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Objectives Acute kidney injury (AKI) remains a leading source of morbidity and mortality after cardiothoracic surgery. Insulin-like growth factor-binding protein 7 (IGFBP7), and tissue inhibitor of metalloproteinases-2 (TIMP-2), are novel early-phase renal biomarkers that have been validated as sensitive predictors of AKI. Here the authors studied the efficacy of these biomarkers for predicting AKI after left ventricular assist device (LVAD) implantation and cardiac transplantation. Design/Setting/Participants/Interventions This was a prospective study of 73 patients undergoing LVAD implantation (n = 37) or heart transplant (n = 36) from 2016 to 2017 at the authors’ center. TIMP-2 and IGFBP7 were measured with the NephroCheck Test on urine samples before surgery and one-to-six hours after surgery. NephroCheck scores were assessed as predictors of moderate/severe AKI (Kidney Disease International Global Outcomes 2/3 creatinine criteria) within 48 hours of surgery, and the association with survival to one year was investigated. Measurements and Main Results The LVAD and transplant cohorts overall were similar in demographics and baseline creatinine (p > 0.05), with the exception of having more African-American patients in the LVAD arm (p = 0.003). Eleven (30%) LVAD and 16 (44%) transplant patients developed moderate/severe AKI. Overall, AKI was associated with postsurgery NephroCheck (odds ratio [95% confidence interval] for 0.1 mg/dL increase: 1.36 [1.04-1.79]; p = 0.03), but not with baseline NephroCheck (p = 0.92). When analyzed by cohort, this effect remained for LVAD (1.68 [1.05-2.71]; p = 0.03) but not for transplant (p = 0.15). Receiver operating characteristic analysis showed postoperative NephroCheck to be superior to baseline creatinine in LVAD (p = 0.046). Furthermore, an increase of 0.1 mg/dL in postoperative NephroCheck was associated with a 10% increase in the risk of mortality (adjusted hazard ratio: 1.11 [1.01-1.21]; p = 0.04) independent of age and body mass index. Conclusion Assessment of TIMP-2 and IGFBP7 within six hours after surgery appeared effective at predicting AKI in patients with LVADs. Larger studies are warranted to validate these findings.

OBJECTIVES The International Society of Heart and Lung Transplantation (ISHLT) criteria for primary graft dysfunction (PGD) after cardiac transplantation have been shown to stratify patient outcomes up to 1 year after transplantation, but scarce data are available regarding outcomes beyond the 1st year. We sought to characterize survival of patients with PGD following cardiac transplantation beyond the 1st year. METHODS A retrospective review of consecutive patients undergoing isolated cardiac transplantation at a single centre between 2012 and 2015 was performed. Patients were diagnosed with none, mild, moderate or severe PGD by the ISHLT criteria. Survival was ascertained from the United Network for Organ Sharing database and chart review. Kaplan–Meier curves were plotted to compare survival. The hazard ratio for mortality associated with PGD severity was estimated using Cox-proportional hazards modelling, with a pre-specified conditional survival analysis at 90 days. RESULTS A total of 257 consecutive patients underwent cardiac transplantation during the study period, of whom 73 (28%) met ISHLT criteria for PGD: 43 (17%) mild, 12 (5%) moderate and 18 (7%) severe. Patients with moderate or severe PGD had decreased survival up to 5 years after transplantation (log-rank P CONCLUSIONS A diagnosis of moderate or severe PGD is associated with increased mortality up to 5 years after cardiac transplantation. However, patients with moderate or severe PGD who survive to post-transplantation day 90 are no longer at increased risk for mortality as compared to those with none or mild PGD.

BACKGROUND Surgical site infections (SSIs) after left ventricular assist device (LVAD) implantation are associated with high mortality, while surgical prophylaxis is variable. METHODS This retrospective study included adult patients who underwent LVAD implantation at a single center. We compared outcomes in patients who received narrow antimicrobial prophylaxis (cefazolin, vancomycin, or both) to those who received broad antimicrobial prophylaxis (any antimicrobial combination targeting gram-positive and gram-negative organisms not included in the narrow group) at 30-day and 1-year postimplantation. Cox-proportional hazards models and log-rank tests were used for survival analysis. RESULTS Among the 39 and 65 patients comprising narrow and broad groups respectively, there was no difference in rate of SSI at 30 days (6.2% vs. 12.8%, p = .290) and 1 year (16.9% vs. 25.6%, p = .435). Comparing narrow to broad prophylaxis, the risk of mortality (hazard ratio [HR] = 0.44, 95% confidence interval [CI] = 0.15-1.35, logrank p = .14), and composite of mortality and infection was reduced (HR = 0.92, 95% CI = 0.45-1.88, logrank p = .83), but did not reach statistical significance. Most culture positive infections were due to gram-positive bacteria (70%) and the most common organisms were the Staphylococcus spp (47%). There were no significant differences in the rate of SSI at 1-year (p = 1.00) and mortality (p = .33) by device type. CONCLUSIONS The rates of infection and all-cause mortality were not different between patients who received narrow or broad prophylaxis. This highlights an opportunity for institutions to narrow their surgical infection prophylaxis protocols to primarily cover gram-positive organisms.

The global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic leading to coronavirus disease 2019 (COVID-19) is straining hospitals. Judicious resource allocation is paramount but difficult due to the unpredictable disease course. Once hospitalized, discerning which patients may progress to critical disease would be valuable for resource planning. Medical records were reviewed for consecutive hospitalized patients with COVID-19 in a large healthcare system in Texas. The main outcome was progression to critical disease within 10 days from admission. Albumin trends from admission to 7 days were analyzed using mixed-effects models, and progression to critical disease was modeled by multivariable logistic regression of laboratory results. Risk models were evaluated in an independent group. Of 153 non-critical patients, 28 (18%) progressed to critical disease. The rate of decrease in mean baseline-corrected (Δ) albumin was −0.08 g/dL/day (95% CI −0.11 to −0.04; p70% of hospitalized cases that progressed to critical COVID-19 disease. We recommend prospectively tracking albumin. This is a globally applicable tool for all healthcare systems.

Background: Heart failure with preserved ejection fraction (HFpEF) patients often have other comorbidities, including obesity, dyslipidemia, hypertension, and diabetes, comprising the metabolic syndrome. The impacts of hemodynamic monitoring via CardioMEMS on these co-morbidities remain unknown. Methods: A retrospective analysis of 29 patients with HFpEF (EF 45% or greater) and CardioMEMS was performed at a single center. Weight, body mass index (BMI), systolic blood pressures (SBP), high-density lipoprotein (HDL), triglycerides (TGL), hemoglobin A1C (HbA1c), and pulmonary artery diastolic pressures (PADP) were assessed at baseline and six months post-implant. Paired t-tests and the Wilcoxon signed-rank test were used, as appropriate, to test differences between time points. Results: These patients were 69% female, with a mean age of 73 years, and 62% had non-ischaemic cardiomyopathies (NICM). At the time of CardioMEMS implantation, average PADP was 20.1 mmHg ± 5.7, weight was 102.6 kg ± 22.7, BMI was 38.0 kg/m2 ± 8.3, SBP was 135 mmHg ± 19, HDL was 42.4 mg/dL ± 11.3, and median TGL was 130 mg/dL (100, 180). At six months we witnessed a decrease by 20.9% in PADP to 15.9 mmHg ± 5.8, (p < 0.001). In addition, the following was noted: weight decreased by 2.5% to 100.0 kg ± 23.2, (p = 0.006), BMI reduced by 2.6% to 37.0 ± 8.2, (p = 0.002), SBP decreased by 6.7% to 126 mmHg ± 16 (p < 0.001), HDL increased by 10.8% to 47 mg/dL ± 11.9 (p < 0.001), and TGL decreased by 15.4% to 110 mg/dL (105, 135) (p = 0.001). 62% of patients were diabetic with no significant improvements in HbA1C values at the 6-month follow-up. Conclusion: The utilization of CardioMEMS to optimize PADP results in an improvement in the comorbidities associated with the metabolic syndrome. Further studies are warranted to validate these findings and delineate clinical significance.

Background In acute decompensated heart failure (ADHF), noninvasive markers that predict morbidity and mortality are limited. Liver stiffness measurement (LSM) increases with hepatic fibrosis; however it may be falsely elevated in patients with ADHF in the absence of liver disease. We investigated whether elevated LSM predicts cardiac outcomes in ADHF. Methods In a prospective study, we examined 52 ADHF patients without liver disease between 2016 and 2017. Patients underwent liver 2D shear wave elastography (SWE) and were followed for 12 months to assess the outcomes of left ventricular assist device (LVAD), heart transplant (HT) or death. Results The median LSM was elevated in patients who received an LVAD or HT within 30-days compared to those who did not (median [IQR]: 55.6 [22.5 - 63.4] vs 13.8 [9.5 - 40.3] kPa, p = 0.049). Moreover, the risk of composite outcome was highest in the 3rd tertile (>39.8 kPa compared to 1st and 2nd combined, HR 2.83, 95% CI 1.20- 6.67, p = 0.02). Each 1-kPa increase in LSM was associated with a 1%-increase in the incidence rate of readmissions (IRR 1.01, 95% CI 1.00-1.02, p = 0.01). Conclusions LSM may serve as a novel noninvasive tool to determine LVAD, HT or death in patients with ADHF. This article is protected by copyright. All rights reserved.

Surgical site infections (SSI) after left ventricular assist device (LVAD) implantation are associated with high mortality, while surgical prophylaxis is variable. This retrospective study included adult patients who underwent LVAD implantation at a single center. We compared outcomes in patients who received narrow antimicrobial prophylaxis (cefazolin, vancomycin or both) to those who received broad antimicrobial prophylaxis (any antimicrobial combination targeting gram-positive and gram-negative organisms not included in the narrow group) at 30 days and 1 year post-implantation. Cox-proportional hazards models and log-rank tests were used for survival analysis. Among the 39 and 65 patients comprising narrow and broad groups respectively, there was no difference in rate of SSI at 30 days (6.2% vs 12.8%, p = 0.290) and 1 year (16.9% vs 25.6%, p = 0.435). Comparing narrow to broad prophylaxis, the risk of mortality [HR (95% CI): 0.44 (0.15. 1.35), logrank P = 0.14], and composite of mortality and infection was reduced [HR (95% CI): 0.92 (0.45, 1.88), logrank P = 0.83], but did not reach statistical significance. Most culture positive infections were due to gram-positive bacteria (70%) and the most common organisms were the Staphylococcus spp (47%). There were no significant differences in the rate of SSI at 1-year (p=1.00) and mortality (p=0.33) by device type. The rates of infection and all-cause mortality were not different between patients who received narrow or broad prophylaxis. This highlights an opportunity for institutions to narrow their surgical infection prophylaxis protocols to primarily cover gram-positive organisms.

Background: Ceftazidime-avibactam is an effective agent for the treatment of tuberculosis (TB) but requires frequent administration because of a short half-life. Due to a longer half-life, ceftriaxone could allow intermittent dosing. Methods: First, we identified the MIC of ceftriaxone with 15 mg/L avibactam in 30 clinical Mycobacterium tuberculosis isolates. Next, 2 ceftriaxone exposure-effect studies in the intracellular hollow fiber model of TB (HFS-TB) that mimics disseminated disease in young children, were performed. Ceftriaxone was administered once or twice daily for 28 days to explore percentage of time that the concentration persisted above MIC (%TMIC) ranging from 0 to 100%. In a third HFS-TB experiment, the “double cephalosporin” regimen of ceftazidime-ceftriaxone-avibactam was examined and analyzed using Bliss Independence. Conclusion: The MIC99 of the clinical strains was 32 mg/L, in the presence of 15 mg/L avibactam. Ceftriaxone %TMIC 54% demonstrated a 4.1 log10 colony-forming units per milliliter M. tuberculosis kill, while %TMIC mediating Emax was 68%. The “double cephalosporin” combination was highly synergistic. Monte Carlo experiments of 10,000 subjects identified the optimal ceftriaxone dose as 100 mg/kg twice a day. Conclusion: The combination of ceftriaxone-avibactam at 100 mg/kg could achieve Emax in >90% of children. The ceftriaxone potent activity M. tuberculosis could potentially shorten therapy in children with disseminated TB.

In patients who underwent transcatheter aortic valve implantation (TAVI), vascular disease is associated with increased risk of mortality. Thoracic aortic calcification (TAC), an objective surrogate of vascular disease, could be a predictor of mortality after TAVI. We aimed to analyze the association between TAC burden and 1-year all-cause mortality in patients who underwent TAVI in a US population. From July 2015 through July 2017, a retrospective review of TAVI procedures was performed at Baylor Scott & White-The Heart Hospital, Plano, Texas. Patients were analyzed for comorbidities, cardiac risk factors, and 30-day and 1-year all-cause mortality. Restricted cubic splines analysis was used to define low, moderate, and high TAC categories. The association between TAC and survival was evaluated using unadjusted and adjusted Cox models. A total of 431 TAVI procedures were performed, of which TAC was measured in 374 (81%) patients. Median (interquartile range) age was 82 (77, 87) years, and 51% were male. Median (interquartile range) STS PROM was 5.6 (4.1, 8.2) %. Overall 30-day and 1-year all-cause mortality was 1% and 10%, respectively. TAC was categorized as low ( 2.9 cm3). At 1 year, all-cause mortality was 16% in patients with high TAC compared with 6% in the low and moderate TAC categories (p = 0.008). Unadjusted and adjusted Cox regression analysis showed a significant increase in mortality for patients with high TAC compared with low TAC (hazard ratio 2.98, 95% confidence interval [1.34-6.63]), but not significant compared with moderate TAC group. TAC is a predictor of late mortality after TAVI. In conclusion, adding TAC to preoperative evaluation may provide an objective, reproducible, and potentially widely available tool that can help in shared decision-making.

We are delighted to see a letter to the editor1 essentially agreeing with the message conveyed through our retrospective observation: that a dynamic, accelerated fall of albumin levels in patients admitted with severe COVID-19 predicts progression to critical COVID-19.2 Our express intent was to spur further clinical investigation. Our conclusion remains unchanged after accounting for pre-existing liver disease. COVID-19 frequently causes a self-limited transaminitis in patients without liver disease. Liver function measured at hospital admission using alanine aminotransferase and aspartate aminotransferase for the patients in our study who progressed to critical disease, compared with those who did not progress, was similar (table …