ECG changes in hospitalised patients with COVID-19 infection.

The coronavirus disease 2019 (COVID-19) commonly involves the respiratory system but increasingly cardiovascular involvement is recognised. We assessed electrocardiogram (ECG) abnormalities in patients with COVID-19. We performed retrospective analysis of the hospital's COVID-19 database from April to May 2020. Any ECG abnormality was defined as: 1) new sinus bradycardia; 2) new/worsening bundle-branch block; 3) new/worsening heart block; 4) new ventricular or atrial bigeminy/trigeminy; 5) new-onset atrial fibrillation (AF)/atrial flutter or ventricular tachycardia (VT); and 6) new-onset ischaemic changes. Patients with and without any ECG change were compared. There were 455 patients included of whom 59 patients (12.8%) met criteria for any ECG abnormality. Patients were older (any ECG abnormality 77.8 ± 12 years vs. no ECG abnormality 67.4 ± 18.2 years, p<0.001) and more likely to die in-hospital (any ECG abnormality 44.1% vs. no ECG abnormality 27.8%, p=0.011). Coxproportional hazard analysis demonstrated any ECG abnormality (hazard ratio [HR] 1.97, 95% confidence interval [CI] 1.12 to 3.47, p=0.019), age (HR 1.03, 95%CI 1.01 to 1.05, p=0.0009), raised high sensitivity troponin I (HR 2.22, 95%CI 1.27 to 3.90, p=0.006) and low estimated glomerular filtration rate (eGFR) (HR 1.73, 95%CI 1.04 to 2.88, p=0.036) were independent predictors of in-hospital mortality. In conclusion, any new ECG abnormality is a significant predictor of in-hospital mortality.

British Society of Echocardiography Departmental Accreditation Standards 2019 with input from the Intensive Care Society.

This article sets out a summary of standards for departmental accreditation set by the British Society of Echocardiography (BSE) Departmental Accreditation Committee. Full accreditation standards are available at www.bsecho.org. The BSE were the first national organisation to establish a quality standards framework for departments that support the practice of individual echocardiographers. This is an updated version which recognises that, not only should all echocardiographers be individually accredited as competent to practice, but that departments also need to be well organised and have the facilities, equipment and processes to ensure the services they deliver are of an appropriate clinical standard. In combination with individual accreditation, departmental accreditation lays down standards to help ensure safe and effective patient care. These standards supersede the 2012 BSE Departmental Accreditation Standards. Standards are set to cover all potential areas of practice, including transthoracic (level 2) echocardiography, transoesophageal echocardiography, stress echocardiography, training, and emergency (level 1) echocardiography. The emergency echocardiography standard is a new addition to departmental accreditation and has been developed with input from the Intensive Care Society.

Inflammatory Biomarkers and Atrial Fibrillation: Potential Role of Inflammatory Pathways in the Pathogenesis of Atrial Fibrillation-induced Thromboembolism.

Inflammation, endothelial dysfunction, and platelet activation contribute to the prothrombotic pro-inflammatory state associated with AF. Inflammatory biomarkers, such as C-reactive protein and interleukin 6, promote the production of tissue factor (TF) and von Willebrand factor (vWF) and aggravate endothelial dysfunction leading to increased coagulation and depressed fibrinolytic activity. The interaction of vWF and glycoprotein Ib (vWF-GPIb) receptor activates 'thrombo-inflammatory' pathways promoting thromboembolism. Moreover, platelet activation driven by plateletleukocyte/ monocyte interaction attribute to AF-related thrombosis. Biochemical pathways such as CD40-CD40 ligand and P-selectin-P-selectin glycoprotein ligand 1 are considered important mediators of platelet-leukocyte interactions in the setting of AF. Further studies are required to address the clinical implications of inflammatory biomarkers in the prediction of AF-related thromboembolism. Indeed, inflammatory pathways could be also considered as therapeutic targets in an effort to reduce the clinical consequences of thromboembolism and improve outcomes in AF.

Atrial fibrillation (acute onset).

INTRODUCTION: Acute atrial fibrillation is rapid, irregular, and chaotic atrial activity of recent onset. Various definitions of acute atrial fibrillation have been used in the literature, but for the purposes of this review we have included studies where atrial fibrillation may have occurred up to 7 days previously. Risk factors for acute atrial fibrillation include increasing age, cardiovascular disease, alcohol, diabetes, and lung disease. Acute atrial fibrillation increases the risk of stroke and heart failure. The condition resolves spontaneously within 24 to 48 hours in more than 50% of people; however, many people will require interventions to control heart rate or restore sinus rhythm. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent embolism, for conversion to sinus rhythm, and to control heart rate in people with recent-onset atrial fibrillation (within 7 days) who are haemodynamically stable? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 26 studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review, we present information relating to the effectiveness and safety of the following interventions: amiodarone, antithrombotic treatment before cardioversion, atenolol, bisoprolol, carvedilol, digoxin, diltiazem, direct current cardioversion, flecainide, metoprolol, nebivolol, propafenone, sotalol, timolol, and verapamil.

Hormone replacement therapy and adverse outcomes in women with atrial fibrillation: an analysis from the atrial fibrillation follow-up investigation of rhythm management trial.

BACKGROUND AND PURPOSE: Hormone replacement therapy (HRT) use has been related to thromboembolism, but whether HRT increases adverse outcomes in females with atrial fibrillation is uncertain. METHODS: We used the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) trial data set that included 1594 women (39.3% of the population, mean age 71±8), of whom 376 (23.6%) were taking HRT at baseline. The primary end point, a composite of all-cause death, stroke, systemic/pulmonary embolism, and myocardial infarction, and secondary outcomes (ie, each individual end point) and major bleeding, were considered. RESULTS: HRT was not independently associated with the primary end point (hazard ratio=0.894; 95% confidence interval, 0.658-1.214; P=0.473) or any secondary outcome. Age (P<0.001), diabetes mellitus (P<0.001), previous stroke (P=0.011), and heart failure (P<0.001) predicted the primary end point. Lack of association between HRT and the primary end point was confirmed in a propensity score-matched control group (hazard ratio=0.966; 95% confidence interval, 0.663-1.409; P=0.858). CONCLUSIONS: HRT does not independently predict mortality, thromboembolism, or bleeding in a large cohort of women with atrial fibrillation.

The impact of heart failure and left ventricular dysfunction in predicting stroke, thromboembolism, and mortality in atrial fibrillation patients: a systematic review.

PURPOSE: Atrial fibrillation (AF) is commonly associated with structural heart disease. Although heart failure (HF) has been proposed as a risk factor for stroke, the coexistence of the 2 diseases increases disproportionally the risk of thromboembolic events. Our objective was to conduct a systematic review to assess the effect of HF on the end points of stroke, systemic embolism (SE), or mortality in patients with AF. METHODS: A literature search was performed to identify studies that examined stroke/ SE in relation to AF and HF. Overall, 405 articles satisfied the preinclusion criteria. FINDINGS: In studies in which HF was based on a clinical diagnosis, HF independently increased stroke/SE in 5 of 13 studies, conferring 1.6- to 3.1-fold increase in risk. When HF was defined as impaired left ventricular (LV) function on echocardiography, the additive risk was evident in 4 of 6 studies, with 1.7- to 2.6-fold increase in the risk of stroke/SE. The data about HF with preserved ejection fraction were less robust, although a recent presentation with acute decompensated HF increased the risk of stroke/SE, irrespective of ejection fraction. IMPLICATIONS: LV systolic impairment as identified by echocardiography is an independent risk factor for stroke/SE, although the magnitude by which it increases the risk of stroke cannot be precisely quantified. Whether a clinical diagnosis of HF is a significant risk factor remains inconclusive, although when the diagnosis is certain (recent decompensation requiring hospitalization), it does seem to be a significant risk factor irrespective of LV systolic function.

Exercise-induced changes in inflammatory processes: Implications for thrombogenesis in cardiovascular disease.

Sedentary lifestyle is a risk factor and a strong predictor for chronic disease and premature death. Low-grade inflammation has been proved a key player in the pathogenesis of cardiovascular disease. Inflammatory processes have been also involved in maintaining the balance between coagulation and fibrinolysis. In addition, an inverse linear dose-response relation between physical activity and mortality risks has also been reported. However, the favorable effects of structured exercise programs and the independent contribution of physical activity to cardiovascular risk are still under investigation. In response to heavy exercise, interleukin-6 (IL-6) is secreted by contracting skeletal muscles, followed by an acute reactant release of C-reactive protein (CRP). Both CRP and IL-6 can stimulate monocyte tissue factor production, provoke platelet hyperreactivity, promote fibrinogen biosynthesis, and enhance microparticle formation and erythrocyte aggregability, thus triggering prothrombotic state. By contrast, regular exercise and physical activity are protective against all-cause mortality through suppressing pro-inflammatory cytokine production, enhancing anti-inflammatory mediators and antioxidant development, and promoting fibrinolytic activity. Low-load resistance exercise also plays an advantageous role in thrombogenesis by reducing inflammatory processes and potentiating fibrinolytic features. In the present review article, we provide an overview of the impact of different modes and intensities of physical activity on vascular inflammation and thrombogenesis.

Desmoteplase as a potential treatment for cerebral ischaemia.

INTRODUCTION: Desmoteplase is an investigational plasminogen activator found in the saliva of the vampire bat, Desmodus rotundus. It has been of scientific interest for over 25 years as it exhibits pharmacological properties that have led to the hypothesis that desmoteplase may be safer and more effective than recombinant tissue plasminogen activator (rtPA) in arterial thromboembolic disease, and in particular, acute ischaemic stroke (AIS). AREAS COVERED: In this review, the authors cover the pharmacological properties of desmoteplase, focussing on how this translates into a theoretical advantage over rtPA in AIS. The authors further present preclinical studies and clinical data on the use of desmoteplase in AIS. EXPERT OPINION: In contrast to rtPA, and despite a similar structure, desmoteplase has demonstrated high selectivity for fibrin and an absence of neurotoxicity in experimental models. Demonstrating such properties in animal models, one would have expected an ambitious clinical study future. Phase II and Phase III clinical studies in patients with AIS demonstrated an excellent safety profile with low risk of symptomatic intracranial haemorrhage compared to rtPA. However, data on clinical and radiological efficacy end points of desmoteplase in AIS are inconclusive. Further Phase III trials are currently underway and their results are eagerly awaited.

Monocyte subsets in coronary artery disease and their associations with markers of inflammation and fibrinolysis.

AIMS: The multiple roles of monocytes in atherogenesis, including inflammation, angiogenesis and repair are attributed to the existence of different monocyte sub-populations. Scarce data are available on changes in phenotype and functional status of human monocyte subsets in patients with coronary artery disease (CAD), especially when monocytes are evaluated as three distinct subsets. METHODS AND RESULTS: Surface expression of receptors implicated in inflammation, repair and activation status (intracellular IKKß) of monocyte subsets was assessed by flow cytometry in 53 patients with CAD and compared to 50 age- and sex-matched healthy controls. Monocyte subsets were defined as CD14++CD16-CCR2+ (Mon1), CD14++CD16+CCR2+ (Mon2), and CD14+CD16++CCR2- (Mon3). Plasma levels of inflammatory cytokines (FACSArray) and fibrinolytic factors (ELISA) were measured in CAD. CAD was associated with reduced expression of CD14 on Mon1 (p = 0.02) and Mon3 (p = 0.036), higher expression of IL6 receptor on Mon1 (p = 0.025) and Mon2 (p = 0.015), CXCR4 on Mon1 (p = 0.035) and Mon3 (p = 0.003), and CD34 on all subsets (all p < 0.007). Monocyte CD163 expression correlated negatively with interleukin (IL)-6 levels (p < 0.01 for all subsets). Expression of vascular endothelial growth factor receptor-1 correlated positively with plasminogen activator inhibitor (PAI)-1 antigen levels (r = 0.47, p = 0.006). In vitro, monocyte subsets derived from CAD patients showed significantly altered responses to endotoxin stimulation compared to monocytes from healthy controls. CONCLUSIONS: There is a complex interplay between phenotype and activity of monocytes and plasma cytokines and fibrinolytic factors. These findings support the presence of unique roles for the three human monocyte subsets in atherogenesis and CAD pathogenesis.

Genetic diversity of the KCNE1 gene and susceptibility to postoperative atrial fibrillation.

BACKGROUND: The human KCNE1 protein forms the ß-subunit of the IKs potassium channel and is important in the regulation of the atrial action potential duration. The purpose of this study was to investigate the association between the nonsynonymous 112G>A mutation of the KCNE1 gene and postcardiac surgery atrial fibrillation (AF). METHODS AND RESULTS: A cohort of patients scheduled for cardiac surgery was prospectively recruited. The genotype of 112G>A polymorphism was determined using polymerase chain reaction/restriction fragment analysis and confirmed with direct sequencing of the polymerase chain reaction product. In total, 509 patients were recruited in the study, of whom 203 (39.9%) had at least 1 qualifying episode of postoperative AF. An increased frequency of the G allele was observed in the postoperative AF group compared with the group without postoperative AF (0.628 vs 0.552, respectively, P = .016). The individual's relative risk of postoperative AF increased as the number of G alleles increased from 1.36 (95% CI 0.89-2.08) for G allele heterozygotes to 1.62 (95% CI 1.08-2.43) for G allele homozygotes (P = .04 for trend). The multivariate analysis revealed the abnormal ejection fraction (odds ratio [OR] 1.585, 95% CI 1.076-2.331, P = .020), age (OR 1.043, 95% CI 1.022-1.064, P < .001), type of surgery (aortic valve replacement) (OR 1.869, 95% CI 1.094-3.194, P = .022), and the 112G>A genotype (OR 1.401 [in additive model], 95% CI 1.052-1.865, P = .021) to be independent predictors of postoperative AF. CONCLUSION: This study confirmed the association of the 112G>A polymorphism and postoperative AF in a cohort of patients undergoing cardiac surgery.

Left ventricular geometry and outcomes in patients with atrial fibrillation: the AFFIRM Trial.

BACKGROUND: Echocardiographically determined left ventricular hypertrophy (LVH) is a marker of cardiovascular disease related to prognosis and clinical outcomes. We sought to determine if LVH is a measure of outcomes in atrial fibrillation (AF) patients. METHODS: We performed a post-hoc analysis of patients with echocardiographic data enrolled in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Trial. Patients were stratified based on gender-adjusted echocardiography derived interventricular septal (IVS) thickness, relative wall thickness (RWT), gender-adjusted LV mass, and type of LV remodeling (normal LV geometry, concentric hypertrophy, eccentric hypertrophy, and concentric remodeling). RESULTS: Of 4060 patients in AFFIRM, echocardiographic data were available in 2433 patients (60%). Multivariate analysis revealed that LVH defined as moderately or severely abnormal IVS thickness was an independent predictor of both all cause mortality (HR 1.46, 95%CI 1.14-1.86, p=0.003) and stroke (HR 1.89, 95%CI 1.17-3.08, p=0.01). This association was confirmed when IVS thickness was assessed as continuous or categorical variable. Concentric LV hypertrophy was associated with the highest rates of all cause mortality (HR 1.53; 95%CI 1.11-2.12; p=0.009). CONCLUSION: An easily obtained echocardiographic index of LVH (IVS thickness) may enhance risk stratification of patients with AF, and raise the possibility that LVH regression should be a therapeutic target in this population.

Cost effectiveness of treatments for stroke prevention in atrial fibrillation: focus on the novel oral anticoagulants.

For more than 5 decades, the only available treatment for the prevention of atrial fibrillation (AF)-related stroke were the vitamin K antagonists. Recently, novel oral anticoagulants (NOAC) have been approved for the prevention of AF-related stroke. In the present article, the cost effectiveness of AF-related stroke-prevention strategies is reviewed. The emphasis on NOACs aims to provide an overview of their impact on health economics based on the published cost-effectiveness analyses. The available evidence suggests that the balance from the efficacy and safety point of view makes the treatment with the NOACs a cost-effective alternative to warfarin. Thus, the NOACs offer efficacy, safety and convenience, as well as cost effectiveness, for stroke prevention in AF.

Development of a novel composite stroke and bleeding risk score in patients with atrial fibrillation: the AMADEUS Study.

BACKGROUND: The aim of the current analysis was to identify independent predictors of the overall clinical outcome of patients with atrial fibrillation (AF), including both stroke/thromboembolism and/or major bleeding. Given the overlap between stroke and bleeding risk factors, a composite risk-stratification score for stroke/thromboembolism or bleeding could potentially be developed. METHODS: We used data from the vitamin K antagonist (VKA) arm (n = 2,293; 65% men; mean age 70 ± 9 years) of the AMADEUS (Evaluating the Use of SR34006 Compared to Warfarin or Acenocoumarol in Patients With Atrial Fibrillation) trial, which was a multicenter, randomized, open-label noninferiority study that compared fixed-dose idraparinux with VKA in patients with AF. We defined two composite end points: end point 1 was the combination of stroke/thromboembolism or major bleeding; end point 2 was defined as the combination of stroke, systemic or venous embolism, myocardial infarction, cardiovascular death, or major bleeding. RESULTS: The independent predictors for composite end point 1 were age (P = .014), previous stroke/transient ischemic attack (P = .049), aspirin use (P = .002), and time in therapeutic range (P = .007). For composite end point 2, similar predictors were evident, plus left ventricular dysfunction (P = .011). Based on the regression models, two novel composite risk-prediction scores were developed and were validated externally in a "real-world" cohort of 441 outpatients with AF receiving anticoagulation treatment. Both composite scores 1 and 2 demonstrated numerically higher discriminatory performance (area under the curve [AUC], 0.728; 95% CI, 0.659-0.798 and AUC, 0.707; 95% CI, 0.655-0.758, for end points 1 and 2, respectively) and a positive net reclassification when compared with currently used risk models (CHADS2 [congestive heart failure, hypertension, age ≥ 75 years, diabetes, prior stroke or transient ischemic attack], CHA2DS2VASc [cardiac failure or dysfunction, hypertension, age ≥ 75 years [doubled], diabetes, stroke (doubled)-vascular disease, age 65 to 74 years, and sex category (female)], and HAS-BLED [hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly]), but the differences were not statistically significant. CONCLUSIONS: We have developed and validated two novel composite scores for stroke/thromboembolism/bleeding that offer good discriminatory and predictive performance. However, these composite risk scores did not perform better than the easier and more practical "traditional" stroke and bleeding risk scores that are currently in use, which allow greater practicality and a more personalized balancing of risks.

Renal function and outcomes in anticoagulated patients with non-valvular atrial fibrillation: the AMADEUS trial.

AIMS: Limited data are available on the impact of renal function on the outcome of patients with atrial fibrillation (AF). METHODS AND RESULTS: AMADEUS was a multicentre, randomized, open-label non-inferiority study that compared fixed-dose idraparinux with conventional anticoagulation by dose-adjusted vitamin K antagonists. We performed a post hoc analysis to assess the impact of renal function on the outcomes of anticoagulated AF patients. The primary efficacy outcome was the composite of stroke/systemic embolism (SE). The principal safety outcome of this analysis was major bleeding. We calculated c-indexes, reflecting the ability for discriminating diseased vs. non-diseased patients, and the net reclassification improvement (NRI, an index of inferior/superior performance of risk estimation scores). Of 4576 patients, 45 strokes and 103 major bleeding events occurred following an average follow-up of 325 ± 164 days. Patients with CrCl >90 mL/min had an annual stroke/SE rate of 0.6% compared with 0.8% for those with CrCl 60-90 mL/min and 2.2% for those with CrCl <60 mL/min (P < 0.001 for linear association). After adjusting for stroke risk factors, patients with CrCl <60 mL/min had more than two-fold higher risk of stroke/SE and almost 60% higher risk of major bleeding compared with those with CrCl ≥60. In patients with the CHA2DS2VASc score 1-2, CrCl <60 mL/min was associated with eight-fold higher stroke risk. When added to the CHA2DS2VASc or CHADS2 scores, CrCl <60 mL/min did not improve the c-indexes for CHADS2 (P = 0.054) or CHA2DS2VASc (P = 0.63) but resulted in significant NRI (0.26, P = 0.02) in this anticoagulated trial cohort. CONCLUSION: Renal impairment (CrCl <60 mL/min) doubles the risk of stroke and increased the risk of major bleeding by almost 60% in anticoagulated patients with AF. Renal impairment was additive to stroke risk prediction scores based on a significant NRI, but no significant improvement in discrimination ability (based on c-indexes) for CHA2DS2VASc or CHADS2 was observed.

Chemokines and atherosclerosis: focus on the CX3CL1/CX3CR1 pathway.

Atherosclerosis is currently considered an inflammatory disease. Much attention has been focused on the potential role of inflammatory mediators as prognostic/diagnostic markers or therapeutic targets of atherosclerotic cardiovascular disease. CX3CL1 (or fractalkine) is a structurally and functionally unique chemokine with a well documented role in atherosclerosis. In its membrane bound form it promotes the firm adhesion of rolling leucocytes onto the vessel wall, while in its soluble form it serves as a potent chemoattractant for CX3CR1-expressing cells. Additionally, CX3CL1 exerts cytotoxic effects on the endothelium as well as anti-apoptotic and proliferative effects on vascular cells, affecting the context and stability of the atherosclerotic plaque. Studies on animal models have shown that the blockade of the CX3CL1/CX3CR1 pathway ameliorates the severity of atherosclerosis, while genetic epidemiology has confirmed that a genetically-defined less active CX3CL1/CX3CR1 pathway is associated with a reduced risk of atherosclerotic disease in humans. Although several studies support an important pathogenic role of CX3CL1/CX3CR1 in atherogenesis and plaque destabilization, this does not necessarily suggest that this pathway is a suitable therapeutic target or that CX3CL1 can serve as a prognostic/diagnostic biomarker. Further studies on the CX3CL1/CX3CR1 chemokine pathway are clearly warranted to justify the clinical relevance of its role in atherosclerosis.

Personalized management of atrial fibrillation: Proceedings from the fourth Atrial Fibrillation competence NETwork/European Heart Rhythm Association consensus conference.

The management of atrial fibrillation (AF) has seen marked changes in past years, with the introduction of new oral anticoagulants, new antiarrhythmic drugs, and the emergence of catheter ablation as a common intervention for rhythm control. Furthermore, new technologies enhance our ability to detect AF. Most clinical management decisions in AF patients can be based on validated parameters that encompass type of presentation, clinical factors, electrocardiogram analysis, and cardiac imaging. Despite these advances, patients with AF are still at increased risk for death, stroke, heart failure, and hospitalizations. During the fourth Atrial Fibrillation competence NETwork/European Heart Rhythm Association (AFNET/EHRA) consensus conference, we identified the following opportunities to personalize management of AF in a better manner with a view to improve outcomes by integrating atrial morphology and damage, brain imaging, information on genetic predisposition, systemic or local inflammation, and markers for cardiac strain. Each of these promising avenues requires validation in the context of existing risk factors in patients. More importantly, a new taxonomy of AF may be needed based on the pathophysiological type of AF to allow personalized management of AF to come to full fruition. Continued translational research efforts are needed to personalize management of this prevalent disease in a better manner. All the efforts are expected to improve the management of patients with AF based on personalized therapy.