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Arrhythmogenic right ventricular cardiomyopathy is an inherited cardiomyopathy, characterized by abnormal cell adhesions, disrupted intercellular signaling, and fibrofatty replacement of the myocardium. These changes serve as a substrate for ventricular arrhythmias, placing patients at risk of sudden cardiac death, even in the early stages of the disease. Current echocardiographic criteria for diagnosing arrhythmogenic right ventricular cardiomyopathy lack sensitivity, but novel markers of cardiac deformation are not subject to the same technical limitations as current guideline-recommended measures. Measuring cardiac deformation using speckle tracking allows for meticulous quantification of global systolic function, regional function, and dyssynchronous contraction. Consequently, speckle tracking to quantify myocardial strain could potentially be useful in the diagnostic process for the determination of disease progression and to assist risk stratification for ventricular arrhythmias and sudden cardiac death. This narrative review provides an overview of the potential use of different myocardial right ventricular strain measures for characterizing right ventricular dysfunction in arrhythmogenic right ventricular cardiomyopathy and its utility in assessing the risk of ventricular arrhythmias.

Aims: Identifying clinical and echocardiographic parameters associated with improvement in systolic function in outpatients with heart failure with reduced ejection fraction (HFrEF) could lead to more targeted treatment improving systolic function and outcome., Methods: In a retrospective cohort study, echocardiographic examinations from the first and final visit of 686 patients with HFrEF at the heart failure clinic at Gentofte Hospital were retrieved and analysed. Parameters associated with left ventricular ejection fraction (LVEF) improvement and survival according to LVEF improvement were assessed using linear regression and Cox regression, respectively. Beta-coefficients (β-coef) are standardised. Strain values are absolute., Results: While undergoing heart failure treatment, 559 (81.5%) patients improved systolic function ( Δ LVEF >0%), with 100 (14.6%) being super responders defined by LVEF improvement >20%. After multivariable adjustment, LVEF improvement was significantly associated with a less impaired global longitudinal strain (β-coef 0.25, p<0.001), higher tricuspid annular plane systolic excursion (β-coef 0.09, p=0.018), smaller left ventricular internal dimension in diastole (β-coef -0.15, p=0.011), lower E-wave/A-wave ratio (β-coef -0.13, p=0.003), higher heart rate (β-coef 0.18, p<0.001) and absence of ischaemic cardiomyopathy (β-coef -0.11, p=0.010) and diabetes (β-coef -0.081, p=0.033) at baseline. Mortality incidence rates differed with LVEF improvement ( Δ LVEF <0% vs Δ LVEF >0%, 8.3 vs 4.3 per 100 person years, p=0.012). Greater improvement in LVEF was associated with significantly lower mortality risk (tertile 1 vs tertile 3, HR 3.23, 95% CI 1.39 to 7.51, p=0.006)., Conclusion: In this outpatient HFrEF cohort, most patients improved systolic function. Heart failure aetiology, comorbidities and echocardiographic measures of heart structure and function were significantly, independently associated with future LVEF improvement. Greater LVEF improvement was significantly associated with lower mortality., Competing Interests: Competing interests: PGJ has received lecture fees from Novo Nordisk and AstraZeneca. TB-S: reports receiving research grants from Sanofi Pasteur, and GE Healthcare, is 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)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Conflict of interest: K.G.S is a member of an advisory board in Sanofi Pasteur. T.B.S. is a steering committee member of the Amgen-financed GALACTIC-HF trial, chief investigator and steering committee chair of the Sanofi Pasteur–financed ‘NUDGE-FLU’ trial, chief investigator and steering committee chair of the Sanofi Pasteur–financed ‘DANFLU-1’ trial, chief investigator and steering committee chair of the Sanofi Pasteur–financed ‘DANFLU-2’ trial, and steering committee member of the ‘LUX-Dx TRENDS Evaluates Diagnostics Sensors in Heart Failure Patients Receiving Boston Scientific’s Investigational ICM System’ trial. He is a member of an advisory board in Sanofi Pasteur, Amgen, and GSK and has received speaker honorarium from Novartis, Sanofi Pasteur, and GSK and research grants from GE Healthcare and Sanofi Pasteur. The remaining authors have nothing to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (© 2022 S. Karger AG, Basel.)

Background COVID-19 infection has been hypothesized to affect left ventricular function; however, the underlying mechanisms and the association to clinical outcome are not understood. The global work index (GWI) is a novel echocardiographic measure of systolic function that may offer insights on cardiac dysfunction in COVID-19. We hypothesized that GWI was associated with disease severity and all-cause death in patients with COVID-19. Methods and Results In a multicenter study of patients admitted with COVID-19 (n=305), 249 underwent pressure-strain loop analyses to quantify GWI at a median time of 4 days after admission. We examined the association of GWI to cardiac biomarkers (troponin and NT-proBNP [N-terminal pro-B-type natriuretic peptide]), disease severity (oxygen requirement and CRP [C-reactive protein]), and all-cause death. Patients with elevated troponin (n=71) exhibited significantly reduced GWI (1508 versus 1707 mm Hg%; P =0.018). A curvilinear association to NT-proBNP was observed, with increasing NT-proBNP once GWI decreased below 1446 mm Hg%. Moreover, GWI was significantly associated with a higher oxygen requirement (relative increase of 6% per 100-mm Hg% decrease). No association was observed with CRP. Of the 249 patients, 37 died during follow-up (median, 58 days). In multivariable Cox regression, GWI was associated with all-cause death (hazard ratio, 1.08 [95% CI, 1.01-1.15], per 100-mm Hg% decrease), but did not increase C-statistics when added to clinical parameters. Conclusions In patients admitted with COVID-19, our findings indicate that NT-proBNP and troponin may be associated with lower GWI, whereas CRP is not. GWI was independently associated with all-cause death, but did not provide prognostic information beyond readily available clinical parameters. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04377035.

Purpose: Several studies have reported thromboembolic events to be common in severe COVID-19 cases. We sought to investigate the relationship between lung ultrasound (LUS) findings in hospitalized COVID-19 patients and the development of venous thromboembolic events (VTE)., Methods: A total of 203 adults were included from a COVID-19 ward in this prospective multi-center study (mean age 68.6 years, 56.7% men). All patients underwent 8-zone LUS, and all ultrasound images were analyzed off-line blinded. Several LUS findings were investigated (total number of B-lines, B-line score, and LUS-scores)., Results: Median time from admission to LUS examination was 4 days (IQR: 2, 8). The median number of B-lines was 12 (IQR: 8, 18), and 44 (21.7%) had a positive B-line score. During hospitalization, 17 patients developed VTE (4 deep-vein thrombosis, 15 pulmonary embolism), 12 following and 5 prior to LUS. In fully adjusted multivariable Cox models (excluding participants with VTE prior to LUS), all LUS parameters were significantly associated with VTE (total number of B-lines: HR = 1.14, 95% CI (1.03, 1.26) per 1 B-line increase), positive B-line score: HR = 9.79, 95% CI (1.87, 51.35), and LUS-score: HR = 1.51, 95% CI (1.10, 2.07), per 1-point increase). The B-line score and LUS-score remained significantly associated with VTE in sensitivity analyses., Conclusion: In hospitalized COVID-19 patients, pathological LUS findings were common, and the total number of B-lines, B-line score, and LUS-score were all associated with VTE. These findings indicate that the LUS examination may be useful in risk stratification and the clinical management of COVID-19. These findings should be considered hypothesis generating., Gov Id: NCT04377035., (© 2021. Società Italiana di Ultrasonologia in Medicina e Biologia (SIUMB).)

Objective: To investigate the incidence of cardiac arrhythmias at six months following traumatic spinal cord injury (SCI) and to compare the prevalence of arrhythmias between participants with cervical and thoracic SCI., Design: A prospective observational study using continuous twenty-four-hour Holter monitoring., Setting: Inpatient rehabilitation unit of a university research hospital and patient home setting., Participants: Fifty-five participants with acute traumatic SCI were prospectively included. For each participant, the SCI was characterized according to the International Standards for Neurological Classification of SCI by the neurological level and severity according to the American Spinal Injury Association Impairment Scale., Outcome Measures: Comparisons between demographic characteristics and arrhythmogenic occurrences as early as possible after SCI (4 ± 2 days) followed by 1, 2, 3, 4 weeks and 6 month time points of Holter monitoring., Results: Bradycardia (heart rate [HR] <50 bpm) was present in 29% and 33% of the participants with cervical (C1-C8) and thoracic (T1-T12) SCI six months after SCI, respectively. The differences in episodes of bradycardia between the two groups were not significant (P < 0.54). The mean maximum HR increased significantly from 4 weeks to 6 months post-SCI (P < 0.001), however mean minimum and maximum HR were not significantly different between the groups at the six-month time point. There were no differences in many arrhythmias between recording periods or between groups at six months., Conclusions: At the six-month timepoint following traumatic SCI, there were no significant differences in occurrences of arrhythmias between participants with cervical and thoracic SCI compared to the findings observed in the first month following SCI.

Background: Lung ultrasound (LUS) is a useful tool for diagnosis and monitoring in patients with active COVID-19-infection. However, less is known about the changes in LUS findings after a hospitalization for COVID-19., Methods: In a prospective, longitudinal study in patients with COVID-19 enrolled from non-ICU hospital units, adult patients underwent 8-zone LUS and blood sampling both during the hospitalization and 2-3 months after discharge. LUS images were analyzed blinded to clinical variables and outcomes., Results: A total of 71 patients with interpretable LUS at baseline and follow up (mean age 64 years, 61% male, 24% with acute respiratory distress syndrome (ARDS)) were included. The follow-up LUS was performed a median of 72 days after the initial LUS performed during hospitalization. At baseline, 87% had pathologic LUS findings in ≥1 zone (e.g. ≥3 B-lines, confluent B-lines or subpleural or lobar consolidation), whereas 30% had pathologic findings at follow-up (p < 0.001). The total number of B-lines and LUS score decreased significantly from hospitalization to follow-up (median 17 vs. 4, p < 0.001 and 4 vs. 0, p < 0.001, respectively). On the follow-up LUS, 28% of all patients had ≥3 B-lines in ≥1 zone, whereas in those with ARDS during the baseline hospitalization (n = 17), 47% had ≥3 B-lines in ≥1 zone., Conclusion: LUS findings improved significantly from hospitalization to follow-up 2-3 months after discharge in COVID-19 survivors. However, persistent B-lines were frequent at follow-up, especially among those who initially had ARDS. LUS seems to be a promising method to monitor COVID-19 lung changes over time., Gov Id: NCT04377035., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Pressure-strain loop analyses is a noninvasive technique capable of evaluating myocardial work. Reference values are needed to benchmark these myocardial work indices for clinical practice., Methods: Healthy participants from a general population study were used to establish reference values for global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) measured by pressure-strain loop analyses. The relation to age and sex was examined. We furthermore examined the proportion of abnormal work indices according to low, intermediate, and high cardiovascular risk by the Framingham risk score., Results: The healthy sample consisted of 1827 participants (median age, 45 years; 39% men). Lower reference values were GWI, 1576 mm Hg%; GCW, 1708 mm Hg%; and GWE, 93.0% and upper reference value for GWW was 159 mm Hg%. Women exhibited significantly higher GWI, GCW, and GWW and lower GWE. Sex significantly modified the association between all indices and age ( P for interaction: 0.001 for GWI, 0.009 for GCW, 0.003 for GWW, and 0.009 for GWE). For men, only GCW increased with age, whereas the other indices did not change with age. For women, GCW increased linearly with increasing age, whereas GWI, GWW, and GWE changed in a curvilinear fashion with age such that GWI increased in younger participants, GWW increased in elderly, and GWE declined concordantly. Abnormalities in myocardial work indices became more frequent with increasing Framingham risk score category (abnormal GWI: 2% versus 4% versus 5%, P =0.001; abnormal GCW: 2% versus 3% versus 4%, P =0.006; abnormal GWW: 3% versus 6% versus 11%, P <0.001; abnormal GWE: 3% versus 4% versus 11%, P <0.001)., Conclusions: Myocardial work indices differ between sexes and change with age in a sex-dependent manner. Accordingly, we established age- and sex-specific reference values from a general population sample. Abnormal work indices become more frequent with higher clinical risk., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT02993172.

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., (© 2021 European Society of Cardiology.)

Background: As lung ultrasound (LUS) has emerged as a diagnostic tool in patients with COVID-19, we sought to investigate the association between LUS findings and the composite in-hospital outcome of ARDS incidence, ICU admission, and all-cause mortality., Methods: In this prospective, multi-center, observational study, adults with laboratory-confirmed SARS-CoV-2 infection were enrolled from non-ICU in-patient units. Subjects underwent an LUS evaluating a total of 8 zones. Images were analyzed off-line, blinded to clinical variables and outcomes. A LUS score was developed to integrate LUS findings: ≥ 3 B-lines corresponded to a score of 1, confluent B-lines to a score of 2, and subpleural or lobar consolidation to a score of 3. The total LUS score ranged from 0-24 per subject., Results: Among 215 enrolled subjects, 168 with LUS data and no current signs of ARDS or ICU admission (mean age 59 y, 56% male) were included. One hundred thirty-six (81%) subjects had pathologic LUS findings in ≥ 1 zone (≥ 3 B-lines, confluent B-lines, or consolidations). Markers of disease severity at baseline were higher in subjects with the composite outcome ( n = 31, 18%), including higher median C-reactive protein (90 mg/L vs 55, P < .001) and procalcitonin levels (0.35 μg/L vs 0.13, P = .033) and higher supplemental oxygen requirements (median 4 L/min vs 2, P = .001). However, LUS findings and score did not differ significantly between subjects with the composite outcome and those without, and were not associated with outcomes in unadjusted and adjusted logistic regression analyses., Conclusions: Pathologic findings on LUS were common a median of 3 d after admission in this cohort of non-ICU hospitalized subjects with COVID-19 and did not differ among subjects who experienced the composite outcome of incident ARDS, ICU admission, and all-cause mortality compared to subjects who did not. These findings should be confirmed in future investigations. The study is registered at Clinicaltrials.gov (NCT04377035)., Competing Interests: Dr Biering-Sørensen discloses relationships with Sanofi Pasteur, GE Healthcare, Amgen, and Novartis. Dr Platz discloses relationships with the National Institutes of Health and Novartis. Dr Ulrik discloses relationships with AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Teva Pharmaceutical, Orion, Novartis, Actelion, Mundipharma, Sanofi Genzyme, ALK- Abelló, and Chiesi. The remaining authors have disclosed no conflicts of interest., (Copyright © 2022 by Daedalus Enterprises.)

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., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

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., (© 2021 European Society of Cardiology.)

Early systolic lengthening and postsystolic shortening may yield prognostic information in cardiovascular high-risk groups. We aimed to investigate the prognostic potential of these patterns in patients with heart failure with reduced ejection fraction (HFrEF), and specifically if the value was greater in patients with ischemic etiology. A total of 884 patients with HFrEF (66 ± 12 years, male 73%, mean EF 28 ± 9%) underwent speckle tracking echocardiography. Of these, 61% suffered from ischemic cardiomyopathy (ICM). Patients were followed for all-cause mortality. We assessed myocardial lengthening during early systole, defined by the early systolic strain index (ESI): [-100x (peak positive strain/maximal strain)] and myocardial shortening after aortic valve closure, defined by the postsystolic strain index (PSI): [100x (postsystolic strain-peak systolic strain)/maximal strain]. During median follow-up of 3.4 [interquartile range 1.9 to 4.8] years, 132 patients (15%) died. ICM modified the relationship between ESI and all-cause mortality (P interaction = 0.008), but not for PSI (P interaction = 0.13). When assessing patients with ICM by Cox proportional hazards models, per 1% increase in ESI (HR 1.09 [1.04 to 1.15], P < 0.001) and PSI (HR 1.02 [1.01 to 1.03], P = 0.002) were associated with all-cause mortality. However, in multivariable models adjusted for clinical, invasive and echocardiographic information, only ESI was a predictor of the endpoint (HR 1.07 [1.00 to 1.13], P = 0.023). In patients with no ICM, neither ESI (HR 0.99 per 1% increase [0.90 to 1.09], P = 0.86) nor PSI (HR 1.00 per 1% increase [0.99 to 1.02], P = 0.88) were associated with all-cause mortality. Our results indicate that in HFrEF patients with ischemic etiology, the ESI may provide some information on prognosis, whereas the prognostic value of PSI is reduced. In patients with HFrEF and no prior exposure to ischemia, the prognostic value of both deformational patterns is reduced., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

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 (GLS WW ), endomyocardial (GLS Endo ), and epimyocardial (GLS Epi ) 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, GLS WW [hazard ratio (HR) 1.16, 95% confidence interval (CI) 1.02-1.31, per 1% decrease] and GLS Epi (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 GLS Epi being the only layer-specific prognosticator in males, while no GLS parameter provides independent prognostic information in females., (© 2021 European Society of Cardiology.)

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., (© 2021 Wiley Periodicals LLC.)

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.)

Aims: Colour tissue Doppler imaging (TDI) M-mode through the mitral leaflet is an easy and precise method to obtain cardiac time intervals including isovolumic contraction time (IVCT), isovolumic relaxation time (IVRT) and systolic ejection time (SET). The myocardial performance index (MPI) is defined as [(IVCT + IVRT)/SET]. Whether cardiac time intervals obtained by the TDI M-mode method can be used to predict outcome in patients with heart failure with reduced ejection fraction (HFrEF) remains unknown., Methods and Results: A total of 997 patients with HFrEF (mean age 67 ± 11 years, 74% male) underwent an echocardiographic examination including TDI. During a median follow-up of 3.4 years (interquartile range 1.9-4.8 years), 165 (17%) patients died. The risk of mortality increased by 9% per 10 ms decrease in SET [per 10 ms decrease: hazard ratio (HR) 1.09, 95% confidence interval (CI) 1.06-1.13; P < 0.001]. The association remained significant even after multivariable adjustment for clinical and echocardiographic parameters (per 10 ms decrease: HR 1.06, 95% CI 1.01-1.11; P = 0.030). The MPI was a significant predictor in an unadjusted model (per 0.1 increase: HR 3.06, 95% CI 1.16-8.06; P = 0.023). However, the association did not remain significant after multivariable adjustment. No significant associations between IVCT or IVRT and mortality were found in unadjusted nor adjusted models. Additionally, SET provided incremental prognostic information with regard to predicting mortality when added to established clinical predictors of mortality in patients with HFrEF., Conclusion: In patients with HFrEF, SET provides independent and incremental prognostic information regarding all-cause mortality., (© 2020 European Society of Cardiology.)

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: 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., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

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.)

Aims: The ratio of early mitral inflow velocity to global diastolic strain rate (E/e'sr) has recently emerged as a novel measure of left ventricular (LV) filling pressure. This new measure has demonstrated to have prognostic value superior to E/e'. This study aimed to investigate the prognostic value of E/e'sr in a large cohort of patients with heart failure with reduced ejection fraction (HFrEF) in relation to all-cause mortality., Methods: We retrospectively studied 897 HFrEF (mean age 66 ± 12 years, 73% male, 59% ischemic cardiomyopathy) patients who underwent speckle tracking echocardiography where E/e'sr along with novel and conventional echocardiographic parameters were obtained. The primary endpoint was defined as all-cause mortality., Results: During follow-up (median: 40 months IQR: 22-57), 137 (15.3%) patients died. Both E/e'sr and E/e' were significantly associated with mortality (E/e'sr: HR 1.03 95%CI [1.02-1.04], p<0.001, per 0.10m increase) and (E/e': HR 1.04 95%CI [1.02-1.06], p = 0.001, per 1unit increase). E/e'sr remained an independent predictor in a multivariable model after adjusting for age, gender, mean arterial pressure, heart rate, BMI, total cholesterol, diabetes mellitus, ischemic cardiomyopathy, LVEF, LVIDd, LVMI, LAVI, TAPSE and LV-GLS (HR 1.02 95%CI [1.01-1.03], p = 0.007) whereas E/e' did not (HR 1.01 95%CI [0.98-1.04], p = 0.57). Furthermore, E/e'sr provided incremental prognostic information beyond a model including known risk factors: age, gender, total cholesterol, mean arterial pressure, heart rate, BMI, smoking status and E/e' (Harrell's C-statistics: 0.72 (0.68-0.77) vs 0.70 (0.66-0.75), p = 0.047)., Conclusions: In HFrEF patients, E/e'sr provides independent and incremental prognostic information regarding all-cause mortality superior to E/e'., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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.)

Objective: This study compared the clinical features, cardiac structure and function evaluated by echocardiography, cardiopulmonary response to exercise and long-term clinical outcomes between patients with heart failure (HF) induced by cancer therapy (CTHF) and heart failure not induced by cancer therapy (NCTHF)., Methods: We evaluated 75 patients with CTHF and 894 with NCTHF who underwent clinically indicated cardiopulmonary exercise testing, and followed these individuals for a median of 4.5 (3.0-5.8) years, during which 187 deaths and 256 composite events (death, heart transplantation and left ventricular (LV) assistant device implantation) occurred., Results: Compared with NCTHF, patients with CTHF were younger, with lower prevalence of cardiovascular comorbidities, higher LV ejection fraction (LVEF), but similar global longitudinal strain. LV diastolic function (higher E/e' ratio) and compliance (higher end-diastolic pressure/LV end-diastolic volume index ratio) were worse in CTHF and were both associated with adverse outcomes. Despite a favourable clinical profile, peak VO 2 and VE/VCO 2 slope were similarly impaired in CTHF and NCTHF. In multivariable Cox regression analysis including clinical characteristics, cardiopulmonary exercise testing variables and LVEF, CTHF was associated with a significantly higher risk of death (HR 2.64; 95% CI 1.53 to 4.55; p=0.001) and composite events (HR 1.79; 95% CI 1.10 to 2.91; p=0.019) compared with NCTHF., Conclusions: CTHF is characterised by a distinct clinical profile, better LVEF but worse LV diastolic properties, and similarly impaired global longitudinal strain, functional capacity and ventilatory efficiency. Accounting for differences in clinical characteristics, CTHF was associated with worse long-term prognosis than NCTHF., Competing Interests: Competing interests: AMS reports receiving research support from Novartis and Bellerophron, and consulting fees from Philips Ultrasound. The other authors have nothing to disclose., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

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.

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.

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: The relationship between ideal cardiovascular health reflected in the cardiovascular health score (CVHS) and valvular heart disease is not known. The purpose of this study was to determine the association of CVHS attainment through midlife to late life with aortic stenosis prevalence and severity in late life., Methods and Results: The following 6 ideal cardiovascular health metrics were assessed in ARIC (Atherosclerosis Risk in Communities) Study participants at 5 examination visits between 1987 and 2013 (visits 1-4 in 1987-1998 and visit 5 in 2011-2013): smoking, body mass index, total cholesterol, blood pressure, physical activity, and blood glucose. Percentage attained CVHS was calculated in 6034 participants as the sum of CVHS at each visit/the maximum possible score. Aortic stenosis was assessed by echocardiography at visit 5 on the basis of the peak aortic valve velocity. Aortic stenosis was categorized sclerosis, mild stenosis, and moderate-to-severe stenosis. Mean age was 76±5 years, 42% were men, and 22% were black. Mean percentage attained CVHS was 63±14%, and the prevalence of aortic stenosis stages were 15.9% for sclerosis, 4.3% for mild stenosis, and 0.7% for moderate-to-severe stenosis. Worse percentage attained CVHS was associated with higher prevalence of aortic sclerosis ( P <0.001 for trend), mild stenosis ( P <0.001), and moderate-to-severe stenosis ( P =0.002), adjusting for age, sex, and race., Conclusions: Greater attainment of ideal cardiovascular health in midlife to late life is associated with a lower prevalence of aortic sclerosis and stenosis in late life in a large cohort of older adults., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: This study aimed to compare the independent and incremental prognostic value of peak oxygen consumption (VO 2 ) and minute ventilation/carbon dioxide production (VE/VCO 2 ) in heart failure (HF) with preserved (HFpEF), midrange (HFmEF), and reduced (HFrEF) ejection fraction (LVEF)., Methods and Results: In 195 HFpEF (LVEF ≥50%), 144 HFmEF (LVEF 40-49%), and 630 HFrEF (LVEF <40%) patients, we assessed the association of cardiopulmonary exercise testing variables with the composite outcome of death, left ventricular assist device implantation, or heart transplantation (256 events; median follow-up of 4.2 years), and 2-year incident HF hospitalization (244 events). In multivariable Cox regression analysis, greater association with outcomes in HFpEF than HFrEF were noted with peak VO 2 (HR [95% confidence interval]: 0.76 [0.67-0.87] versus 0.87 [0.83-0.90] for the composite outcome, P interaction =0.052; 0.77 [0.69-0.86] versus 0.92 [0.88-0.95], respectively for HF hospitalization, P interaction =0.003) and VE/VCO 2 slope (1.11 [1.06-1.17] versus 1.04 [1.03-1.06], respectively for the composite outcome, P interaction =0.012; 1.10 [1.05-1.15] versus 1.04 [1.03-1.06], respectively for HF hospitalization, P interaction =0.019). In HFmEF, peak VO 2 and VE/VCO 2 slope were associated with the composite outcome (0.79 [0.70-0.90] and 1.12 [1.05-1.19], respectively), while only peak VO 2 was related to HF hospitalization (0.81 [0.72-0.92]). In HFpEF and HFrEF, peak VO 2 and VE/VCO 2 slope provided incremental prognostic value beyond clinical variables based on the C-statistic, net reclassification improvement, and integrated diagnostic improvement, with models containing both measures demonstrating the greatest incremental value., Conclusions: Both peak VO 2 and VE/VCO 2 slope provided incremental value beyond clinical characteristics and LVEF for predicting outcomes in HFpEF. Cardiopulmonary exercise testing variables provided greater risk discrimination in HFpEF than HFrEF., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

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.)

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.)