James P. Greelish

Routine Intraoperative Completion Angiography After Coronary Artery Bypass Grafting and 1-Stop Hybrid Revascularization: Results From a Fully Integrated Hybrid Catheterization Laboratory/Operating Room

OBJECTIVES This study sought to report our experience with a routine completion angiogram after coronary artery bypass surgery (CABG) and simultaneous (1-stop) percutaneous coronary intervention (PCI) at the time of CABG performed in the hybrid catheterization laboratory/operating room. BACKGROUND The value of a routine completion angiogram after CABG and 1-stop hybrid CABG/PCI remains unresolved. METHODS Between April 2005 and July 2007, 366 consecutive patients underwent CABG surgery, with (n = 112) or without (n = 254) concomitant 1-stop PCI (hybrid), all with completion angiography before chest closure. Among the 112 1-stop hybrid CABG/PCI patients, 67 (60%) underwent a planned hybrid procedure based on pre-operative assessment, whereas 45 (40%) underwent open-chest PCI (unplanned hybrid) based on intraoperative findings. RESULTS Among the 796 CABG grafts (345 left internal mammary artery, 12 right internal mammary artery/radial, and 439 veins), 97 (12%) angiographic defects were identified. Defects were repaired with either a minor adjustment of the graft (n = 22, 2.8%), with intraoperative open-chest PCI (unplanned hybrid, n = 48, 6%) or with traditional surgical revision (n = 27, 3.4%). Hybrid patients had clinical outcomes similar to standard CABG patients. CONCLUSIONS Routine completion angiography detected 12% of grafts with important angiographic defects. One-stop hybrid coronary revascularization is reasonable, safe, and feasible. Combining the tools of the catheterization laboratory and operating room greatly enhances the options available to the surgeon and cardiologist for patients with complex coronary artery disease.

Minimally invasive mitral valve repair suggests earlier operations for mitral valve disease

OBJECTIVE We began minimally invasive mitral valve surgery in August, 1996, to reduce hospital costs, to improve patient recovery, cosmetic appearance, and to decrease trauma, yet maintain the same quality of surgery. To validate this approach we reviewed our entire experience through May 2002. METHODS From August 1996 to May 2002, we performed 413 minimally invasive mitral valve operations including 51 mitral valve replacements and 362 mitral valve repairs. Excluding 4 robotically assisted repairs, we evaluated 358 patients, using the mitral valve repairs as the basis for this retrospective survey. These operations were performed through a 6- to 8-cm minimally invasive incision, beginning with parasternal and, most recently, lower ministernotomy (181 patients). The mitral valve reparative techniques include repair of 94 prolapsed anterior leaflets, posterior leaflet resection, leaflet advancement, commissuroplasty, Polytetrafluoroethylene (PTFE; Gore-Tex, W. L. Gore & Associates, Inc, Flagstaff, Ariz) chordal placement, and ring annuloplasty. Cannulation sites varied but primarily utilized a miniaturized system of 24F catheters in both the inferior and superior venae cavae with assisted venous suction. The Cosgrove ring was used in 95% of the patients undergoing this procedure. RESULTS The operative mortality was 0/358. Perioperative morbidity included a 26% incidence of new atrial fibrillation, 2% incidence of pacemaker implantation, 0.5% incidence of deep sternal wound infection, and 1.9% incidence of stroke after an operation. There were 10 arterial and 3 venous complications. The mean length of stay was 6 days and 208 patients stayed < or =5 days. Only 25% of the patients underwent homologous blood transfusion. The mean follow-up was 36 months with 1.4% lost to follow-up. There were 12 late deaths and a survival at 5 years of 95%. There were 21 valves requiring reoperation for structural valve failure of 5.8%. The probability of freedom from reoperation at 5 years was 92%. CONCLUSION This study documents the safety of minimally invasive mitral valve repair surgery in 358 patients. It also documents a low incidence of homologous blood use, requirement for post-hospital rehabilitation, and general morbidity.

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. Conclusion— Milrinone use is an independent risk factor for postoperative AF after elective cardiac surgery.

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.

Plasminogen Activator Inhibitor-1 as a Predictor of Postoperative Atrial Fibrillation After Cardiopulmonary Bypass

Background— Postoperative atrial fibrillation (AF), leading to significant morbidity and prolongation of hospital stay, complicates 20% to 40% of surgical procedures requiring cardiopulmonary bypass (CPB). This study tests the hypothesis that biomarkers predict the development of postoperative AF. Methods and Results— We enrolled 253 adult patients undergoing elective cardiac surgery requiring CPB and who were in sinus rhythm at the time of surgery. Blood samples were obtained for measurement of 21 biomarkers immediately after separation from CPB and administration of protamine. Patients who developed postoperative AF (67 subjects, 26.5%) were significantly older (P<0.001), more likely to have a remote history of AF (P<0.001), and tended to be more likely to have had valve surgery (P=0.082). Plasminogen activator inhibitor-1 (P=0.014), interleukin (IL)-6 (P=0.019), and N-terminal prohormone brain natriuretic peptide (P=0.028) concentrations were significantly higher in the blood of patients who developed postoperative AF. Logistic regression identified age (P<0.001), remote history of AF (P=0.001), and postoperative PAI-1 (P=0.036) as independent predictors of postoperative AF. When preoperative PAI-1 antigen concentrations were included in the model age (P<0.001), remote history of AF (P<0.001) and preoperative PAI-1 (P=0.015) were identified as independent predictors of postoperative AF. The Chi-squared Automatic Interaction Detection (CHAID) model indicated that age was the primary determinant for the development of postoperative AF (17% in age ≤67.3 years versus 49% in age >67.3 years). Within younger patients (age ≤67.3 years) without remote history of AF, postoperative PAI-1 antigen concentration next determined risk of AF (13% if PAI-1≤28.5 ng/mL versus 46% if PAI-1>28.5 ng/mL). Conclusion— An elevated preoperative or postoperative PAI-1 antigen concentration is an independent predictor for development of AF after CPB. Studies are needed to determine whether drugs that reduce PAI-1 concentrations can also reduce the risk of postoperative AF.

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 (2.5mg the first 3 days followed by 5mg/day, with the dose reduced to 2.5mg/day on the first postoperative day only), or spironolactone (25mg/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.

Uniform standards do not apply to readmission following coronary artery bypass surgery: a multi-institutional study.

OBJECTIVES Reducing hospital readmissions is a national priority, with coronary artery bypass graft (CABG) surgery slated for upcoming reimbursement decisions. Clear understanding of the elements associated with readmissions is essential for developing a coherent prevention strategy. Patterns of readmission vary considerably based on diagnosis. We therefore sought to clarify the factors most clearly associated with 30-day readmission following CABG surgery in an academically affiliated community hospital network. METHODS All patients undergoing isolated CABG in an 11-hospital network from 2007 to 2011 were entered into a Society of Thoracic Surgeons (STS) compliant registry that tracks hospital readmission within 30 days of surgery. Data were split at random into training and validation groups that were used to create and validate a logistic regression model of pre-, intra-, and postoperative factors associated with readmission. Subanalyses included development of logistic models predicting readmission for the 2 largest institutions individually, and relatedness of readmission to CABG procedure. RESULTS The readmission rate for the entire 4861 patient group was 9.2% and varied between hospitals from 6.1% to 18.0%. Factors associated with readmission were moderate chronic obstructed pulmonary disease (odds ratio [OR], 1.81; 95% confidence interval [CI], 1.04-3.14; P = .036), cerebrovascular disease (OR, 1.56; 95% CI, 1.09-2.24; P = .016), diabetes (OR, 1.44; 95% CI, 1.08-1.93; P = .014), congestive heart failure (OR, 2.12; 95% CI, 1.23-3.66; P = .007), intra-aortic balloon pump (OR, 0.40; 95% CI, 0.19-0.83; P = .015), and use of blood products (OR, 1.76; 95% CI, 1.31-2.37; P = .0002). Although the c statistic for the training model (n = 2341) was 0.643, when applied to the validation dataset (n = 2520) the area under the receiver operating curve was reduced to 0.57. Separate analyses of factors for the 2 largest hospitals revealed marked differences, with only body mass index (OR, 1.08; 95% CI, 1.04-1.12; P = .0001) significantly associated with readmission at 1 hospital, and discharge to extended care (OR, 2.11; 95% CI, 1.02-4.33; P = .043) and renal failure (OR, 2.64; 95% CI, 1.21-5.76; P = .0149) significant at the other hospital. Most readmissions (60.8%) occurred within 10 days of discharge. Nearly one-third (31.3%) were categorized as unlikely to be CABG-related. The mean number of days from surgery to readmission was less for readmissions clearly related to CABG (15.5 ± 6.4 days), compared with those unlikely to be CABG-related (17.4 ± 7.0 days) (P = .05). CONCLUSIONS Analysis of CABG readmission data from a network of community hospitals that vary in size and patient demographic characteristics suggests that there are many nonclinical factors influencing readmission; readmission rates and associated risk factors may vary considerably between centers; earlier readmissions are more likely to be procedure-related than patient-related; and therefore, considerable caution should be exercised in attempting to apply uniform standards or strategies to address post-CABG readmission.

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.

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.

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.