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Noninvasive cardiac imaging by transthoracic echocardiography is among the first-line assessments in evaluation of heart failure patients with preserved ejection fraction (HFpEF). Although systolic function seems preserved by conventional measurers, important information is found through examination of the heart's hemodynamic profile through Doppler and novel echocardiographic measures. These measures aid in establishing the diagnosis of HFpEF and provide valuable prognostic information. Targets of interest include the left ventricle diastolic function, atrial structure and function, and right ventricular function including pulmonary pressures. Contemporary assessments of the hemodynamic profile attainable through echocardiography in HFpEF at rest are reviewed and future directions outlined., Competing Interests: Disclosure T. Biering-Sørensen: Steering Committee member of the Amgen financed GALACTIC-HF trial. Advisory Board: Sanofi Pasteur. Advisory Board: Amgen. Speaker Honorarium: Novartis. Speaker Honorarium: Sanofi Pasteur; Research grant: GE Healthcare (Norway). Research grant: Sanofi Pasteur. M. Sengeløv: None., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Tissue Doppler imaging (TDI) can be used to measure the mitral annular longitudinal displacement (LD) during systole. However, the prognostic utility of global and regional LD in patients with heart failure with reduced ejection fraction (HFrEF) is unknown., Methods: Echocardiographic examinations from 907 patients with HFrEF were analysed obtaining conventional echocardiographic measurements. Regional LD was obtained from colour TDI projections in six mitral annular regions and global LD was calculated as an average., Results: Mean age was 67 years, 26.9% were women and mean left ventricular ejection fraction was 27%. During a median follow-up period of 40 months, 150 (16.5 %) patients died. The risk of dying increased with decreasing tertile of global LD and was approximately five times higher for patients in the lowest tertile compared with the highest (1. tertile vs 3. tertile, HR 4.9, 95% CI: 3.0 to 7.9, p<0.001).Global LD was a significant independent predictor of mortality after adjusting for age, gender, body mass index, pacemaker, heart rate, atrial fibrillation, diabetes and conventional echocardiographic measures and global longitudinal strain: HR 1.16 (95% CI: 1.00 to 1.34, p=0.044) per 1 mm decrease.For regional measures, inferior LD was also a significant independent predictor in the multivariable model: HR 1.16 (95% CI: 1.04 to 1.29, p=0.006) and adding inferior LD to the conventional measures yielded a significant increase in Harrell's C-statistic (95% CI: 0.75 to 0.78, p=0.009)., Conclusion: In patients with HFrEF, global and inferior LD are independent predictors of all-cause mortality. Furthermore, inferior LD proved to be a significant prognosticator when compared with all the conventional echocardiographic parameters., Competing Interests: Competing interests: PG has received lecture fees from Novo Nordisk and AstraZeneca. TB-S reports receiving research grants from Sanofi Pasteur and GE Healthcare, being a Steering Committee member of the Amgen financed GALACTIC‐HF trial, on advisory boards for Sanofi Pasteur and Amgen, and speaker honorariums from Novartis and Sanofi Pasteur., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: We hypothesized that grading of diastolic dysfunction (DDF) according to two DDF grading algorithms and strain imaging yields prognostic information on all-cause mortality in patients with heart failure with reduced ejection fraction (HFrEF)., Methods and Results: We enrolled ambulatory HFrEF (left ventricular ejection fraction < 45%; N = 1 065) patients who underwent echocardiography and speckle tracking assessment of global longitudinal strain (GLS). Patients were stratified according to DDF grades (Grades I-III) according to two contemporary DDF grading algorithms. Prognostic performance was assessed by C-statistics. Of the originally 1 065 enrolled patients, a total of 645 (61%) patients (age: 67 ± 11 years, male: 72%, ejection fraction: 27 ± 9%) were classified according to both DDF grading algorithms. Concordance between the algorithms was moderate (kappa = 0.48) and the reclassification rate was 33%. During a median follow-up of 3.3 years (1.9, 4.7 years), 101 (16%) died from all causes. When comparing DDF Grade I vs. Grade III, both algorithms provided prognostic information [Nagueh: (hazard ratio) HR 2.09, 95% confidence interval (CI),1.32-3.31, P = 0.002; Johansen: HR 2.47, 95% CI, 1.57-3.87, P < 0.001]. However, when comparing DDF Grade II vs. Grade III, only the Johansen algorithm yielded prognostic information (Nagueh: HR 1.04, 95% CI, 0.60-1.77, P = 0.90; Johansen: HR 2.26, 95% CI, 1.35-3.77, P = 0.002). We found no difference in prognostic performance between the two algorithms (C-statistics: 0.604 vs. 0.623, P = 0.24). Assessed by C-statistics, the most powerful predictors of the endpoint from the two algorithms were E/e'-ratio (C-statistics: 0.644), tricuspid regurgitation velocity (C-statistics: 0.625) and E/A-ratio (C-statistics: 0.602). When adding GLS to a combination of these predictors, the prognostic performance increased significantly (C-statistics: 0.705 vs. C-statistics: 0.634, P = 0.028)., Conclusions: Evaluation of DDF in patients with HFrEF yields prognostic information on all-cause mortality. Furthermore, adding GLS to contemporary algorithms of DDF adds novel prognostic information., (© 2019 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

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: Previous studies found that global longitudinal strain is a superior predictor of mortality in male patients with heart failure with reduced ejection fraction (EF). This does not apply to women. Our aim was to investigate sex-specific differences in cardiac function and identify echocardiographic predictors of mortality in women with heart failure with reduced EF., Methods and Results: Echocardiographic examinations were retrieved from 968 patients with heart failure with reduced EF (26.7% women). Images were analyzed offline, and the end point was all-cause mortality. During follow-up (median: 41 months) 163 patients (16.8 %) died. Women had significantly higher left ventricular (LV) EF (27.1% versus 25.4%, P=0.004), global longitudinal strain (-9.9% versus -8.9%, P<0.001), and global circumferential strain (-10.9% versus -9.7%, P<0.001). Moreover, women displayed higher E/e' (14.4 versus 13.0, P=0.004), LV diastolic elastance (1.16 versus 0.75, P<0.001), and lower e' (6.2 cm/s versus 6.9 cm/s, P<0.001). In women, tricuspid annular plane systolic excursion and LV isovolumetric relaxation time were significant predictors of outcome after multivariable adjustment (tricuspid annular plane systolic excursion: hazard ratio, 1.11; 95% CI, 1.04-1.18; P=0.003 per 1 mm decrease; isovolumetric relaxation time: hazard ratio, 1.07; 95% CI, 1.03-1.10; P=0.001 per 5 ms decrease). LVEF and global longitudinal strain were significant predictors in men (LVEF: hazard ratio, 0.94; 95% CI, 0.90-0.99; P=0.014 per 1% increase; global longitudinal strain: hazard ratio, 1.20; 95% CI, 1.04-1.38; P=0.013 per 1% decrease)., Conclusions: Tricuspid annular plane systolic excursion and LV isovolumetric relaxation time provide prognostic information in women but not in men. Hence, in women with heart failure with reduced EF, right ventricular function, and LV diastolic function seem paramount in predicting mortality, whereas LV systolic function is more important in men.

Objectives: The purpose of this study was to investigate the prognostic value of global longitudinal strain (GLS) in heart failure with reduced ejection fraction (HFrEF) patients in relation to all-cause mortality., Background: Measurement of myocardial deformation by 2-dimensional speckle tracking echocardiography, specifically GLS, may be superior to conventional echocardiographic parameters, including left ventricular ejection fraction, in predicting all-cause mortality in HFrEF patients., Methods: Transthoracic echocardiographic examinations were retrieved for 1,065 HFrEF patients admitted to a heart failure clinic. The echocardiographic images were analyzed, and conventional and novel echocardiographic parameters were obtained., Results: Many of the conventional echocardiographic parameters proved to be predictors of mortality. However, GLS remained an independent predictor of mortality in the multivariable model after adjusting for age, sex, body mass index, total cholesterol, mean arterial pressure, heart rate, ischemic cardiomyopathy, percutaneous transluminal coronary angioplasty, coronary artery bypass graft surgery, noninsulin dependent diabetes mellitus, and conventional echocardiographic parameters (hazard ratio [HR]: 1.15; 95% confidence interval [CI]: 1.04 to 1.27; p = 0.008, per 1% decrease). No other echocardiographic parameter remained an independent predictor after adjusting for these variables. Furthermore, GLS had the highest C-statistics of all the echocardiographic parameters and added incremental prognostic value with a significant increase in the net reclassification improvement (p = 0.009). Atrial fibrillation (AF) modified the relationship between GLS and mortality (p value for interaction = 0.036); HR: 1.08 (95% CI: 0.97 to 1.19), p = 0.150 and HR: 1.22 (95% CI: 1.15 to 1.29), p < 0.001, per 1% decrease in GLS for patients with and without AF, respectively. Sex also modified the relationship between GLS and mortality (p value for interaction = 0.047); HR: 1.23 (95% CI: 1.16 to 1.30), p < 0.001 and HR: 1.09 (95% CI: 0.99 to 1.20), p = 0.083, per 1% decrease in GLS for men and women, respectively., Conclusions: GLS is an independent predictor of all-cause mortality in HFrEF patients, especially in male patients without AF. Furthermore, GLS was a superior prognosticator compared with all other echocardiographic parameters., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims Left ventricular (LV) systolic deformation is altered early in the ventricular disease process despite normal LV ejection fraction (LVEF). These alterations seem to be characterized by decreased global longitudinal strain (GLS) and augmented global circumferential strain (GCS). This study aimed to investigate the link between myocardial deformation phenotyping using longitudinal and circumferential strain and risk of incident heart failure (HF) and cardiovascular death (CD). Methods and results The study sample was based on the prospective cohort study the 5th Copenhagen City Heart Study (2011–15). All participants were examined with echocardiography following a pre-defined protocol. A total of 2874 participants were included. Mean age was 53±18 years and 60% were female. During a median follow-up of 3.5 years, a total of 73 developed HF/CD. A U-shaped relationship between GCS and HF/CD was observed. LVEF significantly modified the association between GCS and HF/CD (P for interaction <0.001). The optimal transition point for the effect modification was LVEF < 50%. In multivariable Cox regressions, increasing GCS was significantly associated with HF/CD in participants with LVEF ≥ 50% (hazard ratio [HR]=1.12 [95% confidence interval (CI): 1.02; 1.23] per 1% increase), while decreasing GCS was associated with a higher risk of HF/CD in individuals with LVEF < 50% [HR=1.18 (95% CI: 1.05; 1.31) per 1% decrease]. Conclusions The prognostic utility of GCS is modified by LVEF. In participants with normal LVEF, higher GCS was associated with increased risk of HF/CD, while the opposite was observed in participants with abnormal LVEF. This observation adds important information to our understanding of the pathophysiological evolution of myocardial deformation in cardiac disease progression. [ABSTRACT FROM AUTHOR]

Introduction: COVID-19 has spread globally in waves, and Danish treatment guidelines have been updated following the first wave. We sought to investigate whether the prognostic values of echocardiographic parameters changed with updates in treatment guidelines and the emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, 20E (EU1) and alpha (B.1.1.7), and further to compare cardiac parameters between patients from the first and second wave. Methods: A total of 305 patients hospitalized with COVID-19 were prospectively included, 215 and 90 during the first and second wave, respectively. Treatment in the study was defined as treatment with remdesivir, dexamethasone, or both. Patients were assumed to be infected with the dominant SARS-CoV-2 variant at the time of their hospitalization. Results: Mean age for the first versus second wave was 68.7 ± 13.6 versus 69.7 ± 15.8 years, and 55% versus 62% were males. Left ventricular (LV) systolic and diastolic function was worse in patients hospitalized during the second wave (LV ejection fraction [LVEF] for first vs. second wave = 58.5 ± 8.1% vs. 52.4 ± 10.6%, p < 0.001; and global longitudinal strain [GLS] = 16.4 ± 4.3% vs. 14.2 ± 4.3%, p < 0.001). In univariable Cox regressions, reduced LVEF (hazard ratio [HR] = 1.07 per 1% decrease, p = 0.002), GLS (HR = 1.21 per 1% decrease, p < 0.001), and tricuspid annular plane systolic excursion (HR = 1.18 per 1 mm decrease, p < 0.001) were associated with COVID-related mortality, but only GLS remained significant in fully adjusted analysis (HR = 1.14, p = 0.02). Conclusion: Reduced GLS was associated with COVID-related mortality independently of wave, treatment, and the SARS-CoV-2 variant. LV function was significantly impaired in patients hospitalized during the second wave. [ABSTRACT FROM AUTHOR]

Aims: This study investigated left atrial (LA) parameters as measured on transthoracic echocardiography as predictors of incident heart failure (HF) in a community cohort. Methods and results: In a large general population study (n = 2221), participants underwent a health examination with echocardiography. The maximum and minimum LA volumes indexed to body surface area (LAVImax and LAVImin) were measured and the LA emptying fraction (LAEF) and LA expansion index (LAEI) were calculated. Among 1951 participants without atrial fibrillation or significant valve disease, the mean age was 59 ± 16 years and 58% were women. At baseline, 1% (n = 16) had a left ventricular ejection fraction of <50%, 44% had hypertension, and 10% had diabetes. During follow‐up (median 15.8 years, interquartile range: 11.3–16.2 years), 187 (10%) participants were diagnosed with incident HF. Participants who were diagnosed with HF during follow‐up had a larger LAVImax and LAVImin and a lower LAEF and LAEI compared to participants without HF. In unadjusted analysis, LAVImax, LAVImin, LAEF and LAEI were predictors of incident HF. After multivariable adjustment for clinical and echocardiographic parameters, only LAVImin remained an independent predictor of incident HF (hazard ratio per 1 standard deviation increase: 1.22 [95% confidence interval 1.01–1.47], p = 0.038). Conclusion: In the general population, LAVImin is an independent predictor of incident HF. LAVImax, currently the only LA measure in a routine echocardiographic examination, was not an independent predictor of incident HF. [ABSTRACT FROM AUTHOR]

Background Left atrial (LA) strain parameters have been demonstrated to be valuable predictors of atrial fibrillation (AF) in several patient cohorts. The purpose of this study was to investigate whether LA strain, assessed by two-dimensional speckle-tracking echocardiography, can be used to predict the development of AF in the general population. Methods and results This prospective longitudinal study included 4466 participants from the fifth Copenhagen City Heart Study. All participants underwent a health examination, including echocardiographic measurements of LA strain. Participants with prevalent AF at baseline were excluded. The primary endpoint was incident AF. During a median follow-up period of 5.3 years, 154 (4.3%) participants developed AF. In univariable analysis, peak atrial longitudinal strain (PALS), peak atrial contraction strain (PACS), and LA strain during the conduit phase were significantly associated with the development of AF. PALS [hazard ratio (HR) 1.05, 95% confidence interval (CI) (1.03–1.07), P  < 0.001, per 1% decrease] and PACS (HR 1.08, 95% CI (1.05–1.12), P  < 0.001, per 1% decrease] remained independent predictors of AF in multivariable analysis. In addition, PALS and PACS remained significantly associated with AF development even in participants with normal-sized atria and normal left ventricular (LV) systolic function. Conclusion In the general population, PALS and PACS independently predict incident AF. These findings remained consistent even in participants with normal-sized LA and normal LV systolic function. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aims: The degree of cardiovascular sequelae following COVID‐19 remains unknown. The aim of this study was to investigate whether cardiac function recovers following COVID‐19. Methods and results: A consecutive sample of patients hospitalized with COVID‐19 was prospectively included in this longitudinal study. All patients underwent an echocardiographic examination during hospitalization and 2 months later. All participants were successfully matched 1:1 with COVID‐19‐free controls by age and sex. A total of 91 patients were included (mean age 63 ± 12 years, 59% male). A median of 77 days (interquartile range: 72–92) passed between the two examinations. Right ventricular (RV) function improved following resolution of COVID‐19: tricuspid annular plane systolic excursion (TAPSE) (2.28 ± 0.40 cm vs. 2.11 ± 0.38 cm, P < 0.001) and RV longitudinal strain (RVLS) (25.3 ± 5.5% vs. 19.9 ± 5.8%, P < 0.001). In contrast, left ventricular (LV) systolic function assessed by global longitudinal strain (GLS) did not significantly improve (17.4 ± 2.9% vs. 17.6 ± 3.3%, P = 0.6). N‐terminal pro‐B‐type natriuretic peptide decreased between the two examinations [177.6 (80.3–408.0) ng/L vs. 11.7 (5.7–24.0) ng/L, P < 0.001]. None of the participants had elevated troponins at follow‐up compared to 18 (27.7%) during hospitalization. Recovered COVID‐19 patients had significantly lower GLS (17.4 ± 2.9% vs. 18.8 ± 2.9%, P < 0.001 and adjusted P = 0.004), TAPSE (2.28 ± 0.40 cm vs. 2.67 ± 0.44 cm, P < 0.001 and adjusted P < 0.001), and RVLS (25.3 ± 5.5% vs. 26.6 ± 5.8%, P = 0.50 and adjusted P < 0.001) compared to matched controls. Conclusion: Acute COVID‐19 affected negatively RV function and cardiac biomarkers but recovered following resolution of COVID‐19. In contrast, the observed reduced LV function during acute COVID‐19 did not improve post‐COVID‐19. Compared to the matched controls, both LV and RV function remained impaired. [ABSTRACT FROM AUTHOR]

Aims: Layer‐specific global longitudinal strain (GLS) has been demonstrated to predict outcome in various patient cohorts. However, little is known regarding the prognostic value of layer‐specific GLS in the general population and whether different layers entail differential prognostic information. The aim of the present study was to investigate the prognostic value of whole wall (GLSWW), endomyocardial (GLSEndo), and epimyocardial (GLSEpi) GLS in the general population. Methods and results: A total of 4013 citizens were included in the present study. All 4013 had two‐dimensional speckle tracking echocardiography performed and analysed. Outcome was a composite endpoint of incident heart failure and/or cardiovascular death. Mean age was 56 years and 57% were female. During a median follow‐up time of 3.5 years, 133 participants (3.3%) reached the composite outcome. Sex modified the relationship between all GLS parameters and outcome. In sex‐stratified analysis, no GLS parameter remained significant predictors of outcome in females. In contrast, GLSWW [hazard ratio (HR) 1.16, 95% confidence interval (CI) 1.02–1.31, per 1% decrease] and GLSEpi (HR 1.19, 95% CI 1.04–1.38, per 1% decrease) remained as significant predictors of outcome in males after multivariable adjustment (including demographic, clinical, biochemistry, and echocardiographic parameters). Lastly, only in males did GLS parameters provide incremental prognostic information to general population risk models. Conclusions: In the general population, sex modifies the prognostic value of GLS resulting in GLSEpi being the only layer‐specific prognosticator in males, while no GLS parameter provides independent prognostic information in females. [ABSTRACT FROM AUTHOR]

Aims: The present study had two aims: (i) compare echocardiographic parameters in COVID‐19 patients with matched controls and (2) assess the prognostic value of measures of left (LV) and right ventricular (RV) function in relation to COVID‐19 related death. Methods and results: In this prospective multicentre cohort study, 214 consecutive hospitalized COVID‐19 patients underwent an echocardiographic examination (by pre‐determined research protocol). All participants were successfully matched 1:1 with controls from the general population on age, sex, and hypertension. Mean age of the study sample was 69 years, and 55% were male participants. LV and RV systolic function was significantly reduced in COVID‐19 cases as assessed by global longitudinal strain (GLS) (16.4% ± 4.3 vs. 18.5% ± 3.0, P < 0.001), tricuspid annular plane systolic excursion (TAPSE) (2.0 ± 0.4 vs. 2.6 ± 0.5, P < 0.001), and RV strain (19.8 ± 5.9 vs. 24.2 ± 6.5, P = 0.004). All parameters remained significantly reduced after adjusting for important cardiac risk factors. During follow‐up (median: 40 days), 25 COVID‐19 cases died. In multivariable Cox regression reduced TAPSE [hazard ratio (HR) = 1.18, 95% confidence interval (CI) [1.07–1.31], P = 0.002, per 1 mm decrease], RV strain (HR = 1.64, 95%CI[1.02;2.66], P = 0.043, per 1% decrease) and GLS (HR = 1.20, 95%CI[1.07–1.35], P = 0.002, per 1% decrease) were significantly associated with COVID‐19‐related death. TAPSE and GLS remained significantly associated with the outcome after restricting the analysis to patients without prevalent heart disease. Conclusions: RV and LV function are significantly impaired in hospitalized COVID‐19 patients compared with matched controls. Furthermore, reduced TAPSE and GLS are independently associated with COVID‐19‐related death. [ABSTRACT FROM AUTHOR]