as a ≥15% reduction in LV end-systolic volume 12 months after implantation. The secondary endpoint was time-to-death. Results: The combined assessment of mechanical dyssynchrony and septal scarring showed AUCs ranging between 0.81 (95%CI: 0.74-0.88) and 0.86 (95%CI: 0.79-0.91) for predicting a CRT response, without significant differences between the markers, but significantly higher than mechanical dyssynchrony alone. QRS morphology, QRS duration, and LV ejection fraction were not superior in their prediction. Predictive power was similar in the subgroups of patients with ischemic cardiomyopathy. The combined assessments significantly predicted all-cause mortality at 44 ± 13 months after CRT with a hazard ratio ranging from 0.28 (95%CI: 0.12-0.67) to 0.20 (95%CI: 0.08-0.49). Conclusions: The combined assessment of mechanical dyssynchrony and septal scarring identified CRT responders with high predictive power. Both visual and quantitative markers were highly feasible and demonstrated similar results. This work demonstrates the value of imaging LV mechanics and scarring in CRT candidates, which can already be achieved in a clinical routine.

Echocardiographic assessment of CRT candidates. Does it work equally well in intermediate QRS duration?

Abstract Background The presence of mechanical dyssynchrony – such as apical rocking (ApRock) and septal flash (SF) – on echocardiography is associated with favourable outcome after cardiac resynchronization therapy (CRT). Myocardial scar on the other hand, has a considerable negative impact on CRT response. There is growing evidence that a visual echocardiographic assessment of mechanical dyssynchrony by ApRock, SF and scar predicts CRT response. Little is known however if this works equally well in patients with intermediate QRS duration (120–150ms), where guideline recommendation for CRT is weaker. Methods A total of 400 unselected patients referred for CRT, who fulfil the contemporary guidelines, were enrolled in this multicentre study. Echocardiographic images were visually assessed before CRT implantation, focussing on the presence of ApRock, SF and location and extent of scar segments in the left ventricle (LV), resulting in a CRT response prediction (i.e. Reader Interpretation). Readers were blinded to all patient information other than ischaemic aetiology of heart failure. CRT response was defined as ≥15% reduction in LV end-systolic volume on echocardiography, on average 15 months after device implantation. Results Overall, 321 (80%) patients had a left bundle branch block (LBBB), with an average QRS duration of 166±25ms. Ischemic aetiology of heart failure was found in 131 (33%) patients. Before CRT, ApRock and SF were present in 254 (64%) and 244 (61%) patients, respectively. ApRock and SF alone predicted CRT response with an area under the curve (AUC) of 0.79 (95% CI: 0.74–0.84) and 0.78 (95% CI: 0.73–0.83) (Figure A), while the echocardiographic Reader Interpretation had an AUC of 0.85 (95% CI: 0.81–0.89), with a sensitivity of 89% and a specificity of 82% for the prediction of CRT response (Figure B) (p&amp;lt;0.0001 vs. ApRock and SF alone). A total of 92 patients had a QRS duration of 120–150ms, and 48 of them responded to CRT. In these patients, the AUC of Reader Interpretation was comparable to that of the entire study cohort [0.83 (95% CI: 0.75–0.92)], as was sensitivity and specificity (90% and 79%, respectively, p=0.717 vs. the AUC of the entire cohort) (Figure C). Conclusions A visual assessment of LV function, by means of mechanical dyssynchrony and scar, has an excellent predictive value for CRT response, and requires only apical echocardiographic images. Responders were identified equally well in the challenging subgroup of patients with a QRS duration of 120–150 ms. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): KU Leuven

Low septal to lateral wall 18F-FDG ratio is highly associated with mechanical dyssynchrony in non-ischemic CRT candidates

BackgroundIn order to better understand the concept of mechanical dyssynchrony, a promising hallmark of cardiac resynchronization therapy (CRT) response, we investigated its effect on regional myocardial metabolism and myocardial blood flow (MBF) in non-ischemic CRT candidates.ResultsThirty consecutive non-ischemic CRT eligible patients underwent static 18F-FDG and resting dynamic 13N-NH3 PET/CT. 18F-FDG uptake and MBF for septal and lateral wall were analysed and septal-to-lateral wall ratios (SLR) were calculated. Based on the presence of mechanical dyssynchrony (septal flash and/or apical rocking) on echocardiography, patients were divided into 2 groups, with (n = 23) and without (n = 7) mechanical dyssynchrony.Patients with mechanical dyssynchrony had significantly lower 18F-FDG SUVmean in the septum compared with the lateral wall (5.58 ± 2.65 vs 11.19 ± 4.10, p < 0.0001), while patients without mechanical dyssynchrony had a more homogeneous 18F-FDG distribution (7.33 ± 2.88 vs 8.31 ± 2.50, respectively, p = 0.30). Similarly, MBF was significantly different between the septal and lateral wall in the dyssynchrony group (0.57 ± 0.11 ml/g/min vs 0.92 ± 0.23 ml/g/min, respectively, p < 0.0001), whereas no difference was observed in the non-dyssynchrony group (0.61 ± 0.23 ml/g/min vs 0.77 ± 0.21 ml/g/min, respectively, p = 0.16). 18F-FDG SLR, but not MBF SLR, was associated with the presence of mechanical dyssynchrony and showed a significant inverse correlation with volumetric reverse remodeling after CRT (r = − 0.62, p = 0.001).ConclusionsNon-ischemic heart failure patients with mechanical dyssynchrony demonstrate heterogeneous regional metabolism and MBF compared with patients without dyssynchrony. However, only 18F-FDG SLR appeared to be highly associated with the presence of mechanical dyssynchrony.Trial registrationClinicaltrials, NCT02537782. Registered 2 September 2015.

Quantitative Assessment of Left Ventricular Dysfunction in Fetal Ebstein's Anomaly and Tricuspid Valve Dysplasia

Fetal Ebstein's anomaly and tricuspid valve dysplasia (EA/TVD) are associated with high perinatal mortality relative to pulmonary atresia with intact ventricular septum (PAIVS), despite both requiring redistribution of the cardiac output (CO) to the left ventricle (LV). LV dysfunction is suspected to contribute to adverse outcomes in EA/TVD. We sought to examine global and segmental LV function in fetal EA/TVD with comparison to normal controls and PAIVS. We hypothesized that LV dysfunction in EA/TVD is associated with abnormal LV remodeling and interventricular mechanics. We retrospectively identified 63 cases of fetal EA/TVD (40 with retrograde ductal flow) and 22 cases of PAIVS encountered from 2004 to 2015 and compared findings to 77 controls of comparable gestational age. We measured the combined CO and global LV function using two-dimensional, Doppler-derived, deformational (six-segmental vector velocity imaging) and dyssynchrony indices (DIs; SD of time to peak), and a novel global DI. EA/TVD fetuses demonstrated abnormal LV global systolic function with reduced ejection fraction, fractional area change, and CO, while in PAIVS we observed a normal ejection fraction, fractional area change, and CO. PAIVS, but not EA/TVD, demonstrated increased LV sphericity, suggestive of remodeling, and associated enhanced radial function in the third trimester. In contrast, while EA/TVD fetuses had normal LV segmental longitudinal strain, there was abnormal radial segmental deformation and LV dyssynchrony with increased SD of time to peak and DI. Fetal EA/TVD is associated with a lack of spherical remodeling and presence of mechanical dyssynchrony, which likely contribute to reduced CO and ejection fraction. Clinical monitoring of LV function is warranted in fetal EA/TVD. Further studies incorporating quantification of LV function into prediction models for adverse outcomes are required.

Use of GATED-SPECT for Ventricular Desynchronization Evaluation in Patients with Heart Failure Submitted to Cardiac Resynchronization Therapy

Abstract Background: Approximately 20 to 40% of patients with heart failure do not respond to cardiac resynchronization therapy (CRT). To improve patient selection, phase analysis by myocardial perfusion scintigraphy (GSPECT) was developed. Objectives: To evaluate the clinical and scintigraphic response of patients with heart failure (HF) submitted to CRT using GSPECT. Method: This was an interventional study that included consecutive patients assessed by GSPECT four weeks prior to CRT implantation and six months after it for comparison. These patients also answered the Minnesota Living with Heart Failure Questionnaire (MLHFQ). The categorical variables were compared using Fisher's exact test and chi-square test, whereas Student's t-test was used for numerical variables. The level of statistical significance was set at 5%. The scintigraphic variables analyzed were left ventricular ejection fraction, end-systolic volume, end-diastolic volume, left ventricular mass, standard deviation and bandwidth, as well as QRS duration and the Minnesota Quality of Life Questionnaire score. The presence of mechanical dyssynchrony was defined as standard deviation > 43o. Results: Nine patients were included in the study. After the cardiac resynchronization therapy, there was a significant improvement (p < 0.05) in the end-systolic volume (206 ± 80 mL vs. 158 ± 108 mL), QRS (180 ± 18 ms vs. 120 ± 9 ms), left ventricular mass (248 ± 65 g vs. 193 ± 52 g) and Minnesota Quality of Life Questionnaire score (63 ± 16 vs. 34 ± 20). All patients with scintigraphic criteria of mechanical dyssynchrony showed clinical improvement. Two patients had only electrical dyssynchrony and did not achieve significant clinical improvement, although they showed QRS duration reduction. Conclusion: GSPECT was able to differentiate patients with isolated electrical dyssynchrony from those with associated mechanical dyssynchrony, through the intraventricular dyssynchrony parameters. The cardiac resynchronization therapy is associated with the improvement of both mechanical and electrical dyssynchrony. Pre-implantation GSPECT showed that patients with associated electrical and mechanical dyssynchrony had a better response to cardiac resynchronization therapy than those with isolated electrical dyssynchrony.

Relation between electrical and mechanical dyssynchrony in patients with left bundle branch block: An electro- and vectorcardiographic study.

Current guidelines select patients for cardiac resynchronization therapy (CRT) mainly on electrocardiographic parameters like QRS duration and left bundle branch block (LBBB). However, among those LBBB patients, heterogeneity in mechanical dyssynchrony occurs and might be a reason for nonresponse to CRT. This study assesses the relation between electrocardiographic characteristics and presence of mechanical dyssynchrony among LBBB patients. The study included patients with true LBBB (including mid-QRS notching) on standard 12-lead electrocardiograms. Left bundle branch block-induced mechanical dyssynchrony was assessed by the presence of septal flash on two-dimensional echocardiography. Previously reported electro- and vectorcardiographic dyssynchrony markers were analyzed: global QRS duration (QRSDLBBB ), left ventricular activation time (QRSDLVAT ), time to intrinsicoid deflection (QRSDID ), and vectorcardiographic QRS areas in the 3D vector loop (QRSA3D ). The study enrolled 545 LBBB patients. Septal flash (SF) is present in 52% of patients presenting with true LBBB. Patients with SF are more frequent female, have less ischemic heart disease and smaller left ventricular dimensions. In multivariate analysis longer QRSDLBBB , QRSDLVAT and larger QRSA3D were independently associated with SF. Of all parameters, QRSA3D has the best accuracy to predict SF, although overall accuracy remains moderate (59% sensitivity, 58% specificity). The predictive value of QRSA3D remained constant in both sexes, irrespective of ischemic heart disease, ejection fraction and even when categorizing for QRSDLBBB . In LBBB patients, large QRS areas correlate better with mechanical dyssynchrony compared to wide QRSD intervals. However, the overall accuracy to predict mechanical dyssynchrony by electrocardiographic dyssynchrony markers, even when using complex vectorcardiographic parameters, remains low.

Long-Term Outcome After CRT in the Presence of Mechanical Dyssynchrony Seen With Chronic RV Pacing or Intrinsic LBBB

ObjectivesThe aim of this study was to compare the volumetric response and the long-term survival after cardiac resynchronization therapy (CRT) in patients with intrinsic left bundle branch block (LBBB) versus chronic right ventricular pacing (RVP) with respect to the presence of mechanical dyssynchrony (MD). BackgroundChronic RVP induces an iatrogenic LBBB and asynchronous left ventricular contraction that is potentially reversible by upgrading to CRT. MethodsA total of 914 patients eligible for CRT (117 with conventional pacemakers and 797 with intrinsic LBBB) were included in the study. MD was visually assessed before CRT and was defined as the presence of either apical rocking and/or septal flash on baseline echocardiograms. Patients with a left ventricular end-systolic volume decrease of ≥15% during the follow-up were considered responders. Patients were followed for all-cause mortality during the median follow-up of 48 months (interquartile range: 29 to 66 months). ResultsMD was observed in 51% of patients with RVP versus 77% in patients with intrinsic LBBB (p < 0.001). Patients with RVP and MD had a similar likelihood of volumetric response as did patients with intrinsic LBBB and MD (adjusted odds ratio: 0.71; 95% confidence interval: 0.33 to 1.53; p = 0.385). There was no significant difference in long-term survival between patients with RVP and intrinsic LBBB (adjusted hazard ratio: 1.101; 95% confidence interval: 0.658 to 1.842; p = 0.714). Patients with visual MD and either intrinsic LBBB or RVP had a more favorable survival than those without MD (p < 0.001). ConclusionsThe likelihood of volumetric response and a favorable long-term survival of patients with RVP was similar to those of patients with intrinsic LBBB and were mainly determined by the presence of MD and not by the nature of LBBB.

60 * Greater mechanical dyssynchrony is demonstrated by cardiac magnetic resonance cine imaging amongst heart failure patients awaiting cardiac resynchronisation therapy with strict left bundle branch block

Introduction: The era of cardiac resynchronisation therapy (CRT) has led to improved understanding of left ventricular activation and stricter criteria have been proposed for left bundle branch block (LBBB). These criteria have shown a greater prediction for LV mechanical dyssynchrony with 2D strain echocardiography and cardiac MRI tagging. We have further tested this hypothesis using cardiac cine MRI endocardial tracking technology and also investigated the impact of this measure of mechanical dyssynchrony on CRT response rate. Methods: We investigated a total of 47 patients awaiting CRT with traditional LBBB with a cardiac MRI pre implant. Offline analysis of the cine imaging was undertaken in order to determine the endocardial volume change systolic dyssynchrony index (SDI) of 16 segments. Pre-implant ECGs were analyzed for strict LBBB (QRS ≥ 140ms for men, ≥130ms for women and mid QRS notching/slurring in ≥2 contiguous leads). Reverse remodeling was assessed at 6 months with echocardiography. Response was defined as ≥15% improvement in LV end systolic volume. Results: These patients were aged 66.1±11.7 years, 83% were male, and 45% had an ischaemic etiology. On ECG analysis 83% had strict LBBB. In the strict LBBB group the SDI was 12.3±5.2% where as in the traditional LBBB group it was 6.7±2.5% (p=0.005). Presence of an ischaemic aetiology had no impact on SDI (p=0.216). Linear regression of SDI vs. amount of remodeling (change in LVESV) generates a regression coefficient of 2.02 (p=0.01) and a correlation coefficient of R=0.49 (p=0.01). ROC analysis determines the optimum SDI cut-off for response as 10% with an area under the curve of 0.797, a sensitivity of 81% and a specificity of 79%. Conclusion: In patients with LBBB selected for CRT under current guidance the presence of strict LBBB predicts increased mechanical dyssynchrony demonstrated as SDI with cine MRI. Presence of mechanical dyssynchrony defined as an SDI ≥10% is a good predictor of volumetric response to CRT in this cohort. ![Graphic][1] [1]: /embed/inline-graphic-1.gif

Mechanical Dyssynchrony is Similar in Different Patterns of Left Bundle-Branch Block

BackgroundLeft bundle-branch block (LBBB) and the presence of systolic dysfunction are the major indications for cardiac resynchronization therapy (CRT). Mechanical ventricular dyssynchrony on echocardiography can help identify patients responsive to CRT. Left bundle-branch block can have different morphologic patterns. ObjectiveTo compare the prevalence of mechanical dyssynchrony in different patterns of LBBB in patients with left systolic dysfunction. MethodsThis study assessed 48 patients with ejection fraction (EF) < 40% and LBBB consecutively referred for dyssynchrony analysis. Conventional echocardiography and mechanical dyssynchrony analysis were performed, interventricular and intraventricular, with ten known methods, using M mode, Doppler and tissue Doppler imaging, isolated or combined. The LBBB morphology was categorized according to left electrical axis deviation in the frontal plane and QRS duration > 150 ms. ResultsThe patients' mean age was 60 ± 11 years, 24 were males, and mean EF was 29% ± 7%. Thirty-two had QRS > 150 ms, and 22, an electrical axis between −30° and +90°. Interventricular dyssynchrony was identified in 73% of the patients, while intraventricular dyssynchrony, in 37%-98%. Patients with QRS > 150 ms had larger left atrium and ventricle, and lower EF (p < 0.05). Left electrical axis deviation associated with worse diastolic function and greater atrial diameter. Interventricular and intraventricular mechanical dyssynchrony (ten methods) was similar in the different LBBB patterns (p = ns). ConclusionIn the two different electrocardiographic patterns of LBBB analyzed, no difference regarding the presence of mechanical dyssynchrony was observed.

Could exercise unveil the mystery of non-response to cardiac resynchronization therapy?

Left ventricular mechanical dyssynchrony describes the differences in the timing of contraction between different myocardial segments that are commonly observed in patients with congestive heart failure, particularly in those with depressed LV ejection fraction. Its presence varies with not only the methods of assessment, but also characteristics of the study population including the QRS duration, loading condition, severity of coronary artery disease, LV hypertrophy, and LV remodelling. Therefore, the ECG criteria of QRS width ≥120 ms adopted in the current guidelines may not be optimal for identifying patients who will benefit most from CRT or defining the presence of mechanical dyssynchrony. 6 Analysis of LV dyssynchrony is achieved by different imaging modalities such as echocardiography, from conventional M-mode and Doppler echocardiography to more advanced tissue Doppler imaging (TDI), three-dimensional echocardiography, and speckle tracking imaging, and most of the time, performed at rest. Consequently, lack of mechanical dyssynchrony has been found in about one-third of heart failure patients with QRS duration ≥120 ms. On the other hand, mechanical dyssynchrony occurs in 40‐50% of patients with a narrow QRS complex defined as ,120 ms. 7 Furthermore, numerous studies have suggested that the presence and the extent of LV mechanical dyssynchrony could be a better predictor of response to CRT than QRS duration per se. 5,8 Not until recently, the contribution of exercise to LV mechanical dyssynchrony has been investigated and exercise-induced dyssynchrony has been found to be associated with exacerbation of heart failure symptoms, an increase in mitral regurgitation, and a reduction in exercise capacity. 9‐12 Therefore, it appears that the assessment of LV mechanical dyssynchrony only at rest may not be sufficient in heart failure patients. The landmark study by Lafitte et al. 9 first described how mechanical dyssynchrony was modified by exercise in 65 consecutive patients with LV ejection fraction of ,35% and New York Heart Association class II or III symptoms. Depending on the parameter adopted for assessment and using 20% of change as a cut-off point, LV systolic dyssynchrony increased in 28‐40%, remained the same in 35‐43%, and decreased in 23‐31% of the patients during exercise. On a closer inspection, patients could be categorized into four different groups: patients without dyssynchrony at rest but induced by exercise (exercise-induced dyssynchrony), patients with dyssynchrony at rest which normalized during exercise, patients without dyssynchrony at rest as well as during exercise, and patients with dyssynchrony in both situations. The former two groups warranted further investigation to help understand the relationship with lack of response to CRT, which represented 20‐26% of the study population. In another study in 60 patients with dilated cardiomyopathy and narrow QRS complex (,120 ms), significant mechanical dyssynchrony was observed in 33.3% of patients at rest and in 58.3% during exercise. The dynamic change in standard deviations of the time to peak systolic velocity of the 12 LV segments (Ts-SD or Yu Index) as the dyssynchrony measurement between rest and exercise showed an independent positive association with the change in mitral regurgitation, and an independent inverse correlation with the change in LV stroke volume. 10 Wang et al. 11 reported the occurrence of exercise-evoked systolic dyssynchrony in 11 (33%) of 33 heart failure patients with ejection

Electrical and mechanical dyssynchrony for prediction of cardiac events in patients with systolic heart failure

BackgroundRecent clinical trials have challenged the clinical applicability of mechanical dyssynchrony in predicting cardiac resynchronisation therapy response.ObjectiveTo evaluate whether mechanical dyssynchrony has an additional benefit over QRS duration in predicting...

Is echocardiographic assessment of dyssynchrony useful to select candidates for cardiac resynchronization therapy?

Several multicenter prospective randomized trials have shown that cardiac resynchronization therapy (CRT) improves functional capacity and quality of life in ≈70% of symptomatic heart failure (HF) patients.1 A smaller proportion of these selected patients shows a >5% increase in left ventricular (LV) ejection fraction and a >15% reduction of LV end-systolic volume, indicating reverse remodeling of the LV.2 Finally, CRT reduces morbidity and mortality rates by ≈30% to 40%.3 These data are comparable to those of established pharmacological therapies for HF, including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, and aldosterone antagonists. Of note, CRT is indicated in HF patients who remained symptomatic despite medical therapy; thus, they could be considered nonresponders to medical therapy. However, the precise proportion of nonresponders to medical therapy has not yet been quantified. Response by Abraham and Abraham see p 70 Notwithstanding CRT being a very efficacious and cost-effective treatment, several efforts have been made to reduce the number of nonresponder patients. The issue of patients not responding to CRT is rather complex. There is lack of agreement on the definition of nonresponder (volumetric, functional, or exercise response), the cause of CRT nonresponse is likely multifactorial, and some patients may be too sick to show a meaningful and measurable benefit (“beyond repair”). Currently, we do not know which factors are predicting response to therapy and the relative weight of each of these factors. Therefore, the proportion of patients who are not amenable to CRT remains undefined. Among the factors predicting response to CRT, the presence of mechanical dyssynchrony has been indicated to play a determinant role.4–7 The putative lack of responsiveness to CRT in the absence of mechanical dyssynchrony, together with evidence that mechanical dyssynchrony may exist even when QRS duration is within the normal range, has encouraged investigators to …

Evaluation of Mechanical Dyssynchrony in Children With Idiopathic Dilated Cardiomyopathy and Associated Clinical Outcomes

We studied mechanical dyssynchrony and its association with clinical status in children with idiopathic dilated cardiomyopathy (IDC). The SD of QRS to peak systolic velocity interval by tissue Doppler was measured in 12 left ventricular segments, as a dyssynchrony index (DI), in each child with IDC during a 12-month period. Results were compared with a control cohort. We used the adult-defined DI cutpoint of 32.6 ms to define patients with IDC as "dyssynchronous" or "synchronous" and compared clinical status and outcomes (transplantation listing/death) between these groups. Patients with IDC (n = 23) and controls (n = 14) had similar age, gender, and QRS duration. Patients with IDC had a higher DI than controls (44.8 +/- 23.7 vs 19.9 +/- 8 ms, p <0.0001). A DI >32.6 ms defined mechanical dyssynchrony in 65% of patients with IDC. Dyssynchronous and synchronous patients had similar QRS durations. Age at diagnosis, at dyssynchrony evaluation, and duration of clinical illness were similar in the 2 groups. New York Heart Association score was better in dyssynchronous than in synchronous patients (2 vs 3.1, p <0.05). Number of synchronous and dyssynchronous patients reaching the end point of death or transplantation was similar, although synchronous patients had poorer actuarial survival from the time of diagnosis (hazard ratio 3.25, p = .04). In conclusion, left ventricular mechanical dyssynchrony is prevalent in pediatric IDC. QRS duration alone is inadequate to define dyssynchrony in pediatric IDC, whereas the adult-derived DI of >32.6 ms seems applicable to the pediatric population. In this cohort, the presence of mechanical dyssynchrony was not associated with more severe clinical status or adverse outcomes.

Responders to cardiac resynchronization therapy with narrow or intermediate QRS complexes identified by simple echocardiographic indices of dyssynchrony: The DESIRE study

Cardiac resynchronization therapy (CRT) is recommended for patients with NYHA class III-IV refractory heart failure (HF), ejection fraction <35% and a QRS >120 ms. We attempted to identify responders to CRT from echocardiographic (echo) indices of mechanical dyssynchrony in patients with QRS<150 ms. The study enrolled 51 men and 9 women (mean age: 64.5 years) in NYHA class III (n=54) or IV (n=6) presenting with a mean ejection fraction: 25.7%, LV end-diastolic diameter: 69.1 mm, and QRS=121+/-19 ms. All patients were implanted with a CRT system and followed for 1 year. Implantation was preceded and followed by clinical, functional and Doppler (D)-echo evaluation. The primary combined endpoint included 1) death from any cause, 2) HF-related hospitalisations, and 3) NYHA class at 6 months. Before implant, 27 patients had > or =1 echo criterion of mechanical dyssynchrony (DES+ group) and 33 had no evidence of dyssynchrony (DES- group). At 12 months, 8 patients (4 per group) had died, 7 from HF. As regards the primary endpoint at 6 months, 33 patients (55%) had improved, 10 (16%) were unchanged, and 17 (29%) had deteriorated. Clinical improvement was observed in 19 of 27 DES+ (70%), versus 14 of 33 DES- (42%) patients (P<0.04). Baseline QRS duration did not predict response to CRT. In this population of HF patients with QRS<150 ms, the presence of mechanical dyssynchrony at baseline D-echo examination, but not the QRS width, predicted 6-month clinical response to CRT.