Comorbidity and medication trends in chronic kidney disease and incident atrial fibrillation - A Nationwide Cohort Study.

Introduction Chronic kidney disease (CKD) is associated with increased incidence of atrial fibrillation (AF). Also, patients with AF are prone to adverse kidney outcomes. We examined comorbidities and medication use in patients with CKD and incident AF. Methods The Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) is a nationwide retrospective register-linkage study including data from 168 233 patients with incident AF from 2007 to 2018, with laboratory data from 2010 onwards. Estimated glomerular filtration rate (eGFR) was available for 124 936 patients. The cohort was divided into 5 CKD stages with separate groups for dialysis and kidney transplantation. Results At AF diagnosis eGFR <60ml/min/1.73m2 was found in 27%, while 318 (0.3%) patients were on dialysis, and 188 (0.2%) had a functioning kidney transplant. Lowering eGFR yielded to more comorbidities and medications. During 2010-2018 in patients with eGFR <60ml/min/1.73m2 prevalence of hypertension, dyslipidaemia and diabetes increased from 82% to 88 %, from 50% to 66% and from 25% to 33%, respectively (<0.001). Throughout the observation period, lipid-lowering medication was underused. Conclusions More than one-fourth of patients with incident AF also had CKD stage 3-5 (eGFR <60ml/min/1.73m2). Both comorbidities and medication use increased with worsening kidney function. Prevalence of major cardiovascular (CV) risk factors increased during 2010-2018, but use of survival affecting medications, such as lipid-lowering medication, was suboptimal at all stages of CKD. More attention should be given to the optimal treatment of risk factors in this high CV risk population.

Thromboembolic and bleeding complications after elective cardioversion of atrial fibrillation: a nationwide cohort study.

AIMS: Elective cardioversion (ECV) is routinely used in atrial fibrillation (AF) to restore sinus rhythm. However, it includes a risk of thromboembolism even during adequate oral anticoagulation treatment. The aim of this study was to evaluate the risk of thromboembolic and bleeding complications after ECV in a real-life setting utilizing data from a large AF population. METHODS AND RESULTS: This nationwide register-based study included all (n = 9625) Finnish AF patients undergoing their first-ever ECV between 2012 and 2018. The thromboembolic and bleeding complications within 30 days after ECV were analysed. The mean age of the patients was 67.7 ± 9.9 years, 61.2% were men, and the mean CHA2DS2-VASc score was 2.6 ± 1.6. Warfarin was used in 6245 (64.9%) and non-vitamin K oral anticoagulants (NOACs) in 3380 (35.1%) cardioversions. Fifty-two (0.5%) thromboembolic complications occurred, of which 62% were ischaemic strokes, 25% transient ischaemic attacks, and 13% other systemic embolisms. Thromboembolic events occurred in 14 (0.4%) NOAC-treated patients and in 38 (0.6%) warfarin-treated patients (odds ratio 0.77; confidence interval: 0.42-1.39). The median time from ECV to the thromboembolic event was 2 days, and 78% of the events occurred within 10 days. Age and alcohol abuse were significant predictors of thromboembolic events. Among warfarin users, thromboembolic complications were more common with international normalized ratio (INR) <2.5 than INR ≥2.5 (0.9% vs. 0.4%, P = 0.026). Overall, 27 (0.3%) bleeding events occurred. CONCLUSION: The rate of thromboembolic and bleeding complications related to ECV was low without significant difference between NOAC- and warfarin-treated patients. With warfarin, INR ≥2.5 at the time of cardioversion reduced the risk of thromboembolic complications.

Time-in-therapeutic-range defined warfarin and direct oral anticoagulants in atrial fibrillation: a Nationwide Cohort Study.

BACKGROUND: Little is known how individual time-in-therapeutic-range (TTR) impacts the effectiveness and safety of warfarin therapy compared to direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF). OBJECTIVE: To compare the effectiveness and safety of standard dose DOACs to warfarin in patients with AF, while categorizing warfarin treated patients into quartiles based on their individual TTR. MATERIALS AND METHODS: We conducted a nationwide study including all patients with new-onset AF between 2011 and 2018 in Finland. Hazard ratios (HR) were calculated using Cox regression analysis with the inverse probability of treatment weighted method to assess the risks of ischaemic stroke (IS), intracranial haemorrhage (ICH) and mortality for users of apixaban (n = 12,426), dabigatran (n = 4545), rivaroxaban (n = 12,950) and warfarin (n = 43,548). RESULTS: The median TTR for warfarin users was 72%. Compared to the second best TTR quartile (reference), the risk of IS was higher in the two poorest TTR quartiles, and lower in the best TTR quartile and on rivaroxaban [2.35 (95% confidence interval, 1.85-2.85), 1.44 (1.18-1.75), 0.60 (0.47-0.77) and 0.72 (0.56-0.92)]. These differences were non-significant for apixaban and dabigatran. HR of ICH was 6.38 (4.88-8.35) and 1.87 (1.41-2.49) in the two poorest TTR groups, 1.44 (1.02-1.93) on rivaroxaban, and 0.58 (0.40-0.85) in the best TTR group compared to the reference group. Mortality was higher in the two poorest TTR groups and lowest in the best TTR group. CONCLUSIONS: The outcome was unsatisfactory in the two lowest TTR quartiles - in half of the patients treated with warfarin. The differences between the high TTR groups and standard dose DOACs were absent or modest.

Transcriptomic and spatial dissection of human ex vivo right atrial tissue reveals proinflammatory microvascular changes in ischemic heart disease.

Cardiovascular disease plays a central role in the electrical and structural remodeling of the right atrium, predisposing to arrhythmias, heart failure, and sudden death. Here, we dissect with single-nuclei RNA sequencing (snRNA-seq) and spatial transcriptomics the gene expression changes in the human ex vivo right atrial tissue and pericardial fluid in ischemic heart disease, myocardial infarction, and ischemic and non-ischemic heart failure using asymptomatic patients with valvular disease who undergo preventive surgery as the control group. We reveal substantial differences in disease-associated gene expression in all cell types, collectively suggesting inflammatory microvascular dysfunction and changes in the right atrial tissue composition as the valvular and vascular diseases progress into heart failure. The data collectively suggest that investigation of human cardiovascular disease should expand to all functionally important parts of the heart, which may help us to identify mechanisms promoting more severe types of the disease.

Long-term continuous monitoring of arrhythmias in pigs with insertable cardiac monitors.

Arrhythmia detection is essential when assessing the safety of novel drugs and therapies in preclinical studies. Many short-term arrhythmia monitoring methods exist, including non-invasive ECG and Holter. However, there are no reliable, long-term, non-invasive, or minimally invasive methods for cardiac arrhythmia follow-up in large animals that allows free movement with littermates. A long follow-up time is needed when estimating the impact of long-lasting drugs or therapies, such as gene therapy. We evaluated the feasibility and performance of insertable cardiac monitors (ICMs) in pigs for minimally invasive, long-term monitoring of cardiac arrhythmias that allows free movement and species-specific behavior. Multiple implantation sites were tested to assess signal quality. ICMs recognized reliably many different arrhythmias but failed to detect single extrasystoles. They also over-diagnosed T-waves, resulting in oversensing. Muscle activity and natural startles of the animals caused noise, leading to a heterogeneous signal requiring post-recording evaluation. In spite of these shortcomings, the ICMs showed to be very useful for minimally invasive long-term monitoring of cardiac rhythm in pigs.

Unintended Deformation of Stents During Bifurcation PCI: An OCTOBER Trial Substudy.

BACKGROUND: Unintended deformation of implanted coronary stents can lead to loss of coronary access, stent thrombosis and coronary events during follow-up. The incidence, mechanisms and clinical outcomes of unintended stent deformations (USD) during complex bifurcation stenting are not well characterized. OBJECTIVES: In a prespecified analysis of the OCTOBER (European Trial on Optical Coherence Tomography Optimized Bifurcation Event Reduction) trial, we aimed to: 1) determine the incidence and characterize mechanisms of USD identified by optical coherence tomography (OCT); and 2) evaluate physician's detection and correction of accidental abluminal rewiring and USD. METHODS: OCT scans were analyzed for accidental abluminal rewiring and USD. When USD was identified, the plausible mechanism was determined by analysis of all procedural OCT scans and the corresponding angiograms. RESULTS: USD was identified by the core lab in 9.3% (55/589) of OCT-guided cases. Accidental abluminal rewiring was the cause in 44% (24/55), and guide catheter collision was the cause in 40% (22/55) of cases. USD was found in 18.5% of all cases with left main bifurcation percutaneous coronary intervention. The total incidence of abluminal rewiring was 33 in 32 OCT-guided cases (5.4%) and was corrected by physicians in 18 of 33 appearances (54.5%). The 2-year major adverse cardiac event rate for patients with untreated USD (n = 30) was 23.3%, whereas patients with confirmed or possibly corrected USD (n = 25) had no events during follow-up. CONCLUSIONS: USD was associated with adverse procedural complications and cardiac events during follow-up when not identified and corrected. The predominant mechanisms were undetected abluminal rewiring and guide catheter collision. Left main bifurcation percutaneous coronary intervention was a particular risk with USD detected in 18.5% of cases.

Ischaemic stroke in women with atrial fibrillation: temporal trends and clinical implications.

BACKGROUND AND AIMS: Female sex has been linked with higher risk of ischaemic stroke (IS) in atrial fibrillation (AF), but no prior study has examined temporal trends in the IS risk associated with female sex. METHODS: The registry-linkage Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) study included all patients with AF in Finland from 2007 to 2018. Ischaemic stroke rates and rate ratios were computed. RESULTS: Overall, 229 565 patients with new-onset AF were identified (50.0% women; mean age 72.7 years). The crude IS incidence was higher in women than in men across the entire study period (21.1 vs. 14.9 events per 1000 patient-years, P < .001), and the incidence decreased both in men and women. In 2007-08, female sex was independently associated with a 20%-30% higher IS rate in the adjusted analyses, but this association attenuated and became statistically non-significant by the end of the observation period. Similar trends were observed when time with and without oral anticoagulant (OAC) treatment was analysed, as well as when only time without OAC use was considered. The decrease in IS rate was driven by patients with high IS risk, whereas in patients with low or moderate IS risk, female sex was not associated with a higher IS rate. CONCLUSIONS: The association between female sex and IS rate has decreased and become non-significant over the course of the study period from 2007 to 2018, suggesting that female sex could be omitted as a factor when estimating expected IS rates and the need for OAC therapy in patients with AF.

Caridac vein retroinjections provide an efficient approach for global left ventricular gene transfer with adenovirus and adeno-associated virus.

Heart failure (HF) is a major burden worldwide, and new therapies are urgently needed. Gene therapy is a promising new approach to treat myocardial diseases. However, current cardiac gene delivery methods for producing global myocardial effects have been inefficient. The aim of this study was to develop an endovascular, reproducible, and clinically applicable gene transfer method for global left ventricular (LV) transduction. Domestic pigs (n = 52) were used for the experiments. Global LV myocardium coverage was achieved by three retrograde injections into the three main LV vein branches. The distribution outcome was significantly improved by simultaneous transient occlusions of the corresponding coronary arteries and the main anastomotic veins of the retroinjected veins. The achieved cardiac distribution was visualized first by administering Indian Ink solution. Secondly, AdLacZ (2 × 1012vp) and AAV2-GFP (2 × 1013vg) gene transfers were performed to study gene transduction efficacy of the method. By retrograde injections with simultaneous coronary arterial occlusions, both adenovirus (Ad) and adeno-associated virus (AAV) vectors were shown to deliver an efficient transduction of the LV. We conclude that retrograde injections into the three main LV veins is a potential new approach for a global LV gene transfer.

Critical limb-threatening ischaemia and microvascular transformation: clinical implications.

BACKGROUND AND AIMS: Clinical management of critical limb-threatening ischaemia (CLTI) is focused on prevention and treatment of atherosclerotic arterial occlusions. The role of microvascular pathology in disease progression is still largely unspecified and more importantly not utilized for treatment. The aim of this explorative study was to characterize the role of the microvasculature in CLTI pathology. METHODS: Clinical high-resolution imaging of CLTI patients (n = 50) and muscle samples from amputated CLTI limbs (n = 40) were used to describe microvascular pathology of CLTI at the level of resting muscle blood flow and microvascular structure, respectively. Furthermore, a chronic, low arterial driving pressure-simulating ischaemia model in rabbits (n = 24) was used together with adenoviral vascular endothelial growth factor A gene transfers to study the effect of microvascular alterations on muscle outcome. RESULTS: Resting microvascular blood flow was not depleted but displayed decreased capillary transit time (P < .01) in CLTI muscles. Critical limb-threatening ischaemia muscle microvasculature also exhibited capillary enlargement (P < .001) and further arterialization along worsening of myofibre atrophy and detaching of capillaries from myofibres. Furthermore, CLTI-like capillary transformation was shown to worsen calf muscle force production (P < .05) and tissue outcome (P < .01) under chronic ischaemia in rabbits and in healthy, normal rabbit muscle. CONCLUSIONS: These findings depict a progressive, hypoxia-driven transformation of the microvasculature in CLTI muscles, which pathologically alters blood flow dynamics and aggravates tissue damage under low arterial driving pressure. Hypoxia-driven capillary enlargement can be highly important for CLTI outcomes and should therefore be considered in further development of diagnostics and treatment of CLTI.

Elective Cardiac Procedure Patients Have Low Preoperative Cardiorespiratory Fitness.

Preoperative cardiorespiratory fitness may influence the recovery after cardiac procedure. The aim of this study was to investigate the cardiorespiratory fitness of patients scheduled for elective cardiac procedures, using a six-minute walk test, and compare the results with a population-based sample of Finnish adults. Patients (n=234) awaiting percutaneous coronary intervention or coronary angiography, coronary artery bypass grafting, aortic valve replacement or mitral valve surgery performed the six-minute walk test. VO2max was calculated based on the walk test. The patients were compared to a population-based sample of 60-69-year-old Finnish adults from the FinFit2017 study. The mean six-minute walk test distances (meters) and VO2max (ml/kg/min) of the patient groups were: 452±73 and 24.3±6.9 (coronary artery bypass grafting), 499±84 and 27.6±7.2 (aortic valve replacement), 496±85 and 27.4±7.3 (mitral valve surgery), and 519±90 and 27.3±6.9 (percutaneous coronary intervention or coronary angiography). The population-based sample had significantly greater walk test distance (623±81) and VO2max (31.7±6.1) than the four patient groups (all p-values<0.001). All patient groups had lower cardiorespiratory fitness than the reference population of 60-69-year-old Finnish adults. Particularly the coronary artery bypass grafting group had a low cardiorespiratory fitness, and therefore might be prone to complications and challenging rehabilitation after the operation.

Ischemic Stroke Temporally Associated With New-Onset Atrial Fibrillation: A Population-Based Registry-Linkage Study.

BACKGROUND: Limited data exist on the temporal relationship between new-onset atrial fibrillation (AF) and ischemic stroke and its impact on patients' clinical characteristics and mortality. METHODS: A population-based registry-linkage database includes all patients with new-onset AF in Finland from 2007 to 2018. Ischemic stroke temporally associated with AF (ISTAF) was defined as an ischemic stroke occurring within ±30 days from the first AF diagnosis. Clinical factors associated with ISTAF were studied with logistic regression and 90-day survival with Cox proportional hazards analysis. RESULTS: Among 229 565 patients with new-onset AF (mean age, 72.7 years; 50% female), 204 774 (89.2%) experienced no ischemic stroke, 12 209 (5.3%) had past ischemic stroke >30 days before AF, and 12 582 (5.8%) had ISTAF. The annual proportion of ISTAF among patients with AF decreased from 6.0% to 4.8% from 2007 to 2018. Factors associated positively with ISTAF were higher age, lower education level, and alcohol use disorder, whereas vascular disease, heart failure, chronic kidney disease cancer, and psychiatric disorders were less probable with ISTAF. Compared with patients without ischemic stroke and those with past ischemic stroke, ISTAF was associated with ≈3-fold and 1.5-fold risks of death (adjusted hazard ratios, 2.90 [95% CI, 2.76-3.04] and 1.47 [95% CI, 1.39-1.57], respectively). The 90-day survival probability of patients with ISTAF increased from 0.79 (95% CI, 0.76-0.81) in 2007 to 0.89 (95% CI, 0.87-0.91) in 2018. CONCLUSIONS: ISTAF depicts the prominent temporal clustering of ischemic strokes surrounding AF diagnosis. Despite having fewer comorbidities, patients with ISTAF had worse, albeit improving, survival than patients with a history of or no ischemic stroke. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04645537. URL: https://www.encepp.eu; Unique identifier: EUPAS29845.

Temporal Relation Between Myocardial Infarction and New-Onset Atrial Fibrillation: Results from a Nationwide Registry Study.

Myocardial infarction (MI) and atrial fibrillation (AF) are commonly seen in the same patient. In this study, we evaluated the temporal relations and prognosis of MI and AF. This is a substudy of the nationwide registry-based Finnish Anticoagulation in Atrial Fibrillation (FinACAF) study, comprising all Finnish patients with new-onset AF from 2010 to 2017. Patients with MI and AF were divided into groups depending on the temporal relation between the disease onsets: (1) MI before AF (MIAF), and (4) no MI. The 1-year mortality in the groups were studied with the Cox proportional hazards model. Of the 153,207 patients with new-onset AF (mean age 72.7 years, 50.0% women), 16,265 (10.6%) were diagnosed with MI. Altogether, 8,889 (54.7%) of the patients with MI were in the MIAF group. Of all MIs, 42.2% were diagnosed within 1 year from new-onset AF. The MI>AF group had the worst survival, with an adjusted hazard ratio for death of 3.08 (confidence interval [CI] 2.89 to 3.27) compared with patients without MI. For the MI

Temporal trends of gender disparities in oral anticoagulant use in patients with atrial fibrillation.

AIMS: To investigate sex-specific temporal trends in the initiation of oral anticoagulant (OAC) therapy among patients diagnosed with atrial fibrillation (AF) in Finland between 2007 and 2018. METHODS: The registry-linkage Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) Study included all patients with incident AF in Finland from 2007 to 2018. The primary outcome was the initiation of any OAC therapy. RESULTS: We identified 229,565 patients with new-onset AF (50.0% women; mean age 72.7 years). The initiation of OAC therapy increased continuously during the observation period. While women were more likely to receive OAC therapy overall, after adjusting for age, stroke risk factors and other confounding factors, female sex was associated with a marginally lower initiation of OACs (unadjusted and adjusted hazard ratios comparing women to men: 1.08 (1.07-1.10) and 0.97 (0.96-0.98), respectively). Importantly, the gender disparities in OAC use attenuated and reached parity by the end of the observation period. Furthermore, when only patients eligible for OAC therapy according to the contemporary guidelines were included in the analyses, the gender inequalities in OAC initiation appeared minimal. Implementation of direct OACs for stroke prevention was slightly slower among women. CONCLUSION: This nationwide retrospective cohort study covering all patients with incident AF in Finland from 2007 to 2018 observed that although female sex was initially associated with a lower initiation of OAC therapy, the sex-related disparities resolved over the course of the study period.

Sex Differences in Red Blood Cell Transfusions and 30-Day Mortality in Cardiac Surgery: A Single Center Observational Study.

In cardiac surgery, women have higher short-term mortality and a higher risk of receiving red blood cell (RBC) transfusions than men. This study's aim was to evaluate possible sex differences in RBC transfusions in cardiac surgery and their association with preoperative hemoglobin levels, body mass index, and 30-day mortality. A single-center retrospective study was conducted with 1583 patients (1181 men and 402 women) undergoing cardiac surgery. A total of 64.4% of the women and 33.0% of the men received an RBC transfusion. In a multivariable analysis, female sex was an independent predictor of RBC transfusion (OR 3.88, 95% CI 2.95-5.11, p < 0.001). Other independent predictors of RBC transfusion were age, preoperative hemoglobin level, and body mass index. The women were more likely to receive RBC transfusions than the men, regardless of the type of cardiac surgery. Decreased transfusion risk was found in all higher-than-normal weight categories in the women, but only in the severe obesity category in the men. Preoperative hemoglobin was similarly associated with RBC transfusion in the men and women. The crude 30-day mortality rate was higher in the women than in the men (2.5% vs. 0.9%, p = 0.018). In both sexes, RBC transfusion was associated with an increased probability of death within 30 days.

Plasma N-terminal pro-B-type natriuretic peptide in the detection of aortic valve stenosis.

BACKGROUND: Systolic murmur suggestive of aortic valve origin is a common accidental finding, particularly in the elderly. Usually, it is due to aortic stenosis (AS) or aortic sclerosis (ASc). Currently, echocardiography is used to differentiate AS from ASc. Plasma N-terminal (NT)-prohormone BNP (NT-proBNP) is known to correlate with the severity of AS. We assessed whether NT-proBNP separates AS from ASc. METHODS: The study population consisted of three groups: AS (n = 87, age 77 ± 7 years), ASc (n = 76, age 72 ± 10 years), and healthy controls (n = 101, age 55 ± 10 years). All subjects underwent transthoracic echocardiography and measurement of plasma NT-proBNP. Patients with diseases known to increase NT-proBNP were excluded. RESULTS: The crude plasma NT-proBNP (median; IQR) in AS patients (413; 165-1055 ng/l) was significantly higher compared to ASc patients (96; 53-237 ng/l, p < 0.001) and healthy controls (50; 29-76 ng/l, p < 0.001). After adjusting for the confounding factors (age, coronary artery disease, renal function and diastolic blood pressure), plasma NT-proBNP remained significantly higher in AS patients as compared to ASc (p < 0.002) and controls (p < 0.0001). In the receiver-operating characteristic curve for NT-proBNP to identify AS from ASc and controls, the area under the curve was 0.878 with optimal cutoff of 115 ng/l. In addition, using 115 ng/l to separate AS from ASc yielded sensitivity of 0.885, and negative predictive value of 0.808. CONCLUSIONS: NT-proBNP was sensitive to identify AS and useful to rule out AS in patients with systolic murmur in the left ventricular outflow tract provided the patient does not have coexisting disease known to impact NT-proBNP.

Adenoviral Gene Therapy Vectors in Clinical Use-Basic Aspects with a Special Reference to Replication-Competent Adenovirus Formation and Its Impact on Clinical Safety.

Adenoviral vectors are commonly used in clinical gene therapy. Apart from oncolytic adenoviruses, vector replication is highly undesired as it may pose a safety risk for the treated patient. Thus, careful monitoring for the formation of replication-competent adenoviruses (RCA) during vector manufacturing is required. To render adenoviruses replication deficient, their genomic E1 region is deleted. However, it has been known for a long time that during their propagation, some viruses will regain their replication capability by recombination in production cells, most commonly HEK293. Recently developed RCA assays have revealed that many clinical batches contain more RCA than previously assumed and allowed by regulatory authorities. The clinical significance of the higher RCA content has yet to be thoroughly evaluated. In this review, we summarize the biology of adenovirus vectors, their manufacturing methods, and the origins of RCA formed during HEK293-based vector production. Lastly, we share our experience using minimally RCA-positive serotype 5 adenoviral vectors based on observations from our clinical cardiovascular gene therapy studies.

Agreement between physician- and patient-reported Canadian cardiovascular society scores among patients undergoing elective coronary angiography-The CATS study.

The primary aim of revascularization in stable coronary artery disease (CAD) is symptom relief. The severity of symptoms is usually evaluated by the physician, not by the patient. We examined the agreement between physician- and patient-reported Canadian Cardiovascular Society (CCS) scores among patients scheduled for elective coronary angiography in a cross-sectional study. Patients (n = 650) and cardiologists evaluated the severity of angina symptoms by filling the CCS questionnaire before coronary angiography. Patients were divided into those without CAD (stenosis diameter <50%, n = 445) and those with CAD (stenosis diameter >50%, n = 205). CAD patients were further divided into three groups according to disease severity (single-, double- or triple-vessel disease). The mean age of the patients was 67.6 (9.9) years and 50.6% were women. In 51.8% (95% CI 44.5%-59.0%) of patients with CAD and 51.9% (95% CI 47.0%-56.8%) of those without, physician- and patient reported CCS scores agreed. The physician reported better CCS scores in 33.9% (95% CI 27.6%-40.7%) of patients with CAD and 36.2% (95% CI 31.8%-41.0%) of patients without CAD. The proportions of full or partial agreement between physician- and patient reported CCS scores were similar across the CAD severity groups. To summarize, we observed a significant discrepancy between the physician- and patient-reported symptom severity in patients with or without CAD scheduled for angiography. The physician underestimated the symptoms in third of the cases. Thus, patient-reported symptom severity, rather than physician's evaluation, should be the cornerstone of treatment decisions.

Trends and burden of diabetes in patients with atrial fibrillation during 2007-2018: A Finnish nationwide cohort study.

AIMS: We assessed the temporal trends in the prevalence of diabetes and in its associations with outcomes among patients with atrial fibrillation (AF). METHODS: The registry-based FinACAF study covered all patients with incident AF in Finland between 2007 and 2018. Ischemic stroke (IS) and mortality rates were computed using Poisson regression model. RESULTS: We identified 229565 patients (50.0% female; mean age 72.7 years; mean follow-up 4.0 years) patients with incident AF. The prevalence of diabetes increased steadily from 15.5% in 2007 to 26.3% in 2018. A decrease in IS and mortality rates was observed during the study period both in patients with and without diabetes. Diabetes was associated with IS and mortality (adjusted incidence rate ratios with 95% confidence intervals 1.22 (1.17-1.26) and 1.32 (1.29-1.34), respectively). The impact of diabetes on IS risk remained stable, while its effect on mortality increased slightly during the observation period. CONCLUSIONS: The prevalence of diabetes has increased considerably among patients with AF between 2007 and 2018. There have been substantial improvements in the prognosis of AF patients with diabetes. However, diabetes remains a significant risk factor for IS and mortality in this patient population.

Rural-urban and geographical differences in prognosis of atrial fibrillation in Finland: a nationwide cohort study.

AIMS: Rural-urban disparities have been reported in the outcomes of cardiovascular diseases. We assessed whether rural-urban or other geographical disparities exist in the risk of ischemic stroke (IS) and death in patients with atrial fibrillation (AF) in Finland. METHODS: The registry-based FinACAF cohort study covers all patients with AF from all levels of care in Finland from 2007 to 2018. Patients were divided into rural-urban categories and into hospital districts (HDs) based on their municipality of residence. RESULTS: We identified 222,051 patients (50.1% female; mean age 72.8 years; mean follow-up 3.9 years) with new-onset AF, of whom 15,567 (7.0%) patients suffered IS and 72,565 (32.7%) died during follow-up. The crude IS rate was similar between rural and urban areas, whereas the mortality rate was lower in urban areas (incidence rate ratios (IRRs) with 95% confidence intervals (CIs) 0.97 (0.93-1.00) and 0.92 (0.91-0.93), respectively). However, after adjustments, urban residence was associated with slightly higher IS and mortality rates (IRRs with 95% CIs 1.05 (1.01-1.08) and 1.06 (1.04-1.07), respectively). The highest crude IS rate was in the East Savo HD and the lowest in Åland, whereas the highest crude mortality rate was in the Länsi-Pohja HD and the lowest in the North Ostrobothnia HD (IRRs with 95% CIs compared to Helsinki and Uusimaa HD for IS 1.46 (1.28-1.67) and 0.79 (0.62-1.01), and mortality 1.24 (1.16-1.32) and 0.97 (0.93-1.00), respectively. CONCLUSIONS: Rural-urban differences in prognosis of AF in Finland appear minimal, whereas considerable disparities exist between HDs.