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.

COPD: pulmonary vascular volume associated with cardiac structure and function.

BACKGROUND: Early recognition of cardiac dysfunction in patients with chronic obstructive pulmonary disease (COPD) may prevent future cardiac impairment and improve prognosis. Quantitative assessment of subsegmental and segmental vessel volume by Computed Tomographic (CT) imaging can provide a surrogate of pulmonary vascular remodeling. We aimed to examine the relationship between lung segmental- and subsegmental vessel volume, and echocardiographic measures of cardiac structure and function in patients with COPD. METHODS: We studied 205 participants with COPD, included in a large cohort study of cardiovascular disease in COPD patients. Participants had an available CT scan and echocardiogram. Artificial intelligence (AI) algorithms calculated the subsegmental vessel fraction as the vascular volume in vessels below 10 mm2 in cross-sectional area, indexed to total intrapulmonary vessel volume. Linear regressions were conducted, and standardized ß-coefficients were calculated. Scatterplots were created to visualize the continuous correlations between the vessel fractions and echocardiographic parameters. RESULTS: We found that lower subsegmental vessel fraction and higher segmental vessel volume were correlated with higher left ventricular (LV) mass, LV diastolic dysfunction, and inferior vena cava (IVC) dilatation. Subsegmental vessel fraction was correlated with right ventricular (RV) remodeling, while segmental vessel fraction was correlated with higher pulmonary pressure. Measures of LV mass and right atrial pressure displayed the strongest correlations with pulmonary vasculature measures. CONCLUSION: Pulmonary vascular remodeling in patients with COPD, may negatively affect cardiac structure and function. AI-identified remodeling in pulmonary vasculature may provide a tool for early identification of COPD patients at higher risk for cardiac impairment.

The clinical application of longitudinal layer specific strain as a diagnostic and prognostic instrument in ischemic heart diseases: A systematic review and meta-analysis.

Background: 2-dimensional Speckle-Tracking Echocardiography, to obtain longitudinal layer specific strain (LSS), has recently emerged as a novel and accurate non-invasive imaging technique for diagnosis as well as for prediction of adverse cardiac events. This systematic review and meta-analysis aimed to give an overview of the possible clinical implication and significance of longitudinal LSS. Methods: We conducted a systematic review and meta-analysis with all the studies involving layer specific strain in patients with ischemic heart disease (IHD). Of 40 eligible studies, 9 met our inclusion criteria. Studies that were included either investigated the prognostic value (n = 3) or the diagnostic value (n = 6) of longitudinal LSS. Results: The pooled meta-analysis showed that longitudinal LSS is a significant diagnostic marker for coronary artery disease (CAD) in patients with IHD. Endocardial LSS was found to be a good diagnostic marker for CAD in IHD patients (OR: 1.28, CI95% [1.11-1.48], p < 0.001, per 1% decrease). Epicardial (OR: 1.34, CI95% [1.14-1.56], p < 0.001, per 1% decrease), Mid-Myocardial (OR: 1.24, CI95% [1.12-1.38], p < 0.001, per 1% decrease) and endocardial (OR: 1.21, CI95% [1.09-1.35], p < 0.001, per 1% decrease) LSS all entailed diagnostic information regarding CAD, with epicardial LSS emerging as the superior diagnostic marker for CAD in patients with SAP. Endocardial LSS proved to be the better diagnostic marker of CAD in patients with non-ST elevation acute coronary syndrome (NSTE-ACS). LSS was shown to be a good prognostic maker of adverse cardiac events in IHD patients. Two studies found endocardial circumferential strain to be the good predictor of outcome in CAD patients and when added to baseline characteristics. Epicardial LSS emerged as best predictor in acute coronary syndrome (ACS) patients. Conclusion: In patients with SAP, epicardial LSS was the stronger diagnostic marker while in NSTE-ACS patients, endocardial LSS was the stronger diagnostic marker. In addition, endocardial circumferential strain is the better predictor of adverse outcome in CAD patients whilst in ACS patients, epicardial LSS was found to be a better predictor of outcome.

Association Between Pulmonary Vascular Volume and Cardiac Structure and Function in Patients With Atrial Fibrillation.

Pulmonary vascular abnormalities, quantified from computed tomography scans, have frequently been observed in patients with pulmonary diseases. However, little is known about pulmonary vascular changes in patients with cardiac disease. Thus, we aimed to examine the cardiopulmonary relation in patients with atrial fibrillation (AF) by comparing pulmonary vascular volume (PVV) to echocardiographic measures and AF severity. A total of 742 patients (median age 63 years, 70% men) who underwent ablation for AF were included. Preprocedural cardiac computed tomography was used to measure the total and small-vessel PVV, along with the pulmonary artery to aorta ratio and the degree of emphysema. The association between PVV and echocardiographic parameters was evaluated using a multivariable linear regression analysis. Lower total and small-vessel PVV were associated with more impaired measures of cardiac structure and function, including but not limited to left ventricular ejection fraction and peak atrial longitudinal strain. Patients with reduced total and small-vessel PVV had higher odds of having persistent AF than paroxysmal AF in the unadjusted logistic regression analyses. However, after clinical and echocardiographic adjustments, only reduced small-vessel PVV remained independently associated with persistent AF (odds ratio 1.90, 95% confidence interval 1.26 to 2.87, p = 0.002). In conclusion, pulmonary vascular remodeling is associated with persistent AF and with more impaired measures of cardiac structure and function, providing further insights into heart-lung interactions in this patient group.

Left atrial contractile strain predicts recurrence of atrial tachyarrhythmia after catheter ablation.

BACKGROUND: Despite improvement in treatment strategies of atrial fibrillation (AF), a considerable number of patients still experience recurrence of atrial tachyarrhythmia (ATA) following catheter ablation (CA). This study aimed to investigate the prognostic value of left atrial (LA) deformation analysis in a large group of patients undergoing CA for AF. METHODS: This study included 678 patients with AF. Echocardiography including two-dimensional speckle tracking echocardiography (2DSTE) was performed in all patients prior to CA. Logistic regression analysis was used to assess the association between ATA recurrence and LA strain during reservoir phase (LASr), LA strain during contraction phase (LASct), and LA strain during conduit phase (LAScd). RESULTS: During one-year follow-up, 274 (40%) experienced ATA recurrence. Median age of the included study population was 63.2 years (IQR: 55.5, 69.5) and 485 (72%) were male. Patients with recurrence had lower LASr (22.6% vs. 25.1%, p = 0.001) and LASct (10.7% vs. 12.4%, p < 0.001). No difference in LAScd was observed. After adjusting for potential clinical and echocardiographic confounders LASr (OR = 1.04, CI95% [1.01; 1.07], p = 0.015, per 1% decrease) and LASct (OR = 1.06, CI95% [1.02; 1.11], p = 0.007, per 1% decrease) remained independent predictors of recurrence. However, in patients with a normal-sized LA (LA volume index<34 mL/m2), only LASct remained an independent predictor of recurrence (OR = 1.07, CI95% [1.01; 1.12], p = 0.012, per 1% decrease). CONCLUSION: In patients undergoing CA for AF, LA deformation analysis by 2DSTE could be of use in risk stratification in clinical practice regarding ATA recurrence, even in patients with a normal-sized LA.

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).

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 and reference ranges for left atrial strain by speckle-tracking echocardiography: the Copenhagen City Heart Study.

AIMS: Left atrial (LA) function assessed by two-dimensional speckle-tracking echocardiography has shown increasing clinical and prognostic significance. We sought to establish age- and sex-based normative values of LA strain in the general population and to assess the prognostic yield of lower limits of normality of LA strain in relation to future atrial fibrillation (AF). METHODS AND RESULTS: We determined normative values of peak atrial longitudinal strain (PALS), peak atrial contraction strain (PACS), and LA strain during the conduit phase (LACS) in 1641 healthy participants included in the fifth Copenhagen City Heart Study. In a secondary analysis, a validation cohort of 2016 participants, regardless of health status, were included to assess the prognostic value of the established reference values. In the healthy cohort, median age was 46 years (interquartile range 32-57), 62% were female. Median PALS, PACS, and LACS and corresponding limits of normality in the healthy participants were 39.4% (23.0-67.6%), 15.5% (6.4-28.0%), and 23.7% (8.8-44.8%), respectively. There was a tendency of lower values of PALS and LACS in males and older participants, while PACS tended to increase with advancing age. The established lower limits of normality showed high specificity (range 93-94%) regarding future AF, implying a low risk of developing AF in participants with LA strain above the lower limits of normality in their respective sex and age group. CONCLUSION: We report normal values for LA strain stratified by sex and age. The lower limits of normality showed high specificity regarding future AF.

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.

Longitudinal change in cardiac structure and function following acute coronary syndrome according to culprit coronary artery lesion.

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

Change in global longitudinal strain following acute coronary syndrome and subsequent risk of heart failure.

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

Usefulness of left atrial speckle tracking echocardiography in predicting recurrence of atrial fibrillation after radiofrequency ablation: a systematic review and meta-analysis.

The usefulness of peak atrial longitudinal strain (PALS) in identifying patients at high risk of atrial fibrillation (AF) recurrence after radiofrequency ablation (RFA) has been investigated in several small AF populations. The aim of this systematic review and meta-analysis was to investigate whether PALS predicts recurrence of AF after RFA treatment. MEDLINE, EMBASE and the Cochrane Library were searched. Studies investigating the value of PALS in predicting successful RFA in AF patients were selected. Patients underwent echocardiography prior to RFA. Risk of bias was evaluated using the Quality in Prognosis Studies (QUIPS) Tool. Twelve studies and a total of 1025 patients suffering from paroxysmal or persistent AF were included. Odds ratios (OR) were assessed in a random and fixed effects model for univariable and multivariable pooled analyses respectively. PALS was found to be a significant predictor of AF recurrence after RFA across study populations (Univariable: OR: 1.17, CI95% [1.03-1.34], p = 0.018, per 1% decrease) (Multivariable: OR: 1.16, CI95% [1.09-1.24], p < 0.001, per 1% decrease). Patients with recurrence had significantly lower PALS prior to RFA than patients who maintained sinus rhythm (15.7 ± 5.7% vs. 23.0 ± 7.0%, p = 0.016). A pooled analysis of weighted mean differences (WMD) also showed a significant difference in PALS between the two groups (WMD: - 6.57, CI95% [- 8.49: - 4.65], p < 0.001). Lower values of PALS are associated with an increased risk of AF recurrence after RFA. PALS provides prognostic value in clinical practice.

Echocardiographic abnormalities and predictors of mortality in hospitalized COVID-19 patients: the ECHOVID-19 study.

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.