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BackgroundCardiac resynchronization therapy (CRT) improves symptoms, health-related quality of life and long-term survival in patients with systolic heart failure (HF) and shortens QRS duration. However, up to one third of patients attain no measurable clinical benefit from CRT. An important determinant of clinical response is optimal choice in left ventricular (LV) pacing site. Observational data have shown that achieving an LV lead position at a site of late electrical activation is associated with better clinical and echocardiographic outcomes compared to standard placement, but mapping-guided LV lead placement towards the site of latest electrical activation has never been investigated in a randomized controlled trial (RCT). The purpose of this study was to evaluate the effect of targeted positioning of the LV lead towards the latest electrically activated area. We hypothesize that this strategy is superior to standard LV lead placement.MethodsThe DANISH-CRT trial is a national, double-blinded RCT (ClinicalTrials.gov NCT03280862). A total of 1000 patients referred for a de novo CRT implantation or an upgrade to CRT from right ventricular pacing will be randomized 1:1 to receive conventional LV lead positioning preferably in a non-apical posterolateral branch of the coronary sinus (CS) (control group) or targeted positioning of the LV lead to the CS branch with the latest local electrical LV activation (intervention group). In the intervention group, late activation will be determined using electrical mapping of the CS. The primary endpoint is a composite of death and non-planned HF hospitalization. Patients are followed for a minimum of two years and until 264 primary endpoints occurred. Analyses will be conducted according to the intention-to-treat principle. Enrollment for this trial began in March 2018, and per April 2023, a total of 823 patients have been included. Enrollment is expected to be complete by mid-2024.ConclusionsThe DANISH-CRT trial will clarify whether mapping-guided positioning of the LV lead according to the latest local electrical activation in the CS is beneficial for patients in terms of reducing the composite endpoint of death or non-planned hospitalization for heart failure. Results from this trial are expected to impact future guidelines on CRT. Background: Cardiac resynchronization therapy (CRT) improves symptoms, health-related quality of life and long-term survival in patients with systolic heart failure (HF) and shortens QRS duration. However, up to one third of patients attain no measurable clinical benefit from CRT. An important determinant of clinical response is optimal choice in left ventricular (LV) pacing site. Observational data have shown that achieving an LV lead position at a site of late electrical activation is associated with better clinical and echocardiographic outcomes compared to standard placement, but mapping-guided LV lead placement towards the site of latest electrical activation has never been investigated in a randomized controlled trial (RCT). The purpose of this study was to evaluate the effect of targeted positioning of the LV lead towards the latest electrically activated area. We hypothesize that this strategy is superior to standard LV lead placement. Methods: The DANISH-CRT trial is a national, double-blinded RCT (ClinicalTrials.gov NCT03280862). A total of 1,000 patients referred for a de novo CRT implantation or an upgrade to CRT from right ventricular pacing will be randomized 1:1 to receive conventional LV lead positioning preferably in a nonapical posterolateral branch of the coronary sinus (CS) (control group) or targeted positioning of the LV lead to the CS branch with the latest local electrical LV activation (intervention group). In the intervention group, late activation will be determined using electrical mapping of the CS. The primary endpoint is a composite of death and nonplanned HF hospitalization. Patients are followed for a minimum of 2 years and until 264 primary endpoints occurred. Analyses will be conducted according to the intention-to-treat principle. Enrollment for this trial began in March 2018, and per April 2023, a total of 823 patients have been included. Enrollment is expected to be complete by mid-2024. Conclusions: The DANISH-CRT trial will clarify whether mapping-guided positioning of the LV lead according to the latest local electrical activation in the CS is beneficial for patients in terms of reducing the composite endpoint of death or nonplanned hospitalization for heart failure. Results from this trial are expected to impact future guidelines on CRT. ClinicalTrials.gov identifier: NCT03280862.

Aims Measures of left atrial (LA) function are known to predict both ischaemic stroke and atrial fibrillation in specific patient groups. The aim of this study was to investigate the value of LA reservoir strain for predicting ischaemic stroke in patients undergoing coronary artery bypass grafting (CABG) and investigate whether the presence of postoperative atrial fibrillation (POAF) modified this relationship. Methods and results Patients undergoing isolated CABG were included. The primary endpoint was ischaemic stroke. The association between LA reservoir strain and ischaemic stroke was investigated in uni- and multivariable Cox proportional hazards regression models including adjustment for POAF. We included 542 patients (mean age 67.3±8.9 years, 16.4% female). During a median follow-up period of 3.9 years, 21 patients (3.9%) experienced an ischaemic stroke. In total, 96 patients (17.7%) developed POAF during the index hospitalization. In a multivariable-adjusted Cox proportional hazards regression model, LA reservoir strain was significantly associated with the development of ischaemic stroke [HR (hazard ratio) 1.09 (95% CI 1.02–1.17) per 1% decrease, P = 0.011]. The presence of POAF did not modify this association (p for interaction = 0.07). The predictive value of the LA reservoir strain persisted in multiple sensitivity analyses including restricting the analysis to patients with normal left atrial volumes (LAV Conclusion LA reservoir strain was independently associated with ischaemic stroke in CABG patients. The predictive value of LA reservoir strain was unaffected by the presence of POAF. Prospective studies are warranted to validate the potential usefulness of LA reservoir strain to predict postoperative ischaemic stroke in the setting of CABG.

Acute coronary syndrome (ACS) may lead to adverse remodelling and impaired cardiac function. Limited data exists on the effect of culprit coronary artery lesion site and impact on longitudinal cardiac remodelling. The present study included a total of 299 patients suffering from ACS treated with percutaneous coronary intervention (PCI). All patients had two echocardiographic examinations. The first echocardiography was median 2(IQR: 1;3) days following PCI, while the follow-up echocardiography (FUE) was median 257(IQR: 96;942) days following the first. Patients were grouped based on coronary artery PCI location; left anterior descending artery (LAD), right coronary artery (RCA) or circumflex artery (Cx). Patients with multiple lesions were excluded. Mean age was 63 ± 11 years and 77% were male. At FUE, mean left ventricular ejection fraction was 42 ± 9% and global longitudinal strain (GLS) was - 13 ± 4%. PCI treatment was allocated as 168 LAD lesions, 95 RCA lesions, and 36 Cx lesions. Linear regression analysis showed that patients with a LAD lesion displayed worsening in E/A (mean ∆ = 0.05, β = - 0.196, p = 0.001) and a larger increase in LVEDV (mean ∆ = 33.18 mL, β = 0.135, p = 0.012). Meanwhile patients with Cx lesion were significantly associated with a larger decrease in E/e' (mean ∆ = 2.6, β = - 0.120, p = 0.028). Patients with Cx lesion were observed to have elevated E/e' at baseline, which normalized at FUE. The present study suggests that culprit coronary artery lesion has a differential impact on myocardial remodelling. This information may potentially aid in understanding the pathophysiological differences in cardiac structure and function amongst patients with ACS.

Background The ratio of early mitral inflow velocity to early diastolic strain rate (E/e'sr) is a novel echocardiographic measure to estimate early left ventricular (LV) filling pressure. We hypothesize that E/e'sr is a predictor of outcome following coronary artery bypass grafting (CABG) and that it is superior to the conventionally used E/e'. Methods & results Consecutive patients undergoing isolated CABG at Gentofte Hospital (n = 652) were included. The mean age of the study population was 67 ± 9 years, 84% were male, mean LVEF was 50 ± 11%. Prior to surgery, all patients underwent an extensive echocardiographic examination. The outcome was all-cause mortality. During follow-up (median 3.8 years [IQR: 2.7; 4.9 years]), a total of 73 (11.2%) died. Both E/e' and E/e'sr were significant predictors in univariable models. In a multivariable model, E/e'sr remained an independent predictor of outcome (HR:1.05 [1.01–1.10], p = 0.049, per 10 cm increase) whereas E/e' did not (HR:1.05 [0.99–1.11], p = 0.053, per 1-unit increase). The relationship between E/e'sr, and the outcome was significantly modified by GLS (p for interaction = 0.043). In the multivariable model, E/e'sr was still significantly associated with the outcome in patients with high GLS (≥13.6%) (HR:1.18 [1.02–1.36], p = 0.029) but not in patients with low GLS (HR 1.04 CI95%: [0.99–1.10], p = 0.14). E/e' was not a significant predictor of all-cause mortality after multivariable adjustment in neither of the groups. E/e'sr improved net reclassification with 33% when added to EuroSCOREII. Conclusion Following CABG, preoperative E/e'sr is an independent predictor of all-cause mortality, especially in patients with preserved systolic function and superior to E/e'.

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia following coronary artery bypass grafting (CABG). We hypothesized that measures of left atrial (LA) function would be useful in predicting AF in patients undergoing CABG. Methods and Results In the study, 611 patients were included after CABG. All patients had echocardiograms performed preoperatively and LA functional measurements were assessed. These measurements were LA maximum volume index (LAVmax), LA minimum volume index (LAVmin) and LA emptying fraction (LAEF). The endpoint was AF occurring >14 days after surgery. During the follow-up period of a median of 3.7 years, 52 (9%) developed AF. The mean age was 67 years, 84% were male and the average left ventricle ejection fraction was 50 %. No differences were observed between the patients developing AF and those who did not develop AF. No functional LA measurements were significant predictors of AF in the whole CABG population. However, in patients with normal-sized LA (n=532, events: 49), both LAEF and LAVmin were univariable predictors of AF. When the functional measurements were adjusted for the CHADS score, both LAVmin (HR=1.07 (1.01-1.13), p=0.014 ) and LAEF (HR: 1.02 (1.00-1.03, p= 0.023)), remained significant predictors. Conclusion No echocardiographic measurements were significant predictors of AF after CABG. In patients with a normal LA size, LAVmin as well as LAEF were significant predictors of AF. Keywords: atrial fibrillation; cardiac surgery; left atrium; echocardiography

Global longitudinal strain (GLS) has proven to be a powerful prognostic marker in various patient populations, but the prognostic value of layer-specific GLS has not yet been investigated in patients with suspected stable angina pectoris (SAP). We sought to investigate the prognostic value of layer-specific and whole wall GLS in patients with suspected SAP. From September 2008 to March 2011, 296 consecutive patients with clinically suspected SAP, normal ejection fraction, and no previous cardiac history were enrolled in a prospective cohort study. Patients underwent echocardiography including two-dimensional speckle tracking at rest, exercise stress test, and coronary angiography. The end-point was a composite of incident heart failure, acute myocardial infarction, and cardiovascular death (MACE). Out of the 285 included patients (mean age 61 years, 50% male), 24 (8%) developed MACE during a median follow-up of 3.5 years. Both endocardial [hazard ratio (HR) 1.21, 95% CI 1.08–1.35, p = 0.001], epicardial (HR 1.29, 95% CI 1.12–1.50, p = 0.001) and whole wall GLS (HR 1.25, 1.10–1.42, p = 0.001) were significantly associated with an increased risk of developing MACE during follow-up in univariable Cox regression analysis. In multivariable analysis, only epicardial (HR 1.23, 95% CI 1.00–1.51, p = 0.046) and whole wall GLS (HR 1.20, 95% CI 1.00–1.43, p = 0.049) remained significantly associated with an increased risk of MACE independent of various baseline clinical variables, left ventricular ejection fraction (LVEF), E/eʹ and Duke Score. Layer-specific and whole wall GLS were significant predictors of MACE in this cohort of patients with suspected SAP independent of various baseline clinical variables, LVEF, E/eʹ and Duke Score.

Global Longitudinal Strain (GLS) is a well-established predictor of heart failure (HF) following acute coronary syndrome (ACS). We aim to investigate the prognostic value of GLS obtained at a follow-up consultation, as well as the change in GLS for long-term risk of incident HF. A total of 235 ACS patients had an echocardiogram performed immediately after percutaneous coronary intervention (PCI) and a follow-up echocardiogram (FUE) median 215 (IQR: 71; 878) days after the first echocardiogram. Endpoint was incident HF. Follow-up time after FUE was median 4.8 (IQR: 3.7; 5.6) years. Patients diagnosed with HF before FUE were excluded. Mean age was 63 ± 11 years and 77% were male. Baseline GLS was on average 12.7 ± 3.9%, FUE GLS was on average 13.5 ± 3.9% and mean improvement in GLS was 0.73 ± 3.68% between the 2 echocardiograms. A total of 57 (24%) patients suffered incident HF following the FUE. FUE GLS provided significantly higher prognostic information for risk of incident HF than ∆GLS when assessed by the C-statistics (C-statistics: 0.71 vs. 0.61, P = 0.021). Furthermore, after multivariable adjustments only FUE GLS [HR = 1.15, 95% CI (1.02; 1.29), P = 0.018, per 1% decrease] remained an independent predictor of incident HF. In patients with ACS, who do not develop HF before FUE, FUE GLS was an independent predictor of long-term risk of incident HF while ∆GLS was not.

To explore the association between E-wave propagation index (EPI) as a marker of apical washout and the risk of left ventricular thrombus (LVT) formation in patients with ST-elevation myocardial infarction (STEMI).We performed a post-hoc analysis on 364 prospectively enrolled STEMI patients from a single-center. Non-contrast transthoracic echocardiographic examinations were performed a median of 2 days (IQR:1-3 days) after PCI. The endpoint was LVT formation, identified retrospectively. Univariable and multivariable logistic regression was applied to assess the association between EPI and LVT formation. Multivariable adjustments included LVEF, LAD culprit, prior myocardial infarction, heart rate, and early myocardial relaxation velocity. Area under receiver operating characteristic curves (AUC) was used to assess the diagnostic ability.Among 364 patients, 31 (8.5%) developed LVT. The mean age was 62 years, 75% were men, and mean LVEF was 46%. Patients developing LVT had increased heart rate, lower LVEF, impaired GLS, and more frequently had prior myocardial infarction. Variables associated with low values of EPI included, among others, LVEF, LV aneurysm, and GLS. EPI and LVT formation were significantly associated in the univariable model (OR = 1.87 (1.53-2.28), p 0.001), and EPI showed an AUC of 0.90. After multivariable adjustments, EPI and LVT formation remained significantly associated (OR = 1.79 (1.42-2.27), p 0.001). Patients with an EPI 1.0 had a 23 times higher likelihood of LVT formation (OR = 23.41 (10.06-54.49), p 0.001). EPI and LVT formation are strongly associated in patients with STEMI, with low values of EPI indicating a markedly increased probability of LVT formation.

ObjectiveTo determine the prognostic value of global longitudinal strain (GLS) after coronary artery bypass grafting (CABG).MethodsWe performed a retrospective cohort study on patients undergoing CABG between 2006 and 2011 who had an echocardiogram available for strain analysis. The patients were followed up through nationwide registries for development of all-cause mortality, cardiovascular death (CVD) and major adverse cardiovascular events (MACEs) defined as heart failure hospitalisation and/or CVD. Multivariable Cox regression was applied to adjust for the European System for Cardiac Operative Risk Evaluation II (EuroSCORE-II). Additive value was assessed by Net Reclassification Index (NRI) improvement.ResultsOf the 709 patients included, 80 died during a median follow-up of 3.8 years. Of these, 45 had CVD, and 72 patients experienced MACE. Mean age was 68 years and 85% were men. Left ventricular ejection fraction (LVEF) was 50% and GLS was −13%.GLS was an independent predictor when adjusted for the EuroSCORE-II (all-cause mortality: HR=1.07 (1.01–1.13), p=0.018; CVD: HR=1.11 (1.03–1.20), p=0.007; MACE: HR=1.12 (1.06–1.19), pLVEF modified the association between GLS and outcomes (p for interactionConclusionGLS is an independent predictor of long-term outcomes after CABG. The predictive value appears strongest among patients with preserved LVEF.

Background: Patients with type 2 diabetes (T2D) have increased risk for subclinical myocardial disease. Early systolic lengthening (ESL), a paradoxical stretch of myocardial fibers, is a sensitive marker of myocardial dysfunction. The aims of this study were to investigate the prognostic value of ESL in patients with T2D and to determine if global longitudinal strain (GLS) modifies this relationship. Methods: In this prospective study, speckle-tracking echocardiography was conducted in 703 patients with T2D (62% men; mean age, 63 ± 10 years; median diabetes duration, 11 years; interquartile range, 6–17 years). Patients had no histories of significant heart disease. ESL index was assessed as [−100 × (peak positive systolic strain/maximal strain)] and ESL duration as time from QRS complex on the electrocardiogram to time of peak positive systolic strain. P values ≤ .004 were considered to indicate statistical significance. Results: During a median follow-up time of 4.8 years (interquartile range, 4.1–5.3 years), 86 patients (12%) experienced major adverse cardiovascular events (MACE), a composite of incident heart failure, myocardial infarction, and cardiovascular death. In multivariate models, only the ESL index (hazard ratio [HR], 1.06 per 1% increase; 95% CI, 1.01–1.010; P = .004) but not ESL duration (HR, 1.02 per 1-ms increase; 95% CI, 1.00–1.03; P = .036) were associated with MACE. GLS modified this relationship (P for interaction < .05) such that in patients with low GLS (>−18%), ESL index (HR, 1.06 per 1% increase; 95% CI, 1.02–1.10; P = .003) was associated with MACE, but ESL duration was not (HR, 1.02 per 1-ms increase; 95% CI, 1.00–1.04; P = .005). No associations were found for high GLS (

BACKGROUND Studies suggest cardiac time intervals to be associated with cardiac ischemia. A novel method to assess cardiac time intervals by tissue Doppler echocardiography has been proposed. Cardiac time intervals can assess the myocardial performance index (MPI), which quantifies the proportion of time spent contributing effective myocardial work. We hypothesized that MPI associates with coronary artery lesions detected by cardiac computed tomography (CT) in patients suspected of coronary artery disease (CAD). METHODS We investigated patients referred for cardiac CT under suspicion of CAD who had an echocardiogram performed. Curved m-mode tissue Doppler imaging was used to measure cardiac time intervals and MPI. The outcome was coronary artery lesions, defined as a calcium score > 400 and/or coronary artery stenosis (>70% luminal narrowing). Logistic regression was applied with multivariable models including: (a) SCORE chart risk factors and (b) SCORE chart risk factors, body mass index, dyslipidemia, familial history of CAD, diabetes mellitus, LVEF, and left ventricular mass index. RESULTS Of 404 patients, 41 (10%) had a coronary artery lesion. Overall, 42% were male, mean age was 58 years, and LVEF was 58%. Patients with coronary artery lesions exhibited higher MPI than those without (0.52 vs. 0.44, P

In studies on left-sided valve disease, patients with combined lesions are generally excluded. We aimed to describe the clinical management and prognosis of patients with combined left-sided valve disease.From a single, tertiary care center, a total of 122 patients with combined left-sided valve disease of at least moderate severity were identified and compared with 143 controls with single-lesion valve disease (1VaD) of at least moderate severity. Endpoints were all-cause mortality and the combination of valve intervention and mortality.Overall survival for patients with two-lesion valve disease was significantly lower than that for patients with 1VaD (estimated 3-year survival: 52% versus 73%, P < 0.001). Compared with 1VaD, the combination of aortic stenosis and aortic regurgitation (AS/AR) was associated with a similar overall survival (hazard ratio (HR) (95% confidence interval (CI) ): 0.83 (0.47-1.48), P = 0.53), the combination of AR and mitral regurgitation (AR/MR) with an intermediate survival (HR (95% CI): 1.76 (1.03-3.00), P = 0.039) and the combination of AS and MR (AS/MR) with the poorest survival (HR (95% CI): 3.28 (2.16-4.98), P < 0.001). At 2.2 years of follow-up, the majority of patients in all three groups were either dead or had received valve intervention (AS/AR: 72%, AR/MR: 64%, and AS/MR: 80%).Combined valve disease was relatively rare but was associated with a decreased overall survival. Survival depended on the specific combination of valve lesions, with AS/MR carrying the worst prognosis. The majority of patients in all groups were either dead or had valve intervention performed within 2.2 years.

This study aimed to clarify the diagnostic and prognostic potential of strain rate in patients with suspected stable angina pectoris (SAP). Strain rate by 2-dimensional speckle tracking echocardiography (2DSTE) has been suggested to be able to diagnose coronary artery disease (CAD) and predict cardiovascular events in various patient groups. Prospectively enrolled patients (n = 296) with suspected SAP, no previous cardiac disease, and normal left ventricular ejection fraction were examined by 2DSTE, exercise ECG, and coronary angiography. Obstructive CAD was defined as stenosis ≥ 70% in ≥ 1 coronary artery on coronary angiography (n = 107). Major adverse cardiac events (MACE) included myocardial infarction, heart failure, atrial fibrillation, and stroke. In multivariable analysis adjusted for baseline data, conventional echocardiography, and Duke score, early diastolic strain rate (SRe) was independently associated with significant CAD with a 1.35 increased risk of having CAD per 0.1 decrease in SRe (OR = 1.35, 95% CI 1.03-1.76, P = 0.027). Peak velocity of early diastolic filling (E)/SRe was not associated with significant CAD (OR = 1.14, 95% CI 0.81-1.62, P = 0.445). MACE occurred in 34 patients (12%) during follow-up (median 3.5 years) and both SRe (HR 1.26, 95% CI (1.07-1.49), P = 0.006) and E/SRe (HR 1.24, 95% CI (1.04-1.47), P = 0.017) were independent predictors after multivariable adjustment. In patients with suspected SAP, SRe by 2DSTE was independently associated with presence of CAD. In addition, SRe and E/SRe provided independent and incremental prognostic value for predicting future MACE.

Introduction: The ratio of early mitral inflow velocity to early diastolic strain rate (E/e’sr) is a novel echocardiographic measure to estimate early left ventricular (LV) filling pressure. Hypothesis: We hypothesize that E/e’sr is a predictor of outcome following coronary artery bypass grafting (CABG) and that it is superior to the conventionally used E/e’. Methods: Consecutive patients undergoing isolated CABG at Gentofte Hospital (n=652) were included. Prior to surgery, all patients underwent an extensive echocardiographic examination. The outcome was all-cause mortality. Cox proportional hazard regression models were used to assess the prognostic value of E/e’sr in relation to the outcome. Results: The mean age of the study population was 67±9 years, 84% were male, mean LV ejection fraction was 50±11%. During follow-up (median 3.8 years [IQR: 2.7; 4.9 years]), a total of 73 (11%) died. Both E/e’ and E/e’sr were significant predictors in univariable models. In a multivariable model adjusted for demographic, clinical and echocardiographic covariates, E/e’sr remained an independent predictor of outcome (HR:1.05 [1.01-1.10], p=0.049, per 10cm increase) whereas E/e’ did not (HR:1.05 [0.99-1.11], p=0.053, per 1-unit increase). The relationship between E/e’sr, and the outcome was significantly modified by GLS (p for interaction = 0.043) ( Figure ). In the multivariable model, E/e’sr was still significantly associated with the outcome in patients with high GLS (≥13.6%) (HR:1.18 [1.02-1.36], p=0.029) but not in patients with low GLS (HR 1.04 CI95%: [0.99-1.10], p=0.14). E/e’ was not a significant predictor of all-cause mortality after multivariable adjustment in neither of the groups. E/e’sr improved net reclassification with 0.33 when added to the EuroSCOREII model. Conclusions: Following CABG, preoperative E/e’sr is an independent predictor of all-cause mortality, especially in patients with preserved systolic function and superior to E/e’.

Background: Evolvement in speckle-tracking echocardiography (STE) enable a detailed layer-specific analysis of the right ventricular (RV), which has shown to be a promising way of quantifying RV systolic function. We aimed to evaluate the usefulness layer-specific RV free wall strain (RVFWS) for predicting cardiovascular outcome in patients undergoing coronary artery bypass grafting (CABG). Methods: We studied 317 patients scheduled for CABG, with echocardiography prior to surgery. RV STE was performed to acquire endocardial, midmyocardial, and epicardial RVFWS. The endpoint was a composite of heart failure (HF) or cardiovascular death (CVD). Cox proportional hazards regression were used to assess the prognostic value. The multivariable adjustments included among other age, sex, hypertension and LVEF. Restricted cubic spline models were created to visualize the incidence rate for each RVFWS. Results: Of 317 patients, 30 (9.5%) reached the endpoint at a median follow-up of 3.5 years. The mean age was 67 years, 83% were men, and the mean LVEF was 50%. In univariable analyses all three layers were associated with a higher risk of the outcome (figure). All three layers remained independently associated with the outcome after multivariable adjustment (endo: HR 1.07 (1.01-1.13), mid: HR 1.06 (1.01-1.12), epi: HR 1.06 (1.01-1.11), per 1% absolute decrease). Reduced endo-RVFWS and mid-RVFWS posed a two-fold increased risk of developing HF and/or CV death as compared to those with preserved RVFWS (incidence rate of 3.7 (2.39-5.63) vs. 1.5 (0.76-2.82), events per 100 patient-years for reduced and preserved endo-RVFWS as well as reduced and preserved mid-RVFWS). Patients with reduced epi-RVFWS did not exhibit a higher risk of the outcome as compared to those with preserved epi-RVFWS. Conclusion: In patients undergoing CABG, RVFWS is a predictor of cardiovascular outcomes, and particularly reduced endocardial and midmyocardial RVFWS pose an increased risk of outcome.

Background: The E-wave propagation index (EPI) is a measure of apical blood flow and has been proposed as a risk marker of left ventricular thrombus (LVT) formation. We sought to investigate the association between EPI and LVT in patients with heart failure with reduced ejection fraction (HFrEF). Methods: This was a retrospective cohort study of patients with HFrEF. Follow-up echocardiograms were investigated for development of LVT. EPI was measured at baseline investigation as the velocity time integral of the transmitral E-wave divided by the left ventricular length. Logistic regression was used to investigate the association between EPI and LVT. Multivariable adjustments were made for age, significant mitral regurgitation, apical aneurysm, prior myocardial infarction, and left ventricular ejection fraction (LVEF). Results: Of 785 patients, 24 (3%) developed LVT. Mean age was 66 years, 73% were men, and LVEF was 28%. Those who developed LVT had significantly lower EPI (1.12 vs. 1.36, p=0.02). EPI was significantly associated with LVT in univariable logistic regression (OR=1.16 (1.03-1.31), per 0.1 decrease) (figure). These findings were unchanged after multivariable adjustments (OR=1.15 (1.00-1.31), per 0.1 decrease). The EPI provided an area under the curve of 0.68 with an optimal cutoff of 1.2. This cutoff had a sensitivity of 75%, specificity of 60%, positive predictive value of 6%, and negative predictive value of 99%. A low EPI was associated with a more than 4-fold increased risk of LVT (OR=4.56 (1.79-11.62), p=0.001). Conclusion: Decreasing EPI is associated with a higher risk of LVT. While a low EPI poses a markedly increased risk of LVT, a high EPI may be used to rule out LVT.

PURPOSE: Right ventricular (RV) dysfunction is associated with poor outcome in patients with heart failure. In order to better predict mortality in this patient group we wanted to compare the prognostic value of conventional and advanced RV echocardiographic measures.METHODS: Echocardiographic examinations were retrieved from 701 patients. End point was all-cause mortality and follow-up 100%. RV parameters were measured offline in accordance with current guidelines. Speckle tracking was derived using the algorithm originally designed for the left ventricle.RESULTS: During follow-up (median: 39 months) 118 patients (16.8%) died. RV global longitudinal strain (GLS) and RV free wall strain (FWS) remained associated with mortality after multivariable adjustment independent of Tricuspid annular plane systolic excursion (TAPSE) (RV GLS: HR 1.07, 95%CI 1.02-1.13, p = 0.010, per 1% decrease) (RV FWS: HR 1.05, 95%CI 1.01-1.09, p = 0.010, per 1% decrease). This seemed to be caused by significant associations in men. All RV estimates provided prognostic information incremental to established risk factors and significantly increased C-statistics.CONCLUSIONS: RV GLS and FWS were associated with mortality in HFrEF patients after multivariable adjustment independent of TAPSE. TAPSE, however, remained as the strongest prognosticator in women. More research is needed to identify whether speckle tracking could be superior to conventional RV measures in identifying HFrEF patients with poor outcome.

Background Recent improvements in speckle tracking echocardiography have made sectionalized quantification of layer-specific global longitudinal strain (GLS) possible. Prior studies have reported prognostic value of GLS in several cardiac diseases, however, the use of layer-specific strain has not been investigated in patients undergoing coronary artery bypass grafting (CABG). Purpose To determine the prognostic value of layer-specific GLS for predicting all-cause mortality after CABG. Methods In this retrospective cohort study, consecutive patients undergoing isolated CABG between 2006 and 2011 were included. The patients were followed through nation-wide registries for the endpoint of all-cause mortality. Multivariable Cox regression models adjusted for clinical and echocardiographic baseline characteristics were used to assess the association between layer-specific GLS and all-cause mortality. Cumulative survival was stratified by clinical age and gender-dependent cut-off values for the layer-specific GLS, which was obtained from a large healthy population study. Results Of 641 patients included (mean age 67 years, 84% male), 70 (10.9%) died during follow-up (median 3.8 years [IQR: 2.7; 4.9 years]). Patients who died during follow-up were significantly older (71 years vs. 67 years, P = Conclusion Layer-specific GLS is an independent prognosticator of all-cause mortality after CABG. In multivariable models, GLSepi provided significant prognostic value after adjusting for echocardiographic parameters and EuroScore II. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Research grant from Herlev & Gentofte University Hospital's internal research funds. Figure 1. Kaplan-Meier survival estimatesFigure 2. Incidence rate of all-cause mortality

Postsystolic shortening (PSS) by speckle-tracking echocardiography (STE) is a marker of myocardial ischemia and may improve diagnostic strategy. We sought to evaluate if PSS is associated with the coronary artery calcium score (CACS) and stenosis by computed tomography angiography (CTA) in patients with suspected stable angina pectoris (SAP). We retrospectively studied 437 SAP patients (age 58 ± 11 years, 41% male) who underwent STE, evaluation of CACS and assessment of significant stenosis (≥ 50%) by CTA. The postsystolic index (PSI) was defined as follows: 100x([peak negative strain cardiac cycle − peak negative strain systole])/peak negative strain cardiac cycle. A wall had PSS if any segment within the wall had a PSI ≥ 20%. We defined categories for walls with PSS: 0, 1, 2 and ≥ 3, and CACS: 0, 1–100, 101–400 and > 400. Each additional wall with PSS was associated with a 43% relative increase in CACS (95%CI +9% to +87%, P = 0.010), while each 1% absolute increase in the PSI was associated with a 9% relative increase in CACS (95%CI +1% to +18%, P = 0.031). Walls with PSS (OR 1.81 per 1 wall increase, 95%CI 1.27–2.59, P = 0.001) and the PSI (OR 1.12 per 1% increase, 95%CI 1.04–1.21, P = 0.004) were associated with the occurrence of CACS > 400. Additionally, walls with PSS (OR 1.53 per 1 wall increase, 95%CI 1.21–1.93, P

Aims: The ratio of early mitral inflow velocity to global diastolic strain rate (E/e'sr) has recently emerged as a novel measure of left ventricular (LV) filling pressure. This new measure has demonstrated to have prognostic value superior to E/e’. This study aimed to investigate the prognostic value of E/e'sr in a large cohort of patients with heart failure with reduced ejection fraction (HFrEF) in relation to all-cause mortality. Methods: We retrospectively studied 897 HFrEF (mean age 66 ± 12 years, 73% male, 59% ischemic cardiomyopathy) patients who underwent speckle tracking echocardiography where E/e'sr along with novel and conventional echocardiographic parameters were obtained. The primary endpoint was defined as all-cause mortality. Results: During follow-up (median: 40 months IQR: 22-57), 137 (15.3%) patients died. Both E/e'sr and E/e’ were significantly associated with mortality (E/e'sr: HR 1.03 95%CI [1.02-1.04], p

Background Nearly one-third of heart failure (HF) patients do not respond to cardiac resynchronization therapy (CRT) despite having left bundle branch block (LBBB). The aim of the study was to investigate a novel method of quantifying left ventricular (LV) contractile asymmetry in HF. Methods Patients with HF and LBBB undergoing CRT (n = 89, 37.1% females, 68 ± 9 years, ischemic etiology in 61%, LV ejection fraction 27.1 ± 7.1%) were analyzed. LV longitudinal systolic strain rate values were extracted from curved anatomical M-mode plots of standard long-axis 2D-echocardiography images and cubic spline interpolation was used to generate a 3D-phantom. Index of contractile asymmetry (ICA) was calculated based on standard deviation of differences in strain rate of opposing walls. Average ICA was individually assessed pairwise in 12 opposing 30-degree LV sectors. Reduction in LV end-systolic volume (ESV) ≥15% after 6 months was considered as positive response to CRT. Results CRT response was found in 66 (74.2%) patients. Responders with both ischemic and non-ischemic cardiomyopathy had a higher and more extensive contractile asymmetry at baseline and achieved a greater ICA reduction after CRT than non-responders. Higher baseline ICA predicted higher degree and wider extent of ICA improvement. Also, both ICA at baseline and reduction of ICA correlated with the degree of ESV reduction after CRT. Conclusions Quantification of asymmetrical LV activation in 3D by ICA provides valuable insights into LV contraction in case of LBBB and is a promising tool for improved patient selection for CRT.

Dyspnea is a common clinical challenge in patients with type 2 diabetes and may be a sign of heart failure (HF). We sought to evaluate the predictive value dyspnea with and without an echocardiographic substrate in patients with type 2 diabetes without known heart disease.A total of 724 patients with type 2 diabetes followed at specialized clinics participated in this prospective cohort study. Clinical evaluation, comprehensive echocardiography and follow-up through national registers were performed. An echocardiographic substrate was either left ventricular hypertrophy, increased left atrial size, E/e' 15, or LV ejection fraction50%. The end-points were cardiovascular (CVD) events and all-cause mortality.Median follow-up was 4.8 years [Interquartile range: 4.1, 5.3] for CVD event and 77 patients suffered a CVD event. Dyspnea was significantly associated with CVD event: Hazard ratio (HR): 1.58 (95% confidence interval: 1.01-2.48), p = 0.04. Stratifying by evidence of echocardiographic substrate revealed high risk individuals: CVD event: 0.71 (0.35-1.46), p = NS in patients with dyspnea and no echocardiographic substrate and 2.85 (1.74-4.67), p 0.001 in patients with dyspnea with echocardiographic substrate). This pattern was similar in multivariable analyses. Also, C-statistics improved from 0.66 (0.60-0.72) to 0.69 (0.63-0.75), p 0.001 and net reclassification index was 27.5%(5.0-50.0), p = 0.01 for CVD event. The results were similar for all-cause mortality except dyspnea was only a borderline significant predictor.In patients with type 2 diabetes complaining of dyspnea, identifying an echocardiographic substrate - thus indicating patients with HF - accurately stratifies patients with increased risk of CV events and all-cause mortality.

Twenty-five percent of ischemic strokes (IS) are cryptogenic, but it is estimated that paroxysmal atrial fibrillation (PAF) is the underlying cause in up to a third of cases. We aimed to investigate the predictive value of speckle tracking of the left atrium (LA) in diagnosing PAF in IS patients. We retrospectively studied 186 IS patients with a clinical echocardiographic examination during sinus rhythm. Outcome was PAF defined by at least one reported episode of AF following their IS. Conventional echocardiographic measures were performed. Global longitudinal strain (GLS), LA reservoir-(es), conduit-(ee), contraction-strain (ea) and LA dyssynchrony (standard deviation of time-to-peak es; LA SD-T2P) were obtained by left ventricular and LA speckle tracking. Of 186 patients, 28 (15%) were diagnosed with PAF. PAF-patients did not differ from non-PAF patients with regards to GLS nor SD-TPS, but atrial strain measures were significantly impaired at baseline (es 27 vs. 35%, ee 12 vs. 16%, ea 15 vs. 18%, p

Cardiac resynchronization therapy (CRT) reduces the risk of ventricular arrhythmias (VA) in heart failure (HF) patients with left bundle branch block (LBBB) while the effect is less clear among non-LBBB patients. This study aimed to investigate if absence of LBBB features whether by echocardiography or strict ECG criteria would identify patients at risk of developing VA in a cohort with LBBB according to conventional ECG criteria. Two hundred six CRT candidates were prospectively included from 2 centers. Prior to CRT presence of a typical LBBB contraction pattern was identified using longitudinal strain in the apical 4-chamber view. All preimplantation ECGs were categorized as LBBB or non-LBBB according to Strauss´ strict criteria. Primary end-point was defined as any appropriate antitachycardia pacing (ATP) or shock therapy within 2 years after CRT implantation. A total of 129 (63%) patients had a typical LBBB contraction pattern, while 134 (66%) met the strict ECG criteria. Over 2 years, 45 patients (22%) experienced VA. Absence of a typical LBBB contraction pattern was independently associated with an increased risk of VA (hazard ratio ([HR] 1.89; 95% CI 1.04 to 3.44; p: 0.036). Strict LBBB was not independently associated with the occurrence of VA. Fulfilling neither strict ECG nor echocardiographic criteria for LBBB was associated with a 3.3-fold increase in risk of VA ([HR] 3.34; 95% CI 1.75 to 6.94; (p < 0.001). The risk of VA was almost 2-fold higher if a typical LBBB contraction pattern was absent prior to CRT.

Early systolic lengthening and postsystolic shortening may yield prognostic information in cardiovascular high-risk groups. We aimed to investigate the prognostic potential of these patterns in patients with heart failure with reduced ejection fraction (HFrEF), and specifically if the value was greater in patients with ischemic etiology. A total of 884 patients with HFrEF (66 ± 12 years, male 73%, mean EF 28 ± 9%) underwent speckle tracking echocardiography. Of these, 61% suffered from ischemic cardiomyopathy (ICM). Patients were followed for all-cause mortality. We assessed myocardial lengthening during early systole, defined by the early systolic strain index (ESI): [-100x (peak positive strain/maximal strain)] and myocardial shortening after aortic valve closure, defined by the postsystolic strain index (PSI): [100x (postsystolic strain-peak systolic strain)/maximal strain]. During median follow-up of 3.4 [interquartile range 1.9 to 4.8] years, 132 patients (15%) died. ICM modified the relationship between ESI and all-cause mortality (P interaction = 0.008), but not for PSI (P interaction = 0.13). When assessing patients with ICM by Cox proportional hazards models, per 1% increase in ESI (HR 1.09 [1.04 to 1.15], P

Background Severity and extent of coronary artery disease (CAD) assessed by invasive coronary angiography (ICA) guide treatment and may predict clinical outcome in patients with non–ST-segment elevation acute coronary syndrome (NSTEACS). Objectives This study tested the hypothesis that coronary computed tomography angiography (CTA) is equivalent to ICA for risk assessment in patients with NSTEACS. Methods The VERDICT (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes) trial evaluated timing of treatment in relation to outcome in patients with NSTEACS and included a clinically blinded coronary CTA conducted prior to ICA. Severity of CAD was defined as obstructive (coronary stenosis ≥50%) or nonobstructive. Extent of CAD was defined as high risk (obstructive left main or proximal left anterior descending artery stenosis and/or multivessel disease) or non–high risk. The primary endpoint was a composite of all-cause death, nonfatal recurrent myocardial infarction, hospital admission for refractory myocardial ischemia, or heart failure. Results Coronary CTA and ICA were conducted in 978 patients. During a median follow-up time of 4.2 years (interquartile range: 2.7 to 5.5 years), the primary endpoint occurred in 208 patients (21.3%). The rate of the primary endpoint was up to 1.7-fold higher in patients with obstructive CAD compared with in patients with nonobstructive CAD as defined by coronary CTA (hazard ratio [HR]: 1.74; 95% confidence interval [CI]: 1.22 to 2.49; p = 0.002) or ICA (HR: 1.54; 95% CI: 1.13 to 2.11; p = 0.007). In patients with high-risk CAD, the rate of the primary endpoint was 1.5-fold higher compared with the rate in those with non–high-risk CAD as defined by coronary CTA (HR: 1.56; 95% CI: 1.18 to 2.07; p = 0.002). A similar trend was noted for ICA (HR: 1.28; 95% CI: 0.98 to 1.69; p = 0.07). Conclusions Coronary CTA is equivalent to ICA for the assessment of long-term risk in patients with NSTEACS. (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes [VERDICT]; NCT02061891 )

Diagnostic tests including echocardiography, albuminuria, electrocardiogram (ECG), high-sensitivity troponin I (hs-TnI), and N-terminal prohormone brain natriuretic peptide (NT-proBNP) have been suggested as cardiovascular (CV) risk predictors in type 2 diabetes. We studied the separate and combined prognostic yield of these risk markers.In all, 1030 patients with type 2 diabetes were recruited from specialized clinics in this prospective cohort study. Full echocardiographic evaluation was feasible in 886 patients in sinus rhythm with adequate image quality. ECG was performed in 998 patients. Albuminuria was measured in 1009 and NT-proBNP/hs-TnI in 933 patients. The end point was a composite of CV events.The median follow-up was 4.7 years (interquartile range: 4.0-5.3), and 174 patients experienced a CV disease event. All considered markers, except hs-TnI, were significantly (P .001) associated with the outcome: abnormal echocardiogram (hazard ratio 2.40 [1.70-3.39]), albuminuria 2.01 (1.47-2.76), abnormal ECG (2.27 [1.66-3.08]), high NT-proBNP (150 pg/mL) 3.05 (2.11-4.40), and hs-TnI 1.12 (0.79-1.59). After adjusting for clinical variables, all remained significantly associated with the end point. However, after adjusting for each other, only NT-proBNP150 pg/mL remained significantly associated with the end point (2.07 [1.28-3.34], P .001). Measured by C-statistics, model performance was highest with logThis study identified NT-proBNP over echocardiography, ECG, and albuminuria in risk prediction in patients with type 2 diabetes. The diagnostic yield in considering more than one risk marker was limited in this population.背景: 超声心动图、蛋白尿、心电图(ECG)、高敏肌钙蛋白I(hs-TnI)和N末端前激素脑钠素(NT-proBNP)等诊断试验被认为能够预测2型糖尿病心血管(CV)的危险因素。我们研究了这些风险标记物的单独和联合预测效果。 方法: 在这项前瞻性队列研究中, 从专科诊所共招募1030名2型糖尿病患者。886例窦性心律且图像质量良好的患者进行了超声心动图的全面评估。对998例患者进行心电图检查。1009例患者检测蛋白尿, 933例患者检测NT-proBNP/hs-TnI。终点是CV事件的组合。 结果: 中位随访时间为4.7年(四分位数范围:4.0-5.3), 174名患者经历了心血管疾病事件。除hs-TnI外, 所有考虑的标志物:超声心动图异常(危险比2.40[1.70-3.39])、蛋白尿2.01(1.47-2.76)、心电图异常(2.27[1.66-3.08])、高NT-proBNP(150pg/mL)3.05(2.11-4.40)和hs-TnI 1.12(0.79-1.59) 均与预后显著相关(P0.001)。在调整了临床变量后, 所有这些变量仍然与终点显著相关。然而, 在变量间调整后, 只有NT-proBNP150pg/mL与终点显著相关(2.07[1.28-3.34], P0.001)。通过C-统计量测量, log

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The Independent Research Fund Denmark Background Early systolic lengthening (ESL), a paradoxical stretch of myocardial fibers, has been linked to myocardial viability and contractile dysfunction. We assessed the long-term prognostic potential of ESL in coronary artery bypass graft (CABG) patients. Methods We retrospectively included patients (n = 709; mean age 68 years; 85% men) who underwent speckle tracking echocardiography (median 15 days) prior to CABG. Endpoints were cardiovascular death (CVD) and all-cause mortality. We assessed amplitude of ESL (%), defined as peak positive strain, and duration of ESL (ms), determined as time from Q-wave on the ECG to peak positive strain. We applied Cox proportional hazards models adjusted for the clinical risk tool, EuroSCORE II. Results During median follow-up of 3.8 years [IQR 2.7 to 4.9 years], 45 (6%) experienced CVD and 80 (11%) died. In survival analyses adjusted for EuroSCORE II, amplitude of ESL was associated with CVD (HR 1.37 [95%CI 1.13 to 1.66], P = 0.001) and all-cause mortality (HR 1.31 [95%CI 1.13 to 1.54], P = 0.001). Similar findings applied to duration of ESL and CVD (HR 1.17 [95%CI 1.08 to 1.26], P Conclusions Assessment of ESL provides independent and incremental prognostic information in addition to the EuroSCORE II for CVD and all-cause mortality in CABG patients. The prognostic value was greater in women. Abstract Figure. Prognostic value of ESL amplitude by sex

Funding Acknowledgements Type of funding sources: None. Background Acute coronary syndrome (ACS) has adverse consequences for the myocardium and subsequent cardiac function and structure. No reports exist comparing the differences in impact of culprit coronary artery lesion site on longitudinal remodeling and changes left ventricular structure and function. Method A total of 299 ACS patients treated with PCI were included in the present study. All patients had two echocardiographic examinations performed. The first was performed median 2 (IQR: 1; 3) days following PCI, while the second was performed median 240 (IQR: 81; 881) days after the first. Patients were grouped based on culprit coronary artery lesion (left anterior descending artery (LAD), right coronary artery (RCA) and circumflex artery (Cx)). Patients with multiple lesions were excluded from the present study. Univariable linear regression analysis was utilised to assess the association between culprit coronary artery lesion site and longitudinal change in cardiac structure and function. Results Mean age was 63 ± 11 years and 77% were male. At follow-up, mean left ventricular ejection fraction was 42 ± 9% and global longitudinal strain (GLS) was -13 ± 4%. Culprit coronary artery lesion was allocated as follows; 168 ACS patients were treated in LAD, 95 patients were treated in RCA, and 36 patients were treated in Cx. In the linear regression analysis, LAD patients displayed a greater improvement in GLS (b =-0.116, p = 0.048) compared to the two other lesion sites. LAD patients had the poorest GLS at both baseline and follow-up echocardiography (Figure). RCA lesions were associated with the largest decrease in left atrial maximum volume (LAVmax) (b = -0.156, p = 0.011) and the largest increase in relative wall thickness (RWT) (b = 0.139, p = 0.030), consequently resulting in an LAVmax smaller and an RWT larger at follow-up than other lesion sites (Figure). Lastly, Cx lesions were significantly associated with the largest decrease in ratio between peak early diastolic transmitral flow velocity and peak early diastolic mitral annular tissue velocity (E/e’) (b = -0.262, P Conclusion The present study suggests that culprit coronary artery lesion site has a differential impact on cardiac remodeling. This information can potentially aid the clinical understanding of cardiac structure and function following ACS according to coronary artery lesion site. Abstract Figure

Early diastolic tissue velocity (e’) by tissue Doppler imaging represents an early marker of left ventricular (LV) dysfunction in ischemic heart disease. We assessed the value of e’ for predicting mortality in patients undergoing coronary artery bypass grafting (CABG). We retrospectively investigated patients treated with CABG between 2006-2011. Before surgery, all patients underwent an echocardiogram with tissue Doppler imaging to measure tissue velocities: systolic (s’), e’, and late diastolic (a’). The primary outcome was all-cause mortality. Survival analysis was applied. Improvement of EuroSCORE-II was assessed by net reclassification index. Of 660 patients, 72 (11%) died during a median follow-up time of 3.8 years. Mean age was 68 years, LVEF 50%, and 84% were men. All tissue velocities showed a significant negative association with outcome and e’ provided highest Harrell's C-statistics (c-stat=0.68). After multivariable adjustment for EuroSCORE-II, LV hypertrophy, LV internal diameter, and global longitudinal strain, declining e’ was associated with a higher risk of mortality (HR=1.35 (1.12 to 1.61), p = 0.001, per 1cm/s absolute decrease). LVEF≤40% modified the relationship between both s’ and e’ and outcome (p for interaction=0.021 and 0.024, respectively), such that neither predicted mortality when LVEF was ≤40%. In patients with LVEF>40%, only e’ remained a predictor after multivariable adjustments (HR=1.36 (1.10 to 1.69), p = 0.005, per 1cm/s absolute decrease). A net reclassification index improvement of 0.14 was observed when adding global e’ to the EuroSCORE-II. In conclusion, e’ is an independent predictor of all-cause mortality in patients undergoing CABG, especially in patients with LVEF>40%, and improves the predictive value of EuroSCORE-II.

Background Early systolic lengthening (ESL) and postsystolic shortening are considered highly specific for myocardial ischemia. We aimed to investigate the prognostic potential of both deformational patterns in patients with heart failure (HF) and to determine if a history of ischemic heart disease modified this relationship. Method A total of 884 patients with systolic HF (66±12 years, male 73%, mean ejection fraction 28±9%) underwent speckle tracking echocardiography. Of these, 61% suffered from ischemic cardiomyopathy (ICM). Patients were followed for all-cause mortality. We assessed the ESL index: [−100x (peak positive strain/maximal strain)] and the postsystolic index (PSI): [100x (postsystolic strain/maximal strain)]. Both parameters were averaged across 18 myocardial segments. Results During a median follow-up of 3.4 years [interquartile range 1.9 to 4.8], 132 patients (15%) died. In multivariable survival analyses adjusted for potential confounders (age, sex, BMI, mean arterial pressure, cholesterol, heart rate, CABG/PCI, left ventricular ejection fraction and mass index, left atrial volume index, tricuspid annular plane systolic excursion, E-wave, E/e', deceleration time, and global longitudinal strain) neither the ESL index (HR 1.02 per 1% increase [0.97 to 1.08], P=0.40) nor PSI (HR 1.00 per 1% increase [0.98 to 1.01], P=0.69) were associated with all-cause mortality. ICM modified the relationship (P interaction unadjusted/adjusted=0.001/0.008; Figure) such that per 1% increase in ESL index in patients with ICM was significantly associated with all-cause mortality (unadjusted: HR 1.09 [1.04 to 1.15], P Conclusion Our results indicate that in this cohort of undifferentiated HF patients with reduced ejection fraction the prognostic value of deformational patterns was reduced. However, the ESL index may provide some information on prognosis in patients with ICM. ESL and interaction with ICM Funding Acknowledgement Type of funding source: None

Background Early systolic lengthening (ESL) has recently recognized as a predictor of cardiovascular events in patients with myocardial ischemia. Our aim was to evaluate the prognostic value of ESL in patients with type 2 diabetes. Methods In this prospective study we conducted speckle tracking examinations in 743 patients with type 2 diabetes (62% male; age 63±10 years; diabetes duration 11 [5, 17] years). Patients were free from interventricular conduction disturbances, atrial fibrillation, heart failure and ischemic heart disease at study inclusion. We assessed the ESL index, defined as: (−100 x [peak positive systolic strain / global longitudinal strain (GLS)]), and duration of ESL, defined as time from onset of QRS complex on the electrocardiogram to time of peak positive systolic strain. Measurements were averaged from 18 myocardial segments. Results During the median follow-up time of 4.8 years [IQR 4, 5.3 years], 93 (13%) patients experienced major adverse cardiovascular events (MACE), a composite of incident heart failure, myocardial infarction and cardiovascular death. Because GLS modified the association with MACE (P interaction −15% and high ≤−15%). In patients with low GLS, the ESL index (HR 1.47 per 1% increase [1.12 to 1.93], P=0.005) and ESL duration (HR 1.73 per 1ms increase [1.10 to 2.72], P=0.017) were associated with MACE. Both associations remained significant in multivariable models adjusted for clinical, echocardiographic and speckle tracking measurements (Figure). No associations were found in patients with high GLS (Figure). Conclusion Assessment of ESL yields novel and independent prognostic information on major adverse cardiovascular events in patients with diabetes type 2 and reduced longitudinal strain. Forest plot: ESL and risk of MACE by GLS Funding Acknowledgement Type of funding source: None

Background Novel echocardiographic software allows for layer-specific evaluation of myocardial deformation by 2-dimensional speckle tracking echocardiography. Endocardial, epicardial- and whole wall global longitudinal strain (GLS) may be superior to conventional echocardiographic parameters in predicting all-cause mortality in patients with heart failure with reduced ejection fraction (HFrEF). Purpose The purpose of this study was to investigate the prognostic value of endocardial-, epicardial- and whole wall GLS in patients with HFrEF in relation to all-cause mortality. Methods We included and analyzed transthoracic echocardiographic examinations from 1,015 patients with HFrEF. The echocardiographic images were analyzed, and conventional and novel echocardiographic parameters were obtained. A p value in a 2-sided test Results During a median follow-up time of 40 months, 171 patients (16.8%) died. A lower endocardial (HR 1.17; 95% CI (1.11–1.23), per 1% decrease, p Conclusion Endocardial, epicardial and whole wall GLS are independent predictors of all-cause mortality in patients with HFrEF. Furthermore, endocardial, epicardial and whole wall GLS were superior prognosticators of all-cause mortality compared with all other echocardiographic parameters. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Herlev and Gentofte Hospital

Aims Patients with left axis deviation (LAD) and left bundle branch block (LBBB) show less benefit from cardiac resynchronization therapy (CRT) compared to other LBBB-patients. This study investigates the reasons for this. Methods Sixty-eight patients eligible for CRT were included. Patients were divided into groups according to QRS-axis; normal axis (NA), left axis deviation (LAD) and right axis deviation (RAD). Before CRT implantation CMR imaging was performed to evaluate scar tissue. Echocardiography was performed before and after implantation. The electrical substrate was assessed by measuring interlead electrical delays. Response was evaluated after 8 months by left ventricular (LV) remodelling and clinical response. Results Forty-four (65%) patients were responders in terms of LV remodelling. The presence of LAD was found to be independently associated with a poor LV remodelling non-response OR 0.21 [95% CI 0.06–0.77] ( p = 0.02). Patients with axis deviation had more myocardial scar tissue (1.3 ± 0.6 vs. 0.9 ± 0.6, P = 0.04), more severe LV hypertrophy (14 (64%) and 6 (60%) vs. 7 (29%), P = 0.05) and tended to have a shorter interlead electrical delay than patients with NA (79 ± 40 ms vs. 92 ± 48 ms, P = 0.07). A high scar tissue burden was more pronounced in non-responders (1.4 ± 0.6 vs. 1.0 ± 0.5, P = 0.01). Conclusions LAD in the presence of LBBB is a predictor of poor outcome after CRT. Patients with LBBB and LAD have more scar tissue, hypertrophy and less activation delay.

Despite effective treatment with coronary artery bypass grafting (CABG), patients with coronary artery disease face an elevated risk of heart failure (HF) and cardiovascular (CV) death. Left atrial (LA) strain has previously been shown to be an important determinant of outcomes, including atrial

AIMS Colour tissue Doppler imaging (TDI) M-mode through the mitral leaflet is an easy and precise method to obtain cardiac time intervals including isovolumic contraction time (IVCT), isovolumic relaxation time (IVRT) and systolic ejection time (SET). The myocardial performance index (MPI) is defined as [(IVCT + IVRT)/SET]. Whether cardiac time intervals obtained by the TDI M-mode method can be used to predict outcome in patients with heart failure with reduced ejection fraction (HFrEF) remains unknown. METHODS AND RESULTS A total of 997 patients with HFrEF (mean age 67 ± 11 years, 74% male) underwent an echocardiographic examination including TDI. During a median follow-up of 3.4 years (interquartile range 1.9-4.8 years), 165 (17%) patients died. The risk of mortality increased by 9% per 10 ms decrease in SET [per 10 ms decrease: hazard ratio (HR) 1.09, 95% confidence interval (CI) 1.06-1.13; P

Background: The optimal timing of invasive coronary angiography (ICA) and revascularization in patients with non-ST-segment elevation acute coronary syndrome is not well defined. We tested the hypothesis that a strategy of very early ICA and possible revascularization within 12 hours of diagnosis is superior to an invasive strategy performed within 48 to 72 hours in terms of clinical outcomes. Methods: Patients admitted with clinical suspicion of non-ST-segment elevation acute coronary syndrome in the Capital Region of Copenhagen, Denmark, were screened for inclusion in the VERDICT trial (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography) ( ClinicalTrials.gov NCT02061891). Patients with ECG changes indicating new ischemia or elevated troponin, in whom ICA was clinically indicated and deemed logistically feasible within 12 hours, were randomized 1:1 to ICA within 12 hours or standard invasive care within 48 to 72 hours. The primary end point was a combination of all-cause death, nonfatal recurrent myocardial infarction, hospital admission for refractory myocardial ischemia, or hospital admission for heart failure. Results: A total of 2147 patients were randomized; 1075 patients allocated to very early invasive evaluation had ICA performed at a median of 4.7 hours after randomization, whereas 1072 patients assigned to standard invasive care had ICA performed 61.6 hours after randomization. Among patients with significant coronary artery disease identified by ICA, coronary revascularization was performed in 88.4% (very early ICA) and 83.1% (standard invasive care). Within a median follow-up time of 4.3 (interquartile range, 4.1–4.4) years, the primary end point occurred in 296 (27.5%) of participants in the very early ICA group and 316 (29.5%) in the standard care group (hazard ratio, 0.92; 95% CI, 0.78–1.08). Among patients with a GRACE risk score (Global Registry of Acute Coronary Events) >140, a very early invasive treatment strategy improved the primary outcome compared with the standard invasive treatment (hazard ratio, 0.81; 95% CI, 0.67–1.01; P value for interaction=0.023). Conclusions: A strategy of very early invasive coronary evaluation does not improve overall long-term clinical outcome compared with an invasive strategy conducted within 2 to 3 days in patients with non-ST-segment elevation acute coronary syndrome. However, in patients with the highest risk, very early invasive therapy improves long-term outcomes. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02061891.

AIMS Two-dimensional speckle tracking echocardiography (2DSTE) detects early signs of left ventricular dysfunction; however, it is unknown whether layer-specific global longitudinal strain (GLS) has incremental value in diagnosis of patients with reversible ischemia assessed by single photon emission computed tomography (SPECT). METHODS AND RESULTS Eighty patients with stable angina pectoris (SAP), normal left ventricular ejection fraction (LVEF), and no history of ischemic heart disease were retrospectively identified to have been examined by 2DSTE, SPECT, and coronary angiography (CAG). Patients with a normal SPECT constituted the control group, and patients with a positive SPECT were divided into patients with or without (true- or false- positive SPECT) significant stenosis assessed by CAG. GLS was measured for two myocardial layers (endocardial and epicardial) and as well as mid-myocardial GLS. Patients with reversible ischemia had significantly lower GLS compared to the control group (GLSEndocardial : -19.0 ± 4.4% vs -21.4 ± 3.7%, P = .011; GLSEpicardial : -14.3 ± 2.9% vs -16.3 ± 2.9%, P = .004); GLSMid-myocardial : -16.5 ± 3.6% vs -18.6 ± 3.2%, P = .006. This difference was even more evident in patients with a true-positive SPECT (GLSEndocardial : -18.0 ± 4.4% vs -21.4 ± 3.7%, P

Aims Quantification of systolic function in patients with atrial fibrillation (AF) is challenging. A novel approach, based on RR interval correction, to counteract the varying heart cycle lengths in AF has recently been proposed. Whether this method is superior in patients with systolic heart failure (HFrEF) with AF remains unknown. This study investigates the prognostic value of RR interval-corrected peak global longitudinal strain {GLSc = GLS/[RR^(1/2)]} in relation to all-cause mortality in HFrEF patients displaying AF during echocardiographic examination. Methods and results Echocardiograms from 151 patients with HFrEF and AF during examination were analysed offline. Peak global longitudinal strain (GLS) was averaged from 18 myocardial segments obtained from three apical views. GLS was indexed with the square root of the RR interval {GLSc = GLS/[RR^(1/2)]}. Endpoint was all-cause mortality. During a median follow-up of 2.7 years, 40 patients (26.5%) died. Neither uncorrected GLS (P = 0.056) nor left ventricular ejection fraction (P = 0.053) was significantly associated with all-cause mortality. After RR^(1/2) indexation, GLSc became a significant predictor of all-cause mortality (hazard ratio 1.16, 95% confidence interval 1.02-1.22, P = 0.014, per %/s^(1/2) decrease). GLSc remained an independent predictor of mortality after multivariable adjustment (age, sex, mean heart rate, mean arterial blood pressure, left atrial volume index, and E/e') (hazard ratio 1.17, 95% confidence interval 1.05-1.31, P = 0.005 per %/s^(1/2) decrease). Conclusions Decreasing {GLSc = GLS/[RR^(1/2)]}, but not uncorrected GLS nor left ventricular ejection fraction, was significantly associated with increased risk of all-cause mortality in HFrEF patients with AF and remained an independent predictor after multivariable adjustment.