Cost-effectiveness of an antibacterial envelope for infection prevention in patients undergoing cardiac resynchronization therapy reoperations in Denmark.

AIMS: Use of an absorbable antibacterial envelope during implantation prevents cardiac implantable electronic device infections in patients with a moderate-to-high infection risk. Previous studies demonstrated that an envelope is cost-effective in high-risk patients within German, Italian, and English healthcare systems, but these analyses were based on limited data and may not be generalizable to other healthcare settings. METHODS AND RESULTS: A previously published decision-tree-based cost-effectiveness model was used to compare the costs per quality-adjusted life year (QALY) associated with adjunctive use of an antibacterial envelope for infection prevention compared to standard-of-care intravenous antibiotics. The model was adapted using data from a Danish observational two-centre cohort study that investigated infection-risk patients undergoing cardiac resynchronization therapy (CRT) reoperations with and without an antibacterial envelope (n = 1943). We assumed a cost-effectiveness threshold of €34 125/QALY gained, based on the upper threshold used by the National Institute for Health and Care Excellence (£30 000). An antibacterial envelope was associated with an incremental cost-effectiveness ratio (ICER) of €12 022 per QALY in patients undergoing CRT reoperations, thus indicating that the envelope is cost-effective when compared with standard of care. A separate analysis stratified by device type showed ICERS of €6227 (CRT defibrillator) and €29 177 (CRT pacemaker) per QALY gained. CONCLUSIONS: Cost-effectiveness ratios were favourable for patients undergoing CRT reoperations in the Danish healthcare system, and thus are in line with previous studies. Results from this study can contribute to making the technology available to Danish patients and align preventive efforts in the pacemaker and ICD area.

Risk factors for cardiac implantable electronic device infections: a nationwide Danish study.

AIMS: Cardiac implantable electronic device (CIED) infection is a severe complication to modern management of cardiac arrhythmias. The CIED type and the type of surgery are recognized as risk factors for CIED infections, but knowledge of patient-related risk factors is scarce. This study aimed to identify lifelong patient-related risk factors for CIED infections. METHODS AND RESULTS: Consecutive Danish patients undergoing a CIED implantation or reoperation between January 1996 and April 2018 were included. The cohort consisted of 84 429 patients undergoing 108 494 CIED surgeries with a combined follow-up of 458 257 CIED-years. A total of 1556 CIED explantations were classified as either pocket (n = 1022) or systemic CIED infection (n = 534). Data were cross-linked with records from the Danish National Patient Registry and the Danish National Prescription Registry. Using multiple-record and multiple-event per subject proportional hazard analysis, specific patient-related risk factors were identified but with several variations amongst the subtypes of CIED infection. CIED reoperations were associated with the highest risk of pocket CIED infection but also CIED type, young age, and prior valvular surgery [hazard ratio (HR): 1.62, 95% confidence interval (CI): 1.29-2.04]. Severe renal insufficiency/dialysis (HR: 2.40, 95% CI: 1.65-3.49), dermatitis (HR: 2.80, 95% CI: 1.92-4.05), and prior valvular surgery (HR: 2.09, 95% CI: 1.59-2.75) were associated with the highest risk of systemic CIED infections. Congestive heart failure, ischaemic heart disease, malignancy, chronic obstructive pulmonary disease, and temporary pacing were not significant at multivariate analysis. CONCLUSION: Specific comorbidities and surgical procedures were associated with a higher risk of CIED infections but with variations amongst pocket and systemic CIED infection. Pocket CIED infections were associated with CIED reoperations, young age and more complex type of CIED, whereas systemic CIED infections were associated with risk factors predisposing to bacteraemia.

Rate of device-related infections using an antibacterial envelope in patients undergoing cardiac resynchronization therapy reoperations.

AIMS: Cardiac resynchronization therapy (CRT) reoperations are associated with a particularly high risk of device-related infection (DRI). An antibacterial envelope reduces the occurrence of DRIs in a broad population of moderate-tohigh-risk patients. To investigate the efficacy of an antibacterial envelope in a very high-risk population of patients undergoing CRT reoperation. METHODS AND RESULTS: In this Danish two-centre, observational cohort study, we included consecutive patients who underwent a CRT pacemaker- or defibrillator reoperation procedure between January 2008 and November 2019. We obtained data from the Danish Pacemaker and ICD Register and through systematic medical chart review. Follow-up was restricted to 2 years. A total of 1943 patients were included in the study of which 736 (38%) received an envelope. Envelope patients had more independent risk factors for infection than non-envelope patients. Sixty-seven (3.4%) patients met the primary endpoint of DRI requiring device system extraction; 50 in the non-envelope group and 17 in the envelope group [4.1% vs. 2.3%, adjusted hazard ratio (HR) 0.52, 95% confidence interval (CI) 0.30-0.90; P = 0.021]. This difference persisted in propensity score analysis (HR 0.51, 95% CI 0.29-0.90; P = 0.019). CONCLUSION: Use of an antibacterial envelope was associated with a clinically and statistically significant reduction in DRIs in patients undergoing CRT reoperations. Our results were comparable to those recently reported from a large randomized controlled trial, which is suggestive of a proportional effect of the envelope even in very high-risk patients.

Validation of the national Danish ablation database: a retrospective, registry-based validation study.

Aim.To validate the National Danish Ablation Database (NDAD) by investigating to what extent data in NDAD correspond to medical records.Type of study. Non-blinded, registry-based, retrospective, validation study. Material and methods. A sample of patients who underwent ablation for atrial fibrillation in Denmark between 1 January 2016 and 31 December 2016 were included. By utilizing medical records as gold standard, positive predictive (PPV) and negative predictive values (NPV) for NDAD were assessed and presented as five main categories: arrhythmia characteristics, demographics, cardiac history, complications, and medication. PPV's and NPV's exceeding 90% were considered as high agreement. Results. 597 patients (71.0% males) were included in the study. Median age was 63.1 (IQR: 54.9-68.4) years. The median PPV and NPV estimates across all variables were respectively 90.4% (95% CI: 68%-95.2%) (PPV) and 99.4% (95% CI: 98.4%-99.8%) (NPV) at baseline, and 91.7% (95% CI: 67.4%-95.4%) (PPV) and 99.3% (98.2%-99.3%) (NPV) at follow-up. Conclusion. The data registered in NDAD agrees to a great extent with the patients' medical records, suggesting NDAD is a database with high validity. As a result of low complication rate, the PPV- and NPV-estimates among complication variables were prone to somewhat greater uncertainty compared to the rest.

Anxiety and depression symptoms in Danish patients with an implantable cardioverter-defibrillator: prevalence and association with indication and sex up to 2 years of follow-up (data from the national DEFIB-WOMEN study).

AIMS: To investigate (i) the prevalence of anxiety and depression and (ii) the association between indication for implantable cardioverter-defibrillator (ICD) implantation and sex in relation to anxiety and depression up to 24 months' follow-up. METHODS AND RESULTS: Patients with a first-time ICD, participating in the national, multi-centre, prospective DEFIB-WOMEN study (n = 1496; 18% women) completed the Hospital Anxiety and Depression Scale at baseline, 3, 6, 12, and 24 months. Data were analysed using linear mixed modelling for longitudinal data. Patients with a secondary prophylactic indication (SPI) had higher mean anxiety scores than patients with a primary prophylactic indication (PPI) at baseline, 3, and 12 months and higher mean depression scores at all-time points, except at 24 months. Women had higher mean anxiety scores as compared to men at all-time points; however, only higher mean depression scores at baseline. Overall, women with SPI had higher anxiety and depression symptom scores than men with SPI. Symptoms decreased over time in both women and men. From baseline to follow-up, the prevalence of anxiety (score ≥8) was highest in patients with SPI (13.3-20.2%) as compared to patients with PPI (range 10.0-14.7%). The prevalence of depression was stable over the follow-up period in both groups (range 8.5-11.1%). CONCLUSION: Patients with a SPI reported higher anxiety and depression scores as compared to patients with PPI. Women reported higher anxiety scores than men, but only higher depression scores at baseline. Women with SPI reported the highest anxiety and depression scores overall.

Incidence of device-related infection in 97 750 patients: clinical data from the complete Danish device-cohort (1982-2018).

AIMS: Device-related infection (DRI) is a severe complication to cardiac implantable electronic devices (CIED) therapy. Device-related infection incidence and its risk factors differ between previous studies. We aimed to define the long-term incidence and incidence rates of DRI for different types of CIEDs in the complete Danish device-cohort and identify patient-, operation- and device-related risk factors for DRI. METHODS AND RESULTS: From the Danish Pacemaker (PM) and implantable cardioverter-defibrillator (ICD) Register, we included consecutive Danish patients undergoing CIED implantation or reoperation from January 1982 to April 2018, resulting in 97 750 patients, 128 045 operations and follow-up of in total 566 275 device years (DY). We identified 1827 DRI causing device removals. Device-related infection incidence during device lifetime was 1.19% (1.12-1.26) for PM, 1.91% (1.71-2.13) for ICD, 2.18% (1.78-2.64) for cardiac resynchronization therapy (CRT)-pacemakers (CRT-P), and 3.35% (2.92-3.83) for CRT-defibrillators (CRT-D). Incidence rates in de novo implantations were 2.04/1000 DY for PM, 3.84 for ICD, 4.38 for CRT-P, and 6.76 for CRT-D. Using multiple-record and multiple-event per subject proportional hazard analysis, we identified implantation of complex devices (ICD and CRT), reoperations, prior DRI, male sex, and younger age as significantly associated with higher DRI risk. CONCLUSION: Overall risk of infection was low in PM implantations but considerably higher in CRT systems and after reinterventions. These data support the importance of evaluating all patients considered for CIED therapy thoroughly, in order to identify potential modifiable risk factors and reduce the risk of early reoperations.

Association between right ventricular lead position and clinical outcomes in patients with cardiac resynchronization therapy.

Aims: To evaluate the association between an apical vs. non-apical right ventricular lead position (RV-LP) and clinical outcome in a large nationwide cohort of patients treated with cardiac resynchronization therapy (CRT). Methods and results: We included consecutive Danish patients receiving a CRT device from 2008 to 2012, identified from the Danish Pacemaker and ICD Register. Endpoints were mortality, mortality or hospitalization for heart failure (HF), and clinical response (improvement ≥1 New York Heart Association class at follow-up). Subgroup analysis was made for ischaemic heart disease (IHD) and non-IHD. Cox and logistic regression analyses were used to calculate adjusted HR (aHR) and adjusted odds ratios with 95% confidence intervals (CI). A total of 2883 patients received a CRT device during the period. We excluded 301 patients that did not meet standard CRT indication. In 2391 (93%) of the remaining 2582 patients the RV-LP was defined as apical in 647 (27%) and non-apical in 1744 (73%). After mean 3.2 ± 2 years, 660 patients had died, 1275 patients were hospitalized for HF, and 1021 were responders. With a non-apical RV-LP the aHR for mortality was 0.93 (95% CI 0.0.79-1.10, P = 0.40) and the aHR for the combined endpoint of mortality or HF-hospitalization was 0.89 (95% CI 0.79-0.99, P = 0.03). These findings were significant only in patients with non-IHD. There was no association between clinical response and RV-LP. Conclusion: A non-apical RV-LP is associated with lower risk of meeting the combined endpoint of mortality or hospitalization for HF in patients with CRT. In subgroup analysis, this association was present only in patients with non-IHD.

Association between implantable cardioverter-defibrillator therapy and different lead positions in patients with cardiac resynchronization therapy.

Aims: To evaluate the impact of different right and left ventricular lead positions (RV-LP and LV-LP) on the risk of therapy for ventricular tachycardia/ventricular fibrillation in patients with a cardiac resynchronization therapy device (CRT-D). Methods and results: We performed a large nationwide cohort study on patients in Denmark receiving a CRT-D device from 2008 to 2012 from the Danish Pacemaker and implantable cardioverter defibrillator (ICD) registry. Lead positions were registered during the implantation and categorized as anterior/lateral/posterior and basal/mid-ventricular/apical for the LV-LP, and as apical/non-apical for the RV-LP. Appropriate and inappropriate therapies were registered during follow-up via remote monitoring or at device interrogations. Time to event was summarized with Kaplan-Meier plots, and competed risk regression analysis was used to calculate adjusted hazard ratios (aHR) with 95% confidence intervals (CI). Following variables were included in the analysis: gender, age, heart failure aetiology, New York heart association class, left ventricular ejection fraction, QRS duration, indication (secondary or primary prophylactic), RV-LP, LV-LP, and antiarrhythmic therapy. We included 1643 patients [mean age 68 (±10) years, 1343 (83%) men]. After a mean of 2.0 years, 322 (20%) patients received appropriate and 66 (4%) patients received inappropriate therapy. The aHR for appropriate therapy with a non-apical RV-LP was 0.70 95% CI (0.55-0.87, P = 0.002) as compared with an apical. We observed no significant association between appropriate therapy and LV-LP in left anterior oblique or right anterior oblique views or inappropriate therapy between any lead positions. Conclusion: An apical RV-LP is associated with an increased risk of appropriate therapy for ventricular tachyarrhythmia in patients with a CRT-D device.

Postoperative pain and quality of life after lobectomy via video-assisted thoracoscopic surgery or anterolateral thoracotomy for early stage lung cancer: a randomised controlled trial.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) is used increasingly as an alternative to thoracotomy for lobectomy in the treatment of early-stage non-small-cell lung cancer, but remains controversial and worldwide adoption rates are low. Non-randomised studies have suggested that VATS reduces postoperative morbidity, but there is little high-quality evidence to show its superiority over open surgery. We aimed to investigate postoperative pain and quality of life in a randomised trial of patients with early-stage non-small-cell lung cancer undergoing VATS versus open surgery. METHODS: We did a randomised controlled patient and observer blinded trial at a public university-based cardiothoracic surgery department in Denmark. We enrolled patients who were scheduled for lobectomy for stage I non-small-cell lung cancer. By use of a web-based randomisation system, we assigned patients (1:1) to lobectomy via four-port VATS or anterolateral thoracotomy. After surgery, we applied identical surgical dressings to ensure masking of patients and staff. Postoperative pain was measured with a numeric rating scale (NRS) six times per day during hospital stay and once at 2, 4, 8, 12, 26, and 52 weeks, and self-reported quality of life was assessed with the EuroQol 5 Dimensions (EQ5D) and the European Organisation for Research and Treatment of Cancer (EORTC) 30 item Quality of Life Questionnaire (QLQ-C30) during hospital stay and 2, 4, 8, 12, 26, and 52 weeks after discharge. The primary outcomes were the proportion of patients with clinically relevant moderate-to-severe pain (NRS ≥3) and mean quality of life scores. These outcomes were assessed longitudinally by logistic regression across all timepoints. Data for the primary analysis were analysed by modified intention to treat (ie, all randomised patients with pathologically confirmed non-small-cell lung cancer). This trial is registered with ClinicalTrials.gov, number NCT01278888. FINDINGS: Between Oct 1, 2008, and Aug 20, 2014, we screened 772 patients, of whom 361 were eligible for inclusion and 206 were enrolled. We randomly assigned 103 patients to VATS and 103 to anterolateral thoracotomy. 102 patients in the VATS group and 99 in the thoracotomy group were included in the final analysis. The proportion of patients with clinically relevant pain (NRS ≥3) was significantly lower during the first 24 h after VATS than after anterolateral thoracotomy (VATS 38%, 95% CI 0·28-0·48 vs thoracotomy 63%, 95% CI 0·52-0·72, p=0·0012). During 52 weeks of follow-up, episodes of moderate-to-severe pain were significantly less frequent after VATS than after anterolateral thoracotomy (p<0·0001) and self-reported quality of life according to EQ5D was significantly better after VATS (p=0·014). By contrast, for the whole study period, quality of life according to QLQ-C30 was not significantly different between groups (p=0·13). Postoperative surgical complications (grade 3-4 adverse events) were similar between the two groups, consisting of prolonged air leakage over 4 days (14 patients in the VATS group vs nine patients in the thoracotomy group), re-operation for bleeding (two vs none), twisted middle lobe (one vs three) or prolonged air leakage over 7 days (five vs six), arrhythmia (one vs one), or neurological events (one vs two). Nine (4%) patients died during the follow-up period (three in the VATS group and six in the thoracotomy group). INTERPRETATION: VATS is associated with less postoperative pain and better quality of life than is anterolateral thoracotomy for the first year after surgery, suggesting that VATS should be the preferred surgical approach for lobectomy in stage I non-small-cell lung cancer. FUNDING: Simon Fougner Hartmanns Familiefond, Guldsmed AL & D Rasmussens Mindefond, Karen S Jensens legat, The University of Southern Denmark, The Research Council at Odense University Hospital, and Department of Cardiothoracic Surgery, Odense University Hospital.

Complications after cardiac implantable electronic device implantations: an analysis of a complete, nationwide cohort in Denmark.

AIMS: Complications after cardiac implantable electronic device (CIED) treatment, including permanent pacemakers (PMs), cardiac resynchronization therapy devices with defibrillators (CRT-Ds) or without (CRT-Ps), and implantable cardioverter defibrillators (ICDs), are associated with increased patient morbidity, healthcare costs, and possibly increased mortality. METHODS AND RESULTS: Population-based cohort study in all Danish patients who underwent a CIED procedure from May 2010 to April 2011. Data on complications were gathered on review of all patient charts while baseline data were obtained from the Danish Pacemaker and ICD Register. Adjusted risk ratios (aRRs) with 95% confidence intervals were estimated using binary regression. The study population consisted of 5918 consecutive patients. A total of 562 patients (9.5%) experienced at least one complication. The risk of any complication was higher if the patient was a female (aRR 1.3; 1.1-1.6), underweight (aRR 1.5; 1.1-2.3), implanted in a centre with an annual volume <750 procedures (0-249 procedures: aRR 1.6; 1.1-2.2, 250-499: aRR 2.0; 1.6-2.7, 500-749: aRR 1.5; 1.2-1.8), received a dual-chamber ICD (aRR 2.0; 1.4-2.7) or CRT-D (aRR 2.6; 1.9-3.4), underwent system upgrade or lead revision (aRR 1.3; 1.0-1.7), had an operator with an annual volume <50 procedures (aRR 1.9; 1.4-2.6), or underwent an emergency, out-of-hours procedure (aRR 1.5; 1.0-2.3). CONCLUSION: CIED complications are more frequent than generally acknowledged. Both patient- and procedure-related predictors may identify patients with a particularly high risk of complications. This information should be taken into account both in individual patient treatment and in the planning of future organization of CIED treatment.

Sympathicotomy for isolated facial blushing: long-term follow-up of a randomized trial.

OBJECTIVES: Thoracoscopic sympathicotomy may be an effective treatment for disabling facial blushing in selected patients. Short- and mid-term results are good but very long-term results are scarce in the medical literature and there is no knowledge which extent of sympathicotomy is better long-term for isolated facial blushing. METHODS: We previously randomized 100 patients between a rib-oriented R2 or R2-R3 sympathicotomy for isolated facial blushing, and reported local effects, side effects and quality of life after 12 months. In the present study, we sent identical questionnaires to all patients after a median of 16 years (interquartile range 15-17 years). RESULTS: The response rate was 66%. Overall, 82% reported excellent or satisfactory results on facial blushing, with significant better local effect after R2 sympathicotomy compared with R2-R3 sympathicotomy. Patients who underwent R2 sympathicotomy were also significantly more satisfied with the operation. We found no significant difference between R2 and R2-R3 sympathicotomy in quality of life or rates of compensatory sweating (77%) and recurrence of blushing (41%) which was milder than preoperatively in most patients. CONCLUSIONS: R2 sympathicotomy should be the preferred approach for isolated facial blushing because of better local effect and higher satisfaction rates. Although this was a very long-term follow-up of the only randomized trial of its kind the response rate was limited leaving a risk of undetected bias.

Is interventional technique better than the traditional over-the-wire method for left ventricular lead implantation in cardiac resynchronization therapy?

Background: Interventional cardiac resynchronization therapy (I-CRT) for left ventricular lead (LVL) placement works as a supplement to traditional (over-the-wire) cardiac resynchronization therapy (T-CRT). It has been argued that I-CRT is a time-consuming and complicated procedure. Objective: The purpose of this study was to investigate differences in procedure-related, perioperative, postoperative, and clinical endpoints between I-CRT and T-CRT. Methods: This single-center, retrospective, cohort study included all consecutive patients receiving a CRT-pacemaker/defibrillator between January 1, 2012, and August 31, 2018. Patients underwent T-CRT from January 1, 2012, to June 1, 2015, and I-CRT from January 1, 2016, to August 31, 2018. We obtained data from patient record files, fluoroscopic images, and the Danish Pacemaker and ICD Register. Data were analyzed using Wilcoxon rank-sum/linear regression for continuous variables and the Pearson χ2/Fisher exact for categorical variables. Results: Optimal LVL placement was achieved in 82.7% of the I-CRT group and 76.8% of the T-CRT group (P = .015). In the I-CRT group, 99.0% of LVLs were quadripolar vs 55.3% in the T-CRT group (P <.001). Two or more leads were used during the procedure in 0.7% and 10.5% of all cases in the I-CRT and T-CRT groups, respectively (P <.001). Total implantation time was 81.0 minutes in the I-CRT group and 83.0 minutes in the T-CRT group (P = .41). Time with catheters in the coronary sinus was 45.0 minutes for the I-CRT group vs 37.0 minutes in the T-CRT group, respectively (P <.001). Conclusion: I-CRT did not prolong total implantation time despite longer time with catheters in the coronary sinus. I-CRT allowed more optimal LVL placement, wider use of quadripolar leads, and use of fewer leads during the procedure.

Mortality and appropriate and inappropriate therapy in patients with ischaemic heart disease and implanted cardioverter-defibrillators for primary prevention: data from the Danish ICD Register.

AIMS: To evaluate the incidences of and risk factors predisposing to appropriate and inappropriate shocks and mortality in a 'real-world' population of patients with ischaemic heart disease (IHD) and implantable cardioverter defibrillators (ICD) for primary prevention of sudden cardiac death (SCD). METHODS AND RESULTS: In this nationwide cohort, we prospectively followed 1609 patients with IHD and left ventricular dysfunction from the Danish ICD Register who received an ICD for primary prevention of SCD (1 January 2007 to 30 November 2011). Primary study outcomes were appropriate shocks, inappropriate shocks, and all-cause mortality. Secondary study outcomes included the composite endpoints: appropriate therapy and inappropriate therapy (defined as shock or anti-tachycardia pacing). All-cause mortality was 12.1% during a mean follow-up time of 1.9 ± 1.3 years. Inappropriate shocks and therapy occurred in 2.6% and 3.7% during follow-up, respectively. Appropriate shocks and therapy was identified in 7.8% and 13.4%, respectively. Time-dependent multivariable Cox regression analyses were used to identify risk factors of inappropriate/appropriate shock, therapy and mortality. Implantation of a dual-chamber ICD was associated with increased risk of both inappropriate shocks and any inappropriate therapy compared to single-chamber ICD [hazard ratios (HR) = 2.45; confidence intervals (CI):1.16-5.14 and HR = 2.38; CI:1.28-4.42, respectively]. No excess risk of mortality was associated with any device type. CONCLUSION: In this nationwide study of IHD patients with an ICD for primary prevention of SCD, the incidence of appropriate shocks as well as inappropriate shocks were significantly lower than reported in randomized trials. Implantation of a dual-chamber ICD was associated with more inappropriate shocks compared with single chamber devices.

Cardiac surgery in patients with cardiac implantable electronic devices and risk of device infections: a nationwide nested case-control study.

PURPOSE: 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. Our aim was 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 and 2017. We defined cases as incident systemic CIED infections resulting in device system extraction. Controls were sampled 1:100 on time, age, sex and device type using risk set sampling. Exposure was defined as coronary artery bypass graft, or cardiac heart valve replacement or repair surgery. RESULTS: From a study cohort comprising 67,621 patients, we identified 170 cases and 16,788 controls. In the minimally adjusted model, the incidence rate ratio (IRR) for systemic CIED infection was 6.4 (95% confidence interval (CI) 3.8-10.7) with cardiac surgery, and after additional confounder adjustment, 5.4 (95% CI 3.2-9.2). IRRs were higher with restriction to heart valve replacement surgery (adjusted IRR 7.5, 95% CI 4.0-16.6), and when limiting our exposure time window to one year (adjusted IRR 10.1, 95% CI 4.5-22.3). 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.

Infection after pacemaker implantation: infection rates and risk factors associated with infection in a population-based cohort study of 46299 consecutive patients.

AIMS: Infection is a serious complication of pacemaker (PM) systems. Although the rate of infection has been debated, the figures are largely unknown. We therefore studied the incidence of PM infection and its associated risk factors in the Danish population. METHODS AND RESULTS: Since 1982, all PM implantation and removal procedures performed in Denmark have been prospectively recorded in the Danish Pacemaker Register. All patients (n = 46299) who underwent implantation between 1982 and 2007 were included. The total length of surveillance was 236,888 PM-years. The incidence of infection was calculated according to the total number of PM-years. The incidence of surgical site infection (≤ 365 days after PM implantation) was compared with later infection in first implant and replacement procedures. Multiple-record and multiple-event-per-subject proportional hazards analyses were used to identify the independent risk factors of PM infection. Surgical site infection occurred in 192 cases after first implantation (incidence rate 4.82/1000 PM-years), and in 133 cases after replacement (12.12/1000 PM-years). Infections occurring more than 365 days after the first implantation occurred in 153 cases (1.02/1000 PM-years), and in 118 cases after replacement (3.26/1000 PM-years). Independent factors associated with an increased risk of PM infection were a greater number of PM operations (including replacements), male sex, younger age, implantation during the earliest part of the study period, and absence of antibiotics (P< 0.001). CONCLUSION: The overall risk of infection after PM implantation was low. A greater number of operations augmented the risk of infection. This should be taken into account when considering revisions of PM systems.

Lead complications after cardiac surgery in patients with cardiac implantable electronic devices.

OBJECTIVES: 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. The objective of this study was to examine the risk of lead complications after cardiac surgery in patients with CIEDs. METHODS: We conducted a nationwide nested case-control study. The source population comprised all Danish patients ≥18 of age who underwent a de novo CIED implantation during 1998-2017. For inclusion, patients had to be alive and event free 6 months after implantation. Cases were matched 1:30 to controls on time, age, sex, and device type using risk set sampling. We used conditional logistic regression to estimate incidence rate ratios (IRRs) for the association between cardiac surgery and lead-related reoperation. RESULTS: Our final population consisted of 67 621 patients. We identified 1437 (2.1%) incident cases of lead-related reoperations and 42 698 controls. Risk of lead complications was highest within 6 months of cardiac surgery [IRR 9.7, 95% confidence interval (CI) 6.3-14.8, adjusted IRR 9.6, 95% CI 6.2-14.7], and at 1 year, the relative risk of lead-related reoperation was close to unity (adjusted IRR 1.2, 95% CI 0.8-1.7). CONCLUSIONS: Cardiac surgery was associated with a considerable risk of lead complications in patients with de novo CIEDs.

Rate of permanent cardiac implantable electronic device infections after active fixation temporary transvenous pacing: A nationwide Danish cohort study.

BACKGROUND: Temporary transvenous pacing (TP) has been associated with an increased risk of cardiac implantable electronic device (CIED) infections, but there is little data to document this in contemporary populations. OBJECTIVE: To investigate the impact of active fixation TP on rate of CIED infections in a nationwide cohort of Danish patients. METHODS: We identified all patients who underwent a first-time CIED implantation between 2009 and 2017. Patients were categorized according to TP status at implantation and followed for 1 year. The primary outcome was local or systemic CIED infection resulting in device system removal. The secondary outcomes were systemic CIED infections and hospitalization for infective endocarditis (IE). RESULTS: We included a total of 40,601 CIED patients. A total of 2952 were treated with active fixation TP. The primary outcome was met in 246 patients. Risk of CIED infection at 1 year was 0.61% for patients not treated with TP and 0.65% for patients who were, HR of 1.28 (95% CI 0.80-2.05) and adjusted HR 0.85 (95% CI 0.51-1.42). More systemic CIED infections and IE hospitalizations occurred in TP patients; however, these differences did not persist after confounder adjustment. Cumulative mortality at 1 year was 16.8% in patients with TP vs 8.4% in patients without. CONCLUSION: Active fixation TP was not associated with a higher rate of CIED infections. Patients treated with TP had higher mortality, more systemic CIED infections, and more IE hospitalizations within first year of implantation. Most was attributable to an accumulation of risk factors for infection among TP patients.

Predictors of pocket hematoma after cardiac implantable electronic device surgery: A nationwide cohort study.

Purpose: Clinically significant pocket hematoma (CSH) is a common complication to cardiac implantable electronic device (CIED) surgery. We aimed to evaluate predictors of CSH after CIED surgery. Methods: We performed a nationwide population-based prospective cohort study with systematic patient chart review of all Danish patients undergoing CIED surgery during a 12-month period. Multiple logistic regression analysis was used to estimate adjusted odds ratios (aOR) with 95% confidence intervals for association between predictors and CSH. Results: We included 5918 consecutive patients, 63% males, mean age 72.6 years. A total of 148 (2.5%) patients experienced CSH, including 10 patients (0.2%) requiring re-operation with hematoma evacuation. The risk of CSH was significantly increased in patients treated with aspirin (aOR 1.8; 1.2-2.7), aspirin and clopidogrel (aOR 3.9; 2.3-6.5), or heparin (aOR 2.1; 1.1-4.1), and in patients with INR≥2.0 (aOR 2.0; 1.2-3.2). Patients operated by low-volume operators (aOR 2.7; 1.6-4.6) or undergoing more complex CIED surgery such as cardiac resynchronization therapy (aOR 2.0; 1.1-3.5) or dual-chamber defibrillator (aOR 2.1; 1.2-3.8) also had significantly increased CSH risk. Conclusion: In a large nationwide cohort of consecutive patients undergoing CIED surgery, the risk of CSH was 2.5%, with 0.2% necessitating evacuation. CSH risk was increased both in patients receiving aspirin, dual antiplatelet therapy or continued vitamin K-antagonist therapy. Dual antiplatelet therapy had the highest risk (aOR) of CSH. Both low operator volume and more complex CIED surgery were independently associated with higher CSH risk. These data should be considered when planning CIED surgery.

Microbiological diagnosis in cardiac implantable electronic device infections detected by sonication and next-generation sequencing.

BACKGROUND: Device-related infection (DRI) is a severe complication of treatment with cardiac implantable electronic devices. Identification of the causative pathogen is essential for optimal treatment, but conventional methods often are inadequate. OBJECTIVE: The purpose of this study was to improve microbiological diagnosis in DRI using sonication and next-generation sequencing analysis. The primary objective was identification of causative pathogens. The secondary objective was estimation of the sensitivity of different microbiological methods in detecting the causative pathogen. METHODS: Consecutive patients with clinical signs of DRI between October 2016 and January 2019 from 3 tertiary centers in Denmark were included in the study. Patients underwent a diagnostic approach, including blood cultures and perioperative collection of microbiological samples (pocket swab, pocket tissue biopsies, generator, and leads). Conventional culturing was performed, and device components were sonicated and examined with an amplicon-based metagenomic analysis using next-generation sequencing. The results were compared with a reference standard-identified causative pathogen. RESULTS: In 110 patients with clinical signs of pocket (n = 50) or systemic DRI (n = 60), we collected 109 pocket swabs, 220 pocket tissue biopsies, 106 generators, 235 leads, and a minimum 1 set of blood cultures from 102 patients. Combining all findings, we identified the causative pathogen in 95% of cases, irrespective of DRI type. The usability of each microbiological method differed between DRI types. In pocket DRI, next-generation sequencing analysis of generators achieved sensitivity of 90%. For systemic DRI, blood cultures reached sensitivity of 93%. CONCLUSION: Using a strategy including sonication and next-generation sequencing, we identified the causative pathogen in 95% of DRI. Sensitivity of microbiological methods differed according to the type of DRI.

New onset anxiety and depression in patients with an implantable cardioverter defibrillator during 24 months of follow-up (data from the national DEFIB-WOMEN study).

OBJECTIVE: To examine the cumulative incidence of and covariates' association with new onset anxiety and depression in implantable cardioverter defibrillator (ICD) patients during 24 months of follow-up in patients without depression and anxiety at implant. METHODS: Patients (n = 1040; 155 (14.9%) women; mean age: 64.2 ± 10.6) with a first-time ICD enrolled in the national, multi-center prospective observational DEFIB-WOMEN study comprised the study cohort. We obtained information on demographic and clinical data from the Danish Pacemaker and ICD Register. RESULTS: During 24 months of follow-up, 138 (14.5%) patients developed new onset anxiety and 109 (11.3%) new onset depression. Age ≥ 60 [HR:0.60;95%CI:0.40-0.90] and an anxiety score between 3 and 4 [HR:2.85; 95%CI:1.71-4.75] and 5-7 [HR:5.97; 95%CI:3.77-9.45] on the Hospital Anxiety and Depression Scale (HADS) were associated with different hazards of new onset anxiety during follow-up. Age ≥ 60 [HR:0.62;95%CI:0.42-0.93] and a HADS depression score between 3 and 4 [HR:2.99;95%CI:1.80-4.95] and 5-7 [HR:6.45; 95%CI:4.12-10.10] were associated with different hazards of new onset depression. CONCLUSION: During 24 months of follow-up, respectively 14.5% and 11.3% of patients developed new onset anxiety and depression, suggesting that screening patients at several timepoints, and in particular those with even minimally elevated HADS scores at baseline, may be warranted to identify patients at risk for poor health outcomes.