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Background: When the left ventricle pressure rises during early systole, myocardial fibres with reduced contractility tend to stretch instead of shortening. This interval is known as duration of early systolic lengthening (DESL). We sought to investigate if DESL provides prognostic information on cardiovascular events., Methods and Results: In this prospective study we included 1210 participants from a low-risk general population who underwent speckle tracking echocardiography (men 41%, mean age 56 years, SD 16). Primary endpoints were incident heart failure (HF), myocardial infarction (MI), and cardiovascular death (CVD). We defined DESL as time from onset of Q-wave on the electrocardiogram to peak positive systolic strain. In addition, we assessed the ratio between DESL and duration of cardiac systole, DESLsystole.During median follow-up of 16 years, 90 (7%) developed HF, 50 (4%) MI, and 70 (6%) experienced CVD. Both DESL [hazard ratio (HR) 1.58 95%CI 1.16-2.15, P = 0.004 per 10 ms increase] and DESLsystole (HR 1.74 95%CI 1.24-2.47, P = 0.001 per 1% increase) were predictors of HF. Similarly, DESL (HR 1.40 95%CI 1.09-1.78, P = 0.007 per 10 ms increase) and DESLsystole (HR 1.58 95%CI 1.01-2.49, P = 0.047 per 1% increase) were predictors of MI. No associations were found with CVD. After adjusting for clinical and echocardiographic parameters, the associations remained significant. DESLsystole was superior to systolic echocardiographic parameters for predicting HF (P = 0.012)., Conclusion: DESL and the novel index of DESLsystole provide independent and novel prognostic information on the risk of HF and MI in the general population. Evaluation of DESL should be explored in future echocardiographic studies., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Aims: Colour tissue Doppler imaging (TDI) M-mode through the mitral leaflet is an easy and precise method to obtain cardiac time intervals including the isovolumic contraction time (IVCT), isovolumic relaxation time (IVRT), and ejection time (ET). The myocardial performance index (MPI) was defined as [(IVCT + IVRT)/ET]. Our aim was to investigate if cardiac time intervals can be used to predict atrial fibrillation (AF) in the general population., Methods and Results: A total of 1915 participants from the general population underwent a health examination including TDI echocardiography. The primary endpoint was AF, and the secondary endpoint was complicated AF as assessed by the occurrence of either stroke or heart failure (HF) after the diagnosis of AF. Participants with known AF were excluded (n = 54). During a median follow-up of 11 years, 166 participants (9%) were diagnosed with AF and of these 44 participants (27%) developed HF or stroke. Assessing the association between IVCT and incident AF, the risk increased with 27% per 10 ms increase in IVCT [per 10 ms increase: hazard ratio (HR) 1.27, 95% confidence interval (CI) (1.17-1.38); P < 0.001]. The association remained significant after multivariable adjustment [per 10 ms increase: HR 1.22, 95% CI (1.09-1.35); P < 0.001]. No associations between the IVRT, ET, MPI, and AF remained significant after multivariable adjustment. The IVCT also predicted complicated AF and the association remained significant even after multivariable adjustment [per 10 ms increase: HR 1.39, 95% CI (1.06-1.81); P = 0.015]., Conclusion: In the general population, the IVCT provides novel and independent prognostic information on the long-term risk of AF. Additionally, the IVCT can identify persons in risk of complicated AF., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Aims: Left atrial (LA) enlargement predicts cardiovascular risk. The prognostic value of left atrial peak reservoir strain (LA RS) by two-dimensional speckle tracking in the general population is currently unknown. This study sought to determine the prognostic value of LA RS in the general population., Methods and Results: A total of 385 participants without atrial fibrillation, heart failure (HF), and ischaemic heart disease (IHD) had an echocardiogram including left ventricular and LA speckle-tracking analysis performed. LA RS was averaged from the three apical views. The endpoint was a composite of incident IHD, HF, or cardiovascular death. Median follow-up was 12.6 years (interquartile-range 11.5-12.8 years). Follow-up was 100%. Fifty-one participants (13.3%) reached the composite outcome. LA RS was a univariable predictor of outcome [hazard ratio (HR) 1.25, 95% confidence interval (95% CI) 1.09-1.43; P = 0.002]. However, LA RS did not remain an independent predictor of outcome after adjustment for clinical parameters. The prognostic value was modified by sex (P = 0.011). LA RS predicted the composite outcome in women but not in men when adjusting for clinical parameters (women: HR 1.46, 95% CI 1.05-2.02; P = 0.025) (men: HR 0.96, 95% CI 0.81-1.14; P = 0.65). Further adjustment for echocardiographic parameters did not significantly alter the results. LA RS added incremental prognostic information in addition to SCORE and the American Heart Association/American College of Cardiology Pooled Cohort Equation in women only., Conclusion: LA RS is a univariable predictor of cardiovascular morbidity and mortality in the general population. However, the prognostic value of LA RS is modified by sex. LA RS is an independent predictor of outcome in women but not in men., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.)

Aims: It has previously been demonstrated that the ratio of early mitral inflow velocity to global diastolic strain rate (E/e'sr) is a significant predictor of cardiac events in specific patient populations. The utility of this measurement to predict cardiovascular events in a general population has not been evaluated., Methods and Results: A total of 1238 participants in a general population study underwent a health examination including echocardiography where global longitudinal strain (GLS) and E/e'sr were determined. The primary endpoint was the composite of incident heart failure (HF), acute myocardial infarction (AMI) or cardiovascular death (CVD). During follow-up (median 11 years), 140 (11.3%) participants reached the composite endpoint. E/e'sr was associated with adverse outcome [HR 1.17 95% CI (1.13-1.21); P < 0.001, per 10 cm increase]. After multivariable adjustment for echocardiographic and clinical parameters, E/e'sr remained an independent predictor of the composite endpoint [HR 1.08, 95% CI (1.02-1.13); P = 0.003] as opposed to E/e' [HR 1.03, 95% CI (0.99-1.06); P = 0.11 per 1 unit increase]. Global longitudinal strain modified the relationship between E/e'sr and outcome (P for interaction = 0.015). E/e'sr was a stronger predictor in participants with good systolic function as determined by GLS (GLS > 18%) after multivariable adjustment, when compared to participants with reduced systolic function (GLS < 18%) [HR 1.28 95% CI (1.06-1.54); P = 0.011, and HR 1.08 95% CI (1.02-1.14); P = 0.012, respectively). E/e'sr provided incremental information [Harrell's C-index: 0.839 (0.81-0.87) vs. 0.844 (0.82-0.87); P = 0.045] beyond the SCORE risk chart., Conclusion: In the general population, E/e'sr provides independent and incremental prognostic information regarding cardiovascular morbidity and mortality. Additionally, E/e'sr is a stronger predictor of cardiac events than E/e'.

Background: Post-systolic shortening (PSS) is a novel echocardiographic marker of myocardial dysfunction. Our objective was to assess the prognostic value of PSS in patients following acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI)., Methods: A total of 428 patients hospitalized for ACS (mean age 64 ± 12 years, male 73%) underwent speckle tracking echocardiography following treatment with PCI (median 2 days). The individual endpoints were heart failure (HF), myocardial infarction (MI) and all-cause death. We excluded known HF. Presence of PSS was defined as post-systolic displacement ≥20% of maximum strain in one cardiac cycle. The post-systolic index (PSI) was defined as (100 × [maximum-strain cardiac cycle - peak-systolic strain])/(maximum-strain cardiac cycle)]., Results: During median follow-up of 3.7 years (IQR 0.3, 5.2), 155 patients (36%) experienced HF, 52 (12%) had MI and 87 (20%) died from all causes. Patients experiencing HF had more walls displaying PSS (3.2 vs. 1.9 walls) and higher PSI (22% vs. 12%) (P < 0.001 both). In Cox proportional hazards models adjusted for baseline characteristics, invasive and echocardiographic measurements, the risk of HF increased incrementally with increasing number of walls with PSS (HR 1.28 95%CI 1.12-1.46, P < 0.001 per 1 increase in walls with PSS). The PSI remained an independent predictor of HF after adjustment (HR 1.61 95%CI 1.21-2.12, P = 0.001 per 1% increase). In the same adjusted models, MI and all-cause death were not significantly associated with PSS., Conclusion: Presence of PSS provides novel and independent prognostic information regarding the risk of future HF in patients with ACS following PCI., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Post-systolic shortening (PSS) does not contribute to the ejection of blood and may inhibit diastolic filling. We determined normal values of PSS in healthy subjects and investigated associations with echocardiographic and invasive measures of systolic and diastolic function. We prospectively analyzed participants from the general population (n = 620, mean age 47 ± 14 years) with no cardiovascular disease. Participants underwent echocardiography, including speckle tracking assessment of the post-systolic index (PSI), strain and time. We defined the PSI as: 100 × [(peak global longitudinal strain - peak systolic longitudinal strain)/(peak global longitudinal strain)]. We also included stable patients (n = 44) referred for left ventricle (LV) catheterization and echocardiography. Normal values: median PSI 2.0% (IQR 0.7, 4.8), post-systolic strain 0.4% (IQR 0.2, 0.8) and post-systolic time 22.6 ms (IQR 10.7, 40.8). Sex modified the relationship between PSI and age (P interaction = 0.037), such that PSI increased with age in women but not in men. PSI was associated with diastolic function (e', E/e' and E/A) (P < 0.05 for all), but not with LV ejection fraction (P = 0.08). PSI was associated with invasively measured LV pressure decline in early diastole, dP/dt min ([Formula: see text] = 0.12, P = 0.010), but not with LV pressure rise in early systole, dP/dt max ([Formula: see text]= - 0.05, P = 0.30). A PSI > 5% had 82% specificity and 99% sensitivity for identifying impaired LV systolic and/or diastolic function. Normal values of PSS are modified by sex. The PSI is associated with most validated echocardiographic and invasive measures of cardiac systolic and diastolic function.

Background: The prognostic value of LA functional measures in heart failure patients with reduced ejection fraction (HFrEF) is unclear. Therefore, this study investigated the prognostic value of left atrial (LA) functional measures such as the left atrial emptying fraction (LAEF) and the minimal LA volume compared with left atrial volume index (LAVI) in HFrEF patients., Methods and Results: A total of 818 HFrEF patients with left ventricular ejection fractions <45% underwent echocardiography. LA volumes were determined by the area-length method from the apical 2-chamber and apical 4-chamber views. LAEF, minimal LA volume indexed to body surface area (MinLAVI), and LAVI were calculated. The end point was all-cause mortality. During a median follow-up of 3.3 years (interquartile range 1.8-4.6 years), 121 patients died (14.8%). Follow-up was 100%. In a final multivariable model adjusting for clinical and echocardiographic parameters, LAEF, but not MinLAVI or LAVI, was an independent predictor of all-cause mortality in HFrEF patients: LAEF: hazard ratio (HR) 1.11 (P = .033) per 5% decrease; MinLAVI: HR 1.03 (P = .57) per 5 mL/m 2 increase; LAVI: HR 1.06 (P = .16) per 5 mL/m 2 increase., Conclusions: LAEF is an independent predictor of all-cause mortality in HFrEF patients after multivariable adjustment. LAEF provides incremental prognostic value over LAVI in risk stratification of HFrEF patients., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Influenza infection is a serious event for patients with heart failure (HF). Little knowledge exists about the association between influenza vaccination and outcome in patients with HF. This study sought to determine whether influenza vaccination is associated with improved long-term survival in patients with newly diagnosed HF., Methods: We performed a nationwide cohort study including all patients who were >18 years of age and diagnosed with HF in Denmark in the period of January 1, 2003, to June 1, 2015 (n=134 048). We collected linked data using nationwide registries. Vaccination status, number, and frequency during follow-up were treated as time-varying covariates in time-dependent Cox regression., Results: Follow-up was 99.8% with a median follow-up time of 3.7 years (interquartile range, 1.7-6.8 years). The vaccination coverage of the study cohort ranged from 16% to 54% during the study period. In unadjusted analysis, receiving ≥1 vaccinations during follow-up was associated with a higher risk of death. After adjustment for inclusion date, comorbidities, medications, household income, and education level, receiving ≥1 vaccinations was associated with an 18% reduced risk of death (all-cause: hazard ratio, 0.82; 95% CI, 0.81-0.84; P<0.001; cardiovascular causes: hazard ratio, 0.82; 95% CI, 0.81-0.84; P<0.001). Annual vaccination, vaccination early in the year (September to October), and greater cumulative number of vaccinations were associated with larger reductions in the risk of death compared with intermittent vaccination., Conclusions: In patients with HF, influenza vaccination was associated with a reduced risk of both all-cause and cardiovascular death after extensive adjustment for confounders. Frequent vaccination and vaccination earlier in the year were associated with larger reductions in the risk of death compared with intermittent and late vaccination.

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: To investigate the prognostic value of layer-specific global longitudinal strain (GLS) in predicting heart failure (HF) and cardiovascular death (CD) following acute coronary syndrome (ACS)., Methods and Results: In this retrospective study, 465 ACS patients underwent transthoracic echocardiography following percutaneous coronary intervention (PCI). The primary endpoint was the composite of HF and/or CD with a median follow-up time of 4.6 (0.2-6.3) years. During follow-up 199 patients (42.7%) suffered HF and/or CD (176 developed HF and 38 suffered CD). Absolute endomyocardial global longitudinal strain (GLSendo) (12% vs. 17%, P < 0.001), GLS (11% vs. 14%, P < 0.001), and epimyocardial global longitudinal strain (GLSepi) (9% vs. 13%, P < 0.001) were all reduced in patients with an adverse outcome. In multivariable Cox regressions, which included clinical baseline characteristics and conventional echocardiographic measurements, GLS obtained from all layers remained independently associated with the composite outcome; GLSendo [hazard ratio: 1.19 (1.10-1.28), P < 0.001, per 1% decrease], GLS [hazard ratio 1.24 (1.14-1.35), P < 0.001, per 1% decrease], and GLSepi [hazard ratio 1.26 (1.15-1.39), P < 0.001, per 1% decrease]. No other echocardiographic measures remained independently associated with the composite outcome in these models. Finally, GLS and GLSepi provided incremental prognostic information on the risk of developing the composite endpoint, when added to all other clinical and echocardiographic measures [adding GLS (c-statistics: 0.76 vs. 0.74, P = 0.048) or adding GLSepi (c-statistics: 0.76 vs. 0.74, P = 0.039)]., Conclusion: In ACS patients, layer-specific strain provides independent prognostic information regarding risk of developing HF and/or CD. Furthermore, only GLS and GLSepi provided incremental prognostic information when added to all other significant predictors.

Background: Repolarization is impaired in patients with type 1 diabetes mellitus (T1DM), and repolarization disturbances are associated with an increased mortality. To study cardiac repolarization, we assessed T-wave morphology in patients with T1DM without known heart disease., Methods: 855 T1DM patients without known heart disease were matched 1:2 with 1710 people from a background population. Rate-corrected T-wave morphology markers were obtained. Patients were stratified by albuminuria. Results are mean ± standard deviation., Results: T-waves were flatter (0.398 ± 0.059 vs. 0.382 ± 0.062, p < 0.001) and more asymmetric (0.082 ± 0.068 vs. 0.071 ± 0.084, p = 0.001) in T1DM. Patients with albuminuria had an increased heart rate (normoalbuminuria: 71 ± 13 bpm, microalbuminuria: 75 ± 12 bpm, p < 0.001, macroalbuminuria: 78 ± 12 bpm, p < 0.001) and more asymmetric T-waves (normoalbuminuria: 0.079 ± 0.060, microalbuminuria: 0.094 ± 0.085, p < 0.01, macroalbuminuria: 0.101 ± 0.080, p < 0.01), but the QTc interval remained unchanged., Conclusions: T1DM is associated with changes in T-wave morphology. T-wave asymmetry but not QTc interval is associated with albuminuria in T1DM and may be used for stratification., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background Type 2 diabetes mellitus is closely associated with metabolic risk factors that all contribute to impairment of the left ventricle. The implications of having type 2 diabetes mellitus with well-controlled metabolic risk factors compared to an increasing burden of uncontrolled metabolic risk factors on left ventricular structure and function are not known. Methods and Results We compared patients with type 2 diabetes mellitus (n=751) with different degrees of uncontrolled metabolic risk factors present with a control group of individuals without present uncontrolled metabolic risk factors as recommended by the World Health Organization (n=80). In patients with well-controlled metabolic risk factors, only diastolic but neither structural nor systolic measures were impaired compared to the control group: the (early diastolic mitral inflow velocity)/(atrial diastolic mitral inflow velocity) ratio (median 0.94 [interquartile range 0.80, 1.08] versus 1.11 [0.85, 1.38], P<0.001), lateral early diastolic myocardial velocity at the level of the mitral annulus (mean 9.6 m/s [SD 2.5] versus 10.8 [3.5], P<0.001) and lateral (early diastolic mitral inflow velocity)/(early diastolic myocardial velocity at the level of the mitral annulus) (7.7 [6.5, 10.2] versus 6.3 [4.9, 7.8], P<0.001). With an increasing burden of uncontrolled metabolic risk factors, there were increased left ventricular mass index and wall thicknesses and impaired systolic function measured as global longitudinal strain: control group -15.9 (2.0); 0 uncontrolled risk factors -15.3 (2.4); 1 to 2 -14.6 (2.8); and ≥3 -14.0 (2.8), P<0.001. Within the diabetes mellitus group, there were uni- and multivariable associations of left ventricular measures and systolic blood pressure, body mass index, hemoglobin A 1c , and HDL -cholesterol. Conclusions In patients with type 2 diabetes mellitus, having well-controlled metabolic risk factors was associated with only left ventricular diastolic impairment but not with either structural or even subtle measures of systolic function. Increasing burden of uncontrolled metabolic risk factors was associated with structural and functional impairments.

There are 320,000 diabetes patients in Denmark. Heart failure (HF) is a major cardiovascular complication to diabetes mellitus with increasing prevalence. HF occurs 2-4 times more frequently in diabetes patients, but patients may go undiagnosed for years. Diabetes patients typically suffer from diastolic dysfunction caused by myocardial hyper-trophy and "stiffness" of the left ventricle. This frequent finding has prompted the term "diabetic cardiomyopathy". Echocardiography is a key examination in diagnosing HF and may be warranted to a greater degree in diabetes patients at particular risk.

Background: Cardiovascular death (CVD) is a leading cause of death and constitutes a major burden on society. Left ventricular mechanical dyssynchrony (LVMD), evaluated as SD of time to peak regional longitudinal strain, is a capable predictor of many cardiovascular outcomes related to CVD, including ventricular arrhythmias, but the prognostic utility of LVMD in the general population is unknown. Hence, this study sought to determine the prognostic value of LVMD in the general population in predicting CVD., Methods and Results: A total of 1138 participants underwent a general health examination and an echocardiographic examination including speckle tracking analysis with subsequent calculation of LVMD from time-to-peak regional strain. Primary end point was CVD, and secondary end point was noncardiovascular death. Follow-up was 100%. During a median follow-up of 11.1 years (interquartile range: 10.2-11.3 years), 62 participants suffered CVD (5.5%) while 131 participants experienced noncardiovascular death (11.5%). LVMD was an independent predictor of CVD (subdistribution hazard ratio, 1.04; 95% CI, 1.01-1.06; P=0.004, per 10-ms increase) in competing risk regression treating noncardiovascular death as a competing risk and retained prognostic capability after extensive multivariable adjustment. LVMD was not a significant predictor of noncardiovascular death. LVMD added incremental prognostic information in predicting CVD beyond the Systematic Coronary Risk Evaluation risk chart and a modified version of the American College of Cardiology/American Heart Association Pooled Cohort Equation., Conclusions: Left ventricular mechanical dyssynchrony adds incremental prognostic information in addition to established risk factors in prediction of CVD in individuals from the general population without atrial fibrillation and significant valvular disease.

Aims: Albuminuria-a marker of generalized vascular dysfunction-is a strong predictor of heart failure in patients with type 2 diabetes which may be caused by concomitant myocardial dysfunction reflecting the same underlying pathogenesis., Methods and Results: We included 915 patients with type 2 diabetes from two secondary care centres and stratified according to albuminuria status in normo-, micro-, and macroalbuminuria. We performed comprehensive echocardiography including conventional imaging, tissue Doppler imaging, and 2D speckle tracking. Cardiac remodelling occurred in patients with increasing left ventricular (LV) mass index and LV wall thicknesses with increasing severity of albuminuria. Diastolic measures worsened across groups of albuminuria severity (normo-, micro-, and macroalbuminuria, respectively): septal e' velocity [mean: 6.9 cm/s (SD 1.9), 6.4 (1.7), and 5.9 (1.7), P < 0.001], septal E/e' (median: 10.6 [interquartile range: 8.9-13.2], 12.1 [10.3-14.8], and 12.7 [10.4-16.6], P < 0.001), and left atrial volume index (24.3 mL/m2 [19.1-29.9], 25.7 [20.0-31.6], and 29.0 [22.2-34.9], P < 0.001) In contrast, systolic measures were only impaired in patients with macroalbuminuria: global longitudinal strain (GLS): [-14.6% (2.7) in normo- and -13.3 (2.9) in macroalbuminuria, P < 0.001] and GLS rate [mean: -0.79 s-1 (0.17) in normo- and -0.72 (0.16) in macroalbuminuria, P = 0.001]. The findings persisted in subgroup analyses of patients without known coronary heart disease and with normal ejection fraction and in multivariable adjusted analyses., Conclusion: In patients with type 2 diabetes, microalbuminuria is associated with decreased diastolic function whereas decreased systolic function was only associated with macroalbuminuria supporting the notion of similar pathogenic mechanisms of albuminuria and impaired myocardial function.

Background: Postsystolic shortening (PSS) may occur during myocardial ischemia. We aimed to assess the diagnostic and prognostic potential of PSS in patients with suspected stable angina pectoris (SAP)., Methods: This is a prospective study of patients with suspected SAP (N = 293), no prior cardiac history, and normal ejection fraction, who were examined by speckle-tracking echocardiography, coronary angiography, and exercise electrocardiogram. We excluded patients with known heart disease (ischemia, heart failure, valve disease), bundle branch block, pathological Q-waves, and arrhythmias. PSS was assessed using the postsystolic index (PSI), and categorical presence of PSS was defined as PSI ≥ 20% in one myocardial wall. The primary end point was major adverse cardiovascular events (MACEs), a composite of incident heart failure, myocardial infarction, and stroke. The secondary end point was MACE and revascularization (percutaneous coronary intervention/coronary artery bypass graft)., Results: A stenosis ≥70% in one or more coronary arteries defined significant coronary artery disease (CAD; n = 107). Patients with significant CAD had a higher prevalence of PSS (55% vs 39%; P < .002), and presence of PSS was an independent predictor of significant CAD in multivariable models adjusted for clinical data, exercise test, and echocardiographic measures (odds ratio, 2.45; 95% CI, 1.08-5.60; P = .033). The PSI confirmed this association (odds ratio, 1.71; 95% CI, 1.04-2.82; P = .034 per 1% increase). During median follow-up of 3.5 years (interquartile range, 2.7, 4.1) a total of 25 patients (8.5%) experienced MACE and 46 (15.7%) had the secondary end point. Presence of PSS was a predictor of MACE (hazard ratio, 2.57; 95% CI, 1.12-5.95; P = .028), and the association remained significant in adjusted models. Both presence of PSS and PSI were independent predictors of the secondary end point., Conclusions: In patients with suspected SAP, presence of PSS provides independent diagnostic information on significant CAD and offers novel prognostic information regarding risk of future cardiovascular events., (Copyright © 2018 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Rationale: Atrial fibrillation (AF) is the most common arrhythmia following acute myocardial infarction (AMI). Maximal left atrial (LA) volume is the only echocardiographic atrial parameter employed clinically to assess risk of AF development., Objective: This study sought to determine the prognostic value of left atrial functional measures such as left atrial emptying fraction (LAEF) and left atrial expansion index (LAi) in predicting incident AF in the post-STEMI setting., Methods and Results: STEMI patients treated with primary percutaneous coronary intervention (pPCI) at Gentofte Hospital, Denmark were prospectively enrolled from September 2006 to December 2008 and had an echocardiogram performed a median 2 days (interquartile-range: 1-3 days) following pPCI. LA maximal volume, LA minimal volume, LAEF and LAi were measured from echocardiograms of 373 patients using the area-length method. End point was incident AF. Median follow-up time was 5.6 years (interquartile-range: 5.0-6.1 years), 24 patients (6%) developed incident AF, and follow-up was 100%. In multivariable Cox regression, LAEF and LAi but not maximal LA volume remained independent predictors of AF. Results were similar in competing risk analysis treating all-cause mortality as a competing risk. LAEF and LAi, but not maximal LA volume, added incremental prognostic information in predicting incident AF when added to the CHARGE-AF risk score and the CHA2DS2-VASc score., Conclusion: LAEF and LAi independently predicted incident AF following STEMI and added incremental prognostic information in addition to established predictors of AF. Maximal LA volume was not an independent predictor of incident AF after multivariable adjustment., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Echocardiographic assessment of systolic and diastolic function during atrial fibrillation (AF) is challenging. This study evaluates the prognostic value of strain in patients with AF and suggests a novel approach on how to take into account the varying heart cycle lengths in AF., Methods: Echocardiograms from 204 patients with AF during examination were analyzed offline. Patients with known heart failure (HF) were excluded. Peak global longitudinal strain (GLS) was averaged from 18 myocardial segments. To adjust for the varying heart cycle lengths, we indexed GLS with the square root of the RR-interval, (GLS/√(RR)). The composite endpoint included incident HF, stroke, myocardial infarction and all-cause mortality., Results: During a median follow-up of 2.4 years, 82 patients (40%) reached the composite endpoint. Decreasing GLS/√(RR) was significantly associated with the composite endpoint, and the risk of reaching the endpoint increased significantly per 1%/sec 1/2 decrease in strain (HR 1.13, 95% CI 1.07-1.20, p < 0.001). GLS/√(RR) remained an independent predictor even after adjustment for various risk factors and conventional echocardiography (LVEF and E/e') (HR 1.10, 95% CI: 1.02-1.19, p = 0.017). In contrast, GLS did not remain a significant predictor after adjusting for the same variables (p = 0.07), neither did LVEF (p = 0.11)., Conclusion: Decreasing GLS/√(RR) was significantly associated with increased risk of an adverse outcome and remained an independent predictor after multivariable adjustment. Indexing GLS with the square root of the RR-interval can counteract the variable cycle length in AF patients and GLS/√(RR) offers a more convincing risk-stratification assessment in AF patients compared with GLS., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Following an ischemic event post systolic shortening (PSS) may occur. We investigated the association between PSS in patients with ST-segment elevation myocardial infarction (STEMI) following primary percutaneous coronary intervention (pPCI) and occurrence of cardiovascular events at follow-up. A total of 373 patients admitted with STEMI and treated with pPCI were prospectively included in the study cohort. All patients were examined by echocardiography a median of 2 days after admission (interquartile range, 1-3 days). PSS was measured by color tissue Doppler imaging (TDI) and speckle tracking echocardiography (STE) in six myocardial walls from all three apical projections. During a median follow-up period of 5.4 years (interquartile range, 4.1-6.0 years), 180 events occurred: 59 deaths, 70 heart failures (HF) and 51 new myocardial infarctions (MI). In multivariable analysis adjusting for: age, sex, peak troponin, left ventricle ejection fraction, TIMI flow grade, left ventricle mass index, hypertension and diabetes, presence of PSS by TDI in the culprit region was associated with a nearly twofold increased risk of HF (HR 1.90, 95% CI 1.02-3.53, P = 0.043) and the risk of HF increased incrementally with increasing numbers of walls displaying PSS. The increased risk of HF was confirmed when assessing the post-systolic index by STE (HR 1.29 95% CI 1.09-1.53, P = 0.003, per 1% increase). A regional analysis showed that PSS by TDI in the septal wall was the strongest predictor of HF (HR 1.77, 95% CI 1.08-2.92, P = 0.024). Presence of PSS was not associated with increased risk of death or MI. In patients with STEMI treated with pPCI, the presence of PSS examined by TDI and STE provides prognostic information on development of HF. Presence of PSS in the septal wall is the strongest predictor of HF.

Hypertension may be the most significant cardiovascular risk factor. Few studies have assessed the prognostic value of echocardiography in hypertensive individuals. This study examines the incremental prognostic value of adding echocardiographic parameters to established risk factors in individuals from the general population with and without hypertension. A total of 1294 individuals from the general population underwent a health examination and an echocardiogram including 2-dimensional speckle tracking. Outcome was a composite of ischemic heart disease and heart failure. The prevalence of hypertension was 38.3%. During a median follow-up of 12.5 years (interquartile range, 9.4-12.8 years), 222 participants (17.2%) developed the outcome. Out of these 222 events, 145 (65%) occurred in hypertensive participants, whereas 77 (35%) occurred in nonhypertensive individuals, corresponding to an incidence rate of 32/(1000×person-years) and 8/(1000×person-years), respectively. Follow-up was 100%. After multivariable adjustment, only left ventricular mass index predicted the outcome in hypertensive individuals, whereas only global longitudinal strain predicted the outcome in nonhypertensive individuals. In hypertensive individuals the prognostic value of left ventricular mass index was incremental to SCORE and abnormal ECG status. In nonhypertensive individuals the prognostic value of global longitudinal strain was incremental to SCORE and abnormal ECG status. The prognostic value of echocardiography in predicting cardiovascular outcomes in the general population is altered by hypertension. In hypertensive individuals, left ventricular mass index added incremental prognostic value in addition to established risk factors. In nonhypertensive individuals, global longitudinal strain added incremental prognostic value in addition to established risk factors., (© 2018 American Heart Association, Inc.)

Objectives: To compare mid-term outcomes between patients undergoing proximal left anterior descending artery (LAD) percutaneous coronary intervention (PCI) with second generation drug-eluting stent (DES) or bare-metal stent (BMS)., Background: PCI with BMS and first-generation DES have shown to be safe options for the treatment of proximal LAD stenosis, however associated with considerable reintervention rates. Overall, second-generation DES has proven to be superior to BMS and first-generation DES, nevertheless, its effect for proximal LAD PCI has not previously been reported., Methods: We analyzed 2-year outcomes of 1,100 patients from the BASKET-PROVE I and II trials, referred for proximal LAD PCI with second generation DES (n = 680) or BMS (n = 420)., Results: The cumulative 2-year incidence of major adverse cardiac events (MACE, composite of cardiac death, myocardial infarction (MI) and target vessel revascularization (TVR)) was lower in second generation DES than in BMS treated patients (7.3% vs. 12.3%; HR 0.57, 95% CI 0.39/0.85), mainly driven by a reduced rate of TVR (3.7% vs. 10.0%; HR 0.35, CI 0.21/0.58). No difference was found in cardiac death (1.9% vs. 1.9%; HR 1.01, CI 0.42/2.44) and MI (4.4% vs. 4.7%; HR 0.93, CI 0.53/1.64). The benefit of DES use seemed to be more prominent in female patients with a reduction in MACE (P for interaction = 0.025)., Conclusions: In patients with proximal LAD stenosis, treatment with second-generation DES was associated with reduced 2-year rates of adverse cardiac events and TVR compared to BMS, with reintervention rates similar to those earlier reported from bypass surgery., (© 2017 Wiley Periodicals, Inc.)

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., (© 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Background: Postsystolic shortening (PSS) has been proposed as a novel marker of contractile dysfunction in the myocardium. Our objective was to assess the prognostic potential of PSS on cardiovascular events and death in the general population., Methods and Results: The study design consisted of a prospective cohort study of 1296 low-risk participants from the general population, who were examined by speckle tracking echocardiography. The primary end point was the composite of heart failure, myocardial infarction, and cardiovascular death, defined as major adverse cardiovascular events (MACEs). The secondary end point was all-cause death. The postsystolic index (PSI) was defined as follows: [(maximum strain in cardiac cycle-peak systolic strain)/(maximum strain in cardiac cycle)]×100. PSS was regarded as present if PSI >20%. During a median follow-up of 11 years, 149 participants (12%) were diagnosed as having MACEs and 236 participants (18%) died. Increasing number of walls with PSS predicted both end points, an association that persisted after adjustment for age, sex, estimated glomerular filtration rate, global longitudinal strain, hypertension, heart rate, left ventricular ejection fraction, LV mass index, pro-B-type natriuretic peptide, previous ischemic heart disease, systolic blood pressure, average peak early diastolic longitudinal mitral annular velocity (e'), ratio between peak transmitral early and late diastolic inflow velocity (E/A), and left atrial volume index: MACEs (hazard ratio, 1.35; 95% confidence interval, 1.09-1.67; P =0.006 per 1 increase in walls displaying PSS) and death (hazard ratio, 1.30; 95% confidence interval, 1.08-1.57; P =0.006 per 1 increase in walls displaying PSS). The strongest predictor of end points was ≥2 walls exhibiting PSS. The PSI also predicted increased risk of the end points, and the associations remained significant in multivariable models: MACEs (per 1% increase in PSI: hazard ratio, 1.18; 95% confidence interval, 1.02-1.36; P =0.024) and death (per 1% increase in PSI: hazard ratio, 1.18; 95% confidence interval, 1.05-1.33; P =0.005)., Conclusions: Presence of PSS in the general population provides independent and long-term prognostic information on the occurrence of MACEs and death., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Speckle tracking echocardiography is an emerging technique, which is currently being included in clinical guidelines. We sought to investigate the impact of transducer frequency settings on speckle tracking derived measures. The study comprised of 22 subjects prospectively enrolled for a randomized controlled trial (LOOP-study, Clinicaltrials.gov:NCT02036450). Patients were above 70 years of age with increased risk of stroke, and had an echocardiogram performed, which included focused images of the left ventricle. Focused images were obtained with the transducer frequency set at both 1.7/3.3 and 1.5/3.0 MHz. The images were obtained immediately after each other at the exact same position for the two settings. Speckle tracking was performed in three apical projections, allowing for acquisition of layered global longitudinal strain (GLS) and strain rate measures. Concordance between the frequency settings was tested for endo-, mid-, and epicardial GLS and strain rates by coefficients of variation, bias coefficients and visually displayed by Bland-Altman plots. Bland-Altman plots did not reveal any significant over- or underestimation of any speckle tracking measure. Bias coefficients showed that none of the measurements differed significantly between the two settings (bias for GLS endo  = - 0.07 ± 2.94, p = 0.91; GLS mid  = 0.02 ± 2.70, p = 0.98, GLS epi  = 0.07 ± 2.53, p = 0.90). Coefficients of variation were as follows: GLS endo  = 15.11%, GLS mid  = 15.28%, GLS epi  = 17.26%, systolic strain rate = 15.66%, early diastolic strain rate = 38.46%, late diastolic strain rate = 11%. Changing between transducer frequency settings does not systematically derange speckle tracking measures. One can safely reduce the transducer frequency without compromising the validity of speckle tracking derived measures.

Asymptomatic paroxysmal atrial fibrillation (PAF) is often assumed to be the cause of cryptogenic ischemic strokes (IS) and transient ischemic attacks (TIA). We examined the usefulness of measures obtained by 2D speckle tracking echocardiography and novel left atrial measurements, in the diagnosis of PAF in patients with IS and TIA. We retrospectively included 205 patients who after acute IS or TIA underwent an echocardiogram in sinus rhythm. Patients were designated as PAF-patients if they had one or more reported incidents of AF before or after their echocardiographic examination. None of the conventional echocardiographic parameters were significantly associated with PAF. Of the speckle tracking measurements, only early diastolic strain rate (0.7±0.2 s -1 vs. 0.8±0.3 s -1 , p = 0.048) and global longitudinal displacement (GLD) (3.15 ± 1.40 mm vs. 3.87 ± 1.56 mm, p = 0.007) proved significantly different. Of the left atrial parameters both minimal and maximal left atrium volume divided by left ventricular length (min LAV/LVL and max LAV/LVL, respectively) were significantly impaired (min LAV/LVL: 3.7 ± 2.1 cm 2 vs. 2.8 ± 1.11 cm 2 , p = 0.012; max LAV/LVL: 6.6 ± 3.1 cm 2 vs. 5.6 ± 1.7 cm 2 , p = 0.012). GLD, min max LAV/LVL proved significant after adjustment for age, gender, CHA 2 DS 2 -VASc and NIHSS. By combining information regarding age, GLD, min and max LAV/LVL the diagnostic accuracy of PAF improved, resulting in a significantly increased area under the curve (p = 0.037). In patients with IS and TIA GLD, min and max LAV/LVL were independently associated with the presence of PAF.

Background: Echocardiographic classification of DDF has been widely discussed. The aim of this study was to investigate the independent prognostic value of established echocardiographic measures in a community-based population and create a new classification of DDF., Methods: Within the Copenhagen City Heart Study, a prospective, community-based study, 1851 participants were examined by echocardiography including Tissue Doppler Imaging (TDI) in 2001 to 2003 and followed with regard to MACE (median, 10.9 years)., Results: We found that persons with impaired myocardial relaxation as defined by low peak early diastolic mitral annular velocity e' by TDI had higher incidence of clinical and echocardiographic markers of cardiac dysfunction and increased risk of MACE. Among persons with impaired relaxation, only echocardiographic indices of increased filling pressures such as LAVi≥34 mL/m 2 (HR 1.97 (1.13-3.45, P=.017), E/e' ≥ 17 (HR 1.89 (1.34-2.65), P<.001), and E/A>2 (HR 5.24 (1.91-14.42), P=.001) provided additional and independent prognostic information on MACE. Based on these findings, we created a new classification of DDF where all grades were significant predictors of MACE independently of age, sex, and cardiac clinical risk markers (Mild DDF: HR 1.99 (1.23-3.21), P=.005; Moderate DDF: HR 3.11 (1.81-5.34), P<.001; Severe DDF: HR 4.20 (1.81-9.73), P<.001). Increasing severity of DDF was linearly associated with increasing plasma proBNP concentrations., Conclusions: In the general population, the presence of echocardiographic markers of elevated filling pressures in persons with impaired relaxation increased the risk of MACE significantly. Based on this, we present a new, feasible, and unambiguous classification of DDF capable of accurate risk prediction in the community., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Aims: To evaluate whether the distance from the site of event to an invasive heart centre, acute coronary angiography (CAG)/percutaneous coronary intervention (PCI) and hospital-level of care (invasive heart centre vs. local hospital) is associated with survival in out-of-hospital cardiac arrest (OHCA) patients., Methods and Results: Nationwide historical follow-up study of 41 186 unselected OHCA patients, in whom resuscitation was attempted between 2001 and 2013, identified through the Danish Cardiac Arrest Registry. We observed an increase in the proportion of patients receiving bystander CPR (18% in 2001, 60% in 2013, P < 0.001), achieving return of spontaneous circulation (ROSC) (10% in 2001, 29% in 2013, P < 0.001) and being admitted directly to an invasive centre (26% in 2001, 45% in 2013, P < 0.001). Simultaneously, 30-day survival rose from 5% in 2001 to 12% in 2013, P < 0.001. Among patients achieving ROSC, a larger proportion underwent acute CAG/PCI (5% in 2001, 27% in 2013, P < 0.001). The proportion of patients undergoing acute CAG/PCI annually in each region was defined as the CAG/PCI index. The following variables were associated with lower mortality in multivariable analyses: direct admission to invasive heart centre (HR 0.91, 95% CI: 0.89-0.93), CAG/PCI index (HR 0.33, 95% CI: 0.25-0.45), population density above 2000 per square kilometre (HR 0.94, 95% CI: 0.89-0.98), bystander CPR (HR 0.97, 95% CI: 0.95-0.99) and witnessed OHCA (HR 0.87, 95% CI: 0.85-0.89), whereas distance to the nearest invasive centre was not associated with survival., Conclusion: Admission to an invasive heart centre and regional performance of acute CAG/PCI were associated with improved survival in OHCA patients, whereas distance to the invasive centre was not. These results support a centralized strategy for immediate post-resuscitation care in OHCA patients., (© The Author 2017. Published on behalf of the European Society of Cardiology.)

Purpose: There exists no consensus on the site of E/e' measurement. This study aimed to evaluate the predictive value of septal and lateral E/e' along with the importance of their intra-individual difference., Methods: In 1775 persons from the general population, peak early diastolic velocity (e') was obtained by color tissue Doppler at the septal and lateral mitral annular sites. The endpoint was combined of cardiovascular death or admission due to heart failure or acute myocardial infarction., Results: During a median follow-up of 10.9 years, the endpoint occurred in 227 participants. E/e' septal and E/e' lateral were equally strong predictors of cardiac events; in age- and sex-adjusted models they did not differ in AUC (septal: 0.8385, lateral: 0.8389; p = 0.94) or in continuous NRI (p = 0.84). Models using E/e' average did not improve AUC or NRI, and the intra-individual difference between sites had no predictive value (p = 0.79). E/e' septal was generally higher than E/e' lateral , thus age- and sex-specific normal values were reported for both sites for a population free of cardiac events during 10 years of follow-up., Conclusions: Septal and lateral E/e' are equally useful in predicting cardiac events in the general population. Measuring both sites provides no further predictive value than measuring a single site.

Background: Global longitudinal strain (GLS) is prognostic of adverse cardiovascular outcomes in various patient populations, but the prognostic utility of GLS for long-term cardiovascular morbidity and mortality in the general population is unknown., Methods and Results: A total of 1296 participants in a general population study underwent a health examination, including echocardiography measurement of GLS. The primary end point was the composite of incident heart failure, acute myocardial infarction, or cardiovascular death. During a median follow-up of 11 years, 149 (12%) participants were diagnosed with heart failure, acute myocardial infarction, or cardiovascular death. Lower GLS was associated with a higher risk of the composite end point (hazard ratio, 1.12; 95% confidence interval, 1.08-1.17; P <0.001 per 1% decrease), an association that persisted after multivariable adjustment for age, sex, heart rate, hypertension, systolic blood pressure, left ventricular ejection fraction, left ventricular mass index, left ventricular dimension, deceleration time, left atrium dimension, E / e ', and pro B-type natriuretic peptide (hazard ratio, 1.05; 95% confidence interval, 1.00-1.11; P =0.045 per 1% decrease). GLS provided incremental prognostic information beyond the Framingham Risk Score, the Systemic Coronary Evaluation risk chart, and the modified American College of Cardiology/American Heart Association Pooled Cohort Equation for the composite outcome and incident heart failure. Sex modified the relationship between GLS and outcome such that after multivariable adjustment, GLS was an independent predictor of outcomes in men but not in women (hazard ratio, 1.14; 95% confidence interval, 1.06-1.24; P =0.001, and hazard ratio, 0.99; 95% confidence interval, 0.92-1.07; P =0.81, respectively; P for interaction =0.032)., Conclusions: In the general population, GLS provides independent and incremental prognostic information regarding long-term risk of cardiovascular morbidity and mortality. GLS seems to be a stronger prognosticator in men than in women., (© 2017 American Heart Association, Inc.)

Background: First-generation drug-eluting coronary stents (DES) were introduced in 2003 to 2004, and their use resulted in a considerable reduction in the development of in-stent restenosis at the cost of an increased risk of late stent thromboses., Objectives: This study followed clinical outcomes of patients included in a large randomized trial for 10 years to enable detection of late changes in annual event rates that could necessitate medical attention., Methods: A total of 2,098 unselected all-comer patients (50% with acute coronary syndrome) were randomly assigned to have a first-generation DES implanted. This study recorded the occurrence of a major adverse cardiac event (MACE) assessed as the composite of cardiac death, myocardial infarction, and target vessel revascularization. Stent thromboses were also assessed., Results: Of the 2,098 unselected patients, 73.1% were still alive after 10 years. During the follow-up period, MACE occurred in 346 (32.5%) in the group receiving a sirolimus-eluting stent and in 342 (33.1%) in the group receiving a paclitaxel-eluting stent (hazard ratio: 0.96; 95% confidence interval: 0.83 to 1.11; p = 0.60), with a steady annual rate of 2.6% after the first year. Definite, probable, and possible stent thrombosis appeared in 279 patients (13.3%), with no difference between stent types and with a steady annual rate of 1.3% after the first year., Conclusions: Among the surviving patients, the long-term annual MACE rate and the stent thrombosis rate appeared constant for both stent types, with no apparent late changes. Although there is no need for extraordinary medical attention for these patients, the absence of declines in annual event rates calls for continuous surveillance. (Danish Organization on Randomized Trials With Clinical Outcome II [SORT OUT II]; NCT00388934)., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Although age-associated changes in left ventricular diastolic function are well recognized, limited data exist characterizing measures of diastolic function in older adults, including both reference ranges reflecting the older adult population and prognostically relevant values for incident heart failure (HF), as well as their associations with circulating biomarkers of HF risk., Methods: Among 5801 elderly participants in the ARIC study (Atherosclerosis Risk in Communities; age range, 67-90 years; mean age, 76±5 years; 42% male; 21% black), we determined the continuous association of diastolic measures (tissue Doppler imaging [TDI] e', E/e', and left atrial size) with concomitant N-terminal pro-brain natriuretic peptide and subsequent HF hospitalization or death. We also determined sex-specific 10th and 90th percentile limits for these measures using quantile regression in 401 participants free of prevalent cardiovascular disease and risk factors., Results: Each measure of diastolic function was robustly associated with N-terminal pro-brain natriuretic peptide and incident HF or death. ARIC-based reference limits for TDI e' (4.6 and 5.2 cm/s for septal and lateral TDI e', respectively) were substantially lower than guideline cut points (7 and 10 cm/s, respectively), whereas E/e' and left atrial size demonstrated good agreement with guideline cut points. TDI e' was nonlinearly associated with incident HF or death, with inflection points for risk supportive of ARIC-based limits. ARIC-based limits for diastolic function improved risk discrimination over guideline-based cut points based on the integrated discrimination improvement (P<0.001) and continuous net reclassification improvement (P<0.001), reclassifying 42% of the study population as having normal diastolic function. We replicate these findings in the Copenhagen City Heart Study. With these limits, 46% had normal diastolic function and were at low risk of HF hospitalization or death (1%/y over a mean 1.7-year follow-up), 49% had 1 or 2 abnormal measures and were at intermediate risk (2.4%/y), and all 3 diastolic measures were abnormal in 5% who were at high risk (7.5%/y)., Conclusions: Our findings suggest that left ventricular longitudinal relaxation velocity declines as a part of healthy aging and is largely prognostically benign. The use of age-based normative values when considering an elderly population improves the risk discrimination of diastolic measures for incident HF or death., Competing Interests: The other authors report no disclosures., (© 2016 American Heart Association, Inc.)

Chronic obstructive pulmonary disease (COPD) is associated with long-term all-cause death after percutaneous coronary intervention with bare-metal stents. Regarding other outcomes, previous studies have shown conflicting results and the impact of drug-eluting stent (DES) in this population is not well known. We analyzed 4,605 patients who underwent percutaneous coronary intervention with bare-metal stents (33.1%) or DES (66.9%) from the Basel Stent Kosten-Effektivitats Trial-Prospective Validation Examination trials I and II. COPD patients (n = 283, 6.1%), were older and had more frequently a smoking or cardiovascular event history. At 2-year follow-up, cumulative event rates for patients with versus without COPD were the following: major adverse cardiac events (MACE: composite of cardiac death, nonfatal myocardial infarction, and target vessel revascularization): 15.2% versus 8.1% (p <0.001); all-cause death: 11.7% versus 2.4% (p <0.001); cardiac death: 5.7% versus 1.2% (p <0.001); myocardial infarction: 3.5% versus 1.9% (p = 0.045); definite/probable/possible stent thrombosis: 2.5% versus 0.9% (p = 0.01); and major bleeding: 4.2% versus 2.1% (p = 0.014). After adjusting for confounders including smoking status, COPD remained an independent predictor for MACE (hazard ratio [HR] 1.80, 95% confidence interval [CI] 1.31 to 2.49), all-cause death (HR 3.62, 95% CI 2.41 to 5.45), cardiac death (HR 3.12, 95% CI 1.74 to 5.60), and stent thrombosis (HR 2.39, 95% CI 1.03 to 5.54). We did not find evidence of an interaction between COPD and DES implantation (p for interaction = 0.29) for MACE. In conclusion, COPD is associated with increased 2-year rates of all-cause death, cardiac death, and stent thrombosis after stent implantation. DES use appears to be beneficial also in patients with COPD., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Patients with acute myocardial infarction are at increased risk of developing atrial fibrillation. We aimed to evaluate whether speckle tracking echocardiography improves risk stratification for atrial fibrillation in these patients.The study comprised of 373 patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention. Patients had an echocardiogram performed at a median of 2 days after their STEMI. The echocardiograms consisted of conventional measurements and myocardial strain analysis by speckle tracking from 3 apical projections. The endpoint was a composite of new-onset atrial fibrillation and ischemic stroke. At a median follow-up time of 5.5 years (interquartile range 4.9, 6.1 years), 44 patients developed the endpoint (atrial fibrillation: n = 24, ischemic stroke: n = 24, both: n = 4). Patients who reached the endpoint had significantly reduced systolic function by the left ventricular ejection fraction (LVEF) (43% vs 46%; P = 0.042) and global longitudinal strain (10.9% vs 12.6%; P = 0.004), both being univariable predictors. However, only global longitudinal strain remained a significantly independent predictor (hazard ratio 1.12, 95% confidence interval 1.00; 1.25, P = 0.042, per 1% decrease) after multivariable adjustment for baseline predictors (age, sex, diabetes, hypertension, diastolic dysfunction, and LVEF) using Cox regression. Furthermore, global longitudinal strain resulted in significantly higher c-statistics for prediction of outcome compared with LVEF <45% (0.63 vs 0.52; P = 0.026). When stratified into tertiles of global longitudinal strain, it became evident that patients in the lowest tertile mediated this signal with a 2-fold increased risk compared with the highest tertile (hazard ratio 2.10, 95% confidence interval 1.04; 4.25).Global longitudinal strain predicts atrial fibrillation after STEMI and may add valuable information which can help facilitate arrhythmia detection in these patients.

Several cardiac imaging modalities are able to visualize the left atrium (LA) and, therefore, allow for quantification of both structural and functional properties of this cardiac chamber. In echocardiography, only the maximal LA volume is included in the assessment of diastolic function at the current moment. Numerous studies, however, have shown that functional measures may be superior to the maximal LA volume in several aspects and to possess clinical value even in the absence of structural abnormalities. Such functional measures could prove particularly useful in the setting of predicting atrial fibrillation, which will be a point of focus in this review. Pivotal cardiac magnetic resonance imaging studies have revealed high correlation between LA fibrosis and risk of atrial fibrillation recurrence after catheter ablation, and subsequent multimodality imaging studies have uncovered an inverse relationship between LA reservoir function and degree of LA fibrosis. This has sparked an increased interest into the application of advanced imaging modalities, including both speckle tracking echocardiography and tissue tracking by cardiac magnetic resonance imaging. Even though increasing evidence has supported the use of functional measures and proven its superiority to the maximal LA volume, they have still not been adopted in clinical guidelines. The reason for this discrepancy may rely on the fact that there is little to no agreement on how to technically perform deformation analysis of the LA. Such technical considerations, limitations, and alternate imaging prospects will be addressed in this review., (© 2016 American Heart Association, Inc.)

Background: Recently, genetic studies have suggested a causal relationship between cholesterol remnants and ischemic heart disease. We aimed to determine whether cholesterol remnants and its marker, triglyceride levels, are associated with cardiac function as determined by sensitive echocardiographic measures in a population of patients with type 2 diabetes., Methods: Comprehensive echocardiography including 2D-speckle tracking echocardiography was performed on a representative sample of 924 patients with type 2 diabetes-730 of whom were treated with statins. These were recruited from two large secondary care centers., Results: In multivariable analyses, triglycerides and cholesterol remnants were not associated with left ventricular ejection fraction, but with subtle measures of systolic function, including global longitudinal strain by speckle tracking and longitudinal displacement by tissue Doppler echocardiography: global longitudinal strain [0.33 % (0.14), p = 0.02 per doubling in cholesterol remnants and 0.28 % (0.13), p = 0.03 per doubling in triglyceride levels] and with longitudinal displacement [-0.25 mm (0.10), p = 0.01 per doubling in cholesterol remnants and -0.25 mm (0.09), p = 0.005 per doubling in triglyceride levels]. Subgroup analyses of patients receiving statin therapy and patients without known heart disease revealed similar results, but the association was not present in patients with known heart disease., Conclusion: In patients with type 2 diabetes, subtle decrease in left ventricular function is present with increasing levels of cholesterol remnants and triglyceride levels indicating an effect of these on cardiac function that is not detectable by conventional echocardiography.

Background: The current method for a non-invasive assessment of diastolic dysfunction is complex with the use of algorithms of many different echocardiographic parameters. Total average diastolic longitudinal displacement (LD), determined by colour tissue Doppler imaging (TDI) via the measurement of LD during early diastole and atrial contraction, can potentially be used as a simple and reliable alternative., Methods: In 206 patients, using GE Healthcare Vivid E7 and 9 and Echopac BT11 software, we determined both diastolic LD, measured in the septal and lateral walls in the apical 4-chamber view by TDI, and the degree of diastolic dysfunction, based on current guidelines. Of these 206 patients, 157 had cardiac anomalies that could potentially affect diastolic LD such as severe systolic heart failure (n = 45), LV hypertrophy (n = 49), left ventricular (LV) dilation (n = 30), and mitral regurgitation (n = 33). Intra and interobserver variability of diastolic LD measures was tested in 125 patients., Results: A linear relationship between total average diastolic LD and the degree of diastolic dysfunction was found. A total average diastolic LD of 10 mm was found to be a consistent threshold for the general discrimination of patients with or without diastolic dysfunction. Using linear regression, total average diastolic LD was estimated to fall by 2.4 mm for every increase in graded severity of diastolic dysfunction (β = -0.61, p-value <0.001). Patients with LV hypertrophy had preserved total average diastolic LD despite being classified as having diastolic dysfunction. Reproducibility of LD measures was acceptable., Conclusions: There is strong evidence suggesting that patients with a total average diastolic LD under 10 mm have diastolic dysfunction.

Aims: Patients admitted with chest pain are a diagnostic challenge because the majority does not have coronary artery disease (CAD). Assessment of CAD with coronary computed tomography angiography (CCTA) is safe, cost-effective, and accurate, albeit with a modest specificity. Stress myocardial computed tomography perfusion (CTP) has been shown to increase the specificity when added to CCTA, without lowering the sensitivity. This article describes the design of a randomized controlled trial, CATCH-2, comparing a clinical diagnostic management strategy of CCTA alone against CCTA in combination with CTP., Methods: Patients with acute-onset chest pain older than 50 years and with at least one cardiovascular risk factor for CAD are being prospectively enrolled to this study from 6 different clinical sites since October 2013. A total of 600 patients will be included. Patients are randomized 1:1 to clinical management based on CCTA or on CCTA in combination with CTP, determining the need for further testing with invasive coronary angiography including measurement of the fractional flow reserve in vessels with coronary artery lesions. Patients are scanned with a 320-row multidetector computed tomography scanner. Decisions to revascularize the patients are taken by the invasive cardiologist independently of the study allocation. The primary end point is the frequency of revascularization. Secondary end points of clinical outcome are also recorded., Discussion: The CATCH-2 will determine whether CCTA in combination with CTP is diagnostically superior to CCTA alone in the management of patients with acute-onset chest pain., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: Cardiovascular disease is the most common cause of mortality in type 1 diabetes; patients with albuminuria are at greatest risk. We investigated myocardial function and premature myocardial impairment in type 1 diabetes patients with and without albuminuria compared to controls., Methods: This study included a cross-sectional survey of 1093 type 1 diabetes patients from Steno Diabetes Center and 200 healthy controls. Conventional and tissue Doppler echocardiographic measurements were analysed in multivariable models in normoalbuminuria (n = 760), microalbuminuria (n = 227) and macroalbuminuria (n = 106). Investigators were blinded to degree of albuminuria., Results: For the type 1 diabetes patients, mean age was 49.6 years, 53% were men and mean diabetes duration was 25.5 years. In multivariable models systolic velocity s' did not differ between type 1 diabetes patients with normoalbuminuria and controls (β-coefficient [95% confidence interval]: -0.17 [-0.41; 0.08], p = 0.19), but was impaired between controls and microalbuminuria (-0.53 [-0.84; -0.23], p = 0.001) and macroalbuminuria (-0.59 [-0.96; -0.22], p = 0.002). Diastolic measurements (e', a', e'/a', and E/e') were all significantly impaired in type 1 diabetes, for example, e'/a': normoalbuminuria, microalbuminuria and macroalbuminuria versus controls: -0.38 [-0.52; -0.23], p < 0.001; -0.49 [-0.67; -0.32], p < 0.001; and -0.81 [-1.03; -0.59], p < 0.001. In age-related analyses, myocardial impairment occurred prematurely in type 1 diabetes compared to controls (e.g. E/e' = 8; 9.2 years [normoalbuminuria], 17.3 years [microalbuminuria] and 41.4 years [macroalbuminuria] prematurely, respectively)., Conclusion: In type 1 diabetes patients with albuminuria, both systolic and diastolic functions are impaired, whereas in patients without albuminuria only diastolic function is affected. Myocardial impairment is detectable many years prematurely in type 1 diabetes, especially in patients with albuminuria., (© The Author(s) 2016.)

Aims: Identification of early signs and symptoms of heart disease is important in type 1 diabetes (T1DM). Global longitudinal strain (GLS) by speckle-tracking echocardiography can detect subtle impairments in myocardial function. We investigated the association between myocardial function and degree of dyspnea in patients with normal left ventricular ejection fraction (LVEF) and without known heart disease., Methods: Ambulatory patients from Steno Diabetes Center. Conventional echocardiography and GLS was performed. Patients reported degree of dyspnea according to the NYHA classification. Patients with LVEF≤45% were excluded. Data were analyzed in uni-and multivariable models., Results: A total of 1075 T1DM patients were included. Mean age 49.5years, 52% men, mean diabetes duration 25.8years; 835 (77.7%) reported no dyspnea, 156 (14.5%) NYHA I, 68 (6.3%) NYHA II, and 16 (1.5%) NYHA III-IV. LVEF did not differ between groups of dyspnea in neither univariable nor multivariable models (p>0.1). E/e' was associated with degree of dyspnea in both univariable (p<0.001) and multivariable models (p=0.048). GLS was associated with degree of dyspnea in a dose-response relationship in both univariable (p<0.001) and multivariable models (p<0.001)., Conclusions: Degree of dyspnea is independently associated with impaired myocardial function by GLS in T1DM patients with normal LVEF and without known heart disease., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Global longitudinal systolic strain (GLS) has recently been demonstrated to be a superior prognosticator to conventional echocardiographic measures in patients after myocardial infarction (MI). The aim of this study was to evaluate the prognostic value of regional longitudinal myocardial deformation in comparison to GLS, conventional echocardiography and clinical information., Method: In total 391 patients were admitted with ST-Segment elevation myocardial infarction (STEMI), treated with primary percutaneous coronary intervention and subsequently examined by echocardiography. All patients were examined by tissue Doppler imaging (TDI) and two-dimensional strain echocardiography (2DSE)., Results: During a median-follow-up of 5.3 (IQR 2.5-6.1) years the primary endpoint (death, heart failure or a new MI) was reached by 145 (38.9%) patients. After adjustment for significant confounders (including conventional echocardiographic parameters) and culprit lesion, reduced longitudinal performance in the anterior septal and inferior myocardial regions (but not GLS) remained independent predictors of the combined outcome. Furthermore, inferior myocardial longitudinal deformation provided incremental prognostic information to clinical and conventional echocardiographic information (Harrell's c-statistics: 0.63 vs. 0.67, p = 0.032). In addition, impaired longitudinal deformation outside the culprit lesion perfusion region was significantly associated with an adverse outcome (p<0.05 for all deformation parameters)., Conclusion: Regional longitudinal myocardial deformation measures, regardless if determined by TDI or 2DSE, are superior prognosticators to GLS. In addition, impaired longitudinal deformation in the inferior myocardial segment provides prognostic information over and above clinical and conventional echocardiographic risk factors. Furthermore, impaired longitudinal deformation outside the culprit lesion perfusion region seems to be a paramount marker of adverse outcome.

Aims: Randomized trials of coronary bifurcation stenting have shown better outcomes from a simple (provisional) strategy rather than a complex (planned two-stent) strategy in terms of short-term efficacy and safety. Here, we report the 5-year all-cause mortality based on pooled patient-level data from two large bifurcation coronary stenting trials with similar methodology: the Nordic Bifurcation Study (NORDIC I) and the British Bifurcation Coronary Study: old, new, and evolving strategies (BBC ONE)., Methods and Results: Both multicentre randomized trials compared simple (provisional T-stenting) vs. complex (culotte, crush, and T-stenting) techniques, using drug-eluting stents. We analysed all-cause death at 5 years. Data were collected from phone follow-up, hospital records, and national mortality tracking. Follow-up was complete for 890 out of 913 patients (97%). Both Simple and Complex groups were similar in terms of patient and lesion characteristics. Five-year mortality was lower among patients who underwent a simple strategy rather than a complex strategy [17 patients (3.8%) vs. 31 patients (7.0%); P = 0.04]., Conclusion: For coronary bifurcation lesions, a provisional single-stent approach appears to be associated with lower long-term mortality than a systematic dual stenting technique., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Background: Based on evident sex-related differences in the invasive management of patients presenting with acute myocardial infarction (AMI), we sought to identify predictors of diagnostic coronary angiography (DCA) and to investigate reasons for opting out an invasive strategy in women and men., Methods: The study was designed as a matched cohort study. We randomly selected 250 female cases from a source population of 4000 patients hospitalized with a first AMI in a geographically confined region of Denmark from January 2010 to November 2011. Each case was matched to a male control on age and availability of cardiac invasive facilities at the index hospital. We systematically reviewed medical records for risk factors, comorbid conditions, clinical presentation, and receipt of DCA. Clinical justifications, as stated by the treating physician, were noted for the subset of patients who did not receive a DCA., Results: Overall, 187 women and 198 men received DCA within 60 days (75 % vs. 79 %, hazard ratio: 0.82 [0.67-1.00], p = 0.047).In the subset of patients who did not receive a DCA (n = 114), clinical justifications for opting out an invasive strategy was not documented for 21 patients (18.4 %). Type 2 myocardial infarction was noted in 11 patients (women versus men; 14.5 % vs. 3.8 %, p = 0.06) and identified as a potential confounder of the sex-DCA relationship. Receipt of DCA was predicted by traditional risk factors for ischaemic heart disease (family history of cardiovascular disease, hypercholesterolemia, and smoking) and clinical presentation (chest pain, ST-segment elevations). Although prevalent in both women and men, the presence of relative contraindications did not prohibit the use of DCA., Conclusion: In this matched cohort of patients with a first AMI, women and men had different clinical presentations despite similar age. However, no differences in the distribution of relative contraindications for DCA were found between the sexes. Type 2 MI posed a potentiel confounder for the sex-related differences in the use of DCA. Importantly,clinical justification for opting out an invasive strategy was not documented in almost one fifth of patients not receiving a DCA.

Cardiac time intervals (CTI) are prognostic above and beyond conventional echocardiographic measures. The explanation may be that CTI contain information about both systolic and diastolic measures; this is, however, unknown. The relationship between the CTI and systolic and diastolic function assessed by conventional, tissue Doppler (TDI) and speckle-tracking echocardiography (STE) was investigated. CTI and echocardiographic measurements, including conventional, STE, and TDI echocardiography, were studied in 1088 type 1 diabetes patients without known heart disease randomly selected from the out-patient clinic at Steno Diabetes Center. The CTI were obtained by TDI M-mode through the mitral leaflet and included the isovolumic relaxation time (IVRT), isovolumic contraction time (IVCT), and the myocardial performance index (MPI = (IVRT + IVCT)/ejection time). Standardized beta-values were assessed. Both systolic and diastolic measures associated with CTI. Conventional measures: left ventricular ejection fraction (stand. beta): MPI -0.34, IVRT 0.24, and IVCT -0.21, all p < 0.001. For the TDI measures, the most significant association was found with e': MPI (stand. beta: -0.30, p < 0.001) and IVRT (-0.35, p < 0.001) but no association with IVCT -0.05, p = 0.1). Speckle-tracking derived measures were in general strongly associated with the cardiac time intervals. Thus, global longitudinal strain and MPI (-0.38, p < 0.001), IVRT (-0.23, p < 0.001), and IVCT (-0.10, p < 0.001); and global longitudinal strain rate e and MPI (-0.40, p < 0.001), IVRT (-0.42, p < 0.001), and IVCT (-0.04, p = 0.11). CTI, in particular MPI and IVRT, associate with both systolic and diastolic myocardial function assessed by conventional and newer echocardiographic measures. This may possibly help to explain the prognostic significance of CTI.

A rare genetic variant in the desmosomal gene plakophilin-2 (PKP2) c.419C>T(p.(S140F)) has repeatedly been identified in patients with dilated cardiomyopathy (DCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC). Whether this is a disease-causing variant remains highly controversial. We tested this hypothesis using three approaches. Initially, in a prospective study of 10 407 individuals from the general population, including 2688 who developed heart failure or arrhythmias during >14 years of follow-up, PKP2 c.419C>T was identified in 98 individuals (0.94%). PKP2 genotype was not associated with electrocardiographic or echocardiographic changes, or with plasma levels of probrain natriuretic peptide (all P≥0.05). In c.419C>T carriers versus non-carriers, multifactorially adjusted hazard ratios were 1.26 (95% confidence interval: 0.77-2.07) for heart failure, 1.40 (0.90-2.17) for arrhythmias, 1.15 (0.78-1.71) for end points combined, and 1.33 (0.98-1.80) for all-cause mortality. The cumulative survival as a function of age and PKP2 genotype was similar among carriers and non-carriers (P=0.14). Second, comparing 517 patients referred for genetic testing with 1918 matched controls, odds ratios as a function of c.419C>T genotype were 2.11 (0.50-8.99) for ARVC, 0.72 (0.16-3.28) for hypertrophic cardiomyopathy (HCM)/DCM, and 1.28 (0.46-3.54) for end points combined. Third, in in vitro studies cellular localization of plakophilin-2, plakoglobin, connexin-43, or N-cadherin were similar in cells transfected with wild-type or mutant plakophilin-2. In conclusion, combining epidemiological data, with data on patients referred for genetic testing for ARVC or HCM/DCM, and data from in vitro studies, PKP2 c.419C>T did not associate with heart failure, arrhythmias, or premature death, with ARVC or HCM/DCM, or with effects in vitro, suggesting that this is not a disease-causing variant.

Purpose: To define normal values of the cardiac time intervals obtained by tissue Doppler imaging (TDI) M-mode through the mitral valve (MV). Furthermore, to evaluate the association of the myocardial performance index (MPI) obtained by TDI M-mode (MPITDI) and the conventional method of obtaining MPI (MPIConv), with established echocardiographic and invasive measures of systolic and diastolic function., Methods: In a large community based population study (n = 974), where all are free of any cardiovascular disease and cardiovascular risk factors, cardiac time intervals, including isovolumic relaxation time (IVRT), isovolumic contraction time (IVCT), and ejection time (ET) were obtained by TDI M-mode through the MV. IVCT/ET, IVRT/ET and the MPI ((IVRT+IVCT)/ET) were calculated. We also included a validation population (n = 44) of patients who underwent left heart catheterization and had the MPITDI and MPIConv measured., Results: IVRT, IVRT/ET and MPI all increased significantly with increasing age in both genders (p<0.001 for all). IVCT, ET, IVRT/ET, and MPI differed significantly between males and females, displaying that women, in general exhibit better cardiac function. MPITDI was significantly associated with invasive (dP/dt max) and echocardiographic measures of systolic (LVEF, global longitudinal strain and global strainrate s) and diastolic function (e', global strainrate e)(p<0.05 for all), whereas MPIConv was significantly associated with LVEF, e' and global strainrate e (p<0.05 for all)., Conclusion: Normal values of cardiac time intervals differed between genders and deteriorated with increasing age. The MPITDI (but not MPIConv) is associated with most invasive and established echocardiographic measures of systolic and diastolic function.

Aims: To evaluate the prognostic value of global longitudinal strain (GLS) and basal longitudinal strain (BLS) with the knowledge of coexisting coronary pathology evaluated by multi-detector computed tomography (MDCT) coronary angiography., Background: GLS and BLS are both sensitive markers of myocardial dysfunction and predictors of outcome in asymptomatic aortic stenosis. Aortic stenosis and ischaemic heart disease share risk factors and longitudinal function can be severely reduced in both conditions, why some of the previous findings of impaired regional longitudinal function in asymptomatic aortic stenosis could in fact be explained by silent ischaemic heart disease., Methods and Results: Prospective follow-up of 104 asymptomatic patients with moderate-severe aortic stenosis defined as an aortic valve area <1.5 cm(2). Patients underwent a thorough clinical work-up, advanced echocardiographic analysis and coronary angiography by MDCT. The combined endpoint was indication for aortic valve replacement (AVR) and sudden cardiac death. During a median follow-up of 2.3 years (interquartile range 1.7-3.6) 43 patients (41%) met the endpoint of indication for AVR. The basal (13.4 ± 3.1% vs. 15.7 ± 3.1%) and mid-ventricular segments (14.9 ± 2.7% vs. 16.2 ± 2.9%) were significantly reduced, but with sparing of the apical segments, in patients who later underwent AVR. In various multivariable Cox regression models, including only BLS, but not GLS, remained an independent predictor of AVR., Conclusion: In contrast to GLS, reduced BLS is a significant predictor of future AVR in asymptomatic patients with aortic stenosis, independently of clinical characteristics, conventional echocardiographic measures, and coronary pathology., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

It is often difficult to provide an exact echocardiographic measure of left ventricular systolic function in patients with atrial fibrillation, partly because of the varying cycle length affecting pre and afterload and partly because of the increased heart rate often accompanying this arrhythmia. We sought to elucidate two points: whether it would be possible to correct for the cyclic variance in systolic output, and if global longitudinal strain is preferable to the left ventricular ejection fraction at evaluating systolic function during atrial fibrillation.

Background: Often the underlying cause of cerebral ischemia (CI) cannot be found during a routine diagnostic investigation, but paroxysmal atrial fibrillation (PAF) could be the culprit., Aim: The objective of the study is to investigate whether advanced echocardiography improves the diagnostic approach for PAF in CI., Methods: The study included 286 CI patients with an echocardiogram in sinus rhythm. Patients were divided by PAF occurrence (PAF: n = 86, non-PAF: n = 200). PAF was defined as 1 or more reported episodes of atrial fibrillation. Echocardiograms consisted of conventional measures, tissue Doppler imaging (TDI), and speckle tracking. TDI was performed to acquire myocardial peak velocities during systole/ventricular contraction (global s'), early diastole/ventricular filling (global e'), and late diastole/atrial contraction (global a'). Speckle tracking was performed for myocardial strain analysis, thereby retrieving global longitudinal strain and global strain rate (s, e, a) values., Results: Patients with PAF exhibited significantly impaired atrial contractile measures: global a' (-7.0 cm/second versus -5.7 cm/second, P < .001) and global strain rate a (.97 second(-1) versus .81 second(-1), P < .001). Both were univariable markers of PAF, and along with age remained the only independent significant determinants of PAF after multivariable logistic regression. Area under the curve (AUC) for age, global a', and global strain rate a significantly exceeded AUC for age alone (.79 versus .76, P = .032). Cutoff values with the highest sensitivity and specificity for these 3 parameters improved the diagnostic accuracy (sensitivity = 97%, specificity = 32%, negative predictive value = 95%, and positive predictive value = 38%)., Conclusions: Atrial contractile measures by advanced echocardiography are significant determinants of PAF in CI. However, there is no discriminatory power to make them clinically useful at the current moment., (Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: We hypothesized that the cardiac time intervals reveal reduced myocardial function in persons with hypertension and are strong predictors of future ischemic cardiovascular diseases in the general population., Methods and Results: In a large community-based population study, cardiac function was evaluated in 1915 participants by using both conventional echocardiography and tissue Doppler imaging (TDI). The cardiac time intervals, including the isovolumic relaxation time (IVRT), isovolumic contraction time (IVCT), and ejection time (ET), were obtained by TDI M-mode through the mitral leaflet. IVCT/ET, IVRT/ET, and myocardial performance index [MPI=(IVRT+IVCT)/ET] were calculated. After multivariable adjustment for clinical variables the IVRT, IVRT/ET, and MPI, remained significantly impaired in persons with hypertension (n=826) compared with participants without hypertension (n=1082). Additionally, they displayed a significant dose-response relationship, between increasing severity of elevated blood pressure and increasing left ventricular mass index (P<0.001 for all). Further, during follow-up of a median of 10.7 years, 435 had an ischemic cardiovascular disease (ischemic heart disease, peripheral arterial disease, or stroke). The IVRT/ET and MPI were powerful and independent predictors of future cardiovascular disease, especially in participants with known hypertension. They provide prognostic information incremental to clinical variables from the Framingham Risk Score, the SCORE risk chart, and the European Society of Hypertension/European Society of Cardiology risk chart., Conclusion: The cardiac time intervals identify impaired cardiac function in individuals with hypertension, not only independent of conventional risk factors but also in participants with a normal conventional echocardiographic examination. The IVRT/ET and MPI are independent predictors of future cardiovascular disease especially in participants with known hypertension., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)