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.

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.

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.

Minimally invasive right lateral thoracotomy without aortic cross-clamping: an attractive alternative to repeat sternotomy for reoperative mitral valve surgery.

BACKGROUND AND AIM OF THE STUDY: The study aim was to determine the safety and benefits of minimally invasive mitral valve surgery without aortic cross-clamping for mitral valve surgery after previous cardiac surgery. METHODS: Between January 2006 and August 2008, a total of 90 consecutive patients (38 females, 52 males; mean age 66 +/- 9 years) underwent minimally invasive mitral valve surgery after having undergone previous cardiac surgery. Of these patients, 80 (89%) underwent mitral valve replacement and 10 (11%) mitral valve repair utilizing a small (5 cm) right lateral thoracotomy along the 4th or 5th intercostal space under fibrillatory arrest (mean temperature 28 +/- 2 degrees C). The predicted mortality, calculated using the Society of Thoracic Surgeons (STS) algorithm, was compared to the observed mortality. RESULTS: The mean ejection fraction was 45 +/- 13%, mean NYHA class 3 +/- 1, while 66 patients (73%) had previous coronary artery bypass grafting and 37 (41%) had previous valve surgery. Twenty-six patients (29%) underwent non-elective surgery. Cardiopulmonary bypass was instituted through axillary (n = 19), femoral (n = 70) or direct use aortic (n = 1) cannulation. Operative mortality was 2% (2/90), lower than the STS-predicted mortality of 7%. Three patients (3%) developed acute renal failure postoperatively, one patient (1%) required new-onset hemodialysis, and one (1%) developed postoperative stroke. No patients developed postoperative myocardial infarction. The mean postoperative packed red blood cell transfusion requirement at 48 h was 2 +/- 3 units. CONCLUSION: Minimally invasive right thoracotomy without aortic cross-clamping is an excellent alternative to conventional redo-sternotomy for reoperative mitral valve surgery. The present study confirmed that this technique is safe and effective in reducing operative mortality in high-risk patients undergoing reoperative cardiac surgery.

Extending the use of the pacing pulmonary artery catheter for safe minimally invasive cardiac surgery.

OBJECTIVE: In this study, the therapeutic use of pacing pulmonary artery catheters in association with minimally invasive cardiac surgery was evaluated. DESIGN: A retrospective study. SETTINGS: A single institutional university hospital. PARTICIPANTS: Two hundred twenty-four consecutive patients undergoing minimally invasive cardiac surgery through a small (5-cm) right anterolateral thoracotomy using fibrillatory arrest without aortic cross-clamping. MEASUREMENTS AND MAIN RESULTS: Two hundred eighteen patients underwent mitral valve surgery (97%) alone or in combination with other procedures. Six patients underwent other cardiac operations. In all patients, the pacing pulmonary artery catheter was used intraoperatively to induce ventricular fibrillation during the cooling period, and in the postoperative period it also was used in 37 (17%) patients who needed to be paced, mainly for bradyarrhythmias (51%). There were no complications related to the insertion of the catheters. Six (3%) patients experienced a loss of pacing capture, and 2 (1%) experienced another complication requiring the surgical removal of the catheter. Seven (3%) patients needed postoperative implantation of a permanent pacemaker. CONCLUSIONS: In combination with minimally invasive cardiac surgery, pacing pulmonary artery catheters were therapeutically useful to induce ventricular fibrillatory arrest intraoperatively and for obtaining pacing capability in the postoperative period. Their use was associated with a low number of complications.

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.

Milrinone use is associated with postoperative atrial fibrillation after cardiac surgery.

BACKGROUND: Postoperative atrial fibrillation (AF), a frequent complication after cardiac surgery, causes morbidity and prolongs hospitalization. Inotropic drugs are commonly used perioperatively to support ventricular function. This study tested the hypothesis that the use of inotropic drugs is associated with postoperative AF. METHODS AND RESULTS: We evaluated perioperative risk factors in 232 patients who underwent elective cardiac surgery. All patients were in sinus rhythm at surgery. Sixty-seven patients (28.9%) developed AF a mean of 2.9+/-2.1 days after surgery. Patients who developed AF stayed in the hospital longer (P<0.001) and were more likely to die (P=0.02). Milrinone use was associated with an increased risk of postoperative AF (58.2% versus 26.1% in nonusers; P<0.001). Older age (63.4+/-10.7 versus 56.7+/-12.3 years; P<0.001), hypertension (P=0.04), lower preoperative ejection fraction (P=0.03), mitral valve surgery (P=0.02), right ventricular dysfunction (P=0.03), and higher mean pulmonary artery pressure (27.1+/-9.3 versus 21.8+/-7.5 mm Hg; P=0.001) also were associated with postoperative AF. In multivariable logistic regression, age (P<0.001), ejection fraction (P=0.02), and milrinone use (odds ratio, 4.86; 95% confidence interval, 2.31 to 10.25; P<0.001) independently predicted postoperative AF. When only data from patients with pulmonary artery catheters were analyzed and pulmonary artery pressure was included in the model, age, milrinone use (odds ratio, 4.45; 95% confidence interval, 2.01 to 9.84; P<0.001), and higher pulmonary artery pressure (P=0.02) were associated with an increased risk of postoperative AF. Adding other potential confounders or stratifying analysis by mitral valve surgery did not change the association of milrinone use with postoperative AF. CONCLUSIONS: Milrinone use is an independent risk factor for postoperative AF after elective cardiac surgery.

Combined PCI and minimally invasive heart valve surgery for high-risk patients.

Combined coronary artery valvular heart disease is a major cause of morbidity and mortality in the adult patient population. The standard treatment for such disease has been open heart surgery in which coronary artery bypass grafting (CABG) is performed concurrently with valve surgery using a median sternotomy and cardiopulmonary bypass. With the increasing complexity of patients referred to surgery, some patients may prove to be poor surgical candidates for combined valve and CABG surgery. In certain selected patients who fall into this category, valve surgery and percutaneous coronary intervention (PCI) have been considered a feasible alternative. Conventionally, valve surgery is performed in the cardiac surgical operating room, whereas PCI is carried out in the cardiac catheterization laboratory. Separation of these two procedural suites has presented a logistic limitation because it impedes the concomitant performance of both procedures in one setting. Hence, PCI and valve surgery usually have been performed as a "two-stage" procedure in two different operative suites, with the procedures being separated by hours, days, or weeks. Technologic advancements have made possible the construction of a "hybrid" procedural suite that combines the facilities of a cardiac surgical operating room with those of a cardiac catheterization laboratory. This design has enabled the concept of "one-stage" or "one-stop" PCI and valve surgery, allowing both procedures to be performed in a hybrid suite in one setting, separated by minutes. The advantages of such a method could prove to be multifold by enabling a less invasive surgical approach and improving logistics, patient satisfaction, and outcomes in selected patients.

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.

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.

Transmyocardial revascularization: 5-year follow-up of a prospective, randomized multicenter trial.

BACKGROUND: In prospective randomized trials at 1 year, transmyocardial revascularization (TMR) provided superior relief of angina, decreased rehospitalizations, and improved exercise times. We evaluated 5-year mortality and angina class in "no-option" patients with diffuse coronary artery disease randomized to TMR or continued medical management. METHODS: Two hundred twelve patients with refractory class IV angina who were not candidates for conventional therapy were randomized to receive holmium:yttrium-aluminum-garnet TMR (n = 100) or continued medical management (n = 112) at nine centers. Follow-up included all-cause mortality along with angina class assessment by blinded evaluators. Mean follow-up was 5.7 +/- 0.8 years. RESULTS: Mean angina scores for TMR patients were 4.0 +/- 0.0 at baseline, 1.5 +/- 1.4 at 1 year, and 1.2 +/- 1.1 at a mean of 5 years (p < 0.001). After an average of 5 years, a significantly greater proportion of TMR than medical management patients experienced two or more class improvement in angina (88% versus 44%; p < 0.001). Kaplan-Meier intention-to-treat survival at 5 years was 65% versus 52% (TMR versus medical management; p = 0.05). Cumulative hazard curves demonstrated a significantly reduced risk of late death for TMR patients; average annual mortality beyond 1 year was 8% versus 13% (TMR versus medical management; p = 0.03). CONCLUSIONS: Five-year follow-up of prospectively randomized, no-option class IV angina patients demonstrated significantly increased Kaplan-Meier survival in patients randomized to TMR. The significant angina relief observed 12 months after sole therapy TMR was sustained long term and continued to be superior to that observed for patients maintained on continued medical management alone.

Coronary artery bypass in patients 80 years and over: is off-pump the operation of choice?

BACKGROUND: Octogenarians are at increased risk for perioperative morbidity and mortality after coronary artery bypass. In this study we compared our experience with patients undergoing on-pump coronary artery bypass (CAB) and those undergoing off-pump coronary artery bypass (OPCAB) to assess outcomes. METHODS: We used hospital database analysis in patients 80 years and older who underwent nonemergent coronary artery bypass with (N = 169) and without (N = 60) cardiopulmonary bypass from January 1999 through June 2001. RESULTS: Both groups were at increased perioperative risk based on the Society of Thoracic Surgeons risk model (7.7% OPCAB vs 5.8% CAB, p = 0.03). There were no operative deaths in the OPCAB group but there were eight (4.7%) in the CAB group (p = NS). Perioperative stroke (0% OPCAB vs 7.1% CAB, p = 0.04), prolonged ventilation (1.7% OPCAB vs 11.8% CAB, p = 0.02), and transfusion rate (33% OPCAB vs 70.4% CAB, p < 0.001) were all lower in the OPCAB group. A shorter hospital stay (6.3 days OPCAB vs 11.5 days CAB, p < 0.001) resulted in lower hospital cost in the OPCAB group ($9,363 OPCAB vs $12,312 CAB, p < 0.001). CONCLUSIONS: In this study, off-pump coronary artery bypass grafting in elderly patients was associated with fewer complications, a shorter hospital stay, and lower hospital cost. Off-pump coronary artery bypass grafting may be the operation of choice for octogenarians requiring surgical myocardial revascularization.

Hemodynamics and early clinical performance of the St. Jude Medical Regent mechanical aortic valve.

BACKGROUND: The St. Jude Medical Regent valve is the next-generation bileaflet aortic prosthesis, modified from the currently marketed St. Jude Medical mechanical valve to achieve a larger geometric orifice without changing the existing design of the pivot mechanism or blood-contact surface areas. The present study reports the hemodynamic and early clinical results of an ongoing multicenter trial investigating the performance of the Regent valve. METHODS: Between July 1998 and July 2001, 361 patients at 17 centers in North America and Europe underwent implantation of a Regent mechanical aortic valve prosthesis. Clinical status was prospectively recorded, and echocardiography with Doppler was performed at discharge and at 2 months, 6 months, 1 year, and 2 years after operation. RESULTS: Follow-up to date is 300 patient-years (average, 0.8 +/- 0.7 years per patient; range, 0.0 to 2.7 years). There were low rates of clinical adverse events. Mean gradient at 6 months was 9.7 +/- 5.3 mm Hg, 7.6 +/- 5.2 mm Hg, 6.3 +/- 3.7 mm Hg, 5.8 +/- 3.4 mm Hg, and 4.0 +/- 2.6 mm Hg, respectively, for 19-mm, 21-mm, 23-mm, 25-mm, and 27-mm valves; effective orifice area was 1.6 +/- 0.4 cm2, 2.0 +/- 0.7 cm2, 2.2 +/- 0.9 cm2, 2.5 +/- 0.9 cm2, and 3.6 +/- 1.3 cm2, respectively. Indexed effective orifice area was equal to or greater than 1.0 cm2/m2 for all valve sizes. Left ventricular mass index decreased significantly between early postoperative (165.9 +/- 57.1 g/m2) and 6-month follow-up (137.9 +/- 41.0 g/m2; delta = -28.0 +/- 49.1 g/m2; p < 0.0001). CONCLUSIONS: The St. Jude Medical Regent aortic valve has excellent hemodynamics and early clinical results, with rapid and significant left ventricular mass regression. Long-term clinical assessment is ongoing.

Assessing options for the small aortic root.

Valve selection for the small aortic root is a multifactorial process. Considerations include the effective orifice (EOA) of the implanted valve, annular size, body surface area (BSA), and valvular outflow tract of each patient. To decide if a valve is adequate for a patient, the valve EOA and patient BSA are used to calculate the indexed EOA (EOA/BSA). An indexed EOA <0.85 is associated with significant increases in mean systolic gradient with increase in cardiac output. The gradient remains low when indexed EOA is >0.85, leading to improved left ventricular mass reduction and decreased long-term risk of arrhythmias, congestive heart failure, and death. Biologic valves are usually used in patients aged over 65 years. Stented biologic valves tend to have a low EOA for their size. A 21-mm pericardial valve has an indexed EOA of 0.81 when implanted in a 1.6-m, 58-kg woman, and 0.69 in a 1.7-m, 72-kg man. Stentless valves (xenograft and homograft) have excellent EOAs and consequently very low gradients with good ventricular mass reduction. This allows for insertion of a larger valve, and results in more normal opening and flow dynamics. Hence, the best approach in over 65-year-old aortic valve patients when using a biologic valve is a stentless subcoronary implant. If this is not possible for anatomic reasons, a stented valve with an indexed EOA >0.85 is the best alternative. An option is root replacement with a xenograft or homograft, but the operative risk is significantly increased. The decision in younger patients (aged <65 years) is more complex. In-vivo EOAs for mechanical valves vary greatly; the St. Jude HP and Regent valves have consistently excellent EOAs. Recent results with the St. Jude Regent valve show gradients and left ventricular mass reduction close to those for stentless biologic valves. In a small aortic annulus, the decision must be made to use a more efficient valve (e.g. the Regent) or a biologic stentless valve, to perform annular enlargement (increasing surgical risk), or to tilt the stented valve to be supra-annular in the non-coronary cusp. The subvalvular outflow tract should not be ignored. Septal hypertrophy is not uncommon, and may increase the gradient across the outflow tract just below the valve. Finally, suture techniques (e.g. pledgetted versus interrupted simple sutures) can affect the long-term gradient. Pledgetted sutures can draw tissue underneath the valve and reduce the EOA. In conclusion, multiple factors must be evaluated when deciding which valve to use as a replacement in the small aortic root. These include patient age, lifestyle, pregnancy status, and drug compliance, as well as the indexed EOA of available prosthetic valves and the surgical procedure required for implant.

Impact of small valve size on hemodynamics and left ventricular mass regression with the Toronto SPV stentless aortic bioprosthesis.

BACKGROUND AND AIM OF THE STUDY: The hemodynamic performance of stentless aortic bioprostheses has been previously well described. Because the potential for prosthesis-patient mismatch is greatest for small valves in the aortic position, the present study sought to compare the hemodynamic performance and degree of left ventricular (LV) mass regression between valve sizes for the Toronto SPV valve, with special interest in measures of relief of LV outflow obstruction afforded by the smallest valves. METHODS: This study included 257 patients (178 men, 79 women; mean age 63.5+/-11.4 years; range: 34-93 years) from six investigative centers with complete echocardiography/Doppler data obtained through three years. Valve sizes implanted were 21 mm (n = 11), 23 mm (n = 23), 25 mm (n = 58), 27 mm (n = 83), and 29 mm (n = 82). Echocardiography was performed at discharge, six months, one year, and yearly thereafter, and interpreted in a centralized core laboratory. Mean gradient, effective orifice area (EOA), indexed EOA, and absolute and percent change in LV mass index were used as markers of hemodynamic performance. RESULTS: For all valve sizes, mean and peak gradients fell and EOA increased early after surgery. There were no differences between groups in the degree to which gradients fell, and EOA increased from discharge to one year follow up. At one year, indexed EOA was 0.9 cm2/m2 for valve sizes 21 and 23 mm, and 1.0-1.2 cm2/m2 for sizes 25, 27 and 29 mm. There was statistically significant LV mass regression for all valve sizes (p <0.05), and no differences between valve sizes in the magnitude of absolute or percent change in LV mass index between baseline and three years. CONCLUSION: The Toronto SPV valve demonstrates excellent parameters of hemodynamic performance for all valve sizes, including the smallest valves used in only a minority of patients. Findings of indexed EOA > or = 0.9 cm2/m2, and equivalent degrees of LV mass regression for all valve sizes, reinforces the excellent hemodynamic performance of stentless aortic bioprostheses, and suggests that prosthesis-patient mismatch should be minimized with these valves.