Surgery in patients with infective endocarditis and prognostic importance of patient frailty.

PURPOSE: Surgery is required in 20-50% of patients with infective endocarditis (IE). Frailty increases surgical risk; however, the prognostic implications of frailty in patients undergoing IE-related surgery remain poorly understood. We aimed to assess the association between frailty and all-cause mortality or rehospitalization after discharge (≥ 14 days). METHODS: We identified all IE patients who underwent surgery during admission (2010-2020) in Denmark. The Hospital Frailty Risk Score was used to categorize patients into two frailty risk groups, patients with low frailty scores (< 5 points) and frail patients (≥ 5 points). We analyzed time hospitalized after discharge and all-cause mortality from the date of surgery with a one-year follow-up. Statistical analyses utilized the Kaplan-Meier estimator, Aalen-Johansen estimator, and the Cox regression model. RESULTS: We identified 1282 patients who underwent surgery during admission, of whom 967 (75.4%) had low frailty scores, and 315 (24.6%) were frail. Frail patients were characterized by advanced age, a lower proportion of males, and a higher burden of comorbidities. Frail patients were more hospitalized (> 14 days) in the first post-discharge year (19.1% vs.12.3%) compared to patients with low frailty scores. Additionally, frail patients had higher rates of all-cause mortality including in-hospital deaths (27% vs. 15%) and rehospitalizations (43.5% vs 26.1%) compared to patients with low frailty scores. This was also evident in the adjusted analysis (hazard ratio 1.36 [CI 95% 1.09-1.71]). CONCLUSION: Frailty was associated with an ≈40% increased rate of rehospitalization (≥ 14 days) or death. Further studies are needed to assess the effectiveness of surgery with a focus on frailty to improve prognostic outcomes in these patients.

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.

Short- and Long-Term Mortality for Patients With and Without a Cancer Diagnosis Following Pulmonary Embolism in Denmark, 2000 to 2020: A Nationwide Study.

BACKGROUND: New treatment regimens have been introduced in the past 20 years, which may influence the short- and long-term prognosis for patients with and without a cancer diagnosis following pulmonary embolism. However, newer studies investigating these trends are lacking. Therefore, we aimed to investigate the 30- and 31- to 365-day mortality following pulmonary embolism. METHODS AND RESULTS: Using the Danish nationwide registries, patients with a diagnosis of pulmonary embolism between 2000 and 2020 were included. Age- and sex-standardized 30- and 31- to 365-day mortality was calculated and stratified by cancer status. In total, 60 614 patients (29.6% with recent cancer; mean age, 68.2 years) were included. The 30-day mortality for patients with no recent cancer decreased from 19.1% (95% CI, 17.9%-20.4%) in 2000 to 7.3% (95% CI, 6.7%-8.0%) in 2018 to 2020 (hazard ratio [HR], 0.36 [95% CI, 0.32-0.40]; P<0.001). The 30-day mortality for patients with recent cancer decreased from 32.2% (95% CI, 28.8%-36.6%) to 14.1% (95% CI, 12.7%-15.5%) (HR, 0.38 [95% CI, 0.33-0.44]; P<0.001). The 31- to 365-day mortality for patients with no recent cancer decreased from 12.5% (95% CI, 11.4%-13.6%) to 9.4% (95% CI, 8.6%-10.2%) (HR, 0.73 [95% CI, 0.64-0.83]; P<0.001).The 31- to 365-day mortality for patients with recent cancer remained stable: 39.4% (95% CI, 35.1%-43.7%) to 38.3% (95% CI, 35.9%-40.6%) (HR, 0.97 [95% CI, 0.84-1.12]; P=0.69). CONCLUSIONS: From 2000 to 2020, improvements were observed in 30-day mortality following pulmonary embolism regardless of cancer status. For patients with recent cancer, 31- to 365-day mortality did not improve, whereas a minor improvement was observed for patients without recent cancer.

Initiation of SGLT2 inhibitors and GLP-1 receptor agonists according to level of frailty in people with type 2 diabetes and cardiovascular disease in Denmark: a cross-sectional, nationwide study.

BACKGROUND: Whether frailty influences the initiation of two cardioprotective diabetes drug therapies (ie, SGLT2 inhibitors and GLP-1 receptor agonists) in people with type 2 diabetes and cardiovascular disease is unknown. We aimed to assess rates of initiation of SGLT2 inhibitors and GLP-1 receptor agonists according to frailty in people with type 2 diabetes and cardiovascular disease. METHODS: For this cross-sectional, nationwide study, all people with type 2 diabetes and cardiovascular disease in Denmark between Jan 1, 2015, and Dec 31, 2021, from six Danish health-data registers were identified. People younger than 40 years, with end-stage renal disease, with registered contraindications to SGLT2 inhibitors or GLP-1 receptor agonists, or with previous use of either drug therapy were excluded. The Hospital Frailty Risk Score was used to categorise people as either non-frail, moderately frail, or severely frail. Cox proportional hazards models were used to analyse the association between frailty and initiation of an SGLT2 inhibitor or a GLP-1 receptor agonist. FINDINGS: Of 119 390 people with type 2 diabetes and cardiovascular disease, 103 790 were included. Median follow-up time was 4·5 years (IQR 2·7-6·1) and median age across the three frailty groups was 71 years (64-79). 65 959 (63·6%) of 103 790 people were male and 37 831 (36·5%) were female. At index date, 66 910 (64·5%) people were non-frail, 29 250 (28·2%) were moderately frail, and 7630 (7·4%) were severely frail. Frailty was associated with a significantly lower probability of initiating therapy with an SGLT2 inhibitor or a GLP-1 receptor agonist than in people who were non-frail (moderately frail hazard ratio 0·91, 95% CI 0·88-0·94, p<0·0001; severely frail 0·75, 0·70-0·80, p<0·0001). This association persisted after adjustment for age, sex, socioeconomic status, year of inclusion, duration of type 2 diabetes, duration of cardiovascular disease, polypharmacy, and comorbidity. INTERPRETATION: In people with type 2 diabetes and cardiovascular disease in Denmark, frailty was associated with a significantly lower probability of SGLT2-inhibitor or GLP-1 receptor-agonist initiation, despite their benefits. Formulating clear and updated guidelines on the use of SGLT2 inhibitors and GLP-1 receptor agonists in people who are frail with type 2 diabetes and cardiovascular disease should be a priority. FUNDING: Department of Cardiology, Herlev and Gentofte University Hospital. TRANSLATION: For the Danish translation of the abstract see Supplementary Materials section.

High risk of rehospitalization within one year following a pulmonary embolism-Insights from the Danish nationwide registries from 2000-2020.

AIM: To identify the absolute risk, causes and factors associated with rehospitalization within 1 year of discharge with a pulmonary embolism (PE). METHODS AND RESULTS: Using the Danish nationwide registries, all patients admitted with a first-time PE between 2000 and 2020 and discharged alive were included. Subsequent hospitalizations were categorized and crude cumulative incidences, were used to estimate the absolute risk (AR) of any rehospitalization and specific causes of rehospitalizations. Risk factors for rehospitalization were investigated using cause specific Cox regression models.A total of 55 201 patients were identified. The median age of the study population was 70 years (inter quartile range: 59;79), and the most prevalent comorbidities were cancer (29.3%) and ischemic heart disease (12.7%). The 1-year AR of any rehospitalization after discharge with a PE was 48.6% (95% confidence interval (CI); 48.2%-48.8%). The most common cause for being rehospitalized was due to respiratory disease (1-year AR: 9.5% (95% CI: 9.3%-9.8%)), followed by cardiovascular disease (1-year AR: 6.3% (95% CI: 5.9%-6.5%)), cancer (1-year AR: 6.0% (95% CI: 5.8%-6.4%)), venous thromboembolism (1-year AR: 5.2% (95% CI: 5.0%-5.2%)), and symptom diagnoses (1-year AR: 5.2% (95%CI: 5.0%-5.4%)). Factors that were associated with an increased risk of rehospitalization were cancer, liver disease, chronic obstructive pulmonary disease, chronic kidney disease, and immobilization. CONCLUSION: Patients with PE have a high risk of rehospitalization, with almost half of patients being rehospitalized within 1 year. Identification of high-risk patients may help target interventions aiming at reducing the risk of rehospitalization.

Temporal Trends in Noncardiovascular Morbidity and Mortality Following Acute Myocardial Infarction.

BACKGROUND: Due to improved management, diagnosis, and care of myocardial infarction (MI), patients may now survive long enough to increasingly develop serious noncardiovascular conditions. OBJECTIVES: This study aimed to test this hypothesis by investigating the temporal trends in noncardiovascular morbidity and mortality following MI. METHODS: We conducted a registry-based nationwide cohort study of all Danish patients with MI during 2000 to 2017. Outcomes were cardiovascular and noncardiovascular mortality, incident cancer, incident renal disease, and severe infectious disease. RESULTS: From 2000 to 2017, 136,293 consecutive patients were identified (63.2% men, median age 69 years). The 1-year risk of cardiovascular mortality between 2000 to 2002 and 2015 to 2017 decreased from 18.4% to 7.6%, whereas noncardiovascular mortality decreased from 5.8% to 5.0%. This corresponded to an increase in the proportion of total 1-year mortality attributed to noncardiovascular causes from 24.1% to 39.5%. Furthermore, increases in 1-year risk of incident cancer (1.9%-2.4%), incident renal disease (1.0%-1.6%), and infectious disease (5.5%-9.1%) were observed (all P trend <0.01). In analyses standardized for changes in patient characteristics, the increased risk of cancer in 2015 to 2017 compared with 2000 to 2002 was no longer significant (standardized risk ratios for cancer: 0.99 [95% CI: 0.91-1.07]; renal disease: 1.28 [95% CI: 1.15-1.41]; infectious disease: 1.28 [95% CI: 1.23-1.34]). CONCLUSIONS: Although cardiovascular mortality following MI improved substantially during 2000 to 2017, the risk of noncardiovascular morbidity increased. Moreover, noncardiovascular causes constitute an increasing proportion of post-MI mortality. These findings suggest that further attention on noncardiovascular outcomes is warranted in guidelines and clinical practice and should be considered in the design of future clinical trials.

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.

Risk of Worsening Heart Failure and All-Cause Mortality Following COVID-19 Vaccination in Patients With Heart Failure: A Nationwide Real-World Safety Study.

BACKGROUND: Patients with heart failure are vulnerable to the SARS-CoV-2 infection. However, limited evidence exists on the safety of the SARS-CoV-2 mRNA vaccines in this patient population. The objective of this study was to investigate the risk of all-cause mortality, worsening heart failure, venous thromboembolism, and myocarditis associated with the mRNA vaccines in patients with heart failure. METHODS: Using Danish nationwide registries, 2 cohorts were constructed: (1) all prevalent heart failure patients in 2019 aged 40 to 95 years and (2) all prevalent heart failure patients in 2021 aged 40 to 95 years, who were vaccinated with either of the 2 mRNA vaccines (BNT162B2 or mRNA-1273). The patients in the 2 cohorts were matched 1:1 using exact exposure matching on age, sex, and duration of heart failure. To estimate standardized absolute risks, outcome-specific Cox regression analyses were performed. RESULTS: The total study population comprised 101 786 patients. The median age of the study population was 74 years (interquartile range, 66-81). The standardized risk of all-cause mortality within 90 days was 2.23% (95% CI, 2.10%-2.36%) in the vaccinated cohort and 2.56% (95% CI, 2.43%-2.70%) in the unvaccinated cohort (90-day risk difference, -0.33% [95% CI, -0.52% to -0.15%]). The standardized risk of worsening heart failure within 90 days was 1.10% (95% CI, -1.01% to 1.19%) in the 2021 (vaccinated) cohort and 1.08% (95% CI, 0.99%-1.17%) in the 2019 (unvaccinated) cohort (risk difference, 0.02% [95% CI, -0.11% to 0.15%]). No significant differences were found regarding venous thromboembolism or myocarditis. CONCLUSIONS: Receiving an mRNA vaccine was not associated with an increased risk of worsening heart failure, myocarditis, venous thromboembolism, or all-cause mortality.

Initiation of Medical Therapy for Heart Failure Patients According to Kidney Function: A Danish Nationwide Study.

Background: Use of medical therapies for heart failure (HF) patients with moderate kidney dysfunction is low. We hypothesized that lack of initiation of HF therapy reflects the clinicians' reluctance in very elderly and frail patients more than kidney dysfunction itself. Methods: HF patients were identified from nationwide registers between 2014 and 2021. Information was obtained on eGFR, frailty status, and prescription of HF therapy. Patients were divided into three groups: normal kidney function (eGFR ≥ 60); moderate kidney dysfunction (GFR between 30 and 59); and severe kidney dysfunction (GFR < 30). Multivariate Cox models were used to study the association of eGFR, age, and frailty with use of HF therapy. Results: Of the 42,320 HF patients included those with lower eGFR were significantly older and frailer (median age 74.3 years and 37.8% frail). The crude initiation rate of all three drug classes decreased with decreasing eGFR in a stepwise fashion. After adjusting for age and frailty status, initiation of MRA decreased with decreasing kidney function (moderate kidney function HR 0.80(95% CI 0.77-0.84) and severe kidney function HR 0.24(0.21-0.27)). After adjusting for age and frailty status, initiation of RAS inhibitor and BB was not significantly lower for moderate kidney dysfunction (HR 0.97(0.93-1.02), and HR 1.06(0.97-1.16, respectively)). Initiation of RAS inhibitor was significantly lower for patients with severe kidney dysfunction, HR 0.45(0.41-0.50), but not for BB initiation HR 1.09(1.05-1.14). Conclusion: In a real-world HF cohort, patients with moderate and severe kidney dysfunction were associated with reduced use of MRA irrespective of age and frailty. Reduced use of RASi was associated with severe kidney dysfunction, whereas for patients with moderate kidney dysfunction, reduced use was mainly driven by aging and frailty. Reduced use of BB seemed to be primarily explained by aging and frailty.

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.

Frailty, Treatments, and Outcomes in Older Patients With Myocardial Infarction: A Nationwide Registry-Based Study.

Background Guidelines recommend that patients with myocardial infarction (MI) receive equal care regardless of age. However, withholding treatment may be justified in elderly and frail patients. This study aimed to investigate trends in treatments and outcomes of older patients with MI according to frailty. Methods and Results All patients aged ≥75 years with first-time MI during 2002 to 2021 were identified through Danish nationwide registries. Frailty was categorized using the Hospital Frailty Risk Score. One-year risk and hazard ratios (HRs) for days 0 to 28 and 29 to 365 were calculated for all-cause death. A total of 51 022 patients with MI were included (median, 82 years; 50.2% women). Intermediate/high frailty increased from 26.7% in 2002 to 2006 to 37.1% in 2017 to 2021. Use of treatment increased substantially regardless of frailty: for example, 28.1% to 48.0% (statins), 21.8% to 33.7% (dual antiplatelet therapy), and 7.6% to 28.0% (percutaneous coronary intervention) for high frailty (all P-trend <0.001). One-year death decreased for low frailty (35.1%-17.9%), intermediate frailty (49.8%-31.0%), and high frailty (62.8%-45.6%), all P-trend <0.001. Age- and sex-adjusted 29- to 365-day HRs (2017-2021 versus 2002-2006) were 0.53 (0.48-0.59), 0.62 (0.55-0.70), and 0.62 (0.46-0.83) for low, intermediate, and high frailty, respectively (P-interaction=0.23). When additionally adjusted for treatment, HRs attenuated to 0.74 (0.67-0.83), 0.83 (0.74-0.94), and 0.78 (0.58-1.05), respectively, indicating that increased use of treatment may account partially for the observed improvements. Conclusions Use of guideline-based treatments and outcomes improved concomitantly in older patients with MI, irrespective of frailty. These results indicate that guideline-based management of MI may be reasonable in the elderly and frail.

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.

Mortality in patients with chronic obstructive pulmonary disorder undergoing transcatheter aortic valve replacement: The importance of chronic obstructive pulmonary disease exacerbation.

BACKGROUND: Severe chronic obstructive pulmonary disease (COPD) has been associated with futile outcome after transcatheter aortic valve replacement (TAVR). Data on outcomes according to COPD severity are warranted to aid identification of patients who may not benefit from TAVR. We aimed to examine the association between risk of COPD exacerbation and 1-year mortality after TAVR. METHODS: Using Danish nationwide registries we identified patients undergoing first-time TAVR during 2008-2021 by COPD status. COPD severity levels were defined as low or high risk of acute exacerbation of COPD (AE-COPD) and treatment intensity levels (none or short-term, mono/dual, triple therapy, or home oxygen). Kaplan-Meier functions and adjusted Cox regression models were used to assess 1-year mortality comparing COPD severity groups with patients without COPD. RESULTS: We identified 7,047 patients with TAVR of whom 644 had a history of COPD (low risk of AE-COPD: 439, high risk of AE-COPD: 205). The median age of the TAVR cohort was 81.4 years (IQR: 76.8-85.1) and 55.8% were males. One-year mortality for TAVR patients without COPD was 8.5% (95% CI: 7.8-9.2) and 15.4% (95% CI: 12.5-18.2) for those with COPD (adjusted HR: 1.63 [95% CI: 1.28-2.07]). Patients with low or high risk of AE-COPD had 1-year mortality of 13.1% (95% CI: 9.8-16.3) and 20.2% (95% CI: 14.6-25.8) corresponding to adjusted HRs of 1.31 (95% CI: 0.97-1.78) and 2.44 (95% CI: 1.70-3.50) compared with patients without COPD. Patients with high risk of AE-COPD and no/short term therapy or use of home oxygen represented the subgroups of patients with the highest 1-year mortality (31.6% [95% CI: 14.5-48.7] and 30.9% [95% CI: 10.3-51.6]). CONCLUSION: Among patients undergoing TAVR, increasing risk of exacerbation with COPD was associated with increasing 1-year mortality compared with non-COPD patients. Patients with a high risk of exacerbation with COPD not using any guideline recommended COPD medication and those using home oxygen had the highest 1-year mortality.

Changes in aortic valve replacement procedures in Denmark from 2008 to 2020.

INTRODUCTION: Since 2007, transcatheter aortic valve implantation (TAVI) has emerged as another treatment strategy for severe symptomatic aortic stenosis (AS) compared with surgical aortic valve replacement (SAVR). The objectives were to compare annual rates of aortic valve replacement (AVR) procedures performed in Denmark in the era of TAVI and to assess proportion of AVRs stratified by age with use of age recommendations presented in current guidelines. METHODS: Using Danish nationwide registries, we identified first-time AVRs between 2008 and 2020. Patients who were not diagnosed with AS prior to AVR were excluded RESULTS: The rate of AVRs increased by 39% per million inhabitants from 2008 to 2020. TAVI has steadily increased since 2008, accounting for 64.2% of all AVRs and 72.5% of isolated AVRs by 2020. Number of isolated SAVRs decreased from 2014 and onwards. The proportion of TAVI increased significantly across age groups (<75 and ≥75 years of age, ptrend<0.001), and TAVI accounted for 91.5% of isolated AVR procedures in elderly patients (aged ≥75 years). Length of hospital stay were significantly reduced for all AVRs during the study period (ptrend all<0.001). CONCLUSIONS: The number of AVRs increased from 2008 to 2020 due to adaptation of TAVI, which represented 2/3 of AVRs and more than 70% of isolated AVRs. In elderly patients, the increased use of AVR procedures was driven by TAVI, in agreement with the age recommendations in current guidelines; however, TAVI was used more frequently in patients aged <75 years, accompanied by a flattening use of SAVR.

Percutaneous left atrial appendage occlusion discrepancy between randomised trials and clinical practice.

In patients with atrial fibrillation and previous episodes of bleeding on oral anticoagulant treatment, left atrial appendage occlusion (LAAO) has emerged as an alternative way to decrease the risk of stroke.The use of the procedure has been on the rise, and the news coverage has been dominated by an uncritical acceptance of the benefit of this procedure, which probably have contributed to the increasing number of procedures.This commentary is a presentation and critical appraisal of the available evidence on the efficacy and safety of left atrial appendage closure as stroke prophylaxis.We illustrate that LAAO is supported by limited randomised data risk of serious complications, which we do not believe supports the current widespread use.

Age- and sex-specific trends in the incidence of myocardial infarction in Denmark, 2005 to 2021.

BACKGROUND AND AIMS: Few studies have determined whether the declining incidence of myocardial infarction carries into the current decade, and how it is affected by age and sex. We aimed to determine age- and sex-specific changes in myocardial infarction incidence in Denmark from 2005 through 2021. METHODS: First-time myocardial infarction admissions in adults aged ≥18 years were identified through Danish nationwide registries. Incidence rates per 100,000 persons with 95% confidence intervals (CI) were calculated across calendar year, sex, and age groups (≤49, 50-69, 70-84, ≥85 years). We also presented incidence rate ratios (IRR) with 95% CIs for 2019-2021 compared to 2005-2007. RESULTS: From January 1, 2005, through August 4, 2021, there were 116,481 incident acute myocardial infarctions in approximately 4.5 million Danes aged ≥18 years. Overall incidence rate of myocardial infarction per 100,000 persons decreased in both sexes from 2005 through 2021 (females: 143 to 80; males: 243 to 174) and across all age groups. The steepest declines in incidence were observed for ages ≥85 years (males: 55%, IRR: 0.45 [0.41-0.49]; females: 58%, IRR: 0.42 [0.39-0.45]) and 70-84 years (males: 46%, IRR: 0.54 [0.52-0.57]; females: 52%, IRR: 0.48 [0.46-0.51]). Rates also declined significantly for ages 50-69 (males: 19%, IRR: 0.81 [0.79-0.84]; females: 17%, IRR: 0.83 [0.78-0.88]) and ≥49 years (males: 30%, IRR: 0.70 [0.64-0.76]; females: 37%, IRR: 0.63 [0.54-0.74]). CONCLUSIONS: Declines in the incidence of myocardial infarction continued into the current decade across age groups and sex. However, significantly steeper absolute and relative declines were observed among the oldest age groups (≥70 years).

Gastrointestinal bleeding risk following concomitant treatment with oral glucocorticoids in patients on non-vitamin K oral anticoagulants.

OBJECTIVE: Gastrointestinal bleeding (GIB) risk in relation to concomitant treatment with non-vitamin K oral anticoagulants (NOAC) and oral glucocorticoids is insufficiently explored. We aimed to investigate the short-term risk following coexposure. METHODS: This is a register-based, nationwide Danish study including patients with atrial fibrillation on NOACs during 2012-2018. Patients were defined as exposed to oral glucocorticoids if they claimed a prescription within 60 days prior to GIB. We investigated the associations between GIB and oral glucocorticoid exposure, reporting HRs via a nested case-control design and absolute risk via a cohort design. Matching terms were age, sex, calendar year, follow-up time and NOAC agent. RESULTS: 98 376 patients on NOACs (median age: 75 years (IQR: 68-82), 44% female) were included, and 16% redeemed at least one oral glucocorticoid prescription within 3 years. HRs of GIB were increased comparing exposed with non-exposed patients (<20 mg daily dose, HR 1.54 (95% CI 1.29 to 1.84); ≥20 mg daily dose, HR 2.19 (95% CI 1.81 to 2.65)). 60-day standardised absolute risk of GIB following first claimed oral glucocorticoid prescription increased compared with non-exposed: 60-day absolute risk: 0.71% (95% CI 0.58% to 0.85%) vs 0.38% (95% CI 0.32% to 0.43%). The relative risk was elevated as well: risk ratio of 1.89 (95% CI 1.43 to 2.36). CONCLUSIONS: Concomitant treatment with NOACs and oral glucocorticoids was associated with a short-term rate and risk increase of GIB compared with patients only on NOACs. This could have implications for clinical management, necessitating closer monitoring or other risk mitigation strategies during episodes of cotreatment with oral glucocorticoids.

Outcomes of prolonged dual anti-platelet therapy in patients with acute coronary syndrome undergoing percutaneous coronary intervention: A nationwide registry-based study.

BACKGROUND: Randomized controlled trials have shown a reduced risk of ischemic events and an increased risk of bleeding in patients treated with prolonged dual anti-platelet therapy (DAPT) beyond 12 months following acute coronary syndrome (ACS). We aimed to investigate outcomes of prolonged DAPT vs aspirin monotherapy (ASA) in a real-world population. METHODS AND RESULTS: Using nationwide registries, we identified all patients with ACS who underwent percutaneous coronary intervention and received 12-month DAPT between January 2013 and October 2016. Patients still on DAPT were compared to patients on ASA at index date (15 months after ACS-date) and followed for up to 2 years. Cox regression models were employed to calculate standardized risks of all-cause mortality, major adverse cardiovascular event (MACE), and major bleeding. The study included 7,449 patients, 1,901 on DAPT (median age 66, 72.1% male) and 5,548 on ASA (median age 65, 75.1% male). Standardized absolute 2-year risk of all-cause mortality, MACE, and major bleeding was 2.7%, 3.7%, and 5.4% for DAPT vs 2.2%, 3.8%, and 1.3% for ASA. DAPT was not associated with a significant standardized 2-year risk difference (SRD) of all-cause mortality (SRD: 0.5%, 95% confidence interval [CI]: -0.9 to 1.7) or MACE (SRD: -0.1%, 95% CI -1.8 to 1.6), but a significantly higher risk of major bleeding (SRD: 4.1%, 95% CI 1.8-6.6). CONCLUSIONS: In a nationwide cohort of ACS patients undergoing percutaneous coronary intervention, prolonged DAPT was not significantly associated with a reduced risk of all-cause mortality or MACE, but an increased risk of major bleeding. Future randomized controlled trials should investigate the optimal anti-platelet regimen in this patient group.