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Vascular complications are the most frequent adverse events associated with percutaneous coronary interventions (PCIs) leading to an increase in morbidity and mortality. Puncture of the common femoral artery in its middle segment is proved to decrease the risk of procedure-related vascular complications. Real-time ultrasound-guided puncture of the vessel is effective to decrease access site-related vascular complications but complex to perform. We evaluated whether an ultrasonic preinterventional examination of the femoral puncture site and skin marking of anatomic structures and specific vascular characteristics results in a decrease of access site-related vascular complications in PCIs with transfemoral access. Over a period of 12 months we prospectively examined all puncture sites before elective PCIs with transfemoral access (n = 848) using ultrasound. Presence, extent, and location of plaques and stenoses and exact location of bifurcation of the femoral artery were marked by a sonographer on the skin to guide the interventionists in vascular puncture. Postinterventional access site ultrasound was performed to determine possible access site-related complications. Frequency of vascular access site complications was compared to a control cohort (n = 1,027) that did not undergo ultrasound examination before intervention. With ultrasonic vascular access site management the rate of access site-related vascular complications was decreased from 4.2% to 1.9% (odds ratio 0.44, 0.23 to 0.80, p = 0.005). In conclusion, preinterventional ultrasonic access site examination and skin marking decreases the risk of vascular complications in elective PCI with femoral access.

In this review, we report on electrical modalities, which do not fit the definition of pacemaker, but increase cardiac performance either by direct application to the heart (e. g., post-extrasystolic potentiation or non-excitatory stimulation) or indirectly through activation of the nervous system (e. g., vagal or sympathetic activation). The physiological background of the possible mechanisms of these electrical modalities and their potential application to treat heart failure are discussed.

Objective: To develop and validate a prognostic risk index of cardiovascular mortality after cardiac resynchronisation therapy (CRT). Design: Prospective cohort study. Setting: District general hospital. Patients: 148 patients with heart failure (mean age 66.7 (SD 10.4) years), New York Heart Association class III or IV, LVEF

We sought to determine the unknown effects of cardiac resynchronization therapy (CRT) in patients with a left ventricular ejection fraction (LVEF)35%. Because of its technical limitations, echocardiography (Echo) may underestimate LVEF, compared with cardiovascular magnetic resonance (CMR).Of 157 patients undergoing CRT (New York Heart Association [NYHA] functional class III or IV, QRSor = 120 ms), all of whom had a preimplant Echo-LVEFor =35%, 130 had a CMR-LVEFor =35% (Group A, 19.7 +/- 7.0%[mean +/- standard deviation]) and 27 had a CMR-LVEF35% (Group B, 43.6 +/- 7.7%). All patients underwent a CMR scan at baseline and a clinical evaluation, including a 6-minute walk test and a quality of life questionnaire, at baseline and after CRT.Both groups derived similar improvements in NYHA functional class (A =-1.3, B =-1.2, [mean]), quality of life scores (A =-21.6, B =-33.0; all P0.0001 for changes from baseline), and 6-minute walking distance (A = 64.5, B = 70.1 m; P0.001 and P0.0001, respectively). Symptomatic response rates (increase byor =1 NYHA classes or 25% 6-minute walking distance) were 79% in group A and 92% in group B. Over a maximum follow-up period of 5.9 years for events, patients in group A were at a higher risk of death from any cause, hospitalization for major cardiovascular events (P = 0.0232), or cardiovascular death (P = 0.0411). There were borderline differences in the risk of death from any cause (P = 0.0664) and cardiovascular death or hospitalization for heart failure (P = 0.0526).This observational study suggests that the benefits of CRT extend to patients with a LVEF35%.

Objectives We aimed to assess a novel measure of left ventricular (LV) dyssynchrony, a cardiovascular magnetic resonance-tissue synchronization index (CMR-TSI), in patients with heart failure (HF). A further aim was to determine whether CMR-TSI predicts mortality and major cardiovascular events (MCE) after cardiac resynchronization therapy (CRT). Background Cardiac dyssynchrony is a predictor of mortality in patients with HF. The unparalleled spatial resolution of CMR may render CMR-TSI a predictor of clinical benefit after CRT. Methods In substudy A, CMR-TSI was assessed in 66 patients with HF (age 60.8 ± 10.8 years, LV ejection fraction 23.9 ± 12.1% [mean ± SD]) and 20 age-matched control subjects. In substudy B, CMR-TSI was assessed in relation to clinical events in 77 patients with HF and with a QRS ≥120 ms undergoing CRT. Results In analysis A, CMR-TSI was higher in patients with HF and a QRS Conclusions Myocardial dyssynchrony assessed by CMR-TSI is a powerful independent predictor of mortality and morbidity after CRT.

Background: Data from reduced lead ECG configurations can be transformed to reconstruct a 12-lead ECG. The sensing electrodes of a subcutaneous ICD (S-ICD) could provide a suitable basis for such a system. Reconstruction of a 12-lead ECG from conventional S-ICD vectors has not previously been demonstrated. Hypothesis: A 12-lead ECG signal can be accurately derived from S-ICD electrode vectors. Methods: Participants with ICDs (N=61) underwent 3 minute ECGs with electrodes in the standard S-ICD and 12-lead positions. Participants were randomised to either a training (N=31) or validation (N=30) group. Two participants and one further lead were subsequently excluded from the validation group due to technical faults. The transformation was a linear combination of the 2 independent S-ICD vectors to each of the 8 independent leads of the 12-lead ECG, with coefficients selected that minimized the root mean square error (RMSE) between recorded and derived ECGs when applied to the training group. The transformation was then applied to the validation group and agreement between the recorded and derived lead pairs was measured by Pearson correlation coefficient (r) and normalised RMSE (NRMSE). Results: In total, 335 lead pairs were compared (figure1). Distribution of r and NRMSE were skewed. Mean r = 0.731 (SE 0.021), Median r = 0.903 (SE 0.015). NRMSE Mean = 0.227 (SE 0.011) Median = 0.167 (SE 0.008). 252/335 (75.2%) of all pairs had an r > 0.7 (indicating very strong positive correlation). Figure 1: Example 12-lead ECG, recorded (blue line) and derived (red line). Participant randomly selected from top 20% by mean Pearson correlation coefficient. Conclusions: We have demonstrated reconstruction of a 12-lead ECG from S-ICD vectors. The agreement between derived and measured signals was generally excellent and comparable with other widely accepted reduced lead systems. If perfected, the ability to generate 12-lead data from an S-ICD could help clinicians to localise and treat arrhythmias.

Background Left ventricular (LV) mid-wall fibrosis (MWF), which occurs in about a quarter of patients with non-ischemic cardiomyopathy (NICM), is associated with high risk of pump failure. The mid LV wall is the site of circumferential myocardial fibers. We sought to determine the effect of MWF on LV myocardial mechanics. Methods Patients with NICM (n = 116; age: 62.8 ± 13.2 years; 67 % male) underwent late gadolinium enhancement cardiovascular magnetic resonance (CMR) and were categorized according to the presence (+) or absence (−) of MWF. Feature tracking (FT) CMR was used to assess myocardial deformation. Results Despite a similar LVEF (24.3 vs 27.5 %, p = 0.20), patients with MWF (32 [24 %]) had lower global circumferential strain (Ɛcc: −6.6 % vs −9.4 %, P = 0.004), but similar longitudinal (Ɛll: −7.6 % vs. −9.4 %, p = 0.053) and radial (Ɛrr: 14.6 % vs. 17.8 % p = 0.18) strain. Compared with − MWF, + MWF was associated with reduced LV systolic, circumferential strain rate (−0.38 ± 0.1 vs −0.56 ± 0.3 s−1, p = 0.005) and peak LV twist (4.65 vs. 6.31°, p = 0.004), as well as rigid LV body rotation (64 % vs 28 %, P

Cardiac resynchronization therapy (CRT) devices not only deliver effective treatment but may also serve as valuable diagnostic tools in heart failure management. In the present study, the minutes of daily physical activity and heart rate variability, measured by sensors incorporated into such a device, reflected the effects of CRT and were related to New York Heart Association functional class.

After cardiac catheterization procedures, arterial closure can be achieved by manual compression (MC), using external mechanical compression devices, or by applying vascular closure devices (VCDs) with comparable vascular access site-related complication rates. The aim of the present study was to assess vascular access site-related complications during the implementation of structured sheath removal and MC by paramedics after catheterization procedures. After an observational phase of 3 months to assess the baseline complication rate, a structured 4-level training program was implemented to train assistant personnel, in this case paramedics, in the management of sheath removal by MC. Access site-related complication rates after sheath removal were assessed prospectively and MC by paramedics compared with MC by physicians and application of VCDs. To account for imbalances in procedure- and patient-related risk factors of access-site complications, propensity score-based matching analysis was performed (ClinicalTrials.gov identifier NCT00825331). All consecutive percutaneous transfemoral arterial cardiac catheterization procedures were prospectively assessed over a period of 8 months (n = 3,503). MC was performed in 2,315 cases, of which 180 were performed by paramedics and 2,135 by physicians; VCDs were applied in 1,188 procedures. Rates of access site-related complications were significantly lower for paramedics compared with physicians (p = 0.03) and similar between paramedics and VCDs (p = 0.77). In conclusion a structured program for paramedics to be trained in sheath removal after percutaneous cardiac catheterization procedures can be readily implemented during clinical routine with low in-hospital complication rates.

Radial artery (RA) intima–media thickness (IMT) could be used to study short- and long-term structural vascular adaptation following transradial cardiac catheterization. We aimed at assessing the reliability and reproducibility of RA-IMT measurement. Using high-resolution ultrasound, we studied RA-IMT in 17 patients, who underwent transradial catheterization via the right RA 1 to 12 months before. Radial artery intima–media thickness was measured in both arms, with the left RA as control. Repeated measurements were performed by 2 examiners and offline analyses were performed by independent blinded interpreters. Radial artery intima–media thickness was highly reliable with an interclass correlation coefficient (ICC) of 0.911 [0.870-0.939], a high examiner (ICCexaminer 0.910 [0.883-0.931]), and interpreter agreement (ICCinterpreter 0.963 [0.954-0.971]). Intima–media thickness at the radial access site was significantly increased compared with the contralateral RA (0.30 ± 0.056 vs 0.41 ± 0.055 mm, P < .00001). Radial artery intima–media thickness can be measured reliably using high-resolution ultrasound. Initial data suggest that transradial catheterization leads to long-term structural adaption processes.

Current evidence suggests that regenerative v. degenerative endothelial responses can be integrated in a clinical endothelial phenotype, reflecting the net result between damage from risk factors and endogenous repair capacity. We have previously shown that a cocoa flavanol (CF) intervention can improve endothelial function and increase the regenerative capacity of the endothelium by mobilising circulating angiogenic cells in patients with coronary artery disease (CAD). The aim of the present study was to investigate whether CF can lower the levels of circulating endothelial microparticles (EMP), markers of endothelial integrity, along with improvements in endothelial function. The levels of EMP in the frozen plasma samples of CAD patients were measured along with endothelial function (flow-mediated vasodilation, FMD); n 16, FMD data published previously), and these data were compared with those of young (n 12) and age-matched (n 12) healthy control subjects. The CAD patients exhibited significantly increased levels of EMP along with impaired FMD when compared with the healthy control subjects. The levels of CD144+ and CD31+/41− EMP were inversely correlated with FMD (r − 0·67, P= 0·01 and r − 0·59, P= 0·01, respectively). In these CAD patients, the levels of EMP were measured after they had consumed a drink containing 375 mg of CF (high-CF intervention, HiFI) or 9 mg of CF (macro- and micronutrient-matched low-CF control, LoFl) twice daily over a 30-d period in a randomised, double-blind, cross-over study. After 1 month of HiFI, the levels of CD31+/41− and CD144+ EMP decreased ( − 25 and − 23 %, respectively), but not after LoFl. Our data show that flavanols lower the levels of EMP along with higher endothelial function, lending evidence to the novel concept that flavanols may improve endothelial integrity.

Hemodynamic optimization of cardiac resynchronization therapy (CRT) can be achieved reproducibly and--with bulky, nonimplantable equipment--noninvasively. We explored whether a simple photoplethysmogram signal might be used instead.Twenty patients (age 65 ± 12) with CRT underwent automatic atrioventricular (AV) delay optimization, using a multiple-transitions protocol, at two atrially paced heart rates: just above sinus rate ("slow ApVp," 77 ± 11 beats per minute [bpm]) and 100 bpm ("fast ApVp"). We then retested to assess short-term reproducibility.All 80 optimizations identified an optimum (correctly oriented parabola). At 100 bpm, the simple photoplethysmogram had wider scatter between repeat optimizations than did Finometer: standard deviation of difference (SDD) 22 ms versus 14 ms, respectively, P = 0.028. The simple photoplethysmogram improved in reproducibility when slope (instead of peak) of its signal was used for optimization, becoming as reproducible as Finometer (SDD 14 ms vs 14 ms, P = 0.50). At slow heart rate, reproducibility of simple photoplethysmogram-based optimization worsened from 14 to 22 ms (P = 0.028), and Finometer-based optimization from 14 to 26 ms (P = 0.005). Increasing the number of replicates averaged improved reproducibility. For example, SDD of simple photoplethysmogram optimization (using peak) fell from 62 ms with two replicates to 22 ms with eight replicates (P0.0001). At 100 bpm, the eight-replicate protocol takes ∼12 minutes.A 12-minute protocol of simple photoplethysmographic AV optimization can be processed fully automatically. Blinded test-retest reproducibility of the optimum AV is good and improves with more replicates. If benefits to some patients are not to be neutralized by harm to others, endpoint studies should first test check narrowness of "within-patient error bars."

Cardiac resynchronization therapy (CRT) can improve clinical and cardiac structural status in heart failure patients. The role of baseline diastolic echocardiographic parameters to characterize the likelihood of positive outcomes is not well known. We explored relationships between diastolic parameters and outcomes 6 months after CRT implant in the Predictors of Response to CRT (PROSPECT) Trial.We hypothesized that diastolic echocardiographic parameters were associated with clinical and structural outcomes in CRT patients.For 426 patients in PROSPECT, a prospective observational trial of CRT, baseline E/A ratio, left atrial (LA) area, isovolumic relaxation time, left ventricular inflow deceleration time, E' velocity, and E/E' ratio were evaluated and related to 6-month clinical composite score (CCS) and left ventricular end-systolic volume (LVESV) reduction using Spearman rank-order correlations. Parameters associated with outcomes were analyzed further by discrete categorization.As continuous variables, only E/A ratio and LA area correlated with CCSs (P = 0.017, P = 0.045, respectively) and relative change in LVESV at 6 months (P0.0001, P = 0.001, respectively). As discrete variables, E/A ratio and LA area also correlated with CCSs and LVESV.Diastolic echo parameters E/A ratio and LA area were associated with clinical and structural outcomes in CRT patients at 6 months.

Aims Cardiac resynchronization therapy (CRT) by means of biventricular pacing (BiVP) is well established as a treatment for patients with heart failure (HF). Post-extrasystolic potentiation, (PESP) which involves a transient increase in myocardial contractility following a ventricular extrasystole, can be achieved using extrasystolic stimulation (ESS). On this basis, ESS has been proposed as a therapeutic. We assessed acute haemodynamic effects of ESS in the context of BiVP. Methods and results Patients (n = 5, left ventricular ejection fraction = 125 ms) with HF, received BiVP in combination with right ventricular (RV) ESS (single stimulus or pulse train). Left ventricular (LV) and peripheral arterial pressures were recorded and dP/dt was monitored. Addition of RV ESS to BiVP pacing led to a 21% increase in maximum (max) dP/dt (P < 0.001) and an 8.5 mm Hg increase in a systolic arterial pressure (P < 0.001). The modest fall in end-diastolic pressure (3.3 mmHg, P < 0.001) observed during ESS and BiVP was prevented by maintaining baseline sinus rate. Varying ESS modes or pacing outputs was not associated with differences in haemodynamic parameters. Conclusions Biventricular pacing in combination with ESS, with maintenance of sinus rate, improves myocardial contractility in patients undergoing CRT.

The role of right bundle branch block (RBBB) for the induction of left ventricular (LV) asynchrony is discussed controversially. The objective of this study was to assess presence and degree of LV asynchrony in patients with RBBB, left bundle branch block (LBBB), or left anterior hemiblock (LAH) and normal LV function.We included 15 patients with RBBB, 13 patients with RBBB and concomitant LAH, 10 patients with pure LBBB, and 100 healthy controls into this study. All patients had normal LV function. Interventricular asynchrony was assessed as the difference of the right and LV ejection delay. Intraventricular delay was obtained by tissue synchronicity imaging-guided tissue Doppler imaging measurement.Interventricular and left intraventricular asynchrony were linked to the presence of an LBBB. No left intraventricular asynchrony was noted during pure RBBB; interventricular delays were negative (aortic flow preceding pulmonary flow) in the presence of RBBB.In patients with normal LV function, intraventricular asynchrony depends on the presence of an LBBB and interventricular asynchrony is inversed in the presence of RBBB.

Impact of variability in the measured parameter is rarely considered in designing clinical protocols for optimization of atrioventricular (AV) or interventricular (VV) delay of cardiac resynchronization therapy (CRT). In this article, we approach this question quantitatively using mathematical simulation in which the true optimum is known and examine practical implications using some real measurements. We calculated the performance of any optimization process that selects the pacing setting which maximizes an underlying signal, such as flow or pressure, in the presence of overlying random variability (noise). If signal and noise are of equal size, for a 5-choice optimization (60, 100, 140, 180, 220 ms), replicate AV delay optima are rarely identical but rather scattered with a standard deviation of 45 ms. This scatter was overwhelmingly determined (ρ = −0.975, P

This thesis assesses the mechanisms by which biventricular and left ventricular pacing improves cardiac performance in patients with heart failure. We demonstrated for the first time that CRT results in an improvement in acute haemodynamic variables in heart failure patients with a narrow QRS duration that is comparable to the effects seen in heart failure patients with a broad QRS duration. In addition, we have shown that both biventricular (BIVP) and left ventricular pacing (LVP) significantly reduce external constraint to left ventricular filling, resulting in an increase in effective filling pressure. In heart failure patients with evidence of external constraint at rest, the acute haemodynamic benefits of both BIVP and LVP were principally due to the relief of external constraint and preload recruitment. However, in those patients with evidence of electrical dyssynchrony and a broad QRS duration, a significant haemodynamic benefit was derived from an enhancement in left ventricular contractility, presumably as a result of a reduction in left ventricular dyssynchrony. Patients with external constraint appear to derive a greater haemodynamic benefit from pacing due to the significant increase in stroke work that is associated with relief of external constraint and preload recruitment, in addition to the increase in stroke work derived from enhanced contractility due to a reduction in dyssynchrony. These findings will inform better patient selection for this therapy and also optimisation of pacing strategy in individual patients.

To evaluate the clinical response to cardiac resynchronisation therapy (CRT) in patients with heart failure and a normal QRS duration (120 ms).Single centre.60 patients with heart failure and a normal QRS duration receiving optimal pharmacological treatment (OPT).Patients were randomly assigned to CRT (n=29) or to a control group (OPT, n=31). Cardiovascular magnetic resonance was used in order to avoid scar at the site of left ventricular (LV) lead deployment.The primary end point was a change in 6 min walking distance (6-MWD). Other measures included a change in quality of life scores (Minnesota Living with Heart Failure questionnaire) and New York Heart Association class.In 93% of implantations, the LV lead was deployed over non-scarred myocardium. At 6 months, the 6-MWD increased with CRT compared with OPT (p0.0001), with more patients reaching a ≥25% increase (51.7% vs 12.9%, p=0.0019). Compared with OPT, CRT led to an improvement in quality-of-life scores (p=0.0265) and a reduction in NYHA class (p0.0001). The composite clinical score (survival for 6 months free of heart failure hospitalisations plus improvement by one or more NYHA class or by ≥25% in 6-MWD) was better in CRT than in OPT (83% vs 23%, respectively; p0.0001). Although no differences in total or cardiovascular mortality emerged between OPT and CRT, patients receiving OPT had a higher risk of death from pump failure than patients assigned to CRT (HR=8.41, p=0.0447) after a median follow-up of 677.5 days.CRT leads to an improvement in symptoms, exercise capacity and quality of life in patients with heart failure and a normal QRS duration. (ClinicalTrials.gov number, NCT00480051.).

This study aimed at exploring access site-related vascular complication rates associated with the use of the vascular closure device (VCD) Angio-Seal™ in an unselected patient population undergoing elective as well as emergency coronary angiography or intervention. The VCD Angio-Seal™ is widely used to achieve hemostasis after diagnostic and interventional cardiac procedures. There are only little data on the frequency of vascular complications after the use of the VCD Angio-Seal™ in patients in non-elective settings. In-hospital vascular complications were prospectively assessed in 4,653 consecutive cardiac catheterization procedures, which included 2,772 elective diagnostic and 960 elective percutaneous coronary interventions (PCI), and 921 emergency cardiac catheterizations in patients with NSTEMI/STEMI. In 2,077 procedures manual compression (MC) and in 2,576 procedures VCD was applied. Complication rates for manual compression and VCD use were studied and multivariate analyses performed to disclose predictors for access site-related vascular complications. Vascular complication rates in patients receiving MC to achieve hemostasis were similar to those receiving a VCD (MC 3.4% vs. VCD 3.2%, p = n.s.). Separate analysis of vascular complication rates for subgroups revealed a significant reduction in vascular complications for the PCI group using a VCD (MC 7.7% vs. VCD 3.2%, p = 0.003). In emergencies VCD use lead to a rise in vascular complications (MC 0.9% vs. VCD 6.3%, p

Aims The aim of this study was to determine whether growth differentiation factor-15 (GDF-15) predicts mortality and morbidity after cardiac resynchronization therapy (CRT). Growth differentiation factor-15, a transforming growth factor-β-related cytokine which is up-regulated in cardiomyocytes via multiple stress pathways, predicts mortality in patients with heart failure treated pharmacologically. Methods and results Growth differentiation factor-15 was measured before and 360 days (median) after implantation in 158 patients with heart failure [age 68 ± 11 years (mean ± SD), left ventricular ejection fraction (LVEF) 23.1 ± 9.8%, New York Class Association (NYHA) class III ( n = 117) or IV ( n = 41), and QRS 153.9 ± 28.2 ms] undergoing CRT and followed up for a maximum of 5.4 years for events. In a stepwise Cox proportional hazards model with bootstrapping, adopting log GDF-15, log NT pro-BNP, LVEF, and NYHA class as independent variables, only log GDF-15 [hazard ratio (HR), 3.76; P = 0.0049] and log NT pro-BNP (HR, 2.12; P = 0.0171) remained in the final model. In the latter, the bias-corrected slope was 0.85, the optimism ( O ) was −0.06, and the c -statistic was 0.74, indicating excellent internal validity. In univariate analyses, log GDF-15 [HR, 5.31; 95% confidence interval (CI), 2.31–11.9; likelihood ratio (LR) χ 2 = 14.6; P < 0.0001], NT pro-BNP (HR, 2.79; 95% CI, 1.55–5.26; LR χ 2 = 10.4; P = 0.0004), and the combination of both biomarkers (HR, 7.03; 95% CI, 2.91–17.5; LR χ 2 = 19.1; P < 0.0001) emerged as significant predictors. The biomarker combination was associated with the highest LR χ 2 for all endpoints. Conclusion Pre-implant GDF-15 is a strong predictor of mortality and morbidity after CRT, independent of NT pro-BNP. The predictive value of these analytes is enhanced by combined measurement.

Background. Previous studies have reported dyssynchrony using Tissue Doppler in patients with hypertrophic cardiomyopathy (HCM). In this study we assessed dyssynchrony using speckle tracking echocardiography (STE) in patients with non-obstructive hypertrophic cardiomyopathy vs a healthy control group and in a subgroup of highly symptomatic patients evaluated the acute effects of biventricular pacing on STE and Tissue Doppler (TDI) derived measures of dyssynchrony. Methods. We studied 48 healthy controls (age 48 ±18yrs, 22 males, LVEF 63 ±5%, QRS 86 ±7ms) and 57 patients with HCM (age 54 ±11yrs, 38 males, LVEF 61 ±7%, QRS 110 ±36ms). A subgroup of 15 symptomatic patients with HCM (Peak VO2 Results. Using STE, Tϵ-SD (54.99 ±33.61ms vs 24.55 ±21.18ms p . (All values expressed as mean ±SD) Conclusion. Cardiac resynchronisation therapy significantly reduced dyssynchrony in symptomatic patients with non-obstructive HCM as demonstrated using STE and TDI. Table

Aims: Studies on cardiac resynchronization therapy (CRT) for heart failure have shown a differential response in patients with ischemic (ICM) and non-ischemic cardiomyopathy (NICM). Increasing dyssynchrony has been shown to relate to a poor prognosis in patients with heart failure. We hypothesized that ICM and NICM have varying effects on left ventricular (LV) synchrony. Methods: The recently described cardiovascular magnetic resonance tissue synchronization index (CMR-TSI), which predicts benefit from CRT, was quantified in 181 patients (age: 66.4 ± 10.6 yrs, NYHA class III or IV, LVEF: 23.5 ± 10.8%, QRS = 139.8 ± 32.0 ms) with ICM (n=105) or NICM (n=76) and age-matched, healthy controls (n=24). The maximum time-to-peak radial wall motion in a short axis stack of LV images (steady-steady free precession imaging) was fitted to an empirical sine wave [y = a + b * sin (t/RR + c)]. The CMR-TSI was calculated as the SD of all segmental phase shifts of the radial wall motion extracted from this wave (see Figure for bull’s eye maps). Results: CMR-TSI was higher in ICM (105.8 ± 44.2, ANOVA p ). In multivariate analyses including ICM and NICM patients only, ischemic aetiology emerged as a positive predictor of CMR-TSI, independent of QRS duration, LV end-systolic and end-diastolic volumes, and LVEF (all p Conclusions: ICM is associated with a greater degree of dyssynchrony than NICM, independently of QRS duration, LV volumes and LVEF. These findings may account for the differential response to CRT observed with patients with ICM and NICM.

Objectives:To determine the effect of a posterolateral (PL) left ventricular scar on mortality and morbidity following cardiac resynchronization therapy (CRT). Methods:Sixty-two patients with heart failure (age 67.3 ± 9.6 yrs [mean ± SD], 45 males, New York Heart Association class [NYHA] class III or IV, left ventricular ejection fraction [LVEF]= 35%, left bundle branch block, QRS ≥ 120 ms) underwent late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) for scar imaging. Patients were followed up for 741 (75–1602) days (mean [range]). Results:The presence of a PL scar emerged as an independent predictor of the composite endpoint of cardiovascular death or hospitalization for worsening heart failure (HR: 3.06 [1.63, 7.7, P < 0.0001]) as well as the endpoint of cardiovascular death (HR: 2.63 [1.39, 6.65], P = 0.0016). A transmural PL scar was the strongest predictor of these endpoints (both P < 0.0001). The symptomatic responder rate (improvement by ≥1 NYHA classes or ≥25% in 6-min walking distance) was 83% in the group with non-PL scars, but only 47% in the group with transmural PL scars (P < 0.0001). Pacing over the scar was associated with a higher mortality and morbidity than pacing outside the scar (all P < 0.05). Conclusions:A PL scar is associated with a worse clinical outcome following CRT, particularly if it is transmural. Pacing scarred left ventricular myocardium carries a greater risk of mortality and morbidity than pacing nonscarred myocardium.

We aimed to assess a novel measure of left ventricular (LV) dyssynchrony, a cardiovascular magnetic resonance-tissue synchronization index (CMR-TSI), in patients with heart failure (HF). A further aim was to determine whether CMR-TSI predicts mortality and major cardiovascular events (MCE) after cardiac resynchronization therapy (CRT).Cardiac dyssynchrony is a predictor of mortality in patients with HF. The unparalleled spatial resolution of CMR may render CMR-TSI a predictor of clinical benefit after CRT.In substudy A, CMR-TSI was assessed in 66 patients with HF (age 60.8 +/- 10.8 years, LV ejection fraction 23.9 +/- 12.1% [mean +/- SD]) and 20 age-matched control subjects. In substudy B, CMR-TSI was assessed in relation to clinical events in 77 patients with HF and with a QRSor =120 ms undergoing CRT.In analysis A, CMR-TSI was higher in patients with HF and a QRS120 ms (79.5 +/- 31.2 ms, p = 0.0003) and in those with a QRSor =120 ms (105.9 +/- 55.8 ms, p0.0001) than in control subjects (21.2 +/- 8.1 ms). In analysis B, a CMR-TSIor =110 ms emerged as an independent predictor of the composite end points of death or unplanned hospitalization for MCE (hazard ratio [HR] 2.45; 95% confidence interval [CI] 1.51 to 4.34, p = 0.0002) or death from any cause or unplanned hospitalization for HF (HR 2.15; 95% CI 1.23 to 4.14, p = 0.0060) as well as death from any cause (HR: 2.6; 95% CI 1.29 to 6.73, p = 0.0061) and cardiovascular death (HR 3.82; 95% CI 1.63 to 16.5, p = 0.0007) over a mean follow-up of 764 days.Myocardial dyssynchrony assessed by CMR-TSI is a powerful independent predictor of mortality and morbidity after CRT.

UNLABELLED AF Burden After CRT Implantation. AIMS Cardiac resynchronization therapy (CRT) is increasingly used in congestive heart failure (CHF) patients (with cardiac dyssynchrony). In addition to delivering therapy, CRT devices offer a variety of diagnostic tools for continuous long-term monitoring of clinically relevant information (i.e., occurrence and duration of arrhythmia episodes). METHODS AND RESULTS Eighty-four patients with drug-refractory CHF in NYHA-class II-IV received a CRT device. The response to CRT was assessed by determining NYHA class at baseline and at 3 months follow-up. Atrial fibrillation (AF) burden (defined as time of AF per day) was continuously measured by the device. A significant gradual reduction of AF burden (from 9.88 +/- 12.61 to 4.20 +/- 9.24 [hours/day]) and number of patients experiencing AF episodes (from 26 to 13) were observed during CRT. CONCLUSIONS (1) Diagnostic features for long-term monitoring of physiological variables provide useful information on the state and course of AF and may improve disease management. (2) AF burden reduces over time during the first 3 months after CRT implantation.

Background It may be incorrect to believe that, with a good echocardiographic marker of mechanical dyssynchrony, response to biventricular pacing (BVP) should be predictable with a high r 2 value. Variability between repeat echocardiographic measurements, and between successive dyssynchrony measurements, may reduce r 2 . Both will mandatorily limit the achievable r 2 ; we determine this “contraction factor”. Method and Results We compared correlation coefficients of dyssynchrony indices with response markers, in externally monitored randomised controlled trials (EMRCTs) and highly skilled single centre studies (HSSCSs). ΔLVEF in CRT recipients comprises true CRT effect plus unpredictable spontaneous variability present in control patients (Abstract 85 figure 1, upper panel). The resultant depression in r 2 is calculated. HSSCSs overstate r 2 between dyssynchrony and remodelling response in contrast to EMRCTs (p 2 between differing dyssynchrony markers to commonly used echocardiographic response markers is shown in Abstract 85 figure 1, lower panel. EMRCT data shows maximal r 2 between dyssynchrony and ΔLVEF is 0.57 (ΔESV, 0.54; ΔEDV, 0.50). Dyssynchrony indices9 own variability further contracts observable r 2 values (by x0.68). The overall ceiling to r 2 is between dyssynchrony and ΔLVEF is 0.39 (ΔESV, 0.37; ΔEDV, 0.34). All EMRCT r 2 values obey these statistical limits; 29% of HSSCSs results do not. Conclusions HSSCSs suggest dyssynchrony markers strongly predict response to BVP but EMRCTs cannot confirm this. Natural variability forces observed correlation coefficients between dyssynchrony and response to be low. EMRCTs, being less susceptible to publication bias, reflect this reliably. Frequent citation (without verification in independent cohorts) of the most exuberant values, from HSSCSs creates mathematically unviable, unrealistic, expectations. Simply searching for progressively more extreme correlations is therefore misguided. Rationally, we should concentrate on improving test-retest reproducibility of markers of dyssynchrony and of response.

Background Established methods to determine asynchrony suffer from high intra- and interobserver variability and failed to improve patient selection for cardiac resynchronization therapy (CRT). Thus, there is a need for easy and robust approaches to reliably assess cardiac asynchrony. Methods and Results We performed echocardiography in 100 healthy subjects and 33 patients with left bundle branch block (LBBB). To detect intraventricular asynchrony, we combined two established methods, i.e., tissue synchronization imaging (TSI) and tissue Doppler imaging (TDI). The time intervals from the onset of aortic valve opening (AVO) to the peak systolic velocity (S') were measured separately in six basal segments in the apical four-, two-, and three-chamber view. Color-coded TSI served as an intrinsic plausibility control and helped to identify the correct S' measuring point in the TDI curves. Next, we identified the segment with the shortest AVO-S' interval. Since this segment most likely represents vital and intact myocardium it served as a reference for other segments. Segments were considered asynchronous when the delay between the segment in question and the reference segment was above the upper limit of normal delays derived from the control population. Intra- and interobserver variability were 7.0% and 7.7%, respectively. Conclusion Our results suggest that combination of TDI and TSI with intrinsic plausibility control improves intra- and interobserver variability and allows easy and reliable assessment of cardiac asynchrony.

Aims: Despite a marked difference in the QRS width induced by biventricular (BIVP) and left ventricular pacing (LVP), both modes of pacing are eficacious at improving cardiac function in heart failure patients with left ventricular dyssynchrony, and in a recent study we demonstrated comparable beneits from BIVP and LVP in a patient group with a narrow QRS duration and no observable dyssynchrony. We hypothesised that optimisation of the interventricular pacing interval may further improve LV function. Methods: Twenty ive heart failure patients with a narrow QRS duration and 12 with a broad QRS duration underwent invasive haemodynamic pressure-volume studies at the time of pacemaker implantation. Absolute left ventricular stroke work (LVSW) and dP/dtMAX were determined during no pacing (VVI), in biventricular (BIVP), left ventricular (LVP) pacing mode, and over a range of interventricular timing delays. Results: Both dP/dtMAX and LVSW increased signiicantly in response to V-V delays in which the LV led by >20ms. In patients with external constraint, there was a trend towards a greater increase in LVSW with those interventricular delays where the LV was the irst chamber paced, compared with patients without external constraint, in whom near-simultaneous interventricular delays ranging from the RV leading by 12ms to the LV leading by 20ms appeared to be optimal. Conclusion: Although many would argue that the optimal V-V delay shows great variability and must be individualized, we have demonstrated optimal V-V delays in patient groups based on the presence or absence of external constraint.

Background In patients with non-ischemic dilated cardiomyopathy (NIDCM), mid-wall fibrosis (MWF) is associated with a higher risk of hospitalizations and death from pump failure and sudden cardiac death. The mechanical effects of MWF remain unexplored. Strain measures derived from feature tracking-CMR (FT-CMR) have been validated against myocardial tagging. Methods Patients (n = 84, age: 57.7 ± 14.7 yrs, [mean ± SD], LVEF: 25.7 ± 11.1%) with newly diagnosed NIDCM underwent late gadolinium enhancement CMR (inversion-recovery technique 10 min after the administration of gadolinium-DTPA (0.1 mmol/kg). Peak systolic cir

Background Intuitively, cardiac dyssynchrony is the inevitable result of myocardial injury. We hypothezised that radial dyssynchrony reflects left ventricular remodeling, myocardial scarring, QRS duration and impaired LV function and that, accordingly, it is detectable in all patients with heart failure. Methods 225 patients with heart failure, grouped according to QRS duration of Results Compared to 50 healthy controls (21.8 ± 6.3 ms [mean ± SD]), CMR-TSI was higher in A (74.8 ± 34.6 ms), B (92.4 ± 39.5 ms) and C (104.6 ± 45.6 ms) (all p < 0.0001). Adopting a cut-off CMR-TSI of 34.4 ms (21.8 plus 2xSD for controls) for the definition of dyssynchrony, it was present in 91% in A, 95% in B and 99% in C. Amongst patients in NYHA class III or IV, with a LVEF120 ms, 99% had dyssynchrony. Amongst those with a QRS(-0.033 LVEF) ms, p < 0.0001). Conclusion Radial dyssynchrony is almost universal in patients with heart failure. This vies against the notion that a lack of response to CRT is related to a lack of dyssynchrony.