Gender difference in clinical and genetic characteristics of Brugada syndrome: SADS-TW BrS registry.

BACKGROUND: Brugada syndrome (BrS) is a heritable sudden cardiac death (SCD) disease with male predominance. Information on gender difference of BrS remains scarce. AIM: To investigate the gender difference of BrS in Han Chinese. DESIGN: We consecutively enrolled 169 BrS patients (153 males and 16 females) from Han Chinese in Taiwan from 1998 to 2017. METHODS: Clinical characteristics, electrocardiographic parameters and SCN5A mutation status were compared between genders. RESULTS: The percentage of family history of SCD in females was slightly higher (31.3% vs. 15%, P = 0.15). Females exhibited longer QTc (457.8 ± 33.0 vs. 429.5 ± 42.1 ms, P < 0.01). Regarding cumulative event occurrence by age, Mantel-Cox test showed females had earlier age of onset of first cardiac events (SCD or syncope) than males (P = 0.049), which was mainly attributed to syncope (P < 0.01). Males with SCD exhibited longer QRS duration (114.2 ± 26.8 vs. 104.8 ± 15.3 ms, P = 0.02) and QTc (442.5 ± 57.4 vs. 422.9 ± 28.8 ms, P = 0.02). Males with syncope exhibited longer PR interval (181.2 ± 33.7 vs. 165.7 ± 27.1 ms, P = 0.01), whereas females with SCD or syncope had a trend towards slower heart rates (69.1 ± 9.6 vs. 82.2 ± 16.3 bpm, P = 0.10) than female with no or mild symptoms. There was no difference in the percentage of SCN5A mutation between genders. CONCLUSION: Gender difference is present in BrS. Females have longer QTc and suffer from syncope earlier than males. Risk of SCD in males is associated with boarder QRS complex and longer QTc, whereas risk of syncope is associated with longer PR interval in males and slower heart rate in females.

C-reactive protein gene polymorphism predicts the risk of thromboembolic stroke in patients with atrial fibrillation: a more than 10-year prospective follow-up study.

Essentials We studied the C-reactive protein (CRP) gene on stroke risk in atrial fibrillation (AF) patients. 725 patients with CRP triallelic polymorphism genotype were followed-up for more than 10 years. Patients with the A-390/T-390 allele of the CRP gene were more likely to get ischemic stroke. The triallelic polymorphism of the CRP is related to ischemic stroke in AF patients. SUMMARY: Background Little evidence is available regarding the impact of genetic polymorphisms on the risk of thromboembolic stroke in patients with atrial fibrillation (AF). An increasing body of evidence is demonstrating that inflammatory responses play an important role in the pathophysiology of AF. Objectives To investigate the effect of genetic polymorphisms of the C-reactive protein (CRP) gene on the incidence of thromboembolic stroke in patients with AF. Methods A total of 725 AF patients were longitudinally followed up for > 10 years; this is the largest and longest AF follow-up cohort with genetic data. CRP promoter triallelic polymorphisms (C-390A and C-390T) were genotyped, and CRP levels were divided into four quartiles. Results Patients with higher CRP levels were more likely to develop thromboembolic stroke than those with lower CRP levels (P<0.001, log-rank test for comparison of four quartiles). After adjustment for conventional risk factors, patients with higher CRP levels were more likely to develop thromboembolic stroke than those in the lowest CRP quartile (hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.08-4.81; the lowest CRP quartile was the reference group). Patients carrying the A-390 or T-390 allele had higher CRP levels (3.35 ± 2.71 mg L-1 versus 2.43 ± 2.00 mg L-1 ), and were more likely to develop thromboembolic stroke, even after adjustment for conventional risk factors (HR 2.07, 95% CI 1.23-3.48). Conclusion The CRP triallelic polymorphism and the CRP level are associated with the risk of incident thromboembolic stroke in patients with AF.

Statin use reduces the risk of dementia in elderly patients: a nationwide data survey and propensity analysis.

OBJECTIVES: The objective of this study was to examine the association between the use of statins and the risk of newly diagnosed dementia in an elderly population. DESIGN, SETTING AND PARTICIPANTS: Random samples of 1,000,000 individuals covered by the National Health Insurance in Taiwan were included in the analysis. All participants were 65 years or older without dementia and either did or did not start treatment with statins from 1 August 1997 to 31 December 2010. Patients with established dementia before the start of treatment were excluded. Baseline characteristics were matched (by propensity score) in those who did and did not receive statins. RESULTS: A total of 57,669 subjects were included in the analysis with approximately 12 years of follow-up. Propensity score matching identified 2003 patients who received statins and another 2003 patients who did not with comparable baseline characteristics. Adjusted hazard ratios (HRs) for dementia were significantly inversely associated with total or daily equivalent statin dosage (total accumulated dose: HRs 0.829, 0.720 and 0.385 from T1 to T3 vs. control, P < 0.001 for trend; mean daily dose: HRs 0.667, 0.798 and 0.503 from T1 to T3 vs. control, P < 0.001). The results remained robust after propensity adjustment. CONCLUSION: Independent of traditional risk factors, there was a decrease in newly diagnosed cases of dementia in elderly patients who had received a high total or daily dose of statins. The more potent statins (e.g. atorvastatin and rosuvastatin) seemed to be particularly effective in the prevention of dementia.

A functional variant in the promoter region regulates the C-reactive protein gene and is a potential candidate for increased risk of atrial fibrillation.

OBJECTIVES: In a large population-based cohort, the level of C-reactive protein (CRP) in patients at baseline predicts an increased risk of future development of atrial fibrillation (AF). The mechanism of this increased risk is unknown. Furthermore, both the molecular effects of CRP on atrial myocytes and fibroblasts and whether genetic variants in the CRP gene predispose to AF are also unknown. METHODS: A genetic association study between CRP gene polymorphisms and AF was performed in two independent populations (I: 100 AF patients and 101 controls; II: 348 AF patients and 356 controls), with functional studies to elucidate the mechanism of association. RESULTS: Three polymorphisms (T-861C, A-821G and C-390A/C-390T) were found in the 1-kb promoter of CRP. A triallelic polymorphism (C-390A/C-390T) captured all haplotype information and determined the CRP gene promoter activity and the plasma CRP level, and was in nearly complete linkage disequilibrium with G1059C polymorphism in exon 2. The -390A variant was associated with a higher CRP gene promoter activity, a higher plasma CRP level and a higher risk of AF. Patients with AF also had a higher plasma CRP level than controls. CRP significantly increased the inward L-type calcium current in atrial myocytes with no changes in other ionic currents. CRP did not affect the expressions of type I alpha 1 (COL1A1), type III alpha 1 (COL3A1) and type 1 alpha 2 (COL1A2) procollagens in atrial fibroblasts. CONCLUSION: A CRP gene promoter triallelic polymorphism was associated with CRP gene promoter activity, determined the plasma level of CRP, and predicted the risk of AF. The mechanism of this may be via augmention of calcium influx by CRP in atrial myocytes, but not because of atrial fibrosis.

Differential association of proinflammatory cytokines with left ventricular diastolic dysfunction in subjects with and without continuous ambulatory peritoneal dialysis.

BACKGROUND AND AIMS: The association between inflammation and left ventricular (LV) diastolic dysfunction in continuous ambulatory peritoneal dialysis (CAPD) and non-CAPD patients is not established. The objective of this study was to test the above association and whether inflammation interacts with CAPD to increase LV diastolic dysfunction risks. METHODS AND RESULTS: 120 subjects with normal creatinine levels and 101 CAPD patients were recruited. Echocardiographic parameters were assessed in all patients. The participants were classified as having LV diastolic dysfunction by echocardiographic findings including mitral inflow E/A ratio < 1, deceleration time > 220 cm/s, or decreased peak annular early diastolic velocity in tissue Doppler imaging. Blood was sampled at the baseline for measurement of inflammation markers, including tissue necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Subjects with LV diastolic dysfunction had higher proinflammation cytokines levels in both groups. Inflamed markers correlated significantly with echocardiography parameters for LV diastolic dysfunction in patients receiving CAPD. In a multivariate regression analysis adjusting for all the factors associated with LV diastolic dysfunction, inflammation is still significantly associated with left ventricular diastolic dysfunction (TNF-alpha, OR: 2.6, 95% CI: 2.0-3.35, p < 0.001; IL-6, OR: 1.26, 95% CI: 1.25-1.26, p = 0.01). In addition, the interaction of CAPD and inflammation significantly contributed to the development of LV diastolic dysfunction (CAPD∗ TNF-α: OR: 1.45, 95% CI: 1.13-1.79, P = 0.004). CONCLUSION: We found inflammation plays a vital role for LV diastolic dysfunction especially in CAPD patients. A synergistic effect between CAPD and inflammation, especially TNF-α, would further aggravate LV diastolic dysfunction.

Demonstrating the pharmacogenetic effects of angiotensin-converting enzyme inhibitors on long-term prognosis of diastolic heart failure.

The objective of this study was to evaluate the effects of angiotensin-converting enzyme (ACE) inhibitors and pharmacogenetic interaction on the survival of the patients with diastolic heart failure (DHF). A total of 285 subjects with DHF confirmed by echocardiography were recruited in the period between 1995 and 2003. Baseline characteristics (age, sex, prior history, medication, and echocardiographic findings) and genetic polymorphisms (ACE gene insertion/deletion (I/D) polymorphism; T174M, M235T, G-6A, A-20C, G-152A, and G-217A polymorphisms of the angiotensinogen (AGT) gene; and A1166C polymorphisms of the angiotensin II type I receptor (AT1R)) were collected and matched (by propensity score) in those who received and those who did not receive ACE inhibitors. The patients were followed up to 10 years. Kaplan-Meier curves and Cox regression models were used to demonstrate the survival trend. The 85 patients who received ACE inhibitors and the other 85 patients who did not were found to have comparable baseline characteristics and polymorphism distribution. Prescription of ACE inhibitors was associated with a significant decrease in overall mortality (hazard ratio (HR), 0.45; 95% confidence interval (CI), 0.24-0.83; P=0.01), and a lower rate of cardiovascular events at 4000 days (HR, 0.53; 95% CI, 0.32-0.90; P=0.02). In addition, ACE I/D gene D allele was associated with higher overall mortality as compared with the I allele (HR, 2.04; P=0.003). This effect was diminished in those who received ACE inhibitors. The use of ACE inhibitor was associated with a significant decrease in long-term mortality and cardiovascular events in the patients with DHF. Genetic variants in the renin-angiotensin system genes were also associated, but their effects could be modified by the use of ACE inhibitors.

Efficacy and safety of valsartan/hydrochlorothiazide fixed-dose combination compared with amlodipine monotherapy as first-line therapy for mild to moderate hypertension.

This double-blind, active- and randomized-controlled study compared the efficacy and safety of a fixed-dose combination of valsartan/hydrochlorothiazide 80 mg/12.5 mg once daily (n = 32) with amlodipine monotherapy 5 mg once daily (n = 33) for 8 weeks in patients with mild to moderate hypertension. Non-inferiority of valsartan/hydrochlorothiazide to amlodipine was demonstrated by comparable reductions in sitting systolic blood pressure (SBP), sitting diastolic blood pressure (DBP), and daytime, night-time and 24-h SBP and DBP on ambulatory blood pressure monitoring. Between-group comparisons of adverse events and changes in laboratory parameters did not reach statistical significance, except for uric acid which showed a significant increase in the valsartan/hydrochlorothiazide group compared with the amlodipine group, but was still below the laboratory's upper limit of normal. In conclusion, the use of the fixed-dose combination of valsartan/hydrochlorothiazide 80 mg/12.5 mg once daily as a starting regimen in patients with mild to moderate hypertension was shown to have non-inferior efficacy and comparable safety for daily practice compared with amlodipine 5 mg once daily monotherapy.

Rupture of mitral chordae tendineae: adding to the list of hypertension complications.

BACKGROUND: Many patients with chordae tendineae rupture (CTR) of the mitral valve have obscure aetiologies. The association between pre-existing hypertension and idiopathic CTR was investigated. METHODS: 494 patients with CTR were identified by searching the computer database. For each patient with idiopathic CTR, three matched controls without CTR who were admitted to the same hospital for bone fractures were included. RESULTS: Among the 494 patients with CTR, 351 patients (71%) had idiopathic CTR, and 143 patients (29%) had secondary CTR. The prevalence of pre-existing hypertension was significantly higher in the idiopathic than in the secondary CTR group (50.9% vs 14.6%, p<0.001). The odds ratio was 6.0 (95% CI 3.6 to 10.1). The percentage of patients without adequate blood pressure control was also higher in the idiopathic than in the secondary CTR group (23.1% vs 4.9%, p<0.001). When compared with the fracture group, patients with idiopathic CTR also had a significantly higher prevalence of hypertension (50.9% vs 14.9%, p<0.001), and the odds ratio was 5.9 (95% CI 4.5 to 7.8). After correction for age, the odds ratio of having hypertension was 3.6 (95% CI 2.1 to 6.3) and 6.6 (p<0.001, 95% CI 5.0 to 8.8) when compared with the secondary CTR group and fracture group respectively. CONCLUSIONS: There is a strong association between pre-existing hypertension and idiopathic CTR. Whether or not this disease can be prevented by controlling hypertension deserves further investigation.

Renin-angiotensin system gene polymorphisms and diastolic heart failure.

BACKGROUND: Diastolic heart failure (DHF) refers to an abnormality of diastolic distensibility, filling or relaxation of the left ventricle. The genetic study of DHF is scarce in the literature. The association of renin-angiotensin system (RAS) and DHF are well known. We hypothesized that RAS genes might be the susceptible genes for DHF and conducted a case-control study to prove the hypothesis. MATERIALS AND METHODS: A total of 1452 consecutive patients were analysed and 148 patients with a diagnosis of DHF confirmed by echocardiography were recruited. We had two control populations. The first controls consisted of 286 normal subjects while the second were 148 matched controls selected on a 1-to-1 basis by age, sex, hypertension, diabetes and medication use. The angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism; multilocus polymorphisms of the angiotensinogen gene; and the A1166C polymorphisms of the angiotensin II type I receptor (AT(1)R) gene were genotyped. RESULTS: In a single-locus analysis, the odds ratios (ORs) for DHF were significant with the ACE DD genotype and the AT(1)R 1166 CC plus AC genotype. In addition, the concomitant presence of ACE DD and AT(1)R 1166 CC/AC genotypes synergistically increased the predisposition to DHF. CONCLUSIONS: Genetic variants in the RAS genes may determine an individual's risk to develop DHF. There is also a synergistic gene-gene interaction between the RAS genes in the development of DHF.

Relation of Chlamydia pneumoniae infection in Taiwan to angiographically demonstrated coronary artery disease and to the presence of acute myocardial infarction or unstable angina pectoris.

Reports of the association of Chlamydia pneumoniae (C. pneumoniae) infection with coronary artery disease (CAD) are scarce in the Oriental population. We therefore conducted a case-control study to explore this issue in Taiwan. There were 242 consecutive subjects (166 men and 76 women) who underwent cardiac catheterization at the National Taiwan University Hospital Cardiac Catheterization Laboratory. Patients with CAD (n = 156) had > or = 1 coronary artery lesion of > 50% diameter stenosis on angiography. Controls (n = 86) had no demonstrable CAD angiographically. Antibodies to C. pneumoniae were tested by using an enzyme-linked immunosorbent assay. The prevalence of antibodies to C. pneumoniae was as follows: immunoglobulin-G (IgG), 50% (122 of 242 patients); immunoglobulin-A (IgA), 72% (176 of 242 patients); and either IgG or IgA, 79% (192 of 242 patients ). The odds ratio (OR) for CAD with either IgG or IgA was 1.4 (95% confidence interval [CI] 0.7 to 2.7, p = 0.31). After adjusting for the known CAD risk factors, the OR decreased to 0.8 (95% CI 0.3 to 2.1, p = 0.60). The OR for unstable angina or acute myocardial infarction with the presence of either IgG or IgA was 0.5 (95% CI 0.2 to 1.1, p = 0.08) and 0.4 ( 95% CI 0.1 to 1.0, p = 0.049) after adjusting for other risk factors. These results suggest a high prevalence of C. pneumoniae infection in Taiwan. However, C. pneumoniae infection is not associated with angiographically documented CAD, and, in contrast, is a negative predictor for the development of acute coronary syndromes.

Efficacy and safety of imidapril in patients with essential hypertension: a double-blind comparison with captopril.

In this 12-week, double-blind, parallel-group, comparative trial, 57 adult patients with mild-to-moderate hypertension were randomly allocated to receive imidapril or captopril, initially at a dose of 5 mg once a day and 25 mg twice daily, respectively. After 4 weeks of therapy, the dose of each drug was increased twice if diastolic blood pressure (DBP) remained > or =90 mm Hg. Both treatments effectively lowered DBP in a comparable manner. Mean changes from baseline in DBP at 12 weeks were -9.9 mm Hg for imidapril and -8.8 mm Hg for captopril (p = 0.488). Responder rates in patients receiving active treatment for at least 6 weeks were 53.9% for imidapril and 48% for captopril (p = 0.676). Both treatments were well tolerated. Adverse drug reactions were observed in 20.7% (6/29) of the imidapril group and 46.4% (13/28) of the captopril group (p < 0.05). A cough was the most frequent side effect, reported in 13.8% of the imidapril group and 35.7% of the captopril group. The results indicate that imidapril is as effective as captopril in the treatment of hypertension. Imidapril produces less adverse effects compared with captopril.

The glycine allele of a glycine/arginine polymorphism in the beta2-adrenergic receptor gene is associated with essential hypertension in a population of Chinese origin.

BACKGROUND: Several studies implicate polymorphisms in the human beta-adrenergic receptor gene (ADRB2) in the susceptibility to hypertension. We sought to replicate these results in a population of Chinese origin primarily from Taiwan and the San Francisco Bay area. METHODS: We genotyped >800 hypertensive subjects and individuals with low-normal blood pressure that were derived largely from the same families as the hypertensive patients for three polymorphisms in the ADRB2 gene: a C/T transition at position 47 (C-47T) in the 5' leader cistron; another C/T transition that results in a glycine/ arginine substitution at codon 16 (Gly16Arg), and a G/C transversion that causes a glutamate/glutamine substitution at codon 27 (Glu27Gln). RESULTS: The Gly16Arg was significantly associated with hypertension (P < .03). Under a dominant model, for hypertension the relative risk for the Gly/Gly and Gly/Arg genotypes versus the Arg/Arg genotype was 1.35 (95% confidence limits [CL] 1.08, 1.70); for low-normal blood pressure the relative risk was 0.79 (95% CL 0.66, 0.94). This polymorphism explained approximately 1% of the variance in systolic and diastolic blood pressures in our study population. There was no evidence of association between the C-47T and Glu27Gln polymorphisms and hypertension in this population. CONCLUSIONS: The Glyl6 allele in the beta2-adrenergic receptor gene is a susceptibility allele for essential hypertension in a population of Chinese origin.

Successful treatment of aconitine induced life threatening ventricular tachyarrhythmia with amiodarone.

With the increasing trend of cross mixing of populations, aconitine induced poisoning and its related arrhythmias may be more frequently encountered worldwide. However, the clinical experience is often too limited to draw any conclusion on the optimal treatment for tachycardia induced by aconitine intoxication. The clinical presentation, serial electrocardiographic changes, and responses to antiarrhythmic agents are reported in a patient with aconitine induced life threatening ventricular tachyarrhythmia. Amiodarone was effective in suppressing polymorphic ventricular tachycardia, which might provide an example of successful pharmacological intervention in aconitine induced ventricular tachyarrhythmia.

Ultrasonic tissue characterization evaluates myocardial viability and ischemia in patients with coronary artery disease.

To evaluate whether or not ultrasonic tissue characterization (UTC) can detect jeopardized or salvageable myocardium in patients having chronic coronary artery disease, we studied 103 patients with sequential UTC, dobutamine stress echocardiography (DSE) and (201)thallium stress-reinjection single-photon emission computed tomography (T1-SPECT). This revealed that the weighted amplitude of the cyclic modulation of integrated backscatter was larger for the myocardium with less ischemia burden or greater viability (p<0.001). The segments with larger ischemia burden or the nonviable myocardium demonstrated the contrary result. Using the receiver-operating characteristic curve analyses to determine the cutoff value of weighted amplitude for various predictions, UTC can detect ischemia in normokinetic myocardium (kappa = 0.34 compared to DSE or T1-SPECT) and viability in dyssynergic myocardium (kappa = 0.57 compared to DSE and 0.45, to T1-SPECT). These observations show that UTC may prove useful in the identification and pathophysiological understanding of myocardial ischemia and viability.

Expression pattern in a modified equalized kidney cDNA library of hypertensive rat.

BACKGROUND: Genes with important functions and rarely expressed would probably more easily be cloned from a modified equalized kidney cDNA library for further investigation. METHODS: A kidney cDNA library of a spontaneously hypertensive rat was synthesized by a modified equalization method. Inserts of random clones were amplified by PCR and sequenced. Sequences were compared against a nonredundant database in GenBank. The cDNA profile was compared with an expression profile of a mouse renal proximal tubule cDNA library. Seven clones were analyzed by Northern blot analysis. The cDNA ends of two novel genes were amplified by PCR, sequenced and analyzed. RESULTS: 336 cDNA clones were analyzed and grouped into 323 species of transcript with 77 species similar to previously reported genes. Northern blot analysis identified one kidney-specific, one rarely expressed and lung-specific, and another relatively testis-specific gene. Two novel genes were cloned. One was 4.1 kb in length and encoded a 390-amino acid zinc-finger protein. Another was 2.5 kb and encoded a 474-amino acid protein of unknown function. Compared with the expression profile of a mouse renal proximal tubule cDNA library, this kidney library had a lower proportion of ribosomal genes and had a greater proportion of genes for signal transduction and DNA or RNA binding. CONCLUSIONS: Rare or novel genes could be more easily isolated from this library for molecular study of hypertension and renal pathophysiology.

Cloning a novel metallophosphoesterase gene from a kidney cDNA library of hypertensive rat.

BACKGROUND AND PURPOSE: Genetic and environmental factors may contribute to the pathogenesis of essential hypertension. To facilitate genetic studies of hypertension and renal disorders, we sought to clone novel genes from a modified, equalized kidney (MEK) cDNA library of a spontaneously hypertensive rat (SHR). METHODS: A kidney cDNA library of an SHR was synthesized using the modified equalization method. Inserts of 350 random clones were amplified by polymerase chain reaction (PCR) and sequenced, of which 246 were presumably unknown after being compared against a nonredundant database in the GenBank. The cDNA ends of clone 38S were obtained by rapid amplification of cDNA ends, sequenced, and then analyzed with Translate, Prosite, Profile, SignalP, and TMpred programs. RESULTS: The full-length cDNA was 938 bp, and translated into a 182-amino acid protein. The deduced protein had a metallophosphoesterase domain, a signal peptide at its amino end, a protein kinase C phosphorylation site, and a transmembrane domain. Northern blot analysis revealed that this gene was expressed in the heart, brain, spleen, lungs, liver, skeletal muscles, kidneys and testes of Sprague-Dawley rats. A putative protein of Arabidopsis thaliana shares 62% homology with protein 38S, but the two proteins differ in terms of function and structure. CONCLUSIONS: Our results support that protein 38S is a novel membrane metallophosphoesterase, although its function in the kidneys remains to be elucidated. This study also demonstrates the feasibility of using PCR to clone novel genes from our MEK cDNA library.

Brugada syndrome without mutation of the cardiac sodium channel gene in a Taiwanese patient.

We describe a 45-year-old Taiwanese man with specific features of Brugada syndrome but no clinical features of structural heart disease. He was successfully treated with an implantable cardioverter-defibrillator. His electrocardiogram (ECG) patterns changed intermittently. Alpha-adrenoceptor stimulation and beta-adrenoceptor blockade augmented the characteristic ST-segment elevation, whereas alpha-adrenoceptor blockade and beta-adrenoceptor stimulation mitigated the ST-segment elevation. Intravenous procainamide administration did not aggravate ST-segment elevation when ECG had shown coved ST elevation in the right precordial leads. Molecular study did not reveal the same mutations in the cardiac sodium channel gene (SCN5A) as previously reported in Brugada syndrome. This case demonstrates the genetic heterogeneity of SCN5A in Brugada syndrome.

Characteristic findings of body surface potential map during ventricular repolarization in patients with coronary heart disease.

The objective of the present study was to investigate the characteristics of body surface potential map (BSPM) findings during ventricular repolarization in patients with coronary artery disease (CAD). A total of 108 consecutive patients, 99 men and 9 women with angina pectoris and positive treadmill exercise test results as well as angiographically documented CAD underwent BSPM study in a fasting state. Their ages ranged from 30 to 70 years. There were 13 patients with right coronary artery (RCA) lesions, 37 with left anterior descending artery (LAD) lesions, 5 with left circumflex artery (LCX) lesions, 17 with both RCA and LAD lesions, 12 with both LCX and LAD lesions, and 24 with 3-vessel disease. The BSPMs were obtained by using the heart potential map system designed by Toyama et al. There were 59 lead points on the anterior chest wall and 28 on the back. The BSPMs in isopotential distribution were made every one msec throughout the ventricular activation period. The distribution of positive and negative potentials, potential maximum and potential minimum, polarity of potential distribution, and the reversal of potential distribution during ventricular repolarization were analyzed. The following information on BSPMs was obtained: (1) In early ventricular repolarization, the negative potential and the potential minimum appeared abnormally on the anterior thorax. The potential abnormality displayed on the right portion or the inferior portion in patients with RCA lesions, on the middle portion or the left portion in patients with LAD lesions, and on the left-superior portion or the left-middle portion in patients with LCX lesions. In patients with multi-vessel disease, the abnormal potential distribution showed a combined pattern of individual vessel lesions. (2) In some cases, the multipolar potential distribution appeared abnormally during the initial stage and the peak of the T wave. (3) The reversal of potential distribution was observed in about half of the patients. The characteristic findings of the BSPM during ventricular repolarization, including abnormal potential distribution, multipolar potential distribution and reversal of potential distribution, will be of clinical value in patients with CAD.

Newly identified missense mutation reduces lipoprotein lipase activity in Taiwanese patients with hypertriglyceridemia.

Lipoprotein lipase (LPL) plays a crucial role in the regulation of lipoprotein metabolism by hydrolyzing the core triglycerides of circulating chylomicrons and very low-density lipoprotein. Deficiency in this enzyme usually results in disturbances in lipid levels. To understand the molecular defect that leads to a functional deficiency of LPL in patients with hypertriglyceridemia, we looked for mutations of the LPL gene by means of single-strand conformation polymorphism (SSCP) analysis and direct DNA sequencing in 24 patients. A single base C-->G substitution in codon 252 of the LPL gene, encoding a change of a leucine to a valine residue in the mature protein, was found in three women who had hypertriglyceridemia and recurrent pancreatitis. Two of these patients, who were homozygous for the L252V mutation, had variable and occasionally severe hypertriglyceridemia with undetectable or very low LPL activities, respectively. The third woman was heterozygous for this mutation. All three patients had poor post-heparin LPL activity. Site-directed mutagenesis experiments provided in vitro evidence that the mutation of codon 252 was responsible for the loss of LPL activity. In conclusion, we identified a novel LPL mutation that results in decreased LPL activity in Taiwanese patients with hypertriglyceridemia. The assessment of a causative link between the mutation and hyperlipidemia awaits further studies.

Implications of an early reversal pattern of body surface potential maps in coronary artery disease.

During early ventricular depolarization, the normal body surface potential map (BSPM) has a maximal potential that is greater than the absolute value of the minimal potential; this reverses in late depolarization, so that the absolute value of the minimal potential is greater. Nevertheless, an abnormal "early reversal" BSPM pattern has been observed in some patients with cardiovascular disease. To investigate the implications of this abnormal pattern, BSPMs were studied in 100 patients with angiographically proven coronary artery disease (CAD). There were 57 patients (57%; group A) with an abnormal early reversal pattern and 43 (43%; group B) without this early reversal pattern. A significant (> 70% narrowing) CAD lesion was observed in a significantly higher proportion of group A (97%) than group B (77%) patients, although the number of involved coronary arteries was not significantly different between the two groups. The maximal extent of the abnormal negative potential was significantly greater in group A (21.2 +/- 9.6 cm2) than in group B (12.2 +/- 7.5 cm2). The abnormal negative potential lasted significantly longer in group A (22.1 +/- 12.1 msec) than in group B (14.4 +/- 9.2 msec). Similarly, the minimal potential lasted significantly longer in group A (20.1 +/- 11.3 msec) than in group B (11.8 +/- 7.1 msec). These findings suggest that the abnormal early reversal BSPM pattern is a valuable indicator of extensive myocardial lesions and the severity of CAD.