Intraoperative Oxidative Damage and Delirium after Cardiac Surgery.

BACKGROUND: Mechanisms of postoperative delirium remain poorly understood, limiting development of effective treatments. We tested the hypothesis that intraoperative oxidative damage is associated with delirium and neuronal injury and that disruption of the blood-brain barrier modifies these associations. METHODS: In a prespecified cohort study of 400 cardiac surgery patients enrolled in a clinical trial of atorvastatin to reduce kidney injury and delirium, we measured plasma concentrations of F2-isoprostanes and isofurans using gas chromatography-mass spectrometry to quantify oxidative damage, ubiquitin carboxyl-terminal hydrolase isozyme L1 to quantify neuronal injury, and S100 calcium-binding protein B using enzyme-linked immunosorbent assays to quantify blood-brain barrier disruption before, during, and after surgery. We performed the Confusion Assessment Method for the Intensive Care Unit twice daily to diagnose delirium. We measured the independent associations between intraoperative F2-isoprostanes and isofurans and delirium (primary outcome) and postoperative ubiquitin carboxyl-terminal hydrolase isozyme L1 (secondary outcome), and we assessed if S100 calcium-binding protein B modified these associations. RESULTS: Delirium occurred in 109 of 400 (27.3%) patients for a median (10th, 90th percentile) of 1.0 (0.5, 3.0) days. In the total cohort, plasma ubiquitin carboxyl-terminal hydrolase isozyme L1 concentration was 6.3 ng/ml (2.7, 14.9) at baseline and 12.4 ng/ml (7.9, 31.2) on postoperative day 1. F2-isoprostanes and isofurans increased throughout surgery, and the log-transformed sum of intraoperative F2-isoprostanes and isofurans was independently associated with increased odds of postoperative delirium (odds ratio, 3.70 [95% CI, 1.41 to 9.70]; P = 0.008) and with increased postoperative ubiquitin carboxyl-terminal hydrolase isozyme L1 (ratio of geometric means, 1.42 [1.11 to 1.81]; P = 0.005). The association between increased intraoperative F2-isoprostanes and isofurans and increased postoperative ubiquitin carboxyl-terminal hydrolase isozyme L1 was amplified in patients with elevated S100 calcium-binding protein B (P = 0.049). CONCLUSIONS: Intraoperative oxidative damage was associated with increased postoperative delirium and neuronal injury, and the association between oxidative damage and neuronal injury was stronger among patients with increased blood-brain barrier disruption.

Predictors of Stroke After Minimally Invasive Mitral Valve Surgery Without the Cross-Clamp.

Minimally invasive mitral valve surgery (mini-MVS) with hypothermic fibrillatory arrest has been associated with an increased risk of stroke. We aim to investigate the incidence, predictors, and outcomes of stroke in a large cohort of patient who underwent clampless mini-MVS. Between January 2008 and June 2017, we performed 1247 mini-MVSs. The clinical, operative, and postoperative outcomes were analyzed. Univariable and multivariable regression analyses were used to identify predictors of postoperative stroke. The median follow-up was 5.2 years (interquartile range 2.6-7.5). The etiology of mitral valve (MV) disease was degenerative (60.4%, n = 753), functional (12.8%, n = 160), rheumatic (8.7%, n = 109), endocarditis (3.1%, n = 39), and reoperative MV surgery (14.9%, n = 186). The overall incidence of postoperative neurologic event was 2.5% (n = 31/1247). Univariable predictors of stroke were a higher Society of Thoracic Surgeons mortality risk (6.0 ± 11.8% vs 3.3 ± 5.2%, P < 0.001), advanced age, (69.6 ± 12.1 years vs 63.0 ± 13.6 years, P = 0.002), female gender (71.0% vs 46.3%, P = 0.007), and a history of a cerebrovascular accident (22.6% vs 8.7%, P = 0.008). Stroke patients had a higher 30-day mortality (22.6% vs 1.6%, P < 0.001) and a higher risk for long-term mortality (hazard ratio = 5.56, 95% confidence interval [CI] 3.2-9.6, P < 0.001). Advanced age (odds ratio [OR] 2.1; 95% CI 1.1-4.0; P = 0.02), female gender (OR 2.3; 95% CI 0.9-5.2; P = 0.05), and history of cerebrovascular accident (OR 3.1; 95% CI 0.98-10.1; P = 0.05) remained as independent predictors of stroke in the multivariable analysis. Our decade-long experience indicates that clampless mini-MVS is associated with a low incidence of postoperative stroke, and that the predictors of stroke are not specific to this approach.

Altered ADAMTS5 Expression and Versican Proteolysis: A Possible Molecular Mechanism in Barlow's Disease.

BACKGROUND: We hypothesized that gene expression profiles of mitral valve (MV) leaflets from patients with Barlow's disease (BD) are distinct from those with fibroelastic deficiency (FED). METHODS: MVs were obtained from patients with BD (7 men, 3 women; 61.4 ± 12.7 years old) or FED (6 men, 5 women; 54.5 ± 6.0 years old) undergoing operations for severe mitral regurgitation (MR). Normal MVs were obtained from 6 donor hearts unmatched for transplant (3 men, 3 women; 58.3 ± 7.5 years old), and gene expression was assessed using cDNA microarrays. Select transcripts were validated by quantitative reverse-transcription polymerase chain reaction, followed by an assessment of protein levels by immunostaining. RESULTS: The global gene expression profile for BD was clearly distinct from normal and FED groups. A total of 4,684 genes were significantly differential (fold-difference >1.5, p < 0.05) among the three groups, 1,363 of which were commonly altered in BD and FED compared with healthy individuals (eg TGFß2 [transforming growth factor ß2] and TGFß3 were equally upregulated in BD and FED). Most interesting were 329 BD-specific genes, including ADAMTS5 (a disintegrin-like and metalloprotease domain with thrombospondin-type 5), which was uniquely downregulated in BD based on microarrays and quantitative reverse-transcription polymerase chain reaction. Consistent with this finding, the ADAMTS5 substrate versican was increased in BD and conversely lower in FED. CONCLUSIONS: MV leaflets in BD and FED exhibit distinct gene expression patterns, suggesting different pathophysiologic mechanisms are involved in leaflet remodeling. Moreover, downregulation of ADAMTS5 in BD, along with the accumulation of its substrate versican in the valvular extracellular matrix, might contribute to leaflet thickening and enlargement.

Midterm, multicenter clinical and hemodynamic results for the Trifecta aortic pericardial valve.

OBJECTIVE: To evaluate the midterm hemodynamic performance and clinical outcomes of the Trifecta aortic pericardial valve. METHODS: In a multicenter, prospective, nonrandomized, follow-up study, 710 patients underwent surgical implantation of a pericardial stented aortic prosthesis (Trifecta valve; St Jude Medical, St. Paul, Minn). The valve is constructed from bovine pericardium mounted externally onto a titanium stent. Subjects were followed on an annual basis over 6 years. RESULTS: Operations were performed from 2007 to 2009, and mean age was 72.4 ± 9.3 years; 471 of 710 (66.3%) were men. Preoperatively, 361 of 710 (50.8%) of patients were in New York Heart Association class III or IV, and at 6 years postoperatively, 92 of 96 (95.8%) were New York Heart Association class I or II. Six years postoperatively, average mean gradient across all valve sizes was 11.0 mm Hg, and the average effective orifice area index was 0.80 cm2/m2. The proportion of patients without moderate-to-severe valvular regurgitation at 6 years was 95.2% (80/84). Six years postoperatively, freedom from valve-related mortality, nonstructural dysfunction, and paravalvular leak were 98.3%, 98.6%, and 98.9%, respectively, and freedom from reoperation due to structural valve deterioration was 97.3% (95% confidence limits, 98.6-94.7). CONCLUSION: These midterm results demonstrate that the Trifecta valve is a safe and effective valve substitute with excellent hemodynamic performance and durability that is maintained through the 6-year follow-up period.

Severity of pulmonary hypertension and obesity are not associated with worse functional outcomes after pulmonary thromboendarterectomy.

Predictors of functional outcomes in patients with chronic thromboembolic pulmonary hypertension (CTEPH) undergoing pulmonary thromboendarterectomy (PTE) are important to identify preoperatively. We hypothesized that baseline severity of pulmonary hypertension and obesity would not be associated with 6-month functional outcomes after PTE. Clinical and hemodynamic data were collected on consecutive patients undergoing PTE from 2008 to 2014. Patients were stratified according to baseline pulmonary vascular resistance (PVR) and body mass index (BMI). Six-minute walk distance (6MWD), New York Heart Association functional class (FC), and echocardiography were assessed in each group at baseline and 6 months after PTE. Regression analyses were performed to evaluate for associations between functional outcomes and baseline PVR and BMI. Forty-two patients underwent PTE and had 6-month follow up data. In comparisons of patients with high and low baseline PVR, the baseline characteristics, distribution of disease, 6MWD, and FC were similar. Postoperative hemodynamics for both groups were similar. At 6 months, both groups achieved improvements in FC, and there were no between-group differences in the change in 6MWD or FC. In comparisons of obese and nonobese patients, perioperative and FC improvement were similar; however, obese patients achieved a greater improvement in 6MWD than nonobese patients (P = 0.04). In conclusion, our data suggest that baseline severity of CTEPH and obesity were not associated with worse functional outcome. Further studies are needed to confirm these results, as these findings could have implications for patient selection for PTE.

High-Dose Perioperative Atorvastatin and Acute Kidney Injury Following Cardiac Surgery: A Randomized Clinical Trial.

IMPORTANCE: Statins affect several mechanisms underlying acute kidney injury (AKI). OBJECTIVE: To test the hypothesis that short-term high-dose perioperative atorvastatin would reduce AKI following cardiac surgery. DESIGN, SETTING, AND PARTICIPANTS: Double-blinded, placebo-controlled, randomized clinical trial of adult cardiac surgery patients conducted from November 2009 to October 2014 at Vanderbilt University Medical Center. INTERVENTIONS: Patients naive to statin treatment (n = 199) were randomly assigned 80 mg of atorvastatin the day before surgery, 40 mg of atorvastatin the morning of surgery, and 40 mg of atorvastatin daily following surgery (n = 102) or matching placebo (n = 97). Patients already taking a statin prior to study enrollment (n = 416) continued taking the preenrollment statin until the day of surgery, were randomly assigned 80 mg of atorvastatin the morning of surgery and 40 mg of atorvastatin the morning after (n = 206) or matching placebo (n = 210), and resumed taking the previously prescribed statin on postoperative day 2. MAIN OUTCOMES AND MEASURES: Acute kidney injury defined as an increase of 0.3 mg/dL in serum creatinine concentration within 48 hours of surgery (Acute Kidney Injury Network criteria). RESULTS: The data and safety monitoring board recommended stopping the group naive to statin treatment due to increased AKI among these participants with chronic kidney disease (estimated glomerular filtration rate <60 mL/min/1.73 m2) receiving atorvastatin. The board later recommended stopping for futility after 615 participants (median age, 67 years; 188 [30.6%] were women; 202 [32.8%] had diabetes) completed the study. Among all participants (n = 615), AKI occurred in 64 of 308 (20.8%) in the atorvastatin group vs 60 of 307 (19.5%) in the placebo group (relative risk [RR], 1.06 [95% CI, 0.78 to 1.46]; P = .75). Among patients naive to statin treatment (n = 199), AKI occurred in 22 of 102 (21.6%) in the atorvastatin group vs 13 of 97 (13.4%) in the placebo group (RR, 1.61 [0.86 to 3.01]; P = .15) and serum creatinine concentration increased by a median of 0.11 mg/dL (10th-90th percentile, -0.11 to 0.56 mg/dL) in the atorvastatin group vs by a median of 0.05 mg/dL (10th-90th percentile, -0.12 to 0.33 mg/dL) in the placebo group (mean difference, 0.08 mg/dL [95% CI, 0.01 to 0.15 mg/dL]; P = .007). Among patients already taking a statin (n = 416), AKI occurred in 42 of 206 (20.4%) in the atorvastatin group vs 47 of 210 (22.4%) in the placebo group (RR, 0.91 [0.63 to 1.32]; P = .63). CONCLUSIONS AND RELEVANCE: Among patients undergoing cardiac surgery, high-dose perioperative atorvastatin treatment compared with placebo did not reduce the risk of AKI overall, among patients naive to treatment with statins, or in patients already taking a statin. These results do not support the initiation of statin therapy to prevent AKI following cardiac surgery. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00791648.

Perioperative intravenous acetaminophen attenuates lipid peroxidation in adults undergoing cardiopulmonary bypass: a randomized clinical trial.

BACKGROUND: Cardiopulmonary bypass (CPB) lyses erythrocytes and induces lipid peroxidation, indicated by increasing plasma concentrations of free hemoglobin, F2-isoprostanes, and isofurans. Acetaminophen attenuates hemeprotein-mediated lipid peroxidation, reduces plasma and urine concentrations of F2-isoprostanes, and preserves kidney function in an animal model of rhabdomyolysis. Acetaminophen also attenuates plasma concentrations of isofurans in children undergoing CPB. The effect of acetaminophen on lipid peroxidation in adults has not been studied. This was a pilot study designed to test the hypothesis that acetaminophen attenuates lipid peroxidation in adults undergoing CPB and to generate data for a clinical trial aimed to reduce acute kidney injury following cardiac surgery. METHODS AND RESULTS: In a prospective double-blind placebo-controlled clinical trial, sixty adult patients were randomized to receive intravenous acetaminophen or placebo starting prior to initiation of CPB and for every 6 hours for 4 doses. Acetaminophen concentrations measured 30 min into CPB and post-CPB were 11.9 ± 0.6 µg/mL (78.9 ± 3.9 µM) and 8.7 ± 0.3 µg/mL (57.6 ± 2.0 µM), respectively. Plasma free hemoglobin increased more than 15-fold during CPB, and haptoglobin decreased 73%, indicating hemolysis. Plasma and urinary markers of lipid peroxidation also increased during CPB but returned to baseline by the first postoperative day. Acetaminophen reduced plasma isofuran concentrations over the duration of the study (P = 0.05), and the intraoperative plasma isofuran concentrations that corresponded to peak hemolysis were attenuated in those subjects randomized to acetaminophen (P = 0.03). Perioperative acetaminophen did not affect plasma concentrations of F2-isoprostanes or urinary markers of lipid peroxidation. CONCLUSIONS: Intravenous acetaminophen attenuates the increase in intraoperative plasma isofuran concentrations that occurs during CPB, while urinary markers were unaffected. TRIAL REGISTRATION: ClinicalTrials.gov NCT01366976.

The effect of postoperative medical treatment on left ventricular mass regression after aortic valve replacement.

OBJECTIVE: The study objective was to analyze factors associated with left ventricular mass regression in patients undergoing aortic valve replacement with a newer bioprosthesis, the Trifecta valve pericardial bioprosthesis (St Jude Medical Inc, St Paul, Minn). METHODS: A total of 444 patients underwent aortic valve replacement with the Trifecta bioprosthesis from 2007 to 2009 at 6 US institutions. The clinical and echocardiographic data of 200 of these patients who had left ventricular hypertrophy and follow-up studies 1 year postoperatively were reviewed and compared to analyze factors affecting left ventricular mass regression. RESULTS: Mean (standard deviation) age of the 200 study patients was 73 (9) years, 66% were men, and 92% had pure or predominant aortic valve stenosis. Complete left ventricular mass regression was observed in 102 patients (51%) by 1 year postoperatively. In univariate analysis, male sex, implantation of larger valves, larger left ventricular end-diastolic volume, and beta-blocker or calcium-channel blocker treatment at dismissal were significantly associated with complete mass regression. In the multivariate model, odds ratios (95% confidence intervals) indicated that male sex (3.38 [1.39-8.26]) and beta-blocker or calcium-channel blocker treatment at dismissal (3.41 [1.40-8.34]) were associated with increased probability of complete left ventricular mass regression. Patients with higher preoperative systolic blood pressure were less likely to have complete left ventricular mass regression (0.98 [0.97-0.99]). CONCLUSIONS: Among patients with left ventricular hypertrophy, postoperative treatment with beta-blockers or calcium-channel blockers may enhance mass regression. This highlights the need for close medical follow-up after operation. Labeled valve size was not predictive of left ventricular mass regression.

Hypertension is associated with preamyloid oligomers in human atrium: a missing link in atrial pathophysiology?

BACKGROUND: Increasing evidence indicates that proteotoxicity plays a pathophysiologic role in experimental and human cardiomyopathy. In organ-specific amyloidoses, soluble protein oligomers are the primary cytotoxic species in the process of protein aggregation. While isolated atrial amyloidosis can develop with aging, the presence of preamyloid oligomers (PAOs) in atrial tissue has not been previously investigated. METHODS AND RESULTS: Atrial samples were collected during elective cardiac surgery in patients without a history of atrial arrhythmias, congestive heart failure, cardiomyopathy, or amyloidosis. Immunohistochemistry was performed for PAOs using a conformation-specific antibody, as well as for candidate proteins identified previously in isolated atrial amyloidosis. Using a myocardium-specific marker, the fraction of myocardium colocalizing with PAOs (PAO burden) was quantified (green/red ratio). Atrial samples were obtained from 92 patients, with a mean age of 61.7±13.8 years. Most patients (62%) were male, 23% had diabetes, 72% had hypertension, and 42% had coronary artery disease. A majority (n=62) underwent aortic valve replacement, with fewer undergoing coronary artery bypass grafting (n=34) or mitral valve replacement/repair (n=24). Immunostaining detected intracellular PAOs in a majority of atrial samples, with a heterogeneous distribution throughout the myocardium. Mean green/red ratio value for the samples was 0.11±0.1 (range 0.03 to 0.77), with a value ≥0.05 in 74 patients. Atrial natriuretic peptide colocalized with PAOs in myocardium, whereas transthyretin was located in the interstitium. Adjusting for multiple covariates, PAO burden was independently associated with the presence of hypertension. CONCLUSION: PAOs are frequently detected in human atrium, where their presence is associated with clinical hypertension.

Quantitative Imaging of Preamyloid Oligomers, a Novel Structural Abnormality, in Human Atrial Samples.

Abnormalities in atrial myocardium increase the likelihood of arrhythmias, including atrial fibrillation (AF). The deposition of misfolded protein, or amyloidosis, plays an important role in the pathophysiology of many diseases, including human cardiomyopathies. We have shown that genes implicated in amyloidosis are activated in a cellular model of AF, with the development of preamyloid oligomers (PAOs). PAOs are intermediates in the formation of amyloid fibrils, and they are now recognized to be the cytotoxic species during amyloidosis. To investigate the presence of PAOs in human atrium, we developed a microscopic imaging-based protocol to enable robust and reproducible quantitative analysis of PAO burden in atrial samples harvested at the time of elective cardiac surgery. Using PAO- and myocardial-specific antibodies, we found that PAO distribution was typically heterogeneous within a myocardial sample. Rigorous imaging and analysis protocols were developed to quantify the relative area of myocardium containing PAOs, termed the Green/Red ratio (G/R), for a given sample. Using these methods, reproducible G/R values were obtained when different sections of a sample were independently processed, imaged, and analyzed by different investigators. This robust technique will enable studies to investigate the role of this novel structural abnormality in the pathophysiology of and arrhythmia generation in human atrial tissue.

Heme Oxygenase-1 and Acute Kidney Injury following Cardiac Surgery.

BACKGROUND: Intraoperative hemolysis and inflammation are associated with acute kidney injury (AKI) following cardiac surgery. Plasma-free hemoglobin induces heme oxygenase-1 (HO-1) expression. HO-1 degrades heme but increases in experimental models of AKI. This study tested the hypothesis that plasma HO-1 concentrations are associated with intraoperative hemolysis and are increased in patients that develop AKI following cardiac surgery. METHODS: We measured plasma HO-1, free hemoglobin, and inflammatory markers in 74 patients undergoing cardiopulmonary bypass (CPB). AKI was defined as an increase in serum creatinine concentration of 50% or 0.3 mg/dl within 72 h of surgery. RESULTS: Twenty-eight percent of patients developed AKI. HO-1 concentrations increased from 4.2 ± 0.2 ng/ml at baseline to 6.6 ± 0.5 ng/ml on postoperative day (POD) 1 (p < 0.001). POD1 HO-1 concentrations were 3.1 ng/ml higher (95% CI 1.1-5.1) in AKI patients, as was the change in HO-1 from baseline to POD1 (4.4 ± 1.3 ng/ml in AKI patients vs. 1.5 ± 0.3 ng/ml in no-AKI patients, p = 0.006). HO-1 concentrations remained elevated in AKI patients even after controlling for AKI risk factors and preoperative drug therapy. Peak-free hemoglobin concentrations correlated with peak HO-1 concentrations on POD1 in patients that developed AKI (p = 0.02). Duration of CPB and post-CPB IL-6 and IL-10 concentrations were also associated with increased HO-1 on POD1. CONCLUSION: Plasma HO-1 is increased in patients that develop AKI, and CPB duration, hemolysis, and inflammation are associated with increased HO-1 concentrations following cardiac surgery. Strategies that alter hemolysis and HO-1 expression during cardiac surgery may affect risk for AKI.

Suture technique does not affect hemodynamic performance of the small supra-annular Trifecta bioprosthesis.

OBJECTIVE: The study objective was to evaluate whether aortic valve replacement with the Trifecta valve (St Jude Medical Inc, St Paul, Minn) using simple sutures produces better hemodynamic performance than valve replacement with noneverting pledget-reinforced sutures. METHODS: We analyzed prospectively acquired 1-year hemodynamic data of patients with small aortic annulus sizes who were enrolled in a multicenter trial of the Trifecta aortic valve bioprosthesis and underwent aortic valve replacement with a 19-mm or 21-mm bioprosthesis between August 2007 and November 2009. We compared preoperative clinical information and 1-year postoperative hemodynamic data for noneverting pledget-reinforced sutures (group 1) versus everting mattress sutures or simple sutures (group 2). RESULTS: A total of 346 patients underwent aortic valve replacement: 269 in group 1 and 77 in group 2. Preoperative demographic characteristics for the 2 groups were similar. For groups 1 and 2, the mean gradient was 10.4±4.7 mm Hg and 11.1±4.4 mm Hg for 19-mm valves, respectively, and 8.4±3.5 mm Hg and 8.8±3.6 mm Hg for 21-mm valves, respectively; the effective orifice area was 1.40 cm2 and 1.25 cm2 for 19-mm valves, respectively, and 1.57 cm2 and 1.50 cm2 for 21-mm valves, respectively. The rate of severe prosthesis-patient mismatch (indexed effective orifice area≤0.65 cm2/m2) was 18.6% (n=11) and 25% (n=6) for 19-mm valves, respectively, and 10.9% (n=20) and 16.3% (n=8) for 21-mm valves, respectively. CONCLUSIONS: The suture method did not affect hemodynamic performance of supra-annular bioprostheses in patients with small aortic annulus sizes. Choice of suture technique should be determined by surgeon experience and local anatomic features.

Minimally invasive fibrillating mitral valve replacement for patients with advanced cardiomyopathy: a safe and effective approach to treat a complex problem.

OBJECTIVE: The optimal management of mitral regurgitation (MR) in patients with cardiomyopathy has been controversial. Minimally invasive fibrillating mitral valve replacement (mini-MVR) might limit postoperative morbidity and mortality by minimizing recurrent MR. We hypothesized that mini-MVR with complete chordal sparing would offer low mortality and halt left ventricular (LV) remodeling in patients with severe cardiomyopathy and severe MR. METHODS: From January 2006 to August 2009, 65 patients with an LV ejection fraction (LVEF) of ≤35% underwent mini-MVR. The demographic, echocardiographic, and clinical outcomes were analyzed. RESULTS: The operative mortality compared with the Society of Thoracic Surgeons-predicted mortality was 6.2% versus 6.6%. It was 5.6% versus 7.4% for patients with an LVEF of ≤20% and 8.3% versus 17.9% among patients with a Society of Thoracic Surgeons-predicted mortality of ≥10%. At a median follow-up of 17 months, no recurrent MR or change in the LV dimensions or LVEF had developed, but the right ventricular systolic pressure had decreased (P=.02). At the first postoperative visit and latest follow-up visit, the New York Heart Association class had decreased from 3.0±0.6 to 1.7±0.7 and 2.0±1.0, respectively (P<.0001 for both). Patients with an LVEF of ≤20% and LV end-diastolic diameter of ≥6.5 cm were more likely to meet a composite of death, transplantation, or LV assist device insertion (P=.046). CONCLUSIONS: Our results have shown that mini-MVR is safe in patients with advanced cardiomyopathy and resulted in no recurrent MR, stabilization of the LVEF and LV dimensions, and a decrease in right ventricular systolic pressure. This mini-MVR technique can be used to address severe MR in patients with advanced cardiomyopathy.

The St Jude Medical Trifecta aortic pericardial valve: results from a global, multicenter, prospective clinical study.

BACKGROUND: The St Jude Medical Inc (St Paul, Minn) Trifecta valve is a novel aortic biological prosthesis that incorporates several design features, including a true supra-annular sewing cuff, a stent design that maximizes valve hemodynamics while minimizing leaflet stresses, and an ethanol-based anticalcification technology. This study establishes the safety and early clinical and hemodynamic performance of the Trifecta valve. METHODS: The Trifecta bioprosthesis was implanted in 1014 eligible patients between 2007 and 2009 at 31 centers. The mean age of the population was 72.5 ± 9.0 years, of whom 650 (64.1%) were male and 364 (35.9%) were female. Eighty-two subjects (8.1%) had undergone previous open surgery. Indications for aortic valve replacement surgery included stenosis in 556 patients (54.8%), regurgitation in 61 patients (6.0%), and mixed pathology in 397 patients (39.2%). RESULTS: The overall follow-up included 844.3 late patient-years. Early (≤ 30 day) mortality occurred in 18 patients (1.8%), and there were 23 late (≥ 31 days) deaths yielding a linearized mortality rate of 2.72% per late patient-year. There were 27 early thromboembolic events, including 8 (0.8%) strokes, 17 (1.7%) reversible neurologic events, and 2 (0.2%) systemic embolic events. There were no instances of early valve thrombosis, endocarditis, or clinically significant hemolysis. There were 16 late thromboembolic events (linearized rate of 1.90% per year of follow-up), including 4 strokes and 12 reversible neurologic events. In total, there were 5 late valve explants, including 1 structural deterioration and 4 prosthetic valve endocarditis cases. Overall, freedom from valve explant was 99.4% at 2 years. At the time of discharge, average mean gradients ranged from 9.3 to 4.1 mm Hg and effective orifice area ranged from 1.58 to 2.50 cm(2) for valve sizes 19 to 29 mm, respectively. CONCLUSIONS: The St Jude Medical Trifecta valve is a unique pericardial bioprosthesis with design elements that provide excellent hemodynamic performance while providing ease of implantation. Long-term follow-up continues to confirm the promising results of this innovative bioprosthesis.

Angiotensin-converting enzyme inhibition or mineralocorticoid receptor blockade do not affect prevalence of atrial fibrillation in patients undergoing cardiac surgery.

OBJECTIVE: This study tested the hypothesis that interruption of the renin-angiotensin system with either an angiotensin-converting enzyme inhibitor or a mineralocorticoid receptor antagonist will decrease the prevalence of atrial fibrillation after cardiac surgery. DESIGN: Randomized double-blind placebo-controlled study. SETTING: University-affiliated hospitals. PATIENTS: Four hundred forty-five adult patients in normal sinus rhythm undergoing elective cardiac surgery. INTERVENTIONS: One week to 4 days prior to surgery, patients were randomized to treatment with placebo, ramipril (2.5 mg the first 3 days followed by 5 mg/day, with the dose reduced to 2.5 mg/day on the first postoperative day only), or spironolactone (25 mg/day). MEASUREMENTS: The primary endpoint was the occurrence of electrocardiographically confirmed postoperative atrial fibrillation. Secondary endpoints included acute renal failure, hyperkalemia, the prevalence of hypotension, length of hospital stay, stroke, and death. MAIN RESULTS: The prevalence of atrial fibrillation was 27.2% in the placebo group, 27.8% in the ramipril group, and 25.9% in the spironolactone group (p=.95). Patients in the ramipril (0.7%) or spironolactone (0.7%) group were less likely to develop acute renal failure than those randomized to placebo (5.4%, p=.006). Patients in the placebo group tended to be hospitalized longer than those in the ramipril or spironolactone group (6.8±8.2 days vs. 5.7±3.2 days and 5.8±3.4 days, respectively, p=.08 for the comparison of placebo vs. the active treatment groups using log-rank test). Compared with patients in the placebo group, patients in the spironolactone group were extubated sooner after surgery (576.4±761.5 mins vs. 1091.3±3067.3 mins, p=.04). CONCLUSIONS: Neither angiotensin-converting enzyme inhibition nor mineralocorticoid receptor blockade decreased the primary outcome of postoperative atrial fibrillation. Treatment with an angiotensin-converting enzyme inhibitor or mineralocorticoid receptor antagonist was associated with decreased acute renal failure. Spironolactone use was also associated with a shorter duration of mechanical ventilation after surgery.

Minimally invasive mitral valve surgery expands the surgical options for high-risks patients.

BACKGROUND: A simplified minimally invasive mitral valve surgery (MIMVS) approach avoiding cross-clamping and cardioplegic myocardial arrest using a small (5 cm) right antero-lateral incision was developed. We hypothesized that, in high-risk patients and in patients with prior sternotomy, this approach would yield superior results compared to those predicted by the Society of Thoracic Surgeons (STS) algorithm for standard median sternotomy mitral valve surgery. METHODS: Five hundred and four consecutive patients (249 males/255 females), median age 65 years (range 20-92 years) underwent MIMVS between 1/06 and 8/09. Median preoperative New York Heart Association function class was 3 (range 1-4). Eighty-two (16%) patients had an ejection fraction ≤35%. Forty-seven (9%) had a STS predicted mortality ≥10%. Under cold fibrillatory arrest (median temperature 28°C) without aortic cross-clamp, mitral valve repair (224/504, 44%) or replacement (280/504, 56%) was performed. RESULTS: Thirty-day mortality for the entire cohort was 2.2% (11/504). In patients with a STS predicted mortality ≥ 10% (range 10%-67%), the observed 30-day mortality was 4% (2/47), lower than the mean STS predicted mortality of 20%. Morbidity in this high-risk group was equally low: 1 of 47 (2%) patients underwent reexploration for bleeding, 1 of 47 (2%) patients suffered a permanent neurologic deficit, none had wound infection. The median length of stay was 8 days (range 1-68 days). CONCLUSIONS: This study demonstrates that MIMVS without aortic cross-clamp is reproducible with low mortality and morbidity rates. This approach expands the surgical options for high-risk patients and yields to superior results than the conventional median sternotomy approach.

Successful treatment of atrioesophageal fistula by cervical esophageal ligation and decompression.

Atrioesophageal fistula is a rare yet devastating complication of transcatheter ablation for atrial fibrillation. This condition requires urgent intervention, but the optimal treatment strategy is yet to be defined. Reported therapies range from endoscopic stenting to direct atrial repair or reconstruction while on cardiopulmonary bypass. Here, we describe the successful management of an atrioesophageal fistula by cervical esophageal ligation and decompression, along with gastric drainage.

Results of completion arteriography after minimally invasive off-pump coronary artery bypass.

BACKGROUND: The benefits of a minimally invasive approach to off-pump coronary artery bypass remain controversial. The value of completion arteriography in validating this technique has not been investigated. METHODS: From April 2007 to October 2009, fifty-six patients underwent isolated minimally invasive coronary artery bypass grafting through a left thoracotomy without cardiopulmonary bypass. Forty-three of these patients underwent completion arteriography. RESULTS: Sixty-five grafts were performed in these 56 patients, (average, 1.2 grafts per patient; range, 1 to 3). Forty-eight grafts were studied in the 43 patients undergoing completion arteriography. There were 4 findings on arteriogram leading to further immediate intervention (8.3%). These included 3 grafts with anastomotic stenoses or spasm requiring stent placement, and 1 patient who had limited dissection in the left internal mammary artery graft and underwent placement of an additional vein graft. These findings were independent of electrocardiographic changes or hemodynamic instability. The remainder of the studies showed no significant abnormalities. There were no deaths. One patient who did not have a completion arteriogram suffered a postoperative myocardial infarction requiring stent placement for anastomotic stenosis. Patients were discharged home an average of 6.8 days postoperatively. There were no instances of renal dysfunction postoperatively attributable to catheterization. CONCLUSIONS: Minimally invasive coronary artery bypass is safe and effective. Findings of completion arteriography occasionally reveal previously under-recognized findings that, if corrected in a timely fashion, could potentially impact graft patency and clinical outcomes. Our experience validates this minimally invasive technique.