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Postsystolic shortening (PSS) by speckle-tracking echocardiography (STE) is a marker of myocardial ischemia and may improve diagnostic strategy. We sought to evaluate if PSS is associated with the coronary artery calcium score (CACS) and stenosis by computed tomography angiography (CTA) in patients with suspected stable angina pectoris (SAP). We retrospectively studied 437 SAP patients (age 58 ± 11 years, 41% male) who underwent STE, evaluation of CACS and assessment of significant stenosis (≥ 50%) by CTA. The postsystolic index (PSI) was defined as follows: 100x([peak negative strain cardiac cycle − peak negative strain systole])/peak negative strain cardiac cycle. A wall had PSS if any segment within the wall had a PSI ≥ 20%. We defined categories for walls with PSS: 0, 1, 2 and ≥ 3, and CACS: 0, 1–100, 101–400 and > 400. Each additional wall with PSS was associated with a 43% relative increase in CACS (95%CI +9% to +87%, P = 0.010), while each 1% absolute increase in the PSI was associated with a 9% relative increase in CACS (95%CI +1% to +18%, P = 0.031). Walls with PSS (OR 1.81 per 1 wall increase, 95%CI 1.27–2.59, P = 0.001) and the PSI (OR 1.12 per 1% increase, 95%CI 1.04–1.21, P = 0.004) were associated with the occurrence of CACS > 400. Additionally, walls with PSS (OR 1.53 per 1 wall increase, 95%CI 1.21–1.93, P

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

Background When the left ventricle pressure rises during early systole, myocardial fibres with reduced contractility tend to stretch instead of shortening. This interval is known as duration of early systolic lengthening (DESL). We sought to investigate if DESL provides prognostic information on cardiovascular events. Methods and results In this prospective study we included 1210 participants from a low-risk general population who underwent speckle tracking echocardiography (men 41%, mean age 56 years, SD 16). Primary endpoints were incident heart failure (HF), myocardial infarction (MI), and cardiovascular death (CVD). We defined DESL as time from onset of Q-wave on the electrocardiogram to peak positive systolic strain. In addition, we assessed the ratio between DESL and duration of cardiac systole, DESLsystole. During median follow-up of 16 years, 90 (7%) developed HF, 50 (4%) MI, and 70 (6%) experienced CVD. Both DESL [hazard ratio (HR) 1.58 95%CI 1.16–2.15, P = 0.004 per 10 ms increase] and DESLsystole (HR 1.74 95%CI 1.24–2.47, P = 0.001 per 1% increase) were predictors of HF. Similarly, DESL (HR 1.40 95%CI 1.09–1.78, P = 0.007 per 10 ms increase) and DESLsystole (HR 1.58 95%CI 1.01–2.49, P = 0.047 per 1% increase) were predictors of MI. No associations were found with CVD. After adjusting for clinical and echocardiographic parameters, the associations remained significant. DESLsystole was superior to systolic echocardiographic parameters for predicting HF (P = 0.012). Conclusion DESL and the novel index of DESLsystole provide independent and novel prognostic information on the risk of HF and MI in the general population. Evaluation of DESL should be explored in future echocardiographic studies.

Paroxysmal atrial fibrillation (PAF) may be the cause of a substantial part of cryptogenic strokes (CS). Echocardiography could assist risk stratification for PAF to select patients in need of prolonged rhythm monitoring. We aimed to assess the value of left atrial (LA) strain and a revised diastolic dysfunction (DDF) model with LA strain for predicting PAF. This was a prospective study of 56 CS patients who had a cardiac monitor implanted for 3 year monitoring for PAF, and an echocardiogram performed prior to monitoring. Conventional echocardiography, global longitudinal strain (GLS) and LA strain were performed. LA speckle tracking provided the LA reservoir strain (LAs). Patients were stratified into high versus low LAs by ROC curves (28.2%), and this cut-off was used to refine DDF grading. During follow-up of median 20 months, 13 (23%) patients were diagnosed with PAF. No conventional echocardiographic parameters differed between patients who developed PAF and those without PAF. However, LAs was significantly impaired in PAF patients (LAs: 30 vs. 27% for non-PAF and PAF, p = 0.046). Low LAs significantly predicted PAF independent of LA volume and GLS [OR 5.88 (1.30; 26.55), p = 0.021]. Revised DDF grading significantly predicted PAF, even when adjusted for the CHADS2 risk-score (OR 1.88 [1.01;3.50], per increase in DDF grade, p for trend = 0.047), which was not the case for conventional DDF grading. In conclusion, LAs associates with PAF independent of GLS and LA size, and may be used to improve the performance of DDF grading for identifying PAF in CS patients.

The aim of this study was to evaluate the association between improvement in left ventricular end-systolic volume (LVESV) with cardiac resynchronization therapy (CRT) and mortality and whether this relationship was modified by the presence of a left bundle branch block (LBBB) electrocardiographic pattern.Left ventricular reverse remodeling in patients receiving CRT has been shown to predict outcomes. However, the extent to which reverse remodeling contributes to long-term survival is not well understood.Changes in LVESV were assessed in MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy) patients receiving CRT with a defibrillator (CRT-D) and echocardiograms available at 1 year (n = 752), stratified by LBBB, relative to long-term all-cause mortality, compared with those with implantable cardioverter-defibrillators (ICDs) only (n = 684).In patients with LBBB, a reduction in LVESV of35% (median) translated into significantly lower risk for long-term mortality (hazard ratio [HR]: 0.34; p 0.001), heart failure (HF) events (HR: 0.21; p 0.001), and HF or death (HR: 0.27; p 0.001) compared with patients with ICDs only. Patients with reductions in LVESV ≤35% had a significantly lower risk for HF, and HF or death, and a nonsignificantly lower rate of death compared with those with ICDs only (HR: 0.74; p = 0.13). Risk reduction in HF events was uniform across all LVESV quartiles. In patients without LBBB, there was no survival benefit (HR: 0.68; p = 0.271) despite an LVESV reduction greater than the median (27.6%). CRT-D patients without LBBB with the least reverse remodeling (quartile 1) had a more than 3-fold increased risk for death compared with those with ICDs only (HR: 3.11; p 0.001).In patients with LBBB, CRT-D-induced reduction in LVESV at 1 year is associated with long-term survival benefit. Despite left ventricular reverse remodeling with CRT-D, there is no survival benefit and potential harm in patients without LBBB.

Dyspnea is a common clinical challenge in patients with type 2 diabetes and may be a sign of heart failure (HF). We sought to evaluate the predictive value dyspnea with and without an echocardiographic substrate in patients with type 2 diabetes without known heart disease.A total of 724 patients with type 2 diabetes followed at specialized clinics participated in this prospective cohort study. Clinical evaluation, comprehensive echocardiography and follow-up through national registers were performed. An echocardiographic substrate was either left ventricular hypertrophy, increased left atrial size, E/e' 15, or LV ejection fraction50%. The end-points were cardiovascular (CVD) events and all-cause mortality.Median follow-up was 4.8 years [Interquartile range: 4.1, 5.3] for CVD event and 77 patients suffered a CVD event. Dyspnea was significantly associated with CVD event: Hazard ratio (HR): 1.58 (95% confidence interval: 1.01-2.48), p = 0.04. Stratifying by evidence of echocardiographic substrate revealed high risk individuals: CVD event: 0.71 (0.35-1.46), p = NS in patients with dyspnea and no echocardiographic substrate and 2.85 (1.74-4.67), p 0.001 in patients with dyspnea with echocardiographic substrate). This pattern was similar in multivariable analyses. Also, C-statistics improved from 0.66 (0.60-0.72) to 0.69 (0.63-0.75), p 0.001 and net reclassification index was 27.5%(5.0-50.0), p = 0.01 for CVD event. The results were similar for all-cause mortality except dyspnea was only a borderline significant predictor.In patients with type 2 diabetes complaining of dyspnea, identifying an echocardiographic substrate - thus indicating patients with HF - accurately stratifies patients with increased risk of CV events and all-cause mortality.

Objectives This study sought to investigate whether left atrial (LA) functional measures predict atrial fibrillation (AF) in the general population. Background Increasing evidence suggests LA functional measures are predictors of AF in several patient groups. Methods In a community-based cohort study, approximately 2,000 individuals underwent a transthoracic echocardiogram. Conventional echocardiographic measures and extended LA measures, including the minimal and maximal LA volumes (LAVmin and LAVmax, respectively) and left atrial emptying fraction (LAEF), were performed. The endpoint was incident AF, and participants with known AF were excluded, which left 1,951 for inclusion. Results Over 11.0 years of follow-up, 184 (9.4%) developed AF. Those who developed AF had significantly larger LA volumes and lower LAEF than participants free of AF. These LA measures were univariable predictors of AF (LAVmax hazard ratio [HR]: 1.10 [95% confidence interval (CI): 1.08 to 1.12] per 1-ml increase, p Conclusions LA functional measures predict AF in the general population and provide prognostic information incremental to clinical risk scores. In individuals without hypertension and nondilated LA, these measures indicate an increased risk of AF.

The ratio of early mitral inflow velocity (E) to early diastolic strain rate (E/e'sr) is a significant predictor of cardiac outcomes in various patient populations. This study aims to evaluate the predictive value of E/e'sr for heart failure, acute myocardial infarction, and death due to cardiovascular disease following acute coronary syndrome (ACS). In total, 432 ACS patients underwent echocardiography following percutaneous coronary intervention. The end point was the composite of heart failure, acute myocardial infarction, and death due to cardiovascular disease. Median follow-up was 4.4 (interquartile range 0.2 to 6.3) years. During the follow-up period, 199 (46.1%) met the composite outcome. Mean value of E/e'sr in patients was 0.70 ± 0.37 m. In univariable Cox regression, E/e'sr was a predictor of the composite outcome (hazard ratio [HR] 1.05 95% confidence interval [CI] 1.03 to 1.07, p0.001, per 0.10 m increase). After multivariable adjustment for demographic and clinical parameters, E/e'sr remained an independent predictor (HR 1.03; 95% CI 1.01 to 1.06; p = 0.013, per 0.10 m increase). Global longitudinal strain (GLS) modified the relation between E/e'sr and outcome (p value for interaction = 0.011). In ACS patients with a relatively preserved systolic function assessed by GLS (GLS ≥ 13.2%), E/e'sr showed to be a significant predictor (HR 1.20; 95% CI 1.06 to 1.36; p = 0.005, per 0.10 m increase). In contrast, E/e'sr was not a significant predictor in ACS patients with impaired systolic function (GLS13.2%; HR 1.02; 95% CI 0.99 to 1.04; p = 0.28). In conclusion, E/e'sr provides important prognostic information regarding cardiovascular morbidity and mortality in ACS patients. However, E/e'sr was not an independent predictor over that of echocardiographic parameters. Furthermore, E/e'sr is a stronger prognosticator in patients with relatively preserved systolic function as opposed to patients with impaired systolic function.

Twenty-five percent of ischemic strokes (IS) are cryptogenic, but it is estimated that paroxysmal atrial fibrillation (PAF) is the underlying cause in up to a third of cases. We aimed to investigate the predictive value of speckle tracking of the left atrium (LA) in diagnosing PAF in IS patients. We retrospectively studied 186 IS patients with a clinical echocardiographic examination during sinus rhythm. Outcome was PAF defined by at least one reported episode of AF following their IS. Conventional echocardiographic measures were performed. Global longitudinal strain (GLS), LA reservoir-(es), conduit-(ee), contraction-strain (ea) and LA dyssynchrony (standard deviation of time-to-peak es; LA SD-T2P) were obtained by left ventricular and LA speckle tracking. Of 186 patients, 28 (15%) were diagnosed with PAF. PAF-patients did not differ from non-PAF patients with regards to GLS nor SD-TPS, but atrial strain measures were significantly impaired at baseline (es 27 vs. 35%, ee 12 vs. 16%, ea 15 vs. 18%, p

Background: Lung ultrasound is a useful tool in the assessment of pulmonary congestion in heart failure that is typically performed and interpreted by physicians at the point-of-care. Aims: To investigate the ability of nurses, students, and paramedics to accurately identify B-lines and pleural effusions for the detection of pulmonary congestion in heart failure and to examine the training necessary. Methods and results: We conducted a systematic review and searched online databases for studies that investigated the ability of nurses, students, and paramedics to perform lung ultrasound and detect B-lines and pleural effusions. Of 979 studies identified, 14 met our inclusion criteria: five in nurses, eight in students, and one in paramedics. After 0–12 h of didactic training and 58–62 practice lung ultrasound examinations, nurses were able to identify B-lines and pleural effusions with a sensitivity of 79–98% and a specificity of 70–99%. In image adequacy studies, medical students with 2–9 h of training were able to acquire adequate images for B-lines and pleural effusions in 50–100%. Only one eligible study investigated paramedic-performed lung ultrasound which did not support the ability of paramedics to adequately acquire and interpret lung ultrasound images after 2 h of training. Conclusions: Our findings suggest that nurses and students can accurately acquire and interpret lung ultrasound images after a brief training period in a majority of cases. The examination of heart failure patients with lung ultrasound by non-clinicians appears feasible and warrants further investigation.

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.

Heart failure (HF) has evolved in an epidemic manner and constitutes a major public health issue. Currently, several prognostic markers and treatment options exist to guide treatment of HF with reduced ejection fraction, but echocardiographic deformation imaging suggests novel pathophysiologic aspects that could help optimize treatment further. Even though no formal treatment options currently exist for patients with HF with preserved ejection fraction, some HF medication does seem to attenuate strain measures. Speckle tracking has furthermore helped characterize this condition and to confer prognostic information. Thus, strain imaging could facilitate novel trials, and thereby hopefully introduce treatment opportunities.

Background: Influenza infection is a serious event for patients with heart failure (HF). Little knowledge exists about the association between influenza vaccination and outcome in patients with HF. This study sought to determine whether influenza vaccination is associated with improved long-term survival in patients with newly diagnosed HF. Methods: We performed a nationwide cohort study including all patients who were >18 years of age and diagnosed with HF in Denmark in the period of January 1, 2003, to June 1, 2015 (n=134 048). We collected linked data using nationwide registries. Vaccination status, number, and frequency during follow-up were treated as time-varying covariates in time-dependent Cox regression. Results: Follow-up was 99.8% with a median follow-up time of 3.7 years (interquartile range, 1.7–6.8 years). The vaccination coverage of the study cohort ranged from 16% to 54% during the study period. In unadjusted analysis, receiving ≥1 vaccinations during follow-up was associated with a higher risk of death. After adjustment for inclusion date, comorbidities, medications, household income, and education level, receiving ≥1 vaccinations was associated with an 18% reduced risk of death (all-cause: hazard ratio, 0.82; 95% CI, 0.81–0.84; P P Conclusions: In patients with HF, influenza vaccination was associated with a reduced risk of both all-cause and cardiovascular death after extensive adjustment for confounders. Frequent vaccination and vaccination earlier in the year were associated with larger reductions in the risk of death compared with intermittent and late vaccination.

Social distancing measures introduced during the coronavirus disease 2019 pandemic have reduced admission rates for various infectious and noninfectious respiratory diseases. We hypothesized that rates of asthma exacerbations would decline following the national lockdown in Denmark.To determine weekly rates of in- and out-of-hospital asthma exacerbations before and during the social distancing intervention implemented on March 12, 2020.All individuals older than 18 years with at least 1 outpatient hospital contact with asthma as the main diagnosis from January 1, 2013, to December 31, 2017, were included. Weekly asthma exacerbation rates from January 1, 2018, to May 22, 2020, were calculated. An interrupted time-series model with the lockdown on March 12, 2020, as the point of interruption was used.A total of 38,225 patients with asthma were identified. The interrupted time-series model showed no immediate fall in exacerbation rates during the first week after March 12, 2020. However, there was a significant decline in weekly exacerbation rates in the following 10 weeks (change in trend for exacerbations requiring hospitalization: -0.75 [95% CI, -1.39 to -0.12]; P.02 and in all asthma exacerbations: -12.2 [95% CI, -19.1 to -5.4; P.001), amounting to a reduction of approximately 1 and 16.5 exacerbations per year per 100 patients in the cohort, respectively.The introduction of the social distancing measures in Denmark did not lead to an immediate reduction in asthma exacerbation rates; however, a gradual decline in exacerbation rates during the following 10-week period was observed.

Aims Left atrial (LA) enlargement predicts cardiovascular risk. The prognostic value of left atrial peak reservoir strain (LA RS) by two-dimensional speckle tracking in the general population is currently unknown. This study sought to determine the prognostic value of LA RS in the general population. Methods and results A total of 385 participants without atrial fibrillation, heart failure (HF), and ischaemic heart disease (IHD) had an echocardiogram including left ventricular and LA speckle-tracking analysis performed. LA RS was averaged from the three apical views. The endpoint was a composite of incident IHD, HF, or cardiovascular death. Median follow-up was 12.6 years (interquartile-range 11.5-12.8 years). Follow-up was 100%. Fifty-one participants (13.3%) reached the composite outcome. LA RS was a univariable predictor of outcome [hazard ratio (HR) 1.25, 95% confidence interval (95% CI) 1.09-1.43; P = 0.002]. However, LA RS did not remain an independent predictor of outcome after adjustment for clinical parameters. The prognostic value was modified by sex (P = 0.011). LA RS predicted the composite outcome in women but not in men when adjusting for clinical parameters (women: HR 1.46, 95% CI 1.05-2.02; P = 0.025) (men: HR 0.96, 95% CI 0.81-1.14; P = 0.65). Further adjustment for echocardiographic parameters did not significantly alter the results. LA RS added incremental prognostic information in addition to SCORE and the American Heart Association/American College of Cardiology Pooled Cohort Equation in women only. Conclusion LA RS is a univariable predictor of cardiovascular morbidity and mortality in the general population. However, the prognostic value of LA RS is modified by sex. LA RS is an independent predictor of outcome in women but not in men.

Aims Assessing left atrial (LA) size and function is an important part of the echocardiographic examination. We sought to assess how LA size and function develop over time, and which clinical characteristics promote atrial remodelling. Methods and results We examined longitudinal changes of the LA between two visits in the Copenhagen City Heart Study (n = 1065). The median time between the examinations was 10.4 years. LA measurements included: maximal LA volume (LAVmax), minimal LA volume (LAVmin), and LA emptying fraction (LAEF). Clinical and echocardiographic accelerators were determined from linear regression. The value of LA remodelling for predicting incident atrial fibrillation (AF) and heart failure (HF) was examined by Cox proportional hazards regressions. During follow-up, LAVmax and LAVmin significantly increased by 8.3 and 3.5 mL/m2, respectively. LAEF did not change. Age and AF were the most impactful clinical accelerators of LA remodelling with standardized beta-coefficients of 0.17 and 0.28 for changes in LAVmax, and 0.18 and 0.38 for changes in LAVmin, respectively. Left ventricular (LV) systolic function, diameter, and mass were also significant accelerators of LA remodelling. Changes in both LAVmax and LAVmin were significantly associated with incident AF [n = 46, ΔLAVmax: HR = 1.06 (1.03–1.09), P Conclusion Both maximal and minimal LA volume increase over time. Clinical accelerators included age and AF. LV structure and systolic function also accelerate LA remodelling. LA remodelling poses an increased risk of clinical outcomes.

The CORTICO-COP trial showed that eosinophil-guided corticosteroid-sparing treatment for acute exacerbation of chronic obstructive pulmonary disease was non-inferior to standard of care and decreased the accumulated dose of systemic corticosteroids that patients were exposed to by approximately 60%. Smoking status has been shown to affect corticosteroid responsiveness. This post hoc analysis investigated whether eosinophil-guided treatment is non-inferior to conventional treatment in current smokers. The main analysis of current smokers showed no significant difference in the primary endpoint, days alive, and out of hospital within 14 days between the control group (mean, 9.8 days, 95% confidence interval (CI), 8.7–10.8) and the eosinophil-guided group (mean, 8.7 days, 95% CI, 7.5–9.9, p = 0.34). Secondary analyses of the number of exacerbations or deaths, the number of intensive care unit admissions or deaths, lung function improvement, and change in health-related quality of life also showed no significant differences between the two groups. The results of a sensitivity analysis of ex-smokers are consistent with the main analysis. Our results suggest that eosinophil-guided treatment is non-inferior to standard of care in current smokers and ex-smokers. Because data on the impact of smoking status on eosinophil-guided treatments are sparse, more randomised trials are needed to confirm our results.

Background and Aims The relation between chronic kidney disease and adverse cardiovascular events is well-established. It is also known that traditional risk factors of cardiovascular disease such as smoking, low-density lipoprotein (LDL) cholesterol and increased blood pressure, cannot fully explain the increased cardiovascular burden observed in patients with chronic kidney disease. In addition, patients with chronic kidney disease do not demonstrate typical clinical symptoms of cardiovascular disease. Thus, good biomarkers for identifying patients at risk and a better understanding of the pathophysiology leading to cardiovascular disease in patients with chronic kidney disease are needed. The objective of the present study was to investigate associations between plasma metabolites and prevalent cardiovascular disease, as well as subclinical cardiovascular disease measured as coronary artery calcification score (CACS), in patients with chronic kidney disease. Method More than 200 metabolic biomarkers, including subclasses of lipoproteins as well as the lipid composition of these, were quantified using nuclear magnetic resonance spectroscopy in 725 patients and 174 controls from the Copenhagen Chronic Kidney Disease Cohort, a single-centre prospective, observational study of non-dialysis patients with stage 1-5 chronic kidney disease. Associations between metabolites and prevalent cardiovascular disease and between metabolites and CACS were determined using multivariable logistic regression and linear regression, respectively. The statistical models were adjusted for traditional cardiovascular risk factors and multiple testing. CACS was determined by CT-scannning and calcium scores were subsequently divided into categories of 0 (no calcification), 1-100, 101-400 and > 400. Results When comparing metabolite concentrations in patients with controls, patients presented with the expected pattern of dyslipidaemia in CKD. We found that they had increased plasma triglyceride concentrations, mainly due to an increase in the triglyceride concentration in very low-density lipoprotein (VLDL) particles, while the concentration of cholesterol in high-density lipoprotein (HDL) particles was decreased. Overall, 85 metabolites were significantly associated with prevalent cardiovascular disease in a model adjusted for eGFR, age and sex (p < 0.001). After further adjusting for diabetes, body mass index, smoking and cholesterol-lowering medication, the significance was lost for all but six metabolites (p < 0.001). The consistent inverse associations with metabolites were primarily involved in HDL metabolism (e.g. ApoA-1, HDL-C and HDL-2). This also applied to the concentration of total lipids in large HDL particles, the concentration of phospholipids in large HDL particles and the the ratio of phospholipids to total lipids in very small VLDL particles. Of the 84 metabolites associated with prevalent cardiovascular disease, 71 were also associated with CACS in a similar pattern. Yet, in the model adjusted for all seven cardiovascular risk factors, only plasma glucose levels as well as the triglyceride content of larger LDL particles remained significant. Conclusion In this study we identified metabolites associated with prevalent cardiovascular disease and subclinical cardiovascular disease (CACS) in patients with CKD. For prevalent cardiovascular disease associations were mainly found for HDL associated metabolites, while CACS was associated with an increase in the triglyceride content of LDL particles and glucose. Further work needs to be done to establish whether these associations are merely a consequence of the cardiovascular burden or whether there is a causal relation.

Background and Aims Chronic kidney disease (CKD) accelerates both atherosclerosis and arterial calcification. The aim of the present study was to explore whether maximal carotid plaque thickness (cPT max) was increased in patients with CKD stage 3 compared to controls and associated with cardiovascular disease and severity of calcification in the carotid and coronary arteries. Method The study group consisted of 200 patients with CKD stage 3 from the Copenhagen CKD Cohort and 121 age- and sex-matched controls. cPT max was assessed by ultrasound and arterial calcification by computed tomography scanning. Results Carotid plaques were present in 58% of patients (n=115) compared with 40% of controls (n=48), P=0.002. Among participants with plaques, cPT max (median, interquartile range) was significantly higher in patients compared with controls (1.9 (1.4-2.3) versus 1.5 (1.2-1.8) mm, P=0.001. Cardiovascular disease was present in 9.4% of patients without plaques (n=85), 23.2% of patients with cPT max 1.0-1.9 mm (n=69) and 34.8% of patients with cPT max >1.9 mm (n=46), P=0.001. Carotid and coronary calcium scores >400 were present in 0.0% and 4.0%, respectively, of patients with no carotid plaques, in 19.1% and 24.2% of patients with cPT max 1.0-1.9 mm, and in 47.5% and 52.6% of patients with cPT max >1.9 mm, P Conclusion This is the first study showing that cPT max is increased in patients with CKD stage 3 compared to controls and closely associated with prevalent cardiovascular disease and severity of calcification in both the carotid and coronary arteries.

Not required.

Objective Hydroxychloroquine has been proposed as a primary prophylactic agent against coronavirus disease 2019 (COVID-19). This study aimed to investigate if patients treated with hydroxychloroquine for a non-COVID-19 indication had a lower risk of verified infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) compared with matched controls. Methods A cohort comprising all persons in Denmark collecting hydroxychloroquine prescriptions in 2020 and 2019 (i.e., both during and before SARS-CoV-2 was confirmed in Denmark), matched by age and sex with controls, was studied. Data were collected using the Danish national registries, which contain complete information on patient health data, prescriptions and microbiological test results. The main outcome was microbiologically verified SARS-CoV-2 infection. Results In total, 5488 hydroxychloroquine users were matched with 54,486 non-users. At baseline, the groups differed in terms of diagnoses of pulmonary disease, cardiovascular disease, renal disease, gastrointestinal/metabolic disease and dementia, as well as treatment with antirheumatic drugs. The final model was adjusted for these potential confounders. Use of hydroxychloroquine for non-COVID-19 indications was not associated with any change in confirmed SARS-CoV-2 (hazard ratio 0.90, 95% confidence interval 0.76–1.07). This result was robust in the propensity-score-matched sensitivity analysis. Conclusion This study, which is the largest to date to investigate the primary prophylactic effect of hydroxychloroquine against SARS-CoV-2, does not support any prophylactic benefit of hydroxychloroquine in the prevention of infection with SARS-CoV-2.

Background On 13 March 2020, the Danish authorities imposed extensive nationwide lockdown measures to prevent the spread of the coronavirus disease 2019 (COVID-19) and reallocated limited healthcare resources. We investigated mortality rates, overall and according to location, in patients with established cardiovascular disease before, during, and after these lockdown measures. Methods and results Using Danish nationwide registries, we identified a dynamic cohort comprising all Danish citizens with cardiovascular disease (i.e. a history of ischaemic heart disease, ischaemic stroke, heart failure, atrial fibrillation, or peripheral artery disease) alive on 2 January 2019 and 2020. The cohort was followed from 2 January 2019/2020 until death or 16/15 October 2019/2020. The cohort comprised 340 392 and 347 136 patients with cardiovascular disease in 2019 and 2020, respectively. The overall, in-hospital, and out-of-hospital mortality rate in 2020 before lockdown was significantly lower compared with the same period in 2019 [adjusted incidence rate ratio (IRR) 0.91, 95% confidence interval (CI) CI 0.87–0.95; IRR 0.95, 95% CI 0.89–1.02; and IRR 0.87, 95% CI 0.83–0.93, respectively]. The overall mortality rate during and after lockdown was not significantly different compared with the same period in 2019 (IRR 0.99, 95% CI 0.97–1.02). However, the in-hospital mortality rate was lower and out-of-hospital mortality rate higher during and after lockdown compared with the same period in 2019 (in-hospital, IRR 0.92, 95% CI 0.88–0.96; out-of-hospital, IRR 1.04, 95% CI1.01–1.08). These trends were consistent irrespective of sex and age. Conclusions Among patients with established cardiovascular disease, the in-hospital mortality rate was lower and out-of-hospital mortality rate higher during lockdown compared with the same period in the preceding year, irrespective of age and sex.

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

Background Liver transplantation is the only curative treatment for patients with end-stage liver disease. Short-term survival has improved due to improved surgical techniques and greater efficacy of immunosuppressive drugs. However, long-term survival has not improved to the same extent as the short-term survival, and the 10-year survival after liver transplantation is 60%. In addition to liver- and transplant-related causes, comorbidities such as cardiovascular, pulmonary, renal, and metabolic diseases have emerged as leading causes of morbidity and mortality in liver transplant recipients. The objective of this study is to assess the burden of comorbidities and identify both liver- and transplant-related risk factors as well as traditional risk factors that contribute to the pathogenesis of comorbidity in liver transplant recipients. Methods/design The Danish Comorbidity in Liver Transplant Recipients (DACOLT) study is an observational, longitudinal study. We aim to include all adult liver transplant recipients in Denmark (n = approx. 600). Participants will be matched by sex and age to controls from the Copenhagen General Population Study (CGPS) and the Copenhagen City Heart Study (CCHS). Physical and biological measures including blood pressure, ankle–brachial index, spirometry, exhaled nitric oxide, electrocardiogram, transthoracic echocardiography, computed tomography (CT) angiography of the heart, unenhanced CT of chest and abdomen and blood samples will be collected using uniform protocols in participants in DACOLT, CGPS, and CCHS. Blood samples will be collected and stored in a research biobank. Follow-up examinations at regular intervals up to 10 years of follow-up are planned. Discussion There is no international consensus standard for optimal clinical care or monitoring of liver transplant recipients. This study will determine prevalence, incidence and risk factors for comorbidity in liver transplant recipients and may be used to provide evidence for guidelines on management, treatment and screening and thereby contribute to improvement of the long-term survival. Trial registration ClinicalTrials.gov: NCT04777032; date of registration: March 02, 2021.

Mortality due to COVID-19 is higher among elderly patients with comorbidities. Even so, prognostication in COVID-19 remains limited.We assessed 90-day mortality stratified by comorbidities, routine biochemical markers and oxygen need in a consecutive single-centre cohort from 2 March to 2 June 2020.We included 263 hospitalised patients with laboratory-confirmed COVID-19. On admission, fitness for intensive care was determined in 254 patients including 98 (39%) with a do-not-resuscitate order. Ninety-day overall mortality was 29%, whereas intensive care unit (ICU) mortality was 35% (14/40). Alcohol abuse, liver disease and elevated urea were strongly associated with mortality in univariable analyses. In a mutually adjusted multivariable analysis, we found an independent incremental increase in 90-day mortality with each increasing age by decade (hazard ratio (HR) = 1.5; 95% confidence interval (CI): 1.2-1.9), Charlson Comorbidity Index (CCI) score (HR = 1.2; 95% CI: 1.0-1.4), number of abnormal blood tests (HR = 1.2; 95% CI: 1.1-1.3) and l/min. of supplemental oxygen (HR = 1.1; 95% CI: 1.1-1.2).The overall mortality was similar to that of other hospitalised patients, whereas the ICU mortality was lower than expected. On admission, each additional age by decade, CCI score, number of abnormal blood tests and magnitude of supplemental oxygen were independently associated with increased mortality.none.not relevant.

Aims: To determine whether a strategy of intensive blood pressure control reduces the risk of heart failure (HF) events consistently across the spectrum of kidney function and albuminuria. Methods and results: SPRINT was a randomized clinical trial in which 9361 individuals ≥50 years, at high risk for or with cardiovascular disease, a systolic blood pressure of 130–180 mmHg, but without diabetes, were randomized to intensive (target 2 and 248 (2.8%) with UACR >300 mg/g. During a median follow-up of 3.2 years (range 0–4.8 years), 160 (1.8%) participants had HF events and 233 (2.6%) had HF events or cardiovascular death. Risks of HF events or cardiovascular death increased from 0.42 (0.34–0.53) per 100 patient-years in patients with eGFR ≥60 mL/min/1.73 m2 and UACR 2 and UACR >300 mg/g. A similar gradient was observed for HF events alone. Both eGFR and UACR were independently, non-linearly associated with HF hospitalization and HF hospitalization or cardiovascular death (test for overall trend, P < 0.001). While the effects of intensive blood pressure control on HF event risk appeared to attenuate at lower eGFR and higher UACR, there was no significant interaction between eGFR or UACR and blood pressure control strategy (continuous and categorical interaction P > 0.05). Conclusion: In SPRINT, eGFR and albuminuria were strong and additive determinants in forecasting HF risk. The effect of intensive blood pressure control in decreasing HF risk did not significantly vary across the spectrum of kidney function or albuminuria. Multidisciplinary pathways, incorporating blood pressure control, are needed for at-risk patients with chronic kidney disease to attenuate HF risk. Trial Registration: ClinicalTrials.gov Identifier NCT01206062.

Ventricular tachycardia (VT) may lead to syncope and sudden cardiac death. Implantable loop recorders (ILR) are recommended in the clinical work-up of patients with unexplained syncope. Our aim was to evaluate if echocardiographic parameters assessed prior to ILR implantation in patients with unexplained syncope may aid in identifying individuals with an increased risk of VT. The present study included 288 ambulatory patients (mean age 58 ± 19 years, 51% women) with syncope (90%) and presyncope (10%) who had an ILR implanted in the diagnostic workup. All patients underwent an echocardiographic examination prior to device implantation (median 3 months [IQR 1 to 6 months]). We examined incident VT, defined as a first-time episode of VT ( 30 s) or non-sustained VT ( 30 s) detected by the ILR. During median follow-up of 2.9 years [IQR 1.3 to 3.5 years] of continuous rhythm monitoring, 36 patients (13%) were diagnosed with incident VT (n = 25 non-sustained VT, n = 11 sustained VT). In unadjusted Cox proportional hazards models, left ventricular (LV) mass index (HR: 1.04 per 1 g/m

Diagnostic tests including echocardiography, albuminuria, electrocardiogram (ECG), high-sensitivity troponin I (hs-TnI), and N-terminal prohormone brain natriuretic peptide (NT-proBNP) have been suggested as cardiovascular (CV) risk predictors in type 2 diabetes. We studied the separate and combined prognostic yield of these risk markers.In all, 1030 patients with type 2 diabetes were recruited from specialized clinics in this prospective cohort study. Full echocardiographic evaluation was feasible in 886 patients in sinus rhythm with adequate image quality. ECG was performed in 998 patients. Albuminuria was measured in 1009 and NT-proBNP/hs-TnI in 933 patients. The end point was a composite of CV events.The median follow-up was 4.7 years (interquartile range: 4.0-5.3), and 174 patients experienced a CV disease event. All considered markers, except hs-TnI, were significantly (P .001) associated with the outcome: abnormal echocardiogram (hazard ratio 2.40 [1.70-3.39]), albuminuria 2.01 (1.47-2.76), abnormal ECG (2.27 [1.66-3.08]), high NT-proBNP (150 pg/mL) 3.05 (2.11-4.40), and hs-TnI 1.12 (0.79-1.59). After adjusting for clinical variables, all remained significantly associated with the end point. However, after adjusting for each other, only NT-proBNP150 pg/mL remained significantly associated with the end point (2.07 [1.28-3.34], P .001). Measured by C-statistics, model performance was highest with logThis study identified NT-proBNP over echocardiography, ECG, and albuminuria in risk prediction in patients with type 2 diabetes. The diagnostic yield in considering more than one risk marker was limited in this population.背景: 超声心动图、蛋白尿、心电图(ECG)、高敏肌钙蛋白I(hs-TnI)和N末端前激素脑钠素(NT-proBNP)等诊断试验被认为能够预测2型糖尿病心血管(CV)的危险因素。我们研究了这些风险标记物的单独和联合预测效果。 方法: 在这项前瞻性队列研究中, 从专科诊所共招募1030名2型糖尿病患者。886例窦性心律且图像质量良好的患者进行了超声心动图的全面评估。对998例患者进行心电图检查。1009例患者检测蛋白尿, 933例患者检测NT-proBNP/hs-TnI。终点是CV事件的组合。 结果: 中位随访时间为4.7年(四分位数范围:4.0-5.3), 174名患者经历了心血管疾病事件。除hs-TnI外, 所有考虑的标志物:超声心动图异常(危险比2.40[1.70-3.39])、蛋白尿2.01(1.47-2.76)、心电图异常(2.27[1.66-3.08])、高NT-proBNP(150pg/mL)3.05(2.11-4.40)和hs-TnI 1.12(0.79-1.59) 均与预后显著相关(P0.001)。在调整了临床变量后, 所有这些变量仍然与终点显著相关。然而, 在变量间调整后, 只有NT-proBNP150pg/mL与终点显著相关(2.07[1.28-3.34], P0.001)。通过C-统计量测量, log

Left ventricular ejection time (LVET) is defined as the time interval from aortic valve opening to aortic valve closure, and is the phase of systole during which the left ventricle ejects blood into the aorta. LVET has been used for several decades to assess left ventricular function and contractility. However, there is a recent interest in LVET as a measure of therapeutic action for novel drugs in patients with heart failure with reduced ejection fraction (HFrEF), since LVET is shortened in these patients. This review provides an overview of the available information on LVET including methods of measuring LVET, mechanistic understanding of LVET, association of LVET with outcomes, mechanisms behind shortened LVET in HFrEF and the potential implications of drugs that affect and normalize LVET.

BACKGROUND Previous studies have identified several echocardiographic markers of cardiac dysfunction in participants with diabetes mellitus, including E/e'. However, previous studies have been limited by short follow-up duration or low statistical power, and none have assessed whether echocardiographic predictors of adverse cardiovascular outcome differ between individuals with DM and individuals without DM. METHODS A total of 1997 individuals from the general population without heart disease had an echocardiogram performed in 2001 to 2003. Diabetes was defined as HbA1c ≥6.5% (≥48 mmol/mol), non-fasted blood glucose ≥11.1 mmol/L or the use of glucose lowering medication. The end-point was a composite of heart failure (HF), ischemic heart disease (IHD) and cardiovascular death (CVD). RESULTS At baseline, a total of 292 participants (15%) had diabetes. Median follow-up time was 12.4 years (interquartile-range: 9.8-12.8 years) and follow-up was 100%. During follow-up, 101 participants (35%) with diabetes and 281 participants without diabetes (16%) reached the composite end-point. The prognostic value of E/e' was significantly modified by diabetes (p for interaction: 0.003). In participants with diabetes, only E/e' remained an independent predictor of outcome in a final multivariable model adjusted for clinical and echocardiographic parameters (HR 1.08, 95% CI 1.00-1.17, p = 0.0041, per 1 increase). In participants without diabetes, left ventricular mass index (LVMI), left ventricular ejection fraction (LVEF) and a' remained independent predictors of outcome when adjusted for clinical and echocardiographic parameters. In individuals with diabetes, only E/e' added incremental prognostic value to risk factors from the SCORE risk chart and the ACC/AHA Pooled Cohort Equation. CONCLUSION In individuals with diabetes from the general population, E/e' is a stronger predictor of cardiovascular mortality and morbidity than in individuals without diabetes and contributes with incremental prognostic value in addition to established cardiovascular risk factors.

Background: \ud In GALACTIC-HF (Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure) (n = 8,256), the cardiac myosin activator, omecamtiv mecarbil, significantly reduced the primary composite endpoint (PCE) of time-to-first heart failure event or cardiovascular death in patients with heart failure and reduced ejection fraction (EF) (≤35%).\ud \ud Objectives: \ud The purpose of this study was to evaluate the influence of baseline EF on the therapeutic effect of omecamtiv mecarbil.\ud \ud Methods: \ud Outcomes in patients treated with omecamtiv mecarbil were compared with placebo according to EF.\ud \ud Results: \ud The risk of the PCE in the placebo group was nearly 1.8-fold greater in the lowest EF (≤22%) compared with the highest EF (≥33%) quartile. Amongst the pre-specified subgroups, EF was the strongest modifier of the treatment effect of omecamtiv mecarbil on the PCE (interaction as continuous variable, p = 0.004). Patients receiving omecamtiv mecarbil had a progressively greater relative and absolute treatment effect as baseline EF decreased, with a 17% relative risk reduction for the PCE in patients with baseline EF ≤22% (n = 2,246; hazard ratio: 0.83; 95% confidence interval: 0.73 to 0.95) compared with patients with EF ≥33% (n = 1,750; hazard ratio: 0.99; 95% confidence interval: 0.84 to 1.16; interaction as EF by quartiles, p = 0.013). The absolute reduction in the PCE increased with decreasing EF (EF ≤22%; absolute risk reduction, 7.4 events per 100 patient-years; number needed to treat for 3 years = 11.8), compared with no reduction in the highest EF quartile.\ud \ud Conclusions: \ud In heart failure patients with reduced EF, omecamtiv mecarbil produced greater therapeutic benefit as baseline EF decreased. These findings are consistent with the drug’s mechanism of selectively improving systolic function and presents an important opportunity to improve the outcomes in a group of patients at greatest risk. (Registrational Study With Omecamtiv Mecarbil/AMG 423 to Treat Chronic Heart Failure With Reduced Ejection Fraction [GALACTIC-HF]; NCT02929329)

Studies have proposed that malaria may lead to electrocardiographic (ECG) changes and pericardial inflammation. We aimed to investigate the frequency of ECG alterations, determined by ECG and Holter monitoring, and pericardial effusion in patients with malaria infection. We performed a prospective observational study of adult patients with uncomplicated malaria in Amazonas, Brazil. Peripheral blood smears, ECG, and bedside echocardiography were conducted before antimalarial treatment and repeated at follow-up after completed treatment. We evaluated the diagnostic value of PR-segment depression, PR-segment elevation, and Spodick's sign for detecting pericardial effusion. A subset of patients underwent Holter monitoring at baseline. Among 98 cases of uncomplicated malaria (55% men; mean age 40 years; median parasite density 1,774/µl), 75 had Plasmodium vivax, 22 Plasmodium falciparum, and 1 had mixed infection. At baseline, 17% (n = 17) had PR-segment depression, 12% (n = 12) PR-segment elevation, 3% (n = 2) Spodick's sign, and the prevalence of pericardial effusion was 9% (n = 9). ECG alterations had sensitivities of 22% to 89% and specificities of 88% to 100% for detecting pericardial effusion at baseline. PR-segment depression had the best accuracy (sensitivity 89%, specificity 90%). Of the 25 patients, 4 patients who did not have pericardial effusion, displayed nonsustained ventricular tachycardia, determined by Holter monitoring (median duration 43 hours). Follow-up examination data were obtained for 71 patients (median 31 days), for whom PR-segment depression, elevation, and pericardial effusion had reduced significantly (p0.05). In conclusion, our findings suggest that ECG alterations may be useful to detect pericardial effusion in malaria and that these findings decrease after completed antimalarial treatment.

Background Systemic corticosteroid administration for severe acute exacerbations of COPD (AECOPD) reduces the duration of hospital stays. Corticosteroid-sparing regimens have showed non-inferiority to higher accumulated dose regimens regarding re-exacerbation risk in patients with AECOPD. However, it remains unclear whether 14-day or 2–5-day regimens would result in shorter admission durations and changes in mortality risk. We explored this by analysing the number of days alive and out of hospital based on two randomised controlled trials with different corticosteroid regimens. Methods We pooled individual patient data from the two available multicentre randomised trials on corticosteroid-sparing regimens for AECOPD: the REDUCE (n = 314) and CORTICO-COP (n = 318) trials. In the 14-day regimen group, patients were older, fewer patients received pre-treatment with antibiotics and more patients received pre-treatment with systemic corticosteroids. Patients randomly allocated to the 14-day and 2–5-day regimens were compared, with adjustment for baseline differences. Results The number of days alive and out of hospital within 14 days from recruitment was higher for the 2–5 day regimen group (mean 8.4 days; 95% confidence interval [CI] 8.0–8.8) than the 14-day regimen patient group (4.2 days; 95% CI3.4–4.9; p p p p = 0.15), new or aggravated hypertension (OR 1.5; 95% CI 0.9–2.7; p = 0.15), or mortality risk (HR 0.8; 95% CI 0.4–1.5; p = 0.45) during the 6-month follow-up period. Conclusion 14-day corticosteroid regimens were associated with longer hospital stays and fewer days alive and out of hospital within 14 days, with no apparent 6-month benefit regarding death or admission to ICU in COPD patients. Our results favour 2–5 day regimens for treating COPD exacerbations. However, prospective studies are needed to validate these findings.

BACKGROUND: The ratio of transmitral early filling velocity to early diastolic strain rate (E/e'sr) may be a more accurate measure of LV filling pressure then ratio of early filling pressure to early tissue velocity. The aim of the study was to investigate the impact of age, sex, obesity, smoking, hypertension, hypercholesterolemia, diabetes, physical activity level, socioeconomic, and psychosocial status on E/e'sr over a decade. Additionally, the predictive value of ΔE/e'sr on future major adverse cardiovascular events (MACE) has never been explored.METHOD: The study included 623 participants from the general population, who participated in the 4th and 5th Copenhagen City Heart Study (CCHS4 and CCHS5). Examinations were median 10 years apart. MACE was the composite endpoint of heart failure, myocardial infarction, and all-cause death.RESULTS: Follow-up time was median 5.7 years, and 43 (7%) experienced MACE. Mean age was 51 ± 14 years, and 43% were male. Mean ΔE/e'sr was 2.1 ± 23.0 cm. After multivariable adjustment for demographic, clinical, and biochemistry variables, high age (stand. β-coef. = .24, P < .001) and mean arterial blood pressure (MAP) (stand. β-coef. = .17, P < .001) were significantly associated with an accelerated increase in E/e'sr In multivariable Cox regression, E/e'sr at CCHS5 and ΔE/e'sr were independent predictors of MACE (HR = 1.20, 95% CI [1.01; 1.42] per 10 cm increase for both). ΔE/e'sr did only provide incremental prognostic value to change in left atrial volume index of the conventional diastolic measurements.CONCLUSION: In the general population, age and MAP were predictors of an accelerated increase in E/e'sr over a decade. E/e'sr at CCHS5 and ΔE/e'sr were independent predictors of future MACE.

AIMS: We assessed the outcome of hospitalized coronavirus disease 2019 (COVID-19) patients with heart failure (HF) compared with patients with other cardiovascular disease and/or risk factors (arterial hypertension, diabetes, or dyslipidaemia). We further wanted to determine the incidence of HF events and its consequences in these patient populations. METHODS AND RESULTS: International retrospective Postgraduate Course in Heart Failure registry for patients hospitalized with COVID-19 and CArdioVascular disease and/or risk factors (arterial hypertension, diabetes, or dyslipidaemia) was performed in 28 centres from 15 countries (PCHF-COVICAV). The primary endpoint was in-hospital mortality. Of 1974 patients hospitalized with COVID-19, 1282 had cardiovascular disease and/or risk factors (median age: 72 [interquartile range: 62-81] years, 58% male), with HF being present in 256 [20%] patients. Overall in-hospital mortality was 25% (n = 323/1282 deaths). In-hospital mortality was higher in patients with a history of HF (36%, n = 92) compared with non-HF patients (23%, n = 231, odds ratio [OR] 1.93 [95% confidence interval: 1.44-2.59], P

Recent studies have suggested that malaria may affect the cardiovascular system. The aim of this systematic review and meta-analysis was to determine the prevalence of cardiovascular complications in symptomatic malaria patients. We searched databases such as Pubmed, Embase, Cochrane, and Web of Science (January 1950–April 2020) for studies reporting on cardiovascular complications in adults and children with malaria. Cardiovascular complications were defined as abnormalities in electrocardiogram (ECG), cardiac biomarkers, and echocardiography on admission or during outpatient examination. Studies of patients with known heart disease or cardiovascular evaluation performed after the start of intravenous antimalarial medication were excluded. The study was registered in International Prospective Register of Systematic Reviews (PROSPERO) (No.: CRD42020167672). The literature search yielded 1,243 studies, and a total of 43 studies with symptomatic malaria patients were included. Clinical studies (n = 12 adults; n = 5 children) comprised 3,117 patients, of which a majority had Plasmodium falciparum (n = 15) and were diagnosed with severe malaria (n = 13). In random-effects models of adults, the pooled prevalence estimate for any cardiovascular complication was 7% (95% CI: 5–9). No meta-analysis was conducted in children, but the range of abnormal ECG was 0–8%, cardiac biomarkers 0–57%, and echocardiography 4–9%. We analyzed 33 cases (n = 10 postmortem), in which the most common cardiovascular pathologies were myocarditis and acute coronary syndrome. All histopathological studies found evidence of parasitized red blood cells in the myocardium. Cardiovascular complications are not uncommon in symptomatic adults and children with malaria. Additional studies investigating malaria and cardiovascular disease are encouraged.

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The Danish Heart Foundation (grant no.: 09-04-R72-A2408-22545, 10-04-R78-A2929-22588, 11-04-R84-A3230-22650, and 18-R125-A8534-22083), and the Heart Centre Research Committee at Rigshospitalet, Copenhagen. Background The relationship between natriuretic peptides and atrial distension is not completely understood. Furthermore, how they can be used together clinically has not been fully explored. Purpose We sought to examine their interrelationship and how they relate to atrial fibrillation (AF) recurrence following catheter ablation. Methods Patients scheduled for catheter ablation as part of a randomized controlled clinical trial were included. Patients who underwent pre-operative echocardiography and had natriuretic peptide measurements performed, specifically mid-regional proANP (MR-proANP) and N-terminal proBNP (NT-proBNP), were included in this analysis. Echocardiography included assessment of atrial distension by left atrial strain. The outcome was AF recurrence at 6 months after a 3-month blanking period. Logistic regression was performed to assess the association between log-transformed natriuretic peptides and AF. Multivariable adjustments were made for age, gender, randomization, and LVEF. Results Out of 99 patients 44 developed AF. No differences in natriuretic peptides nor echocardiographic measures were observed between the outcome groups. Neither MR-proANP nor NT-proBNP were univariable predictors of AF recurrence (MR-proANP: OR = 1.06 (0.99-1.14), p = 0.09, per 10% increase; NT-proBNP: OR = 1.01 (0.98-1.05), p = 0.38, per 10% increase). These findings were unchanged after multivariable adjustments. However, atrial strain significantly modified the association between MR-proANP and AF (p for interaction = 0.009) such that MR-proANP was a significant predictor of AF in patients with high atrial strain values (OR = 1.24 (1.06-1.46), p = 0.008, per 10% increase) but not in patients with low atrial strain values. Among patients with high atrial strain values, an MR-proANP > 116pmol/L was associated with a 10-fold increased risk of AF (OR = 9.78 (2.21-43.33), p = 0.003). figure. Conclusion Atrial natriuretic peptide predicts AF recurrence in patients with preserved atrial distension. Assessing atrial distension by echocardiography may assist the clinical interpretation of atrial natriuretic peptide concentration. Abstract Figure.

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): he Innovation Fund Denmark (grant no.: 12-135225), The Research Foundation for the Capital Region of Denmark, The Danish Heart Foundation (grant no.: 11-04-R83-A3363-22625 and 18-R125-A8534-22083), Aalborg University Talent Management Programme, Arvid Nilssons Fond, Skibsreder Per Henriksen, R. og Hustrus Fond, and Medtronic Background Left atrial (LA) speckle tracking is a novel technique that provides detailed information on atrial function. Its utility for predicting subclinical atrial fibrillation (SCAF) is, however, not well-established. Purpose To investigate whether LA speckle tracking measures are associated with SCAF as detected by long-term continuous rhythm monitoring. Methods This was an echocardiographic substudy of a randomized controlled clinical trial that enrolled elderly individuals (≥70 years) with a CHADS2-score≥2 to either no intervention or implantation of a loop recorder (Reveal LINQ) to detect SCAF (≥6 minutes). A subset of the participants receiving a loop recorder was included in this analysis. An echocardiographic examination was performed, which included conventional measurements and LA speckle tracking. LA speckle tracking allowed for assessment of reservoir, conduit, and contraction strain. Multivariable proportional hazards Cox regression was applied to adjust for the clinical risk score (CHARGE-AF) and net reclassification index (NRI) was used to assess prognostic improvement of this score. Incidence rate curves were constructed using Poisson models. Results Overall, 976 participants were eligible for analysis. Median follow-up time was 3 years (interquartile range: 1.7-4.0 years), during which 284 (29%) were diagnosed with SCAF. The mean age was 74 years, 56% were male, median CHA2DS2-VASc-score was 4. A dilated LA (LA volume≥34ml/m2) was observed in 152 (16%). LA speckle tracking revealed that both LA reservoir strain and contraction strain were univariable predictors of SCAF (HR = 1.05 (1.03-1.06) and HR = 1.07 (1.05-1.10), p Even in participants with normal LA size, both reservoir and contraction strain were independent predictors of SCAF after multivariable adjustment (HR = 1.03 (1.01-1.05), p = 0.001 and HR = 1.06 (1.04-1.09), p Conclusion Decreasing left atrial reservoir and contraction strain are independently associated with an increased risk of SCAF as detected by long-term continuous monitoring and provide incremental prognostic value in addition to clinical risk score. Abstract Figure.

Background Chronic kidney disease accelerates both atherosclerosis and arterial calcification. The aim of the present study was to explore whether maximal carotid plaque thickness (cPTmax) was increased in patients with chronic kidney disease compared to controls and associated with cardiovascular disease and severity of calcification in the carotid and coronary arteries. Methods The study group consisted of 200 patients with chronic kidney disease stage 3 from the Copenhagen Chronic Kidney Disease Cohort and 121 age- and sex-matched controls. cPTmax was assessed by ultrasound and arterial calcification by computed tomography scanning. Results Carotid plaques were present in 58% of patients (n = 115) compared with 40% of controls (n = 48), p = 0.002. Among participants with plaques, cPTmax (median, interquartile range) was significantly higher in patients compared with controls (1.9 (1.4–2.3) versus 1.5 (1.2–1.8) mm), p = 0.001. Cardiovascular disease was present in 9% of patients without plaques (n = 85), 23% of patients with cPTmax 1.0–1.9 mm (n = 69) and 35% of patients with cPTmax >1.9 mm (n = 46), p = 0.001. Carotid and coronary calcium scores >400 were present in 0% and 4%, respectively, of patients with no carotid plaques, in 19% and 24% of patients with cPTmax 1.0–1.9 mm, and in 48% and 53% of patients with cPTmax >1.9 mm, p Conclusions This is the first study showing that cPTmax is increased in patients with chronic kidney disease stage 3 compared to controls and closely associated with prevalent cardiovascular disease and severity of calcification in both the carotid and coronary arteries.

Aims Pre-existing cardiovascular diseases (CVDs) have been proposed to identify patients at higher risk of adverse coronavirus disease 2019 (COVID-19) outcomes, but existing evidence is conflicting. Thus, it is unclear whether pre-existing CVDs are independently important predictors for severe COVID-19.Methods and results In a nationwide Danish cohort of hospital-screened COVID-19 patients aged ≥40, we investigated if pre-existing CVDs predict the 30-day risk of (i) composite outcome of severe COVID-19 and (ii) all-cause mortality. We estimated 30-day risks using a Cox regression model including age, sex, each CVD comorbidity, chronic obstructive pulmonary disease-asthma, diabetes, and chronic kidney disease. To illustrate CVD comorbidities’ importance, we evaluated the predicted risks of death and severe infection, for each sex, along ages 40–85. In total, 4090 COVID-19 hospital-screened patients were observed as of 26 August 2020; 22.1% had ≥1 CVD, 23.7% had severe infection within 30 days and 12.6% died. Predicted risks of both outcomes at age 75 among men with single CVD comorbidities did not differ in clinically meaningful amounts compared with men with no comorbidities risks for the composite outcome of severe infection; women with heart failure (28.2%; 95% CI 21.1–37.0%) or atrial fibrillation (30.0%; 95% CI: 24.2–36.9%) showed modest increases compared with women with no comorbidities (24.0%; 95% CI: 21.4–26.9%).Conclusions The results showing only modest effects of CVDs on increased risks of poor COVID-19 outcomes are important in allowing public health authorities and clinicians to provide more tailored guidance to cardiovascular patients, who have heretofore been grouped together as high risk due to their disease status.

Although infectious diseases have been associated with cardiovascular conditions, little is known about tropical disease burden and hypertension. We hypothesized that a history of tropical infections was associated with hypertension. We examined participants from outpatient clinics in the Amazon Basin who were interviewed about prior exposure to tropical diseases, including dengue, malaria hospitalization, and leishmaniasis. Hypertension was defined as a prior physician diagnosis of hypertension, treatment with anti-hypertensive medication, or a systolic blood pressure ≥140 mmHg and/or a diastolic blood pressure ≥90 mmHg. We used logistic regression models to examine the relationship between tropical infectious disease and hypertension. We included 556 participants (mean age 41 ± 15 years, 61% women) of whom 214 (38%) had hypertension and 354 (64%) had a history of tropical infectious disease. The distribution of tropical diseases was: dengue 270 (76%), malaria hospitalization 104 (29%) and leishmaniasis 48 (14%). Any prior tropical infection was significantly associated with prevalent hypertension (odds ratio 1.76 [95% CI 1.22-2.54], P = 0.003) and the association remained significant after adjusting for age, sex, body mass index, diabetes, hypercholesterolemia, socioeconomic status, smoking, vegetable intake and serum creatinine. Persons with a history of ≥2 tropical infections (n = 64) had the greatest risk of hypertension (odds ratio 2.04 [95% CI 1.15-3.63], P = 0.015). In adjusted models, prior infection with dengue was associated with hypertension (P = 0.006), but no associations were found with malaria hospitalization (P = 0.39) or leishmaniasis (P = 0.98). In conclusion, a history of tropical infectious disease was associated with hypertension. This finding supports the idea that pathogen burden may be related to cardiovascular conditions.

Background There is an urgent need for treatments that can shorten hospitalization and lower the risk of secondary infection and death in patients with corona disease. The ProPac-COVID trial evaluates whether combination therapy with macrolide azithromycin and hydroxychloroquine via anti-inflammation/immune modulation, antiviral efficacy, and pre-emptive treatment of supra-infections can shorten hospitalization duration and reduce the risk of non-invasive ventilation, treatment in the intensive care unit, and death in patients with acute hospital admission and a positive test for 2019-nCoV and symptoms of COVID-19 disease. Methods The ProPAC-COVID is a multi-center, randomized, placebo-controlled, double-blinded clinical trial. The primary outcome is number of days spent alive and out of hospital within 14 days from randomization. Randomization will be in blocks of unknown size, and the final allocation will be stratified for age, site of recruitment, and whether the patient has any chronic lung diseases. Data is analyzed using intention-to-treat (ITT) principles, and main analyses will also be subject to modified ITT analysis and per protocol analysis. Discussion This paper describes the detailed statistical analysis plan for the evaluation of primary and secondary endpoints of the ProPAC-COVID study. Enrolment of patients to the ProPAC-COVID study is still ongoing. The purpose of this paper is to provide primary publication of study results to prevent selective reporting of outcomes, data-driven analysis, and to increase transparency. Trial registration ClinicalTrials.gov NCT04322396. Registered on 26 March 2020.

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 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.

Background Low bicarbonate levels are associated with higher mortality among patients who are hospitalized or have chronic kidney disease. However, the relationship between bicarbonate and mortality among outpatients on antihypertensive treatment is unclear. Purpose To assess the relationship between serum bicarbonate levels, treatment response to intensive blood pressure lowering, and mortality. Methods SPRINT was a randomized, controlled trial in which 9,361 individuals ≥50 years of age, at high cardiovascular (CV) risk, but without diabetes, and a systolic blood pressure (BP) 130–180 mmHg, were randomized to intensive (target systolic BP Results A total of 9,334 (99.7%) individuals had a bicarbonate measurement available at baseline and 9,232 (98.6%) had at least one measurement after baseline. Mean baseline bicarbonate was similar between the two study groups (26.3 mmol/l in both; P=0.84), as was on-treatment bicarbonate (25.2 mmol/l in both; P=0.51). Median follow-up was 3.3 years (range 0–4.8), with 365 deaths from any cause (3.9%) and 102 deaths from CV causes (1.1%) recorded during the study period. Baseline and on-treatment bicarbonate both displayed a significant, U-shaped association with death from any cause (adjusted overall trend, P0.05) (Figure). Low baseline bicarbonate was significantly associated with death from any cause (29 vs. 23–29 mmol/l; P=0.84). Conversely, both low (adj. HR 1.50, 95% CI, 1.14–1.97; P=0.004) and high (adj. HR 4.77, 95% CI, 3.49–6.52; P0.05). Conclusions Baseline and on-treatment serum bicarbonate levels both displayed a U-shaped association with the risk of death. The association was not affected by intensive vs. standard blood pressure lowering. Figure 1 Funding Acknowledgement Type of funding source: None