Association Between Atrial Fibrillation and Occupational Exposure in Firefighters Based on Self-Reported Survey Data.

Background Exposure to inhaled smoke, pollutants, volatile organic compounds, and polycyclic aromatic hydrocarbons in the firefighting environment has been associated with detrimental respiratory and cardiovascular effects, making firefighters a unique population with both personal and occupational risk factors for cardiovascular disease. Some of these exposures are also associated with development of atrial fibrillation. We aimed to study the association of atrial fibrillation and occupational exposure in firefighters. Methods and Results A cross-sectional survey was conducted between October 2018 and December 2019. Data were gathered electronically and stored in a secure REDCap database through Louisiana State University Health Shreveport. Firefighters who were members of at least 1 of 5 preselected professional organizations were surveyed via electronic links distributed by the organizations. The survey queried the number of fires fought per year as a measure of occupational exposure, as well as self-reported cardiovascular disease. A total of 10 860 active firefighters completed the survey, of whom 93.5% were men and 95.5% were aged ≤60 years. Firefighters who fought a higher number of fires per year had a significantly higher prevalence of atrial fibrillation (0-5 fires per year 2%, 6-10 fires per year 2.3%, 11-20 fires per year 2.7%, 21-30 fires per year 3%, 31 or more fires per year 4.5%; P<0.001). Multivariable logistic regression showed that a higher number of fires fought per year was associated with an increased risk of atrial fibrillation (odds ratio 1.14 [95% CI, 1.04-1.25]; P=0.006). Conclusions Firefighters may have an increased risk of atrial fibrillation associated with the number of fires they fight per year. Further clinical and translational studies are needed to explore causation and mechanisms.

Cancer Radiation Therapy May Be Associated With Atrial Fibrillation.

Background: The association of atrial fibrillation (AF) with cancer and cancer types is inconclusive. Similarly, data regarding the association of AF with different cancer therapies are controversial. Objectives: To study the association of AF with cancer subtypes and cancer therapies. Methods: We studied all patients aged 18-89 years who presented to the Feist Weiller Cancer Center, with or without a diagnosis of cancer, between January 2011 and February 2016. Electronic health records were systematically queried for baseline demographics and ICD-9 and ICD-10 codes for specific co-morbidities. Patients with a diagnosis of AF were tabulated based on cross-validation with the ECG database and/or by recorded history. We assessed the prevalence and risk of AF based on cancer diagnosis, specific cancer type, and cancer therapy. Results: A total of 14,600 patients were analyzed. Compared to non-cancer patients (n = 6,801), cancer patients (n = 7,799) had a significantly higher prevalence of AF (4.3 vs. 3.1%; p < 0.001). However, following correction for covariates in a multivariable logistic regression model, malignancy was not found to be an independent risk factor for AF (p = 0.32). While patients with solid tumors had a numerically higher prevalence of AF than those with hematological malignancies (4.3 vs. 4.1%), tumor type was not independently associated with AF (p = 0.13). AF prevalence was higher in patients receiving chemotherapy (4.1%), radiation therapy (5.1%), or both (6.9%) when compared to patients not receiving any therapy (3.6%, p = 0.01). On multivariable logistic regression, radiation therapy remained an independent risk factor for AF for the entire study population (p = 0.03) as well as for the cancer population (p < 0.01). Conclusions: Radiation therapy for cancer is an independent risk factor for AF. The known association between cancer and AF may be mediated, at least in part, by the effects of radiation therapy.

Decreased bioavailability of hydrogen sulfide links vascular endothelium and atrial remodeling in atrial fibrillation.

Oxidative stress drives the pathogenesis of atrial fibrillation (AF), the most common arrhythmia. In the cardiovascular system, cystathionine γ-lyase (CSE) serves as the primary enzyme producing hydrogen sulfide (H2S), a mammalian gasotransmitter that reduces oxidative stress. Using a case control study design in patients with and without AF and a mouse model of CSE knockout (CSE-KO), we evaluated the role of H2S in the etiology of AF. Patients with AF (n = 51) had significantly reduced plasma acid labile sulfide levels compared to patients without AF (n = 65). In addition, patients with persistent AF (n = 25) showed lower plasma free sulfide levels compared to patients with paroxysmal AF (n = 26). Consistent with an important role for H2S in AF, CSE-KO mice had decreased atrial sulfide levels, increased atrial superoxide levels, and enhanced propensity for induced persistent AF compared to wild type (WT) mice. Rescuing H2S signaling in CSE-KO mice by Diallyl trisulfide (DATS) supplementation or reconstitution with endothelial cell specific CSE over-expression significantly reduced atrial superoxide, increased sulfide levels, and lowered AF inducibility. Lastly, low H2S levels in CSE KO mice was associated with atrial electrical remodeling including longer effective refractory periods, slower conduction velocity, increased myocyte calcium sparks, and increased myocyte action potential duration that were reversed by DATS supplementation or endothelial CSE overexpression. Our findings demonstrate an important role of CSE and H2S bioavailability in regulating electrical remodeling and susceptibility to AF.

Arrhythmias and COVID-19: A Review.

Current understanding of the impact of coronavirus disease-2019 (COVID-19) on arrhythmias continues to evolve as new data emerge. Cardiac arrhythmias are more common in critically ill COVID-19 patients. The potential mechanisms that could result in arrhythmogenesis among COVID-19 patients include hypoxia caused by direct viral tissue involvement of lungs, myocarditis, abnormal host immune response, myocardial ischemia, myocardial strain, electrolyte derangements, intravascular volume imbalances, and drug sides effects. To manage these arrhythmias, it is imperative to increase the awareness of potential drug-drug interactions, to monitor QTc prolongation while receiving COVID therapy and provide special considerations for patients with inherited arrhythmia syndromes. It is also crucial to minimize exposure to COVID-19 infection by stratifying the need for intervention and using telemedicine. As COVID-19 infection continues to prevail with a potential for future surges, more data are required to better understand pathophysiology and to validate management strategies.

Flow-driven right-to-left cardiac shunting in a patient with carcinoid heart disease and patent foramen ovale without elevated right atrial pressure: a case report and literature review.

BACKGROUND: Carcinoid heart disease is present in approximately 20% of the patients with carcinoid syndrome and is associated with poor prognosis. It usually manifests with right-sided valvular involvement including tricuspid insufficiency and pulmonary stenosis. Patent foramen ovale (PFO) is present in approximately 50% of the patients with carcinoid heart disease which is twice higher than the general population. Right-to-left shunting through a PFO can occur either due to higher right atrial pressure than left (pressure-driven) or when the venous flow is directed towards the PFO (flow-driven) in the setting of normal intracardiac pressures. We report a rare case of flow-driven right-to-left atrial shunting via PFO in a patient with carcinoid heart disease. CASE SUMMARY: A 54-year-old male with a metastatic neuroendocrine tumour to liver presented with progressive shortness of breath for 5 months. Patient was found to be hypoxic with oxygen saturation of 78% and examination revealed a holosystolic murmur. Arterial blood gas showed oxygen tension of 43 mmHg. A transthoracic and transoesophageal echocardiogram showed aneurysmal inter-atrial septum with a PFO, severe tricuspid regurgitation directed anteriorly towards the inter-atrial septum leading to a marked right-to-left shunt. Right heart catheterization showed right atrial pressure of 8 mmHg, mean pulmonary artery pressure of 12 mmHg, and normal oxygen saturations in the right atrium, right ventricle, and pulmonary arteries. The patient then underwent closure of the PFO along with tricuspid valve and pulmonary valve replacement at an experienced cardiovascular surgical centre and has been asymptomatic since. CONCLUSION: Right-to-left shunting through a PFO in patients with normal right atrial pressure can be successfully treated with closure of the PFO. Thus, understanding the mechanism of intracardiac shunts is important to accurately diagnose and treat this rare and fatal condition.

Atrial Fibrillation Is Associated With Higher Overall Mortality in Patients With Implantable Cardioverter-Defibrillator: A Systematic Review and Meta-Analysis.

Background Implantable cardioverter-defibrillator ( ICD ) improves survival when used for primary or secondary prevention of sudden cardiac death. Whether the benefits of ICD in patients with atrial fibrillation ( AF) are similar to those with normal sinus rhythm ( NSR ) is not well established. The aim of this study is to investigate whether ICD patients with AF are at higher risk of mortality and appropriate shock therapy compared with patients with NSR . Methods and Results Literature was searched and 25 observational studies with 63 283 patients were included in this meta-analysis. We compared the outcomes of (1) all-cause mortality and appropriate shock therapy among AF and NSR patients who received ICD for either primary or secondary prevention and (2) all-cause mortality among AF patients with ICD versus guideline directed medical therapy. All-cause mortality (odds ratio, 2.11; 95% confidence interval, 1.73-2.56; P<0.001) and incidence of appropriate shock therapy (odds ratio, 1.77; 95% confidence interval, 1.47-2.13; P<0.001) were significantly higher in ICD patients with AF as compared to NSR . There was no statistically significant mortality benefit from ICD compared with medical therapy in AF patients (odds ratio, 0.69; 95% confidence interval, 0.42-1.11; P=0.12) based on a separate meta-analysis of 3 studies with 387 patients. Conclusions Overall mortality and appropriate shock therapy are higher in ICD patients with AF as compared with NSR . The impact of ICD on all-cause mortality in AF patients when compared to goal-directed medical therapy is unclear, and randomized controlled trials are needed comparing AF patients with ICD and those who have indications for ICD, but are only on medical therapy.

Diabetes Mellitus Associates with Increased Right Ventricular Afterload and Remodeling in Pulmonary Arterial Hypertension.

BACKGROUND: Diabetes mellitus is associated with left ventricular hypertrophy and dysfunction. Parallel studies have also reported associations between diabetes mellitus and right ventricular dysfunction and reduced survival in patients with pulmonary arterial hypertension. However, the impact of diabetes mellitus on the pulmonary vasculature has not been well characterized. We hypothesized that diabetes mellitus and hyperglycemia could specifically influence right ventricular afterload and remodeling in patients with Group I pulmonary arterial hypertension, providing a link to their known susceptibility to right ventricular dysfunction. METHODS: Using an adjusted model for age, sex, pulmonary vascular resistance, and medication use, associations of fasting blood glucose, glycated hemoglobin, and the presence of diabetes mellitus were evaluated with markers of disease severity in 162 patients with pulmonary arterial hypertension. RESULTS: A surrogate measure of increased pulmonary artery stiffness, elevated pulmonary arterial elastance (P = .012), along with reduced log(pulmonary artery capacitance) (P = .006) were significantly associated with the presence of diabetes mellitus in patients with pulmonary arterial hypertension in a fully adjusted model. Similar associations between pulmonary arterial elastance and capacitance were noted with both fasting blood glucose and glycated hemoglobin. Furthermore, right ventricular wall thickness on echocardiography was greater in pulmonary arterial hypertension patients with diabetes, supporting the link between right ventricular remodeling and diabetes. CONCLUSION: Cumulatively, these data demonstrate that an increase in right ventricular afterload, beyond pulmonary vascular resistance alone, may influence right ventricular remodeling and provide a mechanistic link between the susceptibility to right ventricular dysfunction in patients with both diabetes mellitus and pulmonary arterial hypertension.

A Comparison of Oral Anticoagulant Use for Atrial Fibrillation in the Pre- and Post-DOAC Eras.

INTRODUCTION: Direct oral anticoagulants (DOACs) have seen rapid uptake for the prevention of stroke associated with non-valvular atrial fibrillation (NVAF). It is unclear whether use of DOACs represents direct therapeutic substitution over warfarin or if this coincides with an increase in overall treatment rates. This study sought to describe the difference in oral anticoagulant (OAC) use in the pre-DOAC and post-DOAC eras. METHODS: Incident cases of NVAF were identified from the Truven Marketscan database during the years 2005-2009 ('pre-DOAC') and 2013 ('post-DOAC'). Demographic and clinical characteristics were compared for the overall cohorts and among those who did and did not receive OAC in both time periods. OAC treatment was observed by stroke (CHA2DS2-VASc) and bleed risk (HAS-BLED) scores. Logistic regression was used to compare the individual characteristics associated with OAC use between the study periods. RESULTS: During the pre- and post-DOAC eras, 105,610 and 11,992 NVAF patients were identified. OAC treatment increased from 42.2 to 54.0 % (absolute change 11.8 %, relative change 28.0 %) from the pre- to post-DOAC periods without meaningful differences between the populations. Larger relative increases in OAC treatment were observed for those at high risk of stroke (33.9 % increase) and for those with moderate (30.4 % increase) to high risk (28.6 % increase) of bleed. Other than time period of diagnosis, no patient characteristics differed between those treated with OACs in the pre and post periods. CONCLUSIONS: There has been an overall increase in OAC use in the NVAF population, attributable to both favorable randomized trial results and aggressive marketing of DOACs in the USA.

From bone to heart: a case of MRSA osteomyelitis with haematogenous spread to the pericardium.

We report a case of a 55-year-old woman with a history of type 2 diabetes mellitus, Charcot arthropathy and end-stage renal disease, who presented with a syncopal episode after undergoing haemodialysis. She had a history of methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia from an unknown source 3 months earlier, which was treated with an 8-week course of intravenous antibiotics. At the time of presentation to the emergency room, she was found to be in refractory shock. Bedside echocardiogram was performed, which showed moderate pericardial effusion. The effusion was later found to be due to MRSA, which was identified in blood and in pericardial fluid cultures. The patient was successfully treated with intravenous daptomycin for 6 weeks. Acute osteomyelitis of her right foot was the source of the MRSA, for which a right below-knee amputation was ultimately performed.

Dissecting the unspeakable: a fatal case of aortic dissection.

A 47-year-old man with diabetes and hypertension presented with sudden onset of chest pain and subsequently developed expressive aphasia. Brain imaging revealed multiple areas of ischaemic infarcts. Transoesophageal echocardiogram revealed aortic dissection with a free-floating thrombus on the dissection flap, which was the source of emboli. Given the poor prognosis, surgical intervention was not pursued and artificial support was withdrawn. Aortic dissection is a highly fatal condition with varied presentation including heart failure, myocardial infarction, neurological deficits, abdominal pain or acute renal failure. Aortic dissection is a relatively uncommon but catastrophic condition. A high degree of clinical suspicion is required for early and accurate diagnosis since mortality is high and increases by the hour. The mechanism for stroke in our case was due to an artery-to-artery embolism from a thrombus, which developed on the intimal surface of the dissected artery. This is an infrequent complication with a very unique mechanism.

Metabolic syndrome: a brain disease.

Recent research indicates an association between brain dysfunction and the pathogenesis of metabolic syndrome. To investigate this, we created a Medline search (up to December 2011) of articles in PubMed. The results indicated that refined carbohydrates, saturated and total fat, high levels of ω-6 fatty acids, and low levels of ω-3 fatty acids and other long chain polyunsaturated fatty acids (PUFA), all in conjunction with sedentary behaviour and mental stress can predispose to inflammation. Increased sympathetic activity, with increased secretion of catecholamine, cortisol, and serotonin can cause oxidative stress, which may damage the arcuate nucleus as well as the hypothalamus and macrophages, and the liver may release pro-inflammatory cytokines. These, in conjunction with an underlying deficiency in long chain PUFA, may damage the arcuate nucleus as well as neuropeptide-Y and pro-opiomelanocortin neurons and insulin receptors in the brain, especially during fetal life, infancy, and childhood, resulting in their dysfunction. Of the fatty acids in the brain, 30%-50% are long chain PUFA, which are incorporated in the cell membrane phospholipids. Hence, ω-3 fatty acids, which are also known to enhance parasympathetic activity and increase the secretion of anti-inflammatory cytokines interleukin (IL)-4 and IL-10 as well as acetylcholine in the hippocampus, may be protective. Therefore, treatment with ω-3 fatty acids may be applied for the prevention of metabolic syndrome.

Nutritional aspects of epigenetic inheritance.

The impact of diet and environmental factors on genes concerned with epigenetic inheritance and the mechanism of evolution has grown significantly beyond the Modern Synthesis period. Epigenetic inheritance is the passing of phenotypic change to subsequent generations in ways that are outside the genetic code of DNA. Recently, polymorphisms of the human Delta-5 (fatty acid desaturase, FADS1) and Delta-6 (FADS2) desaturase genes have been described as being associated with the level of several long-chain n-3 and n-6 polyunsaturated fatty acids (PUFAs) in serum phospholipids. Increased consumption of refined starches and sugar increases the generation of superoxide anion in the tissues and free fatty acids (FFA) in the blood. There is an increased amount and activity of nuclear factor-κB (NF-κB), a transcriptional factor regulating the activity of at least 125 genes, most of which are pro-inflammatory. The consumption of glucose may be associated with an increase in 2 other pro-inflammatory transcription factors: activating protein-1 (AP-1), and early growth response protein-1 (Egr-1). AP-1 regulates the transcription of matrix metallo-proteinases and Egr-1 modulates the transcription of tissue factor and plasminogen activator inhibitor-1. It is possible that a complex set of factors, including nutritional factors, come into play during epigenetic inheritance.