Fujio Hayashi

Chlamydia pneumoniae seropositivity predicts the risk of restenosis after percutaneous transluminal coronary angioplasty

Abstract This study was done to evaluate whether anti-Chlamydia pneumoniae seropositivity can be a predictor of restenosis after coronary intervention. Recent studies indicate that latent infection with C. pneumoniae is associated with and could possibly cause atherosclerosis. However, it is unknown whether chronic infection with this microorganism is involved in the mechanism of restenosis after percutaneous transluminal coronary angioplasty. We prospectively studied 78 consecutive patients (90 target lesions) with symptomatic coronary artery disease who underwent successful coronary intervention to a de novo lesion (conventional balloon angioplasty to 31 lesions and stent implantation to 59 lesions). At angioplasty, blood samples were collected to measure the serum level of anti-C. pneumoniae IgG to examine whether seropositive patients were prone to restenosis and whether the seropositivity could predict the risk of restenosis determined by follow-up coronary angiography performed within 6 months after the angioplasty. Restenosis, defined as more than 50% stenosis with an increase of 15% or more in the degree of stenosis from that measured on cineangiograms after angioplasty, developed in 36 of 62 seropositive patients and in 4 of 16 seronegative patients (58% vs 25%, P = 0.025). Lesions in the seropositive patients had a greater mean loss index (mean ± SD 0.75 ± 0.45 vs 0.35 ± 0.41, P < 0.001), which was defined as late loss (luminal diameter reduction at follow-up angiography) divided by acute gain (luminal diameter gain by angioplasty), in late loss (1.07 ± 0.64 mm vs 0.65 ± 0.79 mm, P = 0.019), in percentage of diameter stenosis (57% ± 20% vs 41% ± 21%, P = 0.003) and a lesser mean in minimal luminal diameter (1.18 ± 0.58 mm vs 1.67 ± 0.63 mm, P = 0.002) at follow-up angiography. In a multivariate logistic regression model, anti-C. pneumoniae IgG seropositivity was a strong independent predictor of restenosis compared to the other risk factors (odds ratio = 6.2, P = 0.01). C. pneumoniae could play an important role in the mechanism of restenosis and evaluation of the IgG seropositivity, and may help to identify patients at high risk for restenosis.

Liver fibrogenesis marker, 7S domain of collagen type IV in patients with acutely decompensated heart failure: Correlates, prognostic value and time course.

BACKGROUND Congestion in heart failure (HF) induces multiple organ injury, which may cause remodeling of extracellular matrix. We hypothesized that liver fibrogenesis marker, 7S domain of collagen type IV (P4NP 7S) was correlated with congestion and liver injury in HF. METHODS AND RESULTS We measured serum P4NP 7S in two cohorts. Cohort 1 included 70 patients undergoing catheterization. P4NP 7S was correlated with pulmonary capillary wedge pressure, right ventricular and atrial pressure (r=0.50, P<0.001, r=0.42, P<0.001, r=0.39, P=0.001, respectively) but not with cardiac index (r=-0.05. P=0.7). Cohort 2 included 145 patients with acute HF, in whom we serially measured P4NP 7S at admission, discharge, early (1-month) and late (6-month) post-discharge period. γ-Glutamyltransferase and B-type natriuretic peptide were independently correlated with P4NP 7S at discharge. The cumulative 1-year incidence of death or HF hospitalization was much higher in the 3rd tertile of P4NP 7S than in the 1st and 2nd tertiles (50%, 25%, and 24%, Log-rank P=0.004). P4NP 7S enhanced risk classification when added to conventional risk factors (net reclassification improvement=0.47, P=0.02). In patients without early readmission, P4NP 7S decreased during hospitalization and remained low for up to 6months, whereas in patients with early readmission, P4NP 7S was persistently elevated during hospitalization, further increased at second admission, and remained high at 6months. CONCLUSION P4NP 7S was correlated with hemodynamics. The results shed new light on the pathophysiology of HF.

Myocardial Expression Level of Neural Cell Adhesion Molecule Correlates With Reduced Left Ventricular Function in Human Cardiomyopathy

Background— Recently, we screened for cardiac genes induced by metabolic stress and identified neural cell adhesion molecule (NCAM) as a candidate. This study aimed to clarify the expression pattern of NCAM in human cardiomyopathy. Methods and Results— A total of 64 cardiac tissue samples of patients with dilated cardiomyopathy were dichotomized according to the immunohistochemically determined signal intensity of NCAM staining (NCAM-high and NCAM-low groups). Clinical and hemodynamic data of the patients were compared between the 2 groups. Fibrosis area, left ventricular end-diastolic volume index, and left ventricular diastolic pressure were greater in the NCAM-high group (22.8% versus 11.6%, P<0.05; 130.3±57.6 versus 104.8±31.7 mL/m2, P<0.05; 14.3±8.0 versus 8.8±4.7 mm Hg, P<0.005; respectively). Incidence of cardiac death and admission for worsening heart failure was higher in the NCAM-high group during a follow-up of 6.3 years (log-rank P<0.05). Another 18 tissue samples were analyzed to determine the relationships between expression level of NCAM and major metabolic genes as well as hemodynamic parameters. The mRNA level of NCAM correlated with the serum (r=0.58; P=0.01) and mRNA levels (r=0.61; P=0.008) of brain-derived natriuretic peptides. It was also correlated with the mRNA levels of proliferator-activated receptor-&ggr; coactivator-1 &agr; (r=0.69; P=0.002) and the nuclear respiratory factor 1 (r=0.74; P<0.001). Conclusions— Expression of NCAM was associated with worsening hemodynamic parameters and major metabolic genes. Together with our previous findings, these data support the involvement of NCAM in left ventricular remodeling, revealing new insights into the pathophysiology of heart failure.