Nye-Jan Cheng

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

The Gln–Arg 191 polymorphism of the human paraoxonase gene is not associated with the risk of coronary artery disease among Chinese in Taiwan

Paraoxonase (PON1) is a high density lipoprotein-associated enzyme capable of hydrolyzing lipid peroxides, and thus, might protect lipoproteins from oxidation. A common polymorphism due to an amino acid substitution (Gln-Arg) at codon 191 is considered to be a major determinant of variation in serum PON1 activity. Recent studies have suggested that the PON1-191 polymorphism is an independent risk factor for coronary atherosclerosis in patients with or without diabetes mellitus. The association of PON1-191 polymorphism genotypes and coronary artery disease (CAD) among Chinese subjects in Taiwan was examined. The genotype of 218 angiographically documented CAD patients and the same number of age- and sex-matched control subjects was determined. Genotypes AA, AB and BB were present in 25 (11%), 102 (47%) and 91 (42%) of control subjects, respectively, and in 30 (14%), 96 (44%) and 92 (42%) of CAD patients, respectively (chi2 = 0.57, P = 0.75 between groups). The frequency of the A allele was 0.36 for the control group and 0.35 for CAD patients (P = 0.94). No significant differences in the PON1-191 genotype frequencies could be found between groups when multivariate logistic regression analysis was performed, or different subgroups of age, sex or risk factors were analyzed. Among control subjects, there was also no significant difference between genotypes of the PON1-191 polymorphism and various clinical and lipid variables. In conclusion, our data suggest that there is no association between the Gln-Arg 191 polymorphism of the human PON1 gene and CAD among Chinese subjects in Taiwan.

Angiotensinogen and angiotensin-I converting enzyme gene polymorphisms and the risk of coronary artery disease in Chinese

Abstract The homozygous deletion allele (DD) of the angiotensin-I converting enzyme (ACE) gene and the T235 homozygote of the angiotensinogen (AGT) gene have been reported to be correlated with an increased prevalence of coronary artery disease (CAD) and myocardial infarction (MI). The importance of the DD genotype and T235 homozygote as genetic risk factors for CAD in Chinese remains uncertain. This study included 426 patients who underwent coronary angiography and 180 healthy subjects without clinical evidence of CAD. Coronary angiography identified 268 patients with CAD (CAD group) and 158 patients without CAD. The healthy subjects and patients without angiographic evidence of CAD constituted the control group. Three polymorphisms were studied: an insertion/deletion (I/D) polymorphism of the ACE gene and the T174 M and M235T polymorphisms of the AGT gene. No association was found between any of the three studied polymorphisms and the risk of CAD or MI in Chinese using univariate or multivariate analysis. In multivariate analysis, the relative risks were 1.20 (95% confidence interval = 0.91–1.61, P = 0.20) for the DD genotype, 1.05 (95% CI = 0.82–1.35, P = 0.69) for the T174 homozygote, and 1.19 (95% CI = 0.91–1.55, P = 0.20) for the T235 homozygote. Similarly, no significant difference was found in the frequencies of the DD genotype and the T174 and T235 homozygotes between the control group, the CAD group, the non-MI group, and the MI group when analyzed according to sex, age, or degree of risk. Our data suggest that neither the DD genotype of the ACE I/D polymorphism nor the T174 and T235 homozygotes of the AGT gene confer significant risk for CAD or MI in Chinese.

The G1691A mutation of the coagulation factor V gene (factor V Leiden) is rare in Chinese: an analysis of 618 individuals

Abstract To understand the allele frequency of the G1691A mutation of the coagulation factor V gene (factor V Leiden) in Chinese, 618 Chinese individuals, including 54 cases with venous thrombosis, were analyzed. Only one case in the control group was heterozygous for the 1691G allele and the 1691A allele. Our data suggest that the factor V Leiden is rare in Chinese.

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.

Gender differences in baseline variables, therapies and outcomes in Chinese patients with acute myocardial infarction

We prospectively studied the gender differences of baseline variables, therapies, and outcomes among a cohort of 369 Chinese patients with acute myocardial infarction from 1990 to 1995. There were 277 male and 92 female patients. The male gender had a younger mean (+/-SD) age (61.5+/-10.7 vs. 67.1+/-11.7 years, P<0.0001). Hypercholesterolemia (201.2+/-44.2 vs. 187.5+/-43.7 mg/dl, P=0.0111) and obesity (25.0 vs. 15.9%, P=0.0494) were more prominent in the female. Smoking was more prevalent in the male (78.3 vs. 18.5%, P<0.0001). The male group also had more frequent use of thrombolytic agents (19.1 vs. 9.8%, P=0.0377), beta-blockers (61.7 vs. 47.8%, P=0.0191) and heparin (25.3 vs. 12.0%, P=0.0075); but less use of angiotensin-converting enzyme inhibitors (6.9 vs. 15.2%, P=0.0149). The condition on admission was worse in the female group (Killip classification (1.5+/-0.9 vs. 1.9+/-1.0, P=0.0022), myocardial failure (8.7 vs. 2.9%, P=0.0178) and cardiomegaly (65.2 vs. 53.1%, P=0.0419). During a follow-up duration of 26.4+/-24.1 and 22.9+/-23.9 months respectively, the mortality rate was lower in the male (19.5 vs. 30.4%, P=0.0288). However after adjustment for the effect of age, the differences in Killip classification, myocardial failure, cardiomegaly and mortality became insignificant.

On-line multiplane transesophageal echocardiography for balloon mitral commissurotomy.

This study describes in detail the technique and results of on-line multiplane transesophageal echocardiographic guidance of balloon mitral commissurotomy in 150 consecutive patients with symptomatic mitral stenosis. The mitral valve area improved significantly and there were no in-hospital deaths, strokes, or emergency valve operations.

QT interval is prolonged but QT dispersion is maintained in patients with primary aldosteronism.

The relationship between QT duration and its dispersion in patients with primary hyperaldosteronism is not clearly known. We studied 26 patients (nine males and 17 females) with primary hyperaldosteronism. The serum potassium levels were low (2.32 ± 0.52 mmol/l), did not correlate with serum renin or aldosterone levels, or aldosterone/renin ratio (ARR). The maximum QT intervals (QTmax) were prolonged (502 ± 62 ms), correlated well with ARRs (p = 0.005) and aldosterone levels (p = 0.019), but not to renin (p = 0.517) or potassium levels (p = 0.196). The QT dispersions (QTd) were small (60 ± 28.8 ms) and did not correlate with potassium, renin or aldosterone levels.

Atrioventricular nodal reentry tachycardia with multiple AH jumps: Electrophysiological characteristics and radiofrequency ablation

This article describes the additional use of incremental atrial burst pacing (A1A1) and double atrial extrastimulation with a predefined fast pathway conducted A2 (A1A2A3), rather than single atrial extrastimulation (A1A2) only, to characterize typical atrioventricular nodal reentrant tachycardia (AVNRT). The authors noted an additional 32% of patients had multiple anterograde AV nodal physiology demonstrated when A1A1 or A1A2A3 protocols were deployed compared to more conventional A1A2 protocols. The A2H2max (449 ± 147 vs 339 ± 94 ms) and A3H3max (481 ± 120 vs 389 ± 85 ms) were higher in 31 patients where multiple jumps in the AV nodal conduction curve were obtained (group 1) compared to 192 patients where only single jump was obtained (group 2) (both P < 0.01). Postablation, the degree of reduction of A2H2max (49%) and A3H3max (50%) in group 1 was greater than in group 2 (38% and 42%, respectively, P < 0.05). In seven of group 1 patients in whom A1A2A3 stimulation was required to reveal multiple jumps, the A2H2max remained unchanged after ablation (237 ± 89 vs 214 ± 59, P  > 0.05). A3H3max was the only parameter that shortened significantly after ablation. Generally, successful ablation resulted in loss of multiple discontinuities in A1A1/A1H1 or A2A3/A3H3 curves. In conclusion, a combination of A1A2, A1A1, and A1A2A3 are required to fully elucidate AVNRT. Significant shortening of AHmax or loss of multiple jumps after ablation indicates successful elimination of AVNRT in these patients. (PACE 2003; 26:1849–1855)

Exercise-induced myocardial ischaemia complicated by paroxysmal complete atrioventricular block

This study describes a case of exercise‐induced myocardial ischaemia accompanied by complete atrioventricular block (CAVB). A 59‐year‐old man with major depression, treated with regular imipramine and lithium for 20 years, experienced syncope episodes during exercise. Exercise, testing initially, identified ST depression in the inferior leads, and later found CAVB resulting in syncope and seizure. The patient recovered completely after resuscitation. Myocardial ischaemic markers were negative, but 35% stenosis was detected in the distal left main coronary artery by angiography. The combined use of verapamil, nitrate and aspirin was treated as the possible coronary spasm. Repeat treadmill caused negative ischaemic study or exercise‐induced arrhythmia, 7 days later. The pathophysiology of the very rare exercise‐induced paroxysmal CAVB has been reviewed.