Background-The optimal timing of surgical intervention in asymptomatic patients with severe mitral regurgitation is unclear. We therefore compared the long-term results of early surgery with a conventional treatment strategy. Methods and Results-From 1996 to 2005, 447 consecutive asymptomatic patients (253 men, age 50Ϯ15 years) with severe degenerative mitral regurgitation and preserved left ventricular function were evaluated prospectively. The end point was defined as the composite of operative mortality, cardiac death, repeat mitral valve surgery, and urgent admission due to congestive heart failure during follow-up. Early surgery was performed on 161 patients (operated group), and the conventional treatment strategy was used for 286 patients (conventional treatment group). There were no significant differences between the 2 groups in terms of age, gender, euroSCORE (European System for Cardiac Operative Risk Evaluation), or ejection fraction. During a median follow-up of 1988 days, there were 2 repeat surgeries and no cardiac deaths or operative mortality in the operated group compared with 12 cardiac deaths, 1 repeat surgery, and 22 admissions for congestive heart failure in the conventional treatment group. The estimated actuarial 7-year cardiac mortality rate was 0% in the operated group and 5Ϯ2% in the conventional treatment group (Pϭ0.008), and for 127 propensity score-matched pairs, the estimated actuarial 7-year event-free survival rate was significantly higher in the operated than in the conventional treatment group (99Ϯ1% versus 85Ϯ4%, Pϭ0.007). In the conventional treatment group, baseline grade of pulmonary hypertension (hazard ratio 1.87, 95% CI 1.22 to 2.87, Pϭ0.003), age (hazard ratio 1.02, 95% CI 1.01 to 1.04, Pϭ0.005), and effective regurgitant orifice area (hazard ratio 2.06, 95% CI 1.11 to 3.82, Pϭ0.02) were independent variables that predicted late development of surgical indications or congestive heart failure on Cox multivariate analysis. Conclusions-Compared with conservative management, the strategy of early surgery was associated with an improved long-term event rate by decreasing cardiac mortality and congestive heart failure hospitalization more effectively in patients with severe degenerative mitral regurgitation. Early surgery may therefore further improve clinical outcomes in asymptomatic severe mitral regurgitation with preserved left ventricular systolic function and a high likelihood of mitral valve repair. (Circulation. 2009;119:797-804.)

Background-The optimal timing of surgical intervention remains controversial in asymptomatic patients with very severe aortic stenosis. We therefore compared the long-term results of early surgery and a conventional treatment strategy. Methods and Results-From 1996 to 2006, we prospectively included a total of 197 consecutive asymptomatic patients (99 men; age, 63Ϯ12 years) with very severe aortic stenosis. Patients were excluded if they had angina, syncope, exertional dyspnea, ejection fraction Ͻ0.50, significant mitral valve disease, or age Ͼ85 years. Very severe aortic stenosis was defined as a critical stenosis in the aortic valve area Յ0.75 cm 2 accompanied by a peak aortic jet velocity Ն4.5 m/s or a mean transaortic pressure gradient Ն50 mm Hg on Doppler echocardiography. The primary end point was defined as the composite of operative mortality and cardiac death during follow-up. Early surgery was performed on 102 patients, and a conventional treatment strategy was used for 95 patients. There were no significant differences between the 2 groups in terms of age, gender, European System for Cardiac Operative Risk Evaluation score, or ejection fraction. During a median follow-up of 1501 days, the operated group had no operative mortalities, no cardiac deaths, and 3 noncardiac deaths; the conventional treatment group had 18 cardiac and 10 noncardiac deaths. The estimated actuarial 6-year cardiac and all-cause mortality rates were 0% and 2Ϯ1% in the operated group and 24Ϯ5% and 32Ϯ6% in the conventional treatment group, respectively (PϽ0.001), and for 57 propensity score-matched pairs, the risk of all-cause mortality was significantly lower in the operated group than in the conventional treatment group (hazard ratio, 0.135; 95% confidence interval, 0.030 to 0.597; Pϭ0.008). Conclusions-Compared with the conventional treatment strategy, early surgery in patients with very severe aortic stenosis is associated with an improved long-term survival by decreasing cardiac mortality. Early surgery is therefore a therapeutic option to further improve clinical outcomes in asymptomatic patients with very severe aortic stenosis and low operative risk. (Circulation. 2010;121:1502-1509.)

LD GCV for CMV prophylaxis may not be inferior to the HD regimen in seropositive HT recipients.

The purpose of our study is to compare haemodynamic responses and the ischaemic potential of commonly used inotropes (dopamine, dobutamine and milrinone) using a computer model of the cardiovascular system. Cardiotropic drugs interact with the model by changing ventricular elastance and resistance of the individual circulation. All three drugs increase cardiac index in a dose-dependent manner. Dopamine at medium and high infusion rates increases heart rate, systemic vascular resistance and arterial blood pressure. The associated increase in coronary blood flow, however, is not sufficient to account for increased oxygen demand. Both dobutamine and milrinone decrease vascular resistance and increase coronary blood flow. The more pronounced increase in heart rate associated with dobutamine, however, results in a higher ischaemic potential for this drug. Our simulation demonstrates that although all the drugs studied improve cardiac function in simulated patients with heart failure, milrinone accomplishes this at a lower energy cost. The computer simulation developed can be used to assess the complex effect of cardiotropic drugs and possibly suggest optimal drug therapy in specific clinical situations.

We are grateful to Meurin et al for their interest in our article, 1 and for raising some concerns. They suggested that the results of our study should not help to justify operations for which real benefit is not proved. There were 3 main issues raised in their letter.First, a registry should not be used to compare 2 therapeutic strategies, because too many biases can be involved; patients in the conventional treatment group probably had serious extra cardiac disease more often, as suggested by a higher rate of noncardiac deaths. We have clearly acknowledged nonrandomized assignment of treatment strategies as the major limitation of our study. To minimize selection bias and confounding, we performed propensity score matching, which has been shown to eliminate a greater proportion of baseline differences than stratification or covariate adjustment. For the 57 propensity score-matched pairs, the risk of all-cause mortality was persistently lower in the early surgery group than in the conventional treatment group (hazard ratio 0.135, 95% confidence interval 0.030 to 0.597, Pϭ0.008), and the risk of noncardiac death was similar between the two groups (hazard ratio 0.773, 95% confidence interval, 0.075 to 7.932, Pϭ0.825). Given that no randomized trial data are available, we suggest that the results of our study should be of clinical value to the decision of treatment strategy.Second, our study does not reflect "real life" practice, because baseline characteristics of our study patients were different from those reported in the Euro Heart Survey. 2 Contrary to the Euro Heart Survey, in which 84% of operated patients had preoperative symptoms, patients with any symptoms were excluded in our study, and the mean age of our study patients (63 years) is similar to that of the previous study (60 years), 3 which consecutively included asymptomatic patients only. The prevalence of coronary artery disease and bicuspid valve in clinical studies is also likely to be different according to age, presence or absence of symptoms, and severity of aortic stenosis. We feel strongly that our study patients represent asymptomatic patients with very severe aortic stenosis encountered in real clinical situations.The third concern focused on the absence of exercise testing. The study by Das et al 4 referenced in the letter reported that among 36 patients who developed symptoms, 72% had symptoms during exercise test, and 67% had very severe aortic stenosis. Further studies are needed to explore whether exercise test might have an additional prognostic value in very severe aortic stenosis.We agree that a prospective randomized comparison trial is required to confirm the results of our study, and look forward to working collaboratively for large multicenter prospective trials. DisclosuresNone. Duk