Reproducibility and prognostic ability of chronicity parameters in kidney biopsy - Comprehensive evaluation comparing microscopy and artificial intelligence in digital pathology.

INTRODUCTION: Semi-quantitative scoring of various parameters in renal biopsy is accepted as an important tool to assess disease activity and prognostication. There are concerns on the impact of interobserver variability in its prognostic utility, generating a need for computerized quantification. METHODS: We studied 94 patients with renal biopsies, 45 with native diseases and 49 transplant patients with index biopsies for Polyomavirus nephropathy. Chronicity scores were evaluated using two methods. A standard definition diagram was agreed after international consultation and four renal pathologists scored each parameter in a double-blinded manner. Interstitial fibrosis (IF) score was assessed with five different computerized and AI-based algorithms on trichrome and PAS stains. RESULTS: There was strong prognostic correlation with renal function and graft outcome at a median follow-up ranging from 24 to 42 months respectively, independent of moderate concordance for pathologists scores. IF scores with two of the computerized algorithms showed significant correlation with estimated glomerular filtration rate (eGFR) at biopsy but not at the end of follow-up. There was poor concordance for AI based platforms. CONCLUSION: Chronicity scores are robust prognostic tools despite interobserver reproducibility. AI-algorithms have absolute precision but are limited by significant variation when different hardware and software algorithms are used for quantification.

Single-center Outcomes After Liver Transplantation With SARS-CoV-2-Positive Donors: An Argument for Increased Utilization.

Background: The COVID-19 pandemic has led to an increase in SARS-CoV-2-test positive potential organ donors. The benefits of life-saving liver transplantation (LT) must be balanced against the potential risk of donor-derived viral transmission. Although emerging evidence suggests that the use of COVID-19-positive donor organs may be safe, granular series thoroughly evaluating safety are still needed. Results of 29 consecutive LTs from COVID-19-positive donors at a single center are presented here. Methods: A retrospective cohort study of LT recipients between April 2020 and December 2022 was conducted. Differences between recipients of COVID-19-positive (n = 29 total; 25 index, 4 redo) and COVID-19-negative (n = 472 total; 454 index, 18 redo) deceased donor liver grafts were compared. Results: COVID-19-positive donors were significantly younger (P = 0.04) and had lower kidney donor profile indices (P = 0.04) than COVID-19-negative donors. Recipients of COVID-19-positive donor grafts were older (P = 0.04) but otherwise similar to recipients of negative donors. Donor SARS-CoV-2 infection status was not associated with a overall survival of recipients (hazard ratio, 1.11; 95% confidence interval, 0.24-5.04; P = 0.89). There were 3 deaths among recipients of liver grafts from COVID-19-positive donors. No death seemed virally mediated because there was no qualitative association with peri-LT antispike antibody titers, post-LT prophylaxis, or SARS-CoV-2 variants. Conclusions: The utilization of liver grafts from COVID-19-positive donors was not associated with a decreased overall survival of recipients. There was no suggestion of viral transmission from donor to recipient. The results from this large single-center study suggest that COVID-19-positive donors may be used safely to expand the deceased donor pool.

Comparison Between REVEAL Lite 2 and COMPERA 2.0 for Risk Stratification in Pulmonary Arterial Hypertension.

BACKGROUND: Risk stratification is the cornerstone of the management of pulmonary arterial hypertension (PAH). Current European Society of Cardiology/European Respiratory Society guidelines recommend using the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) three-strata risk model at baseline and the COMPERA 2.0 four-strata model at follow-up. However, the guidelines did not take into consideration other available risk scores such as the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) Lite 2. RESEARCH QUESTION: Is REVEAL Lite 2 better at discriminating risk than the COMPERA risk assessment models at baseline or follow-up evaluations? STUDY DESIGN AND METHODS: This study analyzed data from patients with PAH consecutively enrolled between June 2011 and February 2022 in the PAH registry at our expert Pulmonary Hypertension Center. Patients were stratified according to REVEAL Lite 2 and COMPERA three- and four-strata risk scores at baseline and follow-up to predict the composite outcome for lung transplantation or death. Receiver-operating characteristic curves in predicting the binary outcome at 3, 5, and 7 years were plotted. Areas under the curve of the scores were compared by using the χ2 test. The performance of the scores was determined according to Harrel's C statistic. RESULTS: A total of 296 patients were included for baseline and 196 for follow-up evaluation. The overall transplant-free survival in the patient population at 1, 3, 5, and 7 years was 93.6%, 81.3%, 75.1%, and 68.8%, respectively. At baseline, the C statistic of REVEAL Lite 2 was 0.74 (95% CI, 0.69-0.80), compared with 0.68 (95% CI, 0.63-0.74) for the COMPERA four-strata model and 0.63 (95% CI, 0.58-0.69) for the COMPERA three-strata model. All C statistic differences between REVEAL Lite 2 and the other models were statistically significant at baseline. INTERPRETATION: Our analysis showed that REVEAL Lite 2 was better at baseline at discriminating risk in this patient population. Future guidelines should consider including REVEAL Lite 2 in the management algorithm to help clinicians make informed decisions. Further analysis in larger cohorts could help validate these findings.

Effect of a Hispanic outreach program on referral and liver transplantation volume at a single center.

BACKGROUND: Although Hispanic patients have high rates of end-stage liver disease and liver cancer, for which liver transplantation (LT) offers the best long-term outcomes, they are less likely to receive LT. Studies of end-stage renal disease patients and kidney transplant candidates have shown that targeted, culturally relevant interventions can increase the likelihood of Hispanic patients receiving kidney transplant. However, similar interventions remain largely unstudied in potential LT candidates. METHODS: Referrals to a single center in Texas with a large Hispanic patient population were compared before (01/2018-12/2019) and after (7/2021-6/2023) the implementation of a targeted outreach program. Patient progress toward LT, reasons for ineligibility, and differences in insurance were examined between the two eras. RESULTS: A greater proportion of Hispanic patients were referred for LT after the implementation of the outreach program (23.2% vs 26.2%, p = 0.004). Comparing the pre-outreach era to the post-outreach era, more Hispanic patients achieved waitlisting status (61 vs 78, respectively) and received a LT (971 vs 82, respectively). However, the proportion of Hispanic patients undergoing LT dropped from 30.2% to 20.3%. In the post-outreach era, half of the Hispanic patients were unable to get LT for financial reasons (112, 50.5%). CONCLUSIONS: A targeted outreach program for Hispanic patients with end-stage liver disease effectively increased the total number of Hispanic LT referrals and recipients. However, many of the patients who were referred were ineligible for LT, most frequently for financial reasons. These results highlight the need for additional research into the most effective ways to ameliorate financial barriers to LT in this high-need community.

Enhanced recovery after surgery may mitigate the risks associated with robotic-assisted fundoplication in lung transplant patients.

INTRODUCTION: A history of lung transplantation is a risk factor for poor outcomes in patients undergoing laparoscopic fundoplication. We wanted to determine whether enhanced recovery after a robotic-assisted surgery program would mitigate these risks. METHODS: We performed a single-center retrospective analysis of the Society of Thoracic Surgery database for patients who underwent elective antireflux procedures from 1/2018 to 2/2021 under the enhanced recovery after surgery program using robotic assistance. We identified the patient and surgical characteristics, morbidity, length of stay, and 30-day readmission rates. RESULTS: Among 386 patients who underwent barrier creation, 41 had previously undergone a lung transplant, either bilateral (n = 28) or single (n = 13). There were no significant differences in postoperative complications (9.8% vs. 5.2%, p = 0.27), median hospital length of stay (1 d vs. 1 d, p = 0.28), or 30-day readmission (7.3% vs. 4.9%, p = 0.46). Bivariate analysis showed that older age (p = 0.03), history of DVT/PE (p < 0.001), history of cerebrovascular events (p = 0.03), opioid dependence (p = 0.02), neurocognitive dysfunction (p < 0.001), and dependent functional status (p = 0.02) were associated with postoperative complications. However, lung transplantation was not associated with an increased risk of postoperative complications (p = 0.28). DISCUSSION: The risk of surgical complications in patients with a history of lung transplantation may be mitigated by the combination of ERAS and minimally invasive surgery such as robot-assisted surgery.

Effectiveness of combined plasma cell therapy and costimulation blockade based desensitization regimen in heart transplant candidates.

BACKGROUND: Desensitization is one of the strategies to reduce antibodies and facilitate heart transplantation in highly sensitized patients. We describe our center's desensitization experience with combination of plasma cell (PC) depletion therapy (with proteasome inhibitor or daratumumab) and costimulation blockade (with belatacept). METHODS: We reviewed five highly sensitized patients who underwent desensitization therapy with plasma cell depletion and costimulation blockade. We evaluated the response to therapy by measuring the changes in cPRA, average MFI, and number of positive beads > 5000MFI. RESULTS: Five patients, mean age of 56 (37-66) years with average cPRA of 98% at 5000 MFI underwent desensitization therapy. After desensitization, mean cPRA decreased from 98% to 70% (p = .09), average number of beads > 5000 MFI decreased from 59 to 37 (p = .15), and average MFI of beads > 5000 MFI decreased from 16713 to 13074 (p = .26). CONCLUSION: Combined PC depletion and CoB could be a reasonable strategy for sustained reduction in antibodies in highly sensitized patients being listed for heart transplantation.

Osteocalcin protects islet identity in low-density lipoprotein receptor knockout mice on high-fat diet.

Metabolic syndrome (MetS) is an increasing global health threat and strong risk factor for type 2 diabetes (T2D). MetS causes both hyperinsulinemia and islet size overexpansion, and pancreatic ß-cell failure impacts insulin and proinsulin secretion, mitochondrial density, and cellular identity loss. The low-density lipoprotein receptor knockout (LDLr-/-) model combined with high-fat diet (HFD) has been used to study alterations in multiple organs, but little is known about the changes to ß-cell identity resulting from MetS. Osteocalcin (OC), an insulin-sensitizing protein secreted by bone, shows promising impact on ß-cell identity and function. LDLr-/- mice at 12 months were fed chow or HFD for 3 months ± 4.5 ng/h OC. Islets were examined by immunofluorescence for alterations in nuclear Nkx6.1 and PDX1 presence, insulin-glucagon colocalization, islet size and %ß-cell and islet area by insulin and synaptophysin, and mitochondria fluorescence intensity by Tomm20. Bone mineral density (BMD) and %fat changes were examined by Piximus Dexa scanning. HFD-fed mice showed fasting hyperglycemia by 15 months, increased weight gain, %fat, and fasting serum insulin and proinsulin; concurrent OC treatment mitigated weight increase and showed lower proinsulin-to-insulin ratio, and higher BMD. HFD increased %ß and %islet area, while simultaneous OC-treatment with HFD was comparable to chow-fed mice. Significant reductions in nuclear PDX1 and Nkx6.1 expression, increased insulin-glucagon colocalization, and reduction in ß-cell mitochondria fluorescence intensity were noted with HFD, but largely prevented with OC administration. OC supplementation here suggests a benefit to ß-cell identity in LDLr-/- mice and offers intriguing clinical implications for countering metabolic syndrome.

Work relative value units undervalue the clinical effort associated with teaching cases: An ACS-NSQIP analysis.

PURPOSE: Work-relative-value-units (wRVUs) are a core metric of faculty effort but do not account for the additional work associated with intraoperative teaching. This study introduces and assesses an indexed effort, wRVU per minute (wRVU index). We hypothesize that there is a significant decrease in the calculated wRVU index among teaching cases. METHODS: We queried the ACS-NSQIP database for 7 core Emergency General Surgery procedures and records were stratified into teaching vs non-teaching, and emergent vs non-emergent procedures. We utilized multivariable generalized linear models to determine factors associated with increased operative time and decreased wRVU index. RESULTS: Data were available for 953,967 cases from 2005 to 2010. For all cases, teaching vs non-teaching, the median wRVU index was 0.16 vs 0.21 (p â€‹< â€‹0.001). There was a positive association between teaching cases and decreased wRVU index for all cases. CONCLUSION: The wRVU index was 24% lower for teaching cases when compared to non-teaching cases despite controlling for patient-specific factors. This finding highlights the need for further evaluation of the current wRVU framework.

Anti-Tuberculosis Potential of OJT008 against Active and Multi-Drug-Resistant Mycobacterium Tuberculosis: In Silico and In Vitro Inhibition of Methionine Aminopeptidase.

Despite the recent progress in the diagnosis of tuberculosis (TB), the chemotherapeutic management of TB continues to be challenging. Mycobacterium tuberculosis (Mtb), the etiological agent of TB, is classified as the 13th leading cause of death globally. In addition, 450,000 people were reported to develop multi-drug-resistant TB globally. The current project focuses on targeting methionine aminopeptidase (MetAP), an essential protein for the viability of Mtb. MetAP is a metalloprotease that catalyzes the excision of the N-terminal methionine (NME) during protein synthesis, allowing the enzyme to be an auspicious target for the development of novel therapeutic agents for the treatment of TB. Mtb possesses two MetAP1 isoforms, MtMetAP1a and MtMetAP1c, which are vital for Mtb viability and, hence, a promising chemotherapeutic target for Mtb therapy. In this study, we cloned and overexpressed recombinant MtMetAP1c. We investigated the in vitro inhibitory effect of the novel MetAP inhibitor, OJT008, on the cobalt ion- and nickel ion-activated MtMetAP1c, and the mechanism of action was elucidated through an in silico approach. The compound's potency against replicating and multi-drug-resistant (MDR) Mtb strains was also investigated. The induction of the overexpressed recombinant MtMetAP1c was optimized at 8 h with a final concentration of 1 mM Isopropyl ß-D-1-thiogalactopyranoside. The average yield from 1 L of Escherichia coli culture for MtMetAP1c was 4.65 mg. A preliminary MtMetAP1c metal dependency screen showed optimum activation with nickel and cobalt ions occurred at 100 µM. The half-maximal inhibitory concentration (IC50) values of OJT008 against MtMetAP1c activated with CoCl2 and NiCl2 were 11 µM and 40 µM, respectively. The in silico study showed OJT008 strongly binds to both metal-activated MtMetAP1c, as evidenced by strong molecular interactions and a higher binding score, thereby corroborating our result. This in silico study validated the pharmacophore's metal specificity. The potency of OJT008 against both active and MDR Mtb was <0.063 µg/mL. Our study reports OJT008 as an inhibitor of MtMetAP1c, which is potent at low micromolar concentrations against both active susceptible and MDR Mtb. These results suggest OJT008 is a potential lead compound for the development of novel small molecules for the therapeutic management of TB.

Sex differences in myocardial remodeling and extracellular volume in aortic regurgitation.

Whether sex differences exist in the cardiac remodeling related to aortic regurgitation (AR) is unclear. Cardiac magnetic resonance (CMR) is the current non-invasive reference standard for cardiac remodeling assessment and can evaluate tissue characteristics. This prospective cohort included patients with AR undergoing CMR between 2011 and 2020. We excluded patients with confounding causes of remodeling. We quantified left ventricular (LV) volume, mass, AR severity, replacement fibrosis by late Gadolinium enhancement (LGE), and extracellular expansion by extracellular volume fraction (ECV). We studied 280 patients (109 women), median age 59.5 (47.2, 68.6) years (P for age = 0.25 between sexes). Women had smaller absolute LV volume and mass than men across the spectrum of regurgitation volume (RVol) (P ≤ 0.01). In patients with ≥ moderate AR and with adjustment for body surface area, indexed LV end-diastolic volume and mass were not significantly different between sexes (all P > 0.5) but men had larger indexed LV end systolic volume and lower LV ejection fraction (P ≥ 0.01). Women were more likely to have NYHA class II or greater symptoms than men but underwent surgery at a similar rate. Prevalence and extent of LGE was not significantly different between sexes or across RVol. Increasing RVol was independently associated with increasing ECV in women, but not in men (adjusted P for interaction = 0.03). In conclusion, women had lower LV volumes and mass than men across AR severity  but their ECV increased with higher regurgitant volume, while ECV did not change in men. Indexing to body surface area did not fully correct for the cardiac remodeling differences between men and women. Women were more likely to have symptoms but underwent surgery at a similar rate to men. Further research is needed to determine if differences in ECV would translate to differences in the course of AR and outcomes.

Relation of Left Ventricular Diastolic Function to Global Fibrosis Burden: Implications for Heart Failure Risk Stratification.

BACKGROUND: Left ventricular (LV) diastolic function is primarily assessed by means of echocardiography, which has limited utility in detecting fibrosis. Cardiac magnetic resonance (CMR) readily detects and quantifies fibrosis. OBJECTIVES: In this study, the authors sought to determine the association of LV diastolic function by echocardiography with CMR-determined global fibrosis burden and the incremental value of fibrosis with diastolic function grade in prediction of total mortality and heart failure hospitalizations. METHODS: A total of 549 patients underwent comprehensive echocardiography and CMR within 30 days. Echocardiography was used to assess LV diastolic function, and CMR was used to determine LV volumes, mass, ejection fraction, replacement fibrosis, and percentage extracellular volume fraction (ECV). RESULTS: Normal diastolic function was present in 142 patients; the rest had diastolic dysfunction grades I to III, except for 18 (3.3%) with indeterminate results. The event rate was higher in patients with diastolic dysfunction compared with patients with normal diastolic function (33.4% vs 15.5; P < 0.001). The model including LV diastolic function grades II and III predicted composite outcome (C-statistic: 0.71; 95% CI: 0.67-0.76), which increased by adding global fibrosis burden (C-statistic: 0.74, 95% CI: 0.70-0.78; P = 0.02). For heart failure hospitalizations, the competing risk model with LV diastolic function grades II and III was good (C-statistic: 0.78; 95% CI: 0.74-0.83) and increased significantly with the addition of global fibrosis burden (C-statistic: 0.80; 95% CI: 0.76-0.85; P = 0.03). CONCLUSIONS: Higher grades of diastolic dysfunction are seen in patients with replacement fibrosis and increased ECV. Fibrosis burden as determined with the use of CMR provides incremental prognostic information to echocardiographic evaluation of LV diastolic function.

Progress in Combined Liver-lung Transplantation at a Single Center.

Combined liver-lung transplantation is an uncommon, although vital, procedure for patients with simultaneous end-stage lung and liver disease. The utility of lung-liver transplant has been questioned because of initial poor survival outcomes, particularly when compared with liver-alone transplant recipients. Methods: A single-center, retrospective review of the medical records of 19 adult lung-liver transplant recipients was conducted, comparing early recipients (2009-2014) with a recent cohort (2015-2021). Patients were also compared with the center's single lung or liver transplant recipients. Results: Recent lung-liver recipients were older (P = 0.004), had a higher body mass index (P = 0.03), and were less likely to have ascites (P = 0.02), reflecting changes in the etiologies of lung and liver disease. Liver cold ischemia time was longer in the modern cohort (P = 0.004), and patients had a longer posttransplant length of hospitalization (P = 0.048). Overall survival was not statistically different between the 2 eras studied (P = 0.61), although 1-y survival was higher in the more recent group (90.9% versus 62.5%). Overall survival after lung-liver transplant was equivalent to lung-alone recipients and was significantly lower than liver-alone recipients (5-y survival: 52%, 51%, and 75%, respectively). Lung-liver recipient mortality was primarily driven by deaths within 6 mo of transplant due to infection and sepsis. Graft failure was not significantly different (liver: P = 0.06; lung: P = 0.74). Conclusions: The severity of illness in lung-liver recipients combined with the infrequency of the procedure supports its continued use. However, particular attention should be paid to patient selection, immunosuppression, and prophylaxis against infection to ensure proper utilization of scarce donor organs.

Surgical Treatment of Atrioesophageal Fistula: A Systematic Review.

BACKGROUND: Atrioesophageal fistula is a rare and morbid complication of ablation therapy for atrial fibrillation. Surgery provides increased survival; however, which surgical approach provides the best outcome is unclear. METHODS: We performed a retrospective analysis of cases in the literature and at our institution. We characterized patients by presenting symptoms, diagnostic method, surgical therapy with different approaches, and survival. RESULTS: In total, 219 patients were found, with 216 patients identified from 122 papers in the literature and 3 patients from our institutional database (2000-2022). The most common presenting symptoms included fever/chill (71.8%) and neurologic deficiency (62.9%). The overall survival for this cohort was 47%. Patients who had an operation had significantly improved survival compared with those who did not have an operation (71.9.3% vs 11%, P < .001). Patients who survived after surgical intervention typically underwent right thoracotomy (45.1%), patch repair of the left atrium (61.1%), and primary repair of the esophagus (68.3%) on cardiopulmonary bypass (84.8%) with a flap between the 2 organs (84.6%). Patients who had cardiopulmonary bypass had increased survival (39 of 45 [86.7%]) compared with those who did not have cardiopulmonary bypass (7 of 17 [41.2%], P < .001). CONCLUSIONS: Patients with atrioesophageal fistula should undergo surgical intervention. A patch repair of the left atrium and primary repair of the esophagus with a flap between the organs during cardiopulmonary bypass is the most common successful repair. Cardiopulmonary bypass may allow better débridement and repair of the left atrium, which may provide a survival advantage in the treatment of this rare disease.

Influence of Cardiac Remodeling on Clinical Outcomes in Patients With Aortic Regurgitation.

BACKGROUND: Quantitative cardiac magnetic resonance (CMR) outcome studies in aortic regurgitation (AR) are few. It is unclear if volume measurements are beneficial over diameters. OBJECTIVES: This study sought to evaluate the association of CMR quantitative thresholds and outcomes in AR patients. METHODS: In a multicenter study, asymptomatic patients with moderate or severe AR on CMR with preserved left ventricular ejection fraction (LVEF) were evaluated. Primary outcome was development of symptoms or decrease in LVEF to <50%, development of guideline indications for surgery based on LV dimensions, or death under medical management. Secondary outcome was the same as the primary outcome, excluding surgery for remodeling indications. We excluded patients who underwent surgery within 30 days of CMR. Receiver-operating characteristic analyses for the association with outcomes were performed. RESULTS: We studied 458 patients (median age: 60 years; IQR: 46-70 years). During a median follow-up of 2.4 years (IQR: 0.9-5.3 years), 133 events occurred. Optimal thresholds were regurgitant volume of 47 mL and regurgitant fraction of 43%, indexed LV end-systolic (iLVES) volume of 43 mL/m2, indexed LV end-diastolic volume of 109 mL/m2, and iLVES diameter of 2 cm/m2. In multivariable regression analysis, iLVES volume of ≥43 mL/m2 (HR: 2.53; 95% CI: 1.75-3.66; P < 0.001) and indexed LV end-diastolic volume of ≥109 mL/m2 were independently associated with the outcomes and provided additional discrimination improvement over iLVES diameter, whereas iLVES diameter was independently associated with the primary outcome but not the secondary outcome. CONCLUSIONS: In asymptomatic AR patients with preserved LVEF, CMR findings can be used to guide management. CMR-based LVES volume assessment performed favorably compared to LV diameters.

Differences in Myocardial Remodeling and Tissue Characteristics in Chronic Isolated Aortic and Mitral Regurgitation.

BACKGROUND: The left ventricular hemodynamic load differs between aortic regurgitation (AR) and primary mitral regurgitation (MR). We used cardiac magnetic resonance to compare left ventricular remodeling patterns, systemic forward stroke volume, and tissue characteristics between patients with isolated AR and isolated MR. METHODS: We assessed remodeling parameters across the spectrum of regurgitant volume. Left ventricular volumes and mass were compared against normal values for age and sex. We calculated forward stroke volume (planimetered left ventricular stroke volume-regurgitant volume) and derived a cardiac magnetic resonance-based systemic cardiac index. We assessed symptom status according to remodeling patterns. We also evaluated the prevalence of myocardial scarring using late gadolinium enhancement imaging, and the extent of interstitial expansion via extracellular volume fraction. RESULTS: We studied 664 patients (240 AR, 424 primary MR), median age of 60.7 (49.5-69.9) years. AR led to more pronounced increases in ventricular volume and mass compared with MR across the spectrum of regurgitant volume (P<0.001). In ≥moderate regurgitation, AR patients had a higher prevalence of eccentric hypertrophy (58.3% versus 17.5% in MR; P<0.001), whereas MR patients had normal geometry (56.7%) followed by myocardial thinning with low mass/volume ratio (18.4%). The patterns of eccentric hypertrophy and myocardial thinning were more common in symptomatic AR and MR patients (P<0.001). Systemic cardiac index remained unchanged across the spectrum of AR, whereas it progressively declined with increasing MR volume. Patients with MR had a higher prevalence of myocardial scarring and higher extracellular volume with increasing regurgitant volume (P value for trend <0.001), whereas they were unchanged across the spectrum of AR (P=0.24 and 0.42, respectively). CONCLUSIONS: Cardiac magnetic resonance identified significant heterogeneity in remodeling patterns and tissue characteristics at matched degrees of AR and MR. Further research is needed to examine if these differences impact reverse remodeling and clinical outcomes after intervention.

Pre-transplant Biomarkers of Immune Dysfunction Improve Risk Assessment of Post-transplant Mortality Compared to Conventional Clinical Risk Scores.

Introduction: There is a critical need to accurately stratify liver transplant (LT) candidates' risk of post-LT mortality prior to LT to optimize patient selection and avoid futility. Here, we compare previously described pre-LT clinical risk scores with the recently developed Liver Immune Frailty Index (LIFI) for prediction of post-LT mortality. LIFI measures immune dysregulation based on pre-LT plasma HCV IgG, MMP3 and Fractalkine. LIFI accurately predicts post-LT mortality, with LIFI-low corresponding to 1.4% 1-year post-LT mortality compared with 58.3% for LIFI-high (C-statistic=0.85). Methods: LIFI was compared to MELD, MELD-Na, MELD 3.0, D-MELD, MELD-GRAIL, MELD-GRAIL-Na, UCLA-FRS, BAR, SOFT, P-SOFT, and LDRI scores on 289 LT recipients based on waitlist data at the time of LT. Survival, hazard of early post-LT death, and discrimination power (C-statistic) were assessed. Results: LIFI showed superior discrimination (highest C-statistic) for post-LT mortality when compared to all other risk scores, irrespective of biologic MELD. On univariate analysis, the LIFI showed a significant correlation with mortality 6-months, as well as 1-, 3-, and 5-years. No other pre-LT scoring system significantly correlated with post-LT mortality. On bivariate adjusted analysis, African American race (p<0.05) and pre-LT cardiovascular disease (p=0.053) were associated with early- and long-term post-LT mortality. Patients who died within 1-yr following LT had a significantly higher incidence of infections, including 30-day and 90-day incidence of any infection, pneumonia, abdominal infections, and UTI (p<0.05). Conclusions: LIFI, which measures pre-LT biomarkers of immune dysfunction, more accurately predicts risk of post-LT futility compared with current clinical predictive models. Pre-LT assessment of immune dysregulation may be critical in predicting mortality after LT and may optimize selection of candidates with lowest risk of futile outcomes.

Prevalence and Clinical Implications of Tricuspid Valve Prolapse Based on Magnetic Resonance Diagnostic Criteria.

BACKGROUND: Tricuspid valve prolapse (TVP) is an uncertain diagnosis with unknown clinical significance because of a scarcity of published data. OBJECTIVES: In this study, cardiac magnetic resonance was used to: 1) propose diagnostic criteria for TVP; 2) evaluate the prevalence of TVP in patients with primary mitral regurgitation (MR); and 3) identify the clinical implications of TVP with regard to tricuspid regurgitation (TR). METHODS: Forty-one healthy volunteers were analyzed to identify normal tricuspid leaflet displacement and propose criteria for TVP. A total of 465 consecutive patients with primary MR (263 with mitral valve prolapse [MVP] and 202 with nondegenerative mitral valve disease [non-MVP]) were phenotyped for the presence and clinical significance of TVP. RESULTS: The proposed TVP criteria included right atrial displacement of ≥2 mm for the anterior and posterior tricuspid leaflets and ≥3 mm for the septal leaflet. Thirty-one (24%) subjects with single-leaflet MVP and 63 (47%) with bileaflet MVP met the proposed criteria for TVP. TVP was not evident in the non-MVP cohort. Patients with TVP were more likely to have severe MR (38.3% vs 18.9%; P < 0.001) and advanced TR (23.4% of patients with TVP demonstrated moderate or severe TR vs 6.2% of patients without TVP; P < 0.001), independent of right ventricular systolic function. CONCLUSIONS: TR in subjects with MVP should not be routinely considered functional, as TVP is a prevalent finding associated with MVP and more often associated with advanced TR compared with patients with primary MR without TVP. A comprehensive assessment of tricuspid anatomy should be an important component of the preoperative evaluation for mitral valve surgery.