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.

Episodic monoplane transesophageal echocardiography impacts postoperative management of the cardiac surgery patient.

OBJECTIVE: A new slender, flexible, and miniaturized disposable monoplane transesophageal TEE probe has been approved for episodic hemodynamic transesophageal echocardiographic monitoring. The authors hypothesized that episodic monoplane TEE with a limited examination would help guide the postoperative management of high-risk cardiac surgery patients. DESIGN: The authors analyzed the initial consecutive observational experience with the miniaturized transesophageal echocardiography monitoring system (ClariTEE, ImaCor, Uniondale, New York). SETTING: Single institution in a university setting. PARTICIPANTS: Unstable cardiac surgery patients. INTERVENTIONS: The authors assessed fluid responsiveness, echocardiographic data, and concordance among hemodynamic data. MEASUREMENTS AND MAIN RESULTS: From June 2010 to February 2011, 21 unstable cardiac surgery patients with postoperative instability were identified. Two patients (10%) required reoperation for bleeding and tamponade physiology. Right ventricular dysfunction was diagnosed by episodic TEE monitoring in 7 patients (33%), while hypovolemia was documented in 12 patients (57%). Volume responsiveness was documented in 11 patients. In this observational study, discordance between hemodynamic monitoring and episodic TEE was qualitatively observed in 14 patients (66%). CONCLUSION: The authors demonstrated the ability of episodic monoplane TEE to identify discordance between hemodynamic monitoring to better define clinical scenarios in unstable cardiac surgery patients. For these challenging patients, limited episodic TEE assessment has become a cornerstone of ICU care in this institution.

Obesity and oxidative stress predict AKI after cardiac surgery.

Obesity increases oxidative stress, endothelial dysfunction, and inflammation, but the effect of obesity on postoperative AKI is not known. We examined the relationship between body mass index (BMI) and AKI in 445 patients undergoing cardiac surgery and whether oxidative stress (F(2)-isoprostanes), inflammation (IL-6), or antifibrinolysis (plasminogen activator inhibitor-1 [PAI-1]) contribute to any identified relationship. Overall, 112 (25%) of the 445 patients developed AKI. Higher BMI was independently associated with increased odds of AKI (26.5% increase per 5 kg/m(2) [95% confidence interval, 4.3%-53.4%]; P=0.02). Baseline F(2)-isoprostane (P=0.04), intraoperative F(2)-isoprostane (P=0.003), and intraoperative PAI-1 (P=0.04) concentrations also independently predicted AKI. BMI no longer predicted AKI after adjustment for the effect of F(2)-isoprostanes, suggesting that obesity may affect AKI via effects on oxidative stress. In contrast, adjustment for IL-6 or PAI-1 did not substantially alter the association between BMI and AKI. Further, deconstruction of the obesity-AKI relationship into direct (i.e., independent of candidate pathways) and indirect (i.e., effect of BMI on AKI via each candidate pathway) effects indicated that F(2)-isoprostanes, but not IL-6 or PAI-1, partially mediate the relationship between obesity and AKI (P=0.001). In conclusion, obesity independently predicts AKI after cardiac surgery, and oxidative stress may partially mediate this association.

Technique for Salvage Reconstruction of Shredded Left Main Coronary Artery After Rotablator Injury.

We report the technique needed to effectively repair a left main coronary artery shredding after rotational atherectomy and destruction of the left main coronary artery. The patient had been deemed inoperable at another center because of diffuse distal coronary disease. The complication led to cardiac tamponade and hemodynamic collapse, necessitating cardiopulmonary resuscitation and salvage surgery. This is perhaps the first case in the literature to show a successful repair of such a complex and significant left main, left anterior descending, and left circumflex coronary artery rupture in a patient in extremis.

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 surgery for valvular heart disease.

OPINION STATEMENT: Valvular heart disease imposes varying degrees of stress on the myocardium, which, untreated, leads to eventual ventricular dysfunction. The pathophysiologic mechanisms by which these lesions act depend not only on the affected valve, but also the degree to which they causes stenosis, regurgitation, or both. The goal of patient treatment is to identify and correct the defect before irreversible ventricular changes have occurred. Historically, the conventional surgical approach for valvular disease was via median sternotomy. Minimally invasive valve surgery (MIVS) refers to alternative surgical techniques, which avoid the trans-sternal approach. The objective is to (1) minimize surgical trauma, (2) reduce blood utilization, and (3) hasten postoperative convalesce. These goals are accomplished through the use of partial sternal, para-sternal, or thoracotomy incisions and can be adapted to robotic technologies. As with all evolving surgical techniques, the therapeutic aim of valve repair or replacement must be performed at or above the same standard of conventional surgery. Outcomes must not be sacrificed for the sake of better cosmesis. In addition, percutaneous catheter-based valvular interventions have seen rapid advances. These emerging technologies have dramatically broadened the therapeutic options, especially for an ever-increasing group of high-risk patients. As expected with all minimally invasive techniques, the major differences in the hard outcomes of mortality and major morbidity are seen in these highest risk groups. However, intermediate and low risk patients receive a tremendous benefit with regard to shortened hospital stay and quicker functional recovery. With the myriad of interventional options now available, the clinical challenge now is how best to individualize the treatment approach to a given patient providing the most durable result in order to alleviate symptoms and preserve myocardial function.

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.

Adenosine receptor-mediated adhesion of endothelial progenitors to cardiac microvascular endothelial cells.

Intracoronary delivery of endothelial progenitor cells (EPCs) is an emerging concept for the treatment of cardiovascular disease. Enhancement of EPC adhesion to vascular endothelium could improve cell retention within targeted organs. Because extracellular adenosine is elevated at sites of ischemia and stimulates neovascularization, we examined the potential role of adenosine in augmenting EPC retention to cardiac microvascular endothelium. Stimulation of adenosine receptors in murine embryonic EPCs (eEPCs) and cardiac endothelial cells (cECs) rapidly, within minutes, increased eEPC adhesion to cECs under static and flow conditions. Similarly, adhesion of human adult culture-expanded EPCs to human cECs was increased by stimulation of adenosine receptors. Furthermore, adenosine increased eEPC retention in isolated mouse hearts perfused with eEPCs. We determined that eEPCs and cECs preferentially express functional A1 and A2B adenosine receptor subtypes, respectively, and that both subtypes are involved in the regulation of eEPC adhesion to cECs. We documented that the interaction between P-selectin and its ligand (P-selectin glycoprotein ligand-1) plays a role in adenosine-dependent eEPC adhesion to cECs and that stimulation of adenosine receptors in cECs induces rapid cell surface expression of P-selectin. Our results suggest a role for adenosine in vasculogenesis and its potential use to stimulate engraftment in cell-based therapies.

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.

Recurrent atrial myxoma: resection for Carney complex through a minimally invasive approach.

Carney's complex is an autosomal dominant syndrome characterized by recurrent atrial myxomas with concurrent endocrinopathies and characteristic dermatologic features. We present the case of a woman who presented with a recurrent atrial myxoma after two previous resections for myxomas through median sternotomies. As a consequence, we utilized a minimally invasive right thoracotomy approach. We discuss the clinical and pathologic features of Carney complex and the importance of identifying individuals and families with this condition for treatment and counseling.

Preoperative optimization of multi-organ failure following acute myocardial infarction and ischemic mitral regurgitation by placement of a transthoracic intra-aortic balloon pump.

BACKGROUND: The management of acute myocardial infarction with resultant acute ischemic mitral regurgitation and acute multi-organ failure can prove to be a very challenging scenario. The presence of concomitant vascular disease can only serve to further compromise the complexity of the situation. We demonstrate a new indication for the transthoracic intra-aortic balloon pump as a preoperative means of unloading the heart and improving clinical outcome in such high-risk patients with severe vascular disease. METHODS: We present the case of a 75-year-old man with a history of severe vascular disease who was transferred emergently to Vanderbilt University Medical Center with an acute inferolateral wall myocardial infarction resulting in severe acute ischemic mitral regurgitation and acute multi-organ failure. He presented with shock liver (serum glutamic-oxaloacetic transaminase [SGOT] of 958), renal failure (creatinine of 3.0), and respiratory failure with a pH of 7.18. Emergent cardiac catheterization revealed 100% occlusion of the left circumflex artery as well as severe ileofemoral disease. The advanced nature of his ileofemoral disease was such that the arterial access catheter occluded the right femoral artery. The duration of time that the catheter was in the artery led to transient limb ischemia with an elevation of his creatine phosphokinase (CPK) to 10,809. Balloon angioplasty followed by stent placement was successfully performed, which restored flow to the coronary vessel. Given the grave nature of the patient's condition, we were very concerned that immediate operative intervention for his condition would entail prohibitively high risk. In fact, the Society of Thoracic Surgeons predicted risk adjusted mortality was calculated to be 56%. In order to minimize patient mortality and morbidity, it was critical to help restore perfusion and organ recovery. Therefore, we decided that the chances for this patient's survival would improve if his condition could be optimized by placement of an intra-aortic balloon pump before undergoing surgery. Given the limb ischemia following arterial sheath insertion, femoral placement of an intra-aortic balloon pump was not an option. Placement of the intra-aortic balloon pump was attempted via a left subclavian artery cutdown, but was not successful. Therefore, a sternotomy was performed, and we placed a transthoracic intra-aortic balloon pump in order to stabilize the patient's hemodynamics and allow for organ recovery. RESULTS: The patient showed immediate improvement, and 4 days later, the multi-organ failure resolved and he successfully underwent mitral valve replacement. The patient was ultimately discharged to a local rehabilitation facility in satisfactory condition. CONCLUSION: This case demonstrates the utility of a transthoracic intra-aortic balloon pump as a preoperative means of stabilization in very high risk patients with severe peripheral vascular disease in whom the conventional approaches are not possible.

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.

Idiopathic mitral valve disease in a patient presenting with Axenfeld-Rieger syndrome.

A 33-year-old, previously healthy male presented with respiratory distress and underwent intubation. A physical examination revealed a holosystolic murmur and pupillary abnormalities. Echocardiography revealed a flail anterior mitral valve leaflet with ruptured chordae and severe mitral regurgitation. The patient underwent urgent mitral valve replacement and tolerated the procedure well. The mitral valve leaflet was myxomatous and calcified -- an unusual find in such a patient. An ophthalmology consultation was obtained and the patient diagnosed with Axenfeld-Rieger syndrome, a disorder of the anterior ocular chamber that has been associated with cardiac malformations. The present case report adds to the body of literature which suggests a correlation between Axenfeld-Rieger syndrome and valvular abnormalities. Hence, it is believed prudent that patients with Axenfeld-Rieger syndrome should undergo echocardiographic screenings for valvular abnormalities.

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.