Severe respiratory failure and torsades de pointes induced by disopyramide in a patient with myasthenia gravis.

Class 1a anti-arrhythmic drugs are often used for the treatment of atrial fibrillation (AF), but it is not well known that myasthenia gravis (MG)-like symptoms can be generated by their anti-cholinergic effects. We had a patient with MG who developed symptomatic MG aggravation after AF treatment with disopyramide. Symptomatic MG aggravation was followed by Takotsubo-shaped cardiomyopathy, QT prolongation, and torsades de pointes. We suggest that the anti-cholinergic effects of disopyramide can induce MG crisis and should therefore be carefully considered when disopyramide is used to treat AF in patients with MG.

Impact of serum insulin-like growth factor-1 on early prognosis in acute myocardial infarction.

OBJECTIVE: Previous research revealed that a low concentration of serum insulin-like growth factor-1 (IGF-1) is associated with risks of myocardial infarction and heart failure. We hypothesized that the serum IGF-1 level affects clinical outcome in acute myocardial infarction (AMI). We examined the impact of serum IGF-1 in acute phase of AMI on 90-day mortality. PATIENTS AND METHODS: In 54 patients with AMI, we measured serum total IGF-1 concentration on admission, in acute phase (1.9+/-0.5 days) and in chronic phase (28.5+/-6.7 days). We measured plasma brain natriuretic peptide (BNP), glucose and insulin in acute phase, and calculated insulin resistance (HOMA-R). RESULTS: Serum IGF-1 was 135.6+/-51.1 ng/ml on admission and significantly decreased to 105.5+/-42.2 ng/ml in acute phase, and then returned to baseline of 136.7+/-52.2 ng/ml in chronic phase. Five patients died of cardiac reasons within 90 days, all of whom had lower IGF-1 on admission and lower IGF-1 in acute phase than their median of 54 patients. Patients with the concentration of IGF-1 on admission below the median (<131 ng/ml) had significantly lower survival rate than those at or above the median (log-rank test p=0.0169). However, patients with BNP concentration at or above the median (> or =227 pg/ml) had a similar survival rate to those below the median (log-rank test p=0.6797). Multivariate analysis clarified that IGF-1 on admission was the sole independent predictor of 90-day mortality (p=0.007, risk ratio=0.927). CONCLUSION: A low concentration of serum IGF-1 on admission was associated with a poor early prognosis of acute myocardial infarction.

High plasma heparin cofactor II activity is associated with reduced incidence of in-stent restenosis after percutaneous coronary intervention.

BACKGROUND: Thrombin plays an important role in the development of atherosclerosis and restenosis after percutaneous coronary intervention. Because heparin cofactor II (HCII) inhibits thrombin action in the presence of dermatan sulfate, which is abundantly present in arterial wall, HCII may affect vascular remodeling by modulating thrombin action. We hypothesized that patients with high plasma HCII activity may show a reduced incidence of in-stent restenosis (ISR). METHODS AND RESULTS: Sequential coronary arteries (n=166) with NIR stent (Boston Scientific Corp) implantation in 134 patients were evaluated before, immediately after, and at 6 months after percutaneous coronary intervention. Patients were divided into the following groups: high HCII (> or =110%, 45 lesions in 36 patients), normal HCII (> or =80% and <110%, 81 lesions in 66 patients), and low HCII (<80%, 40 lesions in 32 patients). Percent diameter stenosis at follow-up in the high-HCII group (18.7%) was significantly lower (P=0.046) than that in the normal-HCII group (30.3%) or the low-HCII group (29.0%). The ISR rate in the high-HCII group (6.7%) was significantly lower than that in the low-HCII group (30.0%) (P=0.0039). Furthermore, multivariate analysis demonstrated that high plasma HCII activity is an independent factor in reducing the incidence of angiographic restenosis (odds ratio, 0.953/1% increase of HCII; 95% CI, 0.911 to 0.998). CONCLUSIONS: The results demonstrate that HCII may have a hitherto unrecognized effect in inhibiting ISR. The effect of HCII may be mediated by inactivating thrombin in injured arteries, thereby inhibiting vascular smooth muscle cell migration and proliferation.

Effect of aspirin treatment on serum concentrations of lipoprotein(a) in patients with atherosclerotic diseases.

BACKGROUND: Increased serum lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerosis. We previously reported that aspirin reduced Lp(a) production by cultured hepatocytes via the reduction of apolipoprotein(a) [apo(a)] gene transcription. METHODS: We evaluated both the effect of aspirin treatment (81 mg/day) on serum Lp(a) concentrations and the correlation between the degree of reduction in serum Lp(a) and the type of apo(a) isoform in 70 patients with coronary artery disease or cerebral infarction. RESULTS: Aspirin lowered serum Lp(a) concentrations to approximately 80% of the baseline values in patients with high Lp(a) concentrations (>300 mg/L). The percentage of decrease in serum Lp(a) was larger in patients with high Lp(a) than in patients with low Lp(a) (<300 mg/L), irrespective of apo(a) isoform size. The decreases in serum Lp(a) in high Lp(a) patients with both the high-molecular-weight and the low-molecular-weight isoforms were positively correlated with the baseline Lp(a) concentrations. CONCLUSIONS: Because the secretory efficiencies of apo(a) in the same isoform are likely to be similar, the difference in serum Lp(a) concentrations in patients having the same apo(a) isoform depends on the transcriptional activity of the apo(a) gene. These findings suggest that aspirin decreases serum Lp(a) concentrations via a decrease in apo(a) gene transcription more effectively in patients with high transcriptional activity of this gene.