Cheng-Wen Chiang

Predictors of Systemic Embolism in Patients with Mitral Stenosis: A Prospective Study

Systemic, especially cerebral, embolism is one of the major causes of illness and death in patients with mitral stenosis [1-5]. Identification of risk factors for embolism may improve the strategies for preventing this event. However, most large studies addressing risk predictors have been retrospective [1, 2, 6-9]. We sought to reappraise this issue in a large, prospective study. Methods Patients Eligible patients were consecutive adults (age 15 years) with mitral stenosis (mitral valve area 2 cm2 according to echocardiographic planimetry) who presented to a university-affiliated medical institution from April 1987 to December 1994. We excluded patients with infective endocarditis and those who were in critical condition because of systemic embolism and died during hospitalization. End Point The study end point was the occurrence of new systemic embolism during follow-up. The diagnosis of systemic embolism was based on symptoms and signs (sudden onset of peripheral arterial ischemic [for example, sudden flank pain with hematuria, abdominal pain with gastrointestinal bleeding, or leg pain with pulse deficit] or neurologic manifestations without prodromes) and on findings from computed tomography, angiography, and surgery. We did not attempt to detect silent emboli. Clinical Variables We assessed nine clinical variables (Table 1): age at enrollment; sex; presence or absence of previous systemic embolism, atrial fibrillation, hypertension, and New York Heart Association class III or IV congestive heart failure; and therapy with anticoagulants, percutaneous balloon mitral commissurotomy, or valvular surgery. Patients were regularly followed at outpatient clinics. Table 1. Clinical and Echocardiographic Variables in 534 Patients with Mitral Stenosis* Echocardiographic Method and Variables Standard transthoracic echocardiography was done at enrollment in all patients by using a Hewlett-Packard 7340, Sonos 1000, or Sonos 1500 echocardiographic system (Hewlett-Packard, Palo Alto, California) interfaced with both 2.5-MHz and 5.0-MHz transducers. Biplane or omniplane transesophageal echocardiography using a 5.0-MHz transducer was also performed in a subgroup of consecutive patients who entered the study from September 1991 to October 1992. Ten echocardiographic variables were examined (Table 1). Mitral valve area was measured by planimetry from two-dimensional echocardiography. When two-dimensional echocardiography of the mitral orifice yielded unsatisfactory results, we used the pressure half-time (T1/2) method (mitral valve area [cm2] = 220/T1/2 ms) [10-12]. We did not use the pressure half-time method when the mitral orifice could be clearly defined by two-dimensional echocardiography because pressure half-time is influenced by many factors other than mitral valve area [13, 14]. Other echocardiographic variables were left atrial diameter at end systole; presence or absence of a left atrial thrombus [15] or left atrial smoky echoes on transthoracic or transesophageal echocardiography [16-18]; presence or absence of impaired left ventricular systolic performance; and presence or absence of significant (moderate or severe) aortic stenosis, aortic regurgitation, mitral regurgitation, tricuspid regurgitation, or pulmonic regurgitation. The degrees of these valvular lesions were semiquantified by using a continuity equation (for aortic stenosis) or color Doppler imaging (for various regurgitations), as described elsewhere [19, 20]. Briefly, significant aortic stenosis refers to an aortic valve area of 1.2 cm2 or less determined by the continuity Equation method RF 19*; significant mitral or tricuspid regurgitation refers to a ratio of regurgitant jet area to left or right atrial area of 20% or more; and significant aortic or pulmonic regurgitation refers to a ratio of jet width to ventricular outflow tract diameter of 25% or more [20]. Left atrial diameter at end systole was measured from an M-mode echocardiogram recorded in parasternal long-axis view. The measurement was made according to the recommendations of the American Society of Echocardiography [21]. To detect left atrial smoky echoes, we used a 5-MHz transducer during transthoracic and transesophageal echocardiography because a 5-MHz transducer is more sensitive than a 2.5-MHz transducer [16]. We chose the term smoky echoes instead of spontaneous echocardiographic contrast (a term frequently used in other studies [6, 7]) because some patients with severe tricuspid regurgitation or right heart failure had bright moving spots (originating from microbubbles) in the venae cavae or hepatic veins that were identical to those seen during contrast echocardiography. Thus, we reserve spontaneous echocardiographic contrast for that echocardiographic pattern and use smoky echoes for the finer, lighter whorling echoes (originating from aggregated erythrocytes) [16-18] that appeared in the left atrium in patients with severe mitral stenosis. Statistical Analysis For each clinical and echocardiographic measure, the log-rank statistic was used to determine whether the overall pattern of the time to development of systemic embolism (embolism-free time) varied among levels of the measure. Mean embolism-free time was estimated by using a nonparametric method that considers censoring [22]. Cox regression was used to examine the significance of the clinical and echocardiographic variables in predicting embolism-free time for patients in sinus rhythm and patients in atrial fibrillation. All analyses were performed by using BMDP Dynamic Release 7.0 [23]. Results Five hundred thirty-four patients were followed for a mean (SD) of 36.9 22.5 months. Of these, 257 patients (48.1%) received anticoagulants throughout the follow-up period. The indications for anticoagulation were the presence of a left atrial thrombus, atrial fibrillation, or a history of systemic embolism; patient compliance with therapy; and lack of risk factors for bleeding. The relatively low percentage of patients receiving anticoagulants in this series was due to minimal patient compliance. During the follow-up period, 60 patients (11.2%) developed a systemic embolism. When Cox regression was performed, significant interaction was found between atrial fibrillation and age, percutaneous balloon mitral commissurotomy, mitral valve area, previous systemic embolism, left atrial thrombus, and anticoagulation. In other words, the significance of these variables depended to some extent on whether the patient was in atrial fibrillation or sinus rhythm. We therefore performed subgroup analyses. Subgroup Analyses Of the 132 patients in sinus rhythm, 12 (9.1%) developed systemic embolism during follow-up. Age (P < 0.001), percutaneous balloon mitral commissurotomy (P = 0.02), and mitral valve area (P = 0.02) were significant predictors in the log-rank analysis (Table 2). Results of the Cox regression showed that age (relative risk [RR], 1.12 [95% CI, 1.04 to 1.21]), left atrial thrombus (RR, 37.1 [CI, 2.82 to 487.8]), mitral valve area (RR, 16.9 [CI, 1.53 to 187.0]), and significant aortic regurgitation (RR, 22.4 [CI, 2.72 to 184.8]) were significant predictors of new systemic embolism (Table 3). No interactions were found among these variables. However, mitral valve area became a nonsignificant predictor (P = 0.12) when patients with percutaneous balloon mitral commissurotomy were excluded from the analysis. Table 2. Subgroup Univariate Analysis of Correlates of Systemic Embolism in Patients with Mitral Stenosis* Table 3. Cox Regression Analysis of Predictors of Systemic Embolism in Patients with Mitral Stenosis* Of the 402 patients in atrial fibrillation, 48 (11.9%) developed systemic embolism. Age (P = 0.01), previous embolism (P = 0.001), and percutaneous balloon mitral commissurotomy (P = 0.003) were significant predictors in the univariate analysis (Table 2). In the multivariate analysis, however, only previous embolism (RR, 3.11 [CI, 1.66 to 5.85]) and percutaneous balloon mitral commissurotomy (RR, 0.37 [CI, 0.18 to 0.79]) remained significant predictors of embolism-free time (Table 3). Again, no interactions were found between these two variables. A subgroup analysis of the 164 patients who underwent baseline transesophageal echocardiography revealed no other significant predictors. Discussion Factors Correlated with Systemic Embolization in Patients with Mitral Stenosis Our prospective study revealed that for patients in sinus rhythm, embolization was related to age, mitral valve area, the presence of a left atrial thrombus, and significant aortic regurgitation. For patients in atrial fibrillation, the significant factors were previous embolism and percutaneous balloon mitral commissurotomy (Table 3). Other retrospective studies have shown that atrial fibrillation [1, 2, 8], age [1, 2, 8], and previous embolism [3] correlate with increased incidence of systemic embolism in patients with mitral stenosis and that age is closely related to the prevalence of atrial fibrillation [24] and to a history of embolization [1, 2, 8]. Several studies have shown that anticoagulation reduces the incidence of systemic embolism in patients with mitral stenosis and atrial fibrillation [25-27]. To the best of our knowledge, however, our study is the first to show that the presence of a left atrial thrombus and significant aortic regurgitation are positive predictors and that percutaneous balloon mitral commissurotomy seems to be a negative predictor. Left Atrial Thrombus and Systemic Embolism in Patients with Mitral Stenosis Who Are in Sinus Rhythm Dislodgement of a left atrial thrombus in patients with mitral stenosis has been thought to lead to systemic embolism. Although a correlation between left atrial thrombus and systemic thrombus would be expected, previous studies have not confirmed such a correlation. We found that the presence of a left atrial thrombus was a positive predictor (RR, 37.1 [CI, 2.82 to 487.8]) for patients in sinus

Video-Assisted Cardiac Surgery in Closure of Atrial Septal Defect

BACKGROUND Video-assisted endoscopy has been applied in the management of a variety of intrathoracic vascular lesions. Here we report its use in the correction of intracardiac congenital defects. METHODS Eight patients (3 male and 5 female) underwent operation for closure of an atrial septal defect. The patients ranged in age from 2.0 to 60.9 years (mean, 19.2 +/- 19.0 years). The patients weighed 11 to 66 kg (mean, 41.3 +/- 23.5 kg). The ratio of pulmonary blood flow to systemic blood flow ranged from 2.0 to 6.0 (mean, 3.4 +/- 1.3). The mean pulmonary artery pressure was 19.7 +/- 4.0 mm Hg (range, 13 to 24 mm Hg). The operations were performed through a right anterior minithoracotomy and guided by video-assisted endoscopic techniques under femorofemoral or femoral-right atrial extracorporeal circulation. The aorta was not cross-clamped, and the myocardium was protected by continuous coronary perfusion with hypothermic fibrillatory arrest (rectal temperature, 22.0 degrees +/- 2.0 degrees C). Transesophageal echocardiographic monitoring was maintained during the operations. The right atrium was entered after pericardiotomy. Primary closure of the defect was performed successfully in all patients. Conventional nondisposable instruments were used for dissection, grasping, suturing, and hemostasis. RESULTS The durations of extracorporeal circulation and operation ranged from 47 to 126 minutes (mean, 80 +/- 31 minutes) and from 2.2 to 4.5 hours (mean, 3.1 +/- 0.8), respectively. All patients recovered from the operation rapidly with an uneventful postoperative course. CONCLUSIONS Our experience demonstrates that video-assisted cardiac surgery is technically feasible and can be used with excellent results for the repair of congenital heart defects in general.

Video-assisted mitral valve operations

BACKGROUND Video-assisted endoscopy has been applied frequently in the management of a variety of surgical diseases. However, it has rarely been applied in mitral valve surgery. METHODS We report 2 patients who received emergency operations for thrombosis of a mitral prosthesis (patient 1, a 68-year-old man) and acute mitral regurgitation due to rupture of anterior chordae (patient 2, a 75-year-old woman). They both had severe congestive heart failure. Cardiogenic shock was noted in patient 2. The mitral valve was approached through a right anterior minithoracotomy with the aid of an endoscope by means of projected images on the video monitor under femorofemoral cardiopulmonary bypass. The aorta was not cross-clamped, and the myocardium was protected by continuous coronary perfusion with hypothermic fibrillatory arrest. The left atrium was entered posterior to the interatrial groove. Thrombectomy and mitral valve repair were performed successfully. RESULTS The duration of extracorporeal circulation was 204 and 147 minutes, respectively. Both patients recovered from the operation rapidly with uneventful postoperative courses. CONCLUSIONS Our preliminary results suggest that video-assisted endoscopic cardiac surgery is technically feasible and could be performed in the milieu of open heart surgery.

Doppler and two-dimensional echocardiographic features of sinus of Valsalva aneurysm

Doppler, contrast, and two-dimensional echocardiograms of 12 aneurysms of the sinus of Valsalva in 10 consecutive patients were analyzed in order to highlight the diagnostic features. The diagnosis were confirmed by surgical and/or catheterization findings. The aneurysms had ruptured in 7 of 12 (58%). Two-dimensional echocardiography prior to the contrast studies was able to delineate the aneurysms in 7 of 12 (58%). The contrast studies outlined two additional aneurysms. The right aneurysms directed anteriorly and caudally. The noncoronary aneurysms formed an extraneous lumen at the posterior part of the aortic root, mimicking aortic dissection. Doppler examinations showed systolic and diastolic turbulence in five of six (83%) of the right aneurysms rupturing into the right ventricular outflow tract. Color Doppler echocardiography showed a left ventricular diastolic turbulence emanating from the aneurysm in a case with a noncoronary aneurysm rupturing into the left ventricle. It is concluded that the principal Doppler, contrast, and two-dimensional echocardiographic features usually allow a rapid correct diagnosis of sinus of Valsalva aneurysm.

The C677T mutation of the methylenetetrahydrofolate reductase gene is not associated with the risk of coronary artery disease or venous thrombosis among Chinese in Taiwan.

Objectives: We sought to investigate the association between the methylenetetrahydrofolate reductase (MTHFR) gene C677T mutation and the risk of coronary artery disease (CAD), myocardial infarction (MI) and venous thrombosis (VT) in a Chinese population in Taiwan. Methods: The subjects included 218 CAD patients, 107 VT patients, and their age- and sex-matched controls. DNA was extracted from the blood and genotypes were determined by polymerase chain reaction, restriction mapping with HinfI and gel electrophoresis. Results: The distribution of MTHFR genotypes was similar in the CAD cases and controls; the genotype TT was present in 6.0% of CAD patients, as compared to 6.9% of CAD control subjects (p = 0.165; odds ratio = 0.86; 95% confidence interval = 0.40–1.85). The frequency of the T allele was also similar in CAD cases and controls (25.5% vs. 24.8%; p = 0.788). There was no significant association between TT homozygosity and the risk of MI. The genotype distributions and the frequency of the T allele were also similar in VT cases and controls. Conclusions: Our data suggest that there is no association between the C677T mutation of the human MTHFR gene and the risk of CAD or VT among Chinese in Taiwan.

Importance of hyperhomocysteinemia as a risk factor for venous thromboembolism in a Taiwanese population. A case-control study.

OBJECTIVE To determine the current status of hyperhomocysteinemia, which is a known risk for venous thrombosis (DVT), in Taiwan. SUBJECTS 101 unselected patients with a minimum of one episode of deep leg DVT, either initial inpatients or current compliant outpatients in a teaching hospital. METHODS Various thrombophilic risks, gene polymorphism and clinical predisposition were evaluated. RESULTS AND CONCLUSIONS Patients presented higher fast total plasma homocysteine (hcy) levels than age- and sex-matched controls did (14.1 vs. 9.94 microM). Based on the 95th percentile of control values, hyperhomocysteinemia had a four- to nine-fold risk for DVT, irrespective of clinical predisposition, as well as other thrombophilic risks surveyed. Polymorphism of a metabolizing enzyme, methylenetetrahydrofolate reductase (MTHFR), was not associated with DVT, although homozygous thermolabile mutation tended to have higher plasma hcy levels. Factor V Leiden was absent in analysis of 80 patients. In complete evaluation (hcy, antithrombin (AT), protein S (PS), protein C (PC), lupus anticoagulant (LA), anticardiolipin antibody) of a subset of 83 patients hyperhomocysteinemia was the most prevalent risk (33.7%), with PC or PS deficiencies following (22.9%). Thus, hyperhomocysteinemia is a prominent risk for DVT in Taiwan.

Characterization of Atrioventricular Nodal Reentry With Continuous Atrioventricular Node Conduction Curve by Double Atrial Extrastimulation

BACKGROUND Characterization of typical atrioventricular nodal reentrant tachycardia (AVNRT) with continuous AVN conduction (A1A2/A2H2) curves by double atrial extrastimulation (A1A2A3) has never been systematically studied. METHODS AND RESULTS This study was composed of 33 patients with typical AVNRT and continuous AVN conduction curves (group 1) and 103 patients with AVNRT and discontinuous AVN conduction curves (group 2). Using A1A2A3 with predefined fast pathway-conducted A2, we examined the effects of slow pathway ablation on the A2A3/A3H3 curves in both groups. In group 1, anterograde AVN effective refractory period (272+/-33 versus 277+/-47 ms, P>0.05) and AVN Wenckebach block cycle length (320+/-45 versus 343+/-59 ms, P>0.05) remained unchanged after ablation. A2H2max was shorter in group 1 than group 2 (237+/-89 versus 395+/-72 ms, P<0.05) at baseline. It shortened in group 2 (395+/-72 versus 221+/-78 ms, P<0.001) but remained unchanged in group 1 (237+/-89 versus 214+/-59 ms, P>0.05) after ablation. A1A2A3 could further disclose discontinuous A2A3/A3H3 curves in 29 patients of group 1. A3H3max shortened in both groups (375+/-81 versus 238+/-82 ms, P<0.001, and 419+/-104 versus 220+/-78 ms, P<0.001, respectively) in a similar fashion. Successful ablation resulted in loss of the left portion of the A2A3/A3H3 curves in the 4 patients of group 1 with continuous A2A3/A3H3 curves. CONCLUSIONS Use of A1A2A3 could expose discontinuous A2A3/A3H3 curves in most patients with continuous A1A2/A2H2 curves. Significant shortening of A3H3max after ablation may be indicative of successful elimination of AVNRT.

Cardiac myxoma - clinical experience in 24 patients

We reviewed our clinical experience in 24 patients with cardiac myxoma. There were 8 males and 16 females, their ages ranged from 14 to 73 (mean, 48) years. Prior to echocardiographic examination, cardiac myxoma was suspected clinically in only 2 cases. The remaining patients were initially diagnosed as having mitral valvar disease (9 cases), infective endocarditis (3 cases), congestive cardiomyopathy (4 cases), pericardial effusion (1 case), systemic embolism of unknown cause (1 case), cerebrovascular accident (2 cases), ventricular septal defect (1 case) and Ebsteins malformation (1 case). The tumor was in the left atrium in 16, in the right atrium in 2, in the biatrium in 1, while one was in the right ventricle and peripheral arterial occlusion had been produced by myxoma without demonstrable cardiac tumors in the other two. Twenty-two patients underwent open heart surgery for excision of myxoma and there was no surgical mortality. Abdominal embolectomy was carried out in 2 patients; one of these 2 patients survived and 1 died. Follow-up for a mean period of 32 months (range 2 to 99 months) was possible in in 18 patients with no evidence of recurrence. We conclude that cardiac myxoma may mimic many cardiovascular diseases, so a high index of suspicion is important for its diagnosis. Echocardiography is the most useful diagnostic screening tool.

Video-Assisted Coronary Artery Bypass Grafting During Hypothermic Fibrillatory Arrest

BACKGROUND Hypothermic fibrillatory arrest without aortic cross-clamping is a technique for quieting the heart during coronary artery bypass grafting. This report reviews the preliminary results with this technique in 4 patients having video-assisted coronary artery bypass grafting. METHODS Four male patients 28.5 to 64.5 years old (mean age, 45.4 years) underwent operation for unstable angina. With video-assisted techniques, coronary artery bypass grafting was performed through a left anterior minithoracotomy with femoral-femoral cardiopulmonary bypass without cross-clamping the aorta. The myocardium was protected by continuous coronary perfusion during hypothermic fibrillatory arrest. RESULTS A left internal thoracic artery graft was anastomosed to the left anterior descending coronary artery in each patient. The posterior descending branch of the right coronary artery was grafted with a pedicled right gastroepiploic artery in 1 patient. The duration of cardiopulmonary bypass was 72 to 127 minutes (mean duration, 92 +/- 21 minutes). The postoperative course of each patient was uneventful. Follow-up (range, 3.9 to 5.8 months; mean follow-up, 4.9 months) was complete for all patients. There were no late deaths. Coronary angiography showed patent grafts. All patients were in New York Heart Association functional class I or II (mean class, 1.25). CONCLUSIONS Hypothermic fibrillatory arrest is a simple and effective method of quieting the heart, thereby providing a motionless operative field for video-assisted coronary artery bypass grafting.

Echocardiographic findings of mobile atrial hepatocellular carcinoma. Report of five cases.

Hepatoma with cardiac metastasis is difficult to diagnose antemortem. Herein we describe five cases of hepatoma with intracardiac metastasis detected with two‐dimensional echocardiography (2DE). The clinical presentations include cardiac murmur, syncope, and chest pain. The 2DE demonstrated a right atrial (RA) mass in each case and the presence of tumor echoes in the inferior vena cava connecting with the RA mass in four. In three cases the cardiac tumor was removed, whereas the other two patients agreed only to liver biopsy, which confirmed the diagnosis. This paper emphasizes the practical utility of 2DE for early detection of intracardiac hepatoma and also describes the clinicopathologic correlation of such a disease entity.