松村 貴由

BACKGROUND: Functional mitral regurgitation (MR) is one of the common and severe complications in patients with dilated cardiomyopathy. The detailed mechanisms that cause functional MR remain to be elucidated. Using two-dimensional transthoracic echocardiography, we investigated the differences in major determinants of MR severity between ischemic cardiomyopathy (ICM) and non-ICM patients. METHODS: We enrolled 103 patients (91 males; age 64+/-12 years) with significant left ventricular (LV) dilatation. They were divided into ICM group (n=69) with significant coronary disease, and non-ICM (n=34) group without coronary disease. We devised a novel and simple parameter; the short-axis sphericity index (SI), to evaluate global LV remodeling, and used coaptation depth (CD) and tenting area (TA) to evaluate mitral deformity. RESULTS: In all cases, CD, TA and left atrium diameter (LAD) correlated positively with maximum regurgitation area (MRA) (r=0.54, 0.57, 0.57; P<0.0001). A negative correlation was observed between MRA and SI (r=-0.33, P=0.0008). There was no significant relationship between MRA and LV ejection fraction (EF). In non-ICM cases, SI tended to be lower with reduced EF. Multivariate stepwise linear regression analysis showed the following equations; ICM: MRA=-9.4+0.81CD+0.21LAD (r2=0.47, P<0.0001), non-ICM: MRA=-7.2+0.17LVDs (LV end systolic diameter) -8.7SI+0.27LAD (r2=0.63, P<0.0001). CONCLUSIONS: The strongest determinants of functional MR severity differ in ICM and non-ICM. While LV diameter and SI (global LV remodeling index) mainly determine the severity in non-ICM, CD that reflects mitral deformity is the major determinant in ICM.

AIMS: To examine the impact of pre-operative atrial fibrillation (AF) on the outcome of mitral valve repair (MVR) for degenerative mitral regurgitation (MR). METHODS AND RESULTS: Among 392 patients with moderate to severe MR who underwent MVR between 1991 and 2002, 283 patients with isolated degenerative MR were followed for 4.7+/-3.3 years. Of 27 deaths, nine were due to cardioembolic events and four were due to left ventricular (LV) dysfunction. When compared with patients with pre-operative AF, those with sinus rhythm (SR) had better survival (96+/-2.1 vs. 87+/-3.2% at 5 years, P=0.002) and higher cardiac event-free rates (96+/-2.0 vs. 75+/-4.4% at 5 years, P<0.001). In patients with pre-operative SR, observed and expected survival were similar (P=0.811). Cox multivariable regression analysis confirmed AF [P=0.027, adjusted hazard ratio (AHR) 2.9] and age as independently predictive of survival, and AF (P=0.002, AHR 3.1), New York Heart Association Class, and LV fractional shortening as independently predictive of cardiac event. CONCLUSION: Death due to LV dysfunction was not frequent and cardioembolic events due to AF were the leading cause for cardiac death. Pre-operative AF became a strong independent predictor of survival and morbidity. Patients with pre-operative SR had excellent prognosis. The benefits of preventing cardioembolic events due to AF validate the indication of MVR for patients with high risk for AF.

The Krüppel-like factor (KLF) family is a recently highlighted group of zinc finger transcription factors given their important biological roles which include the vasculature. KLF2, KLF4, KLF5, and KLF6 are notable factors that have been implicated in developmental as well as pathological vascular processes. In this brief review, we provide an up-to-date summary of the physiological functions and cellular effects as well as transcriptional regulatory mechanisms of the vascular KLFs. Through such, we aim to provide a working view for understanding the pathological actions of KLFs in the vasculature.

Transcriptional regulation in eukaryotes requires an understanding of the regulation of the chromatin structure. Chromatin is the eukaryotic-specific packaging/compaction of DNA with nucleosomal histones. This present review discusses recent advancements made in the field of chromatin-associated transcriptional regulation and their implications to the cardiovasculature.

The optimal timing of surgical correction of severe mitral regurgitation (MR) is important for improved morbidity and mortality. We utilized a scoring system to decide the timing of procedures. Based on clinical features and echocardiographic data, we hypothesized that preoperative semi-quantitation of MR using this scoring system may be useful for predicting prognosis after repair. The MR score was composed of 6 parameters associated with disease severity (i.e., history of heart failure, atrial fibrillation, pulmonary hypertension, left ventricular end-systolic dimension, fractional shortening, and left atrial dimension). The maximum score was 6. Of 267 patients who underwent mitral valve repair in the last 10 years, 191 patients with mitral valve prolapse were studied. Patients were categorized into 2 groups according to MR score (group low [L] : 0 to 2.5 and group high [H]: >/=3.0) irrespective of New York Heart Association functional class. A significant difference in postoperative event-free survival was observed between both groups (p = 0.0014); the adjusted risk ratio was 3.4 (95% confidence interval 1.6 to 7.2). Postoperative echocardiography showed larger left ventricular systolic dimensions (p <0.0001), lower fractional shortening (p = 0.0016), and larger left atrial dimensions (p <0.0001) in group H than group L. Thus, an MR score is a simple way to predict the prognosis of severe MR independently of subjective symptoms in patients undergoing mitral valve repair.

OBJECTIVES: This study sought to determine whether echocardiography before mitral valve repair (MVR) for mitral regurgitation (MR) was predictive of postoperative left ventricular (LV) dysfunction and useful for deciding the optimal timing of repair. BACKGROUND: Some reports have shown that the preoperative echocardiographic data of left ventricular ejection fraction (LVEF) and left ventricular end-systolic diameter (LVDs) were good predictors of postoperative LV dysfunction. However, few reports were based on long-term follow-up data of large numbers of patients who underwent MVR in the last decade. METHODS: A total of 274 patients with moderate or severe MR underwent MVR between October 1, 1991, and September 30, 2000. Among them, 171 patients who had both an operation for isolated MR due to degenerative pathology and a postoperative echocardiogram were studied. Postoperative echocardiograms were performed 3.9 +/- 2.4 years after the operation. The LVEF decreased from 66 +/- 10% before surgery to 63 +/- 11% after surgery (p < 0.0001). On univariate analysis, preoperative LVEF and LVDs correlated with postoperative LVEF (r = 0.41 and r = -0.39, respectively). Overall, postoperative LV dysfunction (defined as LVEF <50%) was not frequent (12%). However, the incidence of postoperative LV dysfunction was high in patients with preoperative LVEF <55% (38%) or LVDs > or =40 mm (23%). CONCLUSIONS: In patients with MR, the echocardiographic data of LVEF and LVDs were good predictors of postoperative LV dysfunction. When a decrease in LVEF or an increase in LVDs is detected, MVR should be considered to preserve postoperative LV function.

BACKGROUND: Recent studies on the etiology of aortic valve disease in the US showed a decrease in rheumatic valve disease and an increase in age-related degenerative disease. The purpose of this study was to describe the etiology of aortic valve disease and its temporal changes in Japan, based on a large number of cases. METHODS: The medical charts of all patients who underwent aortic valve replacement at our institute between 1977 and 1999 were reviewed. Among the 600 patients analyzed, 213 (36%) had pure aortic stenosis, 265 (44%) had pure aortic regurgitation, and 122 (20%) had combined stenosis and regurgitation. RESULTS: The causes were rheumatic change (49%), degenerative change (19%), bicuspid valves (18%), infective endocarditis (5%) and others (9%). Rheumatic disease continued to be the most common cause of aortic stenosis, but its frequency decreased from 100% in 1977-1979 to 37% in 1995-1999. In contrast, the frequency of degenerative change among stenotic valves increased recently from 11% in 1990-1994 to 30% in 1995-1999. Similarly, rheumatic disease remained to be the leading cause of aortic regurgitation, with a decline in frequency from 46% in 1985-1989 to 27% in 1995-1999. The percentage of degenerative change among regurgitant valves did not change appreciably. CONCLUSIONS: There was a shift in the causes of aortic valve disease, with a decrease in rheumatic disease and an increase in degenerative disease. This trend was similar to that observed in the US. These findings suggest the increasing importance of aortic valve disease due to degenerative change.

OBJECTIVES: Whether beta-blocker therapy changes the circulating levels of cytokines as congestive heart failure improves remains uncertain. METHODS: Nine patients with idiopathic dilated cardiomyopathy, who had previously received conventional treatment and were classified as New York Heart Association (NYHA) functional class II, received carvedilol by stepwise dose increase up to 20 mg daily, and the plasma interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) levels were measured. RESULTS: IL-6 was significantly reduced from 0.80 +/- 0.49 pg/ml before therapy to 0.21 +/- 0.08 pg/ml after carvedilol was increased to 20 mg daily (p < 0.05). Moreover, IL-6 level had already decreased significantly compared to the baseline when the dose of carvedilol had reached 10 mg daily (0.28 +/- 0.12 pg/ml, p < 0.05). TNF-alpha levels did not change significantly. CONCLUSIONS: These results demonstrate that IL-6 concentration is significantly decreased by beta-blocker therapy. The efficacy for heart failure may be related to the change of IL-6 concentration.