Thrombin cleaves the high molecular weight forms of basic fibroblast growth factor (FGF-2): a novel mechanism for the control of FGF-2 and thrombin activity.

The fgf-2 gene encodes low molecular weight (LMW, 18 kDa) and high molecular weight (HMW, 22-24 kDa) forms that originate from alternative translation of a single mRNA and exhibit diverse biological functions. HMW fibroblast growth factor-2 (FGF-2) inhibits cell migration and induces cell transformation or growth arrest in a cell type- and dose-dependent fashion. Conversely, LMW FGF-2 upregulates both cell proliferation and migration in most cell types. Although transcriptional and translational regulation of HMW and LMW FGF-2 has been extensively investigated, little is known about post-translational control of their relative expression. Here we report that thrombin, a key coagulation factor and inflammatory mediator, cleaves HMW FGF-2 into an LMW FGF-2-like form that stimulates endothelial cell migration and proliferation. The effect of thrombin on these cell functions requires HMW FGF-2 cleavage. This post-translational control mechanism adds a novel level of complexity to the regulation of FGF-2, and links the activities of thrombin and FGF-2 in patho-physiological processes in which both molecules are expressed.

The genetics of mitral valve prolapse.

Mitral valve prolapse (MVP) is a very common clinical condition that refers to a systolic billowing of one or both mitral valve leaflets into the left atrium. Improvements of echocardiographic techniques and new insights in mitral valve anatomy and physiology have rendered the diagnosis of this condition more accurate and reliable. MVP can be sporadic or familial, demonstrating autosomal dominant and X-linked inheritance. Three different loci on chromosomes 16, 11 and 13 have been found to be linked to MVP, but no specific gene has been described. Another locus on chromosome X was found to cosegregate with a rare form of MVP called 'X-linked myxomatous valvular dystrophy'. MVP is more frequent in patients with connective tissue disorders including Marfan syndrome, Ehlers-Danlos and osteogenesis imperfecta. The purpose of this review is to describe previous studies on the genetics and prevalence of MVP. The report warrants the need for further genetically based studies on this common, albeit not fully understood, clinical entity.

The role of annuloplasty in mitral valve repair.

Mitral valve repair surgery has progressed dramatically since its inception over 40 years ago. As techniques have evolved, complicated mitral valve reconstruction has become commonplace, with durable late results. Likewise, the value of concomitant annuloplasty during valve repair has been firmly established as contributing to late valve repair durability. This review discusses the evolution of annuloplasty techniques and the physiologic reasoning behind various approaches.

Ischemic mitral valve reconstruction and replacement: comparison of long-term survival and complications.

OBJECTIVE: This study reviews the 223 consecutive mitral valve operations for ischemic mitral insufficiency performed at New York University Medical Center between January 1976 and January 1996. The results for mitral valve reconstruction are compared with those for prosthetic mitral valve replacement. METHODS: From January 1976 to January 1996, 223 patients with ischemic mitral insufficiency underwent mitral valve reconstruction (n = 152) or prosthetic mitral valve replacement (n = 71). Coronary artery bypass grafting was performed in 89% of cases of mitral reconstruction and 80% of cases of prosthetic replacement. In the group undergoing reconstruction, 77% had valvuloplasty with a ring annuloplasty and 23% had valvuloplasty with suture annuloplasty. In the group undergoing prosthetic replacement, 82% of patients received bioprostheses and 18% received mechanical prostheses. RESULTS: Follow-up was 93% complete (median 14.6 mo, range 0-219 mo). Thirty-day mortality was 10% for mitral reconstruction and 20% for prosthetic replacement. The short-term mortality was higher among patients in New York Heart Association functional class IV than among those in classes I to III (odds ratio 5.75, confidence interval 1.25-26.5) and was reduced among patients with angina relative to those without angina (odds ratio 0.26, confidence interval 0.05-1.2). The 30-day death or complication rate was similarly elevated among patients in functional class IV (odds ratio 5.53; confidence interval 1.23-25.04). Patients with mitral valve reconstruction had lower short-term complication or death rates than did patients with prosthetic valve replacement (odds ratio 0.43, confidence interval 0.20-0.90). Eighty-two percent of patients with mitral valve reconstruction had no insufficiency or only trace insufficiency during the long-term follow-up period. Five-year complication-free survivals were 64% (confidence interval 54%-74%) for patients undergoing mitral valve reconstruction and 47% (confidence interval 33%-60%) for patients undergoing prosthetic valve replacement. Results of a series of statistical analyses suggest that outcome was linked primarily to preoperative New York Heart Association functional class. CONCLUSIONS: Initial mortalities were similar among patients undergoing prosthetic replacement and valve reconstruction. Poor outcome was primarily related to preexisting comorbidities. Patients undergoing valve reconstruction had fewer valve-related complications. Valve reconstruction resulted in excellent durability and freedom from complications. These findings suggest that mitral valve reconstruction should be considered for appropriate patients with ischemic mitral insufficiency.

Predictors of operative time in multicenter port-access valve registry: institutional differences in learning.

BACKGROUND: The predictors of operative time and the effects of learning in isolated valve operations using port-access techniques have not been defined. METHODS: Analysis of covariance was used to examine the determinants of procedure time, pump time, and aortic clamp time. In the largest prospective, registry of patients undergoing isolated aortic valve replacement (AVR, N=199), mitral repair (MVP, N=307), or mitral replacement (MVR, N=232) using port-access techniques 1997-1999 at 27 institutions. RESULTS: Institutional case volume ranged from one to 214 (median 6). Operative time was longer in redo procedures (5.3 +/- 1.6 vs. 4.4 +/- 1.3 hr, p = 0.0001), longer with MVP or MVR vs. AVR (4.8 +/- 1.2 vs. 5.0 +/- 1.5 vs. 3.8 +/- 1.2 hr, p = 0.0001), and decreased with case number (mean decrease 1.00 +/- 0.19 min/case, p = 0.04). Operative time also varied between institutions (p = 0.001). Rate of learning (decrease in time per case) varied significantly between institutions only for MVP (p = 0.03). Similar analysis showed that pump time and clamp times did not significantly change over time (p > 0.17) but varied significantly between institutions. Institutional volume did not affect operative, pump, or clamp times or rate of learning (decrease in operative time/case). CONCLUSIONS: These prospective registry data demonstrate that, for port-access valve procedures, procedure times continue to improve (learning) even after 100 cases. Procedure time and learning are affected by institutional differences and by the type of procedure, but are little affected by institutional volume. This data provides a model to understand learning of new surgical procedures, and this data suggests that port-access valve procedures can be mastered by a variety of institutions.

Minimally invasive aortic valve replacement: echocardiographic and clinical results.

BACKGROUND: Port access has been described for mitral and bypass surgery. The purpose of this study was to review the clinical and echocardiographic outcomes of aortic valve replacement by use of port access. METHODS: Between 1996 and 1999, 153 port-access aortic valve replacements were performed at our institution. The mean age was 63 years (range 16-91 years); 58% were male. The New York Heart Association mean class was III; 18% were in class IV. Thirteen percent had diabetes, 42% hypertension, 7% prior transient ischemic episode or stroke, 7% lung disease, 3% renal failure, and 13% previous surgery. Echocardiograms were obtained after valve replacement in 125 patients (96 intraoperative transesophageal and 97 transthoracic echoes). RESULTS: Median length of stay was 8 days. There were no intraoperative deaths; 10 patients (6.5%) died in the postoperative period. Stroke occurred in 4 (2.6%), sepsis in 5 (3.3%), renal failure in 5 (3.3%), pneumonia in 3 (2%), and wound infection in 1 (0.7%). Tissue prosthesis was present in 83 and a mechanical prosthesis in 42. No or trace regurgitation was seen on 94 of 96 (98%) postbypass intraoperative echocardiograms and mild on 2. On follow-up echocardiograms, moderate regurgitation was seen in 4 of 97 (4.1%), mild-to-moderate in 2 (2.1%), mild in 18 (18.6%), and no or trace in 71 (73.2%). Of those who had aortic regurgitation on intraoperative or follow-up echocardiograms, it was paravalvular in 8. CONCLUSIONS: Minimally invasive aortic valve replacement with a port-access approach is feasible, even in high-risk patients. Small incisions, a low infection rate, and a short length of stay are attainable. However, the complications associated with traditional aortic valve replacement still occur. Echocardiography is valuable both for intraoperative monitoring and follow-up of this new procedure.

Impact of minimally invasive valvular heart surgery: a case-control study.

BACKGROUND: The port access (PA) approach for valvular heart surgery is widely used, but few studies evaluating outcomes compared with the sternotomy approach have been performed. METHODS: One hundred nine consecutive patients undergoing PA-isolated valve surgery were compared with 88 matched patients who underwent sternotomy-isolated valve surgery before the institution of the PA program. Case matching was performed by age, surgeon, congestive heart failure, position of operated valve, and history of previous surgery. RESULTS: Analysis revealed that PA was associated with similar hospital mortality (p = 0.62), longer bypass times (p < 0.001), shorter length of stay (p = 0.02), fewer transfusions (p = 0.02), and fewer septic complications (p = 0.05). CONCLUSIONS: The PA approach for isolated valvular heart surgery provided patients with significantly improved clinical outcomes in their immediate perioperative course. Further studies are required to measure the impact of the PA approach on the patients' recovery after hospitalization.

Minimally invasive versus sternotomy approaches for mitral reconstruction: comparison of intermediate-term results.

BACKGROUND: This study compares intermediate-term outcomes of mitral valve reconstruction after either the standard sternotomy approach or the new minimally invasive approach. Although minimally invasive mitral valve operations appear to offer certain advantages, such as reduced postoperative discomfort and decreased postoperative recovery time, the intermediate-term functional and echocardiographic efficacy has not yet been documented. METHODS: From May 1996 to February 1999, 100 consecutive patients underwent primary mitral reconstruction through a minimally invasive right anterior thoracotomy and peripheral cardiopulmonary bypass and Port-Access technology (Heartport, Inc, Redwood City, Calif). Outcomes were compared with those for our previous 100 patients undergoing primary mitral repair who were operated on with the standard sternotomy approach. RESULTS: Although patients were similar in age, the patients undergoing the minimally invasive approach had a lower preoperative New York Heart Association classification (2.1 +/- 0.5 vs 2.6 +/- 0.6, P <.001). There was one (1.0%) hospital mortality with the sternotomy approach and no such case with the minimally invasive approach. Follow-up revealed that residual mitral insufficiency was similar between the minimally invasive and sternotomy approaches (0.79 +/- 0.06 vs 0.77 +/- 0.06, P =.89, 0- to 3-point scale); likewise, the cumulative freedom from reoperation was not significantly different (94.4% vs 96.8%, P =.38). Follow-up New York Heart Association functional class was significantly better in the patients undergoing the minimally invasive approach (1.5 +/- 0.05 vs 1.2 +/- 0.05, P <.01). CONCLUSIONS: These findings demonstrate comparable 1-year follow-up results after minimally invasive mitral valve reconstruction. Both echocardiographic results and New York Heart Association functional improvements were compatible with results achieved with the standard sternotomy approach. The minimally invasive approach for mitral valve reconstruction provides equally durable results with marked advantages for the patient and should be more widely adopted.

Late results of isolated mitral annuloplasty for "functional" ischemic mitral insufficiency.

BACKGROUND: Repair of functional ischemic mitral regurgitation (MR) due to annular deformity and leaflet restriction remains a challenge for the surgeon and lacks well-documented outcomes. We investigated outcomes in the treatment of functional ischemic MR corrected by annuloplasty techniques alone. METHODS: From May 1980 to July 1999, 174 patients underwent repair for functional ischemic mitral insufficiency with annuloplasty alone (128 ring annuloplasty; 46 suture annuloplasty). Acute insufficiency was present in 25 (14.4%). Concomitant procedures included CABG (n = 152; 87.4%). Patients were studied longitudinally with annual follow-up and echocardiograms. RESULTS: Overall hospital mortality was 17.8% and was increased by NYHA Class 4 (23.8% vs. 8.7%; p = 0.011), diabetes (25.0% vs. 13.6%; p = 0.059), and chronic mitral insufficiency (16.4% vs. 8.0%; p = 0.070). Multivariate analysis revealed age (beta = 0.099; p = 0.049) and ejection fraction < 30% (beta = 1.260; p = 0.097) as significant predictors of hospital death. Mean postoperative mitral insufficiency was 0.84 +/- 0.86 (scale of 0-4). NYHA Class 4 (beta = 2.33; p = 0.034) and simple suture annuloplasty (beta = 2.08; p = 0.07) were associated with increased risk of late cardiac death. Cumulative incidence of mitral reoperation was 7.7% at 5 years. At follow-up, 89.7% of patients were in NYHA Class 1 or 2 with 83.4% having none or only mild mitral insufficiency. CONCLUSIONS: Ring annuloplasty is associated with a survival benefit when compared to simple suture repair in ischemic patients who require annuloplasty alone to correct the MR. Mitral reconstruction with a ring annuloplasty offers durable results in this homogeneous subset of functional ischemic MR patients. Ischemic mitral insufficiency is associated with significant late mortality.

Beating-heart coronary artery bypass grafting for left ventricular failure assisted by the Abiomed BVS 5000.

Two cases of postmyocardial infarction cardiogenic shock were treated with left ventricular assist device (LVAD) implantation. With the left ventricular function bypassed, beating-heart coronary artery bypass grafting (CABG) was performed. This technique may be useful in the setting of acute myocardial dysfunction where limited coronary revascularization is required.

Minimal access reoperative mitral and aortic valve surgery.

Minimally invasive cardiac surgery has allowed surgeons to perform valve procedures with a morbidity and mortality comparable with conventional resternotomy approaches while reducing postoperative ventilatory and intensive care unit requirements and overall hospital length of stay. Additionally, patient satisfaction with rapid recovery, earlier return to work, and improved cosmetic results has pushed the pendulum of reoperative valve surgery towards minimally invasive techniques. We reviewed our institutional data consisting of 129 patients requiring reoperative valve surgery over the past 4 years, which was accomplished using these minimally invasive approaches.

Late results of mitral valve reconstruction in the elderly.

BACKGROUND: This study attempts to confirm favorable results with mitral valve reconstruction (MVP) in patients greater than or equal to 70 years of age and to examine complication rates by actual analysis. METHODS: Between June of 1980 and December of 1997, 278 patients 70 years of age or older (mean, 75.2 years; range, 70 to 87 years) underwent MVP for mitral regurgitation. Most involved insertion of an annuloplasty ring. Concomitant procedures were performed in 72.3%, and 55.0% required coronary revascularization. RESULTS: For isolated MVP, the in-hospital mortality rate was 6.5% and 17.0% when combined with coronary revascularization. The mortality rate when combined with another valve procedure was 13.2%. The 5-year freedom from late cardiac death was 100% in the isolated MVP group and 79.7% for MVP with a concomitant procedure (p = 0.006). Complications were analyzed using actual (cumulative incidence) analysis to eliminate the competing risk of noncardiac death. Mean NYHA class improved from 3.32 to 1.71 postoperatively. Repair failure was rare, with a 5-year freedom from reoperation of 91.2%. CONCLUSIONS: These findings confirm the favorable outcome of MVP in elderly patients. Late repair failures are rare; comorbid disease is an important predictor of outcome.

Robotic-assisted instruments enhance minimally invasive mitral valve surgery.

BACKGROUND: The potential for totally endoscopic mitral valve surgery has been advanced by the development of minimally invasive techniques. Recently surgical robots have offered instrument access through small ports, obviating the need for a significant thoracotomy. This study tested the hypothesis that a microsurgical robot with 5 degrees of freedom is capable of performing an endoscopic mitral valve replacement (MVR). METHODS: Dogs (n = 6) were placed on peripheral cardiopulmonary bypass; aortic occlusion was achieved with endoaortic clamping and transesophageal echocardiographic control. A small left seventh interspace "service entrance" incision was used to insert sutures, retractor blade, and valve prosthesis. Robotically controlled instruments included a thoracoscope and 5-mm needle holders. MVR was performed using an interrupted suture technique. RESULTS: Excellent visualization was achieved with the thoracoscope. Instrument setup required 25.8 minutes (range 12 to 37); valve replacement required 69.3+/-5.39 minutes (range 48 to 78). MVR was accomplished with normal prosthetic valve function and without misplaced sutures or inadvertent injuries. CONCLUSIONS: This study demonstrates the feasibility of adjunctive use of robotic instrumentation for minimally invasive MVR. Clinical trials are indicated.

Predictors of outcome in a multicenter port-access valve registry.

BACKGROUND: The aim of this study was to examine the predictors of outcome in patients undergoing isolated valve operation using port-access techniques. METHODS: Logistic regression analysis was performed in a prospective, multi-institutional registry of patients undergoing isolated aortic valve replacement (AVR, n = 252), mitral repair (MVP, n = 491), or mitral replacement (MVR, n = 568) using port-access techniques from 1997 to 1999. RESULTS: Endoaortic balloon occlusion was used in 2% (AVR), 93% (MVP), and 90% (MVR) of cases. Conversion to full sternotomy occurred in 3.8% of all cases. For all patients, early mortality was 50 of 1,311 (3.8%) and onset of new atrial fibrillation occurred in 140 of 1,311 (11%) patients. The determinants of 30-day mortality were redo, age, and MVR or AVR. The determinants of reoperation for bleeding were age, reoperation, and MVR. Age was a predictor for stroke, and age and low or medium volume center were predictors of new atrial fibrillation. CONCLUSIONS: Excellent short-term results can be obtained using port-access techniques in isolated mitral or aortic valve operations. Patient outcome is not related to institutional case volume, and the primary determinants of outcome after port-access valve procedures are generally patient-related factors.

Assisted venous drainage presents the risk of undetected air microembolism.

OBJECTIVES: The proliferation of minimally invasive cardiac surgery has increased dependence on augmented venous return techniques for cardiopulmonary bypass. Such augmented techniques have the potential to introduce venous air emboli, which can pass to the patient. We examined the potential for the transmission of air emboli with different augmented venous return techniques. METHODS: In vitro bypass systems with augmented venous drainage were created with either kinetically augmented or vacuum-augmented venous return. Roller or centrifugal pumps were used for arterial perfusion in combination with a hollow fiber oxygenator and a 40-micrometer arterial filter. Air was introduced into the venous line via an open 25-gauge needle. Test conditions involved varying the amount of negative venous pressure, the augmented venous return technique, and the arterial pump type. Measurements were recorded at the following sites: pre-arterial pump, post-arterial pump, post-oxygenator, and patient side. RESULTS: Kinetically augmented venous return quickly filled the centrifugal venous pump with macrobubbles requiring continuous manual clearing; a steady state to test for air embolism could not be achieved. Vacuum-augmented venous return handled the air leakage satisfactorily and microbubbles per minute were measured. Higher vacuum pressures resulted in delivery of significantly more microbubbles to the "patient" (P <.001). The use of an arterial centrifugal pump was associated with fewer microbubbles (P =.02). CONCLUSIONS: Some augmented venous return configurations permit a significant quantity of microbubbles to reach the patient despite filtration. A centrifugal pump has air-handling disadvantages when used for kinetic venous drainage, but when used as an arterial pump in combination with vacuum-assisted venous drainage it aids in clearing air emboli.