Investigator-reported ventricular arrhythmias and mortality in heart failure with mildly reduced or preserved ejection fraction.

AIMS: Few reports have examined the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF) or their relationship with mortality in patients with heart failure with mildly reduced ejection fraction (HFmrEF) or heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: Data from the PARAGON-HF, TOPCAT, I-Preserve, and CHARM-Preserved trials were merged. VT/VF, reported as adverse events, were identified. Patients who experienced VT/VF were compared with patients who did not. The relationship between VT/VF and mortality was examined in time-updated Cox proportional hazard regression models. Variables associated with VT/VF were examined in Cox proportional hazard regression models. The rate of VT/VF in patients with HFmrEF compared with patients with HFpEF was examined in a Cox proportional hazards regression model. Of 13 609 patients, over a median follow-up of 1170 days (interquartile range: 966-1451), 146 (1.1%) experienced an investigator-reported VT/VF (incidence rate 0.3 per 100 person-years). Patients who experienced VT/VF were more likely to be male, have had a myocardial infarction, poorer renal function, more adverse left ventricular remodelling, and higher N-terminal pro-B-type natriuretic peptide (NT-proBNP) than patients who did not. Occurrence of VT/VF was associated with NT-proBNP, history of atrial fibrillation/flutter, male sex, lower ejection fraction, and history of hypertension. VT/VF was associated with all-cause death [adjusted hazard ratio (HR): 3.95, 95% confidence interval (CI): 2.80-5.57; P < 0.001] and cardiovascular death, driven by death from heart failure and not sudden death. Patients with HFmrEF had a higher rate of VT/VF than patients with HFpEF (adjusted HR: 2.19, 95% CI: 1.77-2.71). CONCLUSION: VT/VF was uncommon in patients with HFmrEF and HFpEF. However, such events were strongly associated with mortality and appear to be a marker of disease severity rather than risk of sudden death. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov unique identifier: NCT01920711(PARAGON-HF); NCT00094302 (TOPCAT); NCT00095238 (I-Preserve); NCT00634712 (CHARM-Preserved).

Right Ventricular Free Wall Strain and Effect of Defibrillator Implantation in Patients With Nonischemic Systolic Heart Failure.

BACKGROUND: Patients with nonischemic systolic heart failure have an increased risk of malignant ventricular arrhythmias and sudden cardiovascular death. Because the risk is less pronounced than for patients with ischemic cause of heart failure more discriminating tools are needed to identify patients most likely to benefit from implantable cardioverter-defibrillator (ICD) implantation. Right ventricular (RV) dysfunction is associated with a worse prognosis, but whether RV free wall strain (RV-FWS) measured with echocardiography can identify the patients most likely to benefit from ICD implantation is not known. METHODS AND RESULTS: In this extended follow-up analysis of the Danish Study to Assess the Efficacy of ICDs in Patients with Non-ischemic Systolic Heart Failure on Mortality (DANISH) trial, RV-FWS was measured with echocardiography in 445 patients before randomization. RV dysfunction was defined as an RV-FWS of greater than -20%. The primary end point was all-cause mortality. The median RV-FWS was -18% (quartiles -23% to -14%), and RV dysfunction was measured in 255 patients (57%). During a median follow-up of 5.7 years, 170 patients (38%) died. There was a statistically significant interaction between RV dysfunction and the effect of ICD implantation (P = .003), also after adjusting for known cardiovascular risk factors (P = .01). ICD implantation significantly decreased all-cause mortality in patients with RV dysfunction (hazard ratio 0.54, 95% confidence interval 0.36-0.80, P = .002), but not in patients with normal RV function (hazard ratio 1.34, 95% confidence interval 0.84-2.12, P = .22). CONCLUSIONS: In patients with nonischemic systolic heart failure, RV dysfunction on echocardiography was associated with a greater effect of ICD implantation and could be used to select patients with benefit from ICD treatment.

Incidence of thyroid dysfunction following initiation of amiodarone treatment in patients with and without heart failure: a nationwide cohort study.

AIMS: Thyroid dysfunction is considered the most frequent complication to amiodarone treatment, but data on its occurrence outside clinical trials are sparse. The present study aimed to examine the incidence of thyroid dysfunction following initiation of amiodarone treatment in a nationwide cohort of patients with and without heart failure (HF). METHODS AND RESULTS: In Danish registries, we identified all patients with first-time amiodarone treatment during the period 2000-18, without prior thyroid disease or medication. The primary outcome was a composite of thyroid diagnoses and initiation of thyroid drugs. Outcomes were assessed at 1-year follow-up, and for patients free of events in the first year, in a landmark analysis for the subsequent 5 years. We included 43 724 patients with first-time amiodarone treatment, of whom 16 939 (38%) had HF. At 1-year follow-up, the cumulative incidence and adjusted hazard ratio (HR) of the primary outcome were 5.3% and 1.37 (95% confidence interval 1.25-1.50) in patients with a history of HF and 4.2% in those without HF (reference). In the 1-year landmark analysis, the subsequent 5-year cumulative incidences and adjusted HRs of the primary outcome were 5.3% (reference) in patients with 1-year accumulated dose <27.38 g [corresponding to average daily dose (ADD <75 mg)], 14.0% and HR 2.74 (2.46-3.05) for 27.38-45.63 g (ADD 75-125 mg), 20.0% and HR 4.16 (3.77-4.59) for 45.64-63.88 g (ADD 126-175 mg), and 24.5% and HR 5.30 (4.82-5.90) for >63.88 g (ADD >175 mg). CONCLUSION: Among patients who initiated amiodarone treatment, around 5% had thyroid dysfunction at 1-year follow-up, with a slightly higher incidence in those with HF. A dose-response relationship was observed between the 1-year accumulated amiodarone dose and the subsequent 5-year cumulative incidence of thyroid dysfunction.

All-cause mortality among Danish nursing home residents before and during the COVID-19 pandemic: a nationwide cohort study.

A substantial part of mortality during the COVID-19-pandemic occurred among nursing home residents which caused alarm in many countries. We investigate nursing home mortality in relation to the expected mortality prior to the pandemic. This nationwide register-based study included all 135,501 Danish nursing home residents between 2015 until October 6, 2021. All-cause mortality rates were calculated using a standardization method on sex and age distribution of 2020. Survival probability and lifetime lost for 180 days was calculated using Kaplan Meier estimates. Of 3,587 COVID-19 related deaths, 1137 (32%) occurred among nursing home residents. The yearly all-cause mortality rates per 100,000 person-years in 2015, 2016, and 2017 were 35,301 (95% CI: 34,671-35,943), 34,801 (95% CI: 34,180-35,432), and 35,708 (95% CI: 35,085-36,343), respectively. Slightly elevated mortality rates per 100,000 person-years were seen in 2018, 2019, 2020, and 2021 of 38,268 (95% CI: 37,620-38,929), 36,956 (95% CI: 36,323-37,600), 37,475 (95% CI: 36,838-38,122), and 38,536 (95% CI: 37,798-39,287), respectively. For SARS-CoV-2-infected nursing home residents, lifetime lost difference was 42 days (95% CI: 38-46) in 2020 versus non-infected in 2018. Among vaccinated in 2021, lifetime lost difference was 25 days (95% CI: 18-32) for SARS-CoV-2-infected versus non-infected. Even though a high proportion of COVID-19 fatalities took place in nursing homes and SARS-CoV-2-infection increased the risk of individual death, the annual mortality was only slightly elevated. For future epidemics or pandemics reporting numbers of fatal cases in relation to expected mortality is critical.

Incidence of ischaemic stroke and mortality in patients with acute coronary syndrome and first-time detected atrial fibrillation: a nationwide study.

AIMS: The aim of this study was to examine contemporary data on the 1-year prognosis of patients surviving acute coronary syndrome (ACS) and concomitant first-time detected atrial fibrillation (AF). METHODS AND RESULTS: Using Danish nationwide registries, we identified all patients surviving a first-time admission with ACS from 2000 to 2018 and grouped them into (i) those without AF prior to or during ACS; (ii) those with a history of AF; and (iii) those with first-time detected AF during admission with ACS. With 1 year of follow-up, rates of ischaemic stroke, death, and bleeding were compared between study groups using multivariable adjusted Cox proportional hazards analysis. We included 161 266 ACS survivors: 135 878 (84.2%) without AF, 18 961 (11.8%) with history of AF, and 6427 (4.0%) with first-time detected AF at admission with ACS. Compared to those without AF, the adjusted 1-year rates of outcomes were as follows: ischaemic stroke [hazard ratio (HR) 1.38 (95% CI 1.22-1.56) for patients with history of AF and HR 1.67 (95% CI 1.38-2.01) for patients with first-time detected AF]; mortality [HR 1.25 (95% CI 1.21-1.31) for patients with history of AF and HR 1.52 (95% CI 1.43-1.62) for patients with first-time detected AF]; and bleeding [HR 1.22 (95% CI 1.14-1.30) for patients with history of AF and HR 1.28 (95% CI 1.15-1.43) for patients with first-time detected AF]. CONCLUSION: In patients with ACS, first-time detected AF appeared to be at least as strongly associated with the 1-year rates of ischaemic stroke, mortality, and bleeding as compared with patients with a history of AF.

Outcome of Dialysis-Requiring Acute Kidney Injury in Patients With Infective Endocarditis: A Nationwide Study.

BACKGROUND: Infective endocarditis (IE) may be complicated by acute kidney injury, yet data on the use of dialysis and subsequent reversibility are sparse. METHODS: Using Danish nationwide registries, we identified patients with first-time IE from 2000 to 2017. Dialysis-naïve patients were grouped into: those with and those without dialysis during admission with IE. Continuation of dialysis was followed 1 year postdischarge. Multivariable adjusted Cox proportional hazard analysis was used to examine 1-year mortality for patients surviving IE according to use of dialysis. RESULTS: We included 7307 patients with IE; 416 patients (5.7%) initiated dialysis treatment during admission with IE and these were younger, had more comorbidities and more often underwent cardiac valve surgery compared with nondialysis patients (47.4% vs 20.9%). In patients with both cardiac valve surgery and dialysis treatment (n = 197), 153 (77.7%) initiated dialysis on or after the date of surgery. The in-hospital mortality was 40.4% and 19.0% for patients with and without dialysis, respectively (P < .0001). Of those who started dialysis and survived hospitalization, 21.6% continued dialysis treatment within 1 year after discharge. In multivariable adjusted analysis, dialysis during admission with IE was associated with an increased 1-year mortality from IE discharge, hazard ratio = 1.64 (95% confidence interval, 1.21-2.23). CONCLUSION: In dialysis-naïve patients with IE, approximately 1 in 20 patients initiated dialysis treatment during admission with IE. Dialysis identified a high-risk group with an in-hospital mortality of 40% and an approximate 20% risk of continued dialysis. Those with dialysis during admission with IE showed worse long-term outcomes than those without.

Time to Thrombolysis and Long-Term Outcomes in Patients With Acute Ischemic Stroke: A Nationwide Study.

Background and Purpose: It is well-established that increasing treatment delay reduces the benefits of thrombolysis in patients with acute ischemic stroke. However, most studies focus on short-term outcomes. This study examined long-term outcomes according to time to thrombolysis in patients with first-time ischemic stroke. Methods: In this nationwide cohort study, all Danish patients with first-time ischemic stroke treated with intravenous thrombolysis between 2011 and 2017 and alive at discharge were identified through the Danish Stroke Registry. The association between time from symptom onset to thrombolysis and the long-term rate of the composite of death and recurrent ischemic stroke was examined using multivariable Cox regression and restricted cubic spline analysis. Results: The study population included 6252 patients with first-time ischemic stroke treated with thrombolysis (median age, 69 years [25th­75th percentile 60­78 years], 60% men). The median follow-up was 2.5 years (25th­75th percentile 1.2­4.1 years). The median time to thrombolysis was 138 minutes (25th­75th percentile 101­185 minutes), and the median National Institutes of Health Stroke Scale score at presentation was 5 (25th­75th percentile 3­10). The absolute 3-year risk of the composite outcome was 19.0% (95% CI, 16.4%­21.8%) in the 0 to 90 minute group, 23.3% (21.8%­24.9%) in the 91 to 180 minute group, and 23.8% (21.6%­26.1%) in the 181 to 270 minute group. Compared with thrombolysis within 90 minutes, time to thrombolysis >90 minutes was associated with a higher rate of the composite outcome (91­180 minute: adjusted hazard ratio, 1.25 [95% CI, 1.06­1.48]; 181­270 minutes: adjusted hazard ratio, 1.35 [95% CI, 1.12­1.61]). In restricted cubic spline analysis, the rate of the composite outcome increased with increasing time to thrombolysis and leveled off after 138 minutes. Conclusions: In this nationwide cohort of patients with ischemic stroke, the long-term rate of the composite of death and recurrent ischemic stroke increased with increasing time from symptom onset to initiation of thrombolysis.

Nationwide cardiovascular disease admission rates during a second COVID-19 lockdown.

Societal lockdowns during the first wave of the coronavirus disease 2019 pandemic were associated with decreased admission rates for acute cardiovascular conditions worldwide. In this nationwide Danish study of the first five weeks of a second pandemic lockdown, incidence of new-onset heart failure and atrial fibrillation remained stable, but there was a significant drop in new-onset ischemic heart disease and ischemic stroke during the fourth week of lockdown, which normalized promptly. The observed drops were lower compared to the first Danish lockdown in March 2020; thus, our data suggest that declines in acute cardiovascular disease admission rates during future lockdowns are avoidable.

Incidence of acute coronary syndrome during national lock-down: Insights from nationwide data during the Coronavirus disease 2019 (COVID-19) pandemic.

BACKGROUND: Urgent recognition and treatment are needed in patients with acute coronary syndrome (ACS), however this may be difficult during the Coronavirus disease 2019 (COVID-19) pandemic with a national lock-down. We aimed to examine the incidence of ACS after national lock-down. METHODS: The Danish government announced national lock-down on March 11, 2020 and first phase of reopening was announced on April 6. Using Danish nationwide registries, we identified first-time ACS admissions in (1) January 1 to May 7, 2017-2019, and (2) January 1, 2020 to May 6, 2020. Incidence rates of ACS admissions per week for the 2017 to 2019 period and the 2020 period were computed and incidence rate ratios (IRR) were computed using Poisson regression analysis. RESULTS: The number of ACS admissions were 8,204 (34.6% female, median age 68.3 years) and 2,577 (34.0% female, median age 68.5 years) for the 2017 to 2019- and 2020 period, respectively. No significant differences in IRRs were identified for weeks 1 to 9 (January 1 to March 4) for 2020 compared with week 1 to 9 for 2017 to 2019. In 2020, significant lower IRRs were identified for week 10 (March 5 to 11) IRR = 0.71 (95% confidence intervals [CI]: 0.58 to 0.87), week 11 (12 to 18 March) IRR = 0.68 (0.56 to 0.84), and week 14 (April 2 to April 8) IRR = 0.79 (0.65 to 0.97). No significant differences in IRRs were identified for week 15 to 18 (April 9 to May 6). In subgroup analysis, we identified that the main result was driven by male patients, and patients ≥60 years. CONCLUSIONS: During the COVID-19 pandemic with an established national lock-down we identified a significant decline around 30% in the incidence of ACS admissions. Along with the reopening of society, ACS admissions were stabilized at levels equal to previous years.

Differences in mortality in patients undergoing surgery for infective endocarditis according to age and valvular surgery.

BACKGROUND: Infective endocarditis (IE) is associated with high mortality. Surgery may improve survival and reduce complications, but the balance between benefit and harm is difficult and may be closely related to age and type of surgical intervention. We aimed to examine how age and type of left-sided surgical intervention modified mortality in patients undergoing surgery for IE. METHODS: By crosslinking nationwide Danish registries we identified patients with first-time IE undergoing surgical treatment 2000-2017. Patients were grouped by age < 60 years, 60-75 years, and ≥ 75 years. Multivariable adjusted Cox proportional hazard analysis was used to examine factors associated with 90-day mortality. RESULTS: We included 1767 patients with IE undergoing surgery, 735 patients < 60 years (24.1% female), 766 patients 60-75 years (25.8% female), and 266 patients ≥75 years (36.1% female). The proportions of patients undergoing surgery were 35.3, 26.9, and 9.1% for patients < 60 years, 60-75 years, and > 75 years, respectively. Mortality at 90 days were 7.5, 13.9, and 22.3% (p < 0.001) for three age groups. In adjusted analyses, patients 60-75 years and patients ≥75 years were associated with a higher mortality, HR = 1.84 (95% CI: 1.48-2.29) and HR = 2.47 (95% CI: 1.88-3.24) as compared with patients < 60 years. Factors associated with 90-day mortality were: mitral valve surgery, a combination of mitral and aortic valve surgery as compared with isolated aortic valve surgery, age, diabetes, and prosthetic heart valve implantation prior to IE admission. CONCLUSIONS: In patients undergoing surgery for IE, mortality increased significantly with age and 1 in 5 died above age 75 years. Mitral valve surgery as well as multiple valve interventions augmented mortality further.

High prevalence of erectile dysfunction in male patients with acute stroke was associated with age but not to modifiable cardiovascular risk factors.

Background: Erectile dysfunction (ED) and stroke share common risk factors, and symptoms of ED often precede the development of clinical cardiovascular disease (CVD). However, little is known about how ED is associated with cardiovascular (CV) risk factors in patients who had a stroke and if concomitant ED is a marker of more severe CVD. Aims: We aimed to identify the prevalence of ED and CV risk factors in patients admitted with a stroke or transient ischaemic attack (TIA). Further, we wanted to test if self-reported ED associated with presence of CV risk factors, and if patients with ED had increased stroke severity compared with patients without ED. Methods: This was a post hoc analysis of data retrieved in a cross-sectional survey from two non-comprehensive stroke units in Denmark. Multiple logistic regression adjusted for covariates was performed to investigate the association between CV risk factors and self-reported ED. Results: We included 287 male patients of which 116 (40.4%) had self-reported ED. Advanced age was significantly associated with self-reported ED (reference ≤60 years: OR 3.93, 95% CI 1.84 to 8.37 for men 71-80 years and OR 4.61, 95% CI 1.92 to 11.08 for men >80 years). Self-reported ED was not significantly associated with CV risk factors or stroke severity. Discussion: Four in 10 men with acute stroke or TIA reported to have ED prior to their stroke, and this was associated with age rather than CV risk factors. Hence, self-reported ED was not restricted to the CVD load, nor was ED a risk marker for increased stroke severity. However, our population was of high age with well-established CVD, and the presence of ED may be a stroke risk marker in younger patients who had a stroke. Based on the prevalence, potential treatment of ED should be addressed in stroke recovery.

Comparative Rates of Stroke and Rehospitalization of Atrial Fibrillation in Patients with Perioperative Atrial Fibrillation Following Major Emergency Abdominal Surgery and Patients with Non-perioperative Atrial Fibrillation.

BACKGROUND: Major emergency abdominal surgery is associated with postoperative complications and high mortality. Long-term outcomes in patients with perioperative atrial fibrillation (POAF) have recently received increased attention, especially POAF in non-thoracic surgery. PURPOSE: This study aimed to compare long-term AF related hospitalization and stroke in patients with POAF in relation to major emergency abdominal surgery and in patients with non-perioperative AF. METHODS: We crosslinked data from Danish nationwide registries and identified all patients who underwent major emergency abdominal surgery (2000-2018) and were diagnosed with POAF, and patients who developed AF in a non-perioperative setting. Patients with POAF were matched in a 1:5 ratio on age, sex, year of AF diagnosis and oral anticoagulation (OAC) status at the beginning of follow-up with patients with non-perioperative AF. From discharge, we examined adjusted hazard ratios (HR) of stroke using multivariable Cox regression analysis. RESULTS: The study population comprised 1,041 (out of 42,021 who underwent major emergency abdominal surgery) patients with POAF and 5,205 patients with non-perioperative AF. The median age was 78 years [interquartile range: 71-84] for those initiated on OAC therapy and 78 years [interquartile range: 71-85] for those not initiated on OAC therapy. During the first year of follow up, POAF was associated with similar rates of stroke as non-perioperative AF (patients initiated on OAC: HR 0.96 (95% confidence interval (CI) 0.52-1.77) and patients not initiated on OAC: HR 0.69 (95% CI 0.41-1.15). CONCLUSION: POAF in relation to major emergency abdominal surgery was associated with similar rates of stroke as non-perioperative AF. These results suggest that POAF not only carry an acute burden but also a long-term burden in patients undergoing major emergency abdominal surgery.

Prognostic Impact of Anemia in Patients Undergoing Aortic Valve Replacement: A Nationwide Study.

BACKGROUND: Patients undergoing aortic valve replacement (AVR) have high readmission rates. Several risk factors have been proposed as potential modifiable targets, including anemia. We examined the association between anemia at discharge and subsequent outcomes in these patients. METHODS: Using Danish nationwide registries, we identified all patients who underwent AVR between 2015-2021, were alive at discharge (index date), and had an available hemoglobin (Hb) measurement taken between procedure and discharge. Patients were categorized as having i) moderate/severe anemia (Hb<6.2 mmol/L) or ii) no/mild anemia (Hb≥6.2 mmol). The one-year rates of all-cause mortality, all-cause hospital admission, heart failure (HF) admission, and atrial fibrillation (AF) admission were compared using multivariable Cox regression models. RESULTS: 8,614 patients were identified; 2,847 (33.1%) had moderate/severe anemia (60.2% male, median age 74) and 5,767 (66.9%) had no/mild anemia (68.0% male, median age 76). For these two groups, respectively, the cumulative one-year incidences of the outcomes were: i) all-cause mortality: 5.1% vs. 4.3%; ii) all-cause admission: 53.8% vs. 47.5%; iii) AF admission: 14.0% vs. 11.6%); iv) HF admission: 6.8% vs. 6.2%. In adjusted analysis, moderate/severe anemia, compared with no/mild anemia, was associated with higher rates of all-cause mortality (hazard ratio (HR) 1.27 [95%CI 1.02-1.58]), all-cause admission (HR 1.22 [95%CI 1.14-1.30]), and AF admission (HR 1.23 [95%CI 1.08-1.40]), but not HF admission (HR 1.09 [95%CI 0.91-1.31]). CONCLUSION: In patients undergoing AVR, moderate/severe anemia at discharge, compared with no/mild anemia, was associated with increased all-cause mortality, all-cause hospital admission, and AF admission, but not HF admission, at one-year post-discharge.

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.

Diuretic treatment before and after transcatheter aortic valve implantation: A Danish nationwide study.

OBJECTIVES: We examined loop diuretic treatment before and 1-year after transcatheter aortic valve implantation (TAVI), as a proxy for changes in symptom severity and secondly assessed how changes in loop diuretics related to mortality risk. BACKGROUND: Randomized clinical trials suggest that approximately one third of patients undergoing TAVI do not achieve symptom relief, but "all-comer" data are lacking. METHODS: Using Danish nationwide registries, we identified all citizens, who underwent TAVI from 2008 to 2019 and were alive at 1-year post-discharge. Loop diuretic treatment pre-TAVI and at 1-year post-TAVI were assessed and grouped as receiving 1) no-loop diuretics; 2) low: 1-40 mg of furosemide (or equivalent bumetanide) daily; 3) intermediate: 41-120 mg of furosemide daily; or 4) high: >120 mg furosemide daily. RESULTS: Among the 4431 patients undergoing TAVI, 2173 (49%) patients were not treated with loop diuretics at the time of TAVI, 918 (21%) had low-loop diuretics, 881 (20%) had intermediate-loop diuretics, and 459 (10%) had high-loop diuretics. At 1-year post-TAVI, 893 (20%) patients had increased, 1010 (23%) had reduced, and 2528 (57%) had unchanged loop diuretic treatment. The cumulative 5-year risk of death in patients surviving one year, was 61% (95% CI: 56.4% to 65.3%) in patients with increased and 47% (95% CI: 44.9% to 49.9%) in patients with reduced/unchanged loop diuretic treatment, respectively. In multivariable Cox proportional hazard analysis, increased loop diuretic treatment was associated with a higher risk of death compared with reduced/unchanged loop diuretic treatment (Hazard ratio: 1.4; 95% CI: 1.22 to 1.52). CONCLUSIONS: Among patients undergoing TAVI, surviving one year, one fifth of patients had increased loop diuretic treatment, and a little over one fifth had reduced loop diuretic treatment 1-year post-procedure. In patients with increased diuretic treatment, the risk of death was higher compared to those with reduced/unchanged loop diuretic treatment.

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.

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.

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.

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.

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.