Process mapping strategies to prevent subcutaneous implantable cardioverter-defibrillator infections.

BACKGROUND: Infection remains a major complication of cardiac implantable electronic devices and can lead to significant morbidity and mortality. Implantable devices that avoid transvenous leads, such as the subcutaneous implantable cardioverter-defibrillator (S-ICD), can reduce the risk of serious infection-related complications, such as bloodstream infection and infective endocarditis. While the 2017 AHA/ACC/HRS guidelines include recommendations for S-ICD use for patients at high risk of infection, currently, there are no clinical trial data that address best practices for the prevention of S-ICD infections. Therefore, an expert panel was convened to develop a consensus on these topics. METHODS: An expert process mapping methodology was used to achieve consensus on the appropriate steps to minimize or prevent S-ICD infections. Two face-to-face meetings of high-volume S-ICD implanters and an infectious diseases specialist, with expertise in cardiovascular implantable electronic device infections, were conducted to develop consensus on useful strategies pre-, peri-, and postimplant to reduce S-ICD infection risk. RESULTS: Expert panel consensus on recommended steps for patient preparation, S-ICD implantation, and postoperative management was developed to provide guidance in individual patient management. CONCLUSION: Achieving expert panel consensus by process mapping methodology for S-ICD infection prevention was attainable, and the results should be helpful to clinicians in adopting interventions to minimize risks of S-ICD infection.

Device-related infection associated with increased mortality risk in de novo transvenous implantable cardioverter-defibrillator medicare patients.

INTRODUCTION: Transvenous implantable cardioverter-defibrillators (TV-ICD) infection is a serious complication that frequently requires complete device removal for attempted cure, which can be associated with patient morbidity and mortality. The objective of this study is to assess mortality risk associated with TV-ICD infection in a large Medicare population with de novo TV-ICD implants. METHODS: A survival analysis was conducted using 100% fee-for-service Medicare facility-level claims data to identify patients who underwent de novo TV-ICD implantation between 7/2016 and 1/2018. TV-ICD infection within 2 years of implantation was identified using International Classification of Disease, 10th Edition and current procedural terminology codes. Baseline patient risk factors associated with mortality were identified using the Charlson Comorbidity Index categories. Infection was treated as a time-dependent variable in a multivariate Cox proportional hazards model to account for immortal time bias. RESULTS: Among 26,742 Medicare patients with de novo TV-ICD, 518 (1.9%) had a device-related infection. The overall number of decedents was 4721 (17.7%) over 2 years, with 4555 (17%) in the noninfection group and 166 (32%) in the infection group. After adjusting for baseline patient demographic characteristics and various comorbidities, the presence of TV-ICD infection was associated with an increase of 2.4 (95% CI: 2.08-2.85) times in the mortality hazard ratio. CONCLUSION: The rate of TV-ICD infection and associated mortality in a large, real-world Medicare population is noteworthy. The positive association between device-related infection and risk of mortality further highlights the need to reduce infections.

Diagnosis and management of subcutaneous implantable cardioverter-defibrillator infections based on process mapping.

BACKGROUND: Infection is a well-recognized complication of cardiovascular implantable electronic device (CIED) implantation, including the more recently available subcutaneous implantable cardioverter-defibrillator (S-ICD). Although the AHA/ACC/HRS guidelines include recommendations for S-ICD use, currently there are no clinical trial data that address the diagnosis and management of S-ICD infections. Therefore, an expert panel was convened to develop consensus on these topics. METHODS: A process mapping methodology was used to achieve a primary goal - the development of consensus on the diagnosis and management of S-ICD infections. Two face-to-face meetings of panel experts were conducted to recommend useful information to clinicians in individual patient management of S-ICD infections. RESULTS: Panel consensus of a stepwise approach in the diagnosis and management was developed to provide guidance in individual patient management. CONCLUSION: Achieving expert panel consensus by process mapping methodology in S-ICD infection diagnosis and management was attainable, and the results should be helpful in individual patient management.

Anesthesia for subcutaneous implantable cardioverter-defibrillator implantation: Perspectives from the clinical experience of a U.S. panel of physicians.

BACKGROUND AND OBJECTIVE: Worldwide adoption of the subcutaneous implantable cardioverter-defibrillator (S-ICD) for preventing sudden cardiac death continues to increase, as longer-term evidence demonstrating the safety and efficacy of the S-ICD expands. As a relatively new technology, comprehensive anesthesia guidance for the management of patients undergoing S-ICD placement is lacking. This article presents advantages and disadvantages of different periprocedural sedation and anesthesia options for S-ICD implants including general anesthesia, monitored anesthesia care, regional anesthesia, and nonanesthesia personnel administered sedation and analgesia. METHODS: Guidance, for approaches to anesthesia care during S-ICD implantation, is presented based upon literature review and consensus of a panel of high-volume S-ICD implanters, a regional anesthesiologist, and a cardiothoracic anesthesiologist with significant S-ICD experience. The panel developed suggested actions for perioperative sedation, anesthesia, surgical practices, and a decision algorithm for S-ICD implantation. CONCLUSIONS: While S-ICD implantation currently requires higher sedation than transvenous ICD systems, the panel consensus is that general anesthesia is not required or is obligatory for the majority of patients for the experienced S-ICD implanter. The focus of the implanting physician and the anesthesia services should be to maximize patient comfort and take into consideration patient-specific comorbidities, with a low threshold to consult the anesthesiology team.

Comparison of general obesity and measures of body fat distribution in older adults in relation to cancer risk: meta-analysis of individual participant data of seven prospective cohorts in Europe.

BACKGROUND: We evaluated the associations of anthropometric indicators of general obesity (body mass index, BMI), an established risk factor of various cancer, and body fat distribution (waist circumference, WC; hip circumference, HC; and waist-to-hip ratio, WHR), which may better reflect metabolic complications of obesity, with total obesity-related and site-specific (colorectal and postmenopausal breast) cancer incidence. METHODS: This is a meta-analysis of seven prospective cohort studies participating in the CHANCES consortium including 18 668 men and 24 751 women with a mean age of 62 and 63 years, respectively. Harmonised individual participant data from all seven cohorts were analysed separately and alternatively for each anthropometric indicator using multivariable Cox proportional hazards models. RESULTS: After a median follow-up period of 12 years, 1656 first-incident obesity-related cancers (defined as postmenopausal female breast, colorectum, lower oesophagus, cardia stomach, liver, gallbladder, pancreas, endometrium, ovary, and kidney) had occurred in men and women. In the meta-analysis of all studies, associations between indicators of adiposity, per s.d. increment, and risk for all obesity-related cancers combined yielded the following summary hazard ratios: 1.11 (95% CI 1.02-1.21) for BMI, 1.13 (95% CI 1.04-1.23) for WC, 1.09 (95% CI 0.98-1.21) for HC, and 1.15 (95% CI 1.00-1.32) for WHR. Increases in risk for colorectal cancer were 16%, 21%, 15%, and 20%, respectively per s.d. of BMI, WC, HC, and WHR. Effect modification by hormone therapy (HT) use was observed for postmenopausal breast cancer (Pinteraction<0.001), where never HT users showed an ∼20% increased risk per s.d. of BMI, WC, and HC compared to ever users. CONCLUSIONS: BMI, WC, HC, and WHR show comparable positive associations with obesity-related cancers combined and with colorectal cancer in older adults. For postmenopausal breast cancer we report evidence for effect modification by HT use.

Overweight duration in older adults and cancer risk: a study of cohorts in Europe and the United States.

Recent studies have shown that cancer risk related to overweight and obesity is mediated by time and might be better approximated by using life years lived with excess weight. In this study we aimed to assess the impact of overweight duration and intensity in older adults on the risk of developing different forms of cancer. Study participants from seven European and one US cohort study with two or more weight assessments during follow-up were included (n = 329,576). Trajectories of body mass index (BMI) across ages were estimated using a quadratic growth model; overweight duration (BMI ≥ 25) and cumulative weighted overweight years were calculated. In multivariate Cox models and random effects analyses, a longer duration of overweight was significantly associated with the incidence of obesity-related cancer [overall hazard ratio (HR) per 10-year increment: 1.36; 95 % CI 1.12-1.60], but also increased the risk of postmenopausal breast and colorectal cancer. Additionally accounting for the degree of overweight further increased the risk of obesity-related cancer. Risks associated with a longer overweight duration were higher in men than in women and were attenuated by smoking. For postmenopausal breast cancer, increased risks were confined to women who never used hormone therapy. Overall, 8.4 % of all obesity-related cancers could be attributed to overweight at any age. These findings provide further insights into the role of overweight duration in the etiology of cancer and indicate that weight control is relevant at all ages. This knowledge is vital for the development of effective and targeted cancer prevention strategies.

Escherichia coli kduD encodes an oxidoreductase that converts both sugar and steroid substrates.

A previously unidentified oxidoreductase from Escherichia coli catalyzes the regioselective reduction of eukaryotic steroid hormone 11-deoxycorticosterone (11-DOC) to the valuable bioactive product 4-pregnen-20,21-diol-3-one. In nature, a reduction of C-20 carbonyl of C21 steroids is catalyzed by diverse NAD(P)H-dependent oxidoreductases. Enzymes that possess 20-ketosteroid reductase activity, however, have never before been described in E. coli. Our present study aimed to identify and characterize the E. coli enzyme which possesses 20-ketosteroid reductase activity against eukaryotic steroid hormone 11-DOC. We partially purified the enzyme from E. coli DH5α using protein chromatography techniques. Mass spectrometry revealed the presence of three NADH-specific oxidoreductases in the sample. The genes encoding these oxidoreductases were cloned and overexpressed in E. coli UT5600 (DE3). Only the overexpression of 2-dehydro-3-deoxy-D-gluconate 5-dehydrogenase (KduD) encoded by kduD gene enabled the whole-cell biotransformation of 11-DOC. A 6xHis-tagged version of KduD was purified to homogeneity and found to reduce several eukaryotic steroid hormones and catalyze the conversion of novel sugar substrates. KduD from E. coli is therefore a promiscuous enzyme that has a predicted role in sugar conversion in vivo but can be used for the production of valuable bioactive 20-hydroxysteroids.

Embolization of percutaneous left atrial appendage closure devices: Timing, management and clinical outcomes.

BACKGROUND: Left atrial appendage (LAA) occluder embolization is an infrequent but serious complication. OBJECTIVES: We aim to describe timing, management and clinical outcomes of device embolization in a multi-center registry. METHODS: Patient characteristics, imaging findings and procedure and follow-up data were collected retrospectively. Device embolizations were categorized according to 1) timing 2) management and 3) clinical outcomes. RESULTS: Sixty-seven centers contributed data. Device embolization occurred in 108 patients. In 70.4 % of cases, it happened within the first 24 h of the procedure. The device was purposefully left in the LA and the aorta in two (1.9 %) patients, an initial percutaneous retrieval was attempted in 81 (75.0 %) and surgery without prior percutaneous retrieval attempt was performed in 23 (21.3 %) patients. Two patients died before a retrieval attempt could be made. In 28/81 (34.6 %) patients with an initial percutaneous retrieval attempt a second, additional attempt was performed, which was associated with a high mortality (death in patients with one attempt: 2.9 % vs. second attempt: 21.4 %, p < 0.001). The primary outcome (bailout surgery, cardiogenic shock, stroke, TIA, and/or death) occurred in 47 (43.5 %) patients. Other major complications related to device embolization occurred in 21 (19.4 %) patients. CONCLUSIONS: The majority of device embolizations after LAA closure occurs early. A percutaneous approach is often the preferred method for a first rescue attempt. Major adverse event rates, including death, are high particularly if the first retrieval attempt was unsuccessful. CONDENSED ABSTRACT: This dedicated multicenter registry examined timing, management, and clinical outcome of device embolization. Early embolization (70.4 %) was most frequent. As a first rescue attempt, percutaneous retrieval was preferred in 75.0 %, followed by surgical removal (21.3 %). In patients with a second retrieval attempt a higher mortality (death first attempt: 2.9 % vs. death second attempt: 24.1 %, p < 0.001) was observed. Mortality (10.2 %) and the major complication rate after device embolization were high.

Closure of Iatrogenic Atrial Septal Defect After Placement of Left Atrial Appendage Closure Device.

An 86-year-old woman experienced hypoxia with right-to-left flow across an iatrogenic atrial septal defect after deployment of a left atrial appendage closure device. Emergent closure of the defect was performed with an atrial septal occluder device with resolution of hypoxia. (Level of Difficulty: Intermediate.).

Effect of clazosentan, a selective endothelin A receptor antagonist, and tezosentan, a dual endothelin A/B antagonist, on pulsatile shear stress induced constriction of the iliac in the anaesthetized pig.

1. The effects of changes in mean and pulsatile shear stress on the diameter of the iliac of the anaesthetized pig were investigated in the presence of clazosentan and tezosentan. 2. A total of 17 pigs were used. Mean shear stress was increased by infusing acetylcholine downstream (2-20 µg/min) through the deep femoral artery. Pulsatile shear stress was enhanced first by injecting varying volumes (1-10 mL) of calcium gluconate (stock 10 mg/mL) directly into the left ventricle. Second, by electrical stimulation of the left sympathetic nerves to the heart (1-16 Hz, 4 min duration, supramaximal voltage). 3. An increase in mean shear stress induced a vasodilation that was not altered significantly by the selective endothelin A antagonist clazosentan (10 mg/kg i.v.). Similarly, the vasoconstriction induced by an increase in pulsatile shear stress brought about by either calcium gluconate injections or left sympathetic nerve stimulation was unaffected by clazosentan. However, tezosentan (10 mg/kg i.v.), significantly attenuated the vasoconstriction induced by an increase in pulsatile shear stress. 4. In conclusion, an increase in pulsatile shear stress causes vasoconstriction of the pig iliac artery, which is attenuated by dual endothelin receptor antagonism, but not by specific endothelin A blockade.

Real-world outcomes in cardiac resynchronization therapy patients: design and baseline demographics of the SMART- Registry.

AIMS: The SMART (Strategic MAnagement to optimize response to cardiac Resynchronization Therapy) Registry was designed to assess real-world outcomes for patients receiving a cardiac resynchronization therapy defibrillator (CRT-D) and to better understand which programming and optimization techniques are used and how effective they are. METHODS AND RESULTS: The SMART Registry is a global, multicentre, prospective, observational, post-market CRT-D registry with a planned enrolment of 2000 subjects from a maximum of 200 sites in Europe, North America, and Asia-Pacific region. Each subject will be followed up for a minimum of 12 months. The primary endpoint of CRT response rate at 12 months is defined by a clinical composite score of all-cause mortality, heart failure events, New York Heart Association Class, and quality of life as assessed by a patient global assessment instrument. A subgroup composed of the first 103 consecutive European subjects implanted with an NG4 device will have left ventricular multisite pacing feature enabled at any time during the initial 12 months of follow-up. The primary endpoint for this sub-analysis will be the NG4 PG-related complication-free rate at 36 months. CONCLUSIONS: The SMART Registry achieved its recruitment target in August 2019, with 2014 patients enrolled. The baseline demographics demonstrated that patients were generally older, with greater co-morbidity, and on more contemporary medical therapy than in the key CRT trials. The results of the SMART Registry will determine which programming and optimization techniques are effective in this real-world population.

Device-related infection in de novo transvenous implantable cardioverter-defibrillator Medicare patients.

BACKGROUND: Cardiac device infection is a serious complication of implantable cardioverter-defibrillator (ICD) placement and requires complete device removal with accompanying antimicrobial therapy for durable cure. Recent guidelines have highlighted the need to better identify patients at high risk of infection to assist in device selection. OBJECTIVE: To estimate the prevalence of infection in de novo transvenous (TV) ICD implants and assess factors associated with infection risk in a Medicare population. METHODS: A retrospective cohort study was conducted using 100% Medicare administrative and claims data to identify patients who underwent de novo TV-ICD implantation (July 2016-December 2017). Infection within 720 days of implantation was identified using ICD-10 codes. Baseline factors associated with infection were identified by univariable logistic regression analysis of all variables of interest, including conditions in Charlson and Elixhauser comorbidity indices, followed by stepwise selection criteria with a P ≤ .25 for inclusion in a multivariable model and a backwards, stepwise elimination process with P ≤ .1 to remain in the model. A time-to-event analysis was also conducted. RESULTS: Among 26,742 patients with de novo TV-ICD, 519 (1.9%) developed an infection within 720 days post implant. While more than half (54%) of infections occurred during the first 90 days, 16% of infections occurred after 365 days. Multivariable analysis revealed several significant predictors of infection: age <70 years, renal disease with dialysis, and complicated diabetes mellitus. CONCLUSION: The rate of de novo TV-ICD infection was 1.9%, and identified risk factors associated with infection may be useful in device selection.

Experimental determination and data-driven prediction of homotypic transmembrane domain interfaces.

Interactions between their transmembrane domains (TMDs) frequently support the assembly of single-pass membrane proteins to non-covalent complexes. Yet, the TMD-TMD interactome remains largely uncharted. With a view to predicting homotypic TMD-TMD interfaces from primary structure, we performed a systematic analysis of their physical and evolutionary properties. To this end, we generated a dataset of 50 self-interacting TMDs. This dataset contains interfaces of nine TMDs from bitopic human proteins (Ire1, Armcx6, Tie1, ATP1B1, PTPRO, PTPRU, PTPRG, DDR1, and Siglec7) that were experimentally identified here and combined with literature data. We show that interfacial residues of these homotypic TMD-TMD interfaces tend to be more conserved, coevolved and polar than non-interfacial residues. Further, we suggest for the first time that interface positions are deficient in ß-branched residues, and likely to be located deep in the hydrophobic core of the membrane. Overrepresentation of the GxxxG motif at interfaces is strong, but that of (small)xxx(small) motifs is weak. The multiplicity of these features and the individual character of TMD-TMD interfaces, as uncovered here, prompted us to train a machine learning algorithm. The resulting prediction method, THOIPA (www.thoipa.org), excels in the prediction of key interface residues from evolutionary sequence data.

Effect of submucosal dexamethasone injections in the prevention of postoperative pain, trismus, and oedema associated with mandibular third molar surgery: a systematic review and meta-analysis.

The aim of this systematic review and meta-analysis was to determine whether there are clinically effective reductions in postoperative pain, oedema, and trismus following submucosal dexamethasone administration during impacted mandibular third molar surgery. An electronic database search was conducted up to and including June 2018. Randomized and quasi-randomized trials assessing the effects of submucosal dexamethasone in adult patients undergoing mandibular third molar surgery were included. The mean differences or standardized mean differences were extracted and pooled using the fixed-effects or random-effects model. Seventeen trials were included and independently assessed for risk of bias. There was low quality evidence that submucosal dexamethasone reduces early postoperative pain, early and late postoperative trismus, and late postoperative oedema after mandibular third molar extraction. Moderate quality evidence was found for the reduction of late postoperative pain and early postoperative oedema. The greatest clinical effect of submucosal dexamethasone injection during impacted mandibular third molar surgery was a reduction of early postoperative pain (number needed to treat (NNT) = 4) and early postoperative oedema (NNT = 5). The reduction in trismus was not clinically significant (<5 mm). Further research focusing on strengthening the quality of evidence, investigating potential harms and a definitive protocol for submucosal administration during mandibular third molar surgery is required.

Differentiating atrioventricular nodal reentrant tachycardia from atrioventricular reentrant tachycardia by DeltaHA values during entrainment from the ventricle.

BACKGROUND: Differentiating atrioventricular nodal reentrant tachycardia (AVNRT) from orthodromic atrioventricular reentrant tachycardia (AVRT) can be difficult. The His bundle and atria are activated sequentially over the AV node during entrainment of AVNRT from the ventricle but simultaneously during supraventricular tachycardia (SVT). They are activated in parallel during entrainment of AVRT but sequentially during SVT. OBJECTIVE: The purpose of this study was to test the hypothesis that a DeltaHA (HA((entrainment)) - HA((SVT))) cutoff value of 0 reliably differentiates AVNRT from AVRT. METHODS AND RESULTS: Of 61 patients undergoing electrophysiologic evaluation for paroxysmal SVT, retrograde His-bundle potentials were recorded in 57 (93%) and entrainment performed in 49 (34 AVNRT, 15 AVRT). DeltaHA values during entrainment from the ventricle were significantly longer during AVNRT than AVRT (31 +/- 24 ms vs -38 +/- 31 ms, P <.001). All DeltaHA values were positive (minimum: 3 ms) for AVNRT and negative (maximum: -2 ms) for AVRT. DeltaHA of 0 had sensitivity, specificity. and positive predictive value of 100% for correct diagnosis. CONCLUSION: The DeltaHA criterion during entrainment of tachycardia from the ventricle reliably differentiates AVNRT (positive values) from AVRT (negative values).

Lead-associated endocarditis: the important role of methicillin-resistant Staphylococcus aureus.

BACKGROUND: Infection is a potentially life-threatening complication of cardiac device implantation. Lead-associated endocarditis (LAE) may be the most serious complication since it is associated with a high mortality. METHODS: The medical records of patients referred to our institution for the treatment of LAE between 1999 and 2007 were reviewed. RESULTS: A total of 51 of 107 patients referred for device-related infections met the criteria for LAE. Of these, 19 occurred within 6 months of their most recent procedure (early), while the remaining 32 occurred more than 6 months later (mean = 31.9 months post procedure). Devices included pacemakers in 33 patients and ICDs in 18 patients. The most common organism responsible for infection was Staphylococcus aureus (S. aureus) followed by coagulase-negative staphylocci (22%) and streptococci (12%). Methicillin-resistant S. aureus (MRSA) accounted for 67% of the S. aureus infections. Coagulase-negative staphylococci were responsible for only 26% of early and 19% of late cases. A distant site of infection was common (26/51 = 51%), particularly in patients with MRSA LAE. The device and leads were removed percutaneously in all patients. Only one patient failed to respond to intravenous antibiotics. CONCLUSIONS: Our data suggest that methicillin-resistant S. aureus is an important pathogen in LAE. Since many infections occur months after the last device procedure, hematogenous spread of organisms from a distant site may be an important contributing factor. These data suggest that strategies to prevent hematogenous infection, particularly with S. aureus, are critical in patients with implantable cardiac devices.

The Identification of Risk Factors for Chronic Chikungunya Arthralgia in Grenada, West Indies: A Cross-Sectional Cohort Study.

BACKGROUND: Chikungunya virus (CHIKV) is a re-emerging arboviral pathogen. In 2014, an explosive CHIKV outbreak occurred in Grenada, West Indies, infecting approximately 60% of the population. In approximately 50% of cases, CHIKV infection transitions to painful arthralgia that can persist for years. Elucidation of the risk factors for chronic disease is imperative to the development of effective risk management strategies and specific therapeutics. METHODS: We conducted a cross-sectional study of 240 people who were tested for CHIKV during the outbreak. We administered questionnaires to examine demographic, behavioral, psychological, social, and environmental factors to identify associations with chronic disease. Physical examinations were performed and persistent symptoms were recorded. RESULTS: Ethnicity and socioeconomic status were not associated with risk of chronic joint pain. Female sex increased risk, and age was demonstrated to be predictive of chronic CHIKV sequelae. Mosquito avoidance behaviors did not reduce risk. Patients suffering joint pains, generalized body ache, and weakness in the extremities during acute infection were more likely to develop chronic arthralgia, and an increased duration of acute disease also increased risk. CONCLUSIONS: These data demonstrate that chronic CHIKV affects people across the ethnic and socioeconomic spectrum, and it is not reduced by vector avoidance activity. Increased duration of acute symptoms, in particular acute joint pain, was strongly correlated with the risk of persistent arthralgia, thus effective clinical management of acute CHIKV disease could reduce burden of chronic CHIKV.

Cardiac resynchronization therapy: from creation to evolution--an evidence-based review.

In the past decade, cardiac resynchronization therapy (CRT), achieved by simultaneous left and right ventricular pacing, has emerged as a potent therapeutic option for patients with congestive heart failure. Electrical dyssynchrony, most often manifested by left bundle branch block on the surface 12-lead electrocardiogram, results in mechanical dyssynchrony of the left ventricular septum and free wall, which decreases cardiac efficiency. In patients with ejection fractions <30%, New York Heart Association (NYHA) class III or IV, and QRS width >120 ms, CRT improves clinical parameters such as 6-minute walk distances, quality-of-life scores, and NYHA functional class. Long-term reverse remodeling of the failing ventricle results in reductions in congestive heart failure hospitalizations and mortality independent of defibrillator therapy. While most patients show significant improvement, a small proportion fail to respond. Appropriately identifying patients who will benefit most from CRT and timing the initiation of resynchronization therapy remain areas of intense investigation.