Citations

AbstractBackgroundOptimal timing of cardiovascular implantable electronic device (CIED) re‐implantation following device removal due to infection is undefined. Multinational guidelines reflect this and include no specific recommendation for this timing, while others have recommended waiting at least 14 days in cases of CIED related infective endocarditis (CIED‐IE). The current work seeks to clarify this issue.MethodsWe retrospectively reviewed institutional data at Mayo Clinic, Minnesota of patients aged ≥ 18 years who developed CIED‐IE from January 1, 1991 to February 1, 2016. CIED‐IE was defined as echocardiogram reported device lead or valvular vegetation. Regression analyses were used to relate the risk of clinical outcomes to the interval between CIED removal and re‐implantation and the location of vegetations.ResultsA total of 109 patients met study inclusion criteria. A majority (68.8%) of patients were men and the median age was 68.0 years. Transoesophageal echocardiogram (TEE) was performed in 95.4% of patients, with valve vegetations detected in 33.9% (n = 37). Survival analysis comparing patients in whom device re‐implantation was < 14 days vs. ≥14 days, and further categorized by those with and without valve vegetation, showed a significant difference (P = 0.028); patients with valve vegetation and reimplantation interval < 14 days had the lowest (58.7%) 12‐month survival. When adjusted for valve vegetation, longer time interval for reimplantation trended toward increased hospital length of stay (P = 0.079).ConclusionOur findings suggest that the recommended 14‐day delay between CIED extraction and re‐implantation in CIED‐IE patients is associated with a survival benefit, but longer length of hospital stay following re‐implantation.

Risk of CAD increases at menopause and platelets contribute to the etiology of CAD. We hypothesized that individual variation in platelet procoagulant activity at menopause correlates with the extent of CAD as reflected by coronary artery calcification ( CAC ). We developed several novel and global assays of platelet procoagulant activity: dense (ATP release) and alpha (P‐selectin expression) granule secretion and GPα IIb β 3 fibrinogen‐binding (PAC1 binding) to ADP stimulation, and prostaglandin E 1 (PEG 1 ) sensitivity as a surrogate for prostacyclin sensitivity. Platelets were prepared from venous blood collected from women screened for the Kronos Early Estrogen Prevention Study (n=125; mean±SD age=52.5±2.4 years) within 19.4±9.2 months of last menses. Baseline CAC score was determined. Of conventional CAD risk factors, only systolic blood pressure correlated with positive CAC score (n=23). ATP secretion tended to be less in women with positive CAC scores and was negatively correlated with blood glucose (P<0.001). P‐selectin expression and PAC1 binding increased with total cholesterol (P<0.05). PEG 1 sensitivity increased with increasing age and waist circumference (P<0.05). These results indicate that platelet functions change with age and in association with conventional risk factors for the disease in women at menopause. Supported by the Kronos Longevity Research Institute and NIH HL90639.

Introduction: Cardiovascular implantable electronic devices (CIED) infections are frequently complicated with bloodstream infection (BSI). Complete device removal and prolonged antimicrobial therapy is essential for cure. The frequency of persistent BSI after source control (device extraction) is not well described. This study aims to assess the utility of repeat blood cultures (BC) after device extraction as recommended by the American Heart Association (AHA) guidelines. Methods: We selected patients who presented with BSI in the setting of CIED infection and underwent device removal at Mayo Clinic Rochester between 2012 and 2017. Cases where BC were not drawn prior to extraction, or repeated within 72 hours of device extraction, or met criteria for contamination were excluded. Results: Of 656 patients who underwent CIED extraction for device infection, 190 with post-extraction BC met study criteria. Among the final study cohort (Table 1), 159 patients had negative BC, while 31 had positive BC following CIED extraction. Pre-extraction, the most common causative organism was Staphylococcus aureus (91/190, 48%) (Figure 1a). Post-extraction, 22 of the 31 (71%) cases of persistent BSI were due to S. aureus (Fig 1b). The median duration of BSI was not significantly different between negative and positive BC groups (3 versus 4 days, p=0.92). Conclusions: Majority of patients had resolution of BSI after CIED extraction. S. aureus was the most common cause of persistent BSI post-extraction. Our findings support the AHA guidelines of repeating BC after device extraction, especially for S aureus .

Abstract Background The use of extracorporeal membrane oxygenation (ECMO) in critically ill adults is increasing. There are currently no guidelines for antimicrobial prophylaxis. We analyzed 7 years of prophylactic antimicrobial use across 3 time series for patients on ECMO at our institution in the development, improvement, and streamlining of our ECMO antimicrobial prophylaxis protocol. Methods In this quasi-experimental interrupted time series analysis, we evaluated the impact of an initial ECMO antimicrobial prophylaxis protocol, implemented in 2014, on antimicrobial use and National Healthcare Safety Network–reportable infection rates. Then, following a revision and streamlining of the protocol in November 2018, we reevaluated the same metrics. Results Our study population included 338 intensive care unit patients who received ECMO between July 2011 and November 2019. After implementation of the first version of the protocol, we did not observe significant changes in antimicrobial use or infection rates in these patients; however, following revision and streamlining of the protocol, we demonstrated a significant reduction in broad-spectrum antimicrobial use for prophylaxis in patients on ECMO without any evidence of a compensatory increase in infection rates. Conclusions Our final protocol significantly reduces broad-spectrum antimicrobial use for prophylaxis in patients on ECMO. We propose a standard antimicrobial prophylaxis regimen for patients on ECMO based on current evidence and our experience. Summary: There are no guidelines for antimicrobial prophylaxis in patients on extracorporeal membrane oxygenation (ECMO). A rational approach employing concepts of antimicrobial stewardship can drive logical antimicrobial selection for prophylaxis in patients on ECMO without adversely impacting outcomes.

Background: The identification of blood-borne biomarkers for the diagnosis and prognosis of Alzheimer’s disease and related dementias is more feasible at the population level than obtaining cerebrospinal fluid or neuroimaging markers. Objective: This study determined the association of blood microvesicles, derived from cells of the neurovascular unit, with brain amyloid-β deposition in menopausal women. Methods: A subset of women from the Kronos Early Estrogen Prevention Study underwent brain amyloid-β positron emission tomography three years following cessation of study treatment with placebo (PL, n = 29), transdermal 17β-estradiol (tE2; n = 21), or oral conjugated equine estrogen (oCEE; n = 17). Isolated peripheral venous blood microvesicles were analyzed by digital flow cytometry using fluorophore conjugated antibodies directed toward total tau, amyloid-β 1–42 (Aβ1–42), neuron specific class III β-tubulin (Tuj1), microglia ionized calcium -binding adaptor molecule 1(Iba1), glial fibrillary acid protein (GFAP), and low density lipoprotein receptor-related protein1 (LRP1). Principal components analysis reduced the dimensionality of these selected six markers to two principal components (PCs). Proportional odds ordinal logistic regression analysis was used with amyloid-β deposition regressed on these PCs. Results: Only the number of microvesicles positive for Aβ1–42 differed statistically among prior treatment groups (median [IQR]: 6.06 [2.11, 12.55] in PL; 2.49 [0.73, 3.59] in tE2; and 4.96 [0.83, 10.31] in oCEE; p = 0.032). The joint association between the 2 PCs and brain amyloid-β deposition was significant (p = 0.045). Conclusion: Six selected markers expressing peripheral blood microvesicles derived from cells of the neurovascular unit, when summarized into two principal components, were associated with brain amyloid-β deposition.

Abstract Background A population-based study of infective endocarditis (IE) in Olmsted County, Minnesota, provides a unique opportunity to define temporal and seasonal variations in IE incidence over an extended time period. Methods This was a population-based review of all adults (≥18 years) residing in Olmsted County, Minnesota, with definite or possible IE using the Rochester Epidemiology Project from January 1, 1970, through December 31, 2018. Poisson regression was used to characterize the trends in IE incidence; models were fitted with age, sex, calendar time, and season, allowing for nonlinearity and nonadditivity of their effects. Results Overall, 269 cases of IE were identified over a 49-year study period. The median age of IE cases was 67.2 years, and 33.8% were female. The overall age- and sex-adjusted incidence of IE was 7.9 cases per 100 000 person-years (95% CI, 7.0–8.9), with corresponding rates of 2.4, 2.4, 0.9, and 0.7 per 100 000 person-years for Staphylococcus aureus, viridans group streptococci (VGS), Enterococcus species, and coagulase-negative staphylococci IE, respectively. Temporal trends varied by age, sex, and season, but on average IE incidence increased over time (P = .021). Enterococcal IE increased the most (P = .018), while S. aureus IE appeared to increase but mostly in the winter months (P = .018). Between 1996 and 2018, the incidence of VGS IE was relatively stable, with no statistically significant difference in the trends before and after the 2007 AHA IE prevention guidelines. Conclusions Overall, IE incidence, and specifically enterococcal IE, increased over time, while S. aureus IE was seasonally dependent. There was no statistically significant difference in VGS IE incidence in the periods before and after publication of the 2007 AHA IE prevention guidelines.

Abstract Background Transcatheter aortic valve replacement (TAVR) was initially approved as an alternative to surgery for patients at high surgical risk. However, it is now being considered for patients with intermediate and low surgical risk. This will result in the expansion of patient pool for TAVR; hence it is of interest to ascertain risk of blood stream infection (BSI) and infective endocarditis (IE) following TAVR. We aim to study the incidence, epidemiology and risk factors associated with IE in patients who underwent TAVR and subsequently developed a BSI. Methods A population-based study was conducted in 7 counties in southeastern Minnesota using the expanded Rochester Epidemiology Project (E-REP) for all adult (≥18 years) patients who underwent TAVR from January 1st, 2010 to December 31st, 2018. Transcatheter procedures that included replacement of either the aortic or mitral valve were included. Medical records were screened for development of BSI from time of TAVR until May 15th, 2020. Patients were classified as having BSI only, BSI with IE at outset, or BSI with subsequent development of new IE. ‘Early’ IE was defined as that occurring &lt; 12 months following TAVR, with subsequent cases defined as ‘late’ IE. Results A total of 247 patients underwent TAVR during the study period. There were 24 patients with of BSI and 10 (42%) developed IE with an annual incidence of 5 per 1000 persons-years. Median age for patients who developed IE was 85.4 years. Male gender was affected predominantly (70%). Six developed IE at outset of BSI, while four developed IE subsequent to IE. The median time to development of IE was 791 days following TAVR. There was an equal number of early and late IE cases (n=5). The most common pathogen causing IE was viridians group streptococci (n=4) followed by enterococci and coagulase-negative staphylococci with 2 patients each. Mean Charlson comorbidity index was 6.6. Two patients with IE died before resolution of infection (20%). Conclusion The incidence of BSI and subsequent IE in patients with TAVR was low in our population. Due to the small number of BSI and IE cases, statistical analysis was not feasible. An analysis of all cases seen at Mayo Clinic is planned since the number of cases would be much higher to investigate potential risk factors associated with BSI and IE. Disclosures Larry M. Baddour, MD, Boston Scientific (Consultant) M. Rizwan Sohail, MD, Aziyo Biologics (Consultant)Medtronic Inc (Consultant, Research Grant or Support)

Abstract Background Invasive fungal infection (IFI) in heart transplant recipients is associated with increased mortality and poor outcome. Reports have estimated the risk of 1-year IFI to be 3.4-8.6% with renal replacement therapy, delayed chest closure, and reoperation suggested as risk factors. However, the role of antifungal prophylaxis is unclear, though previous studies have suggested a reduced incidence of invasive Aspergillosis. The transplant program in Mayo Arizona provides 6 months of universal azole prophylaxis for Coccidioides, while Rochester and Florida only provide prophylaxis to high risk patients. We sought to define epidemiology and risk factors for 1-year IFI and determine the effect of antifungal prophylaxis. Methods We conducted a retrospective cohort study of patients undergoing single-organ heart transplantation at Mayo Rochester, Florida, or Arizona from January 2000 to March 2019. We identified baseline characteristics, details of transplant hospitalization such as need for renal replacement therapy, open chest, reoperation, and operative time, receipt of antifungal prophylaxis, and diagnosis of IFI. Multivariable Cox analysis was performed to identify risk factors of time to 1-year IFI. Results A total of 966 heart transplant recipients were identified with a median age of 56 years (IQR 47, 62) and 72% male. 444 patients received antifungal prophylaxis which included 32% fluconazole, 34% itraconazole, 18% voriconazole, 15% echinocandin, and &lt; 1% amphotericin or posaconazole. Over 1-year follow-up, 62 patients developed IFI with a cumulative prevalence of 6.4%. The most common organisms were Aspergillus (50%) and Candida (27%). In a multivariable model, factors associated with 1-year IFI were post-transplant renal replacement therapy (HR 3.34, 95% CI 1.69-6.60; P &lt; 0.001) and antifungal prophylaxis (HR 0.32, 95% CI 0.11-0.96; P=0.042). Operative time, recent hospitalization, open chest, and post-transplant mechanical circulatory support were not associated with 1-year IFI. Conclusion Renal replacement therapy after transplantation is associated with 1-year IFI. Antifungal prophylaxis appears to be protective and further prospective study is warranted to verify this finding. Disclosures All Authors: No reported disclosures

AbstractThe contrasting outcomes of lymphocyte manipulation after solid organ transplantation are allograft rejection and infections, commonly with cytomegalovirus (CMV). Peripheral blood absolute lymphocyte count (ALC) may serve as a predictive marker for these outcomes. Using a retrospective review of clinical and laboratory dataset, we aimed to determine whether a range of ALC (termed “safe ALC corridor”) exists where CMV infection and rejection outcomes are minimal in a cohort of 381 kidney transplant recipients. In an extended Cox model using a time‐dependent covariate for peripheral blood ALC, a value below the cut‐off of 610 cells/uL was associated with the development of CMV infection both in the overall cohort (Hazard Ratio [HR] 2.25 (95% confidence internal [CI] 1.02‐4.96; P = .043) and the subgroup of high‐risk CMV D+/R‐ mismatch patients (HR 2.91 [95% CI 1.09‐7.77]; P = .033). In contrast, a time‐dependent Cox analysis did not show any significant association between ALC and rejection (per IQR decrease, HR 1.2 [95% CI: 0.76‐1.9]; P = .434). Accordingly, a “safe ALC corridor” could not be defined. In conclusion, a low peripheral blood ALC (ie, threshold of 610 cells/uL) can be used to stratify the risk of CMV disease after kidney transplantation.

Abstract Background Infective endocarditis (IE) is the most feared complication of Staphylococcus aureus bacteremia (SAB). Transesophageal echocardiogram (TEE) is generally recommended for all patients with SAB; however, supporting data for this are limited. We previously developed a scoring system, “PREDICT,” that quantifies the risk of IE and identifies patients who would most benefit most from undergoing TEE. The current prospective investigation aims to validate this score. Methods We prospectively screened all consecutive adults (≥18 years) hospitalized with SAB at 3 Mayo Clinic sites between January 2015 and March 2017. Results Of 220 patients screened, 199 with SAB met study criteria and were included in the investigation. Of them, 23 (11.6%) patients were diagnosed with definite IE within 12 weeks of initial presentation based on modified Duke’s criteria. Using the previously derived PREDICT model, the day 1 score of ≥4 had a sensitivity of 30.4% and a specificity of 93.8%, whereas a day 5 score of ≤2 had a sensitivity and negative-predictive value of 100%. Additional factors including surgery or invasive procedure in the past 30 days, prosthetic heart valve, and higher number of positive blood culture bottles in the first set of cultures were associated with increased risk of IE independent of the day 5 risk score. Conclusions We validated the previously developed PREDICT scoring tools for stratifying risk of IE, and the need for undergoing a TEE, among cases of SAB. We also identified other factors with predictive potential, although larger prospective studies are needed to further evaluate possible enhancements to the current scoring system.