Ex Vivo Perfusion With Adenosine A2A Receptor Agonist Enhances Rehabilitation of Murine Donor Lungs After Circulatory Death.

BACKGROUND: Ex vivo lung perfusion (EVLP) enables assessment and rehabilitation of marginal donor lungs before transplantation. We previously demonstrated that adenosine A2A receptor (A2AR) agonism attenuates lung ischemia-reperfusion injury. The current study utilizes a novel murine EVLP model to test the hypothesis that A2AR agonist enhances EVLP-mediated rehabilitation of donation after circulatory death (DCD) lungs. METHODS: Mice underwent euthanasia and 60 minutes warm ischemia, and lungs were flushed with Perfadex and underwent cold static preservation (CSP, 60 minutes). Three groups were studied: no EVLP (CSP), EVLP with Steen solution for 60 minutes (EVLP), and EVLP with Steen solution supplemented with ATL1223, a selective A2AR agonist (EVLP + ATL1223). Lung function, wet/dry weight, cytokines and neutrophil numbers were measured. Microarrays were performed using the Affymetrix GeneChip Mouse Genome 430A 2.0 Array. RESULTS: Ex vivo lung perfusion significantly improved lung function versus CSP, which was further, significantly improved by EVLP + ATL1223. Lung edema, cytokines, and neutrophil counts were reduced after EVLP and further, significantly reduced after EVLP + ATL1223. Gene array analysis revealed differential expression of 1594 genes after EVLP, which comprise canonical pathways involved in inflammation and innate immunity including IL-1, IL-8, IL-6, and IL-17 signaling. Several pathways were uniquely regulated by EVLP + ATL1223 including the downregulation of genes involved in IL-1 signaling, such as ADCY9, ECSIT, IRAK1, MAPK12, and TOLLIP. CONCLUSIONS: Ex vivo lung perfusion modulates proinflammatory genes and reduces pulmonary dysfunction, edema, and inflammation in DCD lungs, which are further reduced by A2AR agonism. This murine EVLP model provides a novel platform to study rehabilitative mechanisms of DCD lungs.

Bilateral Lung Transplantation From a Donor With Heparin-Induced Thrombocytopenia.

We report the case of a 46-year-old male patient with a history of cystic fibrosis who received bilateral lung transplantation from a donor who died secondary to complications of heparin-induced thrombocytopenia. Postoperatively, he exhibited transient focal neurologic deficits and radiographic evidence of multiple cortical and subcortical infarctions. He was treated with a combination of fondaparinux and standard immunosuppressive therapy, made a full recovery, and experienced significantly improved lung function compared to pretransplantation capacity.

Planned cardiac reexploration in the intensive care unit is a safe procedure.

BACKGROUND: Cardiac surgical reexploration is necessary in approximately 5% of all patients. However, the impact of routine, planned reexploration performed in the intensive care unit (ICU) remains poorly defined. This study evaluated postoperative outcomes after cardiac reexplorations to determine the safety and efficacy of a planned approach in the ICU. METHODS: All patients undergoing ICU cardiac reexplorations (2000 to2011) at a single institution were stratified according to a routine, planned ICU approach to reexploration (planned) versus unplanned ICU or operating room reexploration. Patient risk and outcomes were compared by univariate and multivariate analyses. RESULTS: 8,151 total patients underwent cardiac operations, including 267 (3.2%) reexplorations (planned ICU=75% and unplanned ICU=18%). Among planned ICU reexplorations, 38% of patients had an identifiable surgical bleeding source, and 60% underwent reexploration less than 12 hours after the index procedure. Unplanned ICU reexplorations had a higher Society of Thoracic Surgeons (STS) predicted mortality (5% vs 3%, p<0.001) and incurred higher observed mortality (37% vs 6%, p<0.001) and morbidity. Sternal wound infections were rare and were similar between groups (p=0.81). Furthermore, upon STS mortality risk adjustment, unplanned ICU reexplorations were associated with significantly increased odds of mortality (OR=26.6 [7.1, 99.7], p<0.001) compared with planned ICU reexplorations. CONCLUSIONS: Planned reexploration in the ICU is a safe procedure with acceptable mortality and morbidity and low infection rates. Unplanned reexplorations, however, increase postoperative risk and are associated with high mortality and morbidity. These data argue for coordinated, routine approaches to planned ICU reexploration to avoid delay in treatment for postoperative hemorrhage.

NADPH oxidase mediates synergistic effects of IL-17 and TNF-α on CXCL1 expression by epithelial cells after lung ischemia-reperfusion.

Ischemia-reperfusion (I/R) injury leads to increased mortality and morbidity in lung transplant patients. Lung I/R injury involves inflammation contributed by innate immune responses. IL-17 and TNF-α, from iNKT cells and alveolar macrophages, respectively, contribute importantly to lung I/R injury. This study tests the hypothesis that IL-17 and TNF-α synergistically mediate CXCL1 (a potent neutrophil chemokine) production by alveolar type II epithelial (ATII) cells via an NADPH oxidase-dependent mechanism during lung I/R. Using a hilar clamp model, wild-type and p47(phox-/-) (NADPH oxidase-deficient) mice underwent left lung I/R, with or without recombinant IL-17 and/or TNF-α treatment. Wild-type mice undergoing I/R treated with combined IL-17 and TNF-α had significantly enhanced lung dysfunction, edema, CXCL1 production, and neutrophil infiltration compared with treatment with IL-17 or TNF-α alone. However, p47(phox-/-) mice had significantly less pulmonary dysfunction, CXCL1 production, and lung injury after I/R that was not enhanced by combined IL-17-TNF-α treatment. Moreover, in an acute in vitro hypoxia-reoxygenation model, murine ATII cells showed a multifold synergistic increase in CXCL1 expression after combined IL-17-TNF-α treatment compared with treatment with either cytokine alone, which was significantly attenuated by an NADPH oxidase inhibitor. Conditioned media transfer from hypoxia-reoxygenation-exposed iNKT cells and macrophages, major sources of IL-17 and TNF-α, respectively, to ATII cells significantly enhanced CXCL1 production, which was blocked by NADPH oxidase inhibitor. These results demonstrate that IL-17 and TNF-α synergistically mediate CXCL1 production by ATII cells after I/R, via an NADPH oxidase-dependent mechanism, to induce neutrophil infiltration and lung I/R injury.

Surgical outcomes analysis of pediatric peritoneal dialysis catheter function in a rural region.

PURPOSE: The purpose of this study was to analyze the experience with peritoneal dialysis (PD) at a high-volume, single center institution that supports a rural population. METHODS: From 2000 to 2010, 88 children (median age: 1.98 years, [range: 2 days-20.2 years]) received 134 PD catheters for the management of acute and chronic renal failure. The primary outcome of interest was the incidence of primary PD catheter failure (replacement or revision within 60 days). Operative technique, longitudinal outcomes, and time intervals to transplantation were analyzed. RESULTS: Median time to transplant from the institution of dialysis was 1.4 years [range: 0.3-6.4 years]. Primary catheter failure occurred in 24.6% of cases. Infants less than 6 months of age demonstrated an increased incidence of primary catheter failure (p = 0.02). The operative technique for catheter placement was not associated with the incidence of primary failure. Postoperative complications included peritonitis (22.7%), omental plugging (11.9%), pericatheter drainage (9.0%), and exit site infection (3.0%). CONCLUSION: Peritoneal dialysis provides a safe and effective renal replacement therapy for regional pediatric centers that serve a rural population. However, primary catheter failure rates remain high at 24.6%. The surgical technique for placement had no effect on this failure rate in our patient population. Infants less than 6 months of age are at increased risk for primary catheter failure and warrant intensive surveillance.

Adenosine A3 receptor activation attenuates lung ischemia-reperfusion injury.

BACKGROUND: Severe ischemia-reperfusion (IR) injury leads to primary graft dysfunction after lung transplantation. Adenosine receptors modulate inflammation after IR, and the adenosine A3 receptor (A3R) is expressed in lung tissue and inflammatory cells. This study tests the hypothesis that A3R agonism attenuates lung IR injury by a neutrophil-dependent mechanism. METHODS: Wild-type and A3R knockout (A3R-/-) mice underwent 1-hour left lung ischemia followed by 2-hours reperfusion (IR). A selective A3R agonist, Cl-IB-MECA, was administered (100 µg/kg intravenously) 5 minutes prior to ischemia. Study groups included sham, IR, and IR+Cl-IB-MECA (n = 6/group). Lung injury was assessed by measuring lung function, pulmonary edema, histopathology, and proinflammatory cytokines, and myeloperoxidase levels in bronchoalveolar lavage fluid. Parallel in vitro experiments were performed to evaluate neutrophil chemotaxis, and neutrophil activation was measured after exposure to acute hypoxia and reoxygenation. RESULTS: Treatment of wild-type mice with Cl-IB-MECA significantly improved lung function and decreased edema, cytokine expression, and neutrophil infiltration after IR. The Cl-IB-MECA had no effects in A3R-/- mice; Cl-IB-MECA significantly decreased activation of wild-type, but not A3R-/-, neutrophils after acute hypoxia and reoxygenation and inhibited chemotaxis of wild-type neutrophils. CONCLUSIONS: Exogenous activation of A3R by Cl-IB-MECA attenuates lung dysfunction, inflammation, and neutrophil infiltration after IR in wild-type but not A3R-/- mice. Results with isolated neutrophils suggest that the protective effects of Cl-IB-MECA are due, in part, to the prevention of neutrophil activation and chemotaxis. The use of A3R agonists may be a novel therapeutic strategy to prevent lung IR injury and primary graft dysfunction after transplantation.

Primary payer status is significantly associated with postoperative mortality, morbidity, and hospital resource utilization in pediatric surgical patients within the United States.

PURPOSE: Current healthcare reform efforts have highlighted the potential impact of insurance status on patient outcomes. The influence of primary payer status (PPS) within the pediatric surgical patient population remains unknown. The purpose of this study was to examine risk-adjusted associations between PPS and postoperative mortality, morbidity, and resource utilization in pediatric surgical patients within the United States. METHODS: A weighted total of 153,333 pediatric surgical patients were evaluated using the national Kids' Inpatient Database (2003 and 2006): appendectomy, intussusception, decortication, pyloromyotomy, congenital diaphragmatic hernia repair, and colonic resection for Hirschsprung's disease. Patients were stratified according to PPS: Medicare (n=180), Medicaid (n=51,862), uninsured (n=12,539), and private insurance (n=88,753). Multivariable hierarchical regression modeling was utilized to evaluate risk-adjusted associations between PPS and outcomes. RESULTS: Overall median patient age was 12 years, operations were primarily non-elective (92.4%), and appendectomies accounted for the highest proportion of cases (81.3%). After adjustment for patient, hospital, and operation-related factors, PPS was independently associated with in-hospital death (p<0.0001) and postoperative complications (p<0.02), with increased risk for Medicaid and uninsured populations. Moreover, Medicaid PPS was also associated with greater adjusted lengths of stay and total hospital charges (p<0.0001). Importantly, these results were dependent on operation type. CONCLUSIONS: Primary payer status is associated with risk-adjusted postoperative mortality, morbidity, and resource utilization among pediatric surgical patients. Uninsured patients are at increased risk for postoperative mortality while Medicaid patients accrue greater morbidity, hospital lengths of stay, and total charges. These results highlight a complex interaction between socioeconomic and patient-related factors, and primary payer status should be considered in the preoperative risk stratification of pediatric patients.

Cryoablation during left ventricular assist device implantation reduces postoperative ventricular tachyarrhythmias.

BACKGROUND: The number of patients undergoing implantation of a HeartMate II left ventricular assist device (LVAD; Thoratec Corporation, Pleasanton, Calif) is rising. Ventricular tachyarrhythmia (VA) after placement of the device is common, especially among patients with preoperative VA. We sought to determine whether intraoperative cryoablation in select patients reduces the incidence of postoperative VA. METHODS: From January 2009 through September 2010, 50 consecutive patients undergoing implantation of the HeartMate II LVAD were examined. Fourteen of these patients had recurrent preoperative VA. Of those patients with recurrent VA, half underwent intraoperative cryoablation (Cryo: n = 7) and half did not (NoCryo: n = 7). Intraoperatively, patients underwent localized epicardial and endocardial cryoablation via LVAD ventriculotomy. Cryothermal lesions were created to connect scar to fixed anatomic borders in the region of clinical VA. Demographics, risk factors, intraoperative features, and outcomes were analyzed to investigate the feasibility of cryoablation. RESULTS: Thirty-day mortality remained low (n = 1, 2%) among all LVAD recipients. There were no differences in risk factors between groups except that preoperative inotropes were less prevalent in Cryo patients (P = .09). Compared with NoCryo, the Cryo group had significantly decreased postoperative resource use and complications (P < .05). Recurrent postoperative VA did not develop in any of the Cryo patients (P = .02). CONCLUSIONS: Postoperative VA can be minimized by preoperative risk assessment and intraoperative treatment. Localized cryoablation in select patients offers promising early feasibility when performed during HeartMate II LVAD implantation. Further prospective analysis is required to investigate this novel approach.

Orthotopic heart transplant versus left ventricular assist device: a national comparison of cost and survival.

OBJECTIVES: Orthotopic heart transplantation is the standard of care for end-stage heart disease. Left ventricular assist device implantation offers an alternative treatment approach. Left ventricular assist device practice has changed dramatically since the 2008 Food and Drug Administration approval of the HeartMate II (Thoratec, Pleasanton, Calif), but at what societal cost? The present study examined the cost and efficacy of both treatments over time. METHODS: All patients who underwent either orthotopic heart transplantation (n = 9369) or placement of an implantable left ventricular assist device (n = 6414) from 2005 to 2009 in the Nationwide Inpatient Sample were selected. The trends in treatment use, mortality, and cost were analyzed. RESULTS: The incidence of orthotopic heart transplantation increased marginally within a 5-year period. In contrast, the annual left ventricular assist device implantation rates nearly tripled. In-hospital mortality from left ventricular assist device implantation decreased precipitously, from 42% to 17%. In-hospital mortality for orthotopic heart transplantation remained relatively stable (range, 3.8%-6.5%). The mean cost per patient increased for both orthotopic heart transplantation and left ventricular assist device placement (40% and 17%, respectively). With the observed increase in both device usage and cost per patient, the cumulative Left ventricular assist device cost increased 232% within 5 years (from $143 million to $479 million). By 2009, Medicare and Medicaid were the primary payers for nearly one half of all patients (orthotopic heart transplantation, 45%; left ventricular assist device, 51%). CONCLUSIONS: Since Food and Drug Administration approval of the HeartMate II, mortality after left ventricular assist device implantation has decreased rapidly, yet has remained greater than that after orthotopic heart transplantation. The left ventricular assist device costs have continued to increase and have been significantly greater than those for orthotopic heart transplantation. Because of the evolving healthcare economics climate, with increasing emphasis on the costs and comparative effectiveness, a concerted effort at LVAD cost containment and judicious usage is essential to preserve the viability of this invaluable treatment.

Ex vivo rehabilitation of non-heart-beating donor lungs in preclinical porcine model: delayed perfusion results in superior lung function.

OBJECTIVES: Ex vivo lung perfusion (EVLP) is a promising modality for the evaluation and treatment of marginal donor lungs. The optimal timing of EVLP initiation and the potential for rehabilitation of donor lungs with extended warm ischemic times is unknown. The present study compared the efficacy of different treatment strategies for uncontrolled non-heart-beating donor lungs. METHODS: Mature swine underwent hypoxic arrest, followed by 60 minutes of no-touch warm ischemia. The lungs were harvested and flushed with 4°C Perfadex. Three groups (n = 5/group) were stratified according to the preservation method: cold static preservation (CSP; 4 hours of 4°C storage), immediate EVLP (I-EVLP: 4 hours EVLP at 37°C), and delayed EVLP (D-EVLP; 4 hours of CSP followed by 4 hours of EVLP). The EVLP groups were perfused with Steen solution supplemented with heparin, methylprednisolone, cefazolin, and an adenosine 2A receptor agonist. The lungs then underwent allotransplantation and 4 hours of recipient reperfusion before allograft assessment for resultant ischemia-reperfusion injury. RESULTS: The donor blood oxygenation (partial pressure of oxygen/fraction of inspired oxygen ratio) before death was not different between the groups. The oxygenation after transplantation was significantly greater in the D-EVLP group than in the I-EVLP or CSP groups. The mean airway pressure, pulmonary artery pressure, and expression of interleukin-8, interleukin-1ß, and tumor necrosis factor-α were all significantly reduced in the D-EVLP group. Post-transplant oxygenation exceeded the acceptable clinical levels only in the D-EVLP group. CONCLUSIONS: Uncontrolled non-heart-beating donor lungs with extended warm ischemia can be reconditioned for successful transplantation. The combination of CSP and EVLP in the D-EVLP group was necessary to obtain optimal post-transplant function. This finding, if confirmed clinically, will allow expanded use of nonheart-beating donor lungs.

Concomitant tricuspid valve operations affect outcomes after mitral operations: a multiinstitutional, statewide analysis.

BACKGROUND: Mitral valve (MV) disease is often accompanied by concomitant tricuspid valve (TV) disease. This study determined the influence of performing TV procedures in the setting of MV operations within a multiinstitutional patient population. METHODS: From 2001 to 2008, 5,495 MV operations were performed at 17 different statewide centers. Of these, 5,062 patients (age, 63.4 ± 13.0 years) underwent an MV operation and 433 (age, 64.0 ± 14.2 years) underwent combined MV and TV (MV+TV) operations. The influence of concomitant TV procedures on operative death and the composite incidence of major complications was assessed by univariate and multivariate analyses. RESULTS: Patients undergoing MV+TV were more commonly women (62.7% vs 45.5%, p < 0.001), had higher rates of heart failure (73.7% vs 50.9%, p < 0.001), and more frequently underwent reoperations (17.1% vs 7.4%, p < 0.001) compared with MV patients. Other patient characteristics, including preoperative endocarditis (8.5% vs 8.2%, p = 0.78), were similar between groups. MV replacement (63.5%) was more common than repair (36.5%, p < 0.001) in MV+TV operations, and MV+TV operations incurred longer median cardiopulmonary bypass times (181 vs 149 minutes, p < 0.001). Unadjusted operative mortality (6.0% vs 10.4%, p = 0.001) and postoperative complications were higher after MV+TV compared with MV. More important, risk adjustment showed performance of concomitant TV procedures was an independent predictor of operative death (odds ratio, 1.50; p = 0.03) and major complications (odds ratio, 1.39; p = 0.004). CONCLUSIONS: A concomitant TV operation is a proxy for more advanced valve disease. Compared with MV operations alone, simultaneous MV+TV operations are associated with elevated morbidity and death, even after risk adjustment. This elevated risk should be considered during preoperative patient risk stratification.

Contemporary outcomes for surgical mitral valve repair: a benchmark for evaluating emerging mitral valve technology.

OBJECTIVE: The emergence of transcatheter approaches to mitral valve (MV) repair has focused attention on outcomes after surgical MV repair. Results from the EVEREST II trial demonstrated worse short-term major adverse event (MAE) rates for surgical repair. This study analyzes contemporary outcomes of surgical MV repair to establish a benchmark for future therapeutic comparisons. METHODS: From 2003 to 2008, 903 isolated MV repair operations were performed at 13 different statewide cardiac centers. Patients were excluded if they had prior valve operations or mitral stenosis similar to EVEREST II. MAE rate was defined using similar criteria to EVEREST II, including postoperative atrial fibrillation and transfusion of 2 units of blood or more. Univariate analyses and multivariate regression models were applied to identify independent predictors of MAEs after surgical MV repair. RESULTS: Mean patient age was 57.0 ± 13.2 years, and the majority of patients were men (59.0%, 533/903). The prevalence of preoperative risk factors was as follows: stroke 3.9% (35/903), immunosuppression 2.4% (22/903), heart failure 32.1% (290/903), renal failure 3.5% (32/903), and previous coronary artery bypass grafting 3.4% (31/903). Mean ejection fraction was 55.6 ± 11.3%. MAE rate was 29.0% (262/903), including atrial fibrillation 17.6% (159/903), renal failure 1.3% (12/903), stroke 0.9% (8/903), and operative mortality 1.1% (10/903). Multivariate correlates of MAE included the following: advanced age, prior stroke, immunosuppression, and operation time. Importantly, gender, previous coronary bypass grafting, renal failure, and ejection fraction were not independent predictors of MAE. CONCLUSIONS: In the current era, patients undergoing surgical MV repair have low mortality. MAE rate was largely due to postoperative atrial fibrillation. These results may help to stratify which patients may be best served with newer technologies.

Antimicrobial-impregnated surgical incise drapes in the prevention of mesh infection after ventral hernia repair.

BACKGROUND: Antimicrobial surgical incise drapes are used in an effort to lower the risk of mesh infection after hernia repair. The effect such drapes on infection rates was examined. METHODS: Ventral or incisional hernia repairs with mesh from March, 2002, to June, 2006 gathered from the local American College of Surgeons-National Surgical Quality Improvement Project database, chart review, and operating room database were reviewed. Mesh infection was defined as infection necessitating mesh removal. Significant univariate predictors of infection were included in a logistic regression model. Mesh infections were divided into early (0-7 days), midterm (8-50 days), and late (>50 days) onset for subgroup analysis. RESULTS: Five hundred six hernia repairs and 42 mesh infections (8.3%) were identified (range 1-947 days), the latter consisting of seven early (16.7%), 13 midterm (31.0%), and 22 late (53.4%) infections. Antimicrobial-impregnated incise drapes were used in 206 cases in the entire series (59.1%). By multivariable analysis, factors significantly associated with incise drape use were laparoscopic repair (odds ratio [OR] 3.03; p < 0.0001), per-year resident level (OR 1.21; p = 0.0012), high-volume surgeon (OR 1.74; p = 0.021), clean wound classification (OR 2.21; p = 0.0076), current or recent smoking (OR 1.61; p = 0.039), and chronic steroid use (OR 0.31; p = 0.044). Predictors of mesh infection in multivariable analysis were repair of recurrent hernia (OR 3.72; p < 0.0001), current or recent smoking (OR 2.18; p = 0.027), and per-minute operation time (OR 1.007; p = 0.0004). Missed enterotomy was the only factor significantly associated with time to mesh infection (75% in the early group; p < 0.0001). CONCLUSION: At our institution, antimicrobial-impregnated incise drapes are most likely to be used by the highest-volume hernia repair surgeons and more experienced residents in clean, elective, laparoscopic cases. However, reduction in the mesh infection rate was not observed with their use. Independent predictors of mesh infection included repeat surgery, smoking, and longer operating time. The time from operation to mesh infection differed greatly. Not unexpectedly, mesh infection within seven days after implantation was strongly related to a missed enterotomy.

Additive protection against lung ischemia-reperfusion injury by adenosine A2A receptor activation before procurement and during reperfusion.

OBJECTIVE: Adenosine A2A receptor activation during reperfusion improves lung ischemia-reperfusion injury. In this study we sought to determine whether pretreatment of rabbits with a potent and selective adenosine A2A receptor agonist, ATL-313, before transplantation or whether adding ATL-313 to the preservation solution results in equivalent or additional protection compared with ATL-313 added during reperfusion. METHODS: An isolated, ventilated, ex vivo blood-perfused rabbit lung model was used. All groups underwent 2 hours of reperfusion after 18 hours of cold ischemia (4 degrees C). ATL-313 was administered 1 hour before ischemia intravenously, with the preservation solution, and/or during reperfusion. RESULTS: Both pretreatment of donor animals with ATL-313 or adding ATL-313 just during reperfusion improved pulmonary function, but significantly greater improvement was observed when pretreatment and treatment during reperfusion were combined (all P < .05). Myeloperoxidase levels, bronchoalveolar lavage tumor necrosis factor alpha levels, and pulmonary edema were all maximally decreased in the combined treatment group. The administration of an equimolar amount of the potent and highly selective adenosine 2A receptor antagonist, ZM 241385, along with ATL-313, resulted in the loss of protection conferred by ATL-313. CONCLUSIONS: Adenosine A2A receptor activation with ATL-313 results in the greatest protection against lung ischemia-reperfusion injury when given before ischemia and during reperfusion. Improved pulmonary function observed with adenosine A2A receptor activation was correlated with decreased bronchoalveolar lavage tumor necrosis factor alpha and decreased lung myeloperoxidase. The loss of protection observed with the concurrent administration of the adenosine A2A receptor antagonist, ZM 241385, supports that the mechanism of ATL-313 protection is specifically mediated via adenosine A2A receptor activation.

A change in perspective: results for ischemic mitral valve repair are similar to mitral valve repair for degenerative disease.

BACKGROUND: Although the benefits of mitral valve repair for degenerative disease are well established, many consider surgery for functional ischemic mitral regurgitation (MR) less amenable to operative treatment. We hypothesized that mitral valve repair for ischemic MR results in outcomes similar to those for mitral valve repair for degenerative MR. METHODS: Retrospective review of nonemergent mitral valve repairs for an 8-year period revealed 105 patients with functional ischemic MR, of whom 39 were treated for severe tethering (ischemic group), and 245 patients with degenerative MR (degenerative group). RESULTS: Patients in the ischemic group had more comorbidities (p < 0.01) and worse preoperative left ventricular dysfunction (ejection fraction < or = 0.29) compared with patients in the degenerative group; (ischemic, 37.1% [39 of 105] versus degenerative, 2.0% [5 of 245]; p < 0.01). Immediate postrepair transesophageal echocardiogram revealed a 0 to 1+ MR in all patients in both groups (not significant). The hospital mortality rate was 1.9% (2 of 105) in the ischemic group and 1.2% (3 of 245) in the degenerative group (p = 1.00). The 5-year survival rate was 83.9% in the ischemic group and 94.3% in the degenerative group (p < 0.01). Five-year freedom from reoperation for recurrent MR was 100% and 97.5% in the ischemic and degenerative groups, respectively (p = 0.14). Postoperative renal failure and stroke rates were similar between both groups (not significant). The incidence of moderate or greater MR after more than 1 year of follow-up was similar between groups (not significant). CONCLUSIONS: Despite the multiple comorbidities that afflict patients with ischemic MR, mitral valve repair for ischemic and degenerative disease produces comparable and satisfactory outcomes. An aggressive approach to repair of functional ischemic MR, including treatment of tethering, leads to durable results.