Antegrade slow pathway mapping of typical atrioventricular nodal reentrant tachycardia based on direct slow pathway capture.

BACKGROUND: Radiofrequency (RF) ablation of typical atrioventricular nodal reentrant tachycardia (tAVNRT) is performed without revealing out the location of antegrade slow pathway (ASp). In this study, we studied a new electrophysiological method of identifying the site of ASp. METHODS: This study included 19 patients. Repeated series of very high-output single extrastimulations (VhoSESts) were delivered at the anatomical slow pathway region during tAVNRT. Tachycardia cycle length (TCL), coupling interval (CI), and return cycle (RC) were measured and the prematurity of VhoSESts [ΔPM (= TCL - CI)] and the prolongation of RCs [ΔPL (= RC - TCL)] were calculated. Pacing sites were classified into two categories: (i) ASp capture sites [DSPC(+) sites], where two different RCs were shown, and ASp non-capture sites [DSPC(-) sites], where only one RC was shown. RF ablation was performed at DSPC(+) sites and/or sites with catheter-induced mechanical trauma (CIMT) to ASp. RESULTS: DSPC(+) sites were shown in 13 patients (68%). RF ablation was successful in all patients without any degree of atrioventricular block nor recurrence. Total number of RF applications was 1.8 ± 1.1. Minimal distance between successful ablation sites and DSPC(+)/CIMT sites and His bundle (HB) electrogram recording sites was 1.9 ± 0.8 mm and 19.8 ± 6.1 mm, respectively. ΔPL of more than 92.5 ms, ΔPL/TCL of more than 0.286, and ΔPL/ΔPM of more than 1.565 could identify ASp with sensitivity of 100%, 91.1%, and 88.9% and specificity of 92.9%, 97.0%, and 97.6%, respectively. CONCLUSIONS: Sites with ASp capture and CIMT were close to successful ablation sites and could be useful indicators of tAVNRT ablation.

Strain-dependent embryonic lethality and exaggerated vascular remodeling in heparin cofactor II-deficient mice.

Heparin cofactor II (HCII) specifically inhibits thrombin action at sites of injured arterial wall, and patients with HCII deficiency exhibit advanced atherosclerosis. However, the in vivo effects and the molecular mechanism underlying the action of HCII during vascular remodeling remain elusive. To clarify the role of HCII in vascular remodeling, we generated HCII-deficient mice by gene targeting. In contrast to a previous report, HCII(-/-) mice were embryonically lethal. In HCII(+/-) mice, prominent intimal hyperplasia with increased cellular proliferation was observed after tube cuff and wire vascular injury. The number of protease-activated receptor-1-positive (PAR-1-positive) cells was increased in the thickened vascular wall of HCII(+/-) mice, suggesting enhanced thrombin action in this region. Cuff injury also increased the expression levels of inflammatory cytokines and chemokines in the vascular wall of HCII(+/-) mice. The intimal hyperplasia in HCII(+/-) mice with vascular injury was abrogated by human HCII supplementation. Furthermore, HCII deficiency caused acceleration of aortic plaque formation with increased PAR-1 expression and oxidative stress in apoE-KO mice. These results demonstrate that HCII protects against thrombin-induced remodeling of an injured vascular wall by inhibiting thrombin action and suggest that HCII is potentially therapeutic against atherosclerosis without causing coagulatory disturbance.

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.

Heparin cofactor II is a novel protective factor against carotid atherosclerosis in elderly individuals.

BACKGROUND: Thrombin plays a crucial role in atherothrombotic changes. Because heparin cofactor II (HCII) inhibits thrombin actions after binding to dermatan sulfate at injured arterial walls, HCII may negatively regulate thrombin actions in vascular walls. We hypothesized that plasma HCII activity is a preventive factor against atherosclerotic changes, especially in elderly individuals who already have atherosclerotic vascular injuries. METHODS AND RESULTS: Maximum plaque thickness (MPT) in the carotid artery was measured by ultrasonography in 306 Japanese elderly individuals (154 men and 152 women; age, 40 to 91 years; 68.9+/-11.1 years, mean+/-SD). The relevance of cardiovascular risk factors including plasma HCII activity to the severity of MPT was statistically evaluated. Plasma HCII activity decreased with age. Simple linear regression analysis after adjustments for age and sex showed that lipoprotein(a), glycosylated hemoglobin A1c, and presence of diabetes mellitus significantly contributed to an increase in MPT values (r=0.119, P<0.05; r=0.196, P<0.001; and r=0.227, P<0.0001, respectively). In contrast, high-density lipoprotein (HDL) cholesterol and HCII activity were negatively correlated with MPT values (r=-0.117, P<0.05, and r=-0.202, P<0.0005, respectively). Multiple regression analysis revealed that plasma HCII activity and HDL cholesterol independently contributed to the suppression of MPT values and that the antiatherogenic contribution of HCII activity was stronger than that of HDL cholesterol (P<0.001 and P<0.05, respectively). CONCLUSIONS: These results suggest that HCII can be a novel and independent antiatherogenic factor. Moreover, HCII is a stronger predictive factor than HDL cholesterol against carotid atherosclerosis in elderly individuals.

Aggressive antiplatelet therapy before coronary stent implantation in acute coronary syndrome with essential thrombocythemia--a case report.

A 52-year-old man was admitted to the hospital because of unstable angina pectoris. Coronary angiography revealed severe stenosis at a proximal site of the left anterior descending artery. Essential thrombocythemia (ET) was diagnosed on the basis of findings of marked thrombocytosis (106 x 10(4)/microL) and an increased number of immature megakaryocytes in the bone marrow. Because hyperaggregability of platelets was demonstrated by an ex vivo platelet aggregation assay and by elevated plasma levels of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4), antiplatelet therapy with aspirin and ticlopidine and cytoreduction therapy with hydroxyurea were started. This combination treatment resulted in a decrease in the platelet count to less than 60 x 10(4)/microL and decreases in plasma levels of both beta-TG and PF4 to almost normal values. Percutaneous coronary angioplasty and stenting were then performed successfully without thrombotic complications. These findings suggest that combination therapy with antiplatelet and cytoreduction agents before catheter intervention is useful for the prevention of thrombotic complications in patients with acute coronary syndrome associated with essential thrombocythemia.

Heparin cofactor II is an independent protective factor against peripheral arterial disease in elderly subjects with cardiovascular risk factors.

AIM: Heparin cofactor II (HCII) specifically inactivates thrombin action at the injured vascular wall. We have reported that HCII is a protective factor against coronary in-stent restenosis and carotid atherosclerosis; however, it is unclear whether there is any correlation between plasma HCII levels and the development of peripheral arterial disease (PAD). METHODS: Plasma HCII activity and the ankle brachial pressure index (ABI) were determined in 494 elderly subjects with cardiovascular risk factors. PAD was diagnosed by ABI below 0.9, and 62 subjects were diagnosed with PAD. The relationship between factors that affect cardiovascular events and the prevalence of PAD was statistically evaluated. RESULTS: Mean HCII activity in PAD subjects was significantly lower than in non-PAD subjects (87.5+/-19.7% v.s. 94.6+/-17.8%, p=0.009). Multivariate logistic regression analysis showed that age (odds ratio [OR]: 1.062, p=0.0016), current smoking (OR 3.028, p=0.002) and diabetes mellitus (OR 2.656, p=0.008) were independent and progressive determinants of PAD. In contrast, HCII was an independent inhibitory factor of PAD (OR: 0.982, p=0.048). CONCLUSIONS: Plasma HCII activity is inversely related to the prevalence of PAD. HCII may function as the sole protective factor against PAD in elderly people with cardiovascular risk factors.

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.

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.