Background: The Danish government ordered a public lockdown on March 12, 2020, because of the coronavirus disease 2019 (COVID-19) pandemic. We investigated the immediate consequences of such a lockdown for patients with heart failure (HF). Methods: Using the Danish nationwide administrative databases, we investigated the incidence of new-onset HF and hospitalizations for worsening HF before and after the lockdown (January 1 to March 11 versus March 12 to March 31) in 2020 versus 2019. We also investigated the mortality for all patients with HF and in COVID-19–infected patients with HF. Results: Rates of new-onset HF between January 1 and March 11 were comparable for 2020 and 2019 (1.83 versus 1.78 per 10 000 person-years; P =0.19), while hospitalizations for worsening HF were slightly higher in 2020 versus 2019 (1.04 versus 0.93 per 1000 person-years; P =0.02). In the lockdown period, rates of new-onset HF diagnoses (1.26 versus 2.25 per 1000 person-years) and of hospitalizations for worsening HF (0.63 versus 0.99 per 1000 person-years) were significantly lower in 2020 versus 2019 ( P for both, <0.0001). Mortality was similar before and after the national lockdown for the population with HF. We observed 90 HF patients with diagnosed COVID-19 infection, of whom 37% (95% CI, 23%–50%) died within 15 days. Conclusions: The number of patients hospitalized with worsening HF or diagnosed with new-onset HF was markedly reduced after lockdown but has not yet impacted mortality in HF patients at a population-based level. However, these data raise concerns for a potential undertreatment of HF currently that may impact prognosis in the longer term.

Aim To determine the incidence, patient characteristics, and related events associated with new-onset atrial fibrillation (AF) during a national COVID-19 lockdown. Methods and results Using nationwide Danish registries, we included all patients, aged 18–90 years, receiving a new-onset AF diagnosis during the first 3 months of 2019 and 2020. The main comparison was between patients diagnosed during lockdown (12 March 12–1 April 2020) and patients diagnosed in the corresponding period 1 year previously. We found a lower incidence of new-onset AF during the 3 weeks of lockdown compared with the corresponding weeks in 2019 [incidence rate ratios with 95% confidence intervals (CIs) for the 3 weeks: 0.66 (0.56–0.78), 0.53 (0.45–0.64), and 0.41 (0.34–0.50)]. There was a 47% drop in total numbers (562 vs. 1053). Patients diagnosed during lockdown were younger and with a lower CHA2DS2-VASc score, while history of cancer, heart failure, and vascular disease were more prevalent. During lockdown, 30 (5.3%) patients with new-onset AF suffered an ischaemic stroke and 15 (2.7%) died, compared with 45 (4.3%) and 14 (1.3%) patients during the corresponding 2019 period, respectively. The adjusted odds ratio of a related event (ischaemic stroke or all-cause death) during lock-down compared with the corresponding weeks was 1.41 (95% CI 0.93–2.12). Conclusions Following a national lockdown in Denmark, a 47% drop in registered new-onset AF cases was observed. In the event of prolonged or subsequent lockdowns, the risk of undiagnosed AF patients developing complications could potentially translate into poorer outcomes in patients with AF during the COVID-19 pandemic.

Aims We aimed to investigate the long-term cardio-protective effect associated with beta-blocker (BB) treatment in stable, optimally treated myocardial infarction (MI) patients without heart failure (HF). Methods and results Using nationwide registries, we included patients with first-time MI undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI) during admission and treated with both acetyl-salicylic acid and statins post-discharge between 2003 and 2018. Patients with prior history of MI, prior BB use, or any alternative indication or contraindication for BB treatment were excluded. Follow-up began 3 months following discharge in patients alive, free of cardiovascular (CV) events or procedures. Primary outcomes were CV death, recurrent MI, and a composite outcome of CV events. We used adjusted logistic regression and reported standardized absolute risks and differences (ARD) 3 years after MI. Overall, 30 177 stable, optimally treated MI patients were included (58% acute PCI, 26% sub-acute PCI, 16% CAG without intervention). At baseline, 82% of patients were on BB treatment (median age 61 years, 75% male) and 18% were not (median age 62 years, 68% male). BB treatment was associated with a similar risk of CV death, recurrent MI, and the composite outcome of CV events compared with no BB treatment [ARD (95% confidence intervals)] correspondingly; 0.1% (−0.3% to 0.5%), 0.2% (−0.7% to 1.2%), and 1.2% (−0.2% to 2.7%). Conclusions In this nationwide cohort study of stable, optimally treated MI patients without HF, we found no long-term effect of BB treatment on CV prognosis following the patients from 3 months to 3 years after MI admission.

BackgroundWhether there is an association between sleep apnea (SA) and the risk of developing heart failure (HF) is unclear. Furthermore, it has never been established whether continuous positive airway pressure (CPAP) therapy can prevent development of HF. We aimed to investigate SA patients’ risk of developing HF and the association of CPAP therapy.Methods and ResultsUsing nationwide databases, the entire Danish population was followed from 2000 until 2012. patients with SA receiving and not receiving CPAP therapy were identified and compared with the background population. The primary end point was first‐time hospital contact for HF and adjusted incidence rate ratios of HF were calculated using Poisson regression models. Among 4.9 million individuals included, 40 485 developed SA during the study period (median age: 53.4 years, 78.5% men) of whom 45.2% received CPAP therapy. Crude rates of HF were increased in all patients with SA relative to the background population. In the adjusted model, the incidence rate ratios of HF were increased in the untreated SA patients of all ages, compared with the background population. Comparing the CPAP‐treated patients with SA with the untreated patients with SA showed significantly lower incidence rate ratios of HF among older patients.ConclusionsIn this nationwide cohort study, SA not treated with CPAP was associated with an increased risk of HF in patients of all ages. Use of CPAP therapy was associated with a lower risk of incident HF in patients >60 years of age, suggesting a protective effect of CPAP therapy in the elderly.

Background Prevalent diabetes at the time of heart failure (HF) diagnosis is associated with a higher risk of death, but the incidence and prognostic importance of new-onset diabetes in patients with established HF remains unknown. Methods Patients with a first hospitalization for HF in the period 2003–2014 were included and stratified according to history of diabetes. Annual incidence rates of new-onset diabetes were calculated and time-dependent multivariable Cox regression models were used to compare the risk of death in patients with prevalent and new-onset diabetes with patients without diabetes as reference. The model was adjusted for age, sex, duration of HF, educational level and comorbidity. Covariates were continuously updated throughout follow-up. Results A total of 104,522 HF patients were included in the study, of which 21,216 (19%) patients had diabetes at baseline, and 8164 (10%) developed new-onset diabetes during a mean follow-up of 3.9 years. Patients with new-onset diabetes and prevalent diabetes were slightly younger than patients without diabetes (70 vs. 74 and 77, respectively), more likely to be men (62% vs. 60% and 54%), and had more comorbidities expect for ischemic heart disease, hypertension and chronic kidney disease which were more prevalent among patients with prevalent diabetes. Incidence rates of new-onset diabetes increased from around 2 per 100 person-years in the first years following HF hospitalization up to 3 per 100 person-years after 5 years of follow-up. A total of 61,424 (59%) patients died during the study period with event rates per 100 person-years of 21.5 for new-onset diabetes, 17.9 for prevalent diabetes and 13.9 for patients without diabetes. Compared to patients without diabetes, new-onset diabetes was associated with a higher risk of death (adjusted HR 1.47; 95% CI 1.42–1.52) and prevalent diabetes was associated with an intermediate risk (HR 1.19; 95% CI, 1.16–1.21). Conclusion Following the first HF hospitalization, the incidence of new-onset diabetes was around 2% per year, rising to 3% after 5 years of follow-up. New-onset diabetes was associated with an increased risk of death, compared to HF patients with prevalent diabetes (intermediate risk) and HF patients without diabetes.

Aims Reports have suggested an increased risk of aortic and mitral regurgitation associated with oral fluoroquinolones (FQs) resulting in a safety warning published by the European Medicines Agency (EMA). However, these findings have not yet been replicated. Methods and results Using Danish administrative registers, we conducted a nested case-control study in a nationwide cohort of individuals between 2005 and 2018. Cases were defined as the first occurrence of aortic or mitral regurgitation. Exposure of interest was the use of oral FQs. Hazard ratios (HRs) with 95% confidence intervals (95% CI) were obtained by fitting time-dependent Cox regression models, with penicillin V as comparator, to assess the association between FQ use and incident valvular regurgitation. We identified 38 370 cases of valvular regurgitation with 1 115 100 matched controls. FQ exposure was not significantly associated with increased rates of aortic or mitral regurgitation (HR 1.02, 95% CI 0.95–1.09) compared with penicillin V users. Investigating the cumulative defined daily doses (cDDD) of FQs yielded similar results with no significant association between increasing FQ use and valvular regurgitation (e.g. HR 1.08, 95% CI 0.95–1.23 for cDDD &gt;10 compared with cDDD 1–5). These results were consistent across several analyses including a cohort of patients with hypertension and using a case definition based on valvular surgical interventions. Conclusions In a nationwide nested case-control study, FQs were not significantly associated with increased rates of valvular regurgitation. Our findings do not support a possible causal connection between FQ exposure and incident valvular regurgitation.

BACKGROUND: Bleeding safety in relation to use of systemic fluconazole and topical azoles among patients with atrial fibrillation treated with apixaban, rivaroxaban, or dabigatran is insufficiently explored, despite clinical relevance and several reports suggesting associations. METHODS: Using nationwide Danish registers, we identified patients with atrial fibrillation initiated on apixaban, rivaroxaban, or dabigatran from 2012-2018. We investigated associations between bleeding incidents and systemic fluconazole or topical azole treatment using a case-crossover design with 30-day exposure windows and reported odds ratios (OR) with 95% confidence intervals (CI). RESULTS: We included 32,340 (36%), 32,409 (36%), and 24,940 (28%) patients initiated on apixaban, rivaroxaban, and dabigatran, respectively. Patients on apixaban were older (median age: 77 years; interquartile range [IQR] 70-84) compared with rivaroxaban users (median age: 75 years; IQR 68-82) and patients on dabigatran (median age: 73 years; IQR 66-80). Apixaban users had a significantly increased risk of bleeding following exposure to systemic fluconazole: odds ratio (OR) 3.5; 95% confidence interval (CI), 1.4-10.6. No increased risk was found among rivaroxaban and dabigatran users: ORs of 0.9 (95% CI, 0.2-3.0) and 1.7 (95% CI, 0.5-5.6), respectively. As to bleeding risk pertaining to topical azole exposure among apixaban, rivaroxaban, and dabigatran users, no association was found, with corresponding ORs of 0.8 (95% CI, 0.5-1.3); 1.3 (95% CI, 0.9-2.1); and 1.2 (95% CI 0.8-1.8), respectively. CONCLUSION: In patients with atrial fibrillation on either apixaban, rivaroxaban, or dabigatran, an association between an elevated bleeding risk and use of systemic fluconazole was found among patients on apixaban. We found no increased risk of bleeding following co-exposure to topical azoles.

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