Decreased serotonin transporter activity in the mitral valve contributes to progression of degenerative mitral regurgitation.

Degenerative mitral valve (MV) regurgitation (MR) is a highly prevalent heart disease that requires surgery in severe cases. Here, we show that a decrease in the activity of the serotonin transporter (SERT) accelerates MV remodeling and progression to MR. Through studies of a population of patients with MR, we show that selective serotonin reuptake inhibitor (SSRI) use and SERT promoter polymorphism 5-HTTLPR LL genotype were associated with MV surgery at younger age. Functional characterization of 122 human MV samples, in conjunction with in vivo studies in SERT-/- mice and wild-type mice treated with the SSRI fluoxetine, showed that diminished SERT activity in MV interstitial cells (MVICs) contributed to the pathophysiology of MR through enhanced serotonin receptor (HTR) signaling. SERT activity was decreased in LL MVICs partially because of diminished membrane localization of SERT. In mice, fluoxetine treatment or SERT knockdown resulted in thickened MV leaflets. Similarly, silencing of SERT in normal human MVICs led to up-regulation of transforming growth factor ß1 (TGFß1) and collagen (COL1A1) in the presence of serotonin. In addition, treatment of MVICs with fluoxetine not only directly inhibited SERT activity but also decreased SERT expression and increased HTR2B expression. Fluoxetine treatment and LL genotype were also associated with increased COL1A1 expression in the presence of serotonin in MVICs, and these effects were attenuated by HTR2B inhibition. These results suggest that assessment of both 5-HTTLPR genotype and SERT-inhibiting treatments may be useful tools to risk-stratify patients with MV disease to estimate the likelihood of rapid disease progression.

Re-dosing of del Nido cardioplegia in adult cardiac surgery requiring prolonged aortic cross-clamp.

OBJECTIVES: Few data exist on the use of del Nido cardioplegia in adults, specifically during operations requiring prolonged aortic cross-clamp. In this pilot study, we evaluate outcomes of patients undergoing surgery with cross-clamp time >3 h based on re-dosing strategy, using either full dose (FD; 1:4 blood to crystalloid ratio) or dilute (4:1 blood to crystalloid ratio) solution. METHODS: Consecutive adult patients (>18 years) undergoing cardiac surgery from 2012 to 2018 with cross-clamp time >3 h were reviewed. Patients were excluded if del Nido cardioplegia was not used. Patients were categorized into FD or dilute groups based on re-dosing solution. Propensity score matching was used to control for baseline differences between groups. The primary endpoint was in-hospital mortality. Other outcomes examined included: postoperative mechanical support, arrhythmia, stroke, dialysis and cardiac function. RESULTS: Included for analysis were 173 patients (115 male) with median age of 63.8 (interquartile range 53.9-73.1). Major comorbidities included diabetes (45), cerebrovascular disease (34), hypertension (131), atrial fibrillation (52) and previous cardiac surgery (83). There were 108 patients (62%) who received FD re-dosing, while 65 (38%) received dilute. A greater proportion of patients in the dilute group received retrograde delivery, for both induction (32/108 vs 39/65, P < 0.001) and re-dose (50/108 vs 53/65, P < 0.001). After propensity score matching, in-hospital mortality was not different between groups (6/48 vs 1/48, P = 0.131). There were no differences in rates of postoperative mechanical circulatory support, stroke, left ventricular ejection fraction or right ventricle dysfunction. CONCLUSIONS: Del Nido cardioplegia has been used in complex cardiac surgery requiring prolonged cross-clamp. Re-dosing can be performed with either FD or dilute del Nido solution with no statistical difference in outcomes.

Increased hospital volume is associated with reduced mortality after thoracoabdominal aortic aneurysm repair.

OBJECTIVE: Contemporary data on outcomes in open thoracoabdominal aortic aneurysm (TAAA) repair are limited to reports from major aortic referral centers showing excellent outcomes. This study aimed to characterize the national experience of open TAAA repair using national outcomes data, with a primary focus on the association of hospital volume with mortality and morbidity. METHODS: The Nationwide Inpatient Sample was queried from 1998 to 2011, and all patients with a diagnosis of TAAA who underwent open operative repair were included. These patients were further stratified into tertiles based on the operative volume of the institution that performed the operation: low volume (LV), <3 cases/y; medium volume (MV), 3 to 11 cases/y; and high volume (HV), ≥12 cases/y. Baseline demographics as well as perioperative outcomes were compared between these groups. Multivariable logistic regression was performed to determine predictors of operative mortality and morbidity. Subgroup analyses were performed for patients presenting for elective surgery and for those presenting for urgent and emergent surgery. RESULTS: Overall operative mortality was 21% for the entire cohort. Operative mortality was higher at LV (26%) and MV (21%) centers compared with HV centers (15%; P < .001). This difference was similar in both elective surgery (LV, 18%; MV, 14%; HV, 12%; P < .001) and urgent and emergent surgery (LV, 34%; MV, 30%; HV, 19%; P < .001). Furthermore, rates of blood transfusion and acute renal failure were significantly lower in the HV group. Multivariable analysis revealed that compared with the HV group, patients operated on at LV centers (odds ratio [OR], 1.9, 95% confidence interval [CI], 1.7-2.1; P < .001) and MV centers (OR, 1.5; 95% CI, 1.4-1.7; P < .001) had at least 1.5 times the odds of in-hospital mortality. The HV group also had significantly lower odds of dying in the subgroup analyses of both elective surgery and urgent and emergent surgery. Increasing TAAA volume was associated with increased use of distal aortic perfusion (OR, 1.03; 95% CI, 1.02-1.03; P < .001). CONCLUSIONS: Patients with TAAA in the United States operated on at HV centers have significantly lower mortality and morbidity compared with patients operated on at lower volume centers. Consideration of referral to HV centers may be warranted, but further research is required to justify this conclusion.

Higher Institutional Volume Reduces Mortality in Reoperative Proximal Thoracic Aortic Surgery.

OBJECTIVE: This study aims to determine the impact of institutional volume on mortality in reoperative proximal thoracic aortic surgery patients using national outcomes data. METHODS: The Nationwide Inpatient Sample was queried from 1998 to 2011 for patients with diagnoses of thoracic aneurysm and/or dissection who underwent open mediastinal repair. A total of 103,860 patients were identified. A total of 1,430 patients had prior cardiac surgery. Patients were further stratified into groups by institutional aortic volume: low (<12 cases/year), medium (12-39 cases/year), and high (40+ cases/year) volume. Multivariable risk-adjusted analysis accounting for emergent status and aortic dissection among other factors was performed to determine the impact of institutional volume on mortality. RESULTS: Overall mortality was 12% in the reoperative population. When the redo cohort was divided into tertiles, high-volume group had a 5% operative mortality compared with 9 and 15% for the medium- and low-volume groups, respectively. Multivariable analysis revealed that patients operated on at low- (odds ratio [OR] = 5.0, 95% confidence interval [CI]: 2.6-9.6, p < 0.001) and medium-volume centers (OR = 2.1, 95% CI: 1.1-4.2, p = 0.03) had higher odds of mortality when compared with patients operated on at high-volume centers. CONCLUSIONS: High-volume aortic centers can significantly reduce mortality for reoperative aortic surgery, compared with lower volume institutions.

Outcomes of mechanical support for cardiogenic shock associated with late cardiac allograft failure.

BACKGROUND: Late graft failure (LGF) is an unresolved issue after orthotopic heart transplant (OHT). In this study, we report characteristics and outcomes of severe LGF requiring mechanical circulatory support (MCS). METHODS: All patients undergoing OHT from 2000 to 2018 at our center were reviewed. Patients re-admitted to the hospital for late graft failure (>3 months after initial discharge) and developing cardiogenic shock requiring MCS were identified. Outcomes and mortality were evaluated. RESULTS: Twenty-six patients were identified. Median age was 37.3 years (interquartile range: 28.2-47.6) and 69% were male. Median time from initial transplant to MCS was 2.9 years. Etiology of graft failure was rejection in 19 patients (73%), transplant coronary artery disease (tCAD) in 3 (12%), with mixed tCAD or rejection in 4 (15%).

Institutional Marfan syndrome surgical volume influences mitral valve surgical strategy in patients with Marfan syndrome.

BACKGROUND/AIM: The goal of this study was to evaluate trends in mitral valve (MV) operations performed on patients with Marfan syndrome (MfS) and determine the influence of an institution's MfS and MV surgical volume on MV surgical strategy in the US. METHODS: The Nationwide Inpatient Sample was queried from 1998 to 2011 and a total of 1126 patients with MfS were identified who underwent MV operations meeting our inclusion criteria. Linear regression was performed to assess trends of MV repair (MVr) rates over time. Patients were stratified into tertiles depending on the institution's annual MfS and MV surgical volumes. Multivariate analysis was used to determine the impact of institutional MV and MfS surgical volume on whether a patient received an MV replacement (MVR). RESULTS: The MVR rate was 60% for the entire cohort. There was a decreasing trend of MVR rates during the study period (82% in 1998-99 vs 49% in 2010-2011, P < .05). Multivariate analysis revealed that patients operated on at high (odds ratio [OR], 0.65; P < .05) and medium (OR, 0.66; P < .05) volume MfS centers were less likely to undergo MVR when compared to lower-volume MfS centers. In contrast, MV volume was not a significant predictor of surgical strategy in this cohort. CONCLUSION: The national MVR rate in the MfS population is higher than published reports. Data from this study suggest that MfS patients with indications for MV surgery should be referred to high-volume MfS surgical centers to have the best opportunity for MVr.

Atrial arrhythmias after lung transplantation: Incidence and risk factors in 652 lung transplant recipients.

OBJECTIVES: Atrial arrhythmia (AA) after lung transplantation (LTx) is a potentially morbid event often associated with increased length of hospital stay. Predictors of postsurgical AA, however, are incompletely understood. We characterized the incidence and predisposing risk factors for AA in patients undergoing LTx. METHODS: A retrospective analysis of prospectively collected data was conducted to identify LTx recipients between January 2008 and October 2013. Patients were divided into 2 groups on the basis of postoperative AA development. Univariable and multivariable analyses were performed to define differences between groups and identify factors associated with AA. Survival differences were assessed by the use of competing risks methodology. RESULTS: A total of 198 of 652 (30.4%) patients developed AA at a median onset of 5 days after transplant. Increasing age (hazard ratio [HR] 1.03 per additional year, P < .001) and previous coronary artery bypass grafting (HR 2.77, P = .002) were found to be independent risk factors. Counterintuitively, patients with a medical history of AA before LTx had a lower incidence of postoperative AA. Preoperative beta-blocker usage was not a significant predictor of postoperative AA. Postoperative AA was a significant predictor of long-term mortality (HR 1.63, P = .007) when we adjusted for other risk factors. CONCLUSIONS: AA is a common occurrence after LTx, occurring with greatest frequency in the first postoperative week, and results in a significant reduction in long-term survival. Increasing age and before coronary artery bypass grafting were identified as independent risk factors for AA development. Better understanding of these risk factors may improve identification of patients at heightened risk after transplantation.