Nationwide burden of sudden cardiac death among patients with a psychiatric disorder.

BACKGROUND: Patients with psychiatric disorders have increased all-cause mortality compared with the general population. Previous research has shown that there is a fourfold increased risk of sudden cardiac death (SCD) among the young. OBJECTIVE: To investigate the incidence of SCD in patients with psychiatric disorders aged 18-90 years in the Danish population by systematically reviewing all deaths in 1 year. METHODS: We examined all deaths in Denmark among residents aged 18-90 years in 2010 by reviewing death certificates and autopsy reports. All deaths were categorised as non-SCD or SCD based on the available information. Psychiatric disorder was defined according to International Classification of Diseases, 10th revision criteria or by redemption of a prescription for psychotropic medication within 1 year. RESULTS: Of 4.3 million residents in 2010, we observed 45 703 deaths, of which 6002 were due to SCD. Overall, the incidence rate ratio of SCD was 1.79-6.45 times higher among patients with psychiatric disorders than in the general population and was age dependent (p<0.001 across all age groups). When adjusting for age, sex and comorbidities, psychiatric disorders were independently associated with SCD, with a HR of 2.31 (2.19 to 2.43, p<0.001), and HR was highest among patients with schizophrenic disorders, with a HR of 4.51 (3.95 to 5.16, p <0.001). Furthermore, 18-year-old patients with a psychiatric disorder had an expected 10-year excess loss of life. Patients aged 18-40 with a psychiatric disorder had 13% of excess life years lost caused by SCD. CONCLUSION: In this study, the rate of SCD in patients with psychiatric disorders is higher across all age groups than in the general population. Having a psychiatric disorder is independently associated with SCD. Patients with schizophrenic disease had the highest rates of SCD. Life expectancy for an 18-year old with a psychiatric disorder is estimated to be 10 years shorter in comparison with those without this disorder.

Electronic Nudges to Increase Influenza Vaccination in Patients With Chronic Diseases: A Randomized Clinical Trial.

Importance: Despite strong worldwide guideline recommendations, influenza vaccination rates remain suboptimal among young and middle-aged patients with chronic diseases. Effective scalable strategies to increase vaccination are needed. Objective: To investigate whether electronically delivered letter-based nudges informed by behavioral science could increase influenza vaccination uptake among patients aged 18 to 64 years with chronic diseases. Design, Setting, and Participants: Nationwide pragmatic registry-based randomized clinical implementation trial conducted between September 24, 2023, and May 31, 2024, enrolling all Danish citizens aged 18 to 64 years who met criteria for free-of-charge influenza vaccination in light of preexisting chronic disease. All trial data were sourced from nationwide administrative health registries. Intervention: Randomized in 2.45:1:1:1:1:1:1 ratio to no letter (usual care) or 6 different behaviorally informed electronic letters. Main Outcomes and Measures: The primary end point was receipt of influenza vaccination on or before January 1, 2024, assessed in 7 prespecified coprimary comparisons (all intervention groups pooled vs usual care and each individual intervention group vs usual care). Absolute risk difference in proportions and a crude relative risk were calculated for each comparison. Results: A total of 299 881 participants (53.2% [159 454] female, median age, 52.0 [IQR, 39.8-59.0] years) were randomized. Compared with usual care, influenza vaccination rates were higher among those receiving any intervention letter (any intervention letter, 39.6% vs usual care, 27.9%; difference, 11.7 percentage points; 99.29% CI, 11.2-12.2 percentage points; P < .001). Each individual letter type significantly increased influenza vaccination with the largest effect sizes observed with a repeated letter sent 10 days after the initial letter (repeated letter, 41.8% vs usual care, 27.9%; difference, 13.9 percentage points; 99.29% CI, 13.1-14.7 percentage points; P < .001) and a letter emphasizing potential cardiovascular benefits of vaccination (cardiovascular gain, 39.8% vs usual care, 27.9%; difference, 11.9 percentage points; 99.29% CI, 11.1-12.7 percentage points; P < .001). Vaccination rates were improved across major subgroups. Conclusions and Relevance: In a nationwide randomized clinical implementation trial, electronically delivered letter-based nudges markedly increased influenza vaccination compared with usual care among young and middle-aged patients with chronic diseases. The results of this study suggest that simple, scalable, and cost-efficient electronic letter strategies may have substantial public health implications. Trial Registration: ClinicalTrials.gov Identifier: NCT06030739.

Temporal changes in characteristics, incidence, and mortality in patients undergoing surgical intervention for mitral stenosis.

To examine temporal changes in patient characteristics, the incidence rate of surgical intervention, and the three-year mortality rate for patients undergoing surgical intervention for mitral valve stenosis (MS) from 2001 to 2021 in Denmark. Utilizing Danish nationwide registries, we identified all adult patients undergoing first-time surgical intervention for MS (2001-2021). Temporal changes in the incidence rate of surgical intervention across calendar periods were investigated (2001-2005, 2006-2010, 2011-2015, and 2016-2021). Using Kaplan-Meier estimates, we computed temporal changes in three-year all-cause mortality across calendar periods. With multivariable Cox regression analysis, we assessed the adjusted rates of mortality. We included 256 patients (median age 60.3 years, 31.3% males). A stepwise decrease in the burden of chronic heart failure was identified (2001-2005: 54%, and 2016-2021: 20%, p-value < 0.001 for trend), while the burden of atrial fibrillation seemed stable (2001-2005: 51%, and 2016-2021: 46%, p-value = 0.27 for trend). The proportion of patients with rheumatic MS was 64% in 2001-2005 and 33% in 2016-2021, p-value < 0.001 for trend. 28 patients (10.9%) had mitral valve surgery prior to the first-time surgical intervention for MS. A stepwise decrease in the incidence rate of surgical intervention was observed: 3.3 cases per million person-years in 2001-2005 and 2.2 in 2016-2021. The incidence of patients diagnosed with first-time MS remained stable over calendar periods (2001-2005: 54.5 incidences per million person-years, and 2016-2021: 41.9, p-value = 0.46 for trend). The in-hospital mortality was 8.6% and the three-year mortality after surgical discharge was 9.0%, and we found no difference over calendar periods in either crude estimates or adjusted analysis. From nationwide data across three decades, we identified that the incidence of surgical interventiondecreased significantly within the past 20 years, while all-cause mortality remained stable. The burden of heart failure decreased, while the burden of atrial fibrillation remained stable over the study period.

Comparing Glucagon-like peptide-1 receptor agonists versus metformin in drug-naive patients: A nationwide cohort study.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are increasingly being prescribed in drug-naive patients. We aimed to contrast add-on therapy, adherence, and changes in biomarkers, 1 year after treatment initiation with GLP-1 RA or metformin. METHODS: Using Danish nationwide registers, we included incident GLP-1 RA or metformin users from 2018 to 2021 with glycated hemoglobin (HbA1c) ≥ 42 mmol/mol. GLP-1 RA initiators were matched to metformin initiators in a ratio of 1:1 to assess outcomes in prediabetes and diabetes. Main outcomes analyzed were 1-year risk of add-on glucose-lowering medication and 1-year risk of nonadherence. One-year risks were estimated with multiple logistic regression and standardized. Multiple linear regression was used to estimate the average differences in biomarker changes. RESULTS: In total, 1778 individuals initiating GLP-1 RA and metformin were included. After standardizing for various factors, GLP-1 RA compared with metformin was associated with reduced 1-year risk of add-on glucose-lowering treatment in patients with prediabetes (1-year risk ratio [RR]: 0.27, 95% confidence interval [CI]: 0.10-0.44) and diabetes (RR: 0.67, 95% CI: 0.37-0.98). GLP-1 RA was associated with higher 1-year risk of nonadherence among patients with prediabetes (RR: 1.60, 95% CI: 1.45-1.75), but no difference in patients with diabetes (RR: 0.88, 95% CI: 0.70-1.06). Compared to metformin, GLP-1 RA was associated with greater HbA1c reduction (prediabetes: -2.59 mmol/mol 95% CI: -3.10 to -2.09, diabetes: -3.79 mmol/mol, 95% CI: -5.28 to -2.30). CONCLUSIONS: GLP-1 RA was associated with a reduced risk of additional glucose-lowering medication, achieving better glycated hemoglobin control overall. However, among patients with prediabetes, metformin was associated with better adherence.

Incidence and factors associated with mitral valve reoperation in patients undergoing surgery for mitral regurgitation: A nationwide cohort study.

BACKGROUND: When patients undergo surgery for mitral regurgitation, risk of reoperation is of concern. AIMS: To examine the incidence and factors associated with mitral reoperation following surgery for mitral regurgitation according to type of surgery. METHODS: Patients undergoing first-time surgery for mitral regurgitation, 1996-2021, were identified from nationwide registries. According to index surgery, the population was categorized into 1) mitral repair; 2) mechanical prostheses; 3) bioprostheses. Patients were followed from discharge with a maximum of 15 years of follow-up and cumulative incidence of reoperation was examined. Multivariable Cox analysis was used to examine factors associated with reoperation. RESULTS: We identified 6958 patients: 4624 with mitral repair (72 % male, median age 66), 1250 with mechanical prosthesis (52 % male, median age 59), and 1084 with bioprosthesis (57 % male, median age 74). Cumulative incidence of reoperation was 7.3 % for repair (median 7.2 years follow-up), 6.1 % for mechanical prostheses (median 10.9 years follow-up), and 7.1 % for bioprostheses (median 4.5 years follow-up). Within first year, 22.6 % of reoperations were preceded by infective endocarditis. In long-term follow-up, bioprosthetic replacement was associated with a higher reoperation rate, while increasing age, male sex and mechanical prosthesis were associated with lower reoperation rate. CONCLUSIONS: In patients operated for mitral regurgitation, reoperation was infrequent at approximately 7 % for all intervention types during a maximum of 15-year follow-up. In adjusted analysis, bioprosthetic replacement was associated with a higher rate of reoperation, while increasing age, male sex and mechanical prosthesis was associated with a lower rate of reoperation.

Ischaemic cardiotoxicity of aromatase inhibitors in postmenopausal patients with early breast cancer in Denmark: a cohort study of real-world data.

BACKGROUND: For aromatase inhibitor treatment (AIT) in breast cancer, there is an unresolved concern about ischaemic cardiotoxicity. We investigated the association between AIT and ischaemic cardiotoxicity in a prospective cohort of female patients with early breast cancer who received contemporary treatment in Denmark. METHODS: In this prospective cohort study in Denmark, we identified postmenopausal patients of any age diagnosed with breast cancer as recorded in the nationwide Danish Breast Cancer Cooperative Group (DBCG) clinical database between Jan 1, 2009, and Dec 31, 2020, and linked them to other nationwide registries. Exclusion criteria included having a history of other primary cancer, less than 2 years of residency in Denmark, and no inclusion in a treatment protocol according to the DBCG database, including for metastatic or locally advanced breast cancer. Information on demography, hospital diagnoses, filled prescriptions, laboratory testing, and socioeconomic status were recorded. We stratified the patient cohort according to history (yes vs no) of selected cardiovascular disease defined as ischaemic heart disease, ischaemic stroke, and heart failure, and defined the primary outcome as two-point major adverse cardiovascular events (MACE; acute myocardial infarction or ischaemic stroke). We estimated cause-specific hazard ratios (HRs) according to allocation to AIT versus not in an intention-to-treat analysis using a Cox proportional hazards regression model with age as the underlying time scale, adjusting for demographic characteristics, tumour characteristics, and other anti-cancer treatments. FINDINGS: 43 440 postmenopausal patients diagnosed with breast cancer were identified, of whom 32 635 were followed up and included in analyses. Of 29 118 postmenopausal patients with no history of selected cardiovascular disease, we observed 510 two-point MACEs among 22 135 patients allocated to AIT (incidence rate 4·3/1000 person-years of follow-up) and 170 two-point MACEs among 6983 patients not allocated to AIT (4·1/1000 person-years). The adjusted HR was 0·91 (95% CI 0·73-1·14) for patients allocated to AIT versus patients not allocated to AIT. Among 3517 patients with a history of selected cardiovascular disease, we observed 158 two-point MACEs among 2661 patients allocated to AIT (incidence rate 12·4/1000 person-years) and 50 two-point MACEs (12·1/1000 person-years) among 856 patients not allocated to AIT (adjusted HR 0·81 [95% CI 0·58-1·15]). INTERPRETATION: Our findings do not support a clinically relevant ischaemic cardiotoxic potential of AIT in patients with early breast cancer and do not support avoiding AIT prescription in patients with early breast cancer. FUNDING: Bispebjerg and Frederiksberg Hospital, Kræftens Bekæmpelse, Fonden til Lægevidenskabens Fremme, Aase og Ejnar Danielsens Fond, Helsefonden, and Læge Sofus Carl Emil Friis og Hustru Olga Doris Friis' Legat.

Sex differences in cardiac structure and function following acute myocardial infarction: Insights from the PARADISE-MI echocardiographic substudy.

AIMS: The incidence of heart failure hospitalization is higher in women than in men after myocardial infarction (MI). Sex-related differences in left ventricular (LV) remodelling may contribute to the differences in post-MI outcomes. The aim of this study was to assess sex differences in echocardiographic parameters post-MI, and whether the relationship between echocardiographic parameters and clinical outcomes differs by sex. METHODS AND RESULTS: In the PARADISE-MI trial, patients were randomized to sacubitril/valsartan or ramipril within 0.5 to 7 days of high-risk MI. In the pre-specified echocardiographic substudy, 544 patients underwent echocardiography at the time of randomization and after 8 months. We compared key echocardiographic parameters in men and women and their association with primary composite outcome (cardiovascular death or incident heart failure). At baseline, women had higher LV ejection fraction (LVEF), lower LV end-diastolic volume (LVEDV) index, LV end-systolic volume (LVESV) index, and LV mass index. After adjusting for baseline clinical differences, changes in these echocardiographic parameters from baseline to 8 months were not significantly different in women versus men. Lower LVEF, higher LVEDV, LVESV, left atrial volume index, and average E/e' were associated with a higher risk of the primary composite outcome. Sex did not modify the relationship between echocardiographic parameters and clinical outcome. CONCLUSIONS: Despite baseline differences in measures of cardiac function between men and women following acute high-risk MI, there were no significant sex-related changes in chamber size or LV function. Sex did not modify the association between echocardiographic parameters and clinical outcome.

Asymptomatic vs Symptomatic Hypotension With Sacubitril/Valsartan in Heart Failure and Reduced Ejection Fraction in PARADIGM-HF.

BACKGROUND: Hypotension is an important clinical problem in heart failure (HF). OBJECTIVES: This study sought to examine the association between asymptomatic vs symptomatic hypotension and outcomes in PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure). METHODS: In a post hoc analysis of PARADIGM-HF, the efficacy and safety of sacubitril/valsartan compared to enalapril were estimated using time-updated Cox proportional hazards models. The primary outcome was cardiovascular death or HF hospitalization. RESULTS: Among 8,399 patients in PARADIGM-HF, 1,343 (16.0%) experienced only asymptomatic hypotension, and 936 (11.1%) experienced symptomatic hypotension at least once after randomization. Patients with symptomatic hypotension were older and more frequently had cardiovascular comorbidities compared to those developing only asymptomatic hypotension. By contrast, left ventricular ejection fraction was lower in those with asymptomatic hypotension. Patients who experienced either type of hypotension were at higher risk for all outcomes examined. However, the effect of sacubitril/valsartan on the primary outcome was not diminished in patients experiencing hypotension compared to those who did not: the HR for sacubitril/valsartan vs enalapril was 0.80 (95% CI: 0.72-0.89) for no hypotension, 0.87 (95% CI: 0.70-1.08) for asymptomatic hypotension, and 0.51 (95% CI: 0.38-0.69) for symptomatic hypotension (Pinteraction = 0.01), and this was also true for cardiovascular and all-cause deaths. The safety of sacubitril/valsartan vs enalapril was also maintained regardless of the occurrence of hypotension. Discontinuation of randomized treatment was less common with sacubitril/valsartan vs enalapril in patients experiencing asymptomatic and symptomatic hypotension. CONCLUSIONS: Although both asymptomatic and symptomatic hypotension during treatment with sacubitril/valsartan or enalapril were associated with worse outcomes, the benefits of sacubitril/valsartan were maintained (or even enhanced) in patients experiencing hypotension.

The relation between socioeconomic status and invasive haemodynamics at evaluation for advanced heart failure.

AIMS: Socioeconomic deprivation is a risk marker for worse prognosis in patients with heart failure (HF), and a potential barrier to referral for advanced HF evaluation. The relationship between socioeconomic status (SES) and invasive haemodynamics in patients undergoing evaluation for advanced HF therapies is unknown. METHODS: We combined a consecutive clinical registry of patients evaluated for advanced HF with patient-level data on SES (household income, education, workforce status, cohabitant status and distance from home to tertiary HF centre) derived from nationwide registries. Using this information, the cohort was divided into groups of low-, medium- and high degree of socioeconomic deprivation. The associations between SES and invasive haemodynamics were explored with multiple linear regression adjusted for age and sex. RESULTS: A total of 631 patients were included. The median age was 53 years, and 23% were women. Patients in the highest income quartile versus the lowest (Q4 vs. Q1) were older (median age 57 vs. 50 years) and more often male (83% vs. 67%), both P < 0.001. Increasing household income (per 100 000 Danish kroner,1 EUR = 7.4 DKK) was associated with lower pulmonary capillary wedge pressure (PCWP) [-0.18 mmHg, 95% confidence interval (CI) -0.36 to -0.01, P = 0.036] but not significantly associated with central venous pressure (CVP) (-0.07 mmHg, 95% CI -0.21 to 0.06, P = 0.27), cardiac index (-0.004 L/min/m2, 95% CI -0.02 to 0.01, P = 0.60), or pulmonary vascular resistance (PVR) (-0.003 Wood units, 95% CI -0.37 to 0.16, P = 0.84). Comparing the most deprived with the least deprived group, adjusted mean PVR was higher (0.35 Wood units, 95% CI 0.02 to 0.68, P = 0.04), but PCWP (0.66 mmHg, 95% CI -1.49 to 2.82, P = 0.55), CVP (-0.26 mmHg, 95% CI -1.76 to 1.24, P = 0.73) and cardiac index (-0.03 L/min/m2, 95% CI -0.22 to 0.17, P = 0.78) were similar. CONCLUSIONS: Most haemodynamic measurements were similar across layers of SES. Nevertheless, there were some indications of worse haemodynamics in patients with lower household income or a high accumulated burden of socioeconomic deprivation. Particular attention may be warranted in socioeconomically deprived patients to ensure timely referral for advanced HF evaluation.

Excess Risk of Mortality and Hospitalization in Patients with Heart Failure According to Age and Comorbidity - A Nationwide Register Study.

Background: Heart failure (HF) is associated with increased risk of death and a hospitalization, but for patients initiating guideline directed medical therapy, it is unknown how high these risks are compared to the general population - and how this may vary depending on age and comorbidity. Methods: In this retrospective cohort study, we identified patients diagnosed with HF in the period 2011-2017, surviving the initial 120 days after diagnosis. Patients who were on angiotensin converting enzyme inhibitor (ACEi)/ angiotensin receptor blocker (ARB) and beta-blocker were included and matched to 5 non-HF individuals from the background population each based on age and sex. We assessed the 5-year risk of all-cause death, HF and non-HF hospitalization according to sex and age and baseline comorbidity. Results: We included 35,367 patients with HF and 176,835 matched non-HF individuals. Patients with HF had a five-year excess risk (absolute risk difference) of death of 13% (31% [for HF] - 18% [for non-HF]), of HF hospitalization of 17% and of non-HF hospitalization of 24%. Excess risk of death increased with increasing age, whereas the relative risk decreased - for women in their twenties, the excess risk was 7%, risk ratio 7.2, while the excess risk was 18%, risk ratio 1.5 for women in their eighties. Having HF as a 60-year old man was associated with a five-year risk of death similar to a 75-year old man without HF. Further, HF was associated with an excess risk of non-HF hospitalization, ranging from 8% for patients >85 years to 30% for patients <30 years. Conclusion: Regardless of age, sex and comorbidity, HF was associated with excess risk of mortality and non-HF hospitalizations, but the relative risk ratio diminishes sharply with advancing age, which may influence allocation of resources for medical care across populations.

Time of day for vaccination, outcomes, and relative effectiveness of high-dose vs. standard-dose quadrivalent influenza vaccine: A post hoc analysis of the DANFLU-1 randomized clinical trial.

OBJECTIVES: Morning influenza vaccination enhances antibody response. In this post hoc analysis of the DANFLU-1 trial, we sought to evaluate the association between time of day for vaccination (ToV) and outcomes and whether ToV modified the relative effectiveness of high-dose (QIV-HD) vs. standard-dose (QIV-SD) quadrivalent influenza vaccine. METHODS: DANFLU-1 was a pragmatic feasibility trial of QIV-HD vs. QIV-SD. Outcomes included hospitalizations and mortality. For subgroup analysis, the population was dichotomized at median ToV into two groups (early and late). RESULTS: The study population included 12,477 participants. Mean age was 71.7 ± 3.9 years with 5877 (47.1%) female participants. Median ToV was 11.29 AM. Earlier ToV was associated with fewer respiratory hospitalizations independent of vaccine type, which persisted in adjusted analysis (IRR 0.88 per 1-hour decrement (95% CI 0.78- 0.98, p = 0.025). No effect modification by continuous or dichotomous ToV was found. In subgroup analysis, effects consistently favored QIV-HD against hospitalizations for pneumonia or influenza (early: IRR 0.30; late: 0.29), all-cause hospitalizations (early: IRR 0.87; late: 0.86), and mortality (early: HR 0.53; late: 0.50). CONCLUSION: In this exploratory post hoc analysis, earlier ToV was associated with fewer respiratory hospitalizations. The relative effectiveness of QIV-HD vs. QIV-SD was not modified by ToV. Further research is needed to confirm findings. TRIAL REGISTRATION: Clinicaltrials.gov: NCT05048589.

Arrhythmias in congenital heart disease: A nationwide cohort study.

BACKGROUND: As more patients with congenital heart disease (CHD) survive into adulthood, the population of adults with CHD is expanding. This trend is accompanied by an increasing incidence of complications, including arrhythmias. However, the long-term risk of arrhythmias remains sparsely investigated. METHODS: In this observational cohort study, all Danish patients with CHD born from 1977 to 2024 were identified using registries and followed from date of birth until the occurrence of arrhythmia, emigration, death, or end of follow-up (March 2024). The risk of arrhythmias was assessed among patients with CHD and compared to age- and sex-matched controls from the background population. RESULTS: A total of 45,820 patients with CHD (50.9% men) were identified and matched with 183,280 controls from the background population. During a median follow-up of 21.5 years, 2.6% of patients with CHD and 0.2% of controls developed arrhythmias-corresponding to incidence rates (IR) of 1.2 (95% CI 1.2-1.3) and 0.1 (95% CI 0.1-0.1) per 1,000 PY, respectively, and a hazard ratio (HR) of 16.4 (95% CI 14.4-18.7). The most common arrhythmias in patients with CHD were advanced atrioventricular block (IR 0.4 [95% CI 0.4-0.4] per 1,000 PY) and atrial flutter/fibrillation (IR 0.5 [95% CI 0.5-0.6] per 1,000 PY). Patients with malformations of the heart chambers, transposition of the great arteries, tetralogy of Fallot, and atrioventricular septal defect were at the highest risk of arrhythmias. Moreover, the risk of arrhythmias among those with ASD was not negligible. In patients with CHD, arrhythmia was associated with a significantly higher risk of death (HR of 6.9 [95% CI 5.9-8.1]). CONCLUSIONS: Patients with CHD are at significantly higher risk of arrhythmias than the background population, and those with complex CHD are at particularly high risk. In patients with CHD, arrhythmia is associated with an increased risk of death. Additional studies are warranted to investigate how we can improve the diagnosis and management of arrhythmias in CHD.

Infective endocarditis with or without congenital heart disease: clinical features and outcomes.

BACKGROUND AND AIMS: Patients with congenital heart disease (CHD) form a high-risk subgroup for infective endocarditis (IE), necessitating tailored prevention and treatment strategies. However, comprehensive nationwide data comparing IE characteristics and outcomes in patients with and without CHD, including children, are sparse. This study aims to address this gap in knowledge. METHODS: Using Danish nationwide registries, all patients with IE from 1977 to 2021 were identified and stratified on whether they had a diagnosis of CHD, regardless of its complexity. Characteristics prior to and during admission as well as associated outcomes (i.e. in-hospital mortality, 1-year mortality, and 10-year mortality, and IE recurrence) were compared between groups. RESULTS: In total, 14 040 patients with IE were identified, including 895 (6.4%) with CHD. Patients with vs. without CHD were younger at the time of IE diagnosis (median age 38.8 vs. 70.7 years), less comorbid, and more frequently underwent cardiac surgery during admission (35.7% vs. 23.0%, P < .001). Notably, 76% of patients with IE < 18 years of age had CHD. The IE-related bacteraemia differed between groups: Streptococci (29.9%) were the most common in patients with CHD, and Staphylococcus aureus (29.9%) in patients without CHD. Patients with CHD had a significantly lower cumulative incidence of in-hospital mortality (5.7% vs. 17.0%, P < .001) and 1-year mortality (9.9% vs. 31.8%, P < .001) compared with those without CHD. The 10-year cumulative incidence of IE recurrence was similar between groups (13.0% and 13.9%, P = .61). CONCLUSIONS: Patients with CHD who develop IE exhibit distinct characteristics and improved long-term outcomes compared with patients without CHD. Notably, the majority of children and adolescents with IE have underlying CHD.

Endometriosis and Long-Term Cardiovascular Risk: A Nationwide Danish study.

BACKGROUND AND AIMS: Endometriosis, a systemic gynecological disease affecting 10% of women in reproductive age, shares pathophysiological characteristics with cardiovascular disease. However, data on the relationship between endometriosis and cardiovascular outcomes are scarce, prompting this study to address the knowledge-gap. METHODS: Using Danish nationwide registries, women diagnosed with endometriosis (1977-2021) were identified and matched with controls in a 1:4 ratio based on year of birth. The primary outcome was a composite of acute myocardial infarction and ischemic stroke. The secondary outcomes were arrhythmias, heart failure, and mortality. RESULTS: In total, 60,508 women with endometriosis and 242,032 matched controls were included (median age 37.3 years). Women with endometriosis were more comorbid and used more medications than controls. The incidence rates of the composite outcomes were 3.2 (95% confidence interval [CI] 3.2-3.3) and 2.7 (95% CI 2.7-2.8) per 1000 person-years among women with and without endometriosis, respectively. Women with endometriosis had a significantly higher associated rate of the composite outcome compared with controls (unadjusted hazard ratio [HR] 1.18 [95% CI 1.14-1.23], adjusted HR 1.15 [95% CI 1.11-1.20]). Likewise, women with endometriosis were also at significantly increased associated risk of arrhythmias (unadjusted HR 1.24 [95% CI 1.20-1.28], adjusted HR 1.21 [95% CI 1.17-1.25]) and heart failure (unadjusted HR 1.16 [95% CI 1.09-1.22], adjusted HR 1.11 [95% CI 1.05-1.18]) but at decreased risk of mortality (unadjusted HR 0.95 [95% CI 0.92-0.97], adjusted HR 0.93 [95% CI 0.91-0.96]). CONCLUSIONS: Women with endometriosis have a higher associated long-term risk of cardiovascular outcomes compared with controls. Despite subtle absolute risk-differences, the high prevalence of endometriosis underscores the importance of these findings.

Effects of atrial fibrillation screening according to thyroid function: Post-hoc analysis of the randomized LOOP study.

PURPOSE: Subclinical thyroid dysfunction is a marker for atrial fibrillation (AF) and stroke risk. This study explored the effects of AF screening according to thyroid-stimulating hormone (TSH) levels. METHODS: An AF screening trial (the LOOP study) was analyzed post-hoc according to baseline TSH. The primary outcome was stroke or systemic embolism (SE). Secondary outcomes included major bleeding, all-cause death, and the combination of stroke, SE, and cardiovascular death. RESULTS: TSH measurement was available in 6003 of 6004 trial participants, 1500 randomized to implantable loop recorder (ILR) screening for AF and anticoagulation upon detection vs. 4503 to usual care; mean age was 74.7±4.1 years and 2836 (47%) were women. AF detection was approximately triple for ILR vs usual care across TSH tertiles (adjusted p-interaction=0.44). In the first tertile, screening was associated with decreased risk of the primary outcome (hazard ratio 0.52 [0.30-0.90]; p=0.02) and stroke, SE, or cardiovascular death (hazard ratio 0.54 [0.34-0.84]; p=0.006) compared to usual care, while no effect was observed among participants with higher TSH (adjusted p-interaction 0.03 and 0.01, respectively). There was no effect on other outcomes. Analyses of continuous TSH or excluding those with abnormal TSH or thyroid medication showed similar results. CONCLUSION: AF screening and subsequent treatment was associated with decreased stroke risk among participants with low TSH, though the yield of screening was similar across TSH levels. TSH may be useful as a marker to indicate benefit from AF screening vs. overdiagnosis and overtreatment. These findings should be considered exploratory and warrant further study. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT0203645.

Detection of infective endocarditis with [64Cu]Cu-DOTATATE positron emission tomography/computed tomography: a case series.

Background: Infective endocarditis (IE) is a serious and fatal condition, with prosthetic valve endocarditis representing the worst prognosis. The recommended nuclear imaging modality 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography ([18F]FDG PET/CT) has limitations. In this case series, we present two patients with IE scanned with a novel PET tracer [64Cu]Cu-DOTATATE ([64Cu]Cu-[1,4,7,10-tetraazacyclododecane-N,N',N″,N‴-tetra acetic acid]-d-Phe1, Tyr3-octreotate). Case summary: An 84-year-old female patient (Patient 1) with a biological mitral valve prosthesis (MVP) was admitted acutely from the outpatient clinic. Transoesophageal echocardiography showed vegetations on the MVP. The patient underwent [64Cu]Cu-DOTATATE PET/CT, which showed uptake at the site of infection. The patient underwent surgical valve replacement. The post-operative period was without significant complications, and the patient was discharged home. In another case, a 72-year-old male patient (Patient 2) with a medical history of mild mitral valve stenosis, aortic valve stenosis, and gastrointestinal stromal tumour was admitted to the hospital for back and abdominal pain and subfebrile episodes. Transoesophageal echocardiography showed large vegetations in the native aortic valve. The patient underwent [64Cu]Cu-DOTATATE PET/CT, which showed no uptake at the site of the suspected infection. The patient underwent surgical valve replacement. The post-operative period was characterized by Candida albicans sternitis, and after prolonged hospitalization, the patient died of respiratory failure as a complication of sepsis. Discussion: In conclusion, this is the first case series presenting two patients with definite IE (modified Duke criteria), who were scanned with the novel [64Cu]Cu-DOTATATE PET/CT. Patient 1, with endocarditis in the MVP, showed an uptake of the tracer, while Patient 2, with native aortic valve endocarditis, did not show any uptake.

Impact of a 12-week high-intensity interval training intervention on cardiac structure and function after COVID-19 at 12-month follow-up.

In patients previously hospitalised for COVID-19, a 12-week high-intensity interval training (HIIT) intervention has previously been shown to increase left ventricular mass (LVM) immediately after the intervention. In the present study, we examined the effects of the same HIIT scheme on LVM, pulmonary diffusing capacity, symptom severity and functional capacity at 12-month follow-up. In this investigator-blinded, randomised controlled trial, 12 weeks of a supervised HIIT scheme (4 × 4 min, three times a week) was compared to standard care (control) in patients recently discharged from hospital due to COVID-19. At inclusion and at 12-month follow-up, LVM was assessed by cardiac magnetic resonance imaging (cMRI, primary outcome), while pulmonary diffusing capacity for carbon monoxide (DLCOc, secondary outcome) was examined by the single-breath method. Symptom severity and functional status were examined by the Post-COVID-19 Functional Scale (PCFS) and King's Brief Interstitial Lung Disease (KBILD) questionnaire score. Of the 28 patients assessed at baseline, 22 completed cMRI at 12-month follow-up (12.4 ± 0.6 months after inclusion). LVM was maintained in the HIIT but not the standard care group, with a mean between-group difference of 9.68 [95% CI: 1.72, 17.64] g (P = 0.0182). There was no differences in change from baseline to 12-month follow-up between groups in DLCOc % predicted (-2.45 [-11.25, 6.34]%; P = 0.578). PCFS and KBILD improved similarly in the two groups. In individuals previously hospitalised for COVID-19, a 12-week supervised HIIT scheme resulted in a preserved LVM at 12-month follow-up but did not affect pulmonary diffusing capacity or symptom severity.

Temporal trends in infection-related hospitalizations among patients with heart failure: A Danish nationwide study from 1997 to 2017.

BACKGROUND: Despite improved survival, hospitalization is still common among patients with heart failure (HF). OBJECTIVE: This study aimed to examine temporal trends in infection-related hospitalization among HF patients and compare it to temporal trends in the risk of HF hospitalization and death. METHODS: Using Danish nationwide registers, we included all patients aged 18 to 100 years, with HF diagnosed between January 1, 1997 and December 31, 2017, resulting in a total population of 147.737 patients. The outcomes of interest were primarily infection-related hospitalization and HF hospitalization and secondarily all-cause mortality. The Aalen Johansen's estimator was used to estimate 5-year absolute risks for the primary outcomes. Additionally, cox analysis was used for adjusted analyses. RESULTS: The population had a median age of 74 [64, 82] years and 57.6 % were males. Patients with HF had a higher risk of infection over time 16.4 % (95% CI 16.0-16.8) in 1997 to 2001 vs 24.5% (95% CI 24.0-24.9) in 2012 to 2017. In contrast, they had a lower risk of HF hospitalization 26.5% (95% CI 26.1-27.0) in 1997 to 2001 vs 23.2% (95% CI 22.8-23.7) in 2012 to 2017. The risk of infection stratified by infection type showed similar trends for all infection types and marked the risk of pneumonia infection as the most significant in all subintervals. CONCLUSION: In the period from 1997 to 2017, we observed patients with HF had an increased risk of infection-related hospitalization, driven by pneumonia infections. In contrast, the risk of HF hospitalization decreased over time.

Rates of Sudden Death After Myocardial Infarction-Insights From the VALIANT and PARADISE-MI Trials.

Importance: Sudden death is a leading cause of death after acute myocardial infarction (AMI). The Prospective ARNi vs ACE Inhibitor Trial to Determine Superiority in Reducing Heart Failure Events After MI (PARADISE-MI) and Valsartan in Acute Myocardial Infarction (VALIANT) trials enrolled patients with pulmonary congestion and/or left ventricular dysfunction after AMI. Whether the prognosis in such patients has changed over time has not been examined. Objective: To compare the rate of sudden death/resuscitated cardiac arrest (RCA) after AMI in the PARADISE-MI and VALIANT trials. Design, Setting, and Participants: This was a secondary analysis of multicenter randomized clinical trials enrolling patients after AMI. In the primary analysis, the VALIANT cohort was restricted to patients with "PARADISE-MI-like" characteristics (eg, at least 1 augmenting risk factor and no history of heart failure). The baseline characteristics of people in both trials were compared. The VALIANT trial enrolled from December 1998 to June 2001, and the PARADISE-MI trial enrolled between December 2016, and March 2020. The median follow-up in the VALIANT and PARADISE-MI trials was 24.7 and 22 months, respectively. People with AMI, complicated by pulmonary congestion and/or left ventricular dysfunction, were included in the analysis. Exposure: Sudden death after AMI. Results: A total of 5661 patients were included in the PARADISE-MI cohort (mean [SD] age, 63.7 [11.5] years; 4298 male [75.9%]), 9617 were included in the VALIANT (PARADISE-MI-like) cohort (mean [SD] age, 66.1 [11.5] years; 6504 male [67.6%]), and 14 703 patients were included in the VALIANT (total) cohort (mean [SD] age, 64.8 [11.8] years; 10 133 male [68.9%]). In the PARADISE-MI-like cohort of the VALIANT trial, 707 of 9617 participants (7.4%) experienced sudden death/RCA. A total of 148 of 5661 people (2.6%) in the PARADISE-MI trial experienced sudden death/RCA. Sudden death rates were highest in the first month after infarction in both trials: 19.3 (95% CI, 16.4-22.6) per 100 person-years in the VALIANT trial and 9.5 (95% CI, 7.0-12.7) per 100 person-years in the PARADISE-MI trial, and these rates declined steadily thereafter. Compared with the VALIANT cohort, people in the PARADISE-MI trial were more often treated with percutaneous coronary intervention for their qualifying AMI and received a ß-blocker, statin, and mineralocorticoid receptor antagonist more frequently. Conclusions and Relevance: After AMI, the risk of sudden death/RCA was highest in the first month, declining rapidly thereafter. Results revealed that compared with counterparts from 20 years ago, the rate of sudden death/RCA in patients with a reduced left ventricular ejection fraction and/or pulmonary congestion was 2- to 3-fold lower in people receiving contemporary management. Interventions to further protect people in the highest risk first month after infarction are needed. Trial Registration: ClinicalTrials.gov Identifier: NCT02924727.