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AimsWhile clinical trials have suggested that a high ventricular rate is associated with increased risk of heart failure (HF) and mortality, all-comers studies are warranted.ObjectiveTo assess 1-year risk of new-onset diagnosed HF and all-cause mortality among rate-control treated patients presenting with atrial fibrillation (AF) on an electrocardiogram (ECG) according to ventricular rate.Methods and resultsECGs recorded at the Copenhagen General Practitioners Laboratory (2001–15) were used to identify patients with AF. Multivariate Cox proportional hazard regression models were used to compare risk of new-onset HF and all-cause mortality after first ECG presenting with AF according to ventricular rate on ECG [ 110 beats per minute (bpm)]. We identified 7408 patients in treatment with rate control drugs at time of first ECG presenting with AF [median age 78 years (Q1,Q3 = 70–85 years)], 45.8% male, median ventricular rate 83 bpm, (Q1,Q3 = 71–101 bpm)]. During 1-year follow-up, 666 (9.0%) of all patients with AF developed HF and 858 (11.6%) died. Patients with AF ventricular rates 100–110 bpm and >110 bpm had a hazard ratio (HR) of 1.46 (CI: 1.10–1.95) and 2.41 (CI: 1.94–3.00) respectively for new-onset HF, compared with 60–79 bpm. Similarly, patients with AF ventricular rates 100–110 bpm and >110 bpm had a HR of 1.44 (CI: 1.13–1.82) and 1.34 (CI: 1.08–1.65) respectively for all-cause mortality, compared with 60–79 bpm.ConclusionsVentricular rates ≥100 bpm among patients presenting with AF on ECG in treatment with rate control drugs were associated with greater risk of both new-onset HF and all-cause mortality. Aims While clinical trials have suggested that a high ventricular rate is associated with increased risk of heart failure (HF) and mortality, all-comers studies are warranted. Objective To assess 1-year risk of new-onset diagnosed HF and all-cause mortality among rate-control treated patients presenting with atrial fibrillation (AF) on an electrocardiogram (ECG) according to ventricular rate. Methods and results ECGs recorded at the Copenhagen General Practitioners Laboratory (2001-15) were used to identify patients with AF. Multivariate Cox proportional hazard regression models were used to compare risk of new-onset HF and all-cause mortality after first ECG presenting with AF according to ventricular rate on ECG [ 110 beats per minute (bpm)]. We identified 7408 patients in treatment with rate control drugs at time of first ECG presenting with AF [median age 78 years (Q1,Q3 = 70-85 years)], 45.8% male, median ventricular rate 83 bpm, (Q1,Q3 = 71-101 bpm)]. During 1-year follow-up, 666 (9.0%) of all patients with AF developed HF and 858 (11.6%) died. Patients with AF ventricular rates 100-110 bpm and >110 bpm had a hazard ratio (HR) of 1.46 (CI: 1.10-1.95) and 2.41 (CI: 1.94-3.00) respectively for new-onset HF, compared with 60-79 bpm. Similarly, patients with AF ventricular rates 100-110 bpm and >110 bpm had a HR of 1.44 (CI: 1.13-1.82) and 1.34 (CI: 1.08-1.65) respectively for all-cause mortality, compared with 60-79 bpm. Conclusions Ventricular rates >= 100 bpm among patients presenting with AF on ECG in treatment with rate control drugs were associated with greater risk of both new-onset HF and all-cause mortality.

Background Employment is important for physical and mental health and self-esteem and provides financial independence. However, little is known on the prognostic value of employment status prior to admission with acute myocardial infarction (MI). Methods and results Using Danish nationwide registries, all patients between 18 and 60 years with a first-time MI admission (2010–2018) and alive at discharge were included. Rates of all-cause mortality and recurrent MI according to workforce attachment at the time of the event was compared using multivariable Cox regression. Of the 16 060 patients included in the study, 3520 (21.9%) patients were not part of the workforce. Patients who were not part of the workforce were older (52 vs. 51 years), less often men (63% vs. 77%), less likely to have higher education, more often living alone (47% vs. 29%), and more often had comorbidities, including heart failure, atrial fibrillation, hypertension, diabetes, chronic kidney disease, and chronic obstructive pulmonary disease. The absolute 5-year risk of death was 3.3% and 12.8% in the workforce and non-workforce group, respectively. The corresponding rates of recurrent MI were 7.5% and 10.9%, respectively. In adjusted analyses, not being part of the workforce was associated with a significantly higher rate of all-cause mortality [HR: 2.39 (95% CI: 2.01–2.83)] and recurrent MI [1.36 (1.18–1.57)]. Conclusion Among patients of working age who were admitted with MI and alive at discharge, not being part of the workforce was associated with a higher long-term rate of all-cause mortality and recurrent MI.

Background Peak atrial longitudinal strain (PALS) has previously been shown to predict cardiovascular morbidity and mortality in the general population. However, the impact of cardiovascular risk factors on PALS over a decade in participants from the general population is unknown. Purpose The aim of this study was to investigate the impact of cardiovascular risk factors (age, sex, mean arterial pressure (MAP), body mass index (BMI), smoking, total plasma cholesterol, HbA1c, physical activity level, socioeconomic and psychosocial status) on change in PALS over a 10-year period in participants from the general population. Methods The present study included a total of 208 (mean age 61±14 years, 60% female) participants from the general population, who underwent a health examination including two-dimensional speckle tracking echocardiography of the left atrium at baseline examination and follow-up examination. The median time between the examinations was 10 years (interquartile range, 10.2–10.7 years). PALS was calculated as the average from the three apical views. Crude and multivariable linear regression analyses were performed to determine the impact of cardiovascular risk factors on the change in PALS. The multivariable regression model was adjusted for age, sex, MAP, BMI, smoking, total plasma cholesterol, HbA1c, heart rate, eGFR, proBNP and previous ischemic heart disease. All analyses were adjusted for baseline value of PALS (baseline value). Restricted cubic spline curves were constructed to illustrate the relationship between the PALS and continuous cardiovascular risk factors. Results During 10-year follow-up, the average decrease in PALS was 4±16%. In the crude regression model increasing age (standardized = −0.27, p In the multivariable regression model, age (standardized = −0.19, p=0.001), BMI (standardized = −0.18, p=0.001) and smoking (standardized = −0.15, p=0.003) remained independent predictors of an accelerated decrease in PALS. Conclusion In the general population, increasing age, BMI and smoking were independently associated with an accelerated decrease in PALS over a decade. Funding Acknowledgement Type of funding sources: None.

Background Current guidelines, on implantable cardioverter defibrillator (ICD), recommend implantation in patients with an expected survival beyond one year. Information on risk of all-cause mortality among ICD recipients with chronic obstructive pulmonary disease (COPD) according to severity of COPD is lacking. Purpose We examined the association between the severity of COPD and risk of all-cause mortality within one year after first-time ICD implantation. Methods We identified patients ≥18 years old undergoing first-time ICD implantation with COPD using Danish nationwide registries (1 January 2000 to 31 December 2018). All patients were eligible for one-year follow-up. We used concomitant COPD-related pharmacotherapy six months prior to ICD implantation and COPD hospitalisations one year prior to ICD implantation to determine severity of COPD from mild to very severe according to Table 1. Multivariable Cox regression was used to assess risk of one-year all-cause mortality according to severity of COPD. Severity of COPD was adjusted for sex, age, year of implantation, primary prevention, type of ICD, history of atrial fibrillation, stroke, peripheral artery disease, diabetes, cancer, chronic renal disease, and dialysis. Results The study population included 1,536 patients with first-time ICD and COPD. The median age was 69.5 years [25th-75th percentile 63.5–74.3 years], and the majority of patients were males (79.4%). Of these, 896 (58.3%) received an ICD for primary prevention, and 485 (31.6%) had cardiac resynchronisation therapy device with defibrillator (CRT-D). In total, 1,348 (87.8%) patients were diagnosed with heart failure. Patients were grouped according to severity of COPD from mild to very severe: Group 1 (N=666), Group 2 (N=72), Group 3 (N=149), Group 4 (N=445), and Group 5 (N=204). Overall, 154/1,536 (10.0%) ICD recipients with COPD died within one year after first-time ICD implantation. No difference in sex and comorbidities was identified according to the five groups of COPD severity. However, ICD recipients with mild intermittent COPD (Group 1) were the youngest (68.3 years [61.8–73.0 years]). According to our multivariable cox regression in Figure 1, patients with very severe COPD (Group 5) were associated with increased risk of all-cause mortality within one year after first-time ICD implantation (adjusted hazard ratio [HR] 1.90 [95% confidence interval [CI]: 1.21–2.98]), compared with mild intermittent COPD (Group 1). The most common causes of death within one year after ICD implantation were attributed to cardiovascular diseases 95/154 (61.7%), respiratory diseases 15/154 (9.7%), and endocrine disorders 12/154 (7.8%). Conclusion In this nationwide study, very severe chronic obstructive pulmonary disease was associated with increased risk of all-cause mortality within one year after first-time implantation of implantable cardioverter defibrillator. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Independent Research Fund Denmark

Background The benefit of cardiac implantable electronic devices (CIEDs) is challenged by the risk of procedure-related complications and lead explantation. Whether patient comorbidity burden is associated with risk of lead explantation Purpose We assessed the risk of lead explantation and its association with comorbidity burden within 6 months after first-time CIED implantation. Methods The study population comprised patients ≥18 years old with first-time CIED implantation (i.e., pacemaker [PM], implantable cardioverter defibrillator [ICD], and cardiac resynchronisation therapy with defibrillator [CRT-D] or without [CRT-P]) using Danish nationwide registries including the Danish Pacemaker and ICD registry (1 January 2000 to 30 June 2018). Patients were followed from their first-time CIED implantation and 6 months forward. Patient comorbidity burden was categorised in four groups according to the Charlson Comorbidity Index (CCI) score: 0 (none), 1–2 (mild), 3–4 (moderate), and ≥5 (severe). Multivariable cause-specific Cox regression was performed to assess risk of lead explantation according to comorbidity burden, with death as competing risk. Comorbidity burden was adjusted for sex, age, type of CIED, and body mass index categories. Results We identified 73,491 patients with first-time CIED implantation including 55,733 (75.8%) with PM, 11,351 (15.5%) with ICD, 2,989 (4.1%) with CRT-P, and 3,418 (4.7%) with CRT-D. In total, 1,049 (1.4%) patients underwent lead explantation. The median age of the study population was 75.1 years [25th-75th percentile 66.2–82.5 years], and 62.1% were male. Patients undergoing lead explantation had higher median CCI score, compared with those not undergoing lead explantation (2 [1–3] and 1 [0–3], respectively). The median age and distribution of sex were similar in both groups. In the multivariable Cox regression model (Figure 1), an increase in patient comorbidity burden was associated with higher hazard ratio [HR] of lead explantation, compared with CCI score 0 (CCI score 1–2: HR=1.38 [95% confidence interval [CI]: 1.12–1.69], CCI score 3–4: HR=1.61 [95% CI: 1.28–2.03], and CCI score ≥5: HR=1.60 [95% CI: 1.25–2.05]). Conclusion Risk of lead explantation within 6 months after first-time implantation of cardiac implantable electronic device was 1.4% and associated with higher comorbidity burden. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Independent Research Fund Denmark

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.

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. Clinicaltrials.gov ID: NCT04377035.

Aims Left atrial enlargement predicts incident atrial fibrillation (AF). However, the prognostic value of peak atrial longitudinal strain (PALS) for predicting incident AF in participants from the general population is currently unknown. Our aim was to investigate if PALS can be used to predict AF and ischaemic stroke in the general population. Methods and results A total of 400 participants from the general population underwent a health examination, including two-dimensional speckle tracking echocardiography of the left atrium. The primary endpoint was incident AF at follow-up. All participants with known AF and prior stroke at baseline were excluded (n = 54). The secondary endpoint consisted of the composite of AF and ischaemic stroke. During a median follow-up of 16 years, 36 participants (9%) were diagnosed with incident AF and 30 (7%) experienced an ischaemic stroke, resulting in 66 (16%) experiencing the composite outcome. PALS was a univariable predictor of AF [per 5% decrease: hazard ratio (HR) 1.42; 95% confidence interval (CI) (1.19–1.69), P Conclusion In a low-risk general population, PALS provides novel prognostic information on the long-term risk of AF and ischaemic stroke in participants aged

BACKGROUND Studies suggest cardiac time intervals to be associated with cardiac ischemia. A novel method to assess cardiac time intervals by tissue Doppler echocardiography has been proposed. Cardiac time intervals can assess the myocardial performance index (MPI), which quantifies the proportion of time spent contributing effective myocardial work. We hypothesized that MPI associates with coronary artery lesions detected by cardiac computed tomography (CT) in patients suspected of coronary artery disease (CAD). METHODS We investigated patients referred for cardiac CT under suspicion of CAD who had an echocardiogram performed. Curved m-mode tissue Doppler imaging was used to measure cardiac time intervals and MPI. The outcome was coronary artery lesions, defined as a calcium score > 400 and/or coronary artery stenosis (>70% luminal narrowing). Logistic regression was applied with multivariable models including: (a) SCORE chart risk factors and (b) SCORE chart risk factors, body mass index, dyslipidemia, familial history of CAD, diabetes mellitus, LVEF, and left ventricular mass index. RESULTS Of 404 patients, 41 (10%) had a coronary artery lesion. Overall, 42% were male, mean age was 58 years, and LVEF was 58%. Patients with coronary artery lesions exhibited higher MPI than those without (0.52 vs. 0.44, P

AimTo determine the risk of adverse outcomes across the spectrum of glycated haemoglobin (HbA1c) levels among hospitalized COVID-19 patients with and without diabetes.Materials and methodsDanish nationwide registries were used to study the association between HbA1c levels and 30-day risk of all-cause mortality and the composite of severe COVID-19 infection, intensive care unit (ICU) admission and all-cause mortality. The study population comprised patients hospitalized with COVID-19 (3 March 2020 to 31 December 2020) with a positive polymerase chain reaction (PCR) test and an available HbA1c ≤ 6 months before the first positive PCR test. All patients had at least 30 days of follow-up. Among patients with diabetes, HbA1c was categorized as 64 mmol/mol. Among patients without diabetes, HbA1c was stratified into ResultsWe identified 3295 hospitalized COVID-19 patients with an available HbA1c (56.2% male, median age 73.9 years), of whom 35.8% had diabetes. The median HbA1c was 54 and 37 mmol/mol among patients with and without diabetes, respectively. Among patients with diabetes, the standardized absolute risk difference of the composite outcome was higher with HbA1c 64 mmol/mol (15.1% [95% CI 6.2% to 24.0%]), compared with HbA1c 59 to 64 mmol/mol (reference). Among patients without diabetes, the standardized absolute risk difference of the composite outcome was greater with HbA1c ConclusionsPatients with COVID-19 and HbA1c 64 mmol/mol had a higher associated risk of the composite outcome. Similarly, among patients without diabetes, varying HbA1c levels were associated with higher risk of the composite outcome.

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. Clinicaltrials.gov ID: NCT04377035.

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 cur-rent 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

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.

Acute respiratory distress syndrome (ARDS) is the primary complication observed in Coronavirus disease-2019 (COVID-19)–related deaths ([1][1]). Additionally, studies have found cardiac biomarkers to be increased in a significant proportion of patients, emphasizing COVID-19–related cardiac injury

Aims Colour tissue Doppler imaging (TDI) M-mode through the mitral leaflet is an easy and precise method to obtain cardiac time intervals including the isovolumic contraction time (IVCT), isovolumic relaxation time (IVRT), and ejection time (ET). The myocardial performance index (MPI) was defined as [(IVCT + IVRT)/ET]. Our aim was to investigate if cardiac time intervals can be used to predict atrial fibrillation (AF) in the general population. Methods and results A total of 1915 participants from the general population underwent a health examination including TDI echocardiography. The primary endpoint was AF, and the secondary endpoint was complicated AF as assessed by the occurrence of either stroke or heart failure (HF) after the diagnosis of AF. Participants with known AF were excluded (n = 54). During a median follow-up of 11 years, 166 participants (9%) were diagnosed with AF and of these 44 participants (27%) developed HF or stroke. Assessing the association between IVCT and incident AF, the risk increased with 27% per 10 ms increase in IVCT [per 10 ms increase: hazard ratio (HR) 1.27, 95% confidence interval (CI) (1.17–1.38); P Conclusion In the general population, the IVCT provides novel and independent prognostic information on the long-term risk of AF. Additionally, the IVCT can identify persons in risk of complicated AF.