Noninvasive detection of total occlusion of the left anterior descending coronary artery with transthoracic Doppler echocardiography.

OBJECTIVES: The purpose of this study was to evaluate the value of transthoracic Doppler echocardiography (TTDE) for the noninvasive detection of total left anterior descending coronary artery (LAD) occlusion. BACKGROUND: Total coronary occlusion is associated with an adverse long-term prognosis, and mechanical revascularization may be required for the patient with total coronary occlusion. However, a noninvasive diagnosis of total coronary occlusion before coronary angiography (CAG) has been difficult, especially in patients without clinical signs. METHODS: We studied 103 consecutive patients who underwent CAG for the evaluation of coronary artery disease. The study group consisted of 16 patients with total LAD occlusion (group A) and 87 patients without total LAD occlusion (group B). Coronary flow velocity in the mid-portion of the LAD was recorded by TTDE. RESULTS: Adequate spectral Doppler recordings of diastolic flow in the LAD were obtained in 98 study patients (95%; 15 patients in group A and 83 patients in group B). In group A, retrograde LAD flow was obtained in 14 (93%) of 15 patients. The mean diastolic velocity of the retrograde flow was 21.0 +/- 6.1 cm/s. In group B, antegrade LAD flow was obtained in all 83 patients (100%). The mean diastolic velocity of the antegrade flow was 21.5 +/- 7.1 cm/s. Retrograde LAD flow by TTDE had a sensitivity of 93% and a specificity of 100% for the detection of total LAD occlusion. CONCLUSIONS: Retrograde flow in the LAD by TTDE is a highly sensitive and specific finding that can be used to noninvasively diagnose total LAD occlusion.

Influence of the CYP2D6*10 allele on the metabolism of mexiletine by human liver microsomes.

AIMS: To study the influence of CYP2D6*10 on the formation of p-hydroxymexiletine (PHM) and hydroxymethylmexiletine (HMM) using microsomes from human liver of known genotypes. METHODS: Microsomes from human livers of genotype CYP2D6*1/*1 (n = 5), *1/*10 (n = 6) and *10/*10 (n = 6) were used in this study. The formation of PHM and HMM was determined by high-performance liquid chromatography. RESULTS: The formation rates of PHM and HMM were decreased by more than 50% and 85% in CYP2D6*1/*10 and *10/*10 microsomes, respectively, compared with *1/*1 microsomes. CONCLUSIONS: The metabolism of mexiletine to form PHM and HMM appears to be impaired to a significant extent in human liver microsomes from hetero- and homozygotes of CYP2D6*10.

Frequencies of CYP2D6 mutant alleles in a normal Japanese population and metabolic activity of dextromethorphan O-demethylation in different CYP2D6 genotypes.

AIMS: To determine the frequencies of 11 CYP2D6 mutant alleles (CYP2D6*2, *3, *4, *5, *8, *10, *11, *12, *14, *17 and *18), and their relation to the metabolic capacity of CYP2D6 in Japanese subjects. METHODS: One hundred and sixty-two unrelated healthy Japanese subjects were genotyped with the polymerase chain reaction amplification method and 35 subjects were phenotyped with dextromethorphan. RESULTS: The frequencies of CYP2D6*2,*5, *10 and *14 were 12.9, 6.2, 38.6 and 2.2% in our Japanese subjects, respectively. CYP2D6*3, *4, *8, *11, *12, *17 and *18 were not detected. The mean log metabolic ratio of dextromethorphan in subjects with genotypes predicting intermediate metabolizers was significantly greater than that of heterozygotes for functional and defective alleles. CONCLUSIONS: CYP2D6*5 and CYP2D6*14 are the major defective alleles found in Japanese subjects. In addition, CYP2D6*10 may play a more important role than previously thought for the treatment of Japanese patients with drugs metabolized by CYP2D6.

Evaluation of the mitral annulus by extracted three-dimensional images in patients with an annuloplasty ring.

We evaluated the capability of extracted 3-dimensional images obtained by multiplane transesophageal echocardiography in the evaluation of nonplanarity and area change of the mitral annulus in patients with an annuloplasty ring. This method is feasible in the evaluation of nonplanarity and area change of mitral annulus in patients with an annuloplasty ring.

[Serial changes in mitral regurgitation after mitral valve repair with artificial chordae tendineae: assessment by transesophageal echocardiography].

Serial changes in mitral regurgitation after anterior mitral valve repair were examined by transesophageal echocardiography (TEE) in 34 of 86 consecutive patients with pure mitral regurgitation who underwent anterior mitral valve repair from 1987 to 1996. The patients were divided into two groups: 15 patients undergoing mitral repair with polytetrafluoroethylene (PTFE; PTFE group) and 19 undergoing conventional mitral repair without PTFE (non-PTFE group). The PTFE group included 11 men and 4 women with a mean age of 52.1 years. They were followed for mean 22.8 +/- 12.0 months. The non-PTFE group included 12 men and 7 women with a mean age of 53.9 years. They were followed for mean 33.9 +/- 20.4 months. Mitral regurgitation jet areas were observed at the time of operation, 1 month after mitral valve repair, and in the late follow-up period. Regurgitation jet areas were 0.7 +/- 0.7, 1.1 +/- 0.9 and 2.5 +/- 2.1 cm2 in the PTFE group, and 1.1 +/- 1.3, 2.4 +/- 1.7, 4.7 +/- 2.9 cm2 in the non-PTFE group. The jet area was significantly smaller in the PTFE group than in the non-PTFE group at 1 month after operation and in the late follow-up period. Moderate to severe regurgitation was observed in two patients (13.3%) in the PTFE group, and eight patients (42.1%) in the non-PTFE group. Mitral valve repair with PTFE showed better results than conventional mitral valve repair without PTFE during the mean follow-up period of 23 months.

[Long-term results of mitral valve repair with artificial chordae tendineae].

The long-term results of mitral valve repair using artificial polytetrafluorethylene (PTFE) chordae were assessed in 61 consecutive patients with pure mitral regurgitation who underwent mitral valve repair with replacement of elongated or ruptured chordae tendineae between 1992 and 1996. There were 36 men and 25 women aged from 14 to 73 years (mean 52.1 +/- 13.8 years). The patients were followed up for between 1 to 73 months (mean 29.3 +/- 17.6 months). Fifty-five patients underwent mitral valve repair of the anterior leaflet and 6 repair of the posterior leaflet. There were two hospital and two late deaths. Actual survival rate at 5 years was 93.1%. Freedom from cardiac events at 5 years was 87.8%. Two patients required reoperation due to hemolysis. There were three occurrences of non-fatal thromboembolism. Although further investigation is necessary in a large population, expanded PTFE sutures are excellent for chordal replacement during mitral valve repair.

Three-dimensional echocardiographic evaluation of configuration and dynamics of the mitral annulus in patients fitted with an annuloplasty ring.

BACKGROUND AND AIMS OF THE STUDY: Three-dimensional (3D) echocardiography permits the objective analysis of structures and of pathologic conditions of complex geometry. Multiplane transesophageal echocardiography (TEE) permits 3D image sets of the heart to be produced from multiple 2D images by rotating the transducer, without changing its position. The purpose of this study was to clarify the capability of 3D echocardiography to evaluate the configuration and dynamics of the mitral annulus in patients fitted with an annuloplasty ring. METHODS: Twenty patients who underwent mitral valve repair for pure mitral regurgitation (10 with a flexible Duran ring and 10 with a rigid Carpentier ring) were studied. Using a multiplane transesophageal probe, sequential tomographic images were obtained by rotating the transducer at 2 degrees angular intervals around a 180 degrees arc. 3D reconstructions were performed to produce dynamic 3D images of the mitral annulus in a manner that simulated visualization from the left atrium. Mitral annular configuration was assessed from volume-rendered display and extractive 3D imaging. Mitral annular area change was evaluated from selected long-axis cut planes. RESULTS: The configuration and dynamics of the mitral annulus were visualized by 3D displays. In patients with a Duran ring, the mitral annulus had a non-planar configuration and mitral annular area changed during cardiac cycle (increased in diastole; reduced in atrial and ventricular systole; percentage reduction 25 +/- 2%). In patients with a Carpentier ring, the mitral annulus had a planar configuration and mitral annular area was effectively unchanged during the cardiac cycle. CONCLUSIONS: 3D echocardiography using a multiplane transesophageal probe is useful in evaluating the configuration and dynamics of the mitral annulus in patients fitted with an annuloplasty ring.

[Intraoperative assessment of mitral valve plasty by transesophageal echocardiography].

Mitral valve repair offers many advantages over prosthetic valve replacement, especially in minimizing the risk of thromboembolism. Intraoperative evaluation of residual mitral regurgitation (MR) is important in this procedure. The present study assessed the usefulness of transesophageal echocardiography (TEE) for the intraoperative assessment of residual MR in patients undergoing mitral valve repair. Intraoperative TEE was performed in 102 consecutive patients before and after mitral valve repair in the operating room. The grade of MR was evaluated according to the maximum MR jet area detected by biplane color Doppler TEE (mild: <4 cm2; moderate: 4 < or = < 7 cm2; severe : 7 cm2 < or =). After the first repair, the manual regurgitant test was performed. Excellent results with no or mild MR assessed by the manual regurgitant test were obtained in 101 patients. However, moderate or severe MR was identified in eight of these 101 (7.9%) patients by TEE after weaning from the cardiopulmonary bypass. Consequently, six of these eight patients underwent repeat mitral valve repair and two patients received prosthetic valve replacement. Satisfactory final operative results were obtained in all 101 patients. The eight patients who needed additional operative procedures followed good clinical courses in hospital. TEE 1 month after operation demonstrated no or mild MR in these eight patients. Intraoperative TEE is useful in the evaluation of residual MR after mitral valve repair. This technique provides indications for immediate additional operative procedures, and can reduce the occurrences of congestive heart failure and reoperation in the early stage after mitral valve repair.

[Serial change of mitral regurgitation after anterior mitral valve repair using polytetrafluorethylene chordae: evaluation by transesophageal echocardiography].

The results of anterior mitral leaflet repair were evaluated by the serial change of mitral regurgitation (MR) using transesophageal echocardiography (TEE) in 24 patients undergoing mitral valve repair for anterior leaflet prolapse during 1988 to 1994, who were examined by TEE immediately after operation, 1 month after operation, and late after operation (mean 15 months). Chordal replacement using polytetra-fluorethylene chordae was performed in 15 patients (PTFE group), and not performed in 9 patients (non-PTFE group). MR jet area late after operation was significantly smaller in the PTFE group than in the non-PTFE group (2.2 +/- 2.3 vs. 4.6 +/- 2.3 cm2, p < 0.05). Moderate to severe MR was observed in four patients (27%) in the PTFE group, and six (67%) in the non-PTFE group late after operation. The thickness of the mitral leaflet before operation was more than 5 mm in all patients with more than moderate MR late after operation in the PTFE group. Chordal replacement using polytetrafluorethylene chordae showed better results compared with conventional mitral valve repair without polytetrafluorethylene chordae over the follow-up period of 15 months.

Serial change of mitral regurgitation after mitral valve repair: comparison of anterior with posterior leaflet lesions.

Mitral valve repair is an important operative procedure for correcting mitral regurgitation (MR). However, serial change of residual MR after operation has not been reported. Serial change of MR after mitral valve repair was evaluated by transesophageal color Doppler echocardiography (TEE). Twenty-six patients undergoing mitral valve repair for MR during 1987 to 1991 were examined by TEE just after operation, 6 months after operation, and late follow-up period (mean 3.7 years). Thirteen patients had a lesion of the anterior mitral leaflet before operation (group A). Thirteen patients had a lesion of the posterior mitral leaflet before operation (group P). The MR area was measured by TEE at each stage after operation. In group A, the MR area at late follow-up increased significantly compared with just after operation (1.1 vs 4.3 cm2, p < 0.001). In group P, the MR area at late follow-up did not increase significantly compared with just after operation (0.6 vs 1.3 cm2, p = NS). In conclusion, MR does not increase after mitral valve repair in patients with posterior mitral valve repair, but MR may increase at late follow-up after operation for anterior mitral valve prolapse.

Three-dimensional analysis of configuration and dynamics in patients with an annuloplasty ring by multiplane transesophageal echocardiography: comparison between flexible and rigid annuloplasty rings.

BACKGROUND AND AIM OF THE STUDY: Multiplane transesophageal echocardiography provides three-dimensional reconstruction of the mitral annulus from multiple cross-sectional views from a stable transducer position by rotating around a central axis. This study was designed to evaluate the effect of the type of annuloplasty ring on mitral annular configuration and dynamics using three-dimensional reconstruction by multiplane transesophageal echocardiography. METHODS: Ten patients who underwent mitral valve repair for pure mitral regurgitation (five patients with flexible Duran ring, five patients with rigid Carpentier ring) and five normal subjects were studied with multiplane transesophageal echocardiography. Three-dimensional configuration of the mitral annulus was obtained from multiple cross-sectional views of multiplane transesophageal echocardiography. RESULTS: In normal subjects, the mitral annulus had a non-planar configuration and reduced its area in systole. In patients with a Duran ring, the mitral annulus had a non-planar configuration and reduced its area in systole. In patients with a Carpentier ring, the mitral annulus had a planar configuration and the mitral annular area did not change during the cardiac cycle. CONCLUSION: Three dimensional reconstruction of the mitral annulus using multiplane transesophageal echocardiography revealed that mitral annular configuration and dynamics are more physiologic in patients with a flexible Duran ring that with a rigid Carpentier ring.

[Mitral valve repair for infectious endocarditis].

Fourteen patients with mitral regurgitation resulting from infectious endocarditis underwent mitral valve repair between December 1988 and July 1994. There were nine males and five females aged from 14 to 70 years (mean 40.2 +/- 19.7 years). Three patients had active endocarditis. Time between the onset of endocarditis symptoms and surgery ranged from 1 to 24 months (mean 8.3 months). Bacterial findings were Streptococcus in eight patients, Staphylococcus in one, and unknown in five. All macroscopically infected tissue was excised in patients with active endocarditis. Carpentier's reconstructive techniques were mainly used. There were no hospital deaths. Mean follow-up was 29 months and complete. Thirteen patients were in New York Heart Association functional class I and one in class II. There were no late deaths, reoperations, recurrent endocarditis, thromboembolic events, or other valve-related morbidity. We conclude that mitral valve repair is an attractive procedure in patients with mitral regurgitation resulting from infectious endocarditis.

Comparison of the Carpentier and Duran prosthetic rings used in mitral reconstruction.

This clinical study was undertaken to evaluate the Duran flexible ring and the Carpentier rigid ring in terms of mitral annulus motion, transmitral flow and left ventricular function. Twenty-six patients (11 receiving rigid rings and 15, flexible rings) with normal sinus rhythm and with no or only trivial mitral valve regurgitation after surgical repair were selected. Angiograms demonstrated no significant differences in left ventricular systolic function between the two groups of patients. The area of the mitral annulus with the flexible ring significantly changed during the cardiac cycle. There were significant differences in the left ventricular fractional shortening (rigid ring, 35.8%; flexible ring, 43.4%) and in the peak velocity (rigid ring, 222 cm/s; flexible ring, 186 cm/s) at peak exercise. These data suggest that the flexible ring interferes less with the normal movements of the mitral annulus during the cardiac cycle, and that, under exercise conditions, it performs better than the rigid ring. We therefore conclude that mitral valve reconstruction using the Duran flexible ring is advantageous in patients with mitral regurgitation due to degenerative disease and sinus rhythm.

[Residual, recurrent mitral regurgitation after mitral valve reconstruction: differences in lesion and operation method].

Patients developing residual or recurrent mitral regurgitation (MR) increased to moderate or severe grade after mitral valve reconstruction for MR were investigated by correlating the lesion and operation method with the echocardiographic course of postoperative MR. Postoperative moderate or severe grade MR [more than 4.0 cm2 color Doppler flow area on postoperative transesophageal echocardiography (TEE)] occurred in 21 of 80 mitral valve reconstruction patients. If residual MR caused more than 2.0 cm2 color Doppler flow area on intraoperative TEE, the MR increased to moderate or severe grade during the follow-up period. Postoperative moderate or severe MR occurred more frequently in lesions of the anterior mitral leaflet than the posterior mitral leaflet (45.8% vs 6.5%, p < 0.001), and in elongated chordae than in torn chordae (52.9% vs 14.3%, p < 0.005). Chordal shortening for elongated chordae could correct MR at operation but MR recurred and increased gradually to moderate or severe grade in half of these cases. Chordal reconstruction with polytetrafluorethylene suture is expected to achieve better results than chordal shortening. The causes of postoperative MR could usually be identified by comparative investigation of echocardiographic course, lesion, and operation method. Postoperative moderate or severe MR occurs more often in lesions of the anterior mitral leaflet or cases of elongated chordae. Residual MR should be suppressed to less than 2.0 cm2 color Doppler flow area on intraoperative TEE.

[Diagnosis of sinus venosus atrial septal defect by transesophageal color Doppler and two-dimensional echocardiography].

Diagnosis of sinus venosus atrial septal defect based on transthoracic color Doppler and two-dimensional echocardiography is often difficult. We recently experienced two cases of sinus venosus atrial septal defect which were correctly diagnosed using transesophageal color Doppler and two-dimensional echocardiography. Transthoracic color Doppler flow imaging did not demonstrate the atrial septal defect or the shunt flow across the defect in either case. Transesophageal two-dimensional echocardiography visualized a defect in the upper most portion of the interatrial septum in one case, and transesophageal color Doppler flow mapping detected a left-to-right shunt across the defect in both cases. Transesophageal color Doppler flow mapping also demonstrated the flow signal of the right upper pulmonary vein into the right atrium near its junction with the superior vena cava in each case. The diagnoses of sinus venosus atrial septal defect and combined partial anomalous pulmonary venous return were confirmed by surgery in both cases. Transesophageal color Doppler and two-dimensional echocardiography are very useful in diagnosing sinus venosus atrial septal defect and combined partial anomalous pulmonary venous return.

(R)-1,2,3,4-tetrahydro[1]benzothieno[2,3-c]pyridines: novel optically active compounds with strong 5-HT1A receptor binding ability exhibiting anticonflict activity and lessening of memory impairment.

(R)-1,2,3,4-Tetrahydro[1]benzothieno[2,3-c]pyridine derivatives (60-114) were synthesized. The (R)-isomers have affinity for the 5-HT1A receptor while the (S)-isomers have no such ability. The affinity of the (R)-isomers was discussed on the basis of structure-activity relationships between the affinity and hydrophobicity of the (R)-isomers. Compounds 71 and 107, which are representative derivative compounds, have anticonflict activity and lessening of memory impairment. In particular, compound 107 cannot bind to receptors other than the 5-HT1A receptor, demonstrating that it is a unique compound with a different mechanism of action from that of conventional anxiolytics.

[Percutaneous transvenous mitral commissurotomy vs open mitral commissurotomy: evaluation of results by color Doppler and two-dimensional echocardiography].

The effects of percutaneous transvenous mitral commissurotomy (PTMC) and open mitral commissurotomy (OMC) were evaluated in 18 patients who underwent PTMC and 16 patients who underwent OMC, before and within one month of the procedure, using two-dimensional and color Doppler echocardiography. There was no significant difference between the two groups in the mitral valve area, the severity of mitral stenosis, or cardiac function before the procedure. The mitral valve area after PTMC as measured by two-dimensional echocardiography and continuous wave Doppler echocardiography increased from 1.07 +/- 0.24 cm2 to 2.01 +/- 0.42 cm2 (p < 0.001), and from 0.99 +/- 0.26 cm2 to 1.76 +/- 0.23 cm2 (p < 0.001), respectively. The mitral valve area after OMC measured by two-dimensional echocardiography and continuous wave Doppler echocardiography increased from 1.04 +/- 0.24 cm2 to 1.78 +/- 0.41 cm2 (p < 0.001), and from 0.95 +/- 0.32 cm2 to 1.62 +/- 0.46 cm2 (p < 0.001), respectively. The mitral valve areas after PTMC did not differ significantly from those after OMC by either method.

[Reliability of biplane transesophageal color Doppler echocardiography in evaluating mitral valve prolapse: comparison with surgical findings].

The reliability of biplane transesophageal color Doppler echocardiography for the evaluation of mitral valve prolapse was assessed by comparison with surgical findings in 27 patients. The mitral valve prolapse site was classified as the medial, central, and lateral portions of the anterior leaflet, and medial, middle, and lateral scallops of the posterior leaflet. The prolapsed sites were determined by the site of systolic displacement using two-dimensional echocardiography, the site of flow acceleration and the direction of the mitral regurgitant jet using color Doppler echocardiography. The sensitivity of transesophageal echocardiography for detecting prolapse at the medial, central, and lateral portions of the anterior leaflet, and the medial, middle and lateral scallops of the posterior leaflet was 91, 100, 86, 83, 100, and 80%, respectively. The specificity was 100, 100, 96, 100, 89, and 100%, respectively. Biplane transesophageal echocardiography is a reliable method for detecting the site of mitral valve prolapse.