Schaff, Hartzell V.

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 beta-Atrial natriuretic factor (beta-ANF) is an antiparallel dimer of alpha-ANF (alpha-ANF) with diminished cyclic GMP generation in vitro. To date, the presence of beta-ANF in the circulation of humans with severe congestive heart failure (CHF) remains controversial. The current study was designed to determine the presence and magnitude of circulating beta-ANF in severe CHF, to correlate plasma beta-ANF with the degree of ventricular dysfunction, and to investigate the role of human plasma and atrial tissue in the degradation of beta-ANF. METHODS AND RESULTS Venous plasma samples were obtained from patients (n = 12) with severe CHF and normal volunteers (n = 8). Total plasma ANF was measured by radioimmunoassay. alpha-ANF and beta-ANF in nonextracted plasma were separated by gel filtration chromatography using a P-6 column. Right atrial tissue samples (n = 5) were collected from a different group of patients at the time of open-heart surgery. 125I beta-ANF and I125 ANF were incubated with atrial tissue or plasma. The corresponding peak areas of beta-ANF were determined by Tamaya Digital Planimeter. beta-ANF represented 61% of total plasma ANF in CHF patients and was not detected in normal human plasma. The elevation of beta-ANF correlated with the severity of ventricular dysfunction. Thirty percent of beta-ANF and 100% alpha-ANF were converted to smaller peptide fragments in atrial tissue no conversion in plasma. CONCLUSIONS beta-ANF is the principal form of circulating ANF in patients with severe CHF and correlates with the degree of left ventricular dysfunction. beta-ANF is not generated from alpha-ANF and may be degraded rapidly in atrial tissue to smaller peptide fragments that do not occur in plasma. As beta-ANF is reported to have reduced biological action, the current studies may support the conclusion that the ANF system in CHF has reduced functional activity despite increases in circulation concentrations.

BACKGROUND Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) are a family of structurally related peptides that participate in the integrated control of renal and cardiovascular function. Previous studies suggest a functional role for these hormonal peptides in cardiorenal regulation in congestive heart failure (CHF). METHODS AND RESULTS The present studies were performed in normal subjects (n = 6) and in patients with mild (New York Heart Association [NYHA] class I to II, n = 20) and severe (NYHA class III to IV, n = 20) CHF by use of radioimmunoassay and immunohistochemical staining (IHCS). Plasma ANP was significantly increased in both mild and severe CHF compared with normal subjects. In contrast, plasma BNP was only moderately increased in the severe CHF group, and plasma CNP concentration was unchanged in CHF compared with normal subjects. Atrial tissue concentrations of the natriuretic peptides did not parallel circulating concentrations. ANP predominated in normal atrial tissue, but BNP predominated in CHF. In ventricular tissue, IHCS staining was present for all three peptides in normal ventricular myocardium and was markedly enhanced in CHF. CONCLUSIONS These studies support a differential regulation of ANP, BNP, and CNP circulating concentrations and tissue activity in human CHF.

BACKGROUND Complete revascularization after coronary artery bypass surgery is a logical goal and improves symptomatic outcome and survival. However, the impact of complete revascularization in patients with three-vessel coronary disease with varying severities of angina and left ventricular dysfunction has not been clearly defined. METHODS AND RESULTS The study was performed as a retrospective analysis of 3,372 nonrandomized surgical patients from the Coronary Artery Surgery Study (CASS) Registry who had three-vessel coronary disease. Group 1 (894 patients) had class I or II angina (Canadian Cardiovascular Society criteria) and group 2 (2,478 patients) had class III or IV angina. In group 1, adjusted cumulative 4-year survivals according to the number of vessels bypassed were 85% (one vessel), 94% (two vessels), 96% (three vessels), and 96% (more than three vessels) (log rank, p = 0.022). Adjusted event-free survival (death, myocardial infarction, definite angina, or reoperation) was not influenced by the number of vessels bypassed, nor was the anginal status among patients remaining alive after 5 years. In group 2, adjusted cumulative 5-year survivals were 78% (one vessel), 85% (two vessels), 90% (three vessels), and 87% (more than three vessels) (log rank, p = 0.074). Adjusted event-free survivals after 6 years were 23% (one vessel), 23% (two vessels), 29% (three vessels), and 31% (more than three vessels) (p = 0.025); at 5 years, those with more complete revascularization were more likely to be asymptomatic or free of severe angina. Among group 2 patients with ejection fractions less than 0.35, 6-year survival was 69% for those with grafts to three or more vessels versus 45% for those with grafts to two vessels (p = 0.04). Placing grafts to three or more vessels was independently associated with improved survival and event-free survival in group 2 but not group 1 patients. The case-fatality rates among 529 patients experiencing a myocardial infarction during follow-up was significantly higher for patients with less complete revascularization. CONCLUSIONS Complete revascularization (grafts to three or more vessels) in patients with three-vessel coronary disease appears to most benefit those with severe angina and left ventricular dysfunction.

BACKGROUND When used to reverse the anticoagulant effect of heparin, protamine sulfate often causes vasodilation that can lead to systemic hypotension. Protamine is rich in the basic amino acid arginine, which is the precursor of endothelial cell synthesis of nitric oxide, and nitric oxide is the active component of endothelium-derived relaxing factor (EDRF). METHODS AND RESULTS To determine whether the hypotensive effect of protamine could be due to stimulated release of EDRF, we studied rings (4-5 mm) of canine coronary, femoral, and renal artery suspended in organ chambers containing physiological salt solution (37 degrees C and 95% O2-5% CO2). Arterial rings with and without endothelium were contracted with prostaglandin F2 alpha (2 x 10(-6) M) and exposed to increasing concentrations of protamine (final organ bath concentration, 40-400 micrograms/ml). In arterial segments without endothelium, protamine caused only a modest decrease in tension. However, protamine induced concentration-dependent relaxation in all arterial segments with endothelium, which was significantly greater than in segments without endothelium (p less than 0.05). The endothelium-dependent relaxation induced by protamine was inhibited by NG-monomethyl-L-arginine (L-NMMA) (10(-5) M), but L-NMMA had no effect on rings without endothelium. The action of L-NMMA could be reversed by L-arginine (10(-4) M) but not D-arginine (10(-4) M). CONCLUSIONS This study demonstrates that protamine stimulates the release of EDRF from arterial endothelium, and that endothelium-dependent vasodilation may be an important cause of systemic hypotension during protamine infusion.

BACKGROUND Maroteaux-Lamy syndrome is a lysosomal storage disease of mucopolysaccharide metabolism (MPS type VI) that may involve the mitral and aortic valves. Affected patients have other skeletal and oropharyngeal malformations that complicate anesthetic and surgical management. METHODS AND RESULTS The present report describes the clinical, echocardiographic, and pathological findings in four patients with Maroteaux-Lamy syndrome. Two of three siblings underwent successful double-valve replacement for aortic and mitral valve stenoses. The third sibling, whose aortic and mitral valves were thick and fibrotic, died from septicemia after hip surgery. A fourth, unrelated patient also had successful double-valve replacement. CONCLUSIONS Our experience emphasizes the potential difficulties in preoperative assessment and surgical treatment as well as the unique problems related to airway management in patients with this syndrome.

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.

Background —The outcome of aortic regurgitation conservatively followed in clinical practice is poorly defined. Methods and Results —Long-term outcome of 246 patients with severe or moderately severe aortic regurgitation diagnosed by color Doppler echocardiography was analyzed. With conservative management, mortality rate was higher than expected (at 10 years, 34±5%, P <0.001) and morbidity was high (10-year rates of 47±6% for heart failure and 62±4% for aortic valve surgery). At 10 years, 75±3% of patients had died or had surgery and 83±3% had had cardiovascular events. In multivariate analysis, predictors of survival were age ( P <0.001), functional class ( P <0.001), comorbidity index ( P =0.033), atrial fibrillation ( P =0.002), and left ventricular end-systolic diameter corrected for body surface area ( P =0.025). Ejection fraction was also an independent predictor of overall survival, including postoperative follow-up of surgically treated patients ( P <0.001). High risk during conservative treatment, with mortality rate in excess of that expected, was noted among patients with severe, even transient, symptoms (24.6% yearly, P <0.001) but also in those with mild (class II) symptoms (6.3% yearly, P =0.02) and in asymptomatic patients with left ventricular ejection fraction <55% (5.8% yearly, P =0.03) or with end-systolic diameter normalized to body surface area ≥25 mm/m 2 (7.8% yearly, P =0.004). Surgery performed during follow-up was independently associated with reduced cardiovascular mortality (adjusted hazard ratio, 0.54; P =0.048). Conclusions —Patients diagnosed with severe aortic regurgitation in clinical practice incur excess mortality and high morbidity, underscoring the serious prognosis of the disease. Surgery, which reduces cardiac mortality rates, should be considered promptly in high-risk patients.

Background —The outcome of aortic valve replacement in patients with severe aortic stenosis, low transvalvular gradient, and severe left ventricular dysfunction is not well known. Methods and Results —Between 1985 and 1995, 52 patients with left ventricular ejection fraction (EF) ≤35% and aortic stenosis with transvalvular mean gradient <30 mm Hg underwent aortic valve replacement. The mean (±SD) preoperative characteristics included EF, 26±8%; aortic valve mean gradient, 23±4 mm Hg; aortic valve area, 0.7±0.2 cm 2 ; and cardiac output, 3.7±1.2 L/min. Simultaneous coronary artery bypass graft surgery was performed in 32 patients (62%). Perioperative (30-day) mortality was 21% (11 of 52 patients). Ten additional patients died during follow-up. Advanced age ( P =0.048) and small aortic prosthesis size ( P =0.03) were significant predictors of hospital mortality by univariate analysis. By multivariate analysis, the only predictor of surgical mortality was smaller prosthesis size. The only predictor of postoperative survival was improvement in postoperative functional class ( P =0.04). Postoperative functional improvement occurred in most patients. Postoperative EF was assessed in 93% of survivors; 74% demonstrated improvement. Positive change in EF was related to smaller preoperative aortic valve area and female sex. Conclusions —Despite severe left ventricular dysfunction, low transvalvular mean gradient, and increased operative mortality, aortic valve replacement was associated with improved functional status. Postoperative survival was related to younger patient age and larger aortic prosthesis size, and medium-term survival was related to improved postoperative functional class.