Sex-Based Differences in Concomitant Tricuspid Repair During Degenerative Mitral Surgery.

BACKGROUND: Women with mitral valve disease have higher rates of tricuspid regurgitation (TR) than men. Although tricuspid valve repair (TVr) decreases the progression of TR, we hypothesize that there may be sex-based differences in concomitant TVr at the time of mitral valve operations. METHODS: Adults undergoing mitral valve operation for degenerative disease with moderate or worse preoperative TR at a high-volume center from 2014 to 2023 were identified. Patients with a previous tricuspid intervention were excluded. A multivariable logistic regression identified predictors of concomitant TVr. To evaluate the clinical impact of not performing TVr, a competing risk model compared development of severe TR or valve-related reoperation by sex among patients without TVr. RESULTS: Most included patients were women (55% [n = 214 of 388]), and the median age was 73 years (quartile 1-quartile 3, 65-79 years). There was no difference in the rate of severe TR by sex (female, 28%; male, 26%; P = .63). The unadjusted rate of concomitant TVr was 57% for women and 73% for men (P < .001). Overall, women had 52% lower adjusted odds of TVr (adjusted odds ratio, 0.48; 95% CI, 0.29-0.81; P = .006), including a lower adjusted rate for moderate TR (47% [95% CI, 45%-49%] vs 66% [95% CI, 64%-69%]) and for severe TR (83% [95% CI, 81%-86] vs 92% [95% CI, 90%-93%]) Among those without TVr, 12% of women and 0% of men had severe TR or required a valve-related reoperation at 4 years (P < .001). CONCLUSIONS: Women with moderate or severe TR undergoing mitral valve operation for degenerative disease were less likely to receive concomitant TVr, severe TR was more likely to develop, or they would more likely need a valve-related reoperation. Evaluation of sex-based treatment differences is imperative to improve outcomes for women.

The relationship between discharge location and cardiac rehabilitation use after cardiac surgery.

BACKGROUND: Cardiac rehabilitation (CR) is a guideline-recommended risk-reduction program offered to cardiac surgical patients. Despite CR's association with better outcomes, attendance remains poor. The relationship between discharge location and CR use is poorly understood. METHODS: This study was a nationwide, retrospective cohort analysis of Medicare fee-for-service claims for beneficiaries undergoing coronary artery bypass grafting and/or surgical aortic valve repair between July 1, 2016, and December 31, 2018. The primary outcome was attendance of any CR session. Discharge location was categorized as home discharge or discharge to extended care facility (ECF) (including skilled nursing facility, inpatient rehabilitation, and long-term acute care). Multivariable logistic regression models evaluated the association between discharge location, CR attendance, and 1-year mortality. RESULTS: Of the 167,966 patients who met inclusion criteria, 34.1% discharged to an ECF. Overall CR usage rate was 53.9%. Unadjusted and adjusted CR use was lower among patients discharged ECFs versus those discharged home (42.1% vs 60.0%; adjusted odds ratio, 0.66; P < .001). Patients discharged to long-term acute care were less likely to use CR than those discharged to skilled nursing facility or inpatient rehabilitation (reference category: home; adjusted odds ratio for long-term acute care, 0.36, adjusted odds ratio for skilled nursing facility, 0.69, and adjusted odds ratio for inpatient rehabilitation, 0.71; P < .001). CR attendance was associated with a greater reduction in adjusted 1-year mortality in patients discharged to ECFs (9.7% reduction) versus those discharged home (4.3% reduction). CONCLUSIONS: In this national analysis of Medicare beneficiaries, discharge to ECF was associated with lower CR use, despite a greater association with improved 1-year mortality. Interventions aimed at increasing CR enrollment at ECFs may improve CR use and advance surgical quality.

Postoperative atrial fibrillation in mitral valve surgery is not benign.

OBJECTIVE: Postoperative atrial fibrillation (POAF) is common after cardiac surgery and is often considered to be benign despite recent data suggesting worse outcomes. There are no guidelines for the amount of POAF that triggers anticoagulation or for postoperative surveillance. We examined the rate of POAF, incidence of neurologic events, development of permanent atrial fibrillation, and mortality in patients undergoing isolated mitral valve surgery at a Mitral Foundation reference center. METHODS: This is a retrospective cohort study of 922 adult patients from 2011 to 2022 with no preoperative history of arrhythmias. Multivariable logistic regression was used to identify independent risk factors for the primary outcomes. Kaplan-Meier analysis and Cox proportional-hazards model were used to characterize long-term survival. RESULTS: The incidence of POAF was 39%. Median follow-up was 4.9 months (interquartile range, 1.1-42.6 months). Diabetes (odds ratio [OR], 2.2; 95% CI, 1.2-4.1; P = .01) and increasing age (OR, 1.1; 95% CI, 1.0-1.1; P < .001) were risk factors for POAF, whereas New York Heart Association functional class was not. POAF was a risk factor for the development of permanent atrial fibrillation (OR, 3.2; 95% CI 1.9-5.4; P < .001), which was associated with increased risk of neurologic events (OR, 3.8; 95% CI, 1.5-9.7; P = .004). Ultimately, patients with POAF had worse unadjusted (P < .001) and adjusted long-term mortality (hazard ratio, 1.8; 95% CI, 1.1-3.1; P = .03). CONCLUSIONS: POAF is associated with an increased rate of neurologic events, portends development of permanent atrial fibrillation, and is associated with worse long-term survival. POAF is not benign and carries a long-term mortality implication.

Surgical outcomes of patients at prohibitive risk who are reconsidered for surgery.

Objectives: Transcatheter treatment of advanced mitral and tricuspid valve disease is largely limited to patients at prohibitive surgical risk, although many are not candidates for transcatheter treatment. Here, we describe surgical outcomes of patients at prohibitive risk who were ineligible for transcatheter therapies to guide surgeons in management of this unique population. Methods: Patients at prohibitive risk, defined per surgeon or cardiologist discretion, who were initially referred for a transcatheter mitral or tricuspid intervention in a multidisciplinary atrioventricular valve clinic, were identified from 2019 to 2022. Preoperative risk, operative outcomes, and long-term mortality were evaluated. Results: A total of 337 patients at prohibitive risk were referred for evaluation in a multidisciplinary atrioventricular valve clinic. Of those, 161 underwent transcatheter therapy, 130 patients underwent continued medical management, and 45 were reevaluated and had high-risk surgery. Among surgical patients, 51% were women with a median age of 76 years (quartile 1-quartile 3, 65-81 years). Most patients presented in heart failure (83%; n = 37 out of 45), and 73% were in New York Heart Association functional class III or IV. Most patients (94%; n = 43) had a mitral valve intervention, of whom 56% (24 out of 43) had a mitral valve replacement. The 30-day mortality rate was 4% (2 out of 45) and major morbidity occurred in 33% (15 out of 45). By Kaplan-Meier analysis, 1-year survival was 86% ± 9%. Conclusions: Select patients at prohibitive risk who were ineligible for transcatheter mitral or tricuspid valve intervention underwent surgery with overall low operative mortality and excellent 1-year survival. Patients a prohibitive risk whose anatomy is not amenable to transcatheter devices should be reconsidered for surgery.

Repeat crossclamp after failed initial degenerative mitral valve repair is safe and successful.

Objective: Surgical risk and long-term outcomes when re-crossclamp is required during degenerative mitral valve repair are unknown. We examined the outcomes of patients who required re-crossclamp for mitral valve reintervention. Methods: Adults undergoing mitral valve repair for degenerative mitral valve disease at a single center from 2007 to 2021 who required more than 1 crossclamp for mitral valve reintervention were included. Outcomes including major morbidity and 30-day mortality were collected. Kaplan-Meier analysis characterized survival and freedom from recurrent mitral regurgitation. Results: A total of 69 patients required re-crossclamp for mitral valve reintervention. Of those, 72% (n = 50) underwent successful re-repair and the remaining underwent mitral valve replacement (28%, n = 19). Major morbidity occurred in 23% (n = 16). There was no 30-day mortality, and median long-term survival was 10.9 years for those undergoing re-repair and 7.2 years for those undergoing replacement (P = .79). Midterm echocardiography follow-up was available for 67% (33/50) of patients who were successfully re-repaired with a median follow-up of 20 (interquartile range, 7-37) months. At late follow-up, 90% of patients had mild or less mitral regurgitation. Of those re-repaired, 2 patients later required mitral valve reintervention. Conclusions: Patients requiring re-crossclamp for residual mitral regurgitation had low perioperative morbidity and no mortality. Most patients underwent successful re-repair (vs mitral valve replacement) with excellent valve function and long-term survival. In the event of unsatisfactory repair at the time of mitral valve repair, attempt at re-repair is safe and successful with the appropriate valvar anatomy.

Alfieri versus conventional repair for bileaflet mitral valve prolapse.

Objective: Mitral valve repair for bileaflet prolapse can be complex, involving multiple chords or resection. The Alfieri technique for bileaflet disease is simple but may be associated with mitral stenosis or recurrent mitral regurgitation. Outcomes of patients with bileaflet prolapse undergoing mitral valve repair using the Alfieri versus conventional chord/resection techniques were compared. Methods: Adults undergoing mitral valve repair for bileaflet prolapse for degenerative disease from 2017 to 2023 were stratified by repair technique. Outcomes including operative mortality and echocardiogram data were compared. Time to event analysis was used to characterize freedom from recurrent mitral regurgitation (moderate or greater mitral regurgitation). Results: Among 188 patients with bileaflet prolapse, 37% (70) were repaired with the Alfieri and the remaining patients were repaired with chords/resection. Compared with chords/resection, patients undergoing the Alfieri had shorter cardiopulmonary bypass and crossclamp times. Operative mortality (0% [0/70] vs 2% [2/118], P = .27) was similar between both techniques. The mean mitral gradient was low and similar for the Alfieri versus chords/resection (3 vs 3, P = .34). Development of recurrent mitral regurgitation at 2 years, incorporating the competing risk of death and mitral reintervention, was 4.3% (95% CI, 1.5%-9.3%) for the Alfieri technique and 5.8% (95% CI, 2.2%-11.8%) for chord/resection (P = .83). Conclusions: Both the Alfieri and chord/resection techniques had low rates of recurrent mitral regurgitation at 2 years. The mitral valve gradient was low and similar regardless of technique; thus, those who received the Alfieri technique did not have an increased rate of mitral stenosis. The Alfieri may be an underused technique for bileaflet prolapse.

Higher risk of urinary tract infections in renal transplant recipients receiving pentamidine versus trimethoprim-sulfamethoxazole (TMP-SMX) for Pneumocystis pneumonia prophylaxis.

Urinary tract infection (UTI) is one of the most common infectious complications among renal transplant patients. Trimethoprim-sulfamethoxazole (TMP-SMX) is routinely used as first-line prophylaxis against Pneumocystis pneumonia (PCP) and other opportunistic infections including UTI. Aerosolized pentamidine is an alternate agent used for PCP prophylaxis; however, it does not provide coverage against uropathogens. This is a retrospective study of 81 renal transplant recipients who received TMP-SMX or aerosolized pentamidine for PCP prophylaxis at our center over 1 year. Survival analysis demonstrated increased cumulative incidence of UTI among patients receiving pentamidine for PCP prophylaxis compared to those receiving TMP-SMX (log-rank test P < .001). Univariate and multivariate Cox proportional hazard regression model showed pentamidine prophylaxis (HR 3.740; 95% CI 1.745-8.016; P = .001) and female sex (HR 4.025; 95% CI 1.770-9.154; P = .001) to independently increase UTI risk. Age, induction agent, graft type, diabetes, and delayed graft function (DGF) were not associated with increased risk. This study concludes that the use of pentamidine for PCP prophylaxis compared to TMP-SMX is associated with increased risk of UTI. Secondary UTI prophylaxis may be considered for patients who are unable to tolerate TMP-SMX and who have other risk factors for UTI; however, the efficacy of this has not been studied.

Development of an Operative Trauma Course in Uganda-A Report of a Three-Year Experience.

BACKGROUND: Trauma is a leading cause of morbidity and mortality in low-income countries. Improved health care systems and training are potential avenues to combat this burden. We detail a collaborative and context-specific operative trauma course taught to postgraduate surgical trainees practicing in a low-resource setting and examine its effect on resident practice. METHOD: Three classes of second year surgical residents participated in trainings from 2017 to 2019. The course was developed and taught in conjunction with local faculty. The most recent cohort logged cases before and after the course to assess resources used during initial patient evaluation and operative techniques used if the patient was taken to theater. RESULTS: Over the study period, 52 residents participated in the course. Eighteen participated in the case log study and logged 117 cases. There was no statistically significant difference in patient demographics or injury severity precourse and postcourse. Postcourse, penetrating injuries were reported less frequently (40 to 21% P < 0.05) and road traffic crashes were reported more frequently (39 to 60%, P < 0.05). There was no change in the use of bedside interventions or diagnostic imaging, besides head CT. Of patients taken for a laparotomy, there was a nonstatistically significant increase in the use of four-quadrant packing 3.4 to 21.7%) and a decrease in liver repair (20.7 to 4.3%). CONCLUSIONS: The course did not change resource utilization; however, it did influence clinical decision-making and operative techniques used during laparotomy. Additional research is indicated to evaluate sustained changes in practice patterns and clinical outcomes after operative skills training.

Endothelial Cell-Derived Interleukin-18 Released During Ischemia Reperfusion Injury Selectively Expands T Peripheral Helper Cells to Promote Alloantibody Production.

BACKGROUND: Ischemia reperfusion injury (IRI) predisposes to the formation of donor-specific antibodies, a factor contributing to chronic rejection and late allograft loss. METHODS: We describe a mechanism underlying the correlative association between IRI and donor-specific antibodies by using humanized models and patient specimens. RESULTS: IRI induces immunoglobulin M-dependent complement activation on endothelial cells that assembles an NLRP3 (NOD-like receptor pyrin domain-containing protein 3) inflammasome via a Rab5-ZFYVE21-NIK axis and upregulates ICOS-L (inducible costimulator ligand) and PD-L2 (programmed death ligand 2). Endothelial cell-derived interleukin-18 (IL-18) selectively expands a T-cell population (CD4+CD45RO+PD-1hiICOS+CCR2+CXCR5-) displaying features of recently described T peripheral helper cells. This population highly expressed IL-18R1 and promoted donor-specific antibodies in response to IL-18 in vivo. In patients with delayed graft function, a clinical manifestation of IRI, these cells were Ki-67+IL-18R1+ and could be expanded ex vivo in response to IL-18. CONCLUSIONS: IRI promotes elaboration of IL-18 from endothelial cells to selectively expand alloreactive IL-18R1+ T peripheral helper cells in allograft tissues to promote donor-specific antibody formation.

ZFYVE21 is a complement-induced Rab5 effector that activates non-canonical NF-κB via phosphoinosotide remodeling of endosomes.

Complement promotes vascular inflammation in transplant organ rejection and connective tissue diseases. Here we identify ZFYVE21 as a complement-induced Rab5 effector that induces non-canonical NF-κB in endothelial cells (EC). In response to membrane attack complexes (MAC), ZFYVE21 is post-translationally stabilized on MAC+Rab5+ endosomes in a Rab5- and PI(3)P-dependent manner. ZFYVE21 promotes SMURF2-mediated polyubiquitinylation and proteasome-dependent degradation of endosome-associated PTEN to induce vesicular enrichment of PI(3,4,5)P3 and sequential recruitment of activated Akt and NF-κB-inducing kinase (NIK). Pharmacologic alteration of cellular phosphoinositide content with miltefosine reduces ZFYVE21 induction, EC activation, and allograft vasculopathy in a humanized mouse model. ZFYVE21 induction distinctly occurs in response to MAC and is detected in human renal and synovial tissues. Our data identifies ZFYVE21 as a Rab5 effector, defines a Rab5-ZFYVE21-SMURF2-pAkt axis by which it mediates EC activation, and demonstrates a role for this pathway in complement-mediated conditions.

Successful treatment of primary donor-derived human herpesvirus-8 infection and hepatic Kaposi Sarcoma in an adult liver transplant recipient.

Kaposi sarcoma (KS) may rarely occur in transplant recipients through primary human herpesvirus-8 (HHV-8) infection from a seropositive donor. This report describes a patient who developed hepatic KS after receiving a split liver transplant from an HHV-8-positive donor. The recipient was treated with liposomal doxorubicin after reduction in immunosuppression led to acute cellular rejection. This treatment achieved regression of KS while preserving allograft function, demonstrating a successful therapeutic strategy for this malignancy.

Subpopulations of M-MDSCs from mice infected by an immunodeficiency-causing retrovirus and their differential suppression of T- vs B-cell responses.

Monocytic (CD11b(+)Ly6G(±/Lo)Ly6C(+)) myeloid derived suppressor cells (M-MDSCs) expand following murine retroviral LP-BM5 infection and suppress ex vivo polyclonal T-cell and B-cell responses. M-MDSCs 3 weeks post LP-BM5 infection have decreased suppression of T-cell, but not B-cell, responses and alterations in the degree of iNOS/NO dependence of suppression. M-MDSCs from LP-BM5 infected mice were sorted into four quadrant populations (Ly6C/CD11b density): all quadrants suppressed B-cell responses, but only M-MDSCs expressing the highest levels of Ly6C and CD11b (Q2) significantly suppressed T-cell responses. Further subdivision of this Q2 population revealed the Ly6C(+/Hi) M-MDSC subpopulation as the most suppressive, inhibiting T- and B-cell responses in a full, or partially, iNOS/NO-dependent manner, respectively. In contrast, the lower/moderate levels of suppression by the Ly6C(+/Lo) and Ly6C(+/Mid) M-MDSC Q2 subpopulations, whether versus T- and/or B-cells, displayed little/no iNOS dependency for suppression. These results highlight differential phenotypic and functional immunosuppressive M-MDSC subsets in a retroviral immunodeficiency model.