While mitral reoperation has been assumed to carry higher surgical risk than first-time mitral surgery, outcomes of this procedure remain uncertain.

To examine characteristics and outcomes associated with mitral valve reoperation and first-time surgery for mitral regurgitation.

Patients undergoing surgery for mitral regurgitation were identified using Danish nationwide registries. The population was categorized into 1) patients undergoing first-time mitral surgery, 2) patients undergoing mitral reoperation. Mortality rates were examined during 180-day follow-up using Reverse Kaplan-Meier and Multivariable Cox-analysis.

In total, 7734 patients underwent surgery for mitral regurgitation. Of these, 428 patients also underwent mitral reoperation. Compared to first-time surgery, reoperated patients were younger (median 64.9 and 66.7 years) and had more cardiovascular comorbidities including atrial fibrillation (61.6 % and 38.8 %) and heart failure (48.7 % and 29.9 %). Median time to reoperation was 2.3 years. Prosthetic replacement was performed in 34.0 % of first-time surgeries and 78.7 % of reoperations. Mortality was 7.1 % following first-time surgery and 10.1 % following reoperation. Following first-time surgery, factors associated with increased mortality rate was prior myocardial infarction (HR = 1.98, 95 %CI 1.62-2.41), heart failure (HR = 1.59, 95 %CI 1.33-1.90), concomitant aortic valve surgery (HR = 1.61-1.27, 95 % CI 1.27-2.02) and bypass grafting (HR = 1.58, 95 %CI 1.31-1.91). Following reoperation, heart failure was associated with increased mortality rate (HR = 2.23, 95 %CI 1.17-4.60).

Patients undergoing mitral reoperation are young but have developed high burden of comorbidities at the time of reoperation. In spite of this, outcomes of mitral reoperation were acceptable, reflecting that this procedure can be performed safely in selected patients.

Fluoroquinolones (FQ) have been associated with aortic aneurysm and aortic dissection (AA/AD) resulting in an official warning. Recently, large-scale epidemiological studies failed to confirm this.

The current study aimed to scrutinize the FQ-AA/AD association through a retrospective nested case-cohort analysis supplemented with animal experimentation. FQ exposure was not associated with increased AA/AD hazard ratios in main and high-risk (elderly ≥65 years, hypertensive, and prevalent aortic disease) populations. Additionally, FQ did not cause increased mortality or aortic interventions in aortic disease patients. In addition, in animal experimentation, ciprofloxacin did not enlarge aortic diameters nor increase arterial stiffness.

Conventional use of FQ should not be avoided when clinically indicated.

Ischemic heart disease (IHD) is the leading cause of mortality in the world with an increasing incidence. One of the interventions to treat IHD is coronary artery bypass grafting (CABG) and people with diabetes mellitus (DM) account for approximately one quarter of all patients who undergo coronary revascularization. Furthermore, people with DM have a higher risk of mortality due to heart failure (HF).

We aim to describe the risk of developing HF after CABG in patients with versus without DM.

Through a large nationwide register-based cohort study, patients who underwent CABG from January 1, 2000 to December 31, 2020 were included. In addition to Cox regression, g-formula methods based on multivariable Cox regression were performed to estimate the absolute risk (AR) and risk difference (RD) of the association between DM status and HF outcome, and between DM status and mortality.

A total of 34,855 patients were included in this study, consisting of 6909 (19.8%) DM patients. The AR of HF after CABG in the 10th year was 35.1% versus 26.4% for patients with versus without DM (p < 0.001), respectively. The RD of HF for each exceeding year (3.7 percentage point (pp.) in the 1st year versus 8.6 pp. in the 10th year) was higher for patients with DM compared to those without DM.

The risk of HF was significantly higher up to ten years after CABG in patients with DM compared to those without DM.

Experimental studies have reported that Factor Xa inhibitors (Xa-Is) have positive effects on cardiac muscles and blood vessels via protease-activated receptor 2 inhibition, suggesting the preventive effects of Xa-Is on cardiovascular events. However, the clinical impact of Xa-Is on cardiovascular disease is unknown.

This study aimed to investigate the incidence of cardiovascular events among older patients with nonvalvular atrial fibrillation (NVAF) taking Xa-Is compared with those taking non-Xa-Is.

We conducted a single-center historical cohort study of consecutive patients with NVAF who were aged ≥80 years and used oral anticoagulants. Xa-Is included rivaroxaban, apixaban, and edoxaban, and non-Xa-Is included dabigatran and warfarin. The outcome of cardiovascular events was defined as a composite outcome of congestive heart failure, arteriosclerotic disease, and cardiovascular death. We compared the 5-year incidence of cardiovascular events between patients taking Xa-Is and those taking non-Xa-Is.

Of 1705 patients aged ≥80 years who were diagnosed with AF, 1092 patients with NVAF were enrolled. Propensity score matching provided 445 patients in each group. The risks of cardiovascular events, congestive heart failure, arteriosclerotic disease, and cardiovascular death were significantly lower in the Xa-I group than in the non-Xa-I group (hazard ratio [95% confidence interval]: 0.43 [0.30-0.61], 0.44 [0.29-0.66], 0.47 [0.22-1.04], and 0.41 [0.23-0.75], respectively).

Among patients with NVAF who were aged ≥80 years, the incidence of cardiovascular events was lower in the Xa-I users than in the non-Xa-I users.

Bacteraemia and infective endocarditis (IE) are rare but severe complications of transcatheter aortic valve implantation (TAVI). Limited data exist on the incidence and microbiological profile of early bacteraemia in this population. This study aimed to evaluate the 6-month incidence of bacteraemia, IE and associated mortality following TAVI.

Using Danish nationwide registries, all patients who underwent TAVI from 2012 to 2021 were identified and matched 1:1 by age, sex and index year with patients who underwent elective coronary angiography (CAG). Outcomes were assessed with cumulative incidence functions and adjusted HRs.

Among 5990 patients with first-time TAVI (57% male, mean age 80 years, SD 6.9), bacteraemia occurred in 4.2% within 6 months, compared with 2.6% in the CAG group (adjusted HR 1.57, 95% CI 1.26 to 1.96). Common pathogens post-TAVI included Streptococci (20%), Coagulase-negative staphylococci (19%) and Enterococci (18%), differing from the CAG group, where Coagulase-negative staphylococci (22%) and Staphylococcus aureus (16%) predominated. IE developed in 1.1% of patients with TAVI versus 0.1% of patients with CAG (adjusted HR 20.01, 95% CI 5.97 to 67.48).

Bacteraemia and IE rates are substantially elevated within 6 months following TAVI compared with elective CAG. The bacterial profile post-TAVI suggests that current prophylactic antibiotic regimens may not provide adequate coverage.

Background: In this prospective study, the prognostic role of ADAMTS13 activity and von Willebrand (VWF) antigen (VWF: Ag) levels in ischemic stroke outcomes was investigated. Methods: Patients diagnosed with acute ischemic stroke were prospectively enrolled in this study, while samples for ADAMTS13 activity and VWF: Ag level measurements were collected upon their admission to our unit. The National Institutes of Health Stroke Scale (NIHSS) score was estimated upon admission and at discharge. The modified Rankin scale for neurologic disability (Rankin) score was estimated based on the patient's history before the stroke onset, during admission (RankinAdm), and at discharge (RankinDis). Results: In the study, 29 patients with a median age of 82.5 (51, 92) were included. In univariate analysis, ADAMTS13 activity during admission was associated with platelet values at the same time point (r = 0.12, p = 0.01) and VWF: Ag levels were associated with age (r = 0.439, p = 0.04), previous ischemic stroke (r = 0.9176, p = 0.031), and glucose levels (r = 0.64, p = 0.049). Associations between ADAMTS13/VWF: Ag Ratio with RankinDis (r = 0.3253, p = 0.03), and the change between RankinDis and RankinAdm (r = 0.1589, p = 0.014) were identified. Additionally, VWF: Ag levels during admission were correlated with RankinDis (r = 0.0072, p = 0.049). Conclusions: These markers might be useful as biomarkers for the prediction of poor outcomes after stroke.

The introduction of evidence-based and structured guidelines has undoubtedly improved the care of cardiologic patients and in many cases simplified decision-making for the treatment team. The European Society of Cardiology in collaboration with the European Association for Cardio-Thoracic Surgery, the American College of Cardiology, the American Heart Association, the American College of Clinical Pharmacy, and the Heart Rhythm Society, and the Canadian Cardiovascular Society/Canadian Heart Rhythm Society have developed guidelines for the management of patients with atrial fibrillation. Because all 3 guidelines refer to almost the same scientific data, their recommendations are undoubtedly largely in agreement. Nevertheless, there are some interesting differences based on different interpretations of the same study, different publication dates, or differences in local conditions and health care resources. The following article aims at lining out these similarities and differences.

Atrial fibrillation (AF) leads to impaired left atrial appendage contractility, increasing the risk of thromboembolic stroke. The left atrial appendage emptying velocity (LAAev) measured on transesophageal echocardiogram (TEE) is a marker of increased thromboembolic risk.

The purpose of this study was to evaluate predictors of reduced LAAev for identifying individuals at increased risk for cardioembolic stroke.

This was a single-center retrospective review of TEEs and clinical charts. Predictors of LAAev <30 cm/s were identified using logistic regression. A risk prediction model was created using stepwise selection in a derivation set (n = 695) and separately tested in a validated set (n = 300).

We included TEEs on 995 patients (age 71.3±12.7 years; female 38.1%; history of AF 82.1%; in AF at evaluation 27.7%; CHA2DS2-VASc score 4.1 ± 1.9; LAAev 41.6 ± 21.0 cm/s). Significant multivariable predictors of LAAev <30 cm/s in derivation set were used to create the CHIRP3M-1 score containing 8 variables: Coronary artery disease (1), congestive Heart failure (1), Increased left atrial volume index ≥42 mL/m2 (1), current Rhythm AF (1), Paroxysmal AF (2), Persistent AF (3), longstanding Persistent/permanent AF (4), and greater than moderate Mitral regurgitation (-1). In the validation set, as compared to intermediate scores (3-4), those with low scores (≤2) and high scores (≥5) had odds ratios for LAAev <30 cm/s of 0.41 (0.21, 0.78, P = .007) and 2.58 (95% confidence interval 1.45-4.61, P = .001), respectively.

We developed and validated a novel risk stratification system to predict reduced LAAev using clinical and echocardiographic variables. This may help refine the stratification of cardioembolic stroke risk.

Sex differences in stroke exist, including variation in stroke risk and outcome. Differences in thrombin generation may contribute to this variation between females and males. To examine this, we assessed sex differences in thrombin generation between females and males with acute ischemic stroke and the relationship to blood cell gene expression. In 97 patients with acute ischemic stroke, thrombin generation was measured by thrombin generation assay. Blood cell gene expression was measured by microarray. Differences in thrombin generation between sexes were identified and the relationship to blood cell gene expression examined. Genes associated with sex differences in thrombin generation were analyzed by functional pathway analysis. Females and males had similar overall capacity to generate thrombin. The peak thrombin generated in females was 468.8 nM (SD 91.6), comparable to males (479.3nM;SD 90.8; p = 0.58). Lag time, time to peak thrombin, and endogenous thrombin potential were also similar between females and males. While overall thrombin generation was comparable between females and males with stroke, differences in genes that promote this thrombin generation exist. Females with high peak thrombin had an increase in genes that promote thrombosis, and platelet activation. In contrast, males with high peak thrombin had a decrease in genes involved in thrombus degradation. Females and males with acute ischemic stroke have similar capacity to generate thrombin, however, differences may exist in how this thrombin generation is achieved, with females having increased thrombin signaling, and platelet activation, and males having decreased thrombus degradation. This suggests regulatory differences in thrombosis may exist between females and males that may contribute to sex differences in stroke.

Hypertension is the leading modifiable risk factor for atrial fibrillation (AF) and is estimated to be present in >70% of AF patients. This Frontiers Review was prepared by 29 expert members of the AF-SCREEN International Collaboration to summarize existing evidence and knowledge gaps on links between hypertension, AF, and their cardiovascular sequelae; simultaneous screening for hypertension and AF; and the prevention of AF through antihypertensive therapy. Hypertension and AF are inextricably connected. Both are easily diagnosed, often silent, and frequently treated inadequately. Together, they additively increase the risk of ischemic stroke, heart failure, and many types of dementia, resulting in greater all-cause mortality, considerable disease burden, and increased health care expenditures. Automated upper arm cuff blood pressure devices with implemented technology can be used to simultaneously detect both hypertension and AF. However, positive screening for AF with an oscillometric blood pressure monitor still requires ECG confirmation. The current evidence suggests that high-risk individuals aged ≥65 years or with treatment-resistant hypertension could benefit from AF screening. Since antihypertensive therapy effectively lowers AF risk, particularly in individuals with left ventricular dysfunction, hypertension should be the key target for AF prediction and prevention rather than merely a comorbidity of AF. Nevertheless, several important gaps in knowledge need to be filled over the next years, including the ideal method and selection of patients for simultaneous screening of hypertension and AF and the optimal antihypertensive drug class and blood pressure targets for AF prevention.

Shared decision-making (SDM) promotes patient awareness about medical conditions and treatments, facilitating patient involvement in care decisions. This two-stage multicenter study evaluated impacts of SDM in Taiwanese adults with atrial fibrillation (AF) eligible for novel oral anticoagulant (NOAC) therapy.

Participants were NOAC-naïve (part I) or dabigatran-experienced (part II). During Stage I, part I participants (n = 124) completed a semi-structured survey (understanding evaluation sections only) before and after viewing SDM materials on stroke prevention for AF. Surveys collected data on anxiety about AF, confidence in healthcare professionals, usefulness of the SDM materials, and perception of different NOACs. During Stage II, part I participants after being prescribed NOACs, and part II participants completed another survey to compare impacts of SDM.

During Stage I, dabigatran was the preferred NOAC after viewing the SDM materials among 90% of part I participants. During Stage II, both part I (n = 87) and part II participants (n = 104) completed another survey. Fewer part I participants were anxious about AF (p < 0.01), and more had confidence in healthcare professionals (p < 0.01) after viewing SDM materials than before. Most part I participants (≥90%) rated the SDM materials as "very helpful". In Stage II, participants viewing SDM before initiating dabigatran had lower anxiety (part I, 43%; part II, 53%; p < 0.01) and a higher trust (part I, 92%; part II, 84%; p < 0.01).

In conclusion, SDM reduced anxiety and improved trust in healthcare professionals among NOAC-naïve participants with AF.

Although certain autoimmune diseases (AIDs) have been associated with an increased rate of heart failure (HF), data on the long-term rate of HF across the spectrum of AIDs are lacking. We investigated the long-term rate of HF in individuals with a history of 28 different AIDs.

Individuals diagnosed with an AID (2000-2021) were identified through Danish nationwide registries. Each patient with AID was matched with four individuals from the background population by age, sex, and year of inclusion. Multivariable Cox regression was used to compare the rate of HF between the AID and the background population, overall and according to individual AIDs. In total, 272 959 patients diagnosed with AID were matched with 1 091 836 individuals without AID (median age 55 years; 62% women; median follow-up 7.9 years). The 10-year cumulative incidence of HF was 5.2% for patients with AID and 3.5% for matched individuals. Patients with any AID had a higher associated rate of HF than matched individuals (hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.52-1.59). Patients with each of the AIDs had a higher associated rate of incident HF compared with matched individuals from the background population, although the association was not statistically significant for Reiter's and Behcet's disease. The highest relative rates were observed in patients with systemic sclerosis (HR 3.31, 95% CI 2.63-4.16) and Addison's disease (HR 3.03, 95% CI 2.35-3.91).

Patients with AID, irrespective of the type, had a higher associated rate of HF compared to the background population. Further research is needed to clarify whether screening for cardiovascular risk is beneficial.

Atrial fibrillation (AF) is a major risk factor for ischemic stroke (IS), but whether the magnitude of this risk has changed over time is unknown.

This study sought to investigate temporal trends in IS rates in patients with incident AF before oral anticoagulant agent (OAC) therapy.

The nationwide FinACAF (Finnish Anticoagulation in Atrial Fibrillation) study covers patients with AF at all levels of care in Finland from 2007 to 2018. A 4-week quarantine period from AF diagnosis was applied, and only follow-up time without OAC therapy was included. Incidence rates of IS were computed in 4-year intervals in relation to sex and non-sex CHA2DS2-VASc (ie, CHA2DS2-VA) score values.

In total, 129,789 patients with new-onset AF were identified (49.2% women; mean age: 71.4 ± 14.5 years). Between the calendar year intervals of 2007-2010 and 2015-2018, the patients' mean CHA2DS2-VA score increased from 2.5 to 3.0, and concurrently the overall IS rate decreased by 25% from 36.7 to 27.6 events per 1,000 patient-years. This trend was driven by a 32% decrease of IS rate in women, particularly among those with higher age and CHA2DS2-VA scores. The IS rate in patients with a CHA2DS2-VA score of 1 was 8.2 events per 1,000 patient-years and remained stable across the study period.

The initial IS risk in AF patients, before the initiation of OAC therapy, has decreased by 25% between 2007 and 2018 despite an increase in both age and stroke risk scores. The decrease has been most pronounced in older women with high stroke risk scores.

Declining cardiovascular mortality rates have been well-documented, yet temporal trends of sudden cardiac death (SCD) in young individuals remain unclear. We provide contemporary nationwide estimates of the temporal trends of SCD in young individuals (1-35 years of age) from 2000 through 2019 and correlate these trends to changes in out-of-hospital cardiac arrest (OHCA) patterns, rates of inherited cardiac diseases, and implantations of implantable cardioverter defibrillators (ICD).

All individuals between 1 and 35 years of age living in Denmark from 2000 through 2019 were included, with annual re-evaluation of the at-risk population in regard to age. Adjudication of SCD cases relied on multiple sources, including death certificates, medical files, and autopsy reports. Information on OHCA, diagnostic rates, and ICD implantations were captured from nationwide administrative registries. Annual incidence rates of SCD were calculated, and temporal trends in SCD incidence were computed as percentage change annualized. Trends in OHCA survival and characteristics, diagnostic rates of inherited cardiac diseases, and ICD implantations were assessed.

During the 20-year study period (47.5 million person-years), 1057 SCDs were identified (median age, 29 years; 69% male). The overall incidence of SCD was 2.2 per 100 000 person-years and declined by 3.31% (95% CI, 2.42-4.20) annually, corresponding to a 49% (95% CI, 38.7-57.6) reduction during the study. Rates of witnessed SCD declined markedly (percentage change annualized -7.03% [95% CI, -8.57 to -5.48]), but we observed no changes in the rate of unwitnessed SCD (percentage change annualized -0.09% [95% CI, -1.48 to 1.31]). Therefore, the proportion of unwitnessed SCD increased by 79% (P<0.001). Survival after OHCA in young individuals (1 to 35 years of age) increased from 3.9% to 28%, mainly because of increased bystander cardiopulmonary resuscitation and defibrillation rates. Diagnostic rates of inherited cardiac diseases increased 10-fold (incidence rate ratio, 10.4 [95% CI, 8.46-12.90]) and the ICD implantation rate increased 2-fold (incidence rate ratio, 1.97 [95% CI, 1.51-2.60]).

SCD incidence rates in young individuals declined by 49% over the past 2 decades. The decline was paralleled by improved survival of OHCA, higher diagnostic rates of inherited cardiac diseases, and higher ICD implantation rates. However, rates of unwitnessed SCD were unchanged, which calls for new perspectives in preventive strategies.

AF is the most common arrhythmia in clinical practice, with a large preponderance in the older (>75 years) adult population. Stroke is the most feared complication of AF, with huge corresponding morbidity and mortality. Anticoagulation is the mainstay for stroke prevention in AF, but is commonly underutilised in clinical practice due to the fear of intracerebral bleeding. Bleeding is the primary concern in older patients with conventional vitamin K antagonist use. Direct oral anticoagulants (DOACs) have been used for a decade in clinical practice and have been found to reduce major bleeds. The advantages of DOAC use in older patients include obviating the need for intermittent international normalised ratio monitoring, fewer drug interactions and reduction in intracerebral haemorrhage. The disadvantages of DOAC use include older patients having to take multiple doses per day and a lack of a universal antidote, as opposed to vitamin K antagonists. However, a lack of head-to-head trials among DOACs and specific randomised controlled trials in older patients preclude a definite conclusion regarding the ideal DOAC that should be used in the older population. Factor XI inhibition is an emerging approach for oral anticoagulation that holds promise for dissociating thrombosis from haemostasis. This provides an additional avenue for reducing bleeding in the older adult population.

The associations between left atrial (LA) size, echocardiographic diastolic parameter (E/A ratio), and incident atrial fibrillation (AF) in older inpatients remain underexplored.

This study aimed to evaluate the relationship between LA size, E/A ratio, and AF risk in older hospitalized patients.

Between January 2015 and May 2023, a total of 2,615 older inpatients (aged ≥ 65 years) were enrolled in this retrospective longitudinal study. Left atrial diameter (LAD) and E/A ratio were measured using transthoracic echocardiography.

Over a median follow-up of 844 days (IQR: 331-1355 days), 209 patients (8.0%) experienced at least one incident of AF. After adjusting for covariates, large LA and high E/A ratio were significantly associated with incident AF, with an 11% increase in risk for each 1 mm increase in LAD over 35 mm (adjusted HR: 1.11, 95% CI: 1.10-1.13) and a 30% increased risk per standard deviation increase in E/A ratio when E/A ratio exceeded 0.65 (adjusted HR: 1.30, 95% CI: 1.23-1.37), P < 0.001. The influence of LA size and E/A ratio on incident AF was more pronounced in the younger subgroup of older adults. Incorporating LAD and E/A ratios into the CHA2DS2-VASc score improved its predictive accuracy (AUC increase = 0.168, P < 0.001).

This study shows that LA size and E/A ratio are key predictors of AF in hospitalized older patients, with age influencing their predictive value. Incorporating these factors into the CHA2DS2-VASc score enhances risk stratification and highlights the need for early AF screening in this group.

In hospitalized older patients, large LA and high E/A ratio are associated with incident AF, and these associations are more pronounced in younger individuals. LAD and E/A ratios provide incremental predictive value for AF beyond the CHA2DS2-VASc score.

Sparse information regarding the long-term risk of acute myocardial infarction (MI) following a transient ischemic attack (TIA) emphasizes further research to guide preventive strategies and risk stratification in patients with a TIA.

We conducted a nationwide cohort study to investigate the 5-year risk of MI and all-cause mortality in patients with a first-time TIA. Patients with a first-time TIA were identified in the Danish Stroke Registry (2013-2020), matched on age, sex, and calendar year (1:4) with the general population and (1:1) with patients with first-time ischemic stroke. The 5-year risks of MI and all-cause mortality were estimated by the Aalen-Johansen and Kaplan-Meier estimators. The groups were compared using Cox regression, while adjusting for cardiovascular comorbidities.

We identified 21 743 patients with TIA, 86 972 matched individuals from the general population, and 21 743 matched control patients with ischemic stroke. Median age was 70 (25th to 75th percentile, 60-78) years; 52% were male. Comorbidity burden was the lowest in general population controls, intermediate in patients with TIA, and the highest in patients with ischemic stroke. The 5-year risk of MI was 2.0% in patients with TIA, 1.5% in the general population (P<0.001), and 2.2% in the ischemic stroke population (P<0.001). After adjustment, these differences in MI rate were similar (TIA versus general population; hazard ratio, 0.99 [95% CI, 0.98-1.02] and TIA versus ischemic stroke; hazard ratio, 0.99 [95% CI, 0.96-1.01]). The 5-year risk of mortality was 17.0% in patients with TIA compared with 14.0% in the general population (P<0.001) and 27.0% in ischemic stroke population (P<0.001). The differences in mortality persisted following adjustments for patients with TIA versus general population (hazard ratio, 1.25 [95% CI, 1.19-1.31]) and for patients with TIA versus ischemic stroke (hazard ratio, 0.43 [95% CI, 0.41-0.46]).

Patients with first-time TIA had a low 5-year incidence of MI, which was not significantly different from that of the general population and patients with first-time ischemic stroke after adjustments for comorbidities. However, patients with TIA had a 25% higher all-cause mortality rate than the general population, which was not readily explained by MI risk. Hence, the findings do not endorse the need to raise further awareness regarding MI in patients with TIA.

To examine whether elevated high-sensitivity troponin-T (hs-TnT) concentrations in patients with paroxysmal supraventricular tachycardia (PSVT) without known cardiovascular disease (CVD) are associated with an increased risk of death.

Patients with de novo PSVT and ≥ 1 measured hs-TnT level from 2013 to 2020 during hospitalization without known CVD were retrospectively identified in the Danish nationwide registries. Elevated hs-TnT was defined as ≥14 ng/l. The primary outcome was all-cause mortality assessed at 0-30 days and 31-365 days, using multivariable Cox regression with average treatment effect, rendering standardized absolute and relative risks. The secondary outcome was a composite endpoint of myocardial infarction, coronary revascularization, stroke, or heart failure-related contact.

A total of 1203 patients were included, with 792 (65.8 %) patients having elevated hs-TnT levels. The standardized mortality risk within 30 days was significantly higher in patients with elevated hs-TnT compared with those with normal concentrations [2.38 %, 95 % confidence interval (CI): 1.38 to 3.37 versus <0.01 %, 95 % CI: <0.01 to <0.01; p = 0.001]. At 31-365 days, the standardized risk of death was 1.51 % (95 % CI: 0 to 3.28) in individuals with a normal hs-TnT and 4.23 % (95 % CI: 2.81 to 5.66) in those with an elevated hs-TnT (p = 0.31). The risk of the composite secondary outcome did not significantly differ between the groups.

In patients with de novo PSVT and without known CVD, elevated hs-TnT concentrations were associated with increased short-term mortality. Long-term mortality was not significantly affected by elevated hs-TnT, likely due to study limitations, and requires further investigation.

Atrial fibrillation (AF) is associated with heart failure (HF). However, it is unclear if postoperative AF (POAF) following non-cardiac surgery differs from non-surgical AF in terms of the risk of HF. We compared the long-term rate of incident HF in patients developing new-onset POAF following non-cardiac surgery with patients who did not develop POAF following non-cardiac surgery and patients with non-surgical non-valvular AF (NVAF).

Using Danish nationwide registries, all patients aged ≥30 years who developed POAF following non-cardiac surgery (1996-2020) were identified and matched in a 1:3 ratio by age, sex, surgery type (only for the surgery group), selected comorbidities, and inclusion year with patients without POAF following non-cardiac surgery and individuals with NVAF, respectively. A total of 2270 patients with POAF were matched with 6810 patients without POAF following non-cardiac surgery, and 1846 patients with POAF were matched with 5538 patients with NVAF. The median follow-up was 7.2 years. Compared with patients without POAF, those with POAF had a higher associated long-term rate of incident HF (2.6 vs. 1.2 events per 100 person-years; adjusted hazard ratio [HR] 2.39, 95% confidence interval [CI] 2.06-2.78). Compared with individuals with NVAF, patients with POAF did not have a significantly different rate of incident HF (2.7 vs. 3.0 events per 100 person-years; adjusted HR 0.89, 95% CI 0.78-1.03).

Patients with new-onset POAF following non-cardiac surgery had a higher associated long-term rate of incident HF compared to those without POAF, with no significant difference in the rate of incident HF when compared to patients with NVAF.

When patients undergo surgery for mitral regurgitation, risk of reoperation is of concern.

To examine the incidence and factors associated with mitral reoperation following surgery for mitral regurgitation according to type of surgery.

Patients undergoing first-time surgery for mitral regurgitation, 1996-2021, were identified from nationwide registries. According to index surgery, the population was categorized into 1) mitral repair; 2) mechanical prostheses; 3) bioprostheses. Patients were followed from discharge with a maximum of 15 years of follow-up and cumulative incidence of reoperation was examined. Multivariable Cox analysis was used to examine factors associated with reoperation.

We identified 6958 patients: 4624 with mitral repair (72 % male, median age 66), 1250 with mechanical prosthesis (52 % male, median age 59), and 1084 with bioprosthesis (57 % male, median age 74). Cumulative incidence of reoperation was 7.3 % for repair (median 7.2 years follow-up), 6.1 % for mechanical prostheses (median 10.9 years follow-up), and 7.1 % for bioprostheses (median 4.5 years follow-up). Within first year, 22.6 % of reoperations were preceded by infective endocarditis. In long-term follow-up, bioprosthetic replacement was associated with a higher reoperation rate, while increasing age, male sex and mechanical prosthesis were associated with lower reoperation rate.

In patients operated for mitral regurgitation, reoperation was infrequent at approximately 7 % for all intervention types during a maximum of 15-year follow-up. In adjusted analysis, bioprosthetic replacement was associated with a higher rate of reoperation, while increasing age, male sex and mechanical prosthesis was associated with a lower rate of reoperation.

The risk of hyperkalemia in relation to different combinations of antihypertensive therapy remains to be elucidated. In this Danish register-based study, we aimed to investigate the risk of developing hyperkalemia in relation to different combinations of antihypertensive therapy. Using incidence density matching, we matched a hyperkalemic patient to five normokalemic patients on eGFR groups, age, sex, and time between study entry and date of potassium measurement. Combination therapies were subdivided into eight groups: beta blockers (BB) + calcium channel blockers (CCB), BB + renin angiotensin system inhibitors (RASi), BB + RASi + mineralocorticoid receptor antagonists (MRA), CCB + RASi, CCB + RASi + thiazides, CCB + thiazides, RASi + thiazides, and other combinations. Multivariable conditional logistic regression was used to estimate the odds of hyperkalemia within 90 days for each of the eight antihypertensive combination therapies. A total of 793 patients with hyperkalemia were matched to 3598 normokalemic patients. In multivariable analysis, odds of developing hyperkalemia when being treated with BB + RASi + MRA was 1.95 (95% CI, 1.39-2.72) compared to RASi + thiazides (reference). CCB + thiazides (OR, 0.76 [95% CI, 0.45-1.28]) and CCB + RASi + Thiazid (OR 0.81 [95% CI, 0.51-1.28]) were among the others not significantly associated with hyperkalemia. Combinations of BB + RASi + MRA were significantly associated with an increased risk of developing hyperkalemia within 90 days of initiating treatment. Patients treated with BB + RASi + MRA within 90 days of treatment initiation, were associated with an increased hyperkalemia risk. When treating hypertensive patients with combination antihypertensive therapy, identifying and monitoring patients with a high risk of dyskalemias is a crucial goal to avoid serious adverse effects and detrimental outcomes related to dyskalemia.

This study investigated the association between modifiable factors and symptom progression in dementia over up to 8 years.

Multilevel growth curve models assessed the role of modifiable risk factors (low education, hearing impairment and its treatment, depression, physical inactivity, diabetes and its treatment, smoking, hypertension and its treatment, obesity, alcohol consumption, social isolation, and visual impairment) on cognitive and functional trajectories in 353 people with dementia.

Higher education was associated with higher initial cognitive status but faster decline. Antidiabetic medication was associated with slower cognitive decline, whereas depression and visual impairment were linked to low baseline functioning and faster cognitive decline.

Several modifiable risk factors influenced symptom progression. Education initially had a protective effect, whereas depressive symptoms were linked to worse symptom progression. Treatment of comorbidities (diabetes, visual impairment) could have a positive impact on dementia symptoms. Modifiable risk factors are promising targets for tertiary prevention.

Modifiable risk factors were associated with symptom progression in dementia over up to 8 years.More education was associated with higher initial cognitive status but faster decline.Depressive symptoms were linked to less favorable symptom progression.Treatment of comorbidities (diabetes, visual impairment) may positively impact the course of symptoms.Modifiable risk factors are promising targets for tertiary prevention.

Transient ischemic attack (TIA) is associated with a higher short-term incidence of stroke. However, long-term data on this association are lacking. Therefore, this study aimed to determine the long-term incidence of ischemic stroke after TIA according to ABCD2 score and to identify factors associated with stroke after TIA.

All Danish patients ≥18 years with first-time TIA were included from the Danish Stroke Registry (2014-2020). The study population was stratified into a high-risk (≥4 points) and low-risk (<4 points) group according to the modified ABCD2 score (age ≥60 years, hypertension, clinical features, and diabetes). The 3-year cumulative incidence of stroke and all-cause mortality was assessed using the Aalen-Johansen and Kaplan-Meier estimators, respectively. Factors associated with 3-year stroke rate were identified using multivariable Cox regression models.

In total, 21,433 patients with first-time TIA were included: 1,280 (6.0%) in the high-risk group and 20,153 (94.0%) in the low-risk group. Patients with high-risk ABCD2 scores were older (median 77.5 [P25-P75 70.8-84.1] vs 70.3 [P25-P75 60.1-78.2]), more often female (53.1%), had more comorbidities (e.g., ischemic heart disease, heart failure, and atrial fibrillation), and received more medication (e.g., any antiplatelet therapy or oral anticoagulants and cholesterol-lowering drugs) at baseline. The 3-year cumulative incidence of stroke after TIA was 6.0% (95% CI 4.6-7.5) in the high-risk group and 4.2% (95% CI 3.9-4.5) in the low-risk group (p = 0.004) with an unadjusted hazard ratio (HR) 1.56 (95% CI 1.21-2.00). Factors associated with 3-year stroke rate included age ≥60 years (HR 2.21, 95% CI 1.76-2.78), current smoking (HR 1.37, 95% CI 1.13-1.65), unilateral weakness (HR 1.25, 95% CI 1.04-1.51), peripheral artery disease (HR 1.53, 95% CI 1.09-2.14), and chronic kidney disease (HR 1.39, 95% CI 1.01-1.90). The 3-year cumulative incidence of all-cause mortality was 28.9% (95% CI 26.1-31.7) in the high-risk group and 10.3% (95% CI 9.9-10.8) in the low-risk group.

Patients with high-risk ABCD2 score had an almost 60% higher associated long-term rate of ischemic stroke compared with those with low-risk ABCD2 score. Future trials focusing on preventive strategies, including evidence-based antithrombotic strategies, especially for the high-risk group are warranted.

Venous thromboembolism (VTE) is a common cause of morbidity and mortality in patients with cancer. There is evidence that specific aberrations in tumour biology contribute to the pathophysiology of this condition. We plan to examine the association between tumour somatic mutations and VTE in an existing cohort of patients with cancer, who were enrolled to the flagship Genomics England 100,000 Genomes Project. Here, we outline an a-priori analysis plan to address this objective, including details on study cohort selection, exposure and outcome definitions, annotation of genetic variants and planned statistical analyses. We will assess the effect of 1) deleterious somatic DNA variants in each gene; 2) tumour mutational burden and 3) tumour mutational signatures on the rate of VTE (outcome) in a pan-cancer cohort. Sensitivity analyses will be performed to examine the robustness of any associations, including adjustment for potentially correlated co-variates: tumour type, stage and systemic anti-cancer therapy. We hope that results from this study may help to identify key genes which are implicated in the development of cancer associated thrombosis, which may shed light on related mechanistic pathways and/or provide data which can be integrated into genetic risk prediction models for these patients.

Although selected autoimmune diseases (AIDs) have been linked to an increased risk of ventricular arrhythmias (VAs), data on the long-term rate of VAs across the spectrum of AIDs are lacking. The aim of this study was to investigate the long-term rate of VAs (a composite of ventricular tachycardia, ventricular fibrillation, ventricular flutter, or cardiac arrest) in individuals with a history of 28 different AIDs.

Individuals diagnosed with an AID (2005-18) were identified through Danish nationwide registries. Each patient with an AID was matched with four individuals from the background population by age and sex. Multivariable Cox regression was used to compare the rate of VAs between the AIDs and background population, overall and according to individual AIDs. In total, 186 733 patients diagnosed with AIDs were matched with 746 932 individuals without AIDs (median age 55 years; 63% female; median follow-up 6.0 years). The 5-year cumulative incidence of VAs was 0.5% for patients with AIDs and 0.3% for matched individuals. Patients with any AIDs had a higher associated rate of VAs than matched individuals {hazard ratio (HR) 1.39 [95% confidence interval (CI), 1.29-1.49]}. The highest HR was observed in patients with systemic sclerosis [3.86 (95% CI, 1.92-7.75)]. The higher rate of VAs in patients with AIDs, compared with individuals from the background population, was more pronounced in patients without ischaemic heart disease or heart failure/cardiomyopathy compared with those with these conditions (Pinteraction <0.05).

Despite a low cumulative incidence, patients with a history of AIDs had a higher relative rate of VAs than matched individuals.

The results from the POET (Partial Oral Treatment of left-sided Endocarditis) trial were published in August 2018 and established noninferiority of oral step-down antibiotic treatment in stabilized patients with infective endocarditis (IE). Data on length of hospital stay (LOS) and safety following the POET trial are warranted.

The goal of this study was to examine changes in LOS and safety (mortality and relapse of bacteremia) before and after POET publication.

Using Danish nationwide registries, patients with first-time IE caused by Streptococcus spp., Enterococcus faecalis, Staphylococcus aureus, or coagulase-negative staphylococci from 2012 to 2021 were identified. Median LOS was examined according to publication date (before and after September 2018). Mortality and relapse of bacteremia at 180 days of follow-up were examined.

We identified 3,008 patients before POET publication (median age 72.8 years) and 1,740 after publication (median age 75.2 years) (P < 0.0001). The median LOS decreased by 8 days: 41 days (Q1-Q3: 29-49 days) before POET publication and 33 days (Q1-Q3: 21-44 days) after POET publication (P < 0.0001). Similar reductions in LOS were seen across microbiological etiologies and age groups. Reduction in LOS was most pronounced in nonsurgically treated patients. Mortality from IE admission to a maximum of 180 days' follow-up was 27.5% before POET publication and 28.3% after publication (P = 0.41). The bacteremia relapse rate within 180 days was 3.5% before POET publication and 1.6% after publication (P = 0.0002).

Following the POET trial, we found a reduction in median LOS of 8 days with no change in mortality and an associated lower rate of relapse of bacteremia.

Patients with kidney failure on maintenance dialysis have a high stroke and bleeding risk. Multivariable prediction models can be used to estimate the risk of ischemic stroke and bleeding. A systematic review and meta-analysis was performed to determine the performance of the existing models in patients on dialysis.

MEDLINE and Embase databases were searched, from inception through 12 January 2024, for studies of prediction models for stroke or bleeding, derived or validated in dialysis cohorts. Discrimination measures for models with c-statistic data from three or more cohorts were pooled by random effects meta-analysis and a 95% prediction interval (PI) was calculated. Risk of bias was assessed using PROBAST. The review was conducted according to the PRISMA statement and the CHARMS checklist.

Eight studies were included in this systematic review. All the included studies validated pre-existing models that were derived in cohorts from the general population. None of the identified studies reported the development of a new dialysis specific prediction model for stroke, while dialysis specific risk scores for bleeding were proposed by two studies. In meta-analysis of c-statistics, the CHA2DS2-VASc, CHADS2, ATRIA, HEMORR(2)HAGES and HAS-BLED scores showed very poor discriminative ability in the dialysis population. Six of the eight included studies were at low or unclear risk of bias and certainty of evidence was moderate.

The existing prediction models for stroke and bleeding have very poor performance in the dialysis population. New dialysis-specific risk scores should be developed to guide clinical decision making in these patients.

Patients with congenital heart disease (CHD) form a high-risk subgroup for infective endocarditis (IE), necessitating tailored prevention and treatment strategies. However, comprehensive nationwide data comparing IE characteristics and outcomes in patients with and without CHD, including children, are sparse. This study aims to address this gap in knowledge.

Using Danish nationwide registries, all patients with IE from 1977 to 2021 were identified and stratified on whether they had a diagnosis of CHD, regardless of its complexity. Characteristics prior to and during admission as well as associated outcomes (i.e. in-hospital mortality, 1-year mortality, and 10-year mortality, and IE recurrence) were compared between groups.

In total, 14 040 patients with IE were identified, including 895 (6.4%) with CHD. Patients with vs. without CHD were younger at the time of IE diagnosis (median age 38.8 vs. 70.7 years), less comorbid, and more frequently underwent cardiac surgery during admission (35.7% vs. 23.0%, P < .001). Notably, 76% of patients with IE < 18 years of age had CHD. The IE-related bacteraemia differed between groups: Streptococci (29.9%) were the most common in patients with CHD, and Staphylococcus aureus (29.9%) in patients without CHD. Patients with CHD had a significantly lower cumulative incidence of in-hospital mortality (5.7% vs. 17.0%, P < .001) and 1-year mortality (9.9% vs. 31.8%, P < .001) compared with those without CHD. The 10-year cumulative incidence of IE recurrence was similar between groups (13.0% and 13.9%, P = .61).

Patients with CHD who develop IE exhibit distinct characteristics and improved long-term outcomes compared with patients without CHD. Notably, the majority of children and adolescents with IE have underlying CHD.

Endometriosis, a systemic gynaecological disease affecting 10% of women in reproductive age, shares pathophysiological characteristics with cardiovascular disease. However, data on the relationship between endometriosis and cardiovascular outcomes are scarce, prompting this study to address the knowledge gap.

Using Danish nationwide registries, women diagnosed with endometriosis (1977-2021) were identified and matched with controls in a 1:4 ratio based on year of birth. The primary outcome was a composite of acute myocardial infarction and ischaemic stroke. The secondary outcomes were arrhythmias, heart failure, and mortality.

In total, 60 508 women with endometriosis and 242 032 matched controls were included (median age 37.3 years). Women with endometriosis were more comorbid and used more medications than controls. The incidence rates of the composite outcomes were 3.2 [95% confidence interval (CI) 3.2-3.3] and 2.7 (95% CI 2.7-2.8) per 1000 person-years among women with and without endometriosis, respectively. Women with endometriosis had a significantly higher associated rate of the composite outcome compared with controls [unadjusted hazard ratio (HR) 1.18 (95% CI 1.14-1.23), adjusted HR 1.15 (95% CI 1.11-1.20)]. Likewise, women with endometriosis were also at significantly increased associated risk of arrhythmias [unadjusted HR 1.24 (95% CI 1.20-1.28) and adjusted HR 1.21 (95% CI 1.17-1.25)] and heart failure [unadjusted HR 1.16 (95% CI 1.09-1.22) and adjusted HR 1.11 (95% CI 1.05-1.18)] but at decreased risk of mortality [unadjusted HR 0.95 (95% CI 0.92-0.97) and adjusted HR 0.93 (95% CI 0.91-0.96)].

Women with endometriosis have a higher associated long-term risk of cardiovascular outcomes compared with controls. Despite subtle absolute risk differences, the high prevalence of endometriosis underscores the importance of these findings.

Atrial fibrillation (AF) is a heart disease affecting millions of Americans. Clinicians evaluate AF-related risk by assessing the temporal pattern, variation, and severity of AF episodes through AF burden (AFB). However, existing prognostic tools based on these metrics are suboptimal, as they do not account for electrical complexity of AF signals. This study introduced Electrical Burden (EB) as a new marker to assess electrical instability and complexity of AF. We also developed a Complexity AF score that incorporates AFB, EB, and Poincaré analysis to assess the severity of AF. Electrocardiogram (ECG) from 50 AF patients in the Long-term AF database were analyzed. EB was calculated using four metrics and combined with AFB and Poincaré metrics to derive the Complexity AF score for each patient. Our results show that AFB, EB, and Poincaré metrics are independent markers, each describing different aspects of AF complexity. The Complexity AF score effectively distinguished between terminated (2.82 ± 1.29, 17 patients) and non-terminated AF groups (4 ± 1.46, 33 patients) (p-value < 0.05). This study emphasizes the importance of EB and Poincaré analysis as an indicator of electrical complexity of AF and highlights the utility of the Complexity AF score in accurately characterizing and stratifying AF to guide management.

Clinicians, researchers, regulators, and other decision-makers increasingly rely on evidence from real-world data (RWD), including data routinely accumulating in health and administrative databases. RWD studies often rely on algorithms to operationalize variable definitions. An algorithm is a combination of codes or concepts used to identify persons with a specific health condition or characteristic. Establishing the validity of algorithms is a prerequisite for generating valid study findings that can ultimately inform evidence-based health care. In this paper, we aim to systematize terminology, methods, and practical considerations relevant to the conduct of validation studies of RWD-based algorithms. We discuss measures of algorithm accuracy, gold/reference standards, study size, prioritization of accuracy measures, algorithm portability, and implications for interpretation. Information bias is common in epidemiologic studies, underscoring the importance of transparency in decisions regarding choice and prioritizing measures of algorithm validity. The validity of an algorithm should be judged in the context of a data source, and one size does not fit all. Prioritizing validity measures within a given data source depends on the role of a given variable in the analysis (eligibility criterion, exposure, outcome, or covariate). Validation work should be part of routine maintenance of RWD sources. This article is part of a Special Collection on Pharmacoepidemiology.