Right Ventricular Function in Arrhythmogenic Right Ventricular Cardiomyopathy: Potential Value of Strain Echocardiography.

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.

Parameters associated with improvement of systolic function in patients with heart failure.

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 (ß-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 (ß-coef 0.25, p<0.001), higher tricuspid annular plane systolic excursion (ß-coef 0.09, p=0.018), smaller left ventricular internal dimension in diastole (ß-coef -0.15, p=0.011), lower E-wave/A-wave ratio (ß-coef -0.13, p=0.003), higher heart rate (ß-coef 0.18, p<0.001) and absence of ischaemic cardiomyopathy (ß-coef -0.11, p=0.010) and diabetes (ß-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.

Link between myocardial deformation phenotyping using longitudinal and circumferential strain and risk of incident heart failure and cardiovascular death.

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.

Cardiac Characteristics of the First Two Waves of COVID-19 in Denmark and the Prognostic Value of Echocardiography: The ECHOVID-19 Study.

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.

Myocardial Work in Patients Hospitalized With COVID-19: Relation to Biomarkers, COVID-19 Severity, and All-Cause Mortality.

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.

Normal Values for Myocardial Work Indices Derived From Pressure-Strain Loop Analyses: From the CCHS.

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.

Lung ultrasound findings following COVID-19 hospitalization: A prospective longitudinal cohort study.

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.

Cardiac arrhythmias six months following traumatic spinal cord injury.

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.

Lung ultrasound findings in hospitalized COVID-19 patients in relation to venous thromboembolic events: the ECHOVID-19 study.

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.

Lung Ultrasound Findings Associated With COVID-19 ARDS, ICU Admission, and All-Cause Mortality.

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).

Measures of left atrial function predict incident heart failure in a low-risk general population: the Copenhagen City Heart Study.

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.

Left atrial strain predicts incident atrial fibrillation in the general population: the Copenhagen City Heart Study.

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.

Recovery of cardiac function following COVID-19 - ECHOVID-19: a prospective longitudinal cohort study.

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.

Prognostic value of right ventricular echocardiographic measures in patients with heart failure with reduced ejection fraction.

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.

Layer-specific global longitudinal strain and the risk of heart failure and cardiovascular mortality in the general population: the Copenhagen City Heart Study.

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.

Noninvasive Hemodynamic Evaluation at Rest in Heart Failure with Preserved Ejection Fraction.

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.

The prognostic value of myocardial deformational patterns on all-cause mortality is modified by ischemic cardiomyopathy in patients with heart failure.

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.

Prognostic value of left ventricular mitral annular longitudinal displacement obtained by tissue Doppler imaging in patients with heart failure with reduced ejection fraction.

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.

Left ventricular systolic ejection time is an independent predictor of all-cause mortality in heart failure with reduced ejection fraction.

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.