Rasmus Rørth

Return to the Workforce After First Hospitalization for Heart Failure: A Danish Nationwide Cohort Study.

Background: Return to work is important financially, as a marker of functional status and for self-esteem in patients developing chronic illness. We examined return to work after first heart failure (HF) hospitalization. Methods: By individual-level linkage of nationwide Danish registries, we identified 21 455 patients of working age (18–60 years) with a first HF hospitalization in the period from 1997 to 2012. Of these patients, 11 880 (55%) were in the workforce before HF hospitalization and comprised the study population. We applied logistic regression to estimate odds ratios for associations between age, sex, length of hospital stay, level of education, income, comorbidity, and return to work. Results: One year after first HF hospitalization, 8040 (67.7%) returned to the workforce, 2981 (25.1%) did not, 805 (6.7%) died, and 54 (0.5%) emigrated. Predictors of return to work included younger age (18–30 versus 51–60 years; odds ratio [OR], 3.12; 95% confidence interval [CI], 2.42–4.03), male sex (OR, 1.22; 95% CI, 1.12–1.34), and level of education (long-higher versus basic school; OR, 2.06; 95% CI, 1.63–2.60). Conversely, hospital stay >7 days (OR, 0.56; 95% CI, 0.51–0.62) and comorbidity including history of stroke (OR, 0.55; 95% CI, 0.45–0.69), chronic kidney disease (OR, 0.46; 95% CI, 0.36–0.59), chronic obstructive pulmonary disease (OR, 0.62; 95% CI, 0.52–0.75), diabetes mellitus (OR 0.76; 95% CI, 0.68–0.85), and cancer (OR, 0.49; 95% CI, 0.40–0.61) were all significantly associated with lower chance of return to work. Conclusions: Patients in the workforce before HF hospitalization had low mortality but high risk of detachment from the workforce 1 year later. Young age, male sex, and a higher level of education were predictors of return to work.

Prognostic Value of N-Terminal Pro-B-Type Natriuretic Peptide Levels in Heart Failure Patients With and Without Atrial Fibrillation

Background Patients with heart failure (HF) and atrial fibrillation (AF) have higher circulating levels of NT-proBNP (N-terminal pro-B-type natriuretic peptide) than HF patients without AF. There is uncertainty about the prognostic importance of a given concentration of NT-proBNP in HF patients with and without AF. We investigated this question in a large cohort of patients with HF and reduced ejection fraction. Methods and Results We studied 14 737 patients with HF and reduced ejection fraction and a measurement of NT-proBNP at time of screening, enrolled in either the PARADIGM-HF trial (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) or the ATMOSPHERE trial (Aliskiren Trial to Minimize Outcomes in Patients With Heart Failure), of whom 3575 (24%) had AF on their baseline ECG. Median (Q1, Q3) levels of NT-proBNP were 1817 pg/mL (1095–3266 pg/mL) in those with AF and 1271 pg/mL (703–2569 pg/mL) in those without (P<0.0001). Patients with AF were older (67 versus 62 years), had worse New York Heart Association class (III/IV; 36% versus 24%), and experienced fewer previous HF hospitalizations (52% versus 61%) or myocardial infarction (30% versus 46%); all P<0.001. We categorized patients with and without AF into 5 NT-proBNP bands: <400, 400 to 999 (reference), 1000 to 1999, 2000 to 2999, and ≥3000 pg/mL. For the primary composite outcome of cardiovascular death or HF hospitalization, event rates differed for patients with and without AF in the lowest band (<400 pg/mL; 8.2 versus 5.0 per 100 patient-years), but not for the higher bands (400–999 pg/mL, 7.4 versus 7.7 per 100 patient-years; 1000–1999 pg/mL, 9.8 versus 11.4 per 100 patient-year; 2000–2999 pg/mL, 13.5 versus 13.4 per 100 patient-years; ≥3000 pg/mL, 22.7 versus 23.0 per 100 patient-years). These findings were consistent whether NT-proBNP was examined as a categorical or continuous variable and before and after adjustment for other prognostic variables. We found similar results for the components of the composite outcome and all-cause mortality. Conclusions HF and reduced ejection fraction patients with AF had higher NT-proBNP than those without AF. However, above a concentration of 400 pg/mL (representing most patients in each group), NT-proBNP had similar predictive value for adverse cardiovascular outcomes, irrespective of AF status. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier NCT00853658 (ATMOSPHERE) and NCT01035255 (PARADIGM-HF).

Employment status at time of first hospitalization for heart failure is associated with a higher risk of death and rehospitalization for heart failure

Employment status at time of first heart failure (HF) hospitalization may be an indicator of both self‐perceived and objective health status. In this study, we examined the association between employment status and the risk of all‐cause mortality and recurrent HF hospitalization in a nationwide cohort of patients with HF.

Employment status at time of first hospitalization for heart failure independently predicts mortality and rehospitalization for heart failure

Doxorubicin induced cardiotoxicity is a well-recognized complication of chemotherapy, and its prevention remains an important challenge in cancer survivorship. An angiogenic hormone prokineticin via its receptor PKR1 promotes angiogenesis, differentiation of cardiac stem cells, and survival of the cardiomyocytes. PKR1 has been recently shown to protect heart against myocardial infarction in mice model. Thus, we hypothesized that PKR1 agonist can be a promising target to prevent doxorubicin-mediated cardiotoxicity. Methods and Results: In vitro, we showed that IS20 attenuates apoptosis induced by DOX treatment in H9c2 cardiomyocytes and human epicardial derived progenitor cells. However, IS20 does not interfere DOX-mediated cytotoxicity in cancer cell line. In vivo, IS20 administration in juvenile mice model promotes survival, proliferation and differentiation of WT1+EPDCs into vasculogenic cells. Similarly, IS20 on chronic mice model preserves vascular structure, reduces apoptosis and inflammation. IS20 also improves systolic and diastolic parameters that impaired by DOX. Conclusions: Multi effects of IS20 on the activation of cardiac progenitor cells, cardiac cells survival, vascular stability and cardiac parameters show a strong cardioprotective potential of PKR1 agonist that can be used in cancer patients during anthracyclines chemotherapy. P2008 Growth differentiation factor 15 as a predictor of acute kidney injury formation IR Vishnevskaya1; HF Barahmeh2 1Government institution “L.T. Malaya Therapy National institute of the National academy of medical sci”, Kharkiv, Ukraine; 2V.N. Karazin Kharkiv National University, Kharkiv, Ukraine The development of acute kidney injury (AKI) in patient with acute coronary syndrome (ACS), especially in those who underwent angiography, is an actual problem, because it worsens the prognosis. In order to diagnose this condition in time the search for biomarkers is going. Stress-induced marker growth differentiation factor 15 (GDF 15), a member of the transforming growth factor-β cytokine superfamily is being actively studied. Purpose: to determine the prognostic significance of GDF 15 and other markers in development of AKI in patients with ACS. Methods: 73 patients were enrolled with different forms of ACS (55 male and 18 female), mean age was 61, 8± 1, 3 years. All patients underwent a baseline investigation which includes: standard electrocardiography, echocardiography, angiography and determination of marker of myocardial necrosis – cardiac troponin T. Based on the results of the examination glomerular filtration rate (GFR) was calculated by Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI). A group of patients has been selected (n=54), their creatinine level was determined during the first 24 hours and after 48 hours. All patients were divided into two groups according to acute kidney injury network classification (AKIN): 21 patient in the first group with negative dynamic (1st stage AKIN and higher), 33 patient in the second group without creatinine dynamic. In addition, the level of GDF 15 was determined during the first day of hospitalization (normal range of GDF 15< 1200 pg / ml). Results: By comparing selected groups significant difference was found in creatinine level and GFR in both groups (p< 0.001; p< 0.01, respectively). The effects of various variables were assessed on formation of AKI in patients with different level of GFR. To identify the main risk factors for AKI, we have used logistic regression (LR): ejection fraction of left ventricle (area under curve (AUC) 0.7; p< 0.01; 95% confidence interval (CI): 0.560 – 0,842), GDF 15 (AUC 0.77; p< 0.03; 95% CI: 0.53 – 0.92) and age (AUC 0.77; p< 0.01) were main risk factors for predicting development of AKI. During the statistical analysis the predictive value for estimated parameters was calculated: GDF 15 > 2200 pg/ml (specificity (Spe) 87%, sensitivity (Se) 65%), ejection fraction of left ventricle >46% (Spe 80 %, Se 71 %), age >55 year (Spe 39 %, Se 96 %) We have developed a prognostic model to predict reduced kidney function formation (AUC 0.8; p < 0.001). This model with 96% of Se and 68% of Spe can predict development of AKI in patients with different levels of GFR after ACS. Conclusion: the prognostic multifactor model can be used in clinical practice to improve risk stratification in patients with ACS to prevent formation of AKI. P2009 Neladenoson, a partial adenosine A1-receptor agonist, improves mitochondrial function in skeletal muscle of dogs with chronic heart failure HN Hani Sabbah1; RC Gupta1; V Singh-Gupta1; K Zhang1; J Xu1; B Albrecht-Kuepper2 1Henry Ford Hospital, Detroit, United States of America; 2Bayer AG, Wuppertal, Germany Funding Acknowledgements: Bayer AG Background: Exercise intolerance (Ex-Int) is a feature of chronic heart failure (HF) and in particular, HF with preserved ejection fraction (HFpEF) and attributable, in part, to skeletal muscle (SM) abnormalities of fiber type composition and mitochondrial (MITO) dysfunction. In patients and dogs with HF, SM aerobic, MITO-dependent, type-I fibers decrease in number while anaerobic type-II fibers increase; a maladaptation that contributes to Ex-Int. We previously showed that chronic therapy with capadenoson, a partial adenosine A1-receptor agonist (pA1RA), improves LV function in HF dogs and therapy with neladenoson (NELA), a novel pA1RA, normalizes MITO function in failing cardiomyocytes. This study examined the effects of NELA on MITO function in SM biopsies from normal (NL) dogs and dogs with microembolization-induced HF. Methods: Fresh SM open biopsies ( ̃6 grams) were obtained from the hind leg Vastus Lateralis muscle of 6 NL and 6 HF anesthetized dogs. Samples were cut into thin sections, divided into 4 equal portions, and one portion each incubated in 0 (vehicle), 3, 10, and 30 nM concentration of NELA respectively for one hour at 37∘C. At end of incubation, MITO were isolated from SM and their function assessed. MITO ADP-stimulated state-3 respiration (ADPresp) was measured using a Strathklein respirometer, MITO complex-IV (COX-IV) activity was measured polarographically and MITO maximum rate of ATP synthesis (ATPsyn) was measured using the bioluminescent ApoSENSOR assay kit. Results: Increasing concentration of NELA had no effect on measures of MITO function in SM from NL dogs (Table). In SM from HF dogs, depressed levels of MITO ADPresp, ATPsyn, and COX-IV activity increased significantly in a dose-dependent manner after exposure to NELA (Table). Conclusions: The results indicate that NELA improves MITO function of SM of dogs with HF. These improvements can potentially reduce/reverse Ex-Int in HF. MITO Function Measures Vehicle 3 nM NELA 10 nM NELA 30 nM NELABackground and purpose: To estimate healthcare resource utilization among patients with heart failure (HF) with preserved (HFpEF) versus reduced (HFrEF) ejection fraction using population data from ...

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.

Microvascular complications in diabetes patients with heart failure and reduced ejection fraction-insights from the Beta-blocker Evaluation of Survival Trial

The role of microvascular complications in the risk conferred by diabetes in heart failure with reduced ejection fraction (HFrEF) is unknown.

Employment status at time of first hospitalization for heart failure is associated with death and rehospitalization for heart failure

Employment status at time of first heart failure (HF) hospitalization may be an indicator of both self‐perceived and objective health status. In this study, we examined the association between employment status and the risk of all‐cause mortality and recurrent HF hospitalization in a nationwide cohort of patients with HF.

POOR PROGNOSIS FOLLOWING DIABETES MELLITUS IN PATIENTS WITH HEART FAILURE: A NATIONWIDE COHORT STUDY

Prevalent diabetes mellitus (DM) is associated with higher risk of death and recurrent heart failure hospitalization (HFH) in patients with HF. However, little is known about the prognosis in HF patients developing DM after HF diagnosis. We examined the risk of death and HFH in HF patients with

Return to the workforce following coronary artery bypass grafting: A Danish nationwide cohort study

BACKGROUND Returning to the workforce after coronary artery bypass grafting (CABG) holds important socioeconomic consequences not only for patients, but the society as well. Yet data on this issue are limited. We examined return to the workforce and associated factors in patients of working age undergoing CABG. METHODS AND RESULTS Using Danish nationwide administrative registries, we identified 6031 patients of working age (18-60years) undergoing isolated CABG (1998-2011) who were part of the workforce 30days prior to admission and alive at discharge. One year after discharge for CABG, 4827 (80.0%) patients had returned to the workforce, 614 (10.2%) were on paid sick leave, 267 (4.4%) received disability pension, 250 (4.1%) were on early retirement, 57 (0.9%) had died, and 16 (0.3%) had emigrated. Factors associated with return to the workforce were identified using multivariable logistic regression. Younger age (18-45 versus 56-60years; odds ratio, 1.89; 95% confidence interval, 1.48-2.42), male sex (1.51, 1.24-1.84), and higher level of education (higher educational level versus basic school; 1.53, 1.05-2.23) and income (highest quartile versus lowest; 3.01, 2.42-3.75) were associated with return to the workforce. Urgency of surgery (emergency versus elective; 0.65, 0.49-0.88), cardiovascular comorbidity, a history of chronic kidney disease (0.49, 0.29-0.84) and liver disease (0.47, 0.28-0.80), as well as additional hospital admissions within the first year post-discharge (>2 versus none; 0.25, 0.19-0.32) were associated with a lower likelihood of returning to the workforce. CONCLUSION One year after discharge for CABG, four out of five patients were part of the workforce and mortality was low. Younger age, male sex, higher socioeconomic status, and absence of major comorbidities were associated with return to the workforce.

Risk of Incident Heart Failure in Patients With Diabetes and Asymptomatic Left Ventricular Systolic Dysfunction

OBJECTIVE Although diabetes is well known to be common in prevalent heart failure (HF) and portends a poor prognosis, the role of diabetes in the development of incident HF is less well understood. We studied the role of diabetes in the transition from asymptomatic left ventricular systolic dysfunction (ALVSD) to overt HF in the prevention arm of the Studies of Left Ventricular Dysfunction (SOLVD-P). RESEARCH DESIGN AND METHODS We examined the development of symptomatic HF, HF hospitalization, and cardiovascular death according to diabetes status at baseline in patients in SOLVD-P. These outcomes were analyzed by using cumulative incidence curves and Cox regression models adjusted for age, sex, and other prognostic factors, including randomized treatment, HF severity, and comorbidity. RESULTS Of the 4,223 eligible participants, 647 (15%) had diabetes at baseline. Patients with diabetes were older and had a higher average weight, systolic blood pressure, and heart rate. During the median follow-up of 36 months, 861 of the 3,576 patients without diabetes (24%) developed HF compared with 214 of the 647 patients with diabetes (33%). In unadjusted analyses, patients with diabetes had a higher risk of development of HF (hazard ratio 1.53 [95% CI 1.32–1.78]; P < 0.001), HF hospitalization (2.04 [1.65–2.52]; P < 0.0001), and the composite outcome of development of HF or cardiovascular death (1.48 [1.30–1.69]; P < 0.001). The effect of enalapril on outcomes was not modified by diabetes status. CONCLUSIONS In patients with ALVSD, diabetes is associated with an increased risk of developing HF. Development of HF is associated with an increased risk of death irrespective of diabetes status.