Tomomitsu Tani

Bilirubin as a prognostic marker in patients with pulmonary arterial hypertension

BackgroundLiver dysfunction reflects the status of heart failure, with congestion and low perfusion of the liver serving as causative mechanisms. Previous studies demonstrated relationship between the results of liver function test and the prognosis in patients with heart failure. However, few studies have examined this relationship in patients with pulmonary arterial hypertension (PAH).MethodsThe subjects were 37 patients with PAH (8 men and 29 women; 18 with idiopathic PAH and 19 with connective tissue disease-associated PAH). A blood test was performed after a 3-month period free from hospitalization and without changes in functional class, treatment, heart sounds, body weight, or heart rate.ResultsIn a mean follow-up period of 635 ± 510 days, 12 patients died due to heart failure, 2 died due to pulmonary hemorrhage, and 23 patients survived. Cox proportional hazard analyses identified functional class (p < 0.001), plasma concentration of brain natriuretic peptide (BNP) (p = 0.001), and hyperbilirubinemia (serum total bilirubin > 1.2 mg/dL; p < 0.001; hazard ratio = 13.31) as predictors of mortality. Patients with hyperbilirubinemia had a worse functional class (P = 0.003), a higher right atrial pressure (p < 0.001), a higher plasma concentration of BNP (p = 0.004), and a larger Doppler right ventricular index of the right ventricle (p = 0.041).ConclusionElevated serum bilirubin is a risk factor for death in patients with PAH.

Usefulness of Electron Beam Tomography in the Prone Position for Detecting Atrial Thrombi in Chronic Atrial Fibrillation

Objective We compared the usefulness of electron beam tomography (EBT) in the prone position relative to that in the supine position for detecting atrial thrombi. Methods We studied 96 patients with chronic atrial fibrillation, of whom 71 were scanned in the supine position and 25 were scanned in the prone position. Electron beam tomography was performed twice after contrast medium injection to obtain early- and late-phase images. Results Filling defects were detected in 13 patients in the supine position by EBT. Transesophageal echocardiography (TEE) revealed a thrombus in the region of the filling defect in 9 patients. In 4 patients, filling defects in the left atrial appendage were not confirmed as thrombi by TEE. Filling defects were detected in 4 patients in the prone position, all of which were confirmed as thrombi by TEE. Conclusion Electron beam tomography in the prone position is an effective technique for reducing false-positive results in the detection of atrial thrombi.

Relationship between fractional flow reserve and residual plaque volume and clinical outcomes after optimal drug-eluting stent implantation: Insight from intravascular ultrasound volumetric analysis

BACKGROUND The underlying cause of FFR reduction and prognostic impact of FFR after optimal DES implantation remain unknown. The study aims were to use intravascular ultrasound (IVUS) to investigate the mechanism responsible for reduced fractional flow reserve (FFR) after optimal drug-eluting stent (DES) implantation and to evaluate FFR effect on clinical outcomes after optimal percutaneous coronary intervention with DES. METHODS Ninety-seven patients treated with optimal DES implantation under IVUS and pullback FFR guidance were followed clinically (median 17.8 months). Post-stenting IVUS examination and pullback FFR recording were performed, and angiographic and IVUS parameters associated with reduced FFR were evaluated. The composite of major adverse cardiac events (MACE), including cardiac death, myocardial infarction, stent thrombosis, and target vessel revascularization, was analyzed. RESULTS Regression analysis showed inverse correlations between post-stent FFR and residual plaque volume index (r=-0.40, p<0.01) and residual percent plaque volume (r=-0.68, p<0.01) in IVUS but no correlation of minimal lesion diameter with quantitative coronary angiography (r=0.07, p=0.50) or IVUS-derived minimal stent area (r=0.02, p=0.84). MACE was observed in 10 patients (10.3%), and FFR after optimal stenting was significantly lower in this group (0.86 ± 0.04 vs 0.91 ± 0.04, p<0.01). The optimal FFR threshold for predicting MACE was 0.90, identified by the receiver operating characteristic curve. CONCLUSIONS Reduced FFR after optimal DES implantation was associated with residual plaque volume identified by IVUS and future adverse cardiac events.

Usefulness of Plasma Brain Natriuretic Peptide Measurement and Tissue Doppler Imaging in Identifying Isolated Left Ventricular Diastolic Dysfunction Without Heart Failure

Left ventricular (LV) diastolic dysfunction carries a substantial risk for the subsequent development of heart failure and reduced survival, even when it is asymptomatic. Plasma brain natriuretic peptide (BNP) level and tissue Doppler imaging indexes provide powerful incremental assessment of LV diastolic function. Accordingly, the aim of this study was to clarify whether these methodologies could identify LV diastolic dysfunction without heart failure in 280 patients with preserved LV ejection fractions (> or =50%) who underwent echocardiography and cardiac catheterization for the evaluation of coronary artery disease. Patients were classified into 2 groups, those with diastolic dysfunction (tau > or =48 ms; n = 91) and those with normal diastolic function (tau <48 ms; n = 189). Plasma BNP > or =22.4 pg/ml, an unexpectedly low value, had sensitivity of 74.7% and specificity of 60.8% for identifying isolated LV diastolic dysfunction; the combined use of BNP > or =22.4 pg/mL and mitral annular velocity during early diastole <7.4 cm/s had relatively low sensitivity of 44.0% but high specificity of 86.8%. In conclusion, using plasma BNP level and with the combination of BNP level and mitral annular velocity during early diastole, invasively proved isolated LV diastolic dysfunction without heart failure could be identified in patients with coronary artery disease.

Relation of Plasma Levels of Adiponectin to Left Ventricular Diastolic Dysfunction in Patients Undergoing Cardiac Catheterization for Coronary Artery Disease

In the present study, we hypothesized that hypoadiponectinemia and hyperleptinemia might be associated with left ventricular (LV) diastolic dysfunction. To test the hypothesis, we examined the relation of the plasma levels of adiponectin and leptin with the indexes of LV diastolic and systolic function (relaxation time constant, end-diastolic pressure, and ejection fraction) in 193 consecutive patients undergoing cardiac catheterization for coronary artery disease (age 69 ± 9 years, 74% men; ejection fraction 68.4 ± 9.9%). Regardless of gender, the adiponectin levels correlated negatively with the relaxation time constant and end-diastolic pressure, and the correlations remained significant after adjustment for potential confounders, including age, body mass index, heart rate, blood pressure, and coronary artery disease severity. Adiponectin levels did not significantly correlate with the ejection fraction in either men or women. The leptin levels did not significantly correlate with the indexes of LV diastolic or systolic function in either men or women. In conclusion, we found that decreased adiponectin levels were associated with LV diastolic dysfunction in patients with known or suspected coronary artery disease.

Prognostic Value of Left Ventricular Diastolic Dysfunction in Patients Undergoing Cardiac Catheterization for Coronary Artery Disease

We hypothesized that left ventricular (LV) diastolic dysfunction assessed by cardiac catheterization may be associated with increased risk for cardiovascular events. To test the hypothesis, we assessed diastolic function by cardiac catheterization (relaxation time constant (Tau) and end-diastolic pressure (EDP)) as well as Doppler echocardiography (early diastolic mitral annular velocity (e′) and a ratio of early diastolic mitral inflow to annular velocities (E/e′)) in 222 consecutive patients undergoing cardiac catheterization for coronary artery disease (CAD). During a followup of 1364 ± 628 days, 5 cardiac deaths and 20 unscheduled cardiovascular hospitalizations were observed. Among LV diastolic function indices, Tau > 48 ms and e′ < 5.8 cm/s were each significantly associated with lower rate of survival free of cardiovascular hospitalization. Even after adjustment for potential confounders (traditional cardiovascular risk factors, the severity of CAD, and cardiovascular medications), the predictive value of Tau > 48 ms and e′ < 5.8 cm/s remained significant. No predictive value was observed in EDP, E/e′, or LV ejection fraction. In conclusion, LV diastolic dysfunction, particularly impaired LV relaxation assessed by both cardiac catheterization and Doppler echocardiography, is independently associated with increased risk for cardiac death or cardiovascular hospitalization in patients with known or suspected CAD.

Fractional flow reserve-guided percutaneous coronary intervention for an intermediate stenosis complicated by a coronary-to-pulmonary artery fistula

A 65-year-old man was referred to our hospital following repetitive chest pain. Invasive coronary angiography showed an intermediate stenosis of the proximal left anterior descending artery (LAD), and a coronary fistula originating distal to the stenosis draining into the main pulmonary artery. To evaluate the functional abnormality arising from the stenosis and coronary steal due to the fistula, fractional flow reserve (FFR) was measured using a pressure wire with pullback recording. The FFR value was 0.74 at the distal LAD, 0.78 distal to the fistula, 0.81 proximal to the fistula (distal to the stenosis), and abruptly increased to 1.0 proximal to the stenosis. Based on these FFR results, percutaneous coronary intervention was performed to the stenosis. After stent placement, the FFR value improved to 0.87 at the distal LAD, and no abrupt pressure gradient was observed beyond the fistula and the stent. FFR-guided intervention with pullback pressure recording could be a useful and practical method to apply in cases with coronary stenosis complicated by coronary fistula in the same vessel.

Increased circulating malondialdehyde-modified low-density lipoprotein levels in patients with ergonovine-induced coronary artery spasm

OBJECTIVE Coronary endothelial dysfunction is thought to underlie the development of coronary artery spasms. Malondialdehyde-modified low-density lipoprotein (MDA-LDL) was suggested as a marker of endothelial damage. This study investigated the diagnostic impact of MDA-LDL on ergonovine-induced coronary spasms. METHODS We included 152 patients with suspected coronary spastic angina. MDA-LDL levels were measured before an ergonovine provocation test. Coronary spasm was defined as total or subtotal occlusion, compared to the relaxed state after nitroglycerin, associated with ischemic ECG changes and concurrent chest pain. Changes in vessel diameter in response to ergonovine were evaluated with quantitative coronary angiography. RESULTS Coronary spasms were observed in 41 patients (27%). MDA-LDL levels were significantly higher in patients with spasms compared to those without spasms (139.9 ± 45.9 U/L vs. 109.6 ± 36.6 U/L, p<0.01). Univariate logistic regression analyses indicated significant relationships between coronary spasms and MDA-LDL (per 10 U/L, odds ratio (OR): 1.20; p<0.01), high-density lipoprotein (per 10 mg/dL, OR: 0.76; p=0.03), smoking (OR: 3.04; p<0.01), and male gender (OR: 3.51; p<0.01). In the multivariate model, MDA-LDL (per 10 U/L, OR: 1.17; p<0.01) remained a significant predictor of coronary spasm. Regression analysis showed a positive correlation between MDA-LDL levels and coronary luminal diameter changes induced by ergonovine (r=0.57, p<0.01). The optimal MDA-LDL threshold for predicting coronary spasm was 121.3 U/L, identified with a receiver operating characteristic curve. CONCLUSIONS Increased circulating MDA-LDL levels were associated with ergonovine-induced coronary artery spasm.

The stenting strategy of drug-eluting stents for coronary artery disease in patients on dialysis

Background: Reports regarding the relationship between the length and diameter of implanted drug-eluting stents and clinical and angiographic outcomes in dialysis patients are limited. Aim: We investigated the efficiency of drug-eluting stents for coronary artery disease in patients on dialysis from the viewpoint of stent sizing. Methods: Sirolimus-eluting stents were implanted in 88 lesions and bare metal stents were implanted in 43 lesions. We compared stenting strategy, major adverse cardiac events, and angiographic results between sirolimus-eluting stent and bare metal stent groups. Results: Stent diameter was smaller and stent length was longer in the sirolimus-eluting stent group than in the bare metal stent group in our routine practices. There was no significant between-group difference in late diameter loss. Rates of angiographic restenosis and target lesion revascularization were significantly higher in the sirolimus-eluting stent group than in the bare metal stent group. Although stent length was significantly longer and stent diameter was smaller in the sirolimus-eluting stent group, sirolimus-eluting stents did not improve the subsequent clinical and angiographic results compared with bare metal stents in dialysis patients. Conclusion: In dialysis patients, a longer length and/or smaller diameter sirolimus-eluting stent implantation was associated with high rates of restenosis and target lesion revascularization compared with bare metal stents.

Pulmonary venous occlusion and death in pulmonary arterial hypertension: survival analyses using radiographic surrogates

BackgroundRecent studies find that a considerable number of patients with pulmonary arterial hypertension (PAH) develop fibrous obstruction of the pulmonary veins. Such obstruction more commonly accompanies connective tissue disorder (CTD)-associated PAH than idiopathic PAH. However, few researchers have gauged the risk of death involving obstruction of the pulmonary veins.MethodsThirty-seven patients with PAH were enrolled (18 patients, idiopathic PAH; 19 patients, CTD-associated PAH). The patients were 49 ± 18 years and had a World Health Organization functional class of 3.2 ± 0.6. Thickening of the interlobular septa, centrilobular ground-glass attenuation, and mediastinal adenopathy were surrogates for obstruction of the pulmonary veins, and were detected by a 16-row multidetector computed tomography scanner.ResultsThe follow-up period was 714 ± 552 days. Fifteen deaths occurred. Thickening of the interlobular septa, centrilobular ground-glass attenuation, and mediastinal adenopathy were found in 37.8%, 24.3%, and 16.2% of patients, respectively. Cox proportional hazard analysis revealed an increased risk of death with each radiographic surrogate (mediastinal adenopathy: p < 0.0001, hazard ratio = 13.9; thickening of interlobular septa: p < 0.001, hazard ratio = 12.0; ground-glass attenuation: p = 0.02, hazard ratio = 3.7). The statistical significance of these relationships was independent of the cause of PAH and plasma concentration of brain natriuretic peptide.ConclusionsThe results of this study imply that obstruction of the pulmonary veins is associated with an increased risk of death in patients with PAH.