BACKGROUND:Culture-negative infective endocarditis (CNIE) remains a diagnostic and therapeutic challenge. Current evidence on this disease is limited by small sample sizes, lack of granularity, and highly selected data. OBJECTIVES:This study sought to provide a granular characterization of CNIE in the modern diagnostic era from the first nationwide cohort of patients with infective endocarditis (IE). METHODS:This study used data from the nationwide Danish NIDUS (NatIonal Danish endocarditis stUdieS) registry, including all patients hospitalized with first-time left-sided IE (2016-2021). Patients were categorized as having CNIE or culture-positive infective endocarditis (CPIE) on the basis of blood cultures, valve tissue cultures, and polymerase chain reaction analyses. The study described patients' medical history, IE-specific disease features, clinical practice patterns, and treatment regimens. RESULTS:Of 2,875 IE patients, 212 (7.4%) had CNIE. Compared with CPIE, CNIE patients were more likely to have congenital heart disease (9.9% vs 2.9%) and less likely to have previous cancer (9.3% vs 14.7%). At admission, CNIE patients presented less frequently with sepsis (7.1% vs 24.6%) and fever (44.3% vs 61.7%), but they presented more often with embolism (25.9% vs 10.8%) and valvular insufficiency (11.3% vs 7.4%). The median size of vegetations was smaller (8 mm vs 10 mm) for patients with CNIE, whereas rates of prosthetic valve infection (22.2% vs 23.1%) and valve surgery (20.3% vs 21.8%) were similar. Positron emission tomography with computed tomography (PET-CT) was commonly used in both groups (67%-68%), and it was diagnostic in 13.1% of CNIE cases and 10.7% of CPIE cases. Among patients with prosthetic valve CNIE, the diagnostic yield of PET-CT was almost 50%. CONCLUSIONS:Using the first nationwide, unselected IE cohort, this study demonstrated a lower proportion of culture-negative cases than reported in previous studies. Patients with CNIE differed from CPIE in clinical presentation and disease characteristics, notably with less frequent fever and sepsis but higher embolic complication rates. However, culture-negative IE is highly heterogeneous and is better defined by distinct subgroups rather than by a single phenotype.

AIMS:Atrial fibrillation (AF) is a risk factor for respiratory syncytial virus (RSV)-related adverse cardiac events. This prespecified analysis of the DAN-RSV trial investigated RSVpreF vaccine effectiveness (VE) against respiratory and cardiovascular outcomes among older adults with and without AF. METHODS AND RESULTS:DAN-RSV was a pragmatic, open-label, individually randomized trial in Denmark during the 2024/2025 winter season. Adults ≥60 years were randomly assigned 1:1 to RSVpreF vaccine or no vaccine. Baseline and endpoint data were obtained from nationwide health registries. The primary endpoint was hospitalization for RSV-related respiratory tract disease, occurring 14 days after study visit until May 31, 2025. Prespecified respiratory and cardiovascular endpoints were assessed by AF status. Among 131,276 participants, 10,126 (7.7%) had a history of AF (mean age 73.2 ± 6.9 years, 30.4% female). AF participants had higher event rates compared with non-AF participants. RSVpreF vaccine lowered the incidence of the primary endpoint with no evidence of effect modification by AF status (AF: VE 80.6% (95%CI -84.7 to 99.6), no AF: VE 84.6% (95%CI 32.3 to 98.3), p-value for interaction >0.99). RSVpreF vaccine was further associated with a lower incidence of all-cause respiratory tract disease hospitalization (AF: VE 25.7% (95%CI -16.9 to 46.1), no AF: VE 13.0% (95%CI -3.3 to 27.8)) and RSV-related and overall cardio-respiratory disease hospitalization with no evidence of effect modification by AF status (p-value for interaction ≥0.45 for all). RSVpreF vaccine was not significantly associated with AF or stroke hospitalizations regardless of AF status (p-value for interaction≥0.34 for all). CONCLUSIONS:In older adults, RSVpreF vaccine was associated with a lower incidence of RSV-related and all-cause respiratory tract disease hospitalizations, as well as RSV-related and all-cause cardio-respiratory disease hospitalizations, with no evidence of effect modification by AF status.

Aims We compared the effects of 'ablate and pace' to pharmacological therapy on mortality and left ventricular ejection fraction (LVEF) in patients with atrial fibrillation (AF), with or without heart failure (HF). Methods and results Articles were identified by searching PubMed, Central, and Embase until 30 June 2024. Inclusion criteria encompassed observational and randomized controlled trials (RCTs) comparing 'ablate and pace' with pharmacological therapy and investigating outcomes of mortality and LVEF in patients with AF. An exclusion criterion was lack of a parallel study design. The primary outcomes were all-cause mortality and the mean difference (MD) in LVEF. Endpoints were assessed through meta-analyses computing relative risks (RRs) and MDs. The clinical diagnosis of HF was used to distinguish between patients with and without HF. Initially, 3837 studies were identified, of which 24 (n = 4292 patients) fulfilled the inclusion criteria, including 17 (n = 3261 patients) that focused on HF. Follow-up time varied from 3 to 96 months. Only in HF patients, 'ablate and pace' reduced mortality significantly with a risk reduction of 36% [RR, 0.64; 95% confidence interval (CI), 0.49-0.85; P < 0.01; n = 10] as compared with pharmacological therapy. Except for two studies, cardiac resynchronization therapy (CRT) was the chosen pace mode. The mortality reduction was independent of study design: RCTs (RR, 0.41; 95% CI, 0.18-0.94; P = 0.04; n = 2) and observational studies (RR, 0.70; 95% CI, 0.55-0.90; P = 0.01; n = 8). 'Ablate and pace' and pharmacological therapy were similar for the LVEF outcome (MD, 1.1; 95% CI, -1.6-3.8; P = 0.39; n = 16), which was independent of both HF and study designs (results not shown). Conclusion 'Ablate and CRT' reduced mortality in HF patients as compared with pharmacological therapy, which was supported by statistical associations in observational studies. A single RCT corroborated the finding.

BACKGROUND AND AIMS:To assess the prevalence of subclinical coronary atherosclerosis and its association with myocardial infarction, death or myocardial infarction, and clinically driven coronary revascularization in asymptomatic women and men in a Danish general population cohort. METHODS:Asymptomatic women (n = 5710, 57%) and men (n = 4293, 43%) >40 years underwent coronary computed tomography angiography. The primary endpoint was myocardial infarction, while secondary endpoints were death or myocardial infarction combined and clinically driven coronary revascularization. RESULTS:From 40 through to >80 years of age, women had less subclinical coronary atherosclerosis than men (P for gender interaction <.0001), both in persons with and without cardiovascular risk factors. Median follow-up was 6.0 years (interquartile range: 3.9-9.5). In individuals with vs without obstructive subclinical coronary atherosclerosis, the adjusted hazard ratio for having a myocardial infarction was 4.1 (95% confidence interval: 1.5-11) in women and 12 (4.6-34) in men (P for gender interaction = .24). Corresponding hazard ratios for death or myocardial infarction combined were 1.9 (1.3-2.9) and 2.7 (1.9-3.9), respectively (P for gender interaction = .30). Finally, corresponding hazard ratios for clinically driven coronary revascularization were 23 (5.2-106) and 34 (11-106), respectively (P for gender interaction = .35). CONCLUSIONS:For the same degree of subclinical coronary atherosclerosis, women may have a lower risk of myocardial infarction than men. These novel findings show that in asymptomatic women and men, the presence of obstructive subclinical coronary atherosclerosis conferred a fourfold and 12-fold risk of myocardial infarction.

Background Patients with recurrent myocardial infarction (MI) are a heterogenous group with high comorbidity burden, risk of complex coronary disease, and at risk of poor outcomes. However, contemporary comparative data are lacking. Methods Consecutive patients with recurrent MI (defined as a new hospital admission for MI >28 days following a first-time MI) in Denmark between 2015 and 2022 were identified through the nationwide registries and matched 1:1 on age and sex to patients with first-time MI. The primary outcome was a composite of all-cause mortality, hospitalization for heart failure (HHF), and further recurrent MI. Standardized risks with 95% confidence intervals (CI) were estimated using cause-specific Cox regression models with first-time MI serving as the reference group. Results A total of 8,397 patients with recurrent MI and 8,397 with first-time MI were included (median age 73, 70.7% male). Patients with recurrent MI had more comorbidities. For the primary composite outcome, patients with recurrent MI had a standardized 1-year risk of 24.0% versus 17.2% among those with first MI (standardized risk ratio [sRR] 1.39 [95% CI: 1.34-1.44]). They also had higher risks of: all-cause mortality, 14.6% versus 11.3% (sRR 1.29 [1.24-1.35]); HHF, 6.6% versus 6.0% (sRR 1.11 [1.00-1.21]), and recurrent MI 6.7% versus 2.2% (sRR 3.01 [2.71-3.45]). Use of guideline-recommended treatments post-dicharge was high, albeit lower than for first-time MI: percutaneous coronary intervention (53.7% versus 64.3%, p<0.001), lipid-lowering treatment (78.1% versus 83.2%, p<0.001), and P2Y12 inhibitor (77.3% versus 82.6%, p<0.001). Conclusion Recurrent MI is associated with a higher risk of all-cause mortality, HHF, and further recurrent MI compared with first-time MI.

BACKGROUND:Glycaemic dysregulation is associated with clinically diagnosed atrial fibrillation (AF), but prior studies have largely relied on limited monitoring of heart rhythm and glucose levels. We investigated whether periods with higher glucose exposure were associated with AF burden and progression in individuals undergoing long-term continuous monitoring and serial haemoglobin A1c (HbA1c) measurements. METHODS:Post-hoc analysis of 884 LOOP Study participants without diabetes undergoing implantable loop recorder (ILR) screening for AF and repeated HbA1c measurements. AF burden, defined as percentage of time in AF, was calculated in the 60-days prior to blood sampling and analysed in groups by highest HbA1c level and using a two-part mixed-effects model, while AF progression was assessed by cumulative AF duration and burden over time. RESULTS:The dataset combined >1 million days of heart rhythm monitoring (including 34,852 with AF) with 3079 HbA1c measurements. The AF burden was 0.52% [0.09-3.45%], 0.78% [0.25-4.07%], and 4.42% [0.98-13.1%], for HbA1c measurements in the normal (≤38 mmol/mol), prediabetic (39-47 mmol/mol), and diabetic (≥48 mmol/mol) range, respectively. A 1 mmol/mol increase in HbA1c was associated with a 5% relative increase in AF burden (adjusted estimate 1.05 [1.00-1.09], p = 0.039). Participants reaching prediabetes or diabetes accumulated longer AF durations and higher AF burden over time compared to participants with consistently normal HbA1c. CONCLUSION:Higher HbA1c levels were associated with higher AF burden and lower HbA1c levels were associated with lower AF burden and less accumulation of AF over time. TRIAL REGISTRATION:ClinicalTrials.gov, identifier: NCT02036450.

BACKGROUND:Complete revascularization is recommended in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease. However, whether the non-culprit lesions should be evaluated using angiography or fractional flow reserve (FFR) remains uncertain. The aim of this study was to evaluate the long-term outcome of patients with STEMI and multivessel disease who had non-culprit FFR-values >0.80 and thus deferred PCI. METHODS:Of the 627 patients included in the DANAMI-3-PRIMULTI trial, 314 patients were randomized to FFR-guided complete revascularization and 280 were included in this substudy. Patients were divided into a PCI-deferral group who had no PCI of non-culprit lesions (FFR > 0.80) (n = 106) and a PCI group encompassing patients treated with PCI of at least one non-culprit lesion (FFR ≤ 0.80 or an angiographical diameter stenosis of ≥90%) (n = 174). The combined endpoint included all-cause mortality, myocardial infarction, or urgent revascularization. RESULTS:During a median follow-up of 10.5 years (IQR 9.8-11.4), the composite outcome occurred in 62 (36%) patients in the PCI group and in 50 (47%) patients in the PCI-deferral group (adjusted HR 0.64, 95% CI: 0.44-0.95, p = 0.025). PCI-deferral was associated with a significantly higher risk of cardiovascular mortality (adjusted HR 0.48, CI 95% 0.24-0.97, p = 0.040) compared to the PCI group. CONCLUSION:In patients with STEMI and multivessel disease, deferring PCI of non-culprit lesions based on FFR > 0.80 was associated with an increased risk of the combination of all-cause mortality, myocardial infarction, or urgent revascularization as well as cardiovascular mortality compared to patients treated with PCI of FFR-positive non-culprit lesions.

Infective endocarditis (IE) often presents with non-specific symptoms, which may delay diagnosis and treatment. Previous studies exploring symptom duration have been limited by small cohorts or single-centre studies. We aimed to investigate patient characteristics, microbial aetiology, treatment, and all-cause mortality of patients with IE according to symptom duration prior to diagnosis. We included all patients with first-time IE from the NatIonal Danish Endocarditis StUdies (NIDUS) registry (2016–2021). Patients with left-sided IE and available symptom duration were stratified as short, intermediate, or prolonged (≤ 7, 8–29, or ≥ 30 days). The primary outcome was six-month mortality. Among 2,938 patients with left-sided IE, median symptom duration was 8 days [IQR:4–20], and 17.6

Patients with diabetes are at higher risk for respiratory syncytial virus (RSV)-related hospitalization and a more severe disease course.1 Although a bivalent RSV prefusion F protein-based (RSVpreF) vaccine recently demonstrated effectiveness against RSV-related respiratory tract disease in an all-comer, older population,2 it is unknown whether individuals with diabetes derive a different degree of benefit from vaccination. The aim of this prespecified analysis of the DAN-RSV trial was to examine RSVpreF vaccine effectiveness (VE) against respiratory and cardiovascular events among persons with and without diabetes.

BACKGROUND:Electrocardiogram (ECG)-derived indices of atrial remodeling have demonstrated predictive value in established atrial fibrillation (AF) but remain unexplored in screening-detected or symptomatic AF. OBJECTIVE:We investigated the prognostic value of implantable loop recorders (ILR) ECG-derived atrial fibrillatory rate (AFR), average f-wave envelope amplitude (FWA), and the organization index derived from the signal's spectral characteristics (ExpDec). METHODS:We analyzed 1411 LOOP study participants (758 men, median age 73 years) with ILR and no prior AF. Baseline AFR, ExpDec, and FWA indices were extracted from AF episodes ≥60 minutes occurring within 1 year after ILR implantation. Multivariate Cox regression assessed associations with all-cause mortality (primary end point) and a composite end point of cardiovascular death (CVD) or heart failure hospitalization (secondary end point). RESULTS:During the first year of monitoring, AF episodes ≥60 minutes were detected in 96 patients (6.8%). Low AFR (<317 fpm), ExpDec (<1.25), and FWA (<97 μV) were associated with increased risk of all-cause mortality (hazard ratio [HR] 95% confidence interval [CI]: 2.5 [1.3-4.8], 2.8 [1.4-5.5], and 2.7 [1.4-5.4], respectively) and similarly for the composite end point of CVD or heart failure hospitalization, although with larger uncertainty (HR [95% CI]: 4.0 [1.6-9.9], 3.7 [1.4-10.1], 2.9 [0.97-8.6], respectively). FWA demonstrated a significant, yet modest, negative correlation with left atrial volume. CONCLUSION:In screening-detected AF, indices of a more organized fibrillatory process (low AFR/ExpDec) and advanced structural abnormalities (low FWA) were associated with increased mortality and heart failure events. F-wave analysis identifies high-risk patients in early AF, potentially enabling targeted interventions.

BACKGROUND:SGLT2 inhibitors (SGLT2i) reduce mortality in left heart failure. In pulmonary arterial hypertension (PAH), preclinical data suggest SGLT2i improve right ventricular function through metabolic modulation and inhibition of vascular remodeling via smooth muscle cell pathways. The DAPAH trial evaluated whether the potential benefits of SGLT2 inhibition translate into clinical efficacy for symptomatic patients on background vasodilator therapy with either PAH or chronic thromboembolic pulmonary hypertension. METHODS:In this single-center, double-blind trial, 52 patients were randomized (1:1) to dapagliflozin 10 mg daily or placebo for 12 weeks. The primary endpoint was change in Peak VO2. Secondary endpoints included invasive hemodynamics, NT-proBNP, 6-minute walk distance (6MWD) and REVEAL Lite 2 scores. RESULTS:Baseline characteristics were balanced (n=52; mean age 66.5 years; 63% female; n=40 PAH, n=12 CTEPH). Fifty-one patients had complete data on Peak VO2. At 12 weeks, there was no significant difference in Peak VO2 (Adjusted Mean Difference: -0.67 mL/kg/min; 95% CI [-1.67, 0.33]; p=0.187). No significant treatment effects were observed for pulmonary vascular resistance (p=0.255), 6MWD (p=0.22), or NT-proBNP trajectory (interaction p=0.681). REVEAL Lite 2 scores showed a small reduction with dapagliflozin (-0.66; 95% CI [-1.25, -0.06]; p=0.031). Metabolic target engagement was evident from a significant reduction in serum urate (P-interaction < 0.001). Dapagliflozin was safe and well-tolerated. CONCLUSION:This randomized study of SGLT2i in pre-capillary PH showed that 12 weeks of dapagliflozin did not significantly improve exercise capacity, hemodynamics, or functional status compared to placebo. CLINICALTRIALS:gov (NCT05179356).

Background Heart failure (HF) prevalence is increasing. In a nationwide cohort study, we investigated temporal trends in care and outcomes of patients with new‐onset HF within vulnerable populations. Methods There were 154 819 patients with new‐onset HF between 2003 and 2022 identified and included using Danish nationwide registries. Eight potentially vulnerable subgroups were defined (aged ≥80 years, women, low income, living alone, mental illness, non‐Western background, frail, and rural residency) and compared with their counterparts. Temporal trends in initiation of guideline‐recommended HF therapy and risk of all‐cause mortality were analyzed. Results Initiation of guideline‐recommended HF therapies (mineralocorticoid‐receptor‐antagonists, β‐blockers, renin‐angiotensin system inhibitors) was generally successful, but initiation of mineralocorticoid receptor antagonists was insufficient in vulnerable patients. Five‐year all‐cause mortality decreased from 2003 to 2007 to 2018 to 2022; however, those aged ≥80 years, frail, and living alone experienced a smaller decrease (aged ≥80 years versus counterpart: adjusted hazard ratio [aHR], 0.74 [95% CI, 0.72–0.76] versus aHR, 0.63 [95% CI, 0.61–0.65]; frail versus counterpart: aHR, 0.74 [95% CI, 0.71–0.77] versus aHR, 0.67 [95% CI, 0.65–0.68]; living alone versus counterpart: aHR, 0.75 [95% CI, 0.73–0.77] versus aHR, 0.62 [95% CI, 0.60–0.64]); and patients with mental illness experienced no improvements (mental illness versus counterpart: aHR, 0.99 [95% CI, 0.87–1.12] versus aHR, 0.68 [95% CI, 0.67–0.70]). Six vulnerable groups had higher aHRs compared with their counterparts in 2018 to 2022. Conclusions Initiation of guideline‐recommended therapies improved over the past 2 decades, but initiation of mineralocorticoid receptor antagonists was inadequate in vulnerable patients. Furthermore, the overall mortality risk declined, but 4 out of the 8 vulnerable groups experienced a lesser decline than their counterparts. Despite improvements, 6 vulnerable groups still had worse outcomes than their counterparts at the end of the study period. Our findings highlight the urgent need for more effort aimed at helping vulnerable subgroups of patients with HF.

Background:Opioid use is frequently reported as a baseline characteristic in transcatheter aortic valve implantation (TAVI) cohorts, yet its prognostic implications have not been examined. Aim:To examine the association between pre-procedural opioid use and post-TAVI outcomes. Methods:Using Danish nationwide registries, we identified patients undergoing TAVI between 2015 and 2022. Patients were categorized according to opioid use within one year before TAVI. We examined one-year all-cause mortality, cumulative days of hospitalization including the composite outcome of death or > 14 cumulative hospitalization days, and a potential opioid dose-response relationship. Adjusted relative risks were estimated using multivariable Cox and logistic regression. Results:We identified 6505 patients: 1265 (19.4%) with opioid use (48.9% male; median age 80 years) and 5240 (80.6%) without (59.4% male; median age 81 years). The two groups were comparable in cardiac comorbidities and malignancy but differed in musculoskeletal (back disorders: 45.9% vs 20.7%; arthropathies 65.3% vs 47.1%) and psychiatric conditions (antidepressants: 18.8% vs. 9.6%; anxiolytics/hypnotics: 23.7% vs. 12.4%). Baseline opioid use was associated with higher post-TAVI mortality (10.4% vs 6.9%; adjusted HR 1.35, 95% CI 1.11-1.66) and increased risk of the composite outcome (OR 1.47, 95% CI 1.25-1.72). A dose-response relationship was observed, with one-year mortality increasing from 7.0% in non-users to 8.8% in low-dose users and 12.1% in high-dose users. Conclusion:Baseline opioid use was associated with increased mortality and hospitalization burden in the year following TAVI, and this relationship was aggravated among high-dose users. The observed associations were most likely driven by the underlying condition of the opioid therapy.

AIMS:Obesity increases the risk of heart failure (HF), partly due to hypervolaemia and excess epicardial adipose tissue (EAT).We aimed to investigate the effect of the sodium glucose co-transporter 2 inhibitor empagliflozin on estimated extracellular volume (eECV) and ventricular EAT mass in non-diabetic patients with overweight or obesity and risk of HF to evaluate the drug's potential for HF prevention. METHODS:In this randomised, double-blind, placebo-controlled trial, we recruited non-diabetic patients with body mass index (BMI) >28kg/m2 and risk of HF. Patients were randomised 1:1 to 180-days empagliflozin 10 mg or placebo. The primary endpoints were the baseline-adjusted mean differences in change of eECV and ventricular EAT mass in the intention-to-treat population with Bonferroni-adjustment for multiplicity. RESULTS:From September 2021 to July 2024, we randomised 191 patients (empagliflozin: 94, placebo: 97) with median age 68 years and median BMI 31·9 kg/m2. Analyses of eECV and EAT included 191 and 165 patients, respectively. Compared to placebo, empagliflozin significantly reduced eECV [empagliflozin, mean change (SD): -0·154 L (0·257); placebo, mean change: -0·029 L (0·261); estimated treatment difference (ETD): -0·123 L, 97.5% CI: -0·211 to -0·035, padj=0·004] but did not affect EAT mass [empagliflozin, mean change: -2·3 g (13·4); placebo, mean change: -3·7 g (15·8); ETD: 1·5 g, 97·5% CI: -3·8 to 6·7, padj=1.00]. CONCLUSION:In high-risk patients with overweight or obesity, treatment with empagliflozin resulted in a potentially favourable reduction in eECV compared to placebo. Meanwhile, the drug did not affect EAT mass.

BACKGROUND:Glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy is increasingly used, but the physiological effects in patients with heart failure and reduced ejection fraction (HFrEF) remain uncertain. Continuously collected data from implantable cardiac devices may enable evaluation of drug effects in a real-world setting. METHODS:In a nationwide Danish retrospective matched cohort study, GLP-1RA initiators with implantable cardiac devices were matched 1:5 to unexposed device recipients by sex and age. Sensor data were assessed from 30 days before to 30 days after initiation. Primary outcomes were changes in heart rate and thoracic impedance. Analyses were adjusted for baseline sensor value, BMI category, hypertension, and type 2 diabetes. Prespecified subgroup analyses were performed in patients with HFrEF. RESULTS:In 666 patients (111 GLP-1RA initiators, 555 matched controls), semaglutide was used in 95% of initiators. Compared with controls, GLP-1RA initiation was associated with higher night heart rate (adjusted difference 2.12 bpm; 95% CI, 1.38 to 2.87), higher daily heart rate (1.46 bpm; 95% CI, 0.65 to 2.06), and higher thoracic impedance (0.66 Ω; 95% CI, 0.17 to 1.15) (all P<0.01). S1 amplitude decreased (-0.09 mG; 95% CI, -0.14 to -0.04; P<0.01). Heart rate increases followed a stepwise pattern across semaglutide dose levels, with an average increase of 2.5 bpm per dose escalation. Findings were directionally consistent in patients with HFrEF (GLP-1RA n=80), with no evidence of effect modification. CONCLUSION:GLP-1RA initiation was associated with measurable changes in device-derived physiology. Larger studies are needed to evaluate clinical implications, including in HFrEF. TRIAL REGISTRATION:Clinicaltrials.gov (NCT06099158).

BACKGROUND:Dental procedures may cause bacteremia, which is considered a risk factor for infective endocarditis (IE). This study sets out to examine whether dental procedures are associated with an increased risk of IE. METHODS:We examined the nationwide time-dependent association between dental procedures and risk of bacteremia and IE among Danes > 18 years on January 1, 2010. Adjusted hazard ratios (HR) for bacteremia and IE were estimated by Cox regression with time-varying exposure (dental visit and three months later). RESULTS:We examined 4,178,514 persons who had dental care (66.9% of residents, median age 44 years [IQR 30-49]). During 9 years of follow-up, 69,928 (1.7%) persons had bacteremia, and 3,754 (0.09%) had IE. Among those with bacteremia or IE in the proximity of dental care (within three months), Streptococci accounted for 16.1% and 26.9%, respectively. The adjusted HRs for bacteremia and IE associated with dental procedures were 0.94 (95% CI 0.92-0.95) and 1.00 (95% CI 0.94-1.08), respectively, compared with non-exposed time. No dose-response relationship for invasive vs non-invasive procedures was found. The IE risk associated with dental care was not different in high-risk patients (prior IE, valve prostheses, or congenital heart disease): HR 0.96 (95% CI 0.83-1.10). CONCLUSION:We did not find an association between dental procedures and bacteremia or IE, and this was irrespective of high-risk cardiac preconditions.

AIMS:To investigate the association between serial high-sensitivity cardiac troponin-T (hs-TnT) concentrations and subsequent heart failure in individuals presenting with suspected acute coronary syndrome (ACS). METHODS AND RESULTS:Utilizing Danish nationwide registries, we identified individuals without known heart failure who underwent serial hs-TnT assessment for suspected ACS between 2012 and 2019. Individuals were categorized based on the hs-TnT concentration patterns from the first to the second measurement (normal, rising, persistently elevated, or falling), the extent of hs-TnT concentration change (≤20%, >20 to 50%, or > 50%), and quartiles of peak hs-TnT levels (≤9 ng/l, 10-19 ng/l, 20-263 ng/l, and ≥ 264 ng/l). Standardized absolute and relative risks of incident hospitalization or outpatient contact for heart failure were computed using cause-specific multivariable Cox regression with average treatment effect modeling. Of 26,835 individuals, 38.8% received a discharge diagnosis of myocardial infarction, 5.1% of unstable angina, and 56.1% of suspected myocardial infarction or chest pain. Within the initial 30 days, 1122/26,835 (4.2%) persons received a heart failure diagnosis, with an additional 707/25,085 (2.8%) diagnosed between days 31-365. Subjects with two normal hs-TnT values exhibited the lowest standardized absolute risk (0-30 days: 0.3%; 31-365 days: 0.4%), while those with persistently elevated concentrations demonstrated the highest risk (0-30 days: 6.6%; 31-365 days: 4.3%). Heart failure risk also exhibited a significant, positive association with peak hs-TnT concentration. CONCLUSIONS:In individuals presenting with suspected ACS, persistent hs-TnT elevation was associated with the highest risk of subsequent heart failure. A dose-response association was observed between peak hs-TnT concentrations and incident heart failure.

AIMS:Recent advancements in transcatheter aortic valve implantation (TAVI) and patient selection have significantly improved the outcomes of TAVI. Yet it is unknown whether patients undergoing TAVI in the modern era have comparable mortality as the general population. METHODS AND RESULTS:All patients undergoing TAVI in Denmark (2015-23) were matched on age and sex with controls from the general population (1:4). Patients were followed from 30-day post-TAVI until death or end of study (12/23). The 5-year all-cause mortality was examined by cumulative incidence functions and Cox-regression analyses. The 5-year all-cause hospitalization burden was analysed among those alive at 5-year post-index. The study included 7250 patients undergoing TAVI [median age 81.2 years (IQR 77.0-84.9), 57.3% men] and 29 000 controls. The absolute risk of death was 39.6% [95% confidence interval (CI) 38.1-41.2] in the TAVI group, compared to 32.2% (95% CI 31.5-32.9) among controls. The associated all-cause mortality was similar between patients undergoing TAVI and controls [adjusted hazard ratio 0.95 (95% CI 0.90-1.01)]. Stratification by age revealed a higher risk of death among the TAVI group aged <80 years compared with controls, while patients aged ≥80 years showed a lower risk of death. Patients undergoing TAVI experienced longer and more frequent hospitalizations compared with controls, while the relative difference decreased over time. CONCLUSION:Our findings suggest that TAVI was associated with long-term mortality and hospitalization rates comparable to the general population. Stratified by age, mortality was higher among TAVI patients <80 years and lower among those ≥80 years. These findings support patient selection, safety, and long-term outcomes of TAVI.