Jacob Moesgaard Larsen

Reference intervals and age and gender dependency for arterial blood gases and electrolytes in adults.

Abstract Background: Although results from blood gas analyzers are frequently used in clinical work surprisingly few and small studies have examined reference intervals for arterial blood gases and acid-base status. We have established reference values based on a large group of healthy people with a wide age distribution. Methods: A group of medical students (n=182) aged 20–32 years old and a group of health professionals aged 21–76 years were used in this study. Arterial samples were analyzed on the blood gas analyzer ABL from RadiometerTM. Age and gender dependency was examined for all analytes and reference intervals were calculated non-parametrically. Results: Females had significantly higher pH and lower PaCO2 (partial pressure of carbon dioxide in an arterial sample), base excess (BE, standard, extra cellular fluid), plasma standard and actual HCO3, when compared to males (p<0.01). However, the differences were minor and common reference intervals were therefore also determined, generally at the same level as previously published. The lactate values were similar among the genders but with a high upper limit of 2.5 mmol/L. The non-smoker group of females and males had similar PaO2 values (partial pressure of oxygen in an arterial sample). However, an age dependent effect was found and PaO2 decreased by 0.29 kPa per decade (confidence interval of slope –0.11 to –0.47 kPa). Electrolytes and anion gap results depicted smaller differences from previous published reference intervals for sodium (136–141 mmol/L) and anion gap (10–16 mmol/L, with potassium included or 6–12 mmol/L without potassium). Conclusions: Reference intervals for analytes on modern blood gas analyzers were established on a large group of healthy people. Gender and age dependency is generally without clinical importance, except for a lower PaCO2 in women and a decreasing PaO2 with higher age.

Single-coil and dual-coil defibrillator leads and association with clinical outcomes in a complete Danish nationwide ICD cohort

BACKGROUND The best choice of defibrillator lead in patients with routine implantable cardioverter-defibrillator (ICD) is not settled. Traditionally, most physicians prefer dual-coil leads but the use of single-coil leads is increasing. OBJECTIVE The purpose of this study was to compare clinical outcomes in patients with single- and dual-coil leads. METHODS All 4769 Danish patients 18 years or older with first-time ICD implants from 2007 to 2011 were included from the Danish Pacemaker and ICD Register. Defibrillator leads were 38.9% single-coil leads and 61.1% dual-coil leads. The primary end point was all-cause mortality. Secondary end points were lowest successful energy at implant defibrillation testing, first shock failure in spontaneous arrhythmias, structural lead failure, and lead extraction outcomes. RESULTS Single-coil leads were associated with lower all-cause mortality with an adjusted hazard ratio of 0.85 (95% confidence interval 0.73-0.99; P = .04). This finding was robust in a supplementary propensity score-matched analysis. However, dual-coil leads were used in patients with slightly higher preimplant morbidity, making residual confounding by indication the most likely explanation for the observed association between lead type and mortality. The lowest successful defibrillation energy was higher using single-coil leads (23.2 ± 4.3 J vs 22.1 ± 3.9 J; P < .001). No significant differences were observed for other secondary end points showing high shock efficacies and low rates of lead failures and extraction complications. CONCLUSION Shock efficacy is high for modern ICD systems. The choice between single-coil and dual-coil defibrillator leads is unlikely to have a clinically significant impact on patient outcomes in routine ICD implants.

Prospective nationwide fluoroscopic and electrical longitudinal follow-up of recalled Riata defibrillator leads in Denmark

BACKGROUND Recalled St. Jude Medical Riata defibrillator leads are prone to insulation failures with externalized conductors (ECs). Longitudinal studies are needed to guide lead management. OBJECTIVE The purpose of this study was to describe the dynamic nature of EC and the association with electrical abnormalities and lead extraction outcomes. METHODS A nationwide cohort established in 2012 of 295 patients with recalled Riata leads with dwell time 5.1 ± 1.1 years, 34 ECs, and 19 electrical abnormalities were followed until death, lead discontinuation with fluoroscopy, or a new 2013 screening with fluoroscopy and device interrogation. RESULTS Fluoroscopic follow-up of 239 patients with normal baseline fluoroscopy revealed incident overt EC in 8 leads and borderline EC in 2 leads after 1.1 ± 0.2 years, with an incidence rate of 3.7 per 100 person-years (95% confidence interval 2.0-6.9). Fluoroscopic follow-up in 27 patients with baseline EC showed an increase in EC length of 4 ± 1 mm (P <.001) after 1.1 ± 0.3 years. Electrical follow-up in 276 patients with normal baseline electrical function demonstrated 20 incident electrical abnormalities after 1.0 ± 0.3 years, with an incidence rate of 7.1 per 100 person-years (95% confidence interval 4.6-11.0). This rate was significantly higher in leads with baseline EC, with an adjusted incidence rate ratio of 4.4 (95% confidence interval 1.7-11.5, P = .002). In 15 extractions, all leads were removed, with 2 major complications. CONCLUSION The development of EC is a dynamic process despite long lead dwell time. ECs are associated with a higher risk of electrical abnormalities. Therefore, lead replacement should be considered, especially in patients with a long life expectancy.

Failure to Treat Life-Threatening Ventricular Tachyarrhythmias in Contemporary Implantable Cardioverter–Defibrillators: Implications for Strategic Programming

Background: In clinical trials, manufacturer-specific, strategic programming of implantable cardioverter–defibrillators (ICDs), including faster detection rates, reduces unnecessary therapy but permits therapy for ventricular tachycardia/ventricular fibrillation (VF). Present consensus recommends a generic rate threshold between 185 and 200 beats per minute, which exceeds the rate tested in clinical trials for some manufacturers. In a case series, we sought to determine the relationship between programmed parameters and failure of modern ICDs to treat VF. Methods and Results: We reviewed cases in which normally functioning ICDs failed to deliver timely therapy for VF from April 2015 to January 2017 at 4 institutions. Of 10 ambulatory patients, 5 died from untreated VF, 4 had cardiac arrests requiring external shocks, and 1 was rescued by a delayed ICD shock. VF did not satisfy programmed detection criteria in 9 patients (90%). Seven of these patients had slowest detection rates that were consistent with generic recommendations but not tested in a peer-reviewed trial for their manufacturer’s ICDs. Manufacturer-specific factors interacted with fast detection rates to withhold therapy, including strict VF episode termination rules, enhancements to minimize T-wave oversensing, and features that restrict therapy to regular rhythms in ventricular tachycardia zones. Untreated VF despite recommended programming accounted for 56% of sudden deaths and 11% of all deaths during the study period. Conclusions: Complex and unanticipated interactions between manufacturer-specific features and generic programming can prevent therapy for VF. More data are needed to assess the risks and benefits of translating evidence-based detection parameters from one manufacturer to another.

Paradoxical thromboembolic stroke during extraction of a recalled St Jude Medical Riata defibrillator lead with conductor externalization

Recalled St Jude Medical Riata leads have a high rate of insulation failures with potential thrombogenic externalized conductors. We report a paradoxical thromboembolic stroke through a persistent foramen ovale during extraction of a lead with externalization. We suggest mandatory transesophageal echocardiography prior to extraction to screen for lead-related thrombosis and routes of right-to-left shunting to reduce risk of thromboembolic complications.

Validation of defibrillator lead performance registry data: insight from the Danish Pacemaker and ICD Register

Aims The validity of registry data on defibrillator lead performance is described only sparsely, despite its clinical importance. This study investigated the validity of defibrillator lead performance registry data in a nationwide and population-based registry. Methods and results We identified all reported surgical interventions due to defibrillator lead events in the Danish Pacemaker and ICD Register (DPIR) from 2000 to 2013. Medical records of all patients (n = 753) were examined blinded for 5 predefined intervention types and 18 reasons for lead intervention. The overall level of agreement for the types of lead intervention had a positive predictive value (PPV) of 89.4% [95% confidence interval (CI): 87.0-91.5%] and an adjusted agreement (κ value) of 0.81 (95% CI: 0.77-0.85) representing an almost perfect match. Regarding the reasons for lead intervention, the overall PPV was 63.0% (95% CI: 54.8-61.7%) with a κ value of 0.60 (95% CI: 0.55-0.64) representing a moderate match with only few subcategories having low PPV. By redistribution of the specific reasons for lead interventions into three categories commonly used to report lead performance, the overall PPV improved to 87.9% (95% CI: 85.2-90.2%) with a κ value of 0.82 (95% CI:0.78-0.86) representing an almost perfect match. Conclusion The validity of data on defibrillator lead performance recorded in the DPIR is excellent for the specific types of lead intervention and good for the specific reasons for defibrillator lead intervention. The validity of the less detailed overall reasons for lead interventions commonly used to report lead performance is also excellent. These findings indicate high registry data quality appropriate for scientific analysis and industry-independent post-marketing surveillance.

Need for real-world data on management of the (potentially) failing lead

This editorial refers to ‘Management of recalled implantable cardioverter-defibrillator leads at generator replacement: a decision analysis model for Fidelis leads’ by H. Burri and C. Combescure, on page 1210. Pacemaker and implantable cardioverter-defibrillator (ICD) therapy have had many successful years with extended indications, lower costs, and prolonged patient survival leading to a continuously growing population of patients with a cardiovascular implantable electronic device (CIED). Despite the fact that the device may present random and systematic failures, the lead connecting the CIED with the heart has turned out to be the ‘weakest link’ in CIED systems.1 The history has shown a series of mistakes in design and engineering giving rise to smaller enclaves of affected patients, e.g. the J-shaped Teletronics Accufix atrial lead. However, it is the combination of the surge in using ICDs for primary prophylaxis in heart failure and the quest for smaller diameter ICD leads that has created a problem of sizable dimensions as a large series of the requested new thinner ICD leads have shown poor long-term performance.2–4 Healthcare authorities and the device industry have learned important lessons regarding both short-term testing and long-term surveillance5 as well as the inferiority of product performance reports based on returned product analysis. Lead-related problems with new products will hopefully decrease in the future. Nevertheless we currently have a large population of patients with either a Medtronic Sprint Fidelis lead with a potential risk of fracture or a St Jude Medical Riata ICD lead prone to insulation defects, in whom we are only beginning to learn the extent and mechanisms of failure. Although the problematic leads have been identified and errors have been corrected in new models (or older models have been …

Fatal cardiac arrhythmia caused by tumor lysis in a patient with diffuse large B-cell lymphoma upon start of R-CHOP

Tumor lysis syndrome is rare in diffuse large cell lymphoma, but it is important to recognize the risk in patients with massive tumor burden and reduced kidney function. Very intense vigilance can be necessary despite adequate prophylactic measures and certain drugs may exacerbate electrolyte derangements.

Uninterrupted dabigatran versus warfarin for ablation in atrial fibrillation

n engl j med 376;17 nejm.org April 27, 2017 1627 From Johns Hopkins Medical Institutions, Baltimore (H.C.); Department of Cardiology– Electrophysiology, University Heart Center Hamburg, Hamburg (S.W.), Department of Cardiology, J.W. Goethe University, Frankfurt (S.H.H.), and Boehringer Ingelheim Pharma, Ingelheim am Rhein (M.N.) — all in Germany; Section of Cardiac Electrophysiology, University of California, San Francisco, San Francisco (E.P.G.); University of Toronto, Toronto (A.V.); Barts Heart Centre, Saint Bartholomew’s Hospital, London (R.S.), and Biometrics and Data Sciences Department, Boehringer Ingelheim, Bracknell (K.G.) — both in the United Kingdom; Division of Cardiology, Saiseikai Kumamoto Hospital Cardiovascular Center, Kumamoto, Japan (K.O.); St. Louis Heart and Vascular, St. Louis (H.S.); Department of Clinical Operations, Boehringer Ingelheim Regional Center Vienna, Vienna (B.B.); Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands (M.A.B.); and Cardiology Department, Miulli Hospital, Acquaviva delle Fonti, Italy (M.G.). Address reprint requests to Dr. Calkins at Johns Hopkins Medical Institutions, Sheikh Zayed Tower 7125R, 1800 Orleans St., Baltimore, MD, or at hcalkins@ jhmi . edu.1. Euthanasia. Amsterdam: Government of the Netherlands (https:/ / www .government .nl/ topics/ euthanasia). 2. Quill TE. Legal regulation of physician-assisted death — the latest report cards. N Engl J Med 2007; 356: 1911-3. 3. Onwuteaka-Philipsen BD, Brinkman-Stoppelenburg A, Penning C, de Jong-Krul GJF, van Delden JJM, van der Heide A. Trends in end-of-life practices before and after the enactment of the euthanasia law in the Netherlands from 1990 to 2010: a repeated cross-sectional survey. Lancet 2012; 380: 908-15. 4. van der Heide A, Onwuteaka-Philipsen BD, Rurup ML, et al. End-of-life practices in the Netherlands under the Euthanasia Act. N Engl J Med 2007; 356: 1957-65. 5. Chambaere K, Vander Stichele R, Mortier F, Cohen J, Deliens L. Recent trends in euthanasia and other end-of-life practices in Belgium. N Engl J Med 2015; 372: 1179-81.