ABSTRACT
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.
Abstract
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 (CV) disease 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, which was reported previously, focused on the epidemiology, pathophysiology, and diagnosis of CV conditions that may be manifest in patients with COVID-19. This second part addresses the topics of: care pathways and triage systems and management and treatment pathways, both of the most commonly encountered CV conditions and of COVID-19; and information that may be considered useful to help patients with CV disease (CVD) to avoid exposure to 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.
Graphical Abstract
Graphical Abstract
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.
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.
Abstract
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.
Graphical Abstract
Abstract
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 (CV) disease 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, which was reported previously, focused on the epidemiology, pathophysiology, and diagnosis of CV conditions that may be manifest in patients with COVID-19. This second part addresses the topics of: care pathways and triage systems and management and treatment pathways, both of the most commonly encountered CV conditions and of COVID-19; and information that may be considered useful to help patients with CV disease (CVD) to avoid exposure to 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.
Graphical Abstract
Graphical Abstract
Lone atrial fibrillation (AF) has been suggested to have a favorable long-term prognosis. Significant interest has been directed at factors predicting arrhythmia progression, and the HATCH score ...(hypertension, age ≥ 75 years, transient ischemic attack or stroke 2 points, COPD, and heart failure 2 points) recently has been proposed as a predictive score for AF progression. We investigated long-term outcomes in a large cohort of newly diagnosed lone AF and whether progression from paroxysmal to permanent AF confers an adverse impact on outcomes, including stroke and thromboembolism.
The study was an observational cohort of 346 patients with newly diagnosed lone AF with a mean follow-up of 12.1 ± 7.3 years.
Baseline paroxysmal AF was confirmed in 242 patients, and of these, 65 (26.9%) subsequently experienced progression to permanent AF. Older age and development of congestive heart failure during follow-up were the multivariate predictors of AF progression (both P < .01), which was documented in 19.8% of patients with a HATCH score of 0 vs 63.2% with a score of 2 (P < .001), although the predictive validity of the HATCH score per se was modest (C statistic, 0.6). The annual rate of thromboembolism and heart failure during follow-up were low (0.4% each), and five patients (1.4%) died. AF progression, development of cardiac diseases, and older age were multivariate predictors of adverse outcomes, including thromboembolism (all P < .05). Baseline CHADS(2) (congestive heart failure, hypertension, age ≥ 75, diabetes mellitus, prior stroke or transient ischemic attack) score was not predictive for thromboembolism (C statistic, 0.50; 95% CI, 0.31-0.69).
This 12-year follow-up study provides confirmatory evidence of a generally favorable prognosis of lone AF, but adverse outcomes (including stroke and thromboembolism) are significantly influenced by age and the (new) development of underlying heart disease. Arrhythmia progression in lone AF is a marker of increased risk for adverse cardiovascular events.
Abstract 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), CHA2 DS2 –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.
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.
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.
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).
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.
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