Temporal trends in utilization of transcatheter aortic valve replacement and patient characteristics: A nationwide study.

AIM: To investigate trends in the utilization of transcatheter aortic valve replacement (TAVR) and changes in the characteristics of patients undergoing first-time TAVR. METHODS: Using Danish nationwide registers, we included all patients undergoing TAVR between 2008 and 2020. To compare patient characteristics, the study population was stratified according to calendar year of procedure: 2008-2010, 2011-2013, 2014-2016, and 2017-2020. RESULTS: We identified 6,097 patients undergoing TAVR with year-by-year increases in TAVR penetration rate. Over time, the age of the patients remained stable (2008-2010: median age 82 year [interquartile range (IQR): 77-86] vs 2017-2020: median age 81 years [IQR: 77-85]). Moreover, there was an increase in male patients (2008-2010: 49.9% vs 2017-2020: 57.4%) and patients with diabetes (2008-2010: 14.2% vs 2017-2020: 19.2%). Conversely, a history of stroke (2008-2010: 15.8% vs 2017-2020: 13.1%), previous myocardial infarction (2008-2010: 22.4% vs 2017-2020: 10.0%), heart failure (2008-2010: 40.5% vs 2017-2020: 25.2%), and peripheral artery disease (2008-2010: 14.8% vs 2017-2020: 10.4) decreased among patients. CONCLUSIONS: TAVR utilization increased markedly in the years 2008-2020. Patients undergoing TAVR had less comorbidity over time while age remained stable. Thus, despite expanding to patients at lower surgical risk, TAVR is still offered mainly to older patients.

Dabigatran and the Risk of Staphylococcus aureus Bacteremia: A Nationwide Cohort Study.

BACKGROUND: Treatment with dabigatran, an oral direct thrombin inhibitor, reduces the virulence of Staphylococcus aureus in in vitro and in vivo models. However, it remains to be determined whether dabigatran reduces the risk of S. aureus infections in humans. We investigated the incidence rate of S. aureus bacteremia (SAB) in patients with atrial fibrillation treated with the direct thrombin inhibitor dabigatran compared with patients treated with the factor Xa-inhibitors rivaroxaban, apixaban, and edoxaban. METHODS: In this observational cohort study, 112 537 patients with atrial fibrillation who initiated treatment with direct oral anticoagulants (August 2011-December 2017) were identified from Danish nationwide registries. The incidence rates of SAB in patients treated with dabigatran versus patients treated with the factor Xa-inhibitors were examined by multivariable Cox regression accounting for time-dynamic changes in exposure status during follow-up. RESULTS: A total of 112 537 patients were included. During a median follow-up of 2.0 years, 186 patients in the dabigatran group and 356 patients in the factor Xa-inhibitor group were admitted with SAB. The crude incidence rate of SAB was lower in the dabigatran group compared with the factor Xa-inhibitor group (22.8 [95% confidence interval [CI], 19.7-26.3] and 33.8 [95% CI, 30.5-37.6] events per 10 000 person-years, respectively). In adjusted analyses, dabigatran was associated with a significantly lower incidence rate of SAB compared with factor Xa-inhibitors (incidence rate ratio, .76; 95% CI, .63-.93). CONCLUSIONS: Treatment with dabigatran was associated with a significantly lower incidence rate of SAB compared with treatment with factor Xa-inhibitors.

Risk of fracture in adults on renal replacement therapy: a Danish national cohort study.

BACKGROUND: Patients on dialysis treatment or living with a transplanted kidney have several risk factors for bone fracture, especially disturbances in mineral metabolism and immunosuppressive therapy. We describe the incidence of fracture in this retrospective national Danish cohort study and explore the influence of age, gender, comorbidity and prescribed medication. METHODS: By individual-level linkage between nationwide administrative registries, the risk of fracture was compared between the group of patients receiving chronic dialysis treatment and patients receiving their first renal transplant in the study period, using the Danish background population as reference group. All three groups were followed up until first fracture, emigration, death or end of study. Cox proportional hazard models with fracture as outcome were fitted to the data. RESULTS: The hazard ratio (HR) for any fracture was 3.14 [95% confidence interval (95% CI):2.97-3.31] in the dialysis group and 1.94 (95% CI: 1.72-2.18) in the renal transplanted group. The HR remained increased, but was modified by adjustment for age, gender, comorbidity and prior fracture [dialysis group: 1.85 (95% CI: 1.75-1.95); renal transplanted group: 1.82 (95% CI: 1.62-2.06)]. Prescribed diuretics, lipid-modifying agents and proton pump inhibitors also modulated the fracture risk. CONCLUSIONS: Patients on dialysis or living with a transplanted kidney have a significantly higher risk of fracture than the Danish background population. Differences in age, gender, drug use and comorbidity only partly explain this increased risk. Further studies are warranted to explore the reason for this increased fracture risk in patients on renal replacement therapy.

Metformin-associated risk of acute dialysis in patients with type 2 diabetes: A nationwide cohort study.

Recent guidelines governing anti-diabetic medications increasingly advocate metformin as first-line therapy in all patients with type 2 diabetes. However, metformin could be associated with increased risk of acute kidney injury (AKI), acute dialysis and lactate acidosis in marginal patients. In a retrospective nationwide cohort study, a total of 168 443 drug-naïve patients with type 2 diabetes ≥50 years, initiating treatment with either metformin or sulphonyl in Denmark between 2000 and 2012 were included in this study (70.7% initiated treatment with metformin); calculation of 1-year risk of acute dialysis was based on g-standardization of cause-specific Cox regression models for acute dialysis, end-stage renal disease and death. One-year risks of acute dialysis were 92.4 per 100 000 (95% CI, 67.1-121.3) and 142.7 per 100 000 (95% CI, 118.3-168.0) for sulphonylurea and metformin, respectively. The metformin-associated 1-year risk of acute dialysis was increased by 50.3 per 100 000 (95% CI, 7.9-88.6), corresponding to a risk ratio of 1.53 (95% CI, 1.06-2.23), and a number needed to harm of 1988, thus providing evidence of potential concerns pertaining to the increasing use of metformin.

Temporal Trends in Patient Characteristics and Outcomes of Transcatheter Aortic Valve Implantation and Surgical Aortic Valve Replacement: A Nationwide Study.

With increased use of transcatheter aortic valve implantation (TAVI) in treatment of aortic stenosis, it is important to evaluate real life data trends in outcomes. This nationwide register-based study aimed to present an outlook on temporal trends in characteristics and outcomes, including mortality. First-time consecutive Danish patients who underwent TAVI from 2010 to 2019 were included in this study. The chi-square and Kruskal-Wallis tests were performed to assess the differences in the characteristics over time and Cochrane-Armitage trend tests were used to examine changes in complications and mortality. Between 2010 and 2019, 4,847 patients (54.6% men, median age 82 [quartile 1 to quartile 3: 77 to 85] years) underwent first-time TAVI. A statistically significant decrease over time was observed for preprocedural hypertension, ischemic heart disease, and heart failure, whereas preexisting chronic obstructive lung disease and preprocedural pacemaker remained stable. We observed a significant decrease in 30- and 90-day postoperative preprocedural pacemaker implantation from 2011 to 2017, with 15.1% and 15.9% in 2011 and 8.6% and 8.9% in 2017, respectively. The incidence of for 30- and 90-day heart failure significantly decreased from 19.3% and 20.3% to 8.5% and 9.1%, respectively. We observed significant changes for 30-day atrial fibrillation, whereas the changes over time for 90-day atrial fibrillation and 30- and 90-day stroke/transient ischemic attack remained insignificant. The all-cause mortality within 30- and 90 days significantly decreased over time from 6.7% and 9.2% in 2011 to 1.5% and 2.7% in 2019 and 2016, respectively. In conclusion, this national study provides general insight on the trends of complications and mortality of TAVI, demonstrating significant reductions over time.

Trends in percutaneous left atrial appendage occlusion and 1-year mortality 2013-2021: A nationwide observational study.

BACKGROUND: Percutaneous left atrial appendage occlusion (LAAO) is increasingly used for stroke prevention in patients with atrial fibrillation and anticoagulant-related complications. Yet, real-life studies evaluating changes in patient characteristics and indications for LAAO remain scarce. METHODS: To evaluate changes in patient characteristics and indications for LAAO defined as 2-year history of intracerebral bleeding, any ischemic stroke/systemic embolism (SE), any non-intracerebral bleeding, other indication, and 1-year mortality. All patients undergoing percutaneous LAAO in Denmark from 2013 to 2021 were stratified into the following year groups: 2013-2015, 2016-2018, and 2019-2021. RESULTS: In total, 1465 patients underwent LAAO. Age remained stable (2013-2015: 74 years versus 2019-2021: 75 years). Patients' comorbidity burden declined, exemplified by CHA2DS2-VASc ≥4 and HAS-BLED ≥3 decreased from 56.7% and 63.7% in 2013-2015 to 40.3% and 45.8% in 2019-2021. Indications for LAAO changed over time with other indication comprising 44.7% in 2019-2021; up from 26.9% in 2013-2015. Conversely, fewer patients had an indication of any ischemic stroke/SE (2013-2015: 30.8% vs 2019-2021: 20.3%) or any non-intracerebral bleeding (2013-2015: 29.4% vs 2019-2021: 23.4%). 1-year mortality was 11.3% for any non-intracerebral bleeding and 6.2% for other indication. CONCLUSION: The LAAO patient-profile has changed considerably. Age remained stable, while comorbidity burden decreased during the period 2013-2021. LAAO is increasingly used in patients with no clinical event history and mortality differs according to indication. Selection of patients to LAAO should be done carefully, and contemporary real-life studies investigating clinical practice could add important insights.

Psoriasis and risk of atrial fibrillation and ischaemic stroke: a Danish Nationwide Cohort Study.

AIMS: Psoriasis is a chronic inflammatory disease and inflammation contributes to the pathogenesis of atrial fibrillation (AF) and ischaemic stroke. We therefore investigated the risk of these endpoints in patients with psoriasis. METHODS AND RESULTS: Cohort study of the entire Danish population followed from 1997 to 2006 by individual-level-linkage of nationwide prospectively recorded registers. Multivariable Poisson's regression and sensitivity analyses were used to assess the psoriasis-related risk of AF and ischaemic stroke. A total of 36 765 patients with mild psoriasis and 2793 with severe psoriasis were compared with 4 478 926 individuals, i.e., the reference population. In patients with mild psoriasis, the adjusted rate ratios (RRs) for AF were 1.50 (1.21-1.86) and 1.16 (1.08-1.24) in patients aged <50 and ≥50 years, respectively. Patients with severe psoriasis had a higher risk of AF with RRs 2.98 (1.80-4.92) in patients aged <50 years and 1.29 (1.01-1.65) in patients aged ≥50 years. Patients with psoriasis also demonstrated a disease severity-dependent increased risk of ischaemic stroke, i.e. RRs 1.97 (1.66-2.34) and 2.80 (1.81-4.34) in patients aged <50 years with mild and severe psoriasis, and RRs 1.13 (1.04-1.21) and 1.34 (1.04-1.71) in patients aged ≥50 years with mild and severe psoriasis, respectively. A range of sensitivity analyses yielded comparable results. CONCLUSION: Psoriasis is associated with increased risk of AF and ischaemic stroke. These novel results add to a growing body of evidence, suggesting that patients with psoriasis could be considered at increased cardiovascular risk.

Nursing Home Admission Following Transcatheter Aortic Valve Replacement: A Danish Nationwide Cohort Study.

BACKGROUND: Loss of autonomy associated with nursing home admission (NHA) is a concern for patients. Yet the incidence of NHA after transcatheter aortic valve replacement (TAVR) is unknown. OBJECTIVES: The aim of this study was to investigate the incidence and factors associated with NHA following TAVR compared with the general population. METHODS: Through Danish registries, patients alive at discharge after TAVR were identified from January 2014 to October 2021. Patients were matched 1:5 on sex, age, and calendar year to the general population. The 3-year cumulative incidence and 95% CI of NHA were estimated using the Aalen-Johansen estimator, accounting for the competing risk for death. Through multivariate cause-specific Cox regression models, factors associated with NHA were examined. RESULTS: In total, 5,312 TAVR patients were matched to 26,560 control subjects with a median age of 81 years and 56.1% males. Comorbidity burden was higher for TAVR patients. The 3-year cumulative incidence of NHA was 6.3% (95% CI: 5.5%-7.1%) for TAVR patients compared with 5.8% (95% CI: 5.4%-6.1%) for the general population. For TAVR patients >85 years of age, the cumulative incidence of NHA was 11.6% (95% CI: 9.5%-13.8%), and the risk for death was 23.3% (95% CI: 20.4%-26.2%). Factors associated with NHA were increasing age, frailty, living alone, and atrial fibrillation. CONCLUSIONS: TAVR was not associated with an increased incidence of NHA compared with the general population. Despite the increased incidence of NHA for TAVR patients >85 years of age, approximately 2 in 3 patients were still alive and not admitted to nursing homes 3 years after TAVR.

Prognosis in patients with atrial fibrillation and CHA2DS2-VASc Score = 0 in a community-based cohort study.

OBJECTIVES: Patients with atrial fibrillation (AF) and a CHA(2) DS(2) -VASc score = 0 have a very low risk of stroke and current guidelines even recommend no antithrombotic therapy to these patients. We investigated the rate and risk of adverse events and the impact of antithrombotic management in a community based cohort of AF patients with a CHA(2)DS(2)-VASc score = 0. METHODS AND RESULTS: Patients with AF seen in our institution between 2000 and 2010 were identified in a database. The adverse outcomes were investigated during follow-up. Among 8,962 patients with AF, 616 (7%) had a congestive heart failure, hypertension, age ≥75 years (doubled), diabetes, stroke/TIA/thromboembolism (doubled), vascular disease (prior myocardial infarction, peripheral artery disease, or aortic plaque), age 65-74 years, sex category (female) (CHA(2)DS(2)-VASc score) = 0. An oral anticoagulant was prescribed in 273 patients (44%), antiplatelet therapy alone in 145 patients (24%), and no antithrombotic treatment in 198 patients (32%). During a follow up of 876 ± 1,135 days (median 244, interquartile range 1,540 days), 38 patients sustained events (10 stroke/thromboembolism, 19 major bleeding, 17 deaths). Among untreated patients, rates of stroke/thromboembolism, major bleeding and mortality were 0.64%, 1.12%, and 1.08% per year. Prescription of oral anticoagulation and/or antiplatelet therapy was not associated with an improved prognosis for stroke/thromboembolism (relative risk [RR] = 0.99, 95% CI 0.25-3.99, P = 0.99), nor improved survival or net clinical benefit (combination of stroke/thromboembolism, bleeding, and death). CONCLUSION: In a real life cohort study, AF patients with CHA(2)DS(2) VASc score = 0 had a low risk of stroke/thromboembolism that was not significantly different between those taking oral anticoagulation, antiplatelet therapy, or no antithrombotic therapy. This supports current guideline recommendations for no antithrombotic therapy in these "truly low-risk" patients.

Prognosis after percutaneous coronary intervention in patients with psoriasis: a cohort study using Danish nationwide registries.

BACKGROUND: Psoriasis is an inflammatory disease associated with increased risk of coronary artery disease. However, the potential impact of psoriasis on the prognosis following percutaneous coronary revascularization (PCI) is unknown. METHODS: The study comprised the entire Danish population undergoing first-time PCI in the period 2002-09. Cox regression models, controlling for age, gender, socioeconomic status, pharmacological treatment, and comorbidity were used to assess the risk of 1) all-cause mortality and 2) a composite endpoint of death, myocardial infarction, and stroke. RESULTS: A total of 53,141 patients with first-time PCI in the study period were identified. Of these, 1074 had mild psoriasis and 315 had severe psoriasis. Patients with severe psoriasis, but not those with mild disease had increased risk of both endpoints compared to patients without psoriasis. The incidence rates for all-cause mortality were 30.5 (CI 29.7-31.3), 29.9 (CI 24.7-36.1), and 47.2 (CI 35.0-63.6) per 1000 patient years for patients without psoriasis, with mild psoriasis, and with severe psoriasis, respectively. Hazard ratios were 1.10 (CI 0.91-1.33) and 1.67 (CI 1.24-2.26) for mild and severe psoriasis, respectively. Patients with severe psoriasis were less likely to receive secondary prevention pharmacotherapy with betablockers, statins and platelet inhibitors. CONCLUSION: This first study of the prognosis following PCI in patients with psoriasis demonstrated an increased risk of all-cause mortality and of a composite of death, myocardial infarction and stroke, respectively, in patients with severe psoriasis compared to patients without psoriasis. Further studies of this novel association are needed.

Mortality at one year after transcatheter aortic valve replacement - Relation of age and comorbidities.

Background: Of patients undergoing transcatheter aortic valve replacement (TAVR), 80-90 % are at extreme, high, or intermediate risk. Patient selection considering futile outcomes in these groups is difficult as significant comorbidity burden is common. Thus, we examined 1-year mortality after TAVR according to age and comorbidities. Methods: Between 2008 and 2021 all Danish TAVR-patients were included. From a multivariate Cox-regression model, significant characteristics associated with 1-year all-cause mortality were identified. The study population was divided into four groups according to number of significant comorbidities present at baseline: Low (0 comorbidities), mild (1 comorbidity), moderate (2 comorbidities), and high (3 or more comorbidities). The 1-year risk of all-cause mortality with 95 % confidence intervals (CI) was estimated by each group. Results: In total, 7,104 patients underwent TAVR. Significant covariates associated with 1-year all-cause mortality were chronic kidney disease, heart failure, chronic obstructive pulmonary disease, peripheral artery disease, and age ≥ 85 years. The four baseline groups comprised low (n = 2,666), mild (n = 2,814), moderate (n = 1,246), and high comorbidity burden (n = 378). The 1-year risk of all-cause mortality was 5.5 % (95 %CI: 4.6-6.4 %) in the low baseline comorbidity burden group. Conversely, the 1-year risk of all-cause mortality was 25.0 % (95 %CI: 20.4-29.3 %) in the high baseline burden group. Conclusions: In a national sample of TAVR patients, readily available information on age and comorbidities, can be used to identify a high-risk group with 25 % 1-year mortality. This provides physicians and patients with an easy-to-understand view on 1-year prognosis after TAVR and may complement patient selection for improved long-term outcomes.

Ischemic Stroke Severity and Mortality in Patients With and Without Atrial Fibrillation.

Background Our objective was to investigate stroke severity and subsequent rate of mortality among patients with and without atrial fibrillation (AF). Contemporary data on stroke severity and prognosis in patients with AF are lacking. Methods and Results First-time ischemic stroke patients from the Danish Stroke Registry (January 2005-December 2016) were included in an observational study. Patients with AF were matched 1:1 by sex, age, calendar year, and CHA2DS2-VASc score with patients without AF. Stroke severity was determined by the Scandinavian Stroke Scale (0-58 points). The rate of death was estimated by Kaplan-Meier plots and multivariable Cox regression. Among 86 458 identified patients with stroke, 17 205 had AF. After matching, 14 662 patients with AF and 14 662 patients without AF were included (51.8% women; median age, 79.6 years [25th-75th percentile, 71.8-86.0]). More patients with AF had very severe stroke (0-14 points) than patients without AF (13.7% versus 7.9%, P<0.01). The absolute rates of 30-day and 1-year mortality were significantly higher for patients with AF (12.1% and 28.4%, respectively) versus patients without AF (8.7% and 21.8%, respectively). This held true in adjusted models for 30-day mortality (hazard ratio [HR], 1.40 [95% CI, 1.30-1.51]). However, this association became nonsignificant when additionally adjusting for stroke severity (HR, 1.10 [95% CI, 1.00-1.23]). AF was associated with a higher rate of 1-year mortality (HR, 1.39 [95% CI, 1.32-1.46]), although it was mediated by stroke severity (HR, 1.15 [95% CI, 1.09-1.23], model including stroke severity). Conclusions In a contemporary nationwide cohort of patients with ischemic stroke, patients with AF had more severe strokes and higher mortality than patients without AF. The difference in mortality was mainly driven by stroke severity.

Association Between Inappropriately Dosed Anticoagulation Therapy With Stroke Severity and Outcomes in Patients With Atrial Fibrillation.

Background Oral anticoagulation (OAC) is effective for stroke prevention in patients with atrial fibrillation. However, some patients experience stroke despite OAC therapy, and knowledge about the impact of prior treatment quality is lacking. Methods and Results Patients with atrial fibrillation on OAC therapy who had a first-time ischemic stroke were identified in the Danish Stroke Registry (2005-2018). Patients treated with vitamin K antagonist (VKA) therapy were compared according to the international normalized ratio just before stroke (international normalized ratio <2 [subtherapeutic], international normalized ratio 2-3 [therapeutic], international normalized ratio >3 [supratherapeutic]), and patients on underdosed, appropriately dosed, and overdosed direct OAC (DOAC) therapy were compared. Stroke severity was determined using the Scandinavia Stroke Scale (0-58 points), and the risk of very severe stroke (0-14 points) was analyzed by multivariable logistic regression. One-year mortality was determined using multivariable Cox regression. A total of 2319 patients with atrial fibrillation and stroke were included; 1196 were taking a VKA (subtherapeutic [46%], therapeutic [43%], supratherapeutic [11%]), and 1123 were taking DOAC (underdosed [23%], appropriately dosed [60%], and overdosed [17%]). Subtherapeutic and supratherapeutic VKA therapy (compared with therapeutic) and underdosed DOAC therapy (compared with appropriate and underdosed DOAC) patients were older, more often women, and more comorbid. Subtherapeutic VKA therapy was associated with very severe stroke (odds ratio [OR], 2.06 [95% CI, 1.28-3.31]), whereas supratherapeutic VKA therapy was not (OR, 1.24 [95% CI, 0.60-2.57]) compared with therapeutic VKA therapy. Patients on subtherapeutic and supratherapeutic VKA therapy had a higher 1-year mortality (hazard ratio [HR], 1.66 [95% CI, 1.29-2.13]); HR, 1.55 [95% CI, 1.08-2.22], respectively) than those on therapeutic VKA therapy. Treatment with underdosed or overdosed DOAC therapy was not associated with very severe stroke (OR, 1.27 [95% CI, 0.76-2.15]; OR, 0.73 [95% CI, 0.37-1.43], respectively) and was not associated with 1-year mortality (HR, 1.09 [95% CI, 0.83-1.44]; HR, 0.82 [95% CI, 0.57-1.18], respectively) than appropriate DOAC. Conclusions Half of the patients with atrial fibrillation with stroke were on inappropriate OAC therapy. Subtherapeutic VKA was associated with worse stroke severity and higher mortality rate than therapeutic VKA therapy. Neither underdosed nor overdosed DOAC was associated with worse outcomes in adjusted models compared with appropriately dosed DOAC. This study supports DOAC as a first-line therapy over VKA.

Ticagrelor and the risk of Staphylococcus aureus bacteraemia and other infections.

AIMS: To investigate the 1-year risks of Staphylococcus aureus bacteraemia (SAB), sepsis, and pneumonia in patients who underwent percutaneous coronary intervention and were treated with ticagrelor vs. clopidogrel. METHODS AND RESULTS: In this nationwide observational cohort study, 26 606 patients who underwent urgent or emergent percutaneous coronary intervention (January 2011-December 2017) and initiated treatment with ticagrelor [N = 20 073 (75.5%); median age 64 years (25th-75th percentile 55-72 years); 74.8% men] or clopidogrel [N = 6533 (24.5%); median age 68 years (25th-75th percentile 58-77 years); 70.2% men] were identified using Danish nationwide registries. The 1-year standardized absolute risks of outcomes was calculated based on cause-specific Cox regression models, and average treatment effects between treatment groups were obtained as standardized differences in absolute 1-year risks. The absolute 1-year risk of SAB was 0.10% [95% confidence interval (CI), 0.05-0.15%] in the ticagrelor group and 0.29% (95% CI, 0.17-0.42%) in the clopidogrel group. Compared with clopidogrel, treatment with ticagrelor was associated with a significantly lower absolute 1-year risk of SAB [absolute risk difference -0.19% (95% CI, -0.32% to -0.05%), P value 0.006]. Likewise, treatment with ticagrelor was associated with a significantly lower absolute 1-year risk of sepsis [0.99% (95% CI, 0.83-1.14%) vs. 1.49% (95% CI, 1.17-1.80%); absolute risk difference -0.50% (95% CI, -0.86% to -0.14%), P value 0.007] and pneumonia [3.13% (95% CI, 2.86-3.39%) vs. 4.56% (95% CI, 4.03-5.08%); absolute risk difference -1.43% (95% CI, -2.03% to -0.82%), P value < 0.001] compared with clopidogrel. CONCLUSION: Treatment with ticagrelor was associated with a significantly lower 1-year risk of SAB, sepsis, and pneumonia compared with clopidogrel.

Body mass index is closely correlated to incident diabetes in patients with heart failure or myocardial infarction.

BACKGROUND: Diabetes in patients with heart failure or myocardial infarction (MI) increases morbidity and mortality, but little is known about the impact of obesity on the risk of developing diabetes in these populations. DESIGN: A cohort of patients consecutively hospitalized with heart failure (n = 3472) or MI (n = 5723) was followed in the period 1995-2006. METHODS: Multivariable Cox proportional-hazard models were used to estimate the risk of developing diabetes according to the World Health Organization body mass index (BMI) classification. Normal weight patients (BMI 18.5-24.9 kg/m(2)) were used as the reference. RESULTS: In both populations, more than half of the patients with a BMI above 34.9 kg/m(2) developed diabetes. In heart failure patients, a BMI above 24.9 kg/m(2) was associated with an increased risk of diabetes for the three BMI groups, i.e. 25.0-29.9 kg/m(2), 30.9-34.9 kg/m(2), and >34.9 kg/m(2), with adjusted hazard ratios (HRs) of 2.16 (95% confidence interval 1.50-3.12), 3.89 (2.61-5.78), and 6.06 (3.79-9.69), respectively. In MI patients, the adjusted HRs in the three corresponding BMI groups were 1.84 (1.44-2.37), 4.31 (3.26-5.69), and 9.50 (6.70-13.46), respectively. Incident diabetes was associated with increased cardiovascular and all-cause mortality risks with adjusted HRs of greater magnitude than in prevalent diabetes. CONCLUSION: BMI was an independent predictor of incident diabetes in patients with either heart failure or MI. More than half of the patients with a BMI above 34.9 kg/m(2) developed diabetes during follow-up. Incident diabetes carries an increased mortality risk.

Vitamin K antagonists vs. direct oral anticoagulants after transcatheter aortic valve implantation in atrial fibrillation.

AIMS: To examine the risk of arterial thromboembolism, bleeding, and all-cause mortality in atrial fibrillation (AF) patients treated with direct oral anticoagulants (DOACs) vs. vitamin K antagonists (VKAs) undergoing transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS: In this nationwide observational cohort study, 735 patients undergoing TAVI from 1 January 2012 to 30 June 2017 with a history of AF and who were treated with oral anticoagulants were identified using data from Danish nationwide registries. Of these, 219 (29.8%) and 516 (70.2%) patients were treated with DOACs and VKAs, respectively. The DOAC group was characterized by a higher prevalence of previous arterial thromboembolism and a lower prevalence of chronic kidney disease compared with the VKA group. The distribution of age, sex, CHA2DS2-VASc and HAS-BLED scores, and concomitant antiplatelet therapy was similar between groups. Compared with VKA, treatment with DOACs was not associated with a significantly different 3-year absolute risk of arterial thromboembolism [9.6% (95% confidence interval, CI 4.7-16.5%) vs. 7.4% (95% CI 4.9-10.5%) in the DOAC and VKA group, respectively], bleeding [14.3% (95% CI 7.6-22.9%) vs. 13.3% (95% CI 9.9-17.1%)], or all-cause mortality [32.7% (95% CI 21.8-44.0%) vs. 32.0% (95% CI 26.8-37.3%)]. In adjusted analyses, treatment with DOACs, when compared with VKAs, was not associated with a significantly different rate of arterial thromboembolism [hazard ratio (HR) 1.23 (95% CI 0.58-2.59)], bleeding [HR 1.14 (95% CI 0.63-2.06)], or all-cause mortality [HR 0.93 (95% CI 0.61-1.40)]. CONCLUSION: In patients with AF undergoing TAVI, treatment with DOACs was not associated with a significantly different risk of arterial thromboembolism, bleeding, or all-cause mortality compared with VKA.

Risk of Thromboembolism Associated With Atrial Fibrillation Following Noncardiac Surgery.

BACKGROUND: The long-term risk of thromboembolism in patients developing new-onset post-operative atrial fibrillation (POAF) following noncardiac surgery is unknown, and data on stroke prophylaxis in this setting are lacking. OBJECTIVES: The purpose of this study was to assess the long-term risk of thromboembolism in patients developing new-onset POAF following noncardiac surgery relative to patients with nonsurgical, nonvalvular atrial fibrillation (NVAF). METHODS: Using Danish nationwide registries, the authors identified all patients who developed POAF following noncardiac surgery from 1996 to 2015. These were matched by age, sex, heart failure, hypertension, diabetes, previous thromboembolism, ischemic heart disease, and year of diagnosis to patients with nonsurgical NVAF in a 1:4 ratio. Comparative long-term risk of thromboembolism was examined by multivariable Cox regression models. RESULTS: In patients undergoing noncardiac surgery, 6,048 (0.4%) developed POAF during hospitalization, with the highest incidences following thoracic/pulmonary, vascular, and abdominal surgery. A total of 3,830 patients with POAF were matched with 15,320 patients with NVAF. Oral anticoagulation therapy was initiated within 30 days post-discharge in 24.3% and 41.3% of these patients, respectively (p value <0.001). The long-term risk of thromboembolism was similar in patients with POAF and NVAF (31.7 events vs. 29.9 events per 1,000 person years; hazard ratio [HR]: 0.95; 95% confidence interval [CI]: 0.85 to 1.07). Anticoagulation therapy during follow-up was associated with a comparably lowered risk of thromboembolic events in patients with POAF (HR: 0.52; 95% CI: 0.40 to 0.67) as well as NVAF (HR: 0.56; 95% CI: 0.51 to 0.62) compared with no anticoagulation therapy. CONCLUSIONS: New-onset POAF following noncardiac surgery was associated with a long-term risk of thromboembolism similar to NVAF.

Long-term Thromboembolic Risk in Patients With Postoperative Atrial Fibrillation After Coronary Artery Bypass Graft Surgery and Patients With Nonvalvular Atrial Fibrillation.

Importance: New-onset postoperative atrial fibrillation (POAF) is a common complication of coronary artery bypass graft (CABG) surgery. However, the long-term risk of thromboembolism in patients who develop POAF after CABG surgery remains unknown. In addition, information on stroke prophylaxis in this setting is lacking. Objective: To examine stroke prophylaxis and the long-term risk of thromboembolism in patients with new-onset POAF after first-time isolated CABG surgery compared with patients with nonsurgical, nonvalvular atrial fibrillation (NVAF). Design, Setting, and Participants: This cohort study used data from a clinical cardiac surgery database and Danish nationwide registries to identify patients undergoing first-time isolated CABG surgery who developed new-onset POAF from January 1, 2000, through June 30, 2015. These patients were matched by age, sex, CHA2DS2-VASc score, and year of diagnosis to patients with nonsurgical NVAF in a 1 to 4 ratio. Data analysis was completed from February 2017 to January 2018. Main Outcomes and Measures: The proportion of patients initiating oral anticoagulation therapy within 30 days and the rates of thromboembolism. Results: A total of 2108 patients who developed POAF after CABG surgery were matched with 8432 patients with NVAF. In the full population of 10 540 patients, the median (interquartile range) age was 69.2 (63.7-74.7) years; 8675 patients (82.3%) were men. Oral anticoagulation therapy was initiated within 30 days postdischarge in 175 patients with POAF (8.4%) and 3549 patients with NVAF (42.9%). The risk of thromboembolism was lower in the POAF group than in the NVAF group (18.3 vs 29.7 events per 1000 person-years; adjusted hazard ratio [HR], 0.67; 95% CI, 0.55-0.81; P < .001). Anticoagulation therapy during follow-up was associated with a lower risk of thromboembolic events in both patients with POAF (adjusted HR, 0.55; 95% CI, 0.32-0.95; P = .03) and NVAF (adjusted HR, 0.59; 95% CI, 0.51-0.68; P < .001) compared with patients who did not receive any anticoagulation therapy. Further, the risk of thromboembolism was not significantly higher in patients with POAF compared with those who did not develop POAF after CABG surgery (adjusted HR, 1.11; 95% CI, 0.94-1.32; P < .24). Conclusions and Relevance: New-onset POAF in patients who had undergone CABG surgery was associated with a lower long-term thromboembolic risk than that of patients who had NVAF. These data do not support the notion that new-onset POAF should be regarded as equivalent to primary NVAF in terms of long-term thromboembolic risk.

Familial clustering of atrial fibrillation and comparative longitudinal outcomes of familial and non-familial atrial fibrillation.

Several studies have suggested that family history of atrial fibrillation (AF) is an important risk factor for AF, with several specific genetic regions now implicated through Genome Wide Association Studies. In addition, familial AF is associated with earlier age of onset and affects patients with fewer comorbid conditions than their non-familial counterparts. While those with familial AF have worse symptoms, all-cause mortality and risk of thromboembolic complications are similar among familial and non-familial AF patients.