Progression of Non-Significant Mitral and Tricuspid Regurgitation after Surgical Aortic Valve Replacement for Aortic Regurgitation.

Little is known about the natural history of non-significant mitral and tricuspid regurgitation (MR and TR) following surgical aortic valve replacement (SAVR) for aortic regurgitation (AR). We retrospectively analyzed 184 patients (median age 64 (IQR, 55-74) years, 76.6% males) who underwent SAVR for AR. Subjects with significant non-aortic valvulopathies, prior/concomitant valvular interventions, or congenital heart disease were excluded. The cohort was evaluated for MR/TR progression and, based on the latter's occurrence, for echocardiographic and clinical indices of heart failure and mortality. By 5.8 (IQR, 2.8-11.0) years post-intervention, moderate or severe MR occurred in 20 (10.9%) patients, moderate or severe TR in 25 (13.5%), and either of the two in 36 (19.6%). Patients who developed moderate or severe MR/TR displayed greater biventricular disfunction and functional limitation and were less likely to be alive at 7.0 (IQR, 3.4-12.1) years compared to those who did not (47.2 vs. 79.7%, p < 0.001). The emergence of significant MR/TR was associated with preoperative atrial fibrillation/flutter, symptomatic heart failure, and above-mild MR/TR as well as concomitant composite graft use, but not with baseline echocardiographic measures of biventricular function and dimensions, aortic valve morphology, or procedural aspects. In conclusion, among patients undergoing SAVR for AR, significant MR/TR developed in one fifth by six years, correlated with more adverse course, and was anticipated by baseline clinical and echocardiographic variables.

Primary cardiac mesothelioma presenting with fulminant recurrent pericarditis: a case report.

Background: Primary pericardial mesothelioma is an extremely rare disease. Prognosis is poor, with little effects of chemo- or radio-therapy. The majority of cases is diagnosed at autopsy. Case summary: A 22-year-old man, who presented with recurrent pericarditis and large pericardial effusion 2 months after a second BNT162b2 COVID-19 vaccine, underwent pericardiocentesis and pericardial window. Pathology specimen of pericardium revealed benign mesothelial inflammation, consistent with acute pericarditis. Four months later, he presented with a large pericardial mass manifesting in heart failure and underwent urgent pericardiectomy. A new pathology specimen immunostaining and fluorescence in situ hybridization analysis revealed pericardial mesothelioma. Despite intensive care, the patient died 3 weeks later. Discussion: Primary pericardial mesothelial should be considered in the differential diagnosis of refractory recurrent pericarditis, even with prior biopsy-proven pericarditis or when a putative trigger (COVID-19 mRNA prior vaccination) is suspected, as was the case in this patient. Tumour diagnosis and identification consist of multimodal imaging and laboratory tests. A multidisciplinary, individualized care approach should be performed.

The clinical value of the endocarditis team: insights from before and after guidelines implementation strategy.

PURPOSE: To evaluate the impact of a multidisciplinary the "Endocarditis Team" (ET) on the course and outcome of infective endocarditis (IE) patients. METHODS: A retrospective before-after study, including hospitalized patients with definite IE, managed before (01.2013-12.2015) and after (01.2016-07.2019) the introduction of an ET. The primary outcomes were defined as 30-day and 1-year mortality and the secondary as conservative vs. invasive strategy, the interval from clinical suspicion of IE to the performance of echocardiography, utilization of multimodality evaluation, time to an invasive procedure, and the duration of hospitalization. RESULTS: Study population included 92 pre-ET and 128 post-ET implementation patients. Baseline characteristics were similar. During the post-ET period compared with pre-ET, we found higher rates of abscesses and extra-cardiac emboli (27.8% vs. 16.3%, p = 0.048); and a higher invasive procedures rate, including lead extraction (15.6% vs. 6.5%, p = 0.035) and noncardiac surgeries (14.8% vs. 6.5%, p = 0.05). Patients managed during the post-ET period had reduced short (8.5% vs. 17.4%, p = 0.048) and long-term mortality (Log-rank = 0.001). In multivariate analysis of risk factors for long-term mortality, period (pre- or post-ET) was not found to be significantly associated with the mortality. CONCLUSION: Establishment of an ET was associated with faster and more intensive evaluation of patients with IE. During the period of an ET activity, mortality rates were reduced compared with the previous period.

Streptococcus gallolyticus endocarditis on a prosthetic tricuspid valve: a case report and review of the literature.

BACKGROUND: Streptococcus gallolyticus subspecies gallolyticus is a known pathogen that causes infective endocarditis, and most cases involve the left heart valves. We present the first reported case of prosthetic tricuspid valve endocarditis caused by this microorganism. Relevant literature is reviewed. CASE PRESENTATION: A 67-year-old Jewish female with a history of a prosthetic tricuspid valve replacement was admitted to the emergency department because of nonspecific complaints including effort dyspnea, fatigue, and a single episode of transient visual loss and fever. No significant physical findings were observed. Laboratory examinations revealed microangiopathic hemolytic anemia and a few nonspecific abnormalities. Transesophageal echocardiogram demonstrated a vegetation attached to the prosthetic tricuspid valve. The involved tricuspid valve was replaced by a new tissue valve, and Streptococcus gallolyticus subspecies gallolyticus was grown from its culture. Prolonged antibiotic treatment was initiated. CONCLUSIONS: Based on this report and the reviewed literature, Streptococcus gallolyticus should be considered as a rare but potential causative microorganism in prosthetic right-sided valves endocarditis. The patient's atypical presentation emphasizes the need for a high index of suspicion for the diagnosis of infective endocarditis.

Long-Term Outcomes After Mitral Valve Replacement and Tricuspid Annuloplasty in Rheumatic Patients.

BACKGROUND: Late tricuspid regurgitation is a common finding in patients with rheumatic valvular disease after mitral valve replacement surgery. However, the long-term benefit of concomitant tricuspid valve annuloplasty has not been established in this population. METHODS: This was a single-center retrospective study in a tertiary hospital. The final cohort included 285 rheumatic patients who underwent either isolated mitral valve replacement (147 patients) or mitral valve replacement with concomitant tricuspid valve annuloplasty (138 patients). Tricuspid regurgitation severity grade was assessed according to current echocardiography guidelines and graded using a 0 to 3 scale (none or trivial, mild, moderate, severe). RESULTS: Patients were followed for a total median duration of 10.8 (interquartile range, 6.8 to 14.5) years. The majority of patients undergoing mitral valve replacement were women, with a median age at operation of 59 (interquartile range, 48 to 68) years. Patients undergoing concomitant tricuspid valve annuloplasty had a 3.4-fold odds of improving their tricuspid regurgitation grade at long-term follow-up by multivariate logistic regression. Furthermore, concomitant tricuspid valve annuloplasty was independently associated with a long-term survival benefit in patients with preoperative moderate or severe tricuspid regurgitation (hazard ratio, 0.44; 95% confidence interval, 0.23 to 0.87; p = 0.018). CONCLUSIONS: This study demonstrates good long-term results in patients with rheumatic heart disease undergoing mitral valve replacement with concomitant tricuspid valve annuloplasty.

Transcatheter Aortic Valve Implantation Futility Risk Model Development and Validation Among Treated Patients With Aortic Stenosis.

Risk-benefit assessment for transcatheter aortic valve implantation (TAVI) is still evolving. A sizeable group of patients do not fully benefit from intervention despite a technically successful procedure. All patients who underwent TAVI with device success and with no Valve Academic Research Consortium (VARC)-2 defined complications were included. Various demographic data, clinical details, and echocardiographic findings were examined. The outcome was defined as 1-year composite of mortality, stroke, lack of functional-class improvement (by New York Heart Association class), and readmissions (≥1 month after the procedure). Logistic regression was used to fit the prediction model. We used a 10-fold cross-validation to validate our results. Of 543 patients, 435 met the inclusion criteria. The mean age was 82 (±6.5) years, 43% were men, and the mean Society of Thoracic Surgeons score was 6.6 (±4.7). At 1 year, 66 of 435 patients (15%) experienced the study end point. The final logistic regression model included diabetes, baseline New York Heart Association functional class, diastolic dysfunction, need for diuretics, mean gradient, hemoglobin level, and creatinine level. The area under the curve was 0.73 and was reduced to 0.71 after validation, with a 97% specificity using a single cutoff. Dividing to low-, medium-, and high-risk groups for futility produced a corresponding prevalence of 6%, 19%, and 59% futility. A web application for the prediction model was developed and provided. In conclusion, this prediction score may provide an important insight and may facilitate identification of patients who, despite a technically successful and uncomplicated procedure, have risk that may outweigh the benefit of a contemplated TAVI.

Assessment and Management of Acute Severe Mitral Regurgitation in the Intensive Care Unit.

BACKGROUND AND AIM OF THE STUDY: Acute severe mitral regurgitation (MR) is a serious medical condition. Whilst clear guidelines exist regarding the management of chronic MR, acute severe MR is usually treated on an individual basis. Currently, few data exist regarding acute MR in the era of primary coronary interventions (PCI). The present study included patients admitted to the Department of Cardiology during recent years with acute severe MR of different etiologies, and an analysis of these data in the light of previous investigations. METHODS: The digital database of the present authors' hospital was searched for patients diagnosed with severe MR between 2008 and 2015. From a total of 228 patients identified, 19 with primary MR and 17 with secondary (functional) MR were admitted to the Department of Cardiology. The clinical data and outcome of these patients were analyzed. RESULTS: Among patients with MR due to acute myocardial infarction (MI), 13 had functional MR and six had MR due to mechanical complications, namely rupture of the papillary muscle or chordae tendineae. Among patients with MR not in the setting of MI, 13 had primary MR and four had functional MR. Patients with MR due to acute MI were more often in cardiogenic shock or had pulmonary edema and had a higher mortality. The strongest predictor of mortality was the presence of shock, followed by female gender, hypertension, age ≥68 years; previous MI and pulmonary edema were also predictors of mortality. In patients with acute MI and secondary MR, PCI to the culprit coronary artery was associated with a lesser degree of MR on follow up. CONCLUSIONS: Patients with severe MR are at high risk of in-hospital death. Patients with functional MR are likely to benefit from prompt PCI to the culprit artery, and for those with primary MR urgent surgery is life-saving.

Monitoring platelet reactivity during prasugrel or ticagrelor washout before urgent coronary artery bypass grafting.

OBJECTIVES: Patients with acute myocardial infarction pretreated with prasugrel or ticagrelor may require urgent coronary artery bypass grafting (CABG). However, prasugrel and ticagrelor withdrawal period is recommended for 5-7 days before planned CABG to enable full platelet recovery. We hypothesized that monitoring sequential platelet reactivity (PR) could identify patients with early platelet recovery who may benefit from earlier surgery before the guideline-recommended 5-7 day delay. PATIENTS AND METHODS: We performed preoperative PR assays in 35 patients with acute myocardial infarction who received prasugrel (60%) or ticagrelor (40%) and required an urgent CABG. When platelet inhibition levels were favorable, on the basis of the VerifyNow assay, surgery was endorsed. CABG-related bleeding parameters were collected and compared with two matched control groups composed of patients who received fewer potent antiplatelet regimens. RESULTS: On the basis of platelet function monitoring, we identified 21 (56.7%) patients with a relatively earlier platelet recovery who underwent CABG before the end of the conventional washout period (5-7 days). For these patients, the washout periods were shortened to an average time of 2.6±1.0 days for ticagrelor and 3.8±1.5 days for prasugrel. CABG-related bleeding parameters were comparable with the two matched control groups. CONCLUSION: A strategy of performing preoperative PR assays can identify patients who recover platelet function in less than 5-7 days after ticagrelor or prasugrel discontinuation. This strategy may provide the basis for performing urgent CABGs earlier than the currently recommended delay. Future, larger studies are required to establish these preliminary findings.

Long-Term Outcomes of 560 Consecutive Patients Treated With Transcatheter Aortic Valve Implantation and Propensity Score-Matched Analysis of Early- Versus New-Generation Valves.

Transcatheter aortic valve implantation (TAVI) is an established treatment for severe aortic stenosis in patients at high or prohibitive surgical risk. Nevertheless, long-term clinical and echocardiographic data are still lacking. We carried out an analysis of 560 consecutive patients who underwent TAVI at our institution from 2008 to 2016 to evaluate temporal changes in TAVI characteristics, predictors of 1-year and long-term outcomes, and to compare the performance of the early- and new-generation valve systems. With time, we have adopted lower risk threshold for patient selection and have been using conscious sedation and transfemoral access preferentially (p <0.001 for all). The incidence of greater than mild PVL decreased from 16% to 7.6%, p = 0.029. Within 5 years, 47% of the patients died, the majority (78%) due to noncardiac causes. Independent predictors of 1-year death included periprocedural aspects (i.e., vascular complications, stroke, and PVL), whereas death occurring later than 1 year was solely related to baseline co-morbidities. Transvalvular gradients and residual regurgitation remained nonclinically significant for up to 5 years of follow-up. New-generation valves were associated with less PVL compared with propensity score-matched early-generation valves (p <0.001). In conclusion, TAVI utilization at our institution has progressed to include lower risk patients with transfemoral access becoming applicable in the great majority. Poor long-term survival is attributable to population factors rather than to procedural factors. Intermediate- and long-term hemodynamics are excellent. PVL has diminished significantly with the new-generation valves. Efforts to improve long- and short-term outcomes remain a therapeutic challenge.

Long-Term Outcomes for Patients With Severe Symptomatic Aortic Stenosis Treated With Transcatheter Aortic Valve Implantation.

Transcatheter aortic valve implantation (TAVI) is an established technique for the treatment of severe symptomatic aortic stenosis. Data on long-term TAVI outcomes, both hemodynamic and clinical, in real-world practice settings are limited. We aim to explore the long-term clinical results in patients with severe symptomatic aortic stenosis using multiple catheter-based options: 360 TAVI-treated patients were followed up for ≤5 years. The Medtronic CoreValve was used in 71% and the Edwards SAPIEN in 26%. The primary end point was all-cause mortality during follow-up. Outcomes were assessed based on the Valve Academic Research Consortium 2 criteria. The mean ± SD patient age was 82.1 ± 6.9 years (56.4% women). The Society of Thoracic Surgeons score was 7.5 ± 4.7. The clinical efficacy end point and time-related valve safety at 3 years was 50% and 81.7%, respectively. The calculated 3- and 5-year survival rates were 71.6% and 56.4%, respectively. Five-year follow-up data were obtained for 54 patients alive; 96.2% of alive patients were in the New York Heart Association class I and II, 4 years after TAVI. No gender differences in all-cause mortality rates were observed (p = 0.58). In multivariate analysis, hospitalization 6 months previous to TAVI (hazard ratio [HR] 1.92, 95% confidence interval [CI] 1.17 to 3.15, p = 0.01), frailty (HR 1.89, 95% CI 1.11 to 3.2, p = 0.02), acute kidney injury (HR 1.93, 95% CI 1.03 to 3.61, p = 0.04), and moderate or more paravalvular aortic regurgitation after TAVI (HR 4.26, 95% CI 2.54 to 7.15, p <0.001) were independent predictors for all-cause mortality. In conclusion, long-term outcomes of TAVI are encouraging. Prevention and early identification of paravalvular leak and acute renal failure after the procedure would improve short- and long-term outcomes.

Treatment of Aortic, Mitral and Tricuspid Structural Bioprosthetic Valve Deterioration Using the Valve-in-Valve Technique.

BACKGROUND AND AIM OF THE STUDY: The percutaneous approach for a failed bioprosthetic valve is an emerging alternative to redo-valve surgery in patients at high surgical risk. The study aim was to describe the treatment of patients with structural bioprosthetic valve deterioration, using the valve-in-valve technique. METHODS: A total of 33 consecutive patients with symptomatic structural bioprosthetic valve deterioration was treated at the authors' institution, using the valve-in-valve technique. RESULTS: The valve-in-valve procedure in the aortic position was performed in 23 patients (mean age 81.4 ± 5.9 years; mean STS score 9.6 ± 5.4). The self-expandable and balloon-expandable devices were used in 21 cases (91.3%) and two cases (8.7%), respectively. Procedures were performed via the trans-femoral, trans-axillary and trans-apical routes in 18 (78.2%), three (13%) and two (8.7%) cases, respectively. After the procedure, all patients were in NYHA class I/II. Survival rates were 95.6% at the one-year follow up. The valve-in-valve procedure in the mitral position was performed in 10 patients (mean age 73.6 ± 15 years; mean STS score 7.7 ± 4.1). All procedures were performed using the balloon-expandable device via the trans-apical route. The composite end point of device success was achieved in all patients. Survival rates were 100% and 75% at one month and two years' follow up, respectively. A single valve-in-valve implantation within a failed tricuspid bioprosthetic valve was also successfully performed. CONCLUSION: In the authors' experience, the valve-in-valve technique for the treatment of a wide range of bioprosthetic valve deterioration modes of failure in different valve positions is safe and very effective.

Tricuspid valve replacement: the effect of gender on operative results.

BACKGROUND AND AIM OF THE STUDY: Tricuspid valve replacement (TVR) is considered a high-risk operation. The study aim was to analyze the authors' eight-year experience with TVR and to characterize the specific risk factors for this operation. METHODS: Between January 2005 and August 2012, a total of 67 patients (46 females, 21 males; mean age 58 +/- 14 years; range: 25-86 years) underwent TVR at the authors' center. Re-do operations were performed in 48 patients (72%), including 37 patients (55%) who had at least two previous surgeries. Isolated TVR was performed in 28 patients (42%). The follow up (mean 28 months) included echocardiography and survival analysis. RESULTS: The overall operative mortality was 17.9% (n = 12, all female). In the latter half of the study period, mortality declined to 11.4% (p = NS). Major postoperative morbidity included prolonged mechanical ventilation (28.4%), low cardiac output (29.8%), and acute renal failure requiring hemodialysis (10.4%). Univariate analysis revealed that female gender (p = 0.007), NYHA class (p = 0.038), serum bilirubin level (p = 0.02) and number of previous cardiac surgeries (p = 0.05) were associated with increased operative mortality. Multivariable analysis demonstrated that reoperation (OR 6.06, p = 0.036) was an independent risk factor for operative mortality or complications. Echocardiography at follow up showed that 92.6% of all patients had tricuspid regurgitation grade < 2. The overall five-year survival rates for males and females were 82% and 53%, respectively (p = 0.03), but five-year survival for operative survivors was similar in males and females (82% versus 73%, p = 0.5). Cox regression analysis showed that age (OR 1.07, p = 0.028) and reoperation (OR 6.1, p = 0.038) were independent risk factors for late mortality. CONCLUSION: TVR remains a high-risk operation, particularly for advanced age and previously operated patients; however, the long-term survival is satisfactory. Typically, women undergo TVR at an older age with a higher mortality rate than men. However, the long-term mortality rate of patients who survived surgery was not associated with gender.

Protein targets of inflammatory serine proteases and cardiovascular disease.

Serine proteases are a key component of the inflammatory response as they are discharged from activated leukocytes and mast cells or generated through the coagulation cascade. Their enzymatic activity plays a major role in the body's defense mechanisms but it has also an impact on vascular homeostasis and tissue remodeling. Here we focus on the biological role of serine proteases in the context of cardiovascular disease and their mechanism(s) of action in determining specific vascular and tissue phenotypes. Protease-activated receptors (PARs) mediate serine protease effects; however, these proteases also exert a number of biological activities independent of PARs as they target specific protein substrates implicated in vascular remodeling and the development of cardiovascular disease thus controlling their activities. In this review both PAR-dependent and -independent mechanisms of action of serine proteases are discussed for their relevance to vascular homeostasis and structural/functional alterations of the cardiovascular system. The elucidation of these mechanisms will lead to a better understanding of the molecular forces that control vascular and tissue homeostasis and to effective preventative and therapeutic approaches.

Open heart reoperations after coronary artery bypass grafting: the role of preoperative imaging with multidetector computed tomography.

BACKGROUND: Injury to patent grafts or cardiac chambers may occur during reoperation after coronary artery bypass grafting. Preoperative spatial localization of bypass grafts with computed tomography may improve the safety of these procedures. OBJECTIVES: To characterize patients who undergo CT before repeat operations after previous coronary artery bypass grafting, and evaluate its benefit in terms of surgical outcome. METHODS: We compared 28 patients who underwent cardiac gated CT angiography before reoperation (CT group) to 45 redo patients who were not evaluated with CT (no-CT group). RESULTS: The two groups were similar in most preoperative and operative characteristics. The CT group, however, included more patients with patent saphenous vein grafts and fewer with emergency operations, acute myocardial infarction and need for intraaortic balloon pump support. During mid-sternotomy, there was no injury to grafts in the CT group, while there were two patent grafts and three right ventricular injuries in the no-CT group. There was no significant difference in perioperative mortality (3.6% vs. 8.9%). The overall complication rate in the CT group was 21.4% compared to 42.2% in the no-CT group (P = 0.07). The only independent predictors of postoperative complications were diabetes mellitus, preoperative stroke and preoperative acute MI. CONCLUSIONS: The patency and proximity of patent grafts to the sternum are well demonstrated by multidetector CT and may provide the surgeon with an important roadmap to avoid potential graft injury. A statistical trend towards reduced complications rate was demonstrated among patients who underwent CT angiography before their repeat cardiac operation. Larger series are required to demonstrate a statistically validated complication-free survival benefit of preoperative CT before repeat cardiac surgery.

Higher levels of serum cytokines and myocardial tissue markers during on-pump versus off-pump coronary artery bypass surgery.

Increased Troponin I levels and pro-inflammatory cytokines have been reported in most patients undergoing cardiac surgery, ascribed to the type and extent of surgery, reperfusion injury, and the method of myocardial protection. We investigated their levels in patients undergoing on-pump (CCAB) or off-pump (OPCAB) coronary artery bypass surgery and whether these correlated with the extent of myocardial injury. One hundred twenty patients were prospectively randomized to undergo OPCAB (n = 60) or CCAB (n = 60). Hemodynamic and respiratory data, as well as serum CK-MB mass fraction, Troponin I, and interleukin (IL)-6, IL-8, and IL-10 levels, were collected perioperatively. Demographic, hemodynamic, and respiratory parameters were similar between the two groups. Troponin I was significantly lower in the OPCAB than in the CCAB group, either at the end of ischemia, end of surgery, 6-hour and 24-hour postoperatively (4 +/- 3, 5 +/- 3, 7 +/- 5, and 8 +/- 3 microg/L, vs. 19 +/- 18, 27 +/- 19, 28 +/- 13.5, and 33 +/- 8.5 microg/L, respectively, p < 0.05). Serum cytokine levels in the OPCAB patients were lower compared to the CCAB group at the end of surgery (32 +/- 35, 25 +/- 30, and 40 +/- 30 pg/ml for IL-6, IL-8, and IL-10 vs. 230 +/- 30, 140 +/- 70, and 125 +/- 50 pg/ml, respectively, p < 0.05). Plasma IL-6 levels correlated with the Troponin I levels at the end of surgery in both groups (r = 0.45, p = 0.01). Thus, OPCAB surgery is associated with reduced levels of Troponin I and activation of cytokines, compared to those in the CCAB group. High levels of these factors could correlate with myocardial damage during coronary artery bypass surgery. This finding warrants further laboratory and clinical confirmation in the future.

[Surgical ventricular restoration--new horizons in the treatment of ischemic cardiomyopathy].

Heart failure is a major health problem with increasing prevalence due to aging of the population and in addition to an increase in effective treatment and early myocardial reperfusion during acute myocardial infarction. Postinfarction left ventricular remodeling is characterized by chamber dilatation with an abnormal spherical shape leading to systolic and diastolic dysfunction frequently associated with mitral valve insufficiency and eventually heart failure. Intensive medical management reduces symptoms and improves survival. However, patients who are in NYHA functional class III or IV still have a poor prognosis. In this review article we will endeavor to summarize the emerging surgical approach "surgical ventricular restoration" for treating ventricular remodeling and ischemic cardiomyopathy. These concepts of restoration of the elliptical shape of the left ventricle and re-establishing the normal structure of the sub-valvular mitral apparatus are performed recently in our department.

Minimally invasive reoperative isolated valve surgery: early and mid-term results.

OBJECTIVE: Minimally invasive, nonsternotomy approaches for valve procedures may reduce the risks associated with cardiac surgery after prior sternotomy and may improve outcomes. We analyzed our institutional experience to test this hypothesis. METHODS: Between 1995 and 2002, 498 patients with previous cardiac operations via sternotomy underwent isolated valve surgery: 337 via median sternotomy (aortic = 160; mitral = 177) and 161 via mini-thoracotomy (aortic = 61; mitral = 100). Data were collected prospectively using the New York State Cardiac Surgery Report Form. RESULTS: Preoperative incidences of congestive heart failure, renal disease, and nonelective procedures were higher in the sternotomy group. Hospital mortality was significantly lower with the minimally invasive approach, 5.6% (9/161) versus 11.3% (38/337) (univariate, p = 0.04). However, multivariate analysis (odds ratio: 95% confidence intervals, p value) revealed that chronic obstructive pulmonary disease (6.6: 1.4 to 3.1, p = 0.001), renal disease (4.1: 1.52 to 11.2, p = 0.01), cerebrovascular disease (2.2: 1.03 to 4.78, p = 0.04), and ejection faction <30% (1.5: 0.96 to 5.5, p = 0.06) were associated with increased mortality. While mean bypass time, cross-clamp times, and stroke rates were comparable between groups, patients undergoing minimally invasive valve surgery had no deep wound infections (0% vs 2.4%, p = 0.05), less need for blood products (p = 0.02), and shorter hospital stays (p = 0.009). Five-year survival was higher with minimally invasive techniques as compared to a sternotomy approach (92.4 +/- 2% and 86.0 +/- 2%, respectively, p = 0.08). CONCLUSIONS: Reoperative valve surgery can be safely performed using a nonsternotomy, minimally invasive approach, with at least equal mortality, less hospital morbidity, decreased hospital length of stay, and slightly favorable mid-term survival as compared to sternotomy.

Matrix metalloproteinase expression in vein grafts: role of inflammatory mediators and extracellular signal-regulated kinases-1 and -2.

Matrix metalloproteinases (MMPs) play key roles in vascular remodeling. We characterized the role of inflammatory mediators and extracellular signal-regulated kinases (ERKs) in the control of arterialized vein graft expression of MMP-9, MMP-2, and membrane-type 1-MMP (MT1-MMP) and of the tissue inhibitor of metalloproteinases-2 (TIMP-2). For this purpose we used a canine model of jugular vein to carotid artery interposition graft and analyzed the vein grafts at various postoperative times (30 min to 28 days) using the contralateral vein as a control. To study the role of ERK-1/2, veins were incubated with the mitogen-activated protein kinase kinase (MEK-1/2) inhibitor UO126 for 30 min before being grafted. Vein graft extracts were analyzed for MMPs, TIMP-2, tumor necrosis factor-alpha (TNF-alpha), polymorphonuclear neutrophil (PMN) infiltration, myeloperoxidase (MPO), and thrombin activity, and for ERK-1/2 activation. Vein graft arterialization resulted in rapid and sustained (8 h to 28 days) upregulation of vein graft-associated MMP-9, MMP-2, MT1-MMP, thrombin activity, and TNF-alpha levels with concomitant TIMP-2 downregulation. MMP-2 activation preceded MT1-MMP upregulation. PMN infiltration and vein graft-associated MPO activity increased within hours after arterialization, indicating a prompt, local inflammatory response. In cultured smooth muscle cells, both thrombin and TNF-alpha upregulated MT1-MMP expression; however, only thrombin activated MMP-2. Inhibition of ERK-1/2 activation blocked arterialization-induced upregulation of MMP-2, MMP-9, and MT1-MMP. Thus, thrombin, inflammatory mediators, and activation of the ERK-1/2 pathway control MMP and TIMP-2 expression in arterialized vein grafts.

Anti-proliferative and anti-inflammatory effects of topical MAPK inhibition in arterialized vein grafts.

Vein graft failure following bypass surgery is a frequent and important clinical problem. The vascular injury caused by arterialization is responsible for vein graft intimal hyperplasia, a lesion generated by medial smooth muscle cell proliferation and migration into the intima, increased extracellular matrix deposition, and formation of a thick neointima. Development of the neointima into a typical atherosclerotic lesion and consequent stenosis ultimately result in vein graft failure. Endothelial damage, inflammation, and intracellular signaling through mitogen-activated protein kinases (MAPKs) have been implicated in the early stages of this process. We therefore investigated the effects of topical inhibition of ERK-1/2 MAPK activation on vascular cell proliferation and apoptosis, and on the inflammatory response in a canine model of vein graft arterialization. For this purpose, vein grafts were incubated with the MEK-1/2 inhibitor, UO126, ex vivo for 30 min before grafting. This treatment effectively abolished arterialization-induced ERK-1/2 activation, decreased medial cell proliferation, and increased apoptosis. UO126 treatment also inhibited the vein graft infiltration by myeloperoxidase-positive inflammatory cells that follows vein graft arterialization. Thus, topical ex vivo administration of MAPK inhibitors can provide a pharmacological tool to prevent or reduce the vascular cell responses that lead to vein graft intimal hyperplasia and graft failure.