Severe mental illness: cardiovascular risk assessment and management.

Patients with severe mental illness (SMI) including schizophrenia and bipolar disorder die on average 15-20 years earlier than the general population often due to sudden death that, in most cases, is caused by cardiovascular disease. This state-of-the-art review aims to address the complex association between SMI and cardiovascular risk, explore disparities in cardiovascular care pathways, describe how to adequately predict cardiovascular outcomes, and propose targeted interventions to improve cardiovascular health in patients with SMI. These patients have an adverse cardiovascular risk factor profile due to an interplay between biological factors such as chronic inflammation, patient factors such as excessive smoking, and healthcare system factors such as stigma and discrimination. Several disparities in cardiovascular care pathways have been demonstrated in patients with SMI, resulting in a 47% lower likelihood of undergoing invasive coronary procedures and substantially lower rates of prescribed standard secondary prevention medications compared with the general population. Although early cardiovascular risk prediction is important, conventional risk prediction models do not accurately predict long-term cardiovascular outcomes as cardiovascular disease and mortality are only partly driven by traditional risk factors in this patient group. As such, SMI-specific risk prediction models and clinical tools such as the electrocardiogram and echocardiogram are necessary when assessing and managing cardiovascular risk associated with SMI. In conclusion, there is a necessity for differentiated cardiovascular care in patients with SMI. By addressing factors involved in the excess cardiovascular risk, reconsidering risk stratification approaches, and implementing multidisciplinary care models, clinicians can take steps towards improving cardiovascular health and long-term outcomes in patients with SMI.

The Danish Nationwide Electrocardiogram (ECG) Cohort.

The electrocardiogram (ECG) is a non-invasive diagnostic tool holding significant clinical importance in the diagnosis and risk stratification of cardiac disease. However, access to large-scale, population-based digital ECG data for research purposes remains limited and challenging. Consequently, we established the Danish Nationwide ECG Cohort to provide data from standard 12-lead digital ECGs in both pre- and in-hospital settings, which can be linked to comprehensive Danish nationwide administrative registers on health and social data with long-term follow-up. The Danish Nationwide ECG Cohort is an open real-world cohort including all patients with at least one digital pre- or in-hospital ECG in Denmark from January 01, 2000, to December 31, 2021. The cohort includes data on standardized and uniform ECG diagnostic statements and ECG measurements including global parameters as well as lead-specific measures of waveform amplitudes, durations, and intervals. Currently, the cohort comprises 2,485,987 unique patients with a median age at the first ECG of 57 years (25th-75th percentiles, 40-71 years; males, 48%), resulting in a total of 11,952,430 ECGs. In conclusion, the Danish Nationwide ECG Cohort represents a novel and extensive population-based digital ECG dataset for cardiovascular research, encompassing both pre- and in-hospital settings. The cohort contains ECG diagnostic statements and ECG measurements that can be linked to various nationwide health and social registers without loss to follow-up.

Temporal trends in characteristics and outcomes after myocardial infarction in patients with and without peripheral artery disease - A Nationwide, register-based follow-up study.

AIM: Patients with peripheral artery disease (PAD) represent a high-risk population with increased morbidity and mortality. We aimed to examine trends in myocardial infarction (MI), PAD and adverse clinical outcomes from years 2000 to 2019. METHODS: This nationwide Danish-based registry study included all patients with MI from years 2000-2019. Patients with PAD were compared to patients without PAD. Temporal changes in PAD prevalence over time was examined using the Cochrane-Armitage trend test, and Cox regression was used to test for between-group significance in all care and outcome measures. RESULTS: A total of 196,635 patients experienced an MI within the study time frame; the prevalence of PAD over time showed a slight increase (p < 0.01). Patients with MI and a concurrent PAD diagnosis elicited a heavier burden of comorbidities. The primary MACE endpoint showed significant decreases in both patients with and without PAD (p < 0.01); the decrease was more marked in patients without a concurrent PAD diagnosis (p < 0.01) alongside with 1-year all-cause mortality (p < 0.01). There was a slight increase in initiation of preventive pharmacotherapy with a prominent increase in initiation of P2Y12-inhibitors post discharge in patients without PAD in comparison to patients with PAD, and the same pattern applied for lipid lowering agents (p < 0.01). Also, there was an increase in revascularization in patients with MI but more markedly in patients without coexisting PAD. CONCLUSIONS: Despite significant decreases in MACE and mortality and significant increases in guideline-recommended care and revascularization over time for MI patients both with and without PAD, improvement in all these measures was less prominent in patients with MI and concomitant PAD.

Serial troponin-I and long-term outcomes in subjects with suspected acute coronary syndrome.

AIMS: It is unclear how serial high-sensitivity troponin-I (hsTnI) concentrations affect long-term prognosis in individuals with suspected acute coronary syndrome (ACS). METHODS AND RESULTS: Subjects who underwent two hsTnI measurements (Siemens TnI Flex® Reagent) separated by 1-7 h, during a first-time hospitalization for myocardial infarction, unstable angina, observation for suspected myocardial infarction, or chest pain from 2012 through 2019, were identified through Danish national registries. Individuals were stratified per their hsTnI concentration pattern (normal, rising, persistently elevated, or falling) and the magnitude of hsTnI concentration change (<20%, >20-50%, or >50% in either direction). We calculated absolute and relative mortality risks standardized to the distributions of risk factors for the entire study population. A total of 20 609 individuals were included of whom 2.3% had died at 30 days, and an additional 4.7% had died at 365 days. The standardized risk of death was highest among persons with a persistently elevated hsTnI concentration (0-30 days: 8.0%, 31-365 days: 11.1%) and lowest among those with two normal hsTnI concentrations (0-30 days: 0.5%, 31-365 days: 2.6%). In neither case did relative hsTnI concentration changes between measurements clearly affect mortality risk. Among persons with a rising hsTnI concentration pattern, 30-day mortality was higher in subjects with a >50% rise compared with those with a less pronounced rise (2.2% vs. <0.1%). CONCLUSION: Among individuals with suspected ACS, those with a persistently elevated hsTnI concentration consistently had the highest risk of death. In subjects with two normal hsTnI concentrations, mortality was very low and not affected by the magnitude of change between measurements.

In this Danish study of >20 000 individuals with suspected heart attack, we confirmed the clinical importance of drawing two consecutive blood samples for measurement of high-sensitivity troponin-I concentrations (a marker of damage to the heart): The risk of death was highest in persons with two elevated high-sensitivity troponin-I concentrations and lowest in those with two normal concentrations.Among persons who had a first normal and a subsequently elevated high-sensitivity troponin-I concentration, a >50% relative rise was associated with significantly higher risk of death at 30 days.

Trends in Medical and Device Therapies Following Incident Heart Failure in Denmark during 1996-2019: A Nationwide Register-Based Follow-Up Study.

Introduction: Data on temporal trends in guideline-based medical and device therapies in real-world chronic heart failure (HF) patients are lacking. Methods: Register-based nationwide follow-ups of temporal trends in characteristics, guideline-recommended therapies, one-year all-cause mortality, and HF rehospitalizations in incident HF patients in Denmark during 1996-2019. Results: Among 291,720 incident HF patients, the age at the onset of HF was stable over time. While initially fairly equal, the sex distribution markedly changed over time with more incidents occurring in men overall. Hypertension and diabetes increased significantly over time, while other comorbidities remained stable. Between 1996 and 2019, significant increases in angiotensin-converting enzyme inhibitor and angiotensin II-receptor blocker (ACEi/ARB) therapy (38.2% to 69.9%), beta-blocker therapy (15.5% to 70.6%), and mineralocorticoid receptor antagonist (MRA) therapy (11.8% to 34.5%) were seen. Angiotensin receptor-neprilysin inhibitor (ARNI) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) were introduced in the middle of the past decade, with minor increases but overall low uses: ARNI (2015: 0.1% vs. 2019: 3.9%) and SGLT2i (2012: <0.1% vs. 2019: 3.9%). Between 1999 and 2019, implantable cardioverter-defibrillator (ICD) use increased significantly: 0.1% to 3-4%. Cardiac resynchronization therapy (CRT) use similarly increased between 2000 and 2019: 0.2% to 2.3%. Between 1996 and 2019, one-year all-cause mortality decreased significantly: 34.6% to 20.9%, as did HF rehospitalizations (6% to 1.3%). Conclusions: Among 291,720 incident HF patients in Denmark during 1996-2019, significant increases in the use of ACEi/ARB, beta-blockers, MRAs, and devices were seen, with concurrent significant decreases in the one-year all-cause mortality and HF rehospitalization rates. The use of CRT, ARNI, and SGLT2i remained low, and MRAs were relatively underutilized, thereby representing future targets to potentially further improve HF prognoses.

Increased risk of cardiovascular disease preceding diagnosis of incident ANCA-associated vasculitis: a Danish nationwide study.

OBJECTIVE: To examine if patients with ANCA-associated vasculitis (AAV) have an increased risk of cardiovascular disease in the months prior to diagnosis of AAV. METHODS: Using a nested case-control framework, patients with Granulomatosis with polyangiitis and Microscopic polyangiitis were identified through Danish Nationwide Registries from 1996-2021 and matched 1:3 with age- and sex-matched controls without AAV. Each control was assigned the same index date (date of AAV-diagnosis) as their corresponding case. Conditional logistic regression was used to compute adjusted Hazard Ratios (HRs) for major adverse cardiovascular events (MACE), ischemic heart disease, coronary angiogram, heart failure, venous thromboembolism, atrial fibrillation, ischemic stroke, pericarditis, and ventricular arrhythmias/ICD-implantation/cardiac arrest (VA/ICD/CA) within 12 months, 6 months, 3 months, 2 months and 1 month before index date. RESULTS: A total of 2371 patients with AAV (median age: 63yrs, 53.7% male) were matched with 7113 controls. The prevalence of any cardiovascular outcome and MACE within 12 months preceding index date were 10.3% and 2.4% for AAV, compared to 3.8% (HR 3.05[2.48-3.75]) and 1.3% (HR 1.98[1.39-2.82]) of controls. The risk of cardiovascular outcomes was similarly increased in temporal proximity to the diagnosis, with the highest HR at 1 month prior to index date: Any cardiovascular outcome (HR 10.73[7.05-16.32]) and MACE (HR 5.78[2.67-12.52]). In individual analysis, a significantly higher rate was observed for all outcomes (excluding VA/ICD/CA). CONCLUSIONS: AAV disease is associated with an increased risk of cardiovascular disease in the months preceding diagnosis, which underlines the importance of early clinical vigilance toward cardiovascular disease.

Peripheral artery disease in patients with schizophrenia as compared to controls.

BACKGROUND: Patients with schizophrenia have an increased prevalence of risk factors for peripheral artery disease (PAD) and is expected to have an increased prevalence of PAD. PAD can be detected utilizing toe-brachial index (TBI) which screens for vascular pathology proximal to the toes. METHODS: Using a cross-sectional design, we defined the subpopulations: (1) Patients diagnosed with schizophrenia less than 2 years before inclusion (SCZ < 2), (2) Psychiatric healthy controls matched to subpopulation 1 on sex, age, and smoking status, and (3) Patients diagnosed with schizophrenia 10 or more years before inclusion (SCZ ≥ 10). TBI was calculated by dividing toe pressures by systolic brachial blood pressure, and PAD was defined by TBI < 0.70. Logistic regression analysis with PAD as outcome and sex, age, smoking status, BMI, skin temperature, diagnosis of schizophrenia, and comorbidities as explanatory variables was conducted. RESULTS: PAD was present in 26.2% of patients diagnosed with SCZ < 2 (17 of 65) and in 18.5% of psychiatric healthy controls (12 of 65) with no statistically significant difference in prevalence rates (p = 0.29). PAD was present in 22.0% of patients diagnosed with SCZ ≥ 10 (31 of 141). In logistic regression, patients diagnosed with SCZ < 2 had an increased odds of PAD with psychiatric healthy controls as reference (Odds ratio = 2.80, 95% confidence interval 1.09-7.23, p = 0.03). The analysis was adjusted for age, sex, smoking status, BMI and comorbidities such as hypertension, diabetes and heart disease. CONCLUSIONS: This study did not find statistically significant increased prevalence rates of PAD in patients with schizophrenia even though patients with SCZ were compared to psychiatric healthy controls using TBI. Utilizing logistic regression PAD was associated with schizophrenia diagnosis within the last 2 years, age and skin temperature. As PAD is initially asymptomatic, screening could be relevant in patients with schizophrenia if other risk factors are prevalent. Further large-scale multicenter studies are warranted to investigate schizophrenia as a potential risk factor for PAD. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT02885792.

Time trends of coronary procedures, guideline-based drugs and all-cause mortality following acute coronary syndrome in patients with bipolar disorder.

AIM: This study analyzed time trends in the use of coronary procedures, guideline-based drugs, and 1-year all-cause and presumed cardiovascular mortality (CV) following acute coronary syndrome (ACS) in patients with and without bipolar disorder (BD). METHOD: Using Danish registries 497 patients with ACS and BD in the period 1996-2016 were matched 1:2 on age, sex and year of ACS to patients without preexisting psychiatric disease. RESULTS: Patients with BD and ACS received fewer coronary angiography (CAG) compared to psychiatric healthy controls (PHC). However, the difference between the populations decreased over time. For percutaneous coronary intervention (PCI) and coronary artery bypass (CABG) no differences in trend over time were found. In general patients with BD redeemed fewer prescriptions of guideline-based tertiary prophylactic drugs compared to PHCs. The difference remains constant over time for all drugs except for acetylsalicylic acid, lipid-lowering drugs and beta blockers, where the difference decreased. The 1-year all-cause mortality gap and the presumed CV mortality gap remained unchanged. CONCLUSION: Despite improvements in treatment disparities regarding CAG, acetylsalicylic acid, lipid-lowering drugs and beta-blockers, the treatment gap remained unchanged concerning PCI and CABG. Likewise, patients with BD experienced a lower rate of the remaining redeemed prescriptions. The overall crude mortality risk ratio for patients with BD experiencing ACS remained unchanged over the study period compared to PHC.

Electrocardiographic P terminal force in lead V1, its components, and the association with stroke and atrial fibrillation or flutter.

BACKGROUND: The electrocardiographic (ECG) marker P terminal force V1 (PTFV1) is generally perceived as a marker of left atrial pathology and has been associated with atrial fibrillation or flutter (AF). OBJECTIVE: The purpose of this study was to determine the association between PTFV1 components (duration and amplitude) and incident AF and stroke/transient ischemic attack (TIA). METHODS: The study included patients with an ECG recorded at the Copenhagen General Practitioners Laboratory in 2001 to 2011. PTFV1 ≥4 mV·ms was considered abnormal. Patients with abnormal PTFV1 were stratified into tertiles based on duration (PTDV1) and amplitude (PTAV1) values. Cox regressions adjusted for age, sex, and relevant comorbidities were used to investigate associations between abnormal PTFV1 components and AF and stroke/TIA. RESULTS: Of 267,636 patients, 5803 had AF and 18,176 had stroke/TIA (follow-up 6.5 years). Abnormal PTFV1 was present in 44,549 subjects (16.7%) and was associated with an increased risk of AF and stroke/TIA. Among patients with abnormal PTFV1, the highest tertile of PTDV1 (78-97 ms) was associated with the highest risk of AF (hazard ratio [HR] 1.37; 95% confidence interval [CI] 1.23-1.52) and highest risk of stroke/TIA (HR 1.13; 95% CI 1.05 -1.20). For PTAV1, the highest tertile (78-126 µV) conferred the highest risk of AF and stroke/TIA (HR 1.20; 95% CI 1.09-1.32; and HR 1.21; 95% CI 1.14-1.25, respectively). CONCLUSION: Abnormal PTFV1 was associated with an increased risk of AF and stroke/TIA. Increasing PTDV1 showed a dose-response relationship with the development of AF and stroke/TIA, whereas the association between PTAV1 and AF was less apparent.

Long-term cardiovascular outcomes and temporal trends in patients diagnosed with ANCA-associated vasculitis: a Danish nationwide registry study.

OBJECTIVES: To examine long-term cardiovascular outcomes and temporal trends among patients with ANCA-associated vasculitis (AAV) using Danish nationwide registries. METHODS: Using a cohort design, we examined patients with granulomatosis with polyangiitis (ICD-10: DM31.3) and microscopic polyangiitis (ICD-10: DM3.17) in Denmark from 1996-2018. Hazard ratios (HRs) of cardiovascular outcomes were compared between patients with AAV and age and gender-matched controls. Counterfactual G-estimation of HRs was performed to estimate 5-year absolute risks. Temporal trends were obtained by grouping cohorts into evenly distributed tertiles according to inclusion year. RESULTS: A total of 2306 patients with AAV (median age: 62.9yrs, 52.6% male) were matched with 6918 controls. Median follow-up was 9.5yrs. Patients with AAV had a higher rate of ischaemic heart disease [HR 1.86 (1.62-2.15)], myocardial infarction [HR 1.62 (1.26-2.09)], coronary angiogram [HR 1.64 (1.37-1.96)], percutaneous coronary intervention [HR 1.56 (1.17-2.07)] and ventricular arrhythmias/implantable-cardioverter-defibrillator (ICD)-implantations [HR 2.04 (1.16-3.57)]. Similarly, an increased rate of heart failure [HR 2.12 (1.77-2.54)], deep vein thrombosis [HR 3.13 (2.43-4.05)], pulmonary embolism [HR 4.04 (3.07-5.32)], atrial fibrillation [HR 2.08 (1.82-2.39)], ischaemic stroke [HR 1.58 (1.31-1.90)] and in-hospital cardiac arrest [HR 2.27 (1.49-3.48)] was observed. The 5-year risk of all outcomes were significantly higher (excluding ventricular arrhythmia/ICD-implantations). For temporal trends among patients with AAV, a decreased 3-year risk of cardiovascular mortality was observed over time. CONCLUSIONS: Patients with AAV are at increased risk of heart failure, atrial-/ventricular arrhythmias, venous thrombotic events, ischaemic stroke and myocardial infarction. Furthermore, patients with AAV were more frequently examined with coronary procedures and underwent more coronary revascularizations. No temporal changes in ischaemic cardiovascular outcomes were observed, albeit the cardiovascular mortality has decreased over time.

Cardiovascular autonomic reflex tests using a handheld device in the diagnosis of cardiovascular autonomic neuropathy in patients with schizophrenia.

Study objective: This study investigated whether schizophrenia and the duration of schizophrenia were associated with cardiovascular autonomic neuropathy (CAN) by using heart rate variability (HRV) as a marker. Design: Cross-sectional study. Setting: The examinations were conducted at the Centre for Psychosis Research and at the Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark. Participants: 240 patients with first-episode and chronic schizophrenia and 180 controls. Interventions: CAN was assessed by the cardiovascular reflex tests (CARTs): HR, RS ratio, E:I ratio, and VM using a handheld device. Main outcome measures: One abnormal CART was interpreted as borderline CAN and ≥2 abnormal CARTs established definitive CAN. Borderline CAN and definitive CAN together was categorized as overall CAN. Analyses were adjusted for age, sex, smoking, overweight, and hypercholesterolemia. Results: A total of 240 patients with schizophrenia (median age 42.5 [28.8, 52.3], 42.9 % women) and 180 controls (median age 45.8 [24.0, 60.1], 47.8 % women) were included, with 50.8 % of patients with schizophrenia having overall CAN compared to 27.2 % among controls. Dividing patients into patients with first-episode and chronic schizophrenia, 32.9 % vs 10 % (p < 0.001) and 59.1 % vs 41 % (p < 0.001) had overall CAN compared with controls, respectively. Schizophrenia was significantly associated with overall CAN (OR, 2.80; 95%CI, 1.75-4.50), with an OR of 2.31 (95%CI, 1.14-4.68) for first-episode schizophrenia and an OR of 2.97 (95%CI, 1.81-4.87) for chronic schizophrenia. Conclusion: It was demonstrated that a diagnosis of schizophrenia was associated with CAN. Patients with chronic schizophrenia had a significantly higher prevalence of CAN compared to patients with first-episode schizophrenia, suggesting an association between the duration of schizophrenia and CAN.

Prognostic implications of serial high-sensitivity cardiac troponin testing among patients with COVID-19: A Danish nationwide registry-based cohort study.

Background: Although troponin elevation is associated with worse outcomes among patients with coronavirus disease 2019 (COVID-19), prognostic implications of serial troponin testing are lacking. We investigated the association between serial troponin measurements and adverse COVID-19 outcomes. Methods: Using Danish registries, we identified COVID-19 patients with a high-sensitivity troponin measurement followed by a second measurement within 1-24 h. All measurements during follow-up were also utilized in subsequent time-varying analyses. We assessed all-cause mortality associated with the absence/presence of myocardial injury (≥1 troponin measurement >99th percentile upper reference limit) and absence/presence of dynamic troponin changes (>20% relative change if first measurement elevated, >50% relative change if first measurement normal). Results: Of 346 included COVID-19 patients, 56% had myocardial injury. Overall, 20% had dynamic troponin changes. In multivariable Cox regression models, myocardial injury was associated with all-cause mortality (HR = 2.56, 95%CI = 1.46-4.51), as were dynamic troponin changes (HR = 1.66, 95%CI = 1.04-2.64). We observed a low incidence of myocardial infarction (4%) and invasive coronary procedures (4%) among patients with myocardial injury. Conclusions: Myocardial injury and dynamic troponin changes determined using serial high-sensitivity troponin testing were associated with poor prognosis among patients with COVID-19. The risk of developing myocardial infarction requiring invasive management during COVID-19 hospitalization was low.

Risk of out-of-hospital cardiac arrest in antidepressant drug users.

Conflicting results have been reported regarding the association between antidepressant use and out-of-hospital cardiac arrest (OHCA) risk. We investigated whether the use of antidepressants is associated with OHCA. METHODS: We conducted a nationwide nested case-control study to assess the association of individual antidepressant drugs within drug classes with the hazard of OHCA. Cases were defined as OHCA from presumed cardiac causes. Cox regression with time-dependent exposure and time-dependent covariates was conducted to calculate hazard ratios (HR) and 95% confidence intervals (95% CIs) overall and in subgroups defined by established cardiac disease and cardiovascular risk factors. Also, we studied antidepressants with and without sodium channel blocking or potassium channel blocking properties separately. RESULTS: During the study period from 2001 to 2015 we observed 10 987 OHCA cases, and found increased OHCA rate for high-dose citalopram (>20 mg) and high-dose escitalopram (>10 mg; HR:1.46 [95% CI:1.27-1.69], HR:1.43 [95% CI:1.16-1.75], respectively) among selective serotonin reuptake inhibitors (reference drug sertraline), and for high-dose mirtazapine (>30; HR:1.59 [95% CI:1.18-2.14]) among the serotonin-norepinephrine reuptake inhibitors or noradrenergic and specific serotonergic antidepressants (reference drug duloxetine). Among tricyclic antidepressants (reference drug amitriptyline), no drug was associated with significantly increased OHCA rate. Increased OHCA rate was found for antidepressants with known potassium channel blocking properties (HR:1.14 [95% CI:1.05-1.23]), but for not those with sodium channel blocking properties. Citalopram, although not statistically significant, and mirtazapine were associated with increased OHCA rate in patients without cardiac disease and cardiovascular risk factors. CONCLUSION: Our findings indicate that careful titration of citalopram, escitalopram and mirtazapine dose may have to be considered due to drug safety issues.

The Relationship Between Valproate and Lamotrigine/Levetiracetam Use and Prognosis in Patients With Epilepsy and Heart Failure: A Danish Register-Based Study.

OBJECTIVE: To compare the hazard for all-cause mortality and mortality due to heart failure (HF) between valproate (VPA) and levetiracetam (LEV)/lamotrigine (LTG) users in patients aged ≥ 65 with comorbidities of epilepsy and HF. METHODS: This was a cohort study using Danish registers during the period from January 1996 to July 2018. The study population included new users of LTG, LEV or VPA. A Cox regression model was used to compute crude and adjusted hazard ratios for the outcome, using an intention-to-treat approach. Average treatment effects (eg, 1-year absolute risks), risk differences and the ratio of risks were computed using the G-formula based on a Cox regression model for the outcomes at the end of the follow-up period. RESULTS: We included 1345 subjects in the study population. VPA users (n = 696), when compared to LTG/LEV users (n = 649), had an increased hazard of mortality due to HF (hazard ratio [HR] 2.39; 95% CI 1.02-5.60) and to all-cause mortality (HR 1.37; 95% CI 1.01-1.85) in both crude and adjusted analyses. The 1-year absolute risks for all-cause mortality were 29% (95% CI 25%-33%) and 22% (95% CI 18%-26%) for VPA and LTG/LEV users. For mortality due to HF, 1-year absolute risks were 5% (95% CI 3%-7%) and 2% (95% CI 1%-4%) for VPA and LTG/LEV users. The average risk ratio, with LTG/LEV as the reference group, was 1.31 (95% CI 1.02-1.71) for all-cause mortality and 2.35 (95% CI 1.11-5.76) for HF mortality. CONCLUSION: In older people with HF and epilepsy, treatment with VPA was associated with a higher risk of all-cause and HF mortality compared to treatment with LTG and LEV.

Hepatic steatosis in patients with schizophrenia: a clinical cross-sectional study.

OBJECTIVE: With hepatic steatosis (HS) being an established risk factor for CVD in the general population, it may also be a predictor of CVD in patients with schizophrenia. The aim of the present study was to investigate if time since schizophrenia diagnosis, body mass index (BMI), sex, metabolic syndrome, alcohol use, smoking, alanine transaminase (ALT), and body fat percentage (as measured by bioelectrical impedance) were associated with HS, determined by computed tomography (CT), in a population of patients diagnosed with schizophrenia. METHODS: Moderate to severe HS (40 CT Hounsfield units as threshold) was determined utilizing non-contrast enhanced CT. The association between the explanatory variables and outcome of HS was assessed using multivariable logistic regression. RESULTS: In the present study, 145 patients diagnosed with schizophrenia (mean age 42.2 years (SD ± 13.8)) were included, with 88 (60.7%) being male. On average, patients had been diagnosed for 14.8 (SD ± 10.7) years. A total of 31 (21.4%) patients had HS as determined by CT. The presence of HS was associated with ALT (OR 1.06, 95% CI (1.02-1.10) per 1 U/L increase), and the presence of metabolic syndrome (OR 62.89, 95% CI (2.03-1949.55)). The presence of HS was not associated with BMI, body fat percentage or time since diagnosis in the multivariable analysis. CONCLUSION: Higher ALT and the presence of metabolic syndrome were associated with HS in patients with schizophrenia utilizing multivariable analysis. The findings suggest that risk factors for HS are similar in both the general population and in patients with schizophrenia.

Periprocedural complications and one-year outcomes after catheter ablation for treatment of atrial fibrillation in elderly patients: a nationwide Danish cohort study.

OBJECTIVES: To investigate complications within 30-days following first-time ablation for atrial fibrillation (AF), including a composite of cardiac tamponade, hematoma requiring intervention, stroke or death, in patients ≥ 75 years of age, compared to patients aged 65-74 years. In addition, one-year all-cause mortality and AF relapse were compared. METHODS & RESULTS: All patients receiving their first catheter ablation for AF between 2012 and 2016 were identified using Danish nationwide registries. Patients aged 65-74 years served as the reference group for patients ≥ 75 years. Relapse of AF within one year was defined as cardioversion following a three-month blanking period, re-ablation or confirmed relapse within follow-up. The composite complication outcome did not differ between the two age groups, with 39/1554 (2.8%) in patients 65-74 years of age, versus 5/199 (2.5%) in older patients (adjusted HR = 0.94), 95% CI: 0.37-2.39, P = 0.896). Patients ≥ 75 years or older had no increased hazard of death within 30 days after the procedure, with an incidence of 3/1554 (0.2%) in younger patients and 2/199 (1.0%) in patients ≥ 75 years of age (adjusted HR = 4.71, 95% CI: 0.78-28.40, P = 0.091). There was no difference in relapse of AF after one year between age groups (≥ 75 years adjusted HR = 1.00, 95% CI: 0.78-1.26, P = 0.969). CONCLUSION: In patients ≥ 75 years of age selected for catheter ablation for AF, the incidence of periprocedural complications, as well as one-year freedom from AF showed no statistical difference, when compared to patients 65-74 years of age.

Temporal trends in patient characteristics, presumed causes, and outcomes following cardiogenic shock between 2005 and 2017: a Danish registry-based cohort study.

AIMS: Most cardiogenic shock (CS) studies focus on acute coronary syndrome (ACS). Contemporary data on temporal trends in patient characteristics, presumed causes, treatments, and outcomes of ACS- and in particular non-ACS-related CS patients are sparse. METHODS AND RESULTS: Using nationwide medical registries, we identified patients with first-time CS between 2005 and 2017. Cochrane-Armitage trend tests were used to examine temporal changes in presumed causes of CS, treatments, and outcomes. Among 14 363 CS patients, characteristics remained largely stable over time. As presumed causes of CS, ACS (37.1% in 2005 to 21.4% in 2017), heart failure (16.3% in 2005 to 12.0% in 2017), and arrhythmias (13.0% in 2005 to 10.9% in 2017) decreased significantly over time; cardiac arrest increased significantly (11.3% in 2005 to 24.5% in 2017); and changes in valvular heart disease were insignificant (11.5% in 2005 and 11.6% in 2017). Temporary left ventricular assist device, non-invasive ventilation, and extracorporeal membrane oxygenation use increased significantly over time; intra-aortic balloon pump and mechanical ventilation use decreased significantly. Over time, 30-day and 1-year mortality were relatively stable. Significant decreases in 30-day and 1-year mortality for patients presenting with ACS and arrhythmias and a significant increase in 1-year mortality in patients presenting with heart failure were seen. CONCLUSION: Between 2005 and 2017, we observed significant temporal decreases in ACS, heart failure, and arrhythmias as presumed causes of first-time CS, whereas cardiac arrest significantly increased. Although overall 30-day and 1-year mortality were stable, significant decreases in mortality for ACS and arrhythmias as presumed causes of CS were seen.

Clinical Heart Failure Among Patients With and Without Severe Mental Illness and the Association With Long-Term Outcomes.

BACKGROUND: Patients with severe mental illness (SMI) including schizophrenia, bipolar disorder, and severe depression have earlier onset of cardiovascular risk factors, predisposing to worse future heart failure (HF) compared with the general population. We investigated associations between the presence/absence of SMI and long-term HF outcomes. METHODS: We identified patients with HF with and without SMI in the Duke University Health System from 2002 to 2017. Using multivariable Cox regression, we examined the primary outcome of all-cause mortality. Secondary outcomes included rates of implantable cardioverter defibrillator use, cardiac resynchronization therapy, left ventricular assist device implantation, and heart transplantation. RESULTS: We included 20 906 patients with HF (SMI, n=898; non-SMI, n=20 008). Patients with SMI presented clinically 7 years earlier than those without SMI. We observed an interaction between SMI and sex on all-cause mortality (P=0.002). Excess mortality was observed among men with SMI compared with men without SMI (hazard ratio, 1.36 [95% CI, 1.17-1.59]). No association was observed among women with and without SMI (hazard ratio, 0.97 [95% CI, 0.84-1.12]). Rates of implantable cardioverter defibrillator use, cardiac resynchronization therapy, left ventricular assist device implantation, and heart transplantation were similar between patients with and without SMI (6.1% versus 7.9%, P=0.095). Patients with SMI receiving these procedures for HF experienced poorer prognosis than those without SMI (hazard ratio, 2.12 [95% CI, 1.08-4.15]). CONCLUSIONS: SMI was associated with adverse HF outcome among men and not women. Despite equal access to procedures for HF between patients with and without SMI, those with SMI experienced excess postprocedural mortality. Our data highlight concurrent sex- and mental health-related disparities in HF prognosis, suggesting that patients with SMI, especially men, merit closer follow-up.

Association between vectorcardiographic QRS area and incident heart failure diagnosis and mortality among patients with left bundle branch block: A register-based cohort study.

BACKGROUND: QRS duration and morphology including left bundle branch block (LBBB) are the most widely used electrocardiogram (ECG) markers for assessing ventricular dyssynchrony and predicting heart failure (HF). However, the vectorcardiographic QRS area may more accurately identify delayed left ventricular activation and HF development. OBJECTIVE: We investigated the association between QRS area and incident HF risk in patients with LBBB. METHODS: By crosslinking data from Danish nationwide registries, we identified patients with a first-time digital LBBB ECG between 2001 and 2015. The vectorcardiographic QRS area was derived from a 12­lead ECG using the Kors transformation method and grouped into quartiles. The endpoint was a composite of HF diagnosis, filled prescriptions for loop diuretics, or death from HF. Cause-specific multivariable Cox regression was used to compute hazard ratios(HR) with 95% confidence intervals(CI). RESULTS: We included 3316 patients with LBBB free from prior HF-related events (median age, 72 years; male, 40%). QRS area quartiles comprised Q1, 36-98 µVs; Q2, 99-119 µVs; Q3, 120-145 µVs; and Q4, 146-295 µVs. During a 5-year follow-up, 31% of patients reached the composite endpoint, with a rate of 39% in the highest quartile Q4. A QRS area in quartile Q4 was associated with increased hazard of the composite endpoint (HR:1.48, 95%CI:1.22-1.80) compared with Q1. CONCLUSIONS: Among primary care patients with newly discovered LBBB, a large vectorcardiographic QRS area (146-295 µVs) was associated with an increased risk of incident HF diagnosis, filling prescriptions for loop diuretics, or dying from HF within 5-years.