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Topological data analysis (TDA) can generate patient-patient similarity networks by analyzing large, complex data and derive new insights that may not be possible with standard statistics. The purpose of this paper was to discover novel phenotypes of chronic primary mitral regurgitation (MR) patients and to analyze their clinical implications using network analysis of echocardiographic data. Patients with chronic moderate to severe primary MR were prospectively enrolled from 11 Asian tertiary hospitals (n = 850; mean age 56.9 ± 14.2 years, 57.9% men). We performed TDA to generate network models using 14 demographic and echocardiographic variables. The patients were grouped by phenotypes in the network, and the prognosis was compared by groups. The network model by TDA revealed 3 distinct phenogroups. Group A was the youngest with fewer comorbidities but increased left ventricular (LV) end-systolic volume, representing compensatory LV dilation commonly seen in chronic primary MR. Group B was the oldest with high blood pressure and a predominant diastolic dysfunction but relatively preserved LV size, an unnoticed phenotype in chronic primary MR. Group C showed advanced LV remodeling with impaired systolic, diastolic function, and LV dilation, indicating advanced chronic primary MR. During follow-up (median 3.5 years), 60 patients received surgery for symptomatic MR or died of cardiovascular causes. Kaplan-Meier curves demonstrated that although group C had the worst clinical outcome (P < 0.001), group B, characterized by diastolic dysfunction, had an event-free survival comparable to group A despite preserved LV chamber size. The grouping information by the network model was an independent predictor for the composite of MR surgery or cardiovascular death (adjusted HR: 1.918; 95% CI: 1.257-2.927; P = 0.003). The patient-patient similarity network by TDA visualized diverse remodeling patterns in chronic primary MR and revealed distinct phenotypes not emphasized currently. Importantly, diastolic dysfunction deserves equal attention when understanding the clinical presentation of chronic primary MR. [Display omitted] [ABSTRACT FROM AUTHOR]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ahj.2004.12.028 Byline: Louis Yik-si Chan (a), Wing Yee Fok (a), John Tai-hung Wong (b), Cheuk Man Yu (b), Tse Ngong Leung (a), Tze Kin Lau (a) Abstract: Assessment of fetal cardiac function is difficult because of limited accessibility. Tissue Doppler imaging (TDI) is a promising technique in assessing diastolic function in adults. There has been sparseness concerning the use of TDI in assessing fetal cardiac function. The aim of this study was to construct reference charts of TDI indices of systolic and diastolic functions of the normal fetal heart. Author Affiliation: (a) Department of Obstetrics and Gynecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China (b) Division of Cardiology, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China Article History: Received 8 September 2004; Accepted 10 December 2004

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ahj.2010.02.034 Byline: William T. Abraham (a), Daniel Gras (b), Cheuk Man Yu (c), Lisa Guzzo (d), Manish S. Gupta (e) Abstract: The aim of the study was to describe the rationale, design, and end points of a randomized, double-blind, controlled trial evaluating frequent systematic optimization of atrioventricular (AV) and interventricular (VV) delays in patients receiving cardiac resynchronization therapy (CRT). Author Affiliation: (a) The Ohio State University, Columbus, OH (b) Nouvelles Cliniques Nantaises, Nantes, France (c) Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, P.R. China (d) St Jude Medical, Brussels, Belgium (e) St Jude Medical, Sylmar, CA Article History: Received 19 April 2009; Accepted 24 February 2010 Article Note: (footnote) RCT Reg #NCT00418314.

Objectives To study the association between the baseline IL-33 and soluble ST2 (sST2) levels with disease remission and progression of carotid atherosclerosis in early rheumatoid arthritis (ERA) patients. Methods A total of 98 ERA patients were enrolled. Disease activity and the presence of carotid plaque were evaluated at baseline and 12 months later. Plasma IL-33 and sST2 levels were determined using enzyme-linked immunosorbent assay kits. Results Baseline IL-33 and sST2 levels were associated with inflammatory markers and cardiovascular (CV) risk factors. Overall, 44(45%), 18(18%), and 21(21%) patients achieved remission based on 28-joint disease activity score (DAS28), Boolean, and simplified disease activity score (SDAI) criteria at 12 months, respectively. Patients with detectable IL-33 at baseline were less likely to achieve DAS28 ( P = 0.010) and SDAI remission ( P = 0.021), while a lower baseline sST2 level was able to predict DAS28, Boolean, and SDAI remission ( P = 0.005, 0.001, and <0.001, respectively). Using multivariate analysis, a lower baseline sST2 level independently predict Boolean (OR = 0.789; P = 0.005) and SDAI remission (0.812; P = 0.008). Regarding carotid atherosclerosis, 9/98(9.2%) patients had plaque progression at 12 months. Baseline IL-33 was detectable in 8/9(89%) and 42/83(51%) of patients with and without plaque progression respectively ( P = 0.029). Baseline detectable IL-33 was an independent predictor for plaque progression after adjusting for traditional CV risk factors ( P = 0.017). Conclusions Lower baseline sST2 levels independently predict disease remission and baseline detectable IL-33 independently predicts carotid plaque progression in ERA patients. This study suggests that inflammation induced by the IL-33/ST2 axis may play a significant role in the development of cardiovascular disease in RA. [ABSTRACT FROM AUTHOR]

Abstract: Background: Current clinical guidelines recommend ultrafiltration (UF) for patients with acute decompensated heart failure (ADHF) who are unresponsive or resistant to diuretics. We systematically reviewed the latest randomized evidence on the efficacy and safety of UF in ADHF. Methods: MEDLINE, EMBASE and the Cochrane database were searched in January 2013 for eligible randomized controlled trials (RCTs) evaluating UF in patients with ADHF. A Mantel–Haenszel random-effects model was used to calculate mean differences (MDs) and odds ratios (ORs) for continuous and dichotomous data, respectively, with 95% confidence intervals (CIs). Results: Data of 12 studies (n=659) were meta-analyzed; follow-up duration ranged from 36h to 12months. Compared to control, treatment of UF was associated with significant fluid removal (MD 1.28, 95% CI 0.43 to 2.12, P=0.003) and weight loss (MD 1.23, 95% CI 0.03 to 2.44, P=0.04), with no significant effects on all-cause mortality (OR 1.08, 95% CI 0.63 to 1.86, P=0.77) or all-cause rehospitalization (OR 0.89, 95% CI 0.39 to 2.00, P=0.77). No significant differences were observed in the analyses of change in serum creatinine or unscheduled medical care; analysis of adverse effects was inconclusive since only one study provided usable data. Conclusions: For patients with ADHF, UF is effective in reducing fluid retention and body weight, with no significant benefits in mortality or rehospitalization. The current limited randomized evidence highlights the need for further well-conducted randomized studies of adequate power to establish the role of UF in ADHF patients for whom conventional HF treatment is unsuccessful or contraindicated. [Copyright &y& Elsevier]

Abstract: Background: Drug-eluting balloons (DEB) are attractive new alternatives to drug-eluting stents (DES) for percutaneous coronary interventions. We aimed to systematically review the efficacy and safety of DEB in the treatment of coronary artery disease (CAD). Methods: MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched in December 2011 for eligible randomized controlled trials. Primary outcomes were target lesion revascularization (TLR), major adverse cardiac events (MACE) and mortality. Secondary outcomes were late lumen loss, minimal lumen diameter and binary restenosis. Results: Five studies involving 349 patients were included. Compared to controls, DEB improved angiographic measures with no significant effect on clinical outcomes in the overall CAD population. There is clear superiority of DEB in patients with in-stent restenosis in TLR (OR 0.17, 95% CI 0.07 to 0.38, p<0.0001, I2 =0%), MACE (OR 0.22, 95% CI 0.10 to 0.51, p=0.0005, I2 =13%), late lumen loss (in-stent: MD −0.51, 95% CI −0.73 to −0.28, p<0.00001, I2 =60%; in-segment: MD −0.51, 95% CI −0.77 to −0.24, p=0.0002, I2 =72%;), minimal lumen diameter (in-stent: MD 0.49, 95% CI 0.05 to 0.93, p=0.03, I2 =85%; in-segment: MD 0.49, 95% CI 0.13 to 0.86, p=0.008, I2 =79%) and binary restenosis (in-stent: OR 0.15, 95% CI 0.05 to 0.47, p=0.001, I2 =37%; in-segment: OR 0.11, 95% CI 0.05 to 0.27, p<0.00001, I2 =17%). Conclusions: Our findings support the current recommendation of using DEB in in-stent restenosis. Large, well-conducted trials are essential in determining the application of DEB in other lesion types as well as exploring device-specific efficacy and safety profiles. [Copyright &y& Elsevier]

Objective: We assessed whether a serum soluble receptor for advanced glycation end product (sRAGE) levels were associated with a progression of carotid atherosclerosis and arterial stiffness indexes in a cohort of early rheumatoid arthritis (RA) patients. Methods: RA patients with symptoms onset <2 years were recruited. Vascular assessments and serum sRAGE levels were measured at baseline and 1 year later. Arterial stiffness was determined by pulse wave velocity and aortic augmentation index (AIx). Carotid intima-media thickness was measured using high-resolution ultrasound. Results: Ninety-four patients completed the 1-year study. Fifty-three (56.4%) achieved disease remission [28-joint disease activity score (DAS28 < 2.6)] at 12 months. Improvement in arterial stiffness was observed as reflected by the significant reductions in AIx and pulse wave velocity. At 12 months, the sRAGE levels increased significantly compared with baseline (939.8 ± 517.7 pg/ml to 1272.1 ± 567.3 pg/ml, P < 0.001). Changes in sRAGE levels were significantly higher in men compared to women (768 ± 510 pg/ml versus 271 ± 490 pg/ml, P < 0.05) and was negatively associated with the change in AIx (r = −0.259, P = 0.023). Changes in sRAGE level were not associated with other demographic, clinical, cardiovascular risk factors or treatment. Using multivariate analysis, the change in sRAGE levels and baseline high-density lipoprotein were independent predictors associated with the change in AIx. Conclusions: Arterial stiffness improved significantly in patients with early RA after effective control of inflammation. Increase in sRAGE level was associated with a decrease in AIx, suggesting that sRAGE may play an important role in the ligand–soluble receptor for advanced glycation end product interaction propagated inflammation and vascular stiffness in these patients. [ABSTRACT FROM AUTHOR]

Abstract: Objective: We aimed to evaluate the effectiveness of transthoracic saline contrast echocardiography (TSCE) in detecting patent foramen ovale (PFO). Background: Transesophageal echocardiography (TEE) is semi-invasive and not ideal for PFO screening. Methods: 112 patients (48 males, 46±14years) with suspected PFO received intravenous agitated-saline contrast at rest and stress (strain and release phases of Valsalva maneuver and coughing). The presence of interatrial shunting was defined as >5 bubbles appearing in the left heart within 3 cardiac cycles. The stage of the maneuver at which interatrial shunting occurred was recorded. The TSCE findings were validated by TEE. Results: TEE identified PFO in 45% of patients. The sensitivities of TSCE in detecting PFO at rest, during strain and release of Valsalva maneuver, and coughing were 12.0%, 38.0%, 80.0% and 94.0% respectively (each p<0.05 when compared to previous stage). Specificities were similar and >95% for all stages. Moreover, the release phase of the maneuver improved the diagnostic accuracy [defined as (number of true positives+true negatives) divided by total in sample] with incremental value over the preceding strain phase (89.2 vs. 70.5%, p<0.001). Conclusions: Patent foramen ovale can be identified confidently with proper conduct of the Valsalva maneuver during the transthoracic saline contrast echocardiography. [Copyright &y& Elsevier]

Whether the relief of chronic right atrial (RA) volume load by device closure of an atrial septal defect (ASD) normalizes RA size is unknown. The present study evaluated the prevalence and determinants of incomplete RA reverse remodeling (RAR) after ASD closure in adults. Transthoracic echocardiography was performed in 44 consecutive patients with secundum ASD (age 43 ± 17 years, 10 men) without a history of atrial arrhythmia shortly before and at 3 months after device closure of ASD. The pulmonary/systemic flow ratio was derived using invasive oximetry. The RA size had significantly decreased at 3 months of follow-up (RA volume index [RAVI] 52 ± 29 to 27 ± 17 ml/m2, p <0.001). Incomplete RAR (defined as a RAVI of ≥21 ml/m2) was detected in 25 patients (57%) after closure. They were older, had a larger pulmonary/systemic flow ratio, a higher pulmonary arterial systolic pressure, more tricuspid regurgitation, and larger RA, left atrial, and right ventricular sizes before closure than those with a normalized right atrium. Before closure, RAVI was the only independent determinant for incomplete RAR (odds ratio 1.115, 95% confidence interval 1.019 to 1.220; p = 0.018). A cutoff value of RAVI of ≥40 ml/m2 has a sensitivity of 84% and specificity of 72% in the receiver operating characteristic curve. The preclosure RAVI correlated moderately with the shunt-duration index, calculated by multiplying the age to pulmonary/systemic flow ratio (r = 0.64, p <0.01). In conclusion, incomplete RAR occurred in >1/2 of the adult patients at 3 months after ASD device closure and was related to excessive preclosure RA dilation. [ABSTRACT FROM AUTHOR]

Abstract: Background: Intrathoracic impedance fluid monitoring has been shown to predict worsening congestive heart failure (CHF) in patients with implantable devices. We developed and externally validated a modified algorithm to identify worsening heart failure (HF) by using intrathoracic impedance. Methods and Results: The modified algorithm was developed by using published data from 81 CHF subjects averaging 259 days of follow-up. Device-measured daily impedance was input to both the existing and the modified intrathoracic impedance fluid monitoring algorithms to determine a reference impedance and a fluid index (FI). Separate validation sets included 326 cardiac resynchronization therapy device (CRT-D) patients with an average 333 days of follow-up (group 1) and 104 CRT-D/implantable cardioverter/defibrillator (ICD) patients followed for an average of 520 days (group 2). Clinicians and patients in group 2 were blinded to impedance and FI data. HF events included adjudicated HF hospitalizations or emergency room visits. Sensitivity was defined as the percentage of HF events preceded by FI exceeding the predefined threshold (60 Ω-d) within the last 2 weeks. Unexplained detections were FI threshold crossing events not followed by a HF event within 2 weeks. The modified algorithm significantly decreased unexplained detections by 30% (P = .01; GEE) in the development set, 30% (P < .001) in the group 1 validation set, and 43% (P < .001) in group 2. Sensitivity did not change significantly in any group. Simulated monthly review of FI threshold crossings identified subjects at significantly greater risk of worsening HF within the next 30 days. Conclusions: A modified intrathoracic impedance based fluid detection algorithm lowered the number of unexplained FI threshold crossings and identified patients at significantly increased immediate risk of worsening HF. [Copyright &y& Elsevier]

Objectives: The aim of this study was to evaluate the role of left ventricular (LV) mechanical dyssynchrony in heart failure with preserved ejection fraction (HFPEF) complicating acute coronary syndrome (ACS). Background: In systolic heart failure, LV mechanical dyssynchrony worsens cardiac function and cardiac resynchronization therapy improves clinical outcome. The role of LV mechanical dyssynchrony in HFPEF complicating ACS is unknown. Methods: One hundred two patients presenting with ACS (ejection fraction ≥50%) and 104 healthy controls were studied using tissue Doppler imaging: group 1 (n = 55) had HFPEF on presentation and group 2 (n = 47) had no clinical HFPEF. The SD of time to peak systolic myocardial velocity and the SD of early diastolic (Te-SD) myocardial velocity of 12 LV segments were obtained for evaluation of dyssynchrony. Longitudinal mean myocardial ejection systolic velocity (mean Sm) and mean early diastolic velocity (mean Em) were measured. Results: Te-SD was greater in group 1 (33 ± 13 ms) than group 2 (21 ± 9 ms) (p < 0.001), and diastolic mechanical dyssynchrony was evident in 35% of patients in group 1 but in only 9% in group 2 (p < 0.001). Conversely, the SD of time to peak systolic myocardial velocity was similar in the 2 ACS groups (34 ± 16 ms vs. 32 ± 18 ms; p = NS), showing a similar prevalence of systolic mechanical dyssynchrony (47% vs. 43%; p = NS). Worsening of the diastolic dysfunction grade was associated with a parallel increase in Te-SD (grades 0, 1, 2, and 3: 16 ± 3 ms, 21 ± 5 ms, 28 ± 9 ms, and 41 ± 17 ms, respectively; p < 0.001). Te-SD correlated negatively with mean Em (r = −0.56, p < 0.001) and positively with peak mitral inflow velocity of the early rapid-filling wave/Em (r = 0.69, p < 0.001); mean myocardial ejection systolic velocity correlated significantly with mean Em (r = 0.56, p < 0.001), SD of time to peak systolic myocardial velocity (r = −0.42, p < 0.001) and Te-SD (r = −0.23, p = 0.001). Multivariate analysis identified peak mitral inflow velocity of the early rapid-filling wave/Em as the only variable independently associated with HFPEF (odds ratio: 1.48, p = 0.001). When peak mitral inflow velocity of the early rapid-filling wave/Em was excluded from the model, Te-SD (odds ratio: 1.13, p < 0.001) and mean Em (odds ratio: 0.37, p < 0.001) became independently associated with HFPEF. Conclusions: LV diastolic mechanical dyssynchrony may impair diastolic function and contribute to the pathophysiology of HFPEF, complicating ACS. [Copyright &y& Elsevier]

Objectives: This study investigated the use of 3-dimensional (3D) echo in quantifying left ventricular mechanical dyssynchrony (LVMD), its interhospital agreement, and potential impact on patient selection. Background: Assessment of LVMD has been proposed as an improvement on conventional criteria in selecting patients for cardiac resynchronization therapy (CRT). Three-dimensional echo offers a reproducible assessment of left ventricular (LV) structure, function, and LVMD and may be useful in selecting patients for this intervention. Methods: We studied 187 patients at 2 institutions. Three-dimensional data from baseline and longest follow-up were quantified for volume, left ventricular ejection fraction (LVEF), and systolic dyssynchrony index (SDI). New York Heart Association (NYHA) functional class was assessed independently. Several outcomes from CRT were considered: 1) reduction in NYHA functional class; 2) 20% relative increase in LVEF; and 3) 15% reduction in LV end-systolic volume. Sixty-two cases were shared between institutions to analyze interhospital agreement. Results: There was excellent interhospital agreement for 3D–derived LV end-diastolic and end- systolic volumes, EF, and SDI (variability: 2.9%, 1%, 7.1%, and 7.6%, respectively). Reduction in NYHA functional class was found in 78.9% of patients. Relative improvement in LVEF of 20% was found in 68% of patients, but significant reduction in LV end-systolic volume was found in only 41.5%. The QRS duration was not predictive of any of the measures of outcome (area under the curve [AUC]: 0.52, 0.58, and 0.57 for NYHA functional class, LVEF, and LV end-systolic volume), whereas SDI was highly predictive of improvement in these parameters (AUC: 0.79, 0.86, and 0.66, respectively). For patients not fulfilling traditional selection criteria (atrial fibrillation, QRS duration <120 ms, or undergoing device upgrade), SDI had similar predictive value. A cutoff of 10.4% for SDI was found to have the highest accuracy for predicting improvement following CRT. Conclusions: The LVMD quantification by 3D echo is reproducible between centers. SDI was an excellent predictor of response to CRT in this selected patient cohort and may be valuable in identifying a target population for CRT irrespective of QRS morphology and duration. [Copyright &y& Elsevier]

Objectives: This study aimed to evaluate the impact of cardiac contractility modulation (CCM) on left ventricular (LV) size and myocardial function. Background: CCM is a device-based therapy for patients with advanced heart failure. Previous studies showed that CCM improved symptoms and exercise capacity; however, comprehensive assessment of LV structure, function, and reverse remodeling is not available. Methods: Thirty patients (60 ± 11 years, 80% male) with New York Heart Association (NYHA) functional class III heart failure, ejection fraction <35%, and QRS <120 ms were assessed at baseline and 3 months. LV reverse remodeling was measured by real-time 3-dimensional echocardiography. Using tissue Doppler imaging, the peak systolic velocity (Sm) and peak early diastolic velocity (Em) were calculated for LV function, while the standard deviation of the time to peak systolic velocity (Ts-SD) and the time to peak early diastolic velocity (Te-SD) were calculated for mechanical dyssynchrony. Results: LV reverse remodeling was evident, with a reduction in LV end-systolic volume by −11.5 ± 10.5% and a gain in ejection fraction by 4.8 ± 3.6% (both p < 0.001). Myocardial contraction was improved in all LV walls, including sites remote from CCM delivery (all p < 0.05); hence, the mean Sm of 12 (2.2 ± 0.6 cm/s vs. 2.5 ± 0.7 cm/s) or 6 basal LV segments (2.5 ± 0.6 cm/s vs. 3.0 ± 0.7 cm/s) were increased significantly (both p < 0.001). In contrast, CCM had no impact on regional or global Em (2.9 ± 1.3 cm/s vs. 2.9 ± 1.1 cm/s), whereas Ts-SD (28.2 ± 11.2 ms vs. 27.9 ± 12.7 ms) and Te-SD (30.0 ± 18.3 ms vs. 30.1 ± 20.7 ms) remained unchanged (all p = NS). Mitral regurgitation was reduced (22 ± 14% vs. 17 ± 15%, p = 0.02). Clinically, there was improvement of NYHA functional class (p < 0.001) and 6-min hall walk distance (p = 0.015). A 24-h Holter monitor showed that premature ventricular contractions were not increased during CCM. Conclusions: CCM improves both global and regional LV contractility, including regions remote from the impulse delivery, and may contribute to LV reverse remodeling and gain in systolic function. Such improvement is unrelated to diastolic function or mechanical dyssynchrony. [Copyright &y& Elsevier]

Objectives: We sought to determine whether early assessment of left ventricular (LV) dyssynchrony by tissue Doppler imaging may predict progressive ventricular enlargement and cardiac dysfunction after acute myocardial infarction (MI). Methods: Forty-seven patients (mean age 59.9 +/- 11.6 years) with normal QRS duration underwent tissue Doppler imaging and contrast-enhanced cardiac magnetic resonance imaging (Ce-MRI) at days 2 to 6, 3 months, and at 1 year after the index MI. Systolic dyssynchrony index (Ts-SD) was calculated from 12 LV segments, and infarct size (IS) by Ce-MRI. Results: The remodeling group (n = 16) (defined as an increase in end-systolic volume > or =10% between 1 year and baseline) had greater initial IS (27.2 +/- 9.6 vs 13.7 +/- 4.1%, P < .001) and Ts-SD (50.9 +/- 12.8 vs 33.6 +/- 7.7 milliseconds, P < .001) than nonremodeling group (n = 31). At 1 year, the remodeling group had progressive increase in Ts-SD and decrease in LV ejection fraction (57.3 +/- 18.5 and 36.0 +/- 7.6%, respectively; both P < .05 vs baseline). Both Ts-SD (odds ratio 1.19 [1.07-1.32], P = .001) and IS (odds ratio 1.65 [1.19-2.29], P = .003) were shown to be independent predictors of progressive LV remodeling. A cutoff value of Ts-SD > or =45 milliseconds predicted LV remodeling at 1 year (sensitivity 90.5%, specificity 90.9%, Area-under-curve 0.907) (P = .0005). Conclusions: Left ventricular systolic dyssynchrony is a newly identified predictor of chronic LV remodeling after acute MI, which is independent and incremental to conventional assessment and IS as measured by Ce-MRI. [ABSTRACT FROM AUTHOR]

Background: This study compared the prevalence and pattern of mechanical dyssynchrony in patients with normal heart and right ventricular apical (RVA) pacing versus patients with systolic heart failure (SHF) and spontaneous left bundle branch block (LBBB). Methods: A total of 112 patients having LBBB pattern on surface electrocardiogram were included (57 with ejection fraction >50% received RVA pacing; 55 had SHF with ejection fraction <35%). Using tissue Doppler imaging, systolic and diastolic dyssynchrony was defined by the standard deviation of the time to peak systolic and peak early diastolic velocity, respectively. Results: Despite comparable QRS duration and LBBB pattern, the prevalence of electromechanical dyssynchrony was significantly lower in the patients with RVA pacing (systolic: 54% vs 73%, χ2 = 4.058, P = .044; diastolic: 32% vs 61%, χ2 = 9.738, P = .002). The presence of coexisting systolic and diastolic dyssynchrony, isolated systolic dyssynchrony, isolated diastolic dyssynchrony, and no dyssynchrony also showed a different distribution between the 2 groups (RVA pacing: 14%, 40%, 18%, and 28%; SHF: 51%, 22%, 11%, and 16%; χ2 = 17.498, P = .001). Furthermore, the SHF group had a higher prevalence of medial wall (ie, septal, anteroseptal, and inferior) delay (56% vs 30%), whereas RVA pacing resulted in more free wall (ie, lateral, posterior and anterior) delay (44% vs 70%) (χ2 = 8.050, P = .005). Conclusions: The prevalence of mechanical dyssynchrony is lower in patients with normal ejection fraction and RVA pacing when compared with patients with SHF and spontaneous LBBB. The pattern of delay in contraction also appears to be different between the 2 groups. [Copyright &y& Elsevier]

Background: Left atrial (LA) volume is a predictor of cardiovascular events in patients with heart failure. Improvement of LA function and reverse remodeling was observed after cardiac resynchronization therapy (CRT). Objective: The purpose of this study was to explore the clinical significance of improvement in LA function after CRT. Methods: Echocardiographic studies were performed before and 3 months after CRT in 97 patients (72 men and 25 women; age 63.8 +/- 13.3 years) with standard CRT indication but no history of atrial fibrillation (AF). LA active emptying fraction based on the change in volumes (LAV-EF) were calculated, and significant improvement in LA function (LA responder) was defined as a relative increase >/=50% from baseline LAV-EF. The primary end-points were newly developed AF detected by ECG or device and all-cause mortality. Results: After 1,200 +/- 705 days of follow-up, LA responders (n = 47 [48.5%]) had a significantly lower incidence of AF (12.8% vs 40%, P = .002) and mortality (17% vs 44%, P = .004) than did LA nonresponders. In Cox proportional hazard analysis, LA responders was the only independent predictor of lower risk of new-onset AF (hazard ratio 0.22, 95% confidence interval 0.08-0.61, P = .003), whereas both LA responders (hazard ratio 0.22, 95% confidence interval 0.09-0.53, P <.001) and left ventricular reverse remodeling (>10% reduction in left ventricular end-systolic volume at 3 months; hazard ratio 0.96, 95% confidence interval 0.93-0.99, P = .03) were independent predictors of lower risk of death after CRT. Conclusion: Improvement of LA function after CRT was associated with a lower incidence of AF and mortality in AF naïve patients with severe heart failure. [ABSTRACT FROM AUTHOR]

The assessment of systolic dyssynchrony by echocardiography is useful in predicting a favorable response to cardiac resynchronization therapy (CRT). Tissue Doppler velocity and tissue Doppler longitudinal strain have been suggested for this purpose. This study compared parameters of systolic dyssynchrony derived from these 2 imaging modalities for their predictive values of CRT response. Two hundred fifty-six patients from 3 different centers who received CRT were followed for 6 ± 3 months. Parameters of systolic dyssynchrony based on tissue Doppler velocity and strain imaging were assessed for the prediction of left ventricular (LV) reverse remodeling (reduction of LV end-systolic volume ≥15%). These included time to peak systolic velocity (or peak strain) of 12 LV segments to calculate the SD (Ts-SD or Tε-SD), maximal difference in delay (Ts-Diff or Tε-Diff), and opposite wall delay (Ts-OW or Tε-OW). The septal-to-lateral delay (Ts-Sep-Lat or Tε-Sep-Lat) was also measured. LV reverse remodeling, defined as improvement in end-systolic volume ≥15%, was observed in 141 patients (55%). All 4 tissue velocity parameters predicted LV reverse remodeling, and the areas under the receiver-operating characteristic curves were 0.86, 0.85, 0.84, and 0.79 for Ts-SD, Ts-Diff, Ts-OW, and Ts-Sep-Lat, respectively (all p <0.001). The cut-off values derived from receiver-operating characteristic curve analysis were 33 ms for Ts-SD, 100 ms for Ts-Diff, 90 ms for Ts-OW, and 60 ms for Ts-Sep-Lat, and their sensitivities were 93%, 92%, 81%, and 70%, with specificities of 78%, 68%, 80%, and 76%, respectively. In contrast, none of the longitudinal strain parameters predicted LV reverse remodeling. The areas under the receiver-operating characteristic curves ranged from 0.49 to 0.53 (all p = NS). The same conclusions were obtained in subgroup analyses of QRS duration (120 to 150 vs >150 ms) and ischemic or nonischemic cause of heart failure. In conclusion, parameters of tissue Doppler longitudinal velocity, but not longitudinal strain, predicted LV reverse remodeling after CRT. [Copyright &y& Elsevier]

Objectives: We sought to examine whether cardiac resynchronization therapy (CRT) improves atrial function and induces atrial reverse remodeling. Background: Cardiac resynchronization therapy is an established therapy for advanced heart failure with prolonged QRS duration, which improves left ventricle (LV) function and is associated with LV reverse remodeling. Methods: A total of 107 heart failure patients (66 ± 11 years) who received CRT and were followed up for 3 months were studied. Atrial function was assessed by M-mode, 2-dimensional echocardiography, transmitral Doppler, tissue Doppler velocity, and strain (ε) imaging. Left atrial (LA) emptying fraction based on the change in areas (LAA-EF) and volumes (LAV-EF) were calculated. The LV reverse remodeling was defined by a reduction of LV end-systolic volume >10%. Results: In the responders of LV reverse remodeling (n = 62), LAA-EF and LAV-EF were significantly increased (p < 0.001). Responders also had significant decrease in LA size area and volumetric measurements, both before (p < 0.05) and after atrial systole (p < 0.001). However, these parameters were unchanged in the nonresponders (n = 45, p = NS). In the responders, tissue Doppler velocity analysis showed improvement of contraction velocity in both left (p = 0.005) and right atria (p = 0.018), whereas ε in both atria were increased in all the phases of cardiac cycle, namely ventricular end-systole (p < 0.001), early diastole (p < 0.001), and late diastole (p = 0.007). Conclusions: Cardiac resynchronization therapy improves both left and right atrial pump function. The increase in atrial ε throughout the cardiac cycle is likely reflecting the improvement of atrial compliance. These changes lead to LA reverse remodeling with reduction of LA size before and after atrial systole. [Copyright &y& Elsevier]

Tissue Doppler imaging (TDI) is evolving as a useful echocardiographic tool for quantitative assessment of left ventricular (LV) systolic and diastolic function. Recent studies have explored the prognostic role of TDI-derived parameters in major cardiac diseases, such as heart failure, acute myocardial infarction, and hypertension. In these conditions, myocardial mitral annular or basal segmental (Sm) systolic and early diastolic (Ea or Em) velocities have been shown to predict mortality or cardiovascular events. In particular, those with reduced Sm or Em values of <3 cm/s have a very poor prognosis. In heart failure and after myocardial infarction, noninvasive assessment of LV diastolic pressure by transmitral to mitral annular early diastolic velocity ratio (E/Ea or E/Em) is a strong prognosticator, especially when E/Ea is ≥15. In addition, systolic intraventricular dyssynchrony measured by segmental analysis of myocardial velocities is another independent predictor of adverse clinical outcome in heart failure subjects, even when the QRS duration is normal. In heart failure patients who received cardiac resynchronization therapy, the presence of systolic dyssynchrony at baseline is associated with favorable LV remodeling, which in turn predicts a favorable long-term clinical outcome. Finally, TDI and derived deformation parameters improve prognostic assessment during dobutamine stress echocardiography. A high mean Sm value in the basal segments of patients with suspected coronary artery disease is associated with lower mortality rate or myocardial infarction and is superior to the wall motion score. [Copyright &y& Elsevier]

Objectives: The present study aimed to examine whether diastolic and systolic asynchrony exist in diastolic heart failure (DHF) and their prevalence and relationship to systolic heart failure (SHF) patients. Background: Few data exist on mechanical asynchrony in DHF. Methods: Tissue Doppler echocardiography was performed in 373 heart failure patients (281 with SHF and 92 with DHF) and 100 normal subjects. Diastolic and systolic asynchrony was determined by measuring the standard deviation of time to peak myocardial systolic (Ts-SD) and peak early diastolic (Te-SD) velocity using a 6-basal, 6-mid-segmental model, respectively. Results: Both heart failure groups had prolonged Te-SD (DHF vs. SHF vs. controls subjects: 32.2 ± 18.0 ms vs. 38.0 ± 25.2 ms vs. 19.5 ± 7.1 ms) and Ts-SD (31.8 ± 17.0 ms vs. 36.7 ± 15.2 ms vs. 17.6 ± 7.9 ms) compared with the control group (all p < 0.001 vs. control subjects). Based on normal values, the DHF group had comparable diastolic (35.9% vs. 43.1%; chi-square = 1.48, p = NS), but less systolic asynchrony than the SHF group (39.1% vs. 56.9%; chi-square = 8.82, p = 0.003). Normal synchrony, isolated systolic, isolated diastolic, and combined asynchrony were observed in 39.1%, 25.0%, 21.7%, and 14.1% of DHF patients, respectively, and these were 25.6%, 31.3%, 17.4%, and 25.6%, correspondingly, in SHF (chi-square = 10.01, p = 0.019). The correlation between systolic and diastolic asynchrony, and between the myocardial velocities and corresponding mechanical asynchrony appeared weak. A wide QRS duration (>120 ms) was rare in DHF (10.9% vs. 37.7% in SHF) (chi-square = 16.69, p < 0.001). Conclusions: Diastolic and/or systolic asynchrony was common in 61% of DHF patients despite narrow QRS complex. The presence of asynchrony was not related to myocardial systolic or diastolic function. Systolic and diastolic asynchrony were not tightly coupled, implying distinct mechanisms. [Copyright &y& Elsevier]

Objectives: This study was designed to evaluate the role of cardiac resynchronization therapy (CRT) in heart failure (HF) patients with narrow QRS complexes (<120 ms) and echocardiographic evidence of mechanical asynchrony. Background: Cardiac resynchronization therapy is currently recommended to advanced HF patients with prolonged QRS duration. Echocardiographic assessment of systolic mechanical asynchrony has been proven useful to predict a favorable response after CRT. Methods: A total of 102 HF patients with New York Heart Association (NYHA) functional class III or IV were enrolled. Among them, 51 had wide QRS (>120 ms) and 51 had narrow QRS (<120 ms). Tissue Doppler imaging (TDI) was employed to select patients with systolic asynchrony (increased asynchrony index) in the narrow-QRS group. Clinical and echocardiographic assessments were performed at baseline and 3 months after CRT. Results: There was a significant reduction of left ventricular (LV) end-systolic volume in both narrow (122 ± 42 cc vs. 103 ± 47 cc, p < 0.001) and wide (148 ± 74 cc vs. 112 ± 64 cc, p < 0.001) QRS groups. Improvement of NYHA functional class (both p < 0.001), maximal exercise capacity (both p < 0.05), 6-min hall-walk distance (both p < 0.01), ejection fraction (both p < 0.001), and mitral regurgitation (both p < 0.005) was also observed. In both groups, the degree of baseline mechanical asynchrony determined LV reverse remodeling to a similar extent, as shown by the superimposed regression lines. Withholding CRT for 4 weeks resulted in loss of echocardiographic benefits. Conclusions: Cardiac resynchronization therapy for HF patients with narrow QRS complexes and coexisting mechanical asynchrony by TDI results in LV reverse remodeling and improvement of clinical status. The amplitude of benefit is similar to the wide-QRS group provided that similar extent of systolic asynchrony is selected. [Copyright &y& Elsevier]

Cardiac resynchronization therapy (CRT) has been shown to reduce symptoms and reverse left ventricular (LV) remodeling. It is not known, however, whether diastolic function will improve after CRT and diastolic asynchrony will predict LV reverse remodeling. Seventy-six patients (mean age 65 ± 12 years, 74% men) who received CRT were studied at baseline and after 3 months. Diastolic function was assessed by transmitral Doppler and tissue Doppler imaging. LV systolic and diastolic asynchrony were assessed by the time to peak myocardial contraction (Ts) and early diastolic relaxation (Te) using the 6 basal, 6 mid-segmental model. There were 42 responders (55%) with LV reverse remodeling (defined as a reduction of LV end-systolic volume ≥15%). Parameters of systolic function were significantly improved only in the responders. For diastolic function, there were reductions of transmitral E velocity in the 2 groups, without any change in atrial velocity or the E/A ratio. Tissue Doppler imaging revealed that myocardial early diastolic velocity was unchanged in responders but was significantly worsened in nonresponders. The systolic asynchrony index (the SD of Ts of 12 LV segments) correlated significantly with LV reverse remodeling (r = −0.64, p <0.001) but not the diastolic asynchrony index (the SD of Te of 12 LV segments) (r = −0.10, p = NS). The systolic asynchrony index was the only independent predictor of reverse remodeling (β = −0.99, 95% confidence interval −1.41 to −0.58, p <0.001). In conclusion, CRT improves systolic function and systolic asynchrony but has a neutral effect on diastolic function and diastolic asynchrony. LV reverse remodeling response is determined by the severity of prepacing systolic asynchrony but not diastolic asynchrony or the diastolic filling pattern. [Copyright &y& Elsevier]

Abstract: Background: Atrial function is an integral part of cardiac function which is often neglected. The presence of coronary artery disease (CAD) may impair atrial function. This study investigated if atrial mechanical dysfunction was present in patients with CAD by tissue Doppler echocardiography (TDI). Methods: Echocardiography with TDI was performed in 118 patients with CAD, and compared with 100 normal controls with comparable age and heart rate. Regional atrial function was assessed at the left (LA) and right (RA) atrial free wall and inter-atrial septum (IAS). The peak regional atrial contraction velocity of (V A) and the timing of mechanical events were compared. Results: The V A in the LA (5.0±2.6 Vs 7.7±2.6 cm/s), IAS (4.8±1.7 Vs 5.7±1.5 cm/s) and RA (6.8±3.1 Vs 9.2±2.9 cm/s) were significantly decreased in patients with CAD when compared with controls (all p <0.001). Patients with impaired systolic function (ejection fraction≤50%) had significantly lower V A in the LA and IAS than those with ejection fraction>50% (both p <0.001); and were lower in those with restrictive filling pattern (RFP) than non-RFP of diastolic dysfunction (both p <0.05). The V A in all the subgroups was lower than controls. In contrast, transmitral atrial velocity was unable to reveal any abnormality except in the subgroup with a RFP. The LA dimension, area and volume were increased in the disease groups, but were largely unchanged in the RA despite abnormal V A. The physiological inter-atrial delay for the onset and peak atrial contraction between the RA and LA were unaffected by CAD. Conclusions: The atrial contractile function in both atria was impaired in the presence of CAD, especially in the LA. This was detected even in patients with preserved systolic function or mild diastolic dysfunction such as non-RFP. Direct assessment of atrial velocity by TDI may better reflect atrial mechanical function than transmitral atrial velocity. [Copyright &y& Elsevier]

Although the beneficial role of cardiac resynchronization therapy (CRT) in selected patients with heart failure is well proven, its effect on the incidence of atrial fibrillation (AF) is unclear. The present study compared the incidence of AF in 36 consecutive patients with chronic heart failure receiving CRT with its incidence in controls matched for age, gender, and left ventricular ejection fraction but not receiving CRT. The findings suggest that patients with CRT had a significantly lower incidence of AF than controls. Further studies to establish the role of CRT in preventing AF and its mechanisms are warranted. [Copyright &y& Elsevier]

Abstract: Background: Cardiac resynchronization therapy (CRT) is now an established therapy for patients with advanced heart failure with electromechanical delay, although nonresponders have been observed. Because natriuretic peptides are relevant markers to reflect the severity of heart failure and filling pressure of cardiac chambers, it may be helpful to assess the efficacy of CRT. Methods and Results: Forty-two patients with heart failure with QRS of >120 msec were recruited; their serial N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels were measured at baseline and at 1 and 3 months after CRT. There was a reduction in NT-proBNP level 1 month after CRT (2655 ± 2242 pg/mL vs 2149 ± 2033 pg/mL; P =.03), which was further reduced at 3 months (1473 ± 1786 pg/mL; P < .001 vs baseline). The reduction of NT-proBNP correlated with the change of left ventricular (LV) end-systolic volume (r =0.53; P =.001) or LV ejection fraction (r =−0.49; P =.002) and with improvement in exercise capacity after CRT for 3 months (r =0.50; P =.002). The patients were classified by the degree of reduction in NT-proBNP as group 1 (reduction of ≥50% vs baseline; n=19) and group 2 (reduction of <50% vs baseline; n=23). The degree of LV reverse remodeling (–31.8 ± 24.7 mL vs −12.6 ± 19.2 mL; P =.007) and gain in LV ejection fraction (+12.5% ± 8.8% vs +4.6% ± 5.8%; P =.002) were significantly better in group 1 than group 2. Both the all-cause mortality rate (Log-rank χ2 =4.01; P =.04) and the composite end-point of mortality rate or hospitalization rate for cardiovascular causes (Log-rank χ2 =4.31; P =.02) were significantly lower in group 1 than in group 2. Conclusion: Serial monitoring of NT-proBNP may be helpful to predict a favorable outcome after CRT. Those who had a reduction of NT-proBNP level of ≥50% were more likely to exhibit a favorable response. [Copyright &y& Elsevier]

Objectives: This study was designed to investigate if tissue synchronization imaging (TSI) is useful to identify regional wall delay and predict left ventricular (LV) reverse remodeling after cardiac resynchronization therapy (CRT). Background: Echocardiographic assessment of systolic asynchrony is helpful to predict a positive response to CRT. Tissue synchronization imaging is a new imaging technique that allows quick evaluation of regional systolic delay. Methods: Tissue synchronization imaging was performed in 56 heart failure patients at baseline and three months after CRT. Regional wall delay was identified on TSI images and the time to regional peak systolic velocity (Ts) in LV was measured by the six-basal-six-mid-segmental model. Eight TSI parameters of systolic asynchrony were computed when Ts was measured in ejection phase or also included postsystolic shortening. Results: Severe lateral wall delay occurred in 17 patients, which predicted LV reverse remodeling (chi-square = 8.13, p = 0.004). Among the eight quantitative parameters of asynchrony, the predictive values were higher for parameters that measured Ts in ejection phase than in postsystolic shortening. The standard deviation of Ts of 12 LV segments in ejection phase (Ts-SD-12-ejection) was most powerful to predict reverse remodeling (r = −0.61, p < 0.001) and gain in ejection fraction (r = 0.53, p < 0.001). The area of the receiver-operating characteristic (ROC) curve was the largest for Ts-SD-12-ejection (0.90, p < 0.001), with a sensitivity of 87% and specificity of 81% at a cutoff of 34.4 ms. The combination of lateral wall delay with Ts-SD-12-ejection gave a sensitivity and specificity of 82% and 87%. Conclusions: Tissue synchronization imaging allows quick evaluation of regional wall delay, and combined with Ts-SD-12-ejection provides a reliable way of predicting reverse remodeling after CRT. [Copyright &y& Elsevier]

A new echocardiographic technology, the timing of regional volumetric changes by 3-dimensional echocardiography, was applied to assess intraventricular mechanical synchronicity in 13 patients who had received cardiac resynchronization therapy (CRT). When biventricular pacing was withheld, left ventricular (LV) asynchrony occurred as reflected by these echocardiographic parameters, whereas LV volume increased and the ejection fraction decreased. Further studies are needed to explore whether this novel method can be used to select suitable candidates for CRT and to predict a favorable response. [Copyright &y& Elsevier]

Biventricular pacing results in left ventricular (LV) reverse remodeling in heart failure patients with wide QRS complexes. This study examines potential predictors of reverse remodeling. Echocardiography with tissue Doppler imaging was performed at baseline and 3 months after biventricular pacing in 30 patients (21 men and 9 women, mean age 62 ± 14 years). There were 17 responders to reverse remodeling (defined as a reduction in LV end-systolic volume by >15%) and 13 nonresponders. Responders had significant improvement in 6-minute hall-walking distance (p = 0.006), metabolic equivalents (p = 0.02), peak oxygen uptake (p = 0.02), New York Heart Association functional class (p <0.001), and quality of life (p <0.001); an increase in the sphericity index (p = 0.007), ejection fraction (p <0.001), and diastolic filling time (p = 0.03); a decrease in myocardial performance index (p = 0.02), isovolumic relaxation time (p = 0.004), and mitral regurgitation (p = 0.007); and an improvement in systolic dyssynchrony (SD of the time to peak myocardial systolic contraction of the 12 LV segments as dyssynchrony index) (45.0 ± 8.3 vs 32.5 ± 14.5 ms, p = 0.003). In contrast, nonresponders only had a small degree of clinical improvement in New York Heart Association class (p = 0.03) and quality-of-life scores (p = 0.03), without any change in cardiac function, and worsening of systolic dyssynchrony (24.8 ± 4.5 vs 34.1 ± 13.5 ms, p = 0.02). When all the above factors were put into univariate and multivariate analyses models, systolic dyssynchrony was the only independent predictor of reverse remodeling (r = −0.76, p <0.001) (β = −1.54, p = 0.007). A preimplant dyssynchrony index of 32.6 ms (+2 SDs from mean of 88 normal controls) was able to totally segregate responders from nonresponders of biventricular pacing. Thus, responders of LV reverse remodeling were associated with improvement in clinical status, cardiac function, and systolic synchronicity. Direct assessment of systolic synchronicity by tissue Doppler imaging is highly accurate in predicting responders to therapy. [Copyright &y& Elsevier]

Background In the PLATO trial, ticagrelor was superior to clopidogrel in reducing cardiovascular events among patients with acute coronary syndrome (ACS) at the expense of increased nonfatal bleeding. Because Asian patients, when compared with non-Asian patients, are believed to be more susceptible to bleeding, we evaluated the effects of ticagrelor compared with clopidogrel in Asian (n = 1,106) and non-Asian (n = 17,515) patients with acute coronary syndrome enrolled in the PLATO study. Methods and Results Interaction between Asian/non-Asian and primary efficacy end point (a composite of vascular death, myocardial infarction, and stroke) and net clinical benefit (composite of primary efficacy end point and coronary artery bypass graft [CABG] surgery or non–CABG-related major bleeding) were evaluated with a Cox proportional hazards model. Baseline demographics and comorbidities were different between Asians and non-Asians. The overall cardiovascular event rates were higher in Asians, but bleeding rates were similar. Despite these observed differences, the effects of ticagrelor versus clopidogrel were not significantly different between Asians and non-Asians with respect to the primary efficacy outcome (hazard ratio for Asians vs non-Asians, 0.84 [95% CI 0.61-1.17] vs 0.85 [95% CI 0.77-0.93], P = .974), net clinical benefit (0.85 [95% CI 0.65-1.11] vs 0.93 [95% CI 0.86-0.99], P = .521), or individual efficacy end points. There was no significant interaction for bleeding (PLATO major bleeding, 1.02 [95% CI 0.70-1.49] vs 1.04 [95% CI 0.95-1.14], P = .938) and other related adverse events with ticagrelor compared with clopidogrel between Asians and non-Asians. Conclusions We observed consistency of effects in Asian patients receiving ticagrelor and clopidogrel in the PLATO study. The relatively modest number of Asian patients in this analysis supports further investigation of larger cohorts to confirm our observations. [ABSTRACT FROM AUTHOR]

Background: In the major trials of cardiac resynchronization therapy (CRT), the survival benefit of the therapy, relative to control subjects, increases with QRS duration. In the non-CRT heart failure population, however, a wide QRS duration is associated with a shorter survival. Relative survival benefit from a therapy, however, is not synonymous with a longer absolute survival. We sought to determine whether baseline QRS duration relates to the absolute survival after CRT. Methods and Results: In this prospective, longitudinal, observational study, 3,319 consecutive patients undergoing CRT (QRS 120-149 ms 26%, QRS 150-199 ms 58%, and QRS ≥200 ms 16%) were assessed in relation to mortality over 10 years. Overall mortality rates (per 100 patient-years) were 9.2%, 9.3%, and 13.3% in the 3 groups, respectively (all P < .001). Cardiac mortality rates were 6.2, 6.0, and 9.9 per 100 patient-years, respectively (all P < .001). Compared with the QRS 120-149 ms group, cardiac mortality was highest in the QRS ≥200 ms group (hazard ratio [HR] 1.72 [95% CI 1.35-2.19], P < .001), independent of age, gender, New York Heart Association class, presence of atrial fibrillation, heart failure etiology, and left ventricular ejection fraction. Median survival after CRT was longest in patients with a width of QRS 120-149 ms and shortest in patients with a QRS ≥200 ms (P < .001). In multivariable analyses, a QRS ≥200 ms emerged as a powerful independent predictor of both overall (HR 1.44 [95% CI 1.07-1.94], P = .017) and cardiac mortality (HR 1.59 [95% CI 1.14-2.24], P = .007). Conclusions: At long-term follow-up, absolute overall and cardiac survival after CRT is similar in patients with a preimplant QRS duration of 120 to 149 ms and 150 to 199 ms but markedly shorter in patients with a QRS ≥200 ms. [Copyright &y& Elsevier]