Temporal changes in the number of European and American guideline recommendations and underlying evidence base for the management of infective: An update of previous published data.

This report aimed to examine temporal changes in the number of recommendations on management of infective endocarditis in the European and American guidelines. The number of recommendations has increased since 2004 without an increment in evidence base in the European iteration. American guidelines have reduced the number of recommendations with a main evidence base of level B.

Role of echocardiography in the diagnosis and clinical management of infective endocarditis.

Infective endocarditis (IE) is a deadly disease, constituting both diagnostic and treatment challenges. A positive outcome requires rapid and accurate diagnosis, and for that, echocardiography unequivocally remains the cornerstone. Transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) have complementary roles and have been markedly improved during the last decades. The transthoracic modality is the recommended first-line approach but may only be sufficient in patients where the probability of IE is low and/or with clear acoustic windows, especially in patients with right-sided IE. The transesophageal modality is superior to TTE in most aspects and is recommended for all other patients. Both TTE and TEE may delineate vegetation location and size, assess for paravalvular extension of infection, and have the added advantage of defining the hemodynamic effects of valvular or device infection. However, echocardiography still has significant limitations, and novel imaging techniques are increasingly being exploited to improve diagnostic potential. Cardiac computed tomography (CT) performs better than TEE in the detection of abscess or pseudoaneurysm, while magnetic resonance imaging (MRI) has limited value in the diagnostic phase of IE but adds knowledge to the evaluation of extracardiac events. Nuclear molecular techniques are evolving as key supplementary methods in difficult-to-diagnose cases. Although newer imaging modalities are undergoing preliminary evaluation and multimodal imaging will play an increasing role in IE, echocardiography will continue to be pivotal in patients with IE for the foreseeable future.

Long-Term Cardiovascular Risk Associated With Treatment of Attention-Deficit/Hyperactivity Disorder in Adults.

BACKGROUND: Incrementing numbers of patients treated for attention-deficit/hyperactivity disorder (ADHD) call for scrutiny concerning long-term drug-safety. OBJECTIVES: This study aims to investigate associations between long-term use of ADHD treatment and cardiovascular outcomes. METHODS: Using nationwide registers, adult patients first-time initiated on ADHD treatment between 1998 and 2020 were identified. Exposure groups were prior users, <1 defined daily dose (DDD) per day, ≥1 DDD per day determined at start of follow-up, and 1 year after patients' first claimed prescription. Outcomes were acute coronary syndromes, stroke, heart failure, and a composite of the above. RESULTS: At start of follow-up, 26,357, 31,211, and 15,696 individuals were correspondingly categorized as prior users (42% female, median age: 30 years [Q1-Q3: 23-41 years]), <1 DDD per day (47% female, median age: 31 years [Q1-Q3: 24-41 years]), and ≥1 DDD per day (47% female, median age: 33 years [Q1-Q3: 25-41 years]), respectively. Comparing ≥1 DDD per day with prior users, elevated standardized 10-year absolute risk of stroke (2.1% [95% CI: 1.8%-2.4%] vs 1.7% [95% CI: 1.5%-1.9%]), heart failure (1.2% [95% CI: 0.9%-1.4%] vs 0.7% [95% CI: 0.6%-0.8%]), and the composite outcome (3.9% [95% CI: 3.4%-4.3%] vs 3.0% [95% CI: 2.8 %-3.2%]) was found-with corresponding risk ratios of 1.2 (95% CI: 1.0-1.5), 1.7 (95% CI: 1.3-2.2), and 1.3 (95% CI: 1.1-1.5). No apparent associations were found for acute coronary syndrome (1.0% [95% CI: 0.8%-1.2%] vs 0.9% [95% CI: 0.8%-1.0%]). CONCLUSIONS: Possible associations between elevated long-term cardiovascular risk and increasing dosage of ADHD treatment use in a young patient group should warrant further investigation.

Patient characteristics, treatment patterns, and prognosis in drug-use-associated infective endocarditis in Denmark from 1999 to 2018.

BACKGROUND: While the proportion of drug-use-associated infective endocarditis (DU-IE) has been increasing during the opioid crisis in the United States, it is unknown whether this is seen in Denmark, where several preventive means have been implemented. We aimed to assess the temporal proportion of DU-IE and examine the rate of IE recurrence and mortality. METHODS: This nationwide cohort study identified all patients with first-time infective endocarditis in 1999-2018. Drug use was defined using ICD-8/10 codes or prescription filling of medication for opioid use disorder. Long-term mortality was examined with a Kaplan-Meier estimator and a multivariate Cox model. The recurrence of IE was examined with the Aalen-Johansen method and a multivariate cause-specific hazard model. RESULTS: We included 8,843 patients with IE: 407 with DU-IE (60.7% male, median age 43.8 years) and 8,436 with non-DU-IE (65.8% male, median age 71.5 years). The proportion of DU-IE decreased from 5.9% to 3.8% during our study period. The one-year cumulative incidence of all-cause mortality was 16.9% (CI 12.9%-20.8%) for patients with DU-IE and 17.3% (CI 16.4%-18.2%) for patients with non-DU-IE. Drug use was associated with higher one-year mortality (adjusted HR 1.64 (CI 1.23%-2.21%)). The 1-year cumulative incidence of IE recurrence was 12.8% (CI 9.3%-16.3%) in patients with DU-IE and 4.3% (CI 3.8%-4.8%) in patients with non-DU-IE. Drug use was associated with a higher 1-year recurrence of IE (adjusted HR 3.39 (CI 2.35-4.88)). CONCLUSION: In Denmark, the proportion of patients with DU-IE fell by one-third from 1999 to 2018. DU-IE was associated with higher mortality and recurrence rates than non-DU-IE.

Prognosis and antithrombotic practice patterns in patients with recurrent and transient atrial fibrillation following acute coronary syndrome: A nationwide study.

BACKGROUND: First-time detected atrial fibrillation (AF) is associated with aggravated prognosis in patients admitted with acute coronary syndrome (ACS). Yet, among patients surviving beyond one year after ACS, it remains unclear how the recurrence of AF within the initial year after ACS affects the risk of stroke. METHODS: With Danish nationwide data from 2000 to 2021, we identified all patients with first-time ACS who were alive one year after discharge (index date). Patients were categorized into: i) no AF; ii) first-time detected AF during ACS admission without a recurrent hospital contact with AF (transient AF); and iii) first-time detected AF during ACS admission with a subsequent recurrent hospital contact with AF (recurrent AF). From index date, two-year rates of ischemic stroke were compared using multivariable adjusted Cox regression analysis. Treatment with antithrombotic therapy was assessed as filled prescriptions between 12 and 15 months following ACS discharge. RESULTS: We included 139,137 patients surviving one year post ACS discharge: 132,944 (95.6%) without AF, 3920 (2.8%) with transient AF, and 2273 (1.6%) with recurrent AF. Compared to those without AF, the adjusted two-year hazard ratios of ischemic stroke were 1.45 (95% CI, 1.22-1.71) for patients with transient AF and 1.47 (95% CI: 1.17-1.85) for patients with recurrent AF. Prescription rates of oral anticoagulation increased over calendar time, reaching 68.3% and 78.7% for transient and recurrent AF, respectively, from 2019 to 2021. CONCLUSION: In patients surviving one year after ACS with first-time detected AF, recurrent and transient AF were associated with a similarly increased long-term rate of ischemic stroke.

High-risk admission prior to transcatheter aortic valve replacement and subsequent outcomes.

BACKGROUND: Severe, symptomatic aortic stenosis may cause heart failure, acute myocardial infarction, or syncope; limited data exist on the occurrence of such events before transcatheter aortic valve replacement (TAVR) and their impact on subsequent outcomes. Thus, we investigated the association between a preceding event and outcomes after TAVR. METHODS: From 2014 to 2021 all Danish patients who underwent TAVR were included. Preceding events up to 180 days before TAVR were identified. A preceding event was defined as a hospitalization for heart failure, acute myocardial infarction, or syncope. The 1-year risk of all-cause death, and cardiovascular or all-cause hospitalization was compared for patients with versus without a preceding event using Kaplan-Meier, Aalen-Johansen, and in Cox regression analyses adjusted for patient characteristics. RESULTS: Of 5,851 patients included, 759 (13.0%) had a preceding event. The median age was 81 years in both groups. Male sex and frailty were more prevalent in patients with a preceding event (males: 64.7% vs 55.2%, frailty: 49.6% vs 40.6%). The most common type of preceding event was a hospitalization for heart failure (n = 524). For patients with a preceding event, the 1-year risk of death was 11.7% (95% CI: 9.4%-14.1%) versus 8.0% (95% CI: 7.2%-8.7%) for patients without. The corresponding adjusted hazard ratio (aHR) was 1.29 (95%CI: 1.01-1.64). Mortality was highest for patients with a preceding event of a heart failure admission (1-year risk: 13.5% [95%CI: 10.5%-16.5%]). Comparing patients with a preceding event to those without, the 1-year risk for cardiovascular rehospitalization was 15.0% versus 8.2% (aHR 1.60 [95%CI: 1.29-1.99]) and 57.6% versus 50.6% for all-cause rehospitalization (aHR 1.08 [95%CI: 0.87-1.20]). CONCLUSIONS: A hospitalization for heart failure, myocardial infarction, or syncope prior to TAVR was associated with a poorer prognosis and could represent a group to focus resource management on. Interventions to prevent preceding events and improvements in pre- and post-TAVR optimization of these patients are warranted.

Sex differences in infective endocarditis: a Danish nationwide study.

PURPOSE: Sex differences in infective endocarditis (IE) are reported, but patient characteristics are sparse and conflicting findings on the association between sex and short-term outcomes demand further research. We aimed to characterize sex differences in IE in terms of patient characteristics, frailty, microbiology, socioeconomic status, management and outcome on a nationwide scale. METHODS: Between 2010 and 2020, we used Danish national registries to characterize patients with IE according to sex using ICD codes and microbiological lab reports. Frailty was assessed with the Hospital Frailty Risk Score. Mortality was reported with Kaplan-Meier estimates. Logistic regression and Cox regression were used for adjusted analyses. RESULTS: We included 6259 patients with IE with 2047 (32.7%) female patients and 4212 (67.3%) male patients. Female patients were older (median age 75.0 years (64.3-82.2) vs. 71.7 (61.7-78.9)) and more frail (Intermediate frailty: 36.5% vs. 33.1%, High frailty: 11.4% vs. 9.2%). Staphylococcus aureus-IE were most common in both sexes (34.6% vs. 28.8%), but fewer female patients had Enterococcus-IE (10.5% vs. 18.1%). Female patients were less surgically treated (14.0% vs. 21.2%). Female sex was associated with increased in-hospital mortality (adj. OR 1.33, 95% CI 1.16-1.52), but no statistically significant difference in associated 1- and 5-year mortality from hospital discharge were identified (adj. HR 1.09, 95% CI 0.95-1.24 and 1.02, 95% CI 0.92-1.12, respectively). CONCLUSION: Female sex is associated with increased in-hospital mortality, but not in long-term mortality as compared with male patients. Female patients have a lower prevalence of Enterococcus-IE and rates of surgery. Further research is needed to understand these differences.

Impact of Acute Kidney Injury After Transcatheter Aortic Valve Replacement: A Nationwide Study.

BACKGROUND: In patients undergoing transcatheter aortic valve replacement (TAVR), the impact of acute kidney injury (AKI) on the prognosis and especially on future kidney function has been sparsely examined, and data from large cohorts are warranted. METHODS AND RESULTS: With Danish nationwide registries, we identified all patients undergoing TAVR from 2014 to 2021 with no previous dialysis treatment. According to 2 plasma creatinine samples, we identified those suffering a postprocedural AKI within 21 days after TAVR. With 1 year of follow-up, we compared the associated rates of dialysis treatment and death between patients with and without an AKI using multivariable Cox analysis. Finally, according to the lowest recorded creatinine sample, we assessed the kidney function among AKI survivors between 90 and 180 days after the index date. We identified 4091 TAVRs: 193 (4.7%) with AKI (55.4% men; median age, 82 years) and 3898 (95.3%) without AKI (57.0% men; median age, 81 years). Compared with those without AKI, patients with AKI showed increased associated 1-year rates of dialysis treatment (hazard ratio [HR], 7.20 [95% CI, 4.10-12.66]) and death (HR, 2.39 [95% CI, 1.59-3.58]). After 6 months, 74% of AKI survivors had complete kidney recovery, 14.7% had incomplete kidney recovery, 6.3% failed to recover, and 5.1% were on dialysis treatment. CONCLUSIONS: We identified that AKI after TAVR was associated with an increased rate of future dialysis treatment and all-cause death. Among survivors, 74% had complete kidney recovery within 6 months.

Microbiological Etiology in Patients with IE Undergoing Surgery and for Patients with Medical Treatment Only: A Nationwide Study from 2010 to 2020.

Microbiological etiology has been associated with surgery for infective endocarditis (IE) during admission, especially Staphylococcus aureus. We aimed to compare patient characteristics, microbiological characteristics, and outcomes by treatment choice (surgery or not). We identified patients with first-time IE between 2010 and 2020 and examined the microbiological etiology of IE according to treatment choice. To identify factors associated with surgery during initial admission, we used the Aalen-Johansen estimator and an adjusted cause-specific Cox model. One-year mortality stratified by microbiological etiology and treatment choice was assessed using unadjusted Kaplan-Meier estimates and an adjusted Cox proportional hazard model. A total of 6255 patients were included, of which 1276 (20.4%) underwent surgery during admission. Patients who underwent surgery were younger (65 vs. 74 years) and less frequently had cerebrovascular disease, cardiovascular disease, diabetes, and chronic kidney disease. Patients with Staphylococcus aureus IE were less likely to undergo surgery during admission (13.6%) compared to all other microbiological etiologies. One-year mortality according to microbiological etiology in patients who underwent surgery was 7.0%, 5.3%, 5.5%, 9.6%, 13.2, and 11.2% compared with 24.2%, 19.1%, 27,6%, 25.2%, 21%, and 16.9% in patients who received medical therapy for Staphylococcus aureus, Streptococcus spp., Enterococcus spp., coagulase-negative Staphylococci, "other microbiological etiologies", and blood culture-negative infective endocarditis, respectively. Patients with IE who underwent surgery differed in terms of microbiology, more often having Streptococci than those who received medical therapy. Contrary to expectations, Staphylococcus aureus was more common among patients who received medical therapy only.

Perioperative Atrial Fibrillation and One-year Clinical Outcomes in Patients Following Major Emergency Abdominal Surgery.

The prevalence and impact of perioperative atrial fibrillation (AF) during an admission for major emergency abdominal surgery are sparsely examined. Therefore, this study aimed to compare the 30-day and 1-year outcomes (AF-related hospitalization, stroke, and all-cause mortality) in patients with and without perioperative AF to their major emergency abdominal surgery. All patients without a history of AF who underwent major emergency abdominal surgery from 2000 to 2019 and discharged alive were identified using Danish nationwide registries. Patients with and without perioperative AF (defined as new-onset AF during the index hospitalization) were matched 1:4 on age, gender, year of surgery, and type of surgery. The cumulative incidences and hazard ratios of outcomes were assessed using a multivariable Cox regression analysis comparing patients with and without perioperative AF. A total of 2% of patients were diagnosed with perioperative AF. The matched cohort comprised 792 and 3,168 patients with and without perioperative AF, respectively (median age 78 years [twenty-fifth to seventy-fifth percentile 70 to 83 years]; 43% men). Cumulative incidences of AF-related hospitalizations, stroke, and mortality 1 year after discharge were 30% versus 3.4%, 3.4% versus 2.7%, and 35% versus 22% in patients with and without perioperative AF, respectively. The 30-day outcomes were similarly elevated among patients with perioperative AF. Perioperative AF during an admission for major emergency abdominal surgery was associated with higher 30-day and 1-year rates of AF-related hospitalization and mortality and similar rates of stroke. These findings suggest that perioperative AF is a prognostic marker of increased morbidity and mortality in relation to major emergency abdominal surgery and warrants further investigation.

Takotsubo syndrome and stroke risk: A nationwide register-based study.

AIMS: Previous small-scale studies have indicated a short-term stroke incidence of 1.0-1.3% following Takotsubo (syndrome). In this nationwide register-based study, we investigated the 90-day risk of ischemic stroke (IS) or transient ischemia attack (TIA) and mortality of patients with Takotsubo. METHODS AND RESULTS: Patients with incident Takotsubo between January 1st 2009 to September 30th 2018 were identified from Danish nationwide registries. Takotsubo patients were age- and sex-matched with background-, atrial fibrillation/flutter- (AF) and myocardial infarction (MI) cohorts. Cumulative incidences and Cox proportional-hazard regression models were used to analyze the following outcomes: 1) composite of IS/TIA and 2) all-cause mortality. A total of 890 patients with Takotsubo were followed for 90 days. The cumulative 90-day incidence of IS/TIA in the Takotsubo-, background-, AF- and MI cohort, was 2.1% (n = 19), 0.1% (n = 4), 1.1% (n = 47) and 1.5% (n = 66), respectively. The cumulative 90-day mortality in the Takotsubo-, background-, AF- and MI cohort was 5.1% (n = 45), 0.3% (n = 13), 1.7% (n = 75) and 5.6% (n = 230), respectively. The adjusted hazard ratio (HR) for 90-day IS/TIA was when compared to the background-, AF- and MI cohort, 26.43 (95% CI: 8.82-79.24), 1.91 (95% CI: 1.09-3.35) and 2.06 (95% CI: 1.12-3.79), respectively. The adjusted HR for 90-day mortality was when compared to the background-, AF- and MI cohort, 14.19 (95% CI: 7.43-27.09), 0.73 (95% CI: 0.52-1.02) and 1.96 (95% CI: 1.25-3.07), respectively. CONCLUSION: Patients with Takotsubo had an increased 90-day hazard for IS/TIA when compared to age- and sex-matched background-, AF- and MI cohorts.

Recurrence of bacteremia and infective endocarditis according to bacterial species of index endocarditis episode.

PURPOSE: In patients surviving infective endocarditis (IE) recurrence of bacteremia or IE is feared. However, knowledge is sparse on the incidence and risk factors for the recurrence of bacteremia or IE. METHODS: Using Danish nationwide registries (2010-2020), we identified patients with first-time IE which were categorized by bacterial species (Staphylococcus aureus, Enterococcus spp., Streptococcus spp., coagulase-negative staphylococci [CoNS], 'Other' microbiological etiology). Recurrence of bacteremia (including IE episodes) or IE with the same bacterial species was estimated at 12 months and 5 years, considering death as a competing risk. Cox regression models were used to compute adjusted hazard ratios of the recurrence of bacteremia or IE. RESULTS: We identified 4086 patients with IE; 1374 (33.6%) with S. aureus, 813 (19.9%) with Enterococcus spp., 1366 (33.4%) with Streptococcus spp., 284 (7.0%) with CoNS, and 249 (6.1%) with 'Other'. The overall 12-month incidence of recurrent bacteremia with the same bacterial species was 4.8% and 2.6% with an accompanying IE diagnosis, while this was 7.7% and 4.0%, respectively, with 5 years of follow-up. S. aureus, Enterococcus spp., CoNS, chronic renal failure, and liver disease were associated with an increased rate of recurrent bacteremia or IE with the same bacterial species. CONCLUSION: Recurrent bacteremia with the same bacterial species within 12 months, occurred in almost 5% and 2.6% for recurrent IE. S. aureus, Enterococcus spp., and CoNS were associated with recurrent infections with the same bacterial species.

Impact of first-time detected atrial fibrillation after transcatheter aortic valve replacement: A nationwide study.

Background: The prognostic implications of new-onset atrial fibrillation (AF) in conjunction with transcatheter aortic valve replacement (TAVR) is sparsely examined. Therefore, we aimed to examine the impact of first-time detected AF after TAVR on all-cause mortality and heart failure (HF). Methods: With Danish nationwide data from 2008 to 2021, we identified all patients who underwent TAVR and were alive 30 days after discharge (index date). Patients were categorized into i) no AF; ii) history of AF; and iii) first-time detected AF within 30 days after discharge. From the index date, two-year rates of all-cause mortality and HF admissions were compared using multivariable adjusted Cox analysis. Results: We identified 6,807 patients surviving 30 days beyond TAVR: 4,229 (62.1%) without AF (55% male, median age 81), 2,283 (33.6%) with history of AF (58% male, median age 82), and 291 (4.3%) with first-time detected AF (56% male, median age 81). Compared with patients without AF, adjusted analysis yielded increased associated hazard ratio (HR) of all-cause mortality in patients with history of AF (1.53 [95% confidence interval [CI], 1.32-1.77]) and in patients with first-time detected AF (2.06 (95%CI, 1.55-2.73]). Further, we observed increased associated HRs of HF admissions in patients with history of AF (1.70 [95%CI, 1.45-1.99]) and in patients with first-time detected AF (1.77 [95%CI, 1.25-2.50]). Conclusion: In TAVR patients surviving 30 days beyond discharge, first-time detected AF appeared to be at least as strongly associated with two-year rates of all-cause mortality and HF admissions, as compared with patients with history of AF.

Patient Characteristics, Microbiology, and Mortality of Infective Endocarditis After Transcatheter Aortic Valve Implantation.

BACKGROUND: Infective endocarditis (IE) after transcatheter aortic valve implantation (TAVI) is associated with high mortality and surgery is rarely performed. Thus, to inform on preventive measures and treatment strategies, we investigated patient characteristics and microbiology of IE after TAVI. METHODS: Using Danish nationwide registries, we identified patients with IE after TAVI, IE after non-TAVI prosthetic valve (nTPV), and native valve IE. Patient characteristics; overall, early (≤12 m), and late IE (>12 m) microbiology; and unadjusted and adjusted mortality were compared. RESULTS: We identified 273, 1022, and 5376 cases of IE after TAVI, IE after nTPV, and native valve IE. Age and frailty were highest among TAVI IE (4.8%; median age: 82 y; 61.9% frail). Enterococcus spp. were common for IE after TAVI (27.1%) and IE after nTPV (21.2%) compared with native valve IE (11.4%). Blood culture-negative IE was rare in IE after TAVI (5.5%) compared with IE after nTPV (15.2%) and native valve IE (13.5%). The unadjusted 90-day mortality was comparable, but the 5-year mortality was highest for IE after TAVI (75.2% vs 57.2% vs 53.6%). In Cox models adjusted for patient characteristics and bacterial etiology for 1-90 days and 91-365 days, there was no significant difference in mortality rates. CONCLUSIONS: Patients with IE after TAVI are older and frailer, enterococci and streptococci are often the etiologic agents, and are rarely blood culture negative compared with other IE patients. Future studies regarding antibiotic prophylaxis strategies covering enterococci should be considered in this setting.

Frailty and Recurrent Hospitalization After Transcatheter Aortic Valve Replacement.

Background For frail patients with limited life expectancy, time in hospital following transcatheter aortic valve replacement is an important measure of quality of life; however, data remain scarce. Thus, we aimed to investigate frailty and its relation to time in hospital during the first year after transcatheter aortic valve replacement. Methods and Results From 2008 to 2020, all Danish patients who underwent transcatheter aortic valve replacement and were alive at discharge were included. Using the validated Hospital Frailty Risk Score, patients were categorized in the low, intermediate, and high frailty groups. Time in hospital and mortality up to 1 year are reported according to frailty groups. In total, 3437 (57.6%), 2277 (38.1%), and 257 (4.3%) were categorized in the low, intermediate, and high frailty groups, respectively. Median age was ≈81 years. Female sex and comorbidity burden were incrementally higher across frailty groups (low frailty: heart failure, 24.1%; stroke, 7.2%; and chronic kidney disease, 4.5%; versus high frailty: heart failure, 42.8%; stroke, 34.2%; and chronic kidney disease, 29.2%). In the low frailty group, 50.5% survived 1 year without a hospital admission, 10.8% were hospitalized >15 days, and 5.8% of patients died. By contrast, 26.1% of patients in the high frailty group survived 1 year without a hospital admission, 26.4% were hospitalized >15 days, and 15.6% died within 1 year. Differences persisted in models adjusted for sex, age, frailty, and comorbidity burden (excluding overlapping comorbidities). Conclusions Among patients undergoing transcatheter aortic valve replacement, frailty is strongly associated with time in hospital and mortality. Prevention strategies for frail patients to reduce hospitalization burden could be beneficial.

Temporal changes in incidence, treatment strategies and 1-year re-admission rates in patients with atrial fibrillation/flutter under 65 years of age: A Danish nationwide study.

AIM: To examine temporal changes in incidence rates of atrial fibrillation/flutter (AF), treatment strategies, and AF readmission rates in patients <65 years. METHODS: Using Danish nationwide registries, we identified patients <65 years with a first-time AF diagnosis from 2000 to 2018. The cohort was categorized according to calendar periods; 2000-2002, 2003-2006, 2007-2010, 2011-2014, and 2015-2018. In this retrospective cohort study the incidence rate (IR) of AF per 100,000 person years (PY), catheter ablation, electrical cardioversion, use of pharmacotherapy, and AF readmission, were investigated in the first year following AF diagnosis. RESULTS: We identified 60,917 patients; 8150 (13.4%) in 2000-2002, 11,898 (19.5%) in 2003-2006, 13,560 (22.3%) in 2007-2010, 14,167 (23.3%) in 2011-2014, and 13,142 (21.6%) in 2015-2018. Apart from 2015 to 2018, a stepwise increase in the crude IR of AF was observed across calendar periods; 2000-2002: 78.7 (95% CI 77.0;80.4), 2003-2006: 86.3 (84.7;87.8), 2007-2010: 97.9 (96.3;99.6), 2011-2014: 102.3 (100.7;104.0), 2015-2018: 93.6 (92.0;95.2). Over the studied time-periods, we found a stepwise increase in the cumulative incidence of catheter ablation (1.2% to 7.6%) electrical cardioversion (2.0% to 8.7%) and treatment with oral anticoagulant therapy (OAC) (28.5% to 47.8%) within the first year of diagnosis. No temporal differences in incidence of 1-year AF readmission were identified (AF-readmissions: 2000-2002: 32.7%, 2003-2006: 31.1%, 2007-2010: 32.2%, 2011-2014: 32.1% and 2015-2018: 31.7%). CONCLUSION: The incidence rate of AF in patients <65 years increased from 2000 to 2018, as did the use of catheter ablation, electrical cardioversion and OAC in the first year following AF diagnosis. 1-year AF readmission incidence remained stable around 32% over the study period.

Temporal trends in the incidence of infective endocarditis in patients with a prosthetic heart valve.

OBJECTIVE: The incidence of infective endocarditis (IE) is increasing, as is the insertion of prosthetic heart valves. We aimed to examine nationwide temporal trends in the incidence of IE in patients with a prosthetic heart valve in Denmark from 1999 to 2018. METHODS: Using the Danish nationwide registries, we identified patients who underwent heart valve implantation (for other reasons than IE) between 1999 and 2018. Crude incidence rates of IE per 1000 person-years (PY) were computed in 2-year intervals. IE incidences were compared using sex-adjusted and age-adjusted incidence rate ratios (IRR) using Poisson regression across calendar periods (1999-2003, 2004-2008, 2009-2013, and 2014-2018). RESULTS: We identified 26 604 patients with first-time prosthetic valve implantation (median age 71.7 years (IQR 62.7-78.0), 63% males). The median follow-up time was 5.4 years (IQR 2.4-9.6). Patients in the time period 2014-2018 were older (median age of 73.9 years (66.2:80.3)), and with a higher burden of comorbidities compared with the time period 1999-2003 (median age of 67.9 years (58.3:74.5)) at the time of implantation. A total of 1442 (5.4%) patients developed IE. The lowest IE incidence rate was 5.4/1000 PY (95% CI 3.9 to 7.4) in 2001-2002, and the highest incidence rate was 10.0/1000 PY (95% CI 8.8 to 11.1) in 2017-2018 with an unadjusted increase during the study period (p=0.003). We found an adjusted IRR of 1.04 (95% CI 1.02 to 1.06) (p<0.0007) per two calendar-years increments. Age-adjusted IRR for men were 1.04 (95% CI 1.01 to 1.07) (p=0.002) per two calendar years increment, and for women 1.03 (95% CI 0.99 to 1.07) (p=0.12), with p=0.32 for interaction. CONCLUSION: In Denmark, the incidence of IE increased during the last 20 years in patients with prosthetic heart valves.

Use of methylphenidate is associated with increased risk of out-of-hospital cardiac arrest in the general population: a nationwide nested case-control study.

AIM: Methylphenidate, a sympathomimetic drug prescribed to treat attention-deficit/hyperactivity disorder (ADHD), is associated with cardiovascular events, but few studies have explored the risk of out-of-hospital cardiac arrest (OHCA). We investigated whether methylphenidate use is associated with OHCA in the general population. METHODS AND RESULTS: Using Danish nationwide registries, we conducted a nested case-control study with OHCA cases of presumed cardiac causes and age/sex/OHCA-date-matched non-OHCA controls from the general population. Conditional logistic regression models with adjustments for well-known risk factors of OHCA were employed to estimate the odds ratio (OR) of OHCA by comparing methylphenidate use with no use of methylphenidate.The study population consisted of 46 578 OHCA cases [median: 72 years (interquartile range: 62-81), 68.8% men] and 232 890 matched controls. Methylphenidate was used by 80 cases and 166 controls, and was associated with an increased OR of OHCA compared with non-users {OR: 1.78 [95% confidence interval (CI): 1.32-2.40]}. The OR was highest in recent starters (OR≤180 days: 2.59, 95% CI: 1.28-5.23). The OR of OHCA associated with methylphenidate use did not vary significantly by age (P-value interaction: 0.37), sex (P-value interaction: 0.94), and pre-existing cardiovascular disease (P-value interaction: 0.27). Furthermore, the ORs remained elevated when we repeated the analyses in individuals without registered hospital-based ADHD (OR: 1.85, 95% CI: 1.34-2.55), without severe psychiatric disorders (OR: 1.98, 95% CI: 1.46-2.67), without depression (OR: 1.93, 95% CI: 1.40-2.65), or in non-users of QT-prolonging drugs (OR: 1.79, 95% CI: 1.27-2.54). CONCLUSION: Methylphenidate use is associated with an increased risk of OHCA in the general population. This increased risk applies to both sexes and is independent of age and the presence of cardiovascular disease.