Orszulak, Thomas A.

BackgroundMitral valve repair has been suggested as providing a better postoperative outcome than valve replacement for mitral regurgitation, but this impression has been obscured by differences in baseline characteristics and has not been confirmed in multivariate analyses.Methods and ResultsThe outcomes in 195 patients with valve repair and 214 with replacement for organic mitral regurgitation were compared using multivariate analysis. All patients had preoperative echocardiographic assessment of left ventricular function. Before surgery, patients with valve repair were less symptomatic than those with replacement (42% in New York Heart Association functional class I or II versus 24%, respectively;P=.001), had less atrial fibrillation (41% versus 53%;P=.017), and had a better ejection fraction (63±9% versus 60±12%,P=.016). After valve repair, compared with valve replacement, overall survival at 10 years was 68±6% versus 52±4% (P=.0004), overall operative mortality was 2.6% versus 10.3% (P=.002), operative mortality in patients under age 75 was 1.3% versus 5.7% (P=.036), and late survival (in operative survivors) at 10 years was 69±6% versus 58±5% (P=.018). Late survival after valve repair was not different from expected survival. After surgery, ejection fraction decreased significantly in both groups but was higher after valve repair (P=.001). Multivariate analysis indicated an independent beneficial effect of valve repair on overall survival (hazard ratio, 0.39;P=.00001), operative mortality (odds ratio, 0.27;P=.026), late survival (hazard ratio, 0.44;P=.001), and postoperative ejection fraction (P=.001).ConclusionsValve repair significantly improves postoperative outcome in patients with mitral regurgitation and should be the preferred mode of surgical correction. The low operative mortality is an incentive for early surgery before ventricular dysfunction occurs.

BACKGROUND Left ventricular dysfunction is a frequent cause of death after successful surgical repair of mitral regurgitation. The role of preoperative echocardiographic left ventricular variables in the prediction of postoperative survival and thus their clinical implications remain uncertain. METHODS AND RESULTS The survival of 409 patients operated on between 1980 and 1989 for pure, isolated, organic mitral regurgitation and with a preoperative echocardiogram (within 6 months of operation) was analyzed. The overall survival was 75% at 5 years (90% of expected), 58% at 10 years (88% of expected), and 44% at 12 years (73% of expected). Operative mortality was 6.6% and markedly improved from 1980 to 1984 (10.7%) to 1985 to 1989 (3.7%). Multivariate analysis showed that age (P = .0003), date of operation (P = .003), and functional class (P = .016) but not left ventricular function were predictors of operative mortality. In the most recent period (1985 to 1989), operative mortality was 12.3% in patients age 75 years or older and 1.1% in patients younger than 75 years. Late survival was analyzed in the operative survivors. Multivariate analysis showed that the most powerful predictor was echocardiographic ejection fraction (EF) (P = .0004), followed by age (P = .0031), creatinine level (P = .0062), systolic blood pressure (P = .0164), and presence of coronary artery disease (P = .0237). The late survival at 10 years was 32 +/- 12% for patients with EF < 50%, 53 +/- 9% for EF 50% to 60%, and 72 +/- 4% for EF > or = 60%. The hazard ratio compared with EF > or = 60% was 2.79 (95% confidence interval, 1.65 to 4.72) for EF < 50% and 1.81 (95% confidence interval, 1.11 to 2.95) for EF 50% to 60%. Echocardiographic EF remained the best predictor of late survival, even when combined with left ventricular angiographic variables. The survival of patients with EF > or = 60% was 100% of expected at 10 years but was better in patients in class I or II than in those in class III or IV (82 +/- 6% versus 59 +/- 6%, respectively, at 10 years; P = .0021). The preoperative predictors of operative and late mortality remained significant independent of the type of surgical correction performed in combined multivariate analyses. CONCLUSIONS In organic mitral regurgitation, (1) operative mortality has markedly decreased recently, being at a low 1.1% in patients younger than 75 years, and is predicted by age and symptoms and not by left ventricular function, and (2) left ventricular EF measured by echocardiography is the most powerful predictor of late survival. These results suggest that surgical treatment should be considered early, even in the absence of severe symptoms, in patients with severe mitral regurgitation, before left ventricular dysfunction occurs.

Background —Surgical correction of mitral regurgitation in patients with no or mild symptoms remains controversial, particularly because the impact of preoperative symptoms on postoperative outcome is unknown. Methods and Results —The long-term outcome of 478 patients with organic mitral regurgitation (199 in NYHA functional class I/II and 279 in class III/IV before surgery) operated on between 1984 and 1991 was analyzed. In patients in NYHA class I/II before surgery compared with those in class III/IV, postoperative long-term survival was higher (at 10 years, 76±5% versus 48±4%, P <0.0001), with lower operative mortality (0.5% versus 5.4%, P =0.003) and better late survival ( P <0.0001). Comparison of observed and expected survival showed identical curves in patients in class I/II before surgery ( P =0.18), whereas excess mortality was observed in patients in class III/IV before surgery ( P <0.0001). Excess mortality associated with severe symptoms was also confirmed in all subgroups (all P <0.003) and in multivariate analysis ( P =0.0036; adjusted hazard ratio [95% CI], 1.81 [1.21 to 2.70]). Conclusions —In patients with organic mitral regurgitation, preoperative functional class III/IV symptoms are associated with excess short- and long-term postoperative mortality independently of all baseline characteristics. These data should lead to consideration of surgical correction of severe organic mitral regurgitation when no or minimal symptoms are present in patients at low operative risk, especially if repair is feasible.

To evaluate the short-term results of percutaneous aortic balloon valvuloplasty, 55 consecutive elderly patients with symptomatic, severe aortic stenosis who were at high risk for surgical intervention underwent the procedure, with follow-up by clinical evaluation and Doppler echocardiography. Over a mean follow-up of 6.2 months, there were three early deaths (less than 30 days) and eight late deaths. Nine patients underwent subsequent aortic valve surgery, and four had repeat balloon valvuloplasty. Doppler echocardiography revealed a reduction in aortic valve mean gradient from 48 +/- 18 to 33 +/- 12 mm Hg after the procedure (p less than 0.0001) but a return to 46 +/- 16 mm Hg at follow-up (p less than 0.05). The aortic valve area increased from 0.54 +/- 0.15 to 0.85 +/- 0.23 cm2 after the procedure (p less than 0.0001), but there was a significant decrease to 0.67 +/- 0.19 cm2 at follow-up (p less than 0.05). Of patients free of aortic valve operation or death after 30 days after the procedure, 76% were severely symptomatic before the procedure as compared with 38% at follow-up. In patients undergoing percutaneous aortic balloon valvuloplasty, there is a continued high short-term mortality and a significant incidence of restenosis over short-term follow-up. Nonetheless, a subset of patients do experience sustained clinical improvement from this procedure.

Background and Purpose— Embolic events have long been thought to occur in patients with cardiac tumors secondary to embolization of tumor fragments; however, there are no large studies examining the epidemiology and occurrence of embolism in this group of patients. Methods— From 1957 to 2006, 323 consecutive patients with primary cardiac tumors were treated surgically at our institution. Of these, patients who experienced an embolic event included 80 (cerebrovascular accident 31 [9.7%], transient ischemic attack 30 [9.3%], and other 19 [6%]). Those with no history of an embolic event (n=243 [75%]) were defined as control subjects. Results— Age was similar between the case and control groups (mean 54.5 versus 53.9 years, P =0.8). A multivariate logistic regression model including tumor location, tumor burden, tumor histology, and cerebrovascular risk factors, indicated that left atrial tumors (OR, 1.95; P =0.04), aortic valve tumors (OR, 4.17; P =0.002), and smaller tumor burden (OR, 2.20; P =0.01) were the most significant factors in the occurrence of embolism ( P <0.001). The presence of mitral regurgitation (OR, 0.12; P =0.006) and decreased functional status (New York Heart Association III/IV; OR, 0.31; P <0.001) were protective against the occurrence of embolism. Follow-up was obtained in 82% at a mean follow-up time of 6.17±6.9 years. There were no recurrent embolic events at follow-up. A Kaplan-Meier survival curve demonstrated no difference in survival between both groups ( P =0.78). Conclusion— Aortic valve and left atrial tumors have the greatest anatomic risk for embolism. Furthermore, patients with smaller tumors, minimal symptomatology, and no evidence of mitral regurgitation have a high risk of embolism. Cardiac tumors can be resected with low early mortality, and late survival after operation in the context of an embolic event is similar to patients with cardiac tumors who undergo resection for other indications.

Background— Primary cardiac tumors are rare but have the potential to cause significant morbidity if not treated in an appropriate and timely manner. To date, however, there have been no studies examining survival characteristics of patients who undergo surgical resection. Methods and Results— From 1957 to 2006, 323 consecutive patients underwent surgical resection of primary cardiac tumors; 163 (50%) with myxomas, 83 (26%) with papillary fibroelastomas, 18 (6%) with fibromas, 12 (4%) with lipomas, 28 (9%) with other benign primary cardiac tumors, and 19 (6%) with primary malignant tumors. Operative (30 day) mortality was 2% (n=6). Univariate analysis indicated that patients who underwent resection of fibromas and myxomas had superior survival characteristics in comparison to the remainder of tumor variants; these results were consistent after adjusting for age at surgery, year of surgery, and cardiovascular risk factors. Based on actuarial characteristics of the 2002 U.S. population, patients who underwent myxoma resection had survival characteristics that were not significantly different from that of an age and gender matched population (SMR 1.11, P =0.57) whereas those who underwent resection of fibromas (SMR 11.17, P =0.002), papillary fibroelastomas (SMR 3.17, P =0.0003), lipomas (SMR 5.0, P =0.0003), other benign tumors (SMR 4.63, P =0.003), and malignant tumors (SMR 101, P <0.0001) had significantly poorer survival characteristics. Furthermore, malignant tumors in younger patients were highly fatal (HR 0.899, P <0.0001). Although the most significant predictor of mortality was tumor histology, survival was also influenced the by the duration of CPB and NYHA III/IV; the impact of these risk factors varied with time. The cumulative incidence of myxoma recurrence was 13% and occurred in a younger population (42 versus 57 years, P =0.003) with the risk of recurrence decreased after 4 years. Conclusions— Surgical resection of primary cardiac tumors is associated with excellent long-term survival; patients with cardiac myxomas have survival characteristics that are not significantly different from that of a general population. Predictors of mortality are primarily related to tumor histology but also include clinical characteristics such as symptomatology and duration of CPB.

Background— This study evaluated long-term results of aortic root replacement and valve-preserving aortic root reconstruction for patients with aneurysms involving the aortic root. Methods and Results— Two-hundred three patients aged 53±16 years (mean±SD; 153 male, 50 female) underwent elective or urgent aortic root surgery from 1971 to 2000 for an aortic root aneurysm: 149 patients underwent a composite valve conduit reconstruction, and 54 patients underwent valve-preserving aortic root reconstruction. Fifty patients had Marfan syndrome. In-hospital and 30-day mortality was 4.0% (8/203) overall: for a composite valve conduit procedure, the corresponding value was 4.0% (6/149) and for valve-preserving procedure, 3.7% (2/54) ( P =NS). Morbidity included 3 strokes (1%), 10 perioperative myocardial infarctions (5%), and 8 reoperations for bleeding (4%). Actuarial survival at 5, 10, 15, and 20 years was 93% (95% confidence interval [CI] = 88% to 97%), 79% (95% CI = 71% to 87%), 67% (95% CI = 57% to 79%), and 52% (95% CI = 36% to 69%), respectively. Freedom from reoperation was 72% (95% CI = 54% to 86%) at 20 years. Complications with anticoagulation occurred in 29 patients; with valve thrombosis, in 2; and with hemorrhage, in 27 (4 life threatening and 23 minor). Freedom from thromboembolism was 91% (95% CI = 77% to 98%) at 20 years. Freedom from endocarditis was 99% (95% CI = 92% to 100%) at 20 years. Multivariate analysis revealed preoperative mitral valve regurgitation (+3 to 4) and older age to be significant predictors of late death ( P ≤0.005), and Marfan syndrome, initial valve-preserving aortic root reconstruction, and need for a concomitant procedure at initial operation to be significant predictors of the need for reoperation ( P ≤0.01). Conclusions— Aortic root replacement for aortic root aneurysms can be done with low morbidity and mortality. Composite valve conduit reconstruction resulted in a durable result. There were few serious complications related to the need for long-term anticoagulation or a prosthetic valve. Reoperation was most commonly required because of failure of the aortic valve when a valve-preserving aortic root reconstruction was performed or for other cardiac or aortic disease elsewhere.

Background Activation of the inflammatory cascade is thought to account for some of the respiratory dysfunction and prolonged mechanical ventilation associated with cardiopulmonary bypass. The objective of this investigation was to identify whether perioperative steroids or hemofiltration during cardiopulmonary bypass, by their attenuation of inflammation, would reduce duration of mechanical ventilation after cardiac surgery. Methods After Institutional Review Board approval and informed consent, 192 patients scheduled to undergo elective primary coronary artery bypass grafting or valvular replacement or repair were randomized in a double-blind prospective study into three groups. One group (Control) received saline at induction and at 6-h intervals for four doses. Another group (Hemofil) received saline and hemofiltration to obtain 27 ml/kg of hemofiltrate. The final group (Steroid) received 1 g methylprednisolone before anesthesia induction and then 4 mg of dexamethasone at 6-h intervals for four doses. All patients underwent normothermic cardiopulmonary bypass and received propofol for postoperative sedation. Separate two-sample comparisons were performed to compare each experimental group versus the control group using the Wilcoxon rank sum test for continuous variables and Fisher exact test for categorical variables. In all cases, two-tailed P values </= 0.05 were considered statistically significant. Results The median time until the patient reached an intermittent mandatory ventilation of 4/min (258.5 versus 385.0 min, respectively; P = 0.02) and tracheal extubation (352.0 versus 518.0 min; P = 0.03) was significantly reduced for group Hemofil but no different for Steroid compared to Control. Conclusions Hemofiltration and steroids are both previously reported to attenuate the inflammatory response but only hemofiltration reduced time to tracheal extubation for adults after cardiopulmonary bypass in this study.

Background Aprotinin and tranexamic acid are routinely used to reduce bleeding in cardiac surgery. There is a large difference in agent price and perhaps in efficacy. Methods In a prospective, randomized, partially blinded study, 168 cardiac surgery patients at high risk for bleeding received either a full-dose aprotinin infusion, tranexamic acid (10-mg/kg load, 1-mg x kg(-1) x h(-1) infusion), tranexamic acid with pre-cardiopulmonary bypass autologous whole-blood collection (12.5% blood volume) and reinfusion after cardiopulmonary bypass (combined therapy), or saline infusion (placebo group). Results There were complete data in 160 patients. The aprotinin (n = 40) and combined therapy (n = 32) groups (data are median [range]) had similar reductions in blood loss in the first 4 h in the intensive care unit (225 [40-761] and 163 [25-760] ml, respectively; P = 0.014), erythrocyte transfusion requirements in the first 24 h in the intensive care unit (0 [0-3] and 0 [0-3] U, respectively; P = 0.004), and durations of time from end of cardiopulmonary bypass to discharge from the operating room (92 [57-215] and 94 [37, 186] min, respectively; P = 0.01) compared with the placebo group (n = 43). Ten patients in the combined therapy group (30.3%) required transfusion of the autologous blood during cardiopulmonary bypass for anemia. Conclusions The combination therapy of tranexamic acid and intraoperative autologous blood collection provided similar reduction in blood loss and transfusion requirements as aprotinin. Cost analyses revealed that combined therapy and tranexamic acid therapy were the least costly therapies.

Background— Calcific aortic stenosis is the third most common cardiovascular disease in the United States. We hypothesized that the mechanism for aortic valve calcification is similar to skeletal bone formation and that this process is mediated by an osteoblast-like phenotype. Methods and Results— To test this hypothesis, we examined calcified human aortic valves replaced at surgery (n=22) and normal human valves (n=20) removed at time of cardiac transplantation. Contact microradiography and micro-computerized tomography were used to assess the 2-dimensional and 3-dimensional extent of mineralization. Mineralization borders were identified with von Kossa and Goldner’s stains. Electron microscopy and energy-dispersive spectroscopy were performed for identification of bone ultrastructure and CaPO 4 composition. To analyze for the osteoblast and bone markers, reverse transcriptase–polymerase chain reaction was performed on calcified versus normal human valves for osteopontin, bone sialoprotein, osteocalcin, alkaline phosphatase, and the osteoblast-specific transcription factor Cbfa1. Microradiography and micro-computerized tomography confirmed the presence of calcification in the valve. Special stains for hydroxyapatite and CaPO 4 were positive in calcification margins. Electron microscopy identified mineralization, whereas energy-dispersive spectroscopy confirmed the presence of elemental CaPO 4 . Reverse transcriptase–polymerase chain reaction revealed increased mRNA levels of osteopontin, bone sialoprotein, osteocalcin, and Cbfa1 in the calcified valves. There was no change in alkaline phosphatase mRNA level but an increase in the protein expression in the diseased valves. Conclusions— These findings support the concept that aortic valve calcification is not a random degenerative process but an active regulated process associated with an osteoblast-like phenotype.