Source-specific nitrate intake and all-cause mortality in the Danish Diet, Cancer, and Health Study.

INTRODUCTION: Nitrate and nitrite are naturally occurring in both plant- and animal-sourced foods, are used as additives in the processing of meat, and are found in water. There is growing evidence that they exhibit a spectrum of health effects, depending on the dietary source. The aim of the study was to examine source-dependent associations between dietary intakes of nitrate/nitrite and both all-cause and cause-specific mortality. METHODS: In 52,247 participants of the Danish Diet, Cancer and Health Study, associations between source-dependent nitrate and nitrite intakes--calculated using comprehensive food composition and national drinking water quality monitoring databases--and all-cause, cardiovascular disease (CVD)-related, and cancer-related mortality over 27 years were examined using restricted cubic splines within Cox proportional hazards models adjusting for demographic, lifestyle, and dietary confounders. Analyses were stratified by factors hypothesised to influence the formation of carcinogenic N-nitroso compounds (namely, smoking and dietary intakes of vitamin C, vitamin E, folate, and polyphenols). RESULTS: Plant-sourced nitrate intake was inversely associated with all-cause mortality [HRQ5vsQ1: 0.83 (0.80, 0.87)] while higher risks of all-cause mortality were seen for higher intakes of naturally occurring animal-sourced nitrate [1.09 (1.04, 1.14)], additive permitted meat-sourced nitrate [1.19 (1.14, 1.25)], and tap water-sourced nitrate [1.19 (1.14, 1.25)]. Similar source-dependent associations were seen for nitrite and for CVD-related and cancer-related mortality except that naturally occurring animal-sourced nitrate and tap water-sourced nitrate were not associated with cancer-related mortality and additive permitted meat-sourced nitrate was not associated with CVD-related mortality. No clear patterns emerged in stratified analyses. CONCLUSION: Nitrate/nitrite from plant sources are inversely associated while those from naturally occurring animal-sources, additive-permitted meat sources, and tap water-sources are positively associated with mortality.

Source-specific nitrate and nitrite intakes and associations with sociodemographic factors in the Danish Diet Cancer and Health cohort.

Background: The dietary source and intake levels of nitrate and nitrite may govern its deleterious versus beneficial effects on human health. Existing evidence on detailed source-specific intake is limited. The objectives of this study were to assess nitrate and nitrite intakes from different dietary sources (plant-based foods, animal-based foods, and water), characterize the background diets of participants with low and high intakes, and investigate how sociodemographic and lifestyle factors associate with intake levels. Methods: In the Danish Diet, Cancer and Health Cohort, sociodemographic and lifestyle information was obtained from participants at enrolment (1993-1997). Source-dependent nitrate and nitrite intakes were calculated using comprehensive food composition databases, with tap water nitrate intakes estimated via the national drinking water quality monitoring database linked with participants' residential addresses from 1978 to 2016. Underlying dietary patterns were examined using radar plots comparing high to low consumers while sociodemographic predictors of source-dependent nitrate intakes were investigated using linear regression models. Results: In a Danish cohort of 55,754 participants aged 50-65 at enrolment, the median [IQR] intakes of dietary nitrate and nitrite were 58.13 [44.27-74.90] mg/d and 1.79 [1.43-2.21] mg/d, respectively. Plant-based foods accounted for ~76% of nitrate intake, animal-based foods ~10%, and water ~5%. Nitrite intake was sourced roughly equally from plants and animals. Higher plant-sourced nitrate intake was associated with healthier lifestyles, better dietary patterns, more physical activity, higher education, lower age and lower BMI. Females and participants who had never smoked also had significantly higher plant-sourced nitrate intakes. Higher water-sourced nitrate intake was linked to sociodemographic risk factors (smoking, obesity, lower education). Patterns for animal-sourced nitrate were less clear. Conclusion: Participants with higher plant-sourced nitrate intakes tend to be healthier while participants with higher water-sourced nitrate intakes tended to be unhealthier than their low consuming counterparts. Future research in this cohort should account for the sociodemographic and dietary predictors of source-specific nitrate intake we have identified.

Relationship between sex, body size, and cardiac resynchronization therapy benefit: A patient-level meta-analysis of randomized controlled trials.

BACKGROUND: Women might benefit more than men from cardiac resynchronization therapy (CRT) and do so at shorter QRS durations. OBJECTIVE: This meta-analysis was performed to determine whether sex-based differences in CRT effects are better accounted for by height, body surface area (BSA), or left ventricular end-diastolic dimension (LVEDD). METHODS: We analyzed patient-level data from CRT trials (MIRACLE, MIRACLE ICD, MIRACLE ICD II, REVERSE, RAFT, COMPANION, and MADIT-CRT) using bayesian hierarchical Weibull regression models. Relationships between QRS duration and CRT effects were examined overall and in sex-stratified cohorts; additional analyses indexed QRS duration by height, BSA, or LVEDD. End points were heart failure hospitalization (HFH) or death and all-cause mortality. RESULTS: Compared with men (n = 5628), women (n = 1439) were shorter (1.62 [interquartile range, 1.57-1.65] m vs 1.75 [1.70-1.80] m; P < .001), with smaller BSAs (1.76 [1.62-1.90] m2 vs 2.02 [1.89-2.16] m2; P < .001). In adjusted sex-stratified analyses, the reduction in HFH or death was greater for women (hazard ratio, 0.54; credible interval, 0.42-0.70) than for men (hazard ratio, 0.77; credible interval, 0.66-0.89; Pinteraction = .009); results were similar for all-cause mortality even after adjustment for height, BSA, and LVEDD. Sex-specific differences were observed only in nonischemic cardiomyopathy. The effect of CRT on HFH or death was observed at a shorter QRS duration for women (126 ms) than for men (145 ms). Indexing QRS duration by height, BSA, or LVEDD attenuated sex-specific QRS duration thresholds for the effects of CRT on HFH or death but not on mortality. CONCLUSION: Although body size partially explains sex-specific QRS duration thresholds for CRT benefit, it is not associated with the magnitude of CRT benefit. Indexing QRS duration for body size might improve selection of patients for CRT, particularly with a "borderline" QRS duration.

Benefit of cardiac resynchronization therapy among older patients: A patient-level meta-analysis.

BACKGROUND: Cardiac resynchronization therapy (CRT) reduces heart failure hospitalizations (HFH) and mortality for guideline-indicated patients with heart failure (HF). Most patients with HF are aged ≥70 years but such patients are often under-represented in randomized trials. METHODS: Patient-level data were combined from 8 randomized trials published 2002-2013 comparing CRT to no CRT (n = 6,369). The effect of CRT was estimated using an adjusted Bayesian survival model. Using age as a categorical (<70 vs ≥70 years) or continuous variable, the interaction between age and CRT on the composite end point of HFH or all-cause mortality or all-cause mortality alone was assessed. RESULTS: The median age was 67 years with 2436 (38%) being 70+; 1,554 (24%) were women; 2,586 (41%) had nonischemic cardiomyopathy and median QRS duration was 160 ms. Overall, CRT was associated with a delay in time to the composite end point (adjusted hazard ratio [aHR] 0.75, 95% credible interval [CI] 0.66-0.85, P = .002) and all-cause mortality alone (aHR of 0.80, 95% CI 0.69-0.96, P = .017). When age was treated as a categorical variable, there was no interaction between age and the effect of CRT for either end point (P > .1). When age was treated as a continuous variable, older patients appeared to obtain greater benefit with CRT for the composite end point (P for interaction = .027) with a similar but nonsignificant trend for mortality (P for interaction = .35). CONCLUSION: Reductions in HFH and mortality with CRT are as great or greater in appropriately indicated older patients. Age should not be a limiting factor for the provision of CRT.

Dietary Vitamin K1 Intake and Incident Aortic Valve Stenosis.

BACKGROUND: Leaflet calcification contributes to the development and progression of aortic valve stenosis. Vitamin K activates inhibitors of vascular calcification and may modulate inflammation and skeletal bone loss. Therefore, we aimed to determine whether higher dietary intakes of vitamin K1 are associated with a lower incidence of aortic stenosis. METHODS: In the Danish Diet, Cancer and Health study, participants aged 50 to 64 years completed a 192-item food frequency questionnaire at baseline, from which habitual intakes of vitamin K1 were estimated. Participants were prospectively followed using linkage to nationwide registers to determine incident aortic valve stenosis (primary outcome) and aortic stenosis with subsequent complications (aortic valve replacement, heart failure, or cardiovascular disease-related mortality; secondary outcome). RESULTS: In 55 545 participants who were followed for a maximum of 21.5 years, 1085 were diagnosed with aortic stenosis and 615 were identified as having subsequent complications. Participants in the highest quintile of vitamin K1 intake had a 23% lower risk of aortic stenosis (hazard ratio, 0.77 [95% CI, 0.63-0.94]) and a 27% lower risk of aortic stenosis with subsequent complications (hazard ratio, 0.73 [95% CI, 0.56-0.95]), compared with participants in the lowest quintile after adjusting for demographics and cardiovascular risk factors. CONCLUSIONS: In this study, a high intake of vitamin K1-rich foods was associated with a lower incidence of aortic stenosis and a lower risk of aortic stenosis with subsequent complications.

Comorbidities and clinical response to cardiac resynchronization therapy: patient-level meta-analysis from eight clinical trials.

AIMS: Patients with heart failure usually have several other medical conditions that might alter the effects of interventions. We investigated whether the burden of comorbidity modified the clinical response to cardiac resynchronization therapy (CRT). METHODS AND RESULTS: Original patient-level data from eight randomized trials exploring the effects of CRT versus no CRT were pooled (BLOCK-HF, MIRACLE, MIRACLE-ICD, MIRACLE-ICD II, RAFT, COMPANION, MADIT-CRT and REVERSE). A prior history of the following comorbidities was considered: episodic or persistent atrial fibrillation (n = 920), coronary artery disease (n = 3732), diabetes (n = 2171), and hypertension (n = 3353). Patients were classified into three groups based on the number of comorbidities: 0, 1-2, or ≥3. The outcomes of interest were time to all-cause mortality and time to the composite outcome of heart failure hospitalization (HFH) or all-cause mortality. Outcomes were evaluated within each comorbidity group using a Bayesian hierarchical Weibull survival regression model. Of 6324 patients, 970 (15%) had no comorbidities, 4052 (64%) had 1-2 and 1302 (21%) had ≥3 comorbidities. The adjusted hazard ratio (aHR) for CRT versus no CRT for all-cause mortality in the overall cohort was 0.79 (95% credible interval [CI] 0.68-0.93) (p = 0.010); for no comorbidities the aHR was 0.54 (95% CI 0.34-0.86), for 1-2 comorbidities was 0.81 (95% CI 0.67-0.97) and for ≥3 comorbidities was 0.83 (95% CI 0.64-1.07) (no significant interaction between CRT and comorbidity burden: p = 0.13). For the endpoint of HFH or all-cause mortality, the aHR for the overall cohort was 0.74 (95% CI 0.65-0.84) (p = 0.001), for no comorbidities was 0.69 (95% CI 0.50-0.94), for 1-2 comorbidities was 0.77 (95% CI 0.66-0.90) and for ≥3 comorbidities was 0.68 (95% CI 0.55-0.82) (no significant interaction between CRT and comorbidity burden: p = 0.081). CONCLUSION: In a meta-analysis of patient-level data from eight major trials, the totality of evidence suggests that CRT reduces HFH and/or all-cause mortality even when several comorbid diseases are present. CLINICAL TRIAL REGISTRATION: NCT00271154, NCT00251251, NCT00267098, NCT00180271.

Higher Habitual Dietary Intakes of Flavanols and Anthocyanins Differentially Associate with Lower Incidence of Ischemic Stroke Subtypes-A Follow-Up Analysis.

BACKGROUND: We previously reported that habitual consumption of dietary flavanol oligomers + polymers and anthocyanins is associated with a lower risk of ischemic stroke. However, no studies have investigated their relationship with ischemic stroke subtypes. OBJECTIVES: In this follow-up analysis, we aimed to examine the association of flavanol oligomers + polymers and anthocyanin intake with ischemic stroke subtypes, including the following: 1) large-artery atherosclerosis, 2) cardioembolism, 3) small-vessel occlusion, 4) other determined etiology, and 5) undetermined etiology. METHODS: Participants (n = 55,094) from the Danish Diet, Cancer, and Health Study were followed up for <16 y for first-time ischemic stroke events, which were classified according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. Intakes of flavanol oligomers + polymers and anthocyanins were calculated from food frequency questionnaires using the Phenol-Explorer database, and their relationships with ischemic stroke subtypes were investigated using restricted cubic splines within Cox proportional hazards models. After multivariable adjustment, higher habitual intakes (quintile 5 compared with quintile 1) of flavanol oligomers + polymers and anthocyanins were associated with a lower risk of specific ischemic stroke subtypes, including large-artery atherosclerosis [flavanol oligomers + polymers, hazard ratio {HR} (95% confidence interval {CI}): 0.64 (0.47, 0.87)], cardioembolism [anthocyanins, HR (95% CI): 0.45 (0.25, 0.82)], and small-vessel occlusion [flavanol oligomers + polymers, HR (95% CI): 0.65 (0.54, 0.80); anthocyanins, HR (95% CI): 0.79 (0.64, 0.97)], but not stroke of other determined or undetermined etiology. CONCLUSIONS: Higher habitual intakes of flavanols and anthocyanins are differentially associated with a lower risk of ischemic stroke from atherosclerosis and/or cardioembolism but not with other subtypes.

Prevalence of sleep apnea in unselected patients with atrial fibrillation by a home-monitoring device: The DAN-APNO study.

Background: Sleep apnea (SA), a modifiable risk factor in - atrial fibrillation (AF), is associated with worse outcomes in AF. We aimed to assess the prevalence and severity of SA in patients with AF, and, subsequently, to assess the positive predictive value (PPV) of moderate to severe SA by a home-monitoring device in comparison to cardio-respiratory monitoring (CRM) in consecutive patients with AF. Methods: This cross-sectional study recruited unselected patients with AF without known SA from an out-patient clinic at Department of Cardiology, Herlev-Gentofte University Hospital. Participants underwent four consecutive nights of sleep-recording with the home-monitoring device NightOwl™ (NO). Moderate SA was defined as an Apnea-Hypopnea Index (AHI) of 15-29 and severe SA as ≥ 30 AHI. Participants with moderate to severe SA was offered CRM for validation of the diagnosis. Results: We included 126 patients with AF with a median age of 68 (interquartile range: 60-75) years, 42 (33 %) women, 70 (56 %) hypertension, 61 (48 %) hyperlipidemia and 49 (39 %) heart failure. NO detected severe SA in 36 (29 %) of patients with AF, moderate SA in 35 (28 %), mild SA in 45 (36 %) and no SA in 10 (8 %). Of 71 patients with moderate to severe SA by NO, 38 patients underwent CRM and the PPV of NO was 0.82 (31/38) to diagnose moderate SA and 0.92 (22/24) to diagnose severe SA by CRM. Conclusion: Moderate to severe SA by NO was highly prevalent in patients with AF without known SA. A home-monitoring device such as NO could be an easy and feasible SA screening tool in patients with AF.

Cardiac resynchronization therapy in patients with a prior history of atrial fibrillation: Insights from four major clinical trials.

AIMS: To investigate the association of cardiac resynchronization therapy (CRT) on outcomes among participants with and without a history of atrial fibrillation (AF). METHODS: Individual-patient-data from four randomized trials investigating CRT-Defibrillators (COMPANION, MADIT-CRT, REVERSE) or CRT-Pacemakers (COMPANION, MIRACLE) were analyzed. Outcomes were time to a composite of heart failure hospitalization or all-cause mortality or to all-cause mortality alone. The association of CRT on outcomes for patients with and without a history of AF was assessed using a Bayesian-Weibull survival regression model adjusting for baseline characteristics. RESULTS: Of 3964 patients included, 586 (14.8%) had a history of AF; 2245 (66%) were randomized to CRT. Overall, CRT reduced the risk of the primary composite endpoint (hazard ratio [HR]: 0.69, 95% credible interval [CI]: 0.56-0.81). The effect was similar (posterior probability of no interaction = 0.26) in patients with (HR: 0.78, 95% CI: 0.55-1.10) and without a history of AF (HR: 0.67, 95% CI: 0.55-0.80). In these four trials, CRT did not reduce mortality overall (HR: 0.82, 95% CI: 0.66-1.01) without evidence of interaction (posterior probability of no interaction = 0.14) for patients with (HR: 1.09, 95% CI: 0.70-1.74) or without a history of AF (HR: 0.70, 95% CI: 0.60-0.97). CONCLUSION: The association of CRT on the composite endpoint or mortality was not statistically different for patients with or without a history of AF, but this could reflect inadequate power. Our results call for trials to confirm the benefit of CRT recipients with a history of AF.

Vitamin K1 Intake and Incident Diabetes in the Danish Diet, Cancer, and Health Study.

CONTEXT: Observational studies have reported lower risks of type 2 diabetes with higher vitamin K1 intake, but these studies overlook effect modification due to known diabetes risk factors. OBJECTIVE: To identify subgroups that might benefit from vitamin K1 intake, we examined associations between vitamin K1 intake and incident diabetes overall and in subpopulations at risk of diabetes. METHODS: Participants from the prospective cohort, the Danish Diet, Cancer, and Health Study, with no history of diabetes were followed up for diabetes incidence. The association between intake of vitamin K1, estimated from a food frequency questionnaire completed at baseline, and incident diabetes was determined using multivariable-adjusted Cox proportional-hazards models. RESULTS: In 54 787 Danish residents with a median (interquartile range) age of 56 (52-60) years at baseline, 6700 individuals were diagnosed with diabetes during 20.8 (17.3-21.6) years of follow-up. Vitamin K1 intake was inversely and linearly associated with incident diabetes (P < .0001). Compared to participants with the lowest vitamin K1 intake (median:57 µg/d), participants with the highest intakes (median:191 µg/d) had a 31% lower risk of diabetes (HR; 95% CI, 0.69; 0.64-0.74) after multivariable adjustments. The inverse association between vitamin K1 intake and incident diabetes was present in all subgroups (namely, men and women, ever and never smokers, low and high physical activity groups, and in participants who were normal to overweight and obese), with differences in absolute risk between subgroups. CONCLUSION: Higher intake of foods rich in vitamin K1 was associated with a lower risk of diabetes. If the associations observed are causal, our results indicate that more cases of diabetes would be prevented in subgroups at higher risk (men, smokers, participants with obesity, and those with low physical activity).

Cardiac Resynchronization Therapy Improves Outcomes in Patients With Intraventricular Conduction Delay But Not Right Bundle Branch Block: A Patient-Level Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Benefit from cardiac resynchronization therapy (CRT) varies by QRS characteristics; individual randomized trials are underpowered to assess benefit for relatively small subgroups. METHODS: The authors analyzed patient-level data from pivotal CRT trials (MIRACLE [Multicenter InSync Randomized Clinical Evaluation], MIRACLE-ICD [Multicenter InSync ICD Randomized Clinical Evaluation], MIRACLE-ICD II [Multicenter InSync ICD Randomized Clinical Evaluation II], REVERSE [Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction], RAFT [Resynchronization-Defibrillation for Ambulatory Heart Failure], BLOCK-HF [Biventricular Versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block], COMPANION [Comparison of Medical Therapy, Pacing and Defibrillation in Heart Failure], and MADIT-CRT [Multicenter Automatic Defibrillator Implantation Trial - Cardiac Resynchronization Therapy]) using Bayesian Hierarchical Weibull survival regression models to assess CRT benefit by QRS morphology (left bundle branch block [LBBB], n=4549; right bundle branch block [RBBB], n=691; and intraventricular conduction delay [IVCD], n=1024) and duration (with 150-ms partition). The continuous relationship between QRS duration and CRT benefit was also examined within subgroups defined by QRS morphology. The primary end point was time to heart failure hospitalization (HFH) or death; a secondary end point was time to all-cause death. RESULTS: Of 6264 patients included, 25% were women, the median age was 66 [interquartile range, 58 to 73] years, and 61% received CRT (with or without an implantable cardioverter defibrillator). CRT was associated with an overall lower risk of HFH or death (hazard ratio [HR], 0.73 [credible interval (CrI), 0.65 to 0.84]), and in subgroups of patients with QRS ≥150 ms and either LBBB (HR, 0.56 [CrI, 0.48 to 0.66]) or IVCD (HR, 0.59 [CrI, 0.39 to 0.89]), but not RBBB (HR 0.97 [CrI, 0.68 to 1.34]; Pinteraction <0.001). No significant association for CRT with HFH or death was observed when QRS was <150 ms (regardless of QRS morphology) or in the presence of RBBB. Similar relationships were observed for all-cause death. CONCLUSIONS: CRT is associated with reduced HFH or death in patients with QRS ≥150 ms and LBBB or IVCD, but not for those with RBBB. Aggregating RBBB and IVCD into a single "non-LBBB" category when selecting patients for CRT should be reconsidered. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifiers: NCT00271154, NCT00251251, NCT00267098, and NCT00180271.

Recurrent syncope in patients with a pacemaker and bradyarrhythmia.

Background. Pacemakers are used to treat syncope in patients with bradyarrhythmia; however, the risk of recurrent syncope has only been investigated in few and smaller studies. Objective. The aim of this study was to investigate the risk of recurrent syncope after pacemaker implantation in patients with bradyarrhythmia and prior syncope. Methods. This retrospective, population-based cohort study included patients with a prior syncope and implantation of a pacemaker using data from the Danish nationwide registers from 1996 to 2017. Cumulative incidence and cox regression was used to estimate the 5-year incidence and the risk of recurrent syncope, respectively. Results. In total, 11,126 patients (median age: 78 years, interquartile range: 69-85, 56% male) were included and the 5-year cumulative incidence of recurrent syncope was 19.6% (95% confidence interval (CI): 18.8-20.3%). Sinus node dysfunction (hazard ratio [HR]: 1.29, 95%CI: 1.17-1.42) and unspecified type of bradyarrhythmia (HR: 1.32, 95%CI: 1.15-1.52) were associated with an increased risk of syncope compared to advanced atrioventricular (AV) block. Male sex (HR: 1.22, 95%CI: 1.22-1.34), cerebrovascular disease (HR: 1.17, 95%CI: 1.05-1.30), and prior number of syncopes were significantly associated with a higher HR of recurrent syncope. Conclusion. Almost one-in-five patients with bradyarrhythmia and prior syncope who had a pacemaker implanted had a recurrent syncope within five years. A higher risk of syncope was observed among patients with sinus node dysfunction and unspecified type of bradyarrhythmia compared to AV block. Male sex, cerebrovascular disease, and prior number of syncopes were associated risk factors of recurrent syncope.

Intake of dietary flavonoids and incidence of ischemic heart disease in the Danish Diet, Cancer, and Health cohort.

BACKGROUND/OBJECTIVES: Few studies have investigated the association between dietary flavonoid intake, including all major subclasses, and the long-term risk of ischemic heart disease (IHD). We examined whether dietary flavonoid intake associated with IHD incidence, assessing the possible modifying role of sex and smoking, in participants from the Danish Diet, Cancer, and Health study. SUBJECTS/METHODS: In a cohort study design, 54,496 adults (46.8% male), aged 50-64 years, without a history of IHD, were followed for up to 23 years. Habitual dietary flavonoid intake was estimated from food frequency questionnaires using Phenol-Explorer. Incident cases of IHD were identified within Danish nationwide health registries. Restricted cubic splines in Cox proportional hazards models were used to examine associations between flavonoid intake and IHD risk. RESULTS: During follow-up, 5560 IHD events were recorded. No overall association was seen between total flavonoid intake, nor any subclass, and IHD, following adjustment for demographics, lifestyle, and dietary confounders. Stratified by sex and smoking status, higher intakes of specific subclasses associated with lower IHD risk among ever-smokers [Q5 vs. Q1 flavonols HR (95% CI): 0.90 (0.82, 0.99); flavanol oligo+polymers: 0.88 (0.80, 0.97)], but not among never-smokers, nor either sex specifically. CONCLUSIONS: While we did not find clear evidence that higher habitual dietary flavonoid intake was associated with lower IHD risk, these results do not exclude the possibility that certain subclasses may have a protective role in prevention of IHD among population sub-groups; this was evident among smokers, who are at a higher risk of atherosclerosis.

Treatment patterns for oral anticoagulants in older patients with atrial fibrillation: a retrospective, cross-sectional, nationwide study from Denmark.

OBJECTIVES: Atrial fibrillation (AF) is a predominant risk factor of ischaemic stroke and treatment with oral anticoagulants (OACs) is recommended in all patients with risk factors. This study sought to examine treatment patterns of OACs in older patients with AF. DESIGN: Retrospective, cross-sectional study. SETTING: Danish nationwide administrative and clinical registers and databases. PARTICIPANTS: A total of 40 027 patients, >75 years of age, after their first hospital contact due to AF between 2010 and 2018. PRIMARY AND SECONDARY OUTCOMES MEASURES: The primary event of interest was claimed prescriptions for OACs within 180 days after first hospital contact due to AF. Proportions of patients treated with OACs were estimated and clinical factors associated with the probability of receiving OAC treatment were identified using adjusted logistic regression models. RESULTS: A total of 40 027 patients were included with a slight majority of women (54%). The median age was 81 years (IQR 78-86). We found that an overall 32 235 patients (81%) were prescribed an OAC after their first hospital contact due to AF with a marked increase in the proportion of patients treated from 2010 to 2018. Factors related to a decreased probability of receiving treatment were bleeding risk factors such as a history of haemorrhagic stroke (OR 0.21, 95% CI 0.16 to 0.27), any bleeding (OR 0.58, 95% CI 0.53 to 0.62) as well as markers of frailty such as osteoporosis (OR 0.78, 95% CI 0.71 to 0.85). CONCLUSION: In this large nationwide study, we found that in older patients with AF, the overall rates of OAC prescription were generally high (~80%) and increasing during the last decade. Factors associated with not receiving guideline recommended OAC treatment were generally related to bleeding risk factors or frailty.

Prolonged Cardiogenic Shock Due to Hydrogen Sulfide Intoxication Requiring Long-Term Venoarterial Extracorporeal Membrane Support.

We describe a case of severe biventricular failure and cardiovascular collapse following exposure to the manure gas hydrogen sulfide. Initial tests indicated uncoupling of cellular bioenergetics in addition to myocardial damage. Cardiopulmonary support with venoarterial extracorporeal membrane oxygenation was initiated, and the patient could be successfully weaned from support after 28 days. (Level of Difficulty: Advanced.).

Outcomes of Cardiac Resynchronization Therapy with Image-Guided Left Ventricular Lead Placement at the Site of Latest Mechanical Activation: A Systematic Review and Meta-Analysis.

Aim: To assess evidence for an image-guided approach for cardiac resynchronization therapy (CRT) that targets left ventricular (LV) lead placement at the segment of latest mechanical activation. Methods: A systematic review of EMBASE and PubMed was performed for randomized controlled trials (RCTs) and prospective observational studies from October 2008 through October 2020 that compared an image-guided CRT approach with a non-image-guided approach for LV lead placement. Meta-analyses were performed to assess the association between the image-guided approach and NYHA class improvement or changes in end-systolic volume (LVESV), end-diastolic volume (LVEDV), and ejection fraction (LVEF). Results: From 5897 citations, 5 RCTs including 818 patients (426 image-guided and 392 non-image-guided) were identified. The mean age ranged from 66 to 71 years, 76% were male, and 53% had ischemic cardiomyopathy. Speckle tracking echocardiography was the primary image-guided method in all studies. LV lead placement within the segment of the latest mechanical activation (concordant) was achieved in the image-guided arm in 45% of the evaluable patients. There was a statistically significant improvement in the NYHA class at 6 months (odds ratio 1.66; 95% confidence interval (CI) [1.02, 2.69]) with the image-guided approach, but no statistically significant change in LVESV (MD -7.1%; 95% CI [-16.0, 1.8]), LVEDV (MD -5.2%; 95% CI [-15.8, 5.4]), or LVEF (MD 0.68; 95% CI [-4.36, 5.73]) versus the non-image-guided approach. Conclusion: The image-guided CRT approach was associated with improvement in the NYHA class but not echocardiographic measures, possibly due to the small sample size and a low rate of concordant LV lead placement despite using the image-guided approach. Therefore, our meta-analysis was not able to identify consistent improvement in CRT outcomes with an image-guided approach.

Cardiac resynchronization therapy outcomes with left ventricular lead concordant with latest mechanical activation: A meta-analysis.

BACKGROUND: For cardiac resynchronization therapy (CRT), image-guided approaches targeting left ventricular (LV) lead placement at the site of latest mechanical activation had inconsistent outcomes. We examined evidence for improved CRT outcomes when LV lead placement concordant with latest mechanical activation occurred. METHODS: A review of EMBASE and PubMed was performed for randomized controlled trials or prospective observational studies from October 2008 through October 2020 comparing outcomes with concordant versus discordant LV lead placement. Meta-analyses were performed to assess the association between concordance and death, death or heart failure (HF) hospitalization, ≥ 15% reduction in LV end systolic volume (LVESV), and changes in LVESV or ejection fraction (LVEF). RESULTS: From 5897 citations, nine publications (eight studies) with 1355 patients were selected; 975 with a concordant LV lead and 380 with a discordant lead. Mean age was 66-68 years, 82% were male, and 64% had ischemic cardiomyopathy. Meta-analyses demonstrated a statistically significant reduction in death/HF hospitalization at 2 years (OR 0.38; 95% CI 0.16, 0.92) and LVESV at 6 months (mean difference [MD] -13.4%; 95% CI -6.7%, -20.0%), and an increase in LVEF (MD 4.03; 95% CI 0.77, 7.30) with the concordant LV lead. There were trends toward decreased death at 2 years (OR 0.49; 95% CI 0.19, 1.23) and ≥ 15% reduction in LVESV at 6 months (OR 3.81; 95% CI 0.24, 61.24) with concordant LV lead placement. CONCLUSION: A concordant LV lead was associated with better CRT outcomes. Further study of feasible methods to achieve LV lead concordance is needed.

Flavonoid intakes inversely associate with COPD in smokers.

INTRODUCTION: Higher flavonoid intakes are beneficially associated with pulmonary function parameters; however, their association with chronic obstructive pulmonary disease (COPD) is unknown. This study aimed to examine associations between intakes of 1) total flavonoids, 2) flavonoid subclasses and 3) major flavonoid compounds with incident COPD in participants from the Danish Diet, Cancer and Health study. METHODS: This prospective cohort included 55 413 men and women without COPD, aged 50-65 years at recruitment. Habitual flavonoid intakes at baseline were estimated from a food frequency questionnaire using Phenol-Explorer. Danish nationwide registers were used to identify incident cases of COPD. Associations were modelled using restricted cubic splines within Cox proportional hazards models. RESULTS: During 23 years of follow-up, 5557 participants were diagnosed with COPD. Of these, 4013 were current smokers, 1062 were former smokers and 482 were never-smokers. After multivariable adjustments, participants with the highest total flavonoid intakes had a 20% lower risk of COPD than those with the lowest intakes (quintile 5 versus quintile 1: HR 0.80, 95% CI 0.74-0.87); a 6-22% lower risk was observed for each flavonoid subclass. The inverse association between total flavonoid intake and COPD was present in both men and women but only in current smokers (HR 0.77, 95% CI 0.70-0.84) and former smokers (HR 0.82, 95% CI 0.69-0.97), not never-smokers. Furthermore, higher flavonoid intakes appeared to lessen, but not negate, the higher risk of COPD associated with smoking intensity. CONCLUSION: Dietary flavonoids may be important for partially mitigating the risk of smoking-related COPD. However, smoking cessation should remain the highest priority.

Protocol for detecting unrecognized sleep apnea in patients with atrial fibrillation by a home-monitoring device: the DAN-APNO study.

BACKGROUND: Determining the presence of modifiable risk factors for atrial fibrillation (AF), such as sleep apnea is of clinical importance due to the potential impact targeting these risk factors can have on the progression and burden of AF. Using new digital-based technology is a promising solution to the underreporting of sleep apnea highlighted by academical societies in recent years. The aim of this study is to report the prevalence and severity of sleep apnea in patients with AF and, secondarily, assess the accuracy and feasibility of a new home-screening device for sleep apnea (NightOwl™ by Ectosense). METHODS: DAN-APNO is a cross-sectional study at the Department of Cardiology, Herlev-Gentofte Hospital recruiting patients with AF referred to anticoagulation initiation aged 18 to 90 years without known sleep apnea. At least 150 patients will be recruited and undergo medical history, clinical evaluation, several sleep-apnea questionnaires, and a sleep-recording evaluation for four nights with sleep apnea home-monitoring device NightOwl™. Additionally, the first 20 participants and participants with moderate-severe sleep apnea by screening are referred to cardio-respiratory monitoring (CRM). This clinical evaluation allows the comparison of standard evaluation method and the NightOwl™. Clinical measures include Apnea-Hypopnea Index (AHI), Oxygen Desaturation Index (ODI), pulse rate, as well as questionaries about sleep apnea assessment and the clinical feasibility of the NightOwl™ device. Main outcomes comprise analysis of the prevalence and severity of sleep apnea, and clinical and demographic predictors of moderate and severe sleep apnea. In addition, correlation analyses for accuracy measures between CRM and NightOwl™ will be conducted along with patient ease-of-use and satisfaction questionnaires. DISCUSSION: This study is limited by selection bias; only patients with atrial fibrillation from anticoagulation clinic is asked to participate, which could limit the generalizability of our results. However, this study aims to test whether a miniaturized simple home-monitoring device for detecting sleep apnea in patients with AF potentially can evaluate sleep apnea more conveniently and easier. Trial Registration The study is registered the 18-02-2021 at clinicaltrials.gov with registration number: NCT04760002.

Treatment of older patients with atrial fibrillation by morbidity burden.

AIMS: Older patients with atrial fibrillation (AF) are at risk of adverse outcomes, which is accentuated by comorbidities. We sought to examine the association between morbidity burden and the treatment of older AF patients. METHODS AND RESULTS: Using Danish nationwide registers we included patients ≥70 years of age between 2010 and 2017 at their first hospitalization due to AF. Using multiple logistic regression models we examined the association between morbidity burden and the odds of receiving oral anticoagulants (OACs), anti-arrhythmic drugs (AADs), and rhythm-control procedures (direct current cardioversions and catheter ablations). A total of 48 995 patients were included with a majority of women (54%), with a median age of 80 years [interquartile range (IQR) 75-85], and a median morbidity burden of 2 comorbidities (IQR 1-3). Increasing morbidity burden was associated with decreasing odds of OAC treatment with patients having >5 comorbidities having the lowest odds [odds ratio (OR) 0.38, 95% confidence interval (CI) 0.35-0.42] compared to patients with low morbidity burden (0-1 comorbidities). Having >5 comorbidities were associated with increased odds of AAD treatment (OR 1.90, 95% CI 1.64-2.21) and decreased odds of AF procedures (OR 0.39, 95% CI 0.31-0.48), compared to patients with a low morbidity burden (0-1 comorbidities). Examining morbidity burden continuously revealed similar results. CONCLUSIONS: In older AF patients, multimorbidity was associated with lower odds of receiving OACs and rhythm-control procedures but increased odds of AADs. This presents a clinical conundrum as multimorbid patients potentially benefit the most from treatment with OACs.