Faculty Bibliography

BACKGROUND: Calcific aortic stenosis (CAS) is the most common acquired valvular disorder in industrialized countries. This study investigates the correlation of different known biomarkers for CAS as a first step towards the development of a panel of biomarkers that can be used in prognostic staging. METHODS: Venous blood samples were obtained from both patients with CAS scheduled for surgery and healthy individuals. Plasma levels of fetuin-A, NT-proBNP, BNP, homocysteine and osteopontin were measured by enzyme-linked immunosorbent assay (ELISA). CAS was measured by echocardiography and was defined as an aortic valve area of less than 2.0 cm(2). Non-paired t-tests were used for comparison. RESULTS: CAS was present in 33 subjects (mean age 75.9 y) and absent in 11 subjects (mean age 55.36 y). Individuals with CAS exhibited higher plasma levels of NT-proBNP (1.33 versus 0.73 pmol/mL, P < 0.05), BNP fragment (1.47 versus 0.34 ng/mL P < 0.05), and osteopontin (60.79 versus 25.42 ng/mL P < 0.05) compared with controls. Fetuin-A levels were lower in individuals with CAS than in healthy controls (0.25 versus 0.34g/L, P < 0.05). Asymmetric dimethylarginine (ADMA) were lower (1.08 versus 1.1 micromol/L, P > 0.05) while homocysteine levels (20.34 +/- 2.14 versus 19.23 +/- 4.19 P > 0.05) were higher in the CAS patients. CONCLUSION: This study demonstrates a direct correlation of NT-pro-BNP, BNP, and osteopontin and the presence of CAS, while fetuin A showed an inverse correlation. Plasma ADMA and homocysteine levels were comparable in the CAS patients and healthy individuals. This is the first study in which several biomarkers previously studied independently in patients with CAS have been investigated simultaneously in the same study population

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

A 60-year-old man presented with symptoms from an intracardiac mass. His medical history included retroperitoneal fibrosis (Ormond disease). Magnetic resonance imaging revealed an obstructing bilobular mass in the right atrium, located at the caval junction and extending intramurally into the atria, septum, and right ventricle. En bloc resection of the right atrium, interatrial septum, dome of the left atrium, vena cava, anterior tricuspid annulus, right coronary artery, and partial right ventriculectomy was completed with right ventricular repair, tricuspid valve replacement, and left and right atrial replacement with bovine pericardium. This lesion was a myofibroblastic tumor with the same histologic features as his retroperitoneal fibrosis

BACKGROUND: Functional mitral regurgitation (FMR) is associated with leaflet displacement and tethering. Little is known about regional coaptation zones, including variations in coaptation length (CL) and contributions of anterior and posterior leaflets. Regional coaptation zones were analyzed in patients with normal mitral valves and with FMR. METHODS: Cardiac surgery patients underwent a three-dimensional transesophageal echocardiography. Four-dimensional volumetric datasets were acquired with Doppler interrogation. Offline analysis was performed. Orthogonal views were extracted in diastole and systole. Leaflet dimensions and coaptation distance and depth were examined for posterior and apical displacement of the coaptation zones. RESULTS: Twenty patients were analyzed (10 normal and 10 with 2 to 4+ FMR). Anterior leaflet CL was greater than posterior leaflet CL: 2.2+/-0.6 mm versus 0.9+/-0.3 mm in region 1, 3.2+/-0.7 mm versus 1.2+/-0.6 mm in region 2, and 1.8+/-0.4 mm versus 0.6+/-0.3 mm in region 3 (p<0.001). The FMR was associated with shorter leaflet CLs, with a mean anterior CL of 1.7+/-0.4 mm versus 3.1+/-0.4 mm (p=0.04), and a mean posterior CL of 0.7+/-0.3 mm versus 1.1+/-0.3 mm (p=0.03). The biggest difference in CLs was in A2-P2. Coaptation distance and depth were higher in the FMR group: 21.7+/-1.0 mm versus 17.9+/-1.0 mm (p=0.01), and 8.6+/-0.7 mm versus 5.0+/-0.7 mm (p<0.01). CONCLUSIONS: Mitral valve leaflet CL is asymmetric in normal valves, with anterior dominance. Functional mitral regurgitation is associated with a relocated coaptation zone, regional changes, and diminished coaptation. These data suggest an 'anterior leaflet reserve.' Posterior movement of the coaptation line compensates for annular dilation and presumed left ventricular enlargement in order to maintain competency until inadequate anterior leaflet CL occurs

BACKGROUND: A recent report suggested that a thoracotomy approach for reoperative mitral valve (MV) procedures was associated with an equivalent mortality and an unacceptable risk of stroke. We assessed these outcomes in a single institution's experience. METHODS: From 1992 through 2007, 905 patients underwent reoperative MV procedures. The approach was a median sternotomy in 612 (67.6%), right anterior thoracotomy in 242 (26.7%), and left posterior thoracotomy in 51 (5.6%). Concomitant procedures in 411 patients (67.6%) included aortic procedures in 189, tricuspid procedures in 170, and coronary artery bypass grafting in 90. Hypothermic fibrillation was used in 65 patients. Logistic analysis was used to analyze risk factors and outcomes. RESULTS: Overall mortality was 12.7% (115 of 905), 6.7% (25 of 371) for first time isolated MV reoperations, and 10.1% (50 of 494) for all isolated MV operations. Overall incidence of stroke was 3.8% (34 of 905); 10.9% (9 of 82) with retrograde arterial perfusion and 3.0% (25 of 824) with central aortic cannulation (p < 0.001). For isolated MV reoperations, the incidence of stroke was 4.3% (21 of 494): 2.9% (7 of 241) for antegrade perfusion and 5.5% (14 of 253) for retrograde perfusion (p = 0.15). Risk factors for death were age (p < 0.001), renal failure (p < 0.01), tricuspid valve disease (p < 0.001), chronic obstructive pulmonary disease (odds ratio [OR], 2.9; 95% confidence interval [CI], 1.8 to 4.9; p < 0.001), emergency procedure (OR, 2.9; 95% CI, 1.2 to 6.9; p = 0.02), and ejection fraction less than 0.30 (OR, 1.9; 95% CI, 1.1 to 3.3, p = 0.018). Risk factors for stroke were retrograde perfusion (OR, 4.4; 95% CI, 1.8 to 10.3; p < 0.01) and ejection fraction below 0.30 (OR, 2.1; 95% CI, 0.9 to 5.0; p = 0.09). CONCLUSIONS: The incidence of stroke in reoperative MV operations is associated with perfusion strategies, not with the incisional approach. Reoperative sternotomy and minithoracotomy with central cannulation are both useful for reoperative MV procedures and are associated with low stroke rates

BACKGROUND: Folding plasty (FP) for posterior mitral leaflet repair (PLR) is a technique that reduces the height of the repaired leaflet, closes the gap created by leaflet resection by rotation of residual leaflet, and reduces the need for localized annular plication. This report reviews late outcomes with FP repair. METHODS: From January 1994 to August 2006, 1,402 mitral valve repairs were performed for degenerative disease: 1,012 had PLR and 531 had FP technique. RESULTS: Overall hospital mortality was 2.4% (33 of 1,402 patients) and 1.3% (14 of 1,103 patients) for isolated mitral repair. For those patients with PLR, mortality for all procedures was 1.5% (15 of 1,012 patients) and 1.2% (11 of 891 patients) for isolated PLR repairs. Mortality was 0.9% (5 of 531 patients) for FP. In the last 5 years FP was used in 64.4% of PLR, compared with 35.6% of PLR in the prior era (p < 0.001). The 10-year actuarial freedom from mitral reoperation was 89%; 10-year freedom from reoperation or recurrent severe mitral insufficiency was 86% with FP and 87% without (p = 0.76). The 5-year freedom from reoperation or recurrent severe insufficiency was 89% when an annuloplasty device was used and 62% when not used (p < 0.001). CONCLUSIONS: Repair of posterior leaflet prolapse with FP is straightforward and durable. In our experience, FP is currently used for two thirds of PLR. These data also confirm that valve repair for degenerative disease should include an annuloplasty device for optimal late results

BACKGROUND: Percutaneous mitral repair with the MitraClip device (Evalve, Menlo Park, CA) has been reported. Preserving conventional surgical options in the event of percutaneous treatment failure is important. We describe surgical treatment at varying intervals after the MitraClip procedure in 32 patients. METHODS: One hundred seven patients with moderate-to-severe or severe mitral regurgitation who were either symptomatic (91%) or, if asymptomatic (9%), had evidence of left ventricular dysfunction were enrolled as part of the Endovascular Valve Edge-to-Edge REpair STudy (EVEREST) phase I registry study or as 'roll-in' subjects in the EVEREST II study. Thirty-two of the 107 patients (30%) underwent surgery after an attempted MitraClip procedure. RESULTS: Of the 32 patients undergoing post-clip mitral valve surgery, 23 patients (72%) had one or more clips implanted and 9 patients (28%) received no clip implant. The indications for mitral valve surgery in the 23 patients with a clip included partial clip detachment (n = 10), residual or recurrent mitral regurgitation greater than 2+ (n = 9), and other (atrial septal defect [n = 2], device malfunction [n = 1], and incorrectly diagnosed mitral stenosis [n = 1]). Twenty-seven of 31 patients (87%) underwent the surgical procedure planned before surgery (planned procedure unknown in 1 patient). Four of 25 patients (16%) with planned repair underwent mitral valve replacement. CONCLUSIONS: Standard surgical options were preserved in patients who had surgery after percutaneous repair with the MitraClip device. Successful repair was feasible in the majority of patients after the MitraClip procedure, with repair performed as late as 18 months after clip implantation

BACKGROUND: Short-term results with minimally invasive approaches for mitral valve repair in degenerative disease have been encouraging, with potential for diminishing blood loss and hospital length of stay. Little is known, however, about the long-term efficacy of this approach. This report analyzes a single institution's results over 12 years with minimally invasive mitral repair. METHODS: Since 1986, 3,057 patients have undergone mitral valve repair; 1,601 patients had degenerative disease and are the subject of this report. Minimally invasive mitral repair was done in 1071 patients with a right anterior minithoracotomy and direct vision. Clinical and echocardiographic variables were entered prospectively into a database. RESULTS: Hospital mortality was 2.2% for all patients (36 of 1601); 1.3% for isolated minimally invasive (9 of 712) and 1.3% (3 of 223) for isolated sternotomy mitral valve repair; and 3.6% (24 of 666) for valve repair plus a concomitant cardiac procedure. For isolated valve repair, 8-year freedom from reoperation was 91% +/- 2% for sternotomy and 95% +/- 1% for minimally invasive (p = 0.24), and 8-year freedom from reoperation or severe recurrent insufficiency was 90% +/- 2% for sternotomy and 93% +/- 1% for minimally invasive (p = 0.30). Eight-year freedom from all valve-related complications was 86% +/- 3% for sternotomy and 90% +/- 2% for minimally invasive (p = 0.14). CONCLUSIONS: These data indicate that long-term outcomes after minimally invasive mitral repair are excellent and equivalent to results achieved with sternotomy. In view of previously published advantages of short-term morbidity, minimally invasive approaches to mitral valve surgery deserve expanded use

OBJECTIVE: The inflammatory process of aortic stenosis involves the differentiation of aortic valve myofibroblasts into osteoblasts. Osteopontin, a proinflammatory glycoprotein, both stimulates differentiation of myofibroblasts and regulates the deposition of calcium by osteoblasts. Osteopontin levels are increased in patients with such conditions as end-stage renal disease, ectopic calcification, and autoimmune disease. We hypothesized that increased plasma osteopontin levels might be associated with the presence of aortic valve calcification and stenosis. METHODS: Venous blood from volunteers older than 65 years undergoing routine echocardiographic analysis or aortic valve surgery for aortic stenosis was collected. Plasma osteopontin levels were measured by means of enzyme-linked immunosorbent assay. The presence of aortic stenosis was defined as an aortic valve area of less than 2.0 cm(2). Aortic valve calcification was assessed by using a validated echocardiographic grading system (1, none; 2, mild; 3, moderate; 4, severe). Comparisons were performed with nonpaired t tests. RESULTS: Aortic stenosis was present in 23 patients (mean age, 78 years) and was absent in 7 patients (mean age, 72 years). Aortic valve calcification scores were 3.5 +/- 0.6 and 1.3 +/- 0.5 in patients with and without aortic stenosis, respectively (P < .001). Patients with no or mild aortic valve calcification had lower osteopontin levels compared with patients with moderate or severe aortic valve calcification (406.1 +/- 165.8 vs 629.5 +/- 227.5 ng/mL, P = .01). Similarly, patients with aortic stenosis had higher osteopontin levels compared with patients without aortic stenosis (652.2 +/- 218.7 vs 379.7 +/- 159.9 ng/mL, P < .01). CONCLUSION: Increased levels of plasma osteopontin are associated with the presence of aortic valve calcification and stenosis. These findings suggest that osteopontin might play a functional role in the pathogenesis of calcific aortic stenosis