Prognostic Implications of the Timing of ST-Elevation Myocardial Infarction Development in Relation to COVID-19 Infection.

Background: Patients with ST-segment elevation myocardial infarction (STEMI) and COVID-19 infection have a worse clinical course and prognosis. The prognostic significance of the timing of STEMI in relation to COVID-19 infection was not investigated. Objectives: To assess whether the time of STEMI development in relation to COVID-19 infection (concurrent or following the infection) influenced the short-term prognosis. Methods: This was an observational study of consecutive COVID-19 patients with STEMI admitted to the COVID-hospital Batajnica (February 2021-March 2022). The patients were divided into the "STEMI first" group: patients with STEMI and a positive polymerase chain reaction test for COVID-19, and the "COVID-19 first" group: patients who developed STEMI during COVID-19 treatment. All patients underwent coronary angiography. The primary endpoint was in-hospital all-cause mortality. Results: The study included 87 patients with STEMI and COVID-19 (Mage, 66.7 years, 66% male). The "STEMI first" group comprised 54 (62.1%) patients, and the "COVID-19 first" group included 33 (37.9%) patients. Both groups shared a comparatively high burden of comorbidities, similar angiographic and procedural characteristics, and high percentages of performed percutaneous coronary interventions with stent implantation (90.7% vs. 87.9%). In-hospital mortality was significantly higher in the "COVID-19 first" group compared to the "STEMI first" group (51.5% vs. 27.8%). Following adjustment, the "COVID-19 first" group had a hazard ratio of 3.22 (95% confidence interval, 1.18-8.75, p = .022) for in-hospital all-cause death, compared with the "STEMI first" group (reference). Conclusion: Clinical presentation with COVID-19 infection, followed by STEMI ("COVID-19 first"), was associated with greater short-term mortality compared to patients presenting with STEMI and testing positive for COVID-19 ("STEMI first").

European Society of Cardiology guidance for the diagnosis and management of cardiovascular disease during the COVID-19 pandemic: part 1-epidemiology, pathophysiology, and diagnosis.

AIMS: Since its emergence in early 2020, the novel severe acute respiratory syndrome coronavirus 2 causing coronavirus disease 2019 (COVID-19) has reached pandemic levels, and there have been repeated outbreaks across the globe. The aim of this two-part series is to provide practical knowledge and guidance to aid clinicians in the diagnosis and management of cardiovascular disease (CVD) in association with COVID-19. METHODS AND RESULTS: A narrative literature review of the available evidence has been performed, and the resulting information has been organized into two parts. The first, reported here, focuses on the epidemiology, pathophysiology, and diagnosis of cardiovascular (CV) conditions that may be manifest in patients with COVID-19. The second part, which will follow in a later edition of the journal, addresses the topics of care pathways, treatment, and follow-up of CV conditions in patients with COVID-19. CONCLUSION: This comprehensive review is not a formal guideline but rather a document that provides a summary of current knowledge and guidance to practicing clinicians managing patients with CVD and COVID-19. The recommendations are mainly the result of observations and personal experience from healthcare providers. Therefore, the information provided here may be subject to change with increasing knowledge, evidence from prospective studies, and changes in the pandemic. Likewise, the guidance provided in the document should not interfere with recommendations provided by local and national healthcare authorities.

European Society of Cardiology/Heart Failure Association position paper on the role and safety of new glucose-lowering drugs in patients with heart failure.

Type 2 diabetes mellitus (T2DM) is common in patients with heart failure (HF) and associated with considerable morbidity and mortality. Significant advances have recently occurred in the treatment of T2DM, with evidence of several new glucose-lowering medications showing either neutral or beneficial cardiovascular effects. However, some of these agents have safety characteristics with strong practical implications in HF [i.e. dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RA), and sodium-glucose co-transporter type 2 (SGLT-2) inhibitors]. Regarding safety of DPP-4 inhibitors, saxagliptin is not recommended in HF because of a greater risk of HF hospitalisation. There is no compelling evidence of excess HF risk with the other DPP-4 inhibitors. GLP-1 RAs have an overall neutral effect on HF outcomes. However, a signal of harm suggested in two small trials of liraglutide in patients with reduced ejection fraction indicates that their role remains to be defined in established HF. SGLT-2 inhibitors (empagliflozin, canagliflozin and dapagliflozin) have shown a consistent reduction in the risk of HF hospitalisation regardless of baseline cardiovascular risk or history of HF. Accordingly, SGLT-2 inhibitors could be recommended to prevent HF hospitalisation in patients with T2DM and established cardiovascular disease or with multiple risk factors. The recently completed trial with dapagliflozin has shown a significant reduction in cardiovascular mortality and HF events in patients with HF and reduced ejection fraction, with or without T2DM. Several ongoing trials will assess whether the results observed with dapagliflozin could be extended to other SGLT-2 inhibitors in the treatment of HF, with either preserved or reduced ejection fraction, regardless of the presence of T2DM. This position paper aims to summarise relevant clinical trial evidence concerning the role and safety of new glucose-lowering therapies in patients with HF.

Heart failure in dilated non-ischaemic cardiomyopathy.

Heart failure (HF) is the prevailing cause of morbidity and mortality in patients with dilated non-ischaemic cardiomyopathy (DCM) and DCM is one of several causes of HF, with several distinct epidemiological and clinical features which may have important implications for its management and prognosis. This article reviews cardiovascular monitoring of specific characteristics of HF in DCM. DCM is defined as ventricular dilatation and systolic dysfunction in the absence of abnormal loading conditions or significant coronary artery disease, the predominant phenotypes of being HFmrEF or HFrEF. DCM accounts for ∼40% of all cardiomyopathies but its true prevalence among patients with HFrEF is difficult to ascertain with certainty. Compared with patients with other HF aetiologies, individuals with DCM tend to be younger, more likely male and less likely to have associated comorbidities. A genetic aetiology of DCM is deemed responsible for ∼40% of cases. Confirmation of a specific genetic background is clinically relevant (e.g. Duchene or Backer muscular dystrophies, lamin A/C mutation), because those patients may be at a high risk of progressive left ventricular dysfunction or conduction system disease and sudden death, prompting early prophylaxis with an implantable cardioverter defibrillator. However, in most instances, HF in DCM has a multifactorial aetiology, with multiple factors needing to be systematically evaluated and/or monitored, since correction of reversible causes or (e.g. tachycardia-induced cardiomyopathy, alcohol intoxication, iron-overload, cancer therapies etc.) or targeting specific pathophysiological causes could lead to an improvement in clinical status. The treatment of DCM encompasses HF-related pharmacological and device therapies, and aetiology-specific treatments. At present, options for aetiology-related therapies are limited, and their effectiveness mostly requires confirmation from larger scale randomized trials. Whether outcomes of patients with HF in DCM differ from those with other HF aetiologies is unresolved. DCM is attributable for >40% of patients receiving mechanical circulatory support for advanced HF and it is the leading indication for heart transplantation. More aetiology-specific information is needed both in the evaluation and treatment of dilated cardiomyopathy.

Brugada syndrome: A general cardiologist's perspective.

Brugada syndrome (BrS) is one of the commonest inherited primary arrhythmia syndromes typically presenting with arrhythmic syncope or sudden cardiac death (SCD) due to polymorphic ventricular tachycardia and ventricular fibrillation precipitated by vagotonia or fever in apparently healthy adults, less frequently in children. The prevalence of the syndrome (0.01%-0.3%) varies among regions and ethnicities, being the highest in Southeast Asia. BrS is diagnosed by the "coved type" ST-segment elevation≥2mm followed by a negative T-wave in ≥1 of the right precordial leads V1-V2. The typical electrocardiogram in BrS is often concealed by fluctuations between normal, non-diagnostic and diagnostic ST-segment pattern in the same patient, thus hindering the diagnosis. Presently, the majority of BrS patients is incidentally diagnosed, and may remain asymptomatic for their lifetime. However, BrS is responsible for 4-12% of all SCDs and for ~20% of SCDs in patients with structurally normal hearts. Arrhythmic risk is the highest in SCD survivors and in patients with spontaneous BrS electrocardiogram and arrhythmic syncope, but risk stratification for SCD in asymptomatic subjects has not yet been fully defined. Recent achievements have expanded our understanding of the genetics and electrophysiological mechanisms underlying BrS, while radiofrequency catheter ablation may be an effective new approach to treat ventricular tachyarrhythmias in BrS patients with arrhythmic storms. The present review summarizes our contemporary understanding and recent advances in the inheritance, pathophysiology, clinical assessment and treatment of BrS patients.

Stroke prevention in atrial fibrillation and 'real world' adherence to guidelines in the Balkan Region: The BALKAN-AF Survey.

Data on the management of atrial fibrillation (AF) in the Balkan Region are limited. The Serbian AF Association (SAFA) prospectively investigated contemporary 'real-world' AF management in clinical practice in Albania, Bosnia&Herzegovina, Bulgaria, Croatia, Montenegro, Romania and Serbia through a 14-week (December 2014-February 2015) prospective, multicentre survey of consecutive AF patients. We report the results pertinent to stroke prevention strategies. Of 2712 enrolled patients, 2663 (98.2%) with complete data were included in this analysis (mean age 69.1 ± 10.9 years, female 44.6%). Overall, 1960 patients (73.6%) received oral anticoagulants (OAC) and 762 (28.6%) received antiplatelet drugs. Of patients given OAC, 17.2% received non-vitamin K antagonist oral anticoagulants (NOACs). CHA2DS2-VASc score was not significantly associated with OAC use. Of the 'truly low-risk' patients (CHA2DS2-VASc = 0 [males], or 1 [females]) 56.5% received OAC. Time in Therapeutic Range (TTR) was available in only 18.7% of patients (mean TTR: 49.5% ± 22.3%). Age ≥ 80 years, prior myocardial infarction and paroxysmal AF were independent predictors of OAC non-use. Our survey shows a relatively high overall use of OAC in AF patients, but with low quality of vitamin K antagonist therapy and insufficient adherence to AF guidelines. Additional efforts are needed to improve AF-related thromboprophylaxis in clinical practice in the Balkan Region.

Typical chest pain and precordial leads ST-elevation in patients with pacemakers--are we always looking at an acute myocardial infarction?

INTRODUCTION: Electrocardiographic (ECG) diagnosis of acute myocardial infarction (AMI) in patients with paced rhythm is difficult. Sgarbossa's criteria represent helpful diagnostic ECG tool. CASE REPORT: A 57-year-old female patient with paroxysmal atrial fibrillation and a permanent pacemaker presented in the Emergency Department with prolonged typical chest pain and ECG recording suggestive for AMI. Documented ECG changes correspond to the first Sgarbossa's criterion for AMI in patients with dual pacemakers (ST-segment elevation of 5 mn in the presence of the negative QRS complex). The patient was sent to catheterization lab where coronary angiogram reveled normal findings. ECG changes occurred due to pericardial reaction following two interventions: pacemaker implantation a month before and radiofrequency catheter ablation of AV junction two weeks before presentation in Emergency Department. CONCLUSION: This case report points out to the limitations of proposed criteria that aid in the recognition of AMI in patients with underlying paced rhythm and possible cause(s) of transient electrocardiographic abnormalities.

Relation of Biomarkers of Inflammation and Oxidative Stress with Hypertension Occurrence in Lone Atrial Fibrillation.

We compared plasma levels of biomarkers of inflammation (CRP) and oxidation (oxLDL), determined at study inclusion in lone atrial fibrillation (LAF) patients (48.6 ± 11.5 years; 74.0% men) and sinus rhythm controls (49.7 ± 9.3 years; 72.7% men, P > 0.05), and investigated the association of baseline CRP and oxLDL levels with the risk for vascular disease (VD) development (hypertension, cerebrovascular disease, coronary/peripheral artery disease, and pulmonary embolism) during prospective follow-up. Baseline CRP (1.2 [0.7-1.9] mg/L versus 1.1 [0.7-1.6] mg/L) and oxLDL levels (66.3 ± 21.2 U/L versus 57.1 ± 14.6 U/L) were higher in LAF patients (both P < 0.05). Following a median of 36 months, incident VD occurred in 14 (28.0%) LAF patients, all of whom developed arterial hypertension, and in 5 (11.4%) controls (hypertension, n = 4; coronary artery disease, n = 1), P < 0.05. LAF patients developed VD more frequently and at a younger age. Both CRP (HR, 2.54; 95% CI, 1.26-5.12; P = 0.009) and oxLDL (HR, 2.24; 95% CI, 1.14-4.40; P = 0.019) were multivariate predictors of incident hypertension in LAF patients, but not in the controls. Further research should clarify clinical relevance of investigated biomarkers for risk stratification and treatment of LAF patients.

Endothelial (dys)function in lone atrial fibrillation.

Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia in adult population and confers significant thromboembolic risk. Endothelial dysfunction has been recognized as a possible contributor to thrombogenesis in AF. The arrhythmia has been associated with thrombogenic atrial endocardial lesions and evidence of increased circulating biomarkers of endothelial dysfunction (e.g. von Willebrand factor, soluble thrombomodulin, E-selectin, asymmetric dimethylarginine, circulating endothelial cells and microparticles), and impairment of endothelium-dependent vasodilatation in the peripheral and coronary circulation has been reported in AF patients. Increased levels of biomarkers of endothelial origin (e.g. von Willebrand factor, soluble thrombomodulin, E-selectin, asymmetric dimethylarginine) have been associated with adverse outcomes in AF patients. Importantly, endothelial dysfunction has been documented in AF patients without cardio-pulmonary comorbidities or risk factors (so-called 'lone AF'), as well. In this review, we provide an overview of contemporary evidence for the alterations in endothelial function and endothelial injury in AF, with a focus on endothelial (dys)function in lone AF.

The association of CHA2DS2-VASc score and blood biomarkers with ischemic stroke outcomes: the Belgrade stroke study.

BACKGROUND: Many blood biomarkers have a positive association with stroke outcome, but adding blood biomarkers to the National Institutes of Health Stroke Scale (NIHSS) did not significantly improve its discriminatory ability. We investigated the association of the CHA2DS2-VASc score with unfavourable functional outcome (defined as a 30-day modified Rankin Scale [mRS] ≥ 3) in patients presenting with acute ischemic stroke (AIS), and examined whether the addition of blood biomarkers (troponin I [TnI], fibrinogen, C-reactive protein [CRP]) affects the model discriminatory ability. METHODS: We conducted an observational single-centre study of consecutive patients with AIS. All patients were admitted to hospital within 24 hours from the neurological symptoms onset. RESULTS: Of 240 patients (mean age 70.0 ± 8.9 years), unfavourable 30-day outcome occurred in 92 (38.3%). Patients with mRS ≥ 3 were older and more likely to have atrial fibrillation or other comorbidities (all p<0.001). They had higher levels of CRP, fibrinogen, TnI and higher CHA2DS2-VASc and CHADS2 scores (all p<0.05). The adjusted CHA2DS2-VASc score had excellent predictive ability for poor stroke outcome (c-statistic 0.982;95%CI,0.964-1.000, p<0.001). Whilst CRP had the highest sensitivity (83.7%), cardiac TnI was the most specific (97.3%) for prediction of poor stroke outcome (cut-off: >0.09 µg/L). Compared with each of these biomarkers, CHA2DS2-VASc score had significantly better predictive ability for poor stroke outcome (c-statistic for CRP, Fibrinogen and TnI was 0.853;95%CI,0.802-0.895, 0.848;95%CI,0.796-0.891, and 0.792;95%CI,0.736-0.842, all p<0.001, respectively, versus 0.932;95%CI,0.892-0.960, p<0.001 for the CHA2DS2-VASc, all p for the comparisons<0.01). There was no significant difference in the predictive ability of the CHA2DS2-VASc score vs. combinations of the CHA2DS2-VASc and TnI or TnI, fibrinogen and CRP (z statistic 0.369, p = 0.7119; integrated discrimination index 0.00801 and 0.00172, respectively, both p>0.05). CONCLUSIONS: The CHA2DS2-VASc score alone reliably predicts 30-day unfavourable outcome of stroke. Adding blood biomarkers to the CHA2DS2-VASc score did not significantly increase the predictive ability of the model.

Endothelial dysfunction in metabolic and vascular disorders.

Vascular endothelium has important regulatory functions in the cardiovascular system and a pivotal role in the maintenance of vascular health and metabolic homeostasis. It has long been recognized that endothelial dysfunction participates in the pathogenesis of atherosclerosis from early, preclinical lesions to advanced, thrombotic complications. In addition, endothelial dysfunction has been recently implicated in the development of insulin resistance and type 2 diabetes mellitus (T2DM). Considering that states of insulin resistance (eg, metabolic syndrome, impaired fasting glucose, impaired glucose tolerance, and T2DM) represent the most prevalent metabolic disorders and risk factors for atherosclerosis, it is of considerable scientific and clinical interest that both metabolic and vascular disorders have endothelial dysfunction as a common background. Importantly, endothelial dysfunction has been associated with adverse outcomes in patients with established cardiovascular disease, and a growing body of evidence indicates that endothelial dysfunction also imparts adverse prognosis in states of insulin resistance. In this review, we discuss the association of insulin resistance and T2DM with endothelial dysfunction and vascular disease, with a focus on the underlying mechanisms and prognostic implications of the endothelial dysfunction in metabolic and vascular disorders. We also address current therapeutic strategies for the improvement of endothelial dysfunction.

Patient preferences at ten years following initial diagnosis of atrial fibrillation: the Belgrade Atrial Fibrillation Study.

BACKGROUND: Many atrial fibrillation (AF) patients have a poor understanding of the management of this condition. We investigated patient attitudes towards AF and a potential invasive treatment following an average 10-year period of prospective rhythm control in a cohort of newly diagnosed AF patients. METHODS: This was a prospective registry-based study. At the regular annual visit in 2007, patients were asked at random to answer several AF-related questions. RESULTS: Of 390 patients, 277 (71.0%) reported symptom reduction over time, but only 45 (11.5%) reported that they had "got used" to AF; 201 patients (51.5%) stated they would always prefer sinus rhythm, and 280 (71.2%) would accept an invasive AF treatment. Independent predictors for choosing an invasive procedure were younger age, impaired career/working capacity, and male gender (all P < 0.05). CONCLUSION: Our findings suggest that most AF patients prefer sinus rhythm and would readily accept an invasive procedure if it offered the possibility of a cure for their AF.

A comparison of clinical characteristics and long-term prognosis in asymptomatic and symptomatic patients with first-diagnosed atrial fibrillation: the Belgrade Atrial Fibrillation Study.

BACKGROUND: To investigate baseline characteristics and long-term prognosis of carefully characterized asymptomatic and symptomatic patients with atrial fibrillation (AF) in a 'real-world' cohort of first-diagnosed non-valvular AF over a 10-year follow-up period. METHODS AND RESULTS: We conducted an observational, non-interventional, and single-centre registry-based study of consecutive first-diagnosed AF patients. Of 1100 patients (mean age 52.7±12.2 years and mean follow-up 9.9±6.1 years), 146 (13.3%) had asymptomatic AF. Persistent or permanent AF, slower ventricular rate during AF (<100/min), CHA2DS2-VASc score of 0, history of diabetes mellitus and male gender were independent baseline risk factors for asymptomatic AF presentation (all p<0.01) with a good predictive ability of the multivariable model (c-statistic 0.86, p<0.001). Kaplan-Meier 10-year estimates of survival free of progression of AF (log-rank test=33.4, p<0.001) and ischemic stroke (log-rank test=6.2, p=0.013) were significantly worse for patients with asymptomatic AF compared to those with symptomatic arrhythmia. In the multivariable Cox regression analysis, intermittent asymptomatic AF was significantly associated with progression to permanent AF (Hazard Ratio 1.6; 95% CI, 1.1-2.2; p=0.009). CONCLUSIONS: In a 'real-world' setting, patients with asymptomatic presentation of their first-diagnosed AF could have different risk profile and long-term outcomes compared to those with symptomatic AF. Whether more intensive monitoring and comprehensive AF management including AF ablation at early stage following the incident episode of AF and increased quality of oral anticoagulation could alter the long-term prognosis of these patients requires further investigation.

Recent advances in antiarrhythmic drug treatment of atrial fibrillation.

Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia in clinical practice associated with significant morbidity and mortality. With the growing number of the affected individuals, the development of safe and effective treatment options for AF has become a worldwide priority. Currently available antiarrhythmic medications for the restoration and maintenance of sinus rhythm have limitations due to the modest efficacy and a potential for adverseeffects. Although substantial progress has been made in AF-ablation techniques, broad application of these nonpharmacological treatment modalities is limited and antiarrhythmic drug treatment is still the cornerstone and the first-line therapy for the majority of AF patients. Improvements in the understanding of the principal pathophysiological mechanisms of AF obtained in the last several years have provided promising treatment opportunities. New therapeutic options are based on the more selective targeting of ion channels and intercellular connection proteins predominantly expressed in the atria, the restoration of intracellular Ca(2+) homeostasis and the prevention of AF-associated electrical and structural remodeling. In this review, we provide a highlight of the most important pathophysiological mechanisms in AF with a relation to the potential therapeutic interventions, and discuss novel findings regarding the current and future pharmacological AF management and recent patents.

Predictors and prognostic implications of incident heart failure following the first diagnosis of atrial fibrillation in patients with structurally normal hearts: the Belgrade Atrial Fibrillation Study.

AIM: Atrial fibrillation (AF) commonly co-exists with heart failure (HF). The risk factors for and prognostic implications of incident HF development in patients with first-diagnosed AF and structurally normal hearts are poorly defined. In a cohort of patients with first-diagnosed AF and structurally normal hearts on baseline echocardiography, we investigated baseline risk factors for the development of incident HF and tested the hypothesis that incident HF was an independent predictor of adverse outcomes during a mean 10-year follow-up period. METHODS AND RESULTS: This was a registry-based, observational cohort study of 842 patients initially diagnosed between 1992 and 2007 (mean age 51.6 ± 12.4 years), whereby 83 (9.9%) developed HF. The linearized rate of incident HF was 0.97% [95% confidence interval (CI) 0.78-1.19%] per 100 patient-years. Baseline history of hypertension, diabetes mellitus, dilated left atrium, and low-normal LVEF (50-54%) were multivariable predictors of subsequent HF (all P < 0.05). HF development was significantly associated with increased number of hospitalizations, AF progression, any stroke/peripheral thrombo-embolism, ischaemic stroke, cardiovascular death, and all-cause mortality (all P < 0.001). Kaplan-Meier 10-year estimates of survival free of the composite endpoint of AF progression, thrombo-embolism, and mortality were significantly worse for AF patients with incident HF compared with those without HF (68.8%; 95% CI 64.7-72.9 vs. 25.9% 95% CI 15.7-36.1, P < 0.001). CONCLUSION: Underlying co-morbidities or subtle alterations such as mild left atrial dilatation or low-normal LVEF in the absence of overt underlying heart disease are baseline independent risk factors for incident HF during a long-term follow-up. Incident HF was an independent predictor of adverse outcomes in patients initially diagnosed with first-diagnosed AF and structurally normal hearts. These findings could facilitate the identification of AF patients at increased risk for adverse outcomes within the cohort perceived as being at 'low risk' given a structurally normal heart on echocardiography.