SUMMARY In patients treated with sulfinpyrazone, an apparent reduction in the incidence of sudden death and presumed ventricular fibrillation has been reported. Using an intact animal model without microcirculatory thrombosis, we studied the effects of sulfinpyrazone on ischemic myocardium in 58 anesthetized dogs divided into three groups: control untreated (n = 24), group 1 (n = 16), treated daily with 300 mg of sulfinpyrazone for 7 days, and group 2 (n = 18), treated daily with 300 mg of sulfinpyrazone for 7 days but omitting treatment on day 8. Although consistent hemodynamic differences were not apparent, the degree of injury determined by ECG mapping was significantly lower in group 1. The incidence of fibrillation was 54% for control and 0% in group 1. Group 2 had a 44% incidence, suggesting a limited duration of action. The apparent absence of microcirculatory thrombosis in this model suggests other mechanisms of action. A significantly smaller increase in tissue water and Na+ and smaller loss of K+ in group 1 may have contributed to the lower incidence of fibrillation, perhaps through selective prostaglandin inhibition.THE USE of drugs in coronary artery disease that interfere with platelet function' has been prompted by the presumed role of the latter in the pathogenesis of ischemic heart disease.2-' Recent developments on the effects of platelet-active agents on prostaglandin metabolism have suggested several mechanisms that might affect the course of coronary artery disease.5'6 Our studies with aspirin in a canine model have indicated that aspirin did not significantly inhibit formation of experimentally induced platelet thrombus in the epicardial coronary vessels but survival rate was significantly increased.7 In patients treated with sulfinpyrazone in the postinfarction period, there was an apparent reduction in the incidence of sudden death,8 and presumably ventricular fibrillation, an effect that may be independent of antiplatelet activity.9' 10 These considerations prompted us to study the effects of sulfinpyrazone on ischemic myocardium using an animal model with nonthrombotic coronary occlusion, which permitted the study of sulfinpyrazone in the absence of evident platelet microaggregates.Methods Fifty-eight apparently healthy male mongrel dogs that weighed 22-32 kg were used for the study. After an 18-hour period of fasting, all dogs on the day of the experiment were anesthetized with morphine sulfate (3 mg/kg i.m.) and sodium pentobarbital (20 mg/kg i.v.) and were placed on a respiratory pump to maintain adequate ventilation. Through vessels exposed by small skin incisions, catheters were placed under From

Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Karen Elise Jensen’s Foundation Background Cardiac surgery in patients with cardiac implantable electronic devices (CIEDs) has been associated with a higher risk of infective endocarditis, but how it influences risk of CIED-specific infections is not known. Purpose To examine risk of systemic CIED infections after cardiac surgery in patients with CIEDs. Methods Based on data obtained from Danish administrative registries and the Danish Pacemaker and ICD Register, we conducted a case-control study nested within a nationwide cohort of patients who underwent a de novo CIED implantation in Denmark between 1998-2017. Patients entered the study at six months after implantation. We defined cases as incident systemic CIED infections resulting in device system extraction. Controls were sampled 1:100 on age, sex and follow-up time using risk set sampling. Exposure was defined as coronary artery bypass graft (CABG)-, or cardiac heart valve replacement- or repair surgery. Results From a study cohort comprising 67,621 patients, we identified 170 cases and 16,966 controls. In the minimally adjusted model, the incidence rate ratio (IRR) for systemic CIED infection was 6.4 (95% confidence interval (CI) 3.9-17.1) with cardiac surgery, and after confounder adjustment, 7.0 (95% CI 4.1-11.9). IRRs were higher when exposure was restricted to heart valve replacement surgery (adjusted IRR (aIRR) 9.7, 95% CI 5.2-17.8), and when limiting our exposure time window to one year (aIRR 12.7, 95% CI 5.8-27.8). Conclusion Cardiac surgery in patients with de novo CIEDs was associated with a high risk of systemic CIED infections. Highest risk was observed after heart valve replacement surgery, and within the first year of surgery.

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Danish Heart Foundation OnBehalf DEFIB-WOMEN study group Background Patients adjust well to living with an implantable cardioverter defibrillator (ICD), but 20% develop anxiety and depression that may compromise their quality of life (QoL) and increase risk of ventricular tachyarrhythmias and mortality. Purpose We examined the incidence and correlates of new onset anxiety and depression during 24 months of follow-up in ICD patients without depression and anxiety. Methods Patients with a first-time ICD (n = 1040) enrolled in the national, multi-centre prospective observational DEFIB-WOMEN study completed questionnaires on anxiety, depression and physical QoL at baseline, 3-, 6-, 12-, and 24 months. Information on demographic and clinical data was obtained from the Danish Pacemaker and ICD Register. Results During 24 months of follow-up, 46-57 (4%-5%) patients developed new onset anxiety and 42-47 (4%-5%) new onset depression. The incidence of new onset comorbid anxiety and depression was higher with 69-80 (7%-8%). Age [HR:0.54; 95%CI:0.36-0.80], marital status [HR:1.66; 95%CI:1.01-2.73], secondary prevention indication [HR:1.43; 95%CI:1.00-2.04], Type D personality [HR:2.50; 95%CI:1.62-3.86], and lower self-reported physical functioning [HR:1.48; 95%CI:1.00-2.17] were associated with new onset anxiety during follow-up. Age [HR:0.57; 95%CI:0.37-0.89], higher self-reported physical functioning [HR:0.46; 95%CI:0.25-0.85], smoking [HR:2.13; 95%CI:1.33-3.40], Type D personality [HR:2.53; 95%CI: 1.57-4.05], and lower self-reported physical functioning [HR:1.64; 95%CI:1.08-2.48] were associated with new onset depression. Conclusion Between 4%-8% of patients with a first-time ICD with no anxiety or depression at baseline are at risk of new onset anxiety, depression, or comorbid anxiety and depression up to 24 months post implant, suggesting that safeguarding their QoL and prognosis warrants that we screen patients not only at baseline.

Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Karen Elise Jensen’s Foundation Background Manipulation of the heart during cardiac surgery in patients with cardiac implantable electronic devices (CIEDs) may result in lead damage or -displacement, but whether cardiac surgery truly infers an excess risk of lead failure is not known. Purpose The objective of this study was to examine risk of lead complications as a result of cardiac surgery in CIED patients. Methods We conducted a nationwide nested case-control study. Our source population comprised all patients ≥18 of age who underwent a de novo CIED implantation in Denmark between 1998 and 2017. Only patients who were alive and event-free at six months after implantation were eligible for inclusion in the case-control study. Cases were defined as incident lead complications resulting in a revision procedure, and were matched 1:30 to controls using risk set sampling. We used conditional logistic regression to estimate incidence rate ratios (IRRs) for the association between cardiac surgery and lead complications. Results Our population consisted of 61,869 de novo CIED patient. We identified 1324 incident cases of lead complications and 39,708 time-matched controls. 1036 cases and controls underwent cardiac surgery during follow-up; 61 cases (4.5%) and 975 controls (2.5%). Risk of lead-related reoperation was highest within the first six months of cardiac surgery (IRR 10.1, 95% CI 6.5-15.6, adjusted IRR 11.0, 95% CI 7-17.4). At one year, we observed no association between cardiac surgery and lead complications (IRR: 1.0, 95% CI 0.7-1.5 and adjusted IRR: 1.1, 95% CI 0.7-1.6). Conclusion Cardiac surgery was associated with a substantial risk of lead complications in patients with de novo CIEDs. Manipulation of the heart including cannulation of the right atrium is a likely explanation for the subsequent lead problems.