Search

Background: Obesity has recently been shown to have a favorable effect on the prognosis of patients with congestive heart failure (CHF), but only a few such studies are available in Japan. The purpose of the present study was to investigate whether the obesity paradox is still present after adjusting for CHF characteristics., Methods and Results: A total of 219 patients hospitalized with CHF were reviewed, and the impact of body mass index (BMI) on prognosis was examined. Patients were divided into 4 groups according to BMI quartiles. The endpoint was defined as all-cause death or unplanned CHF hospitalization. According to univariate analysis, a higher BMI was associated with better outcomes. High-BMI patients were younger, likely to be male, and had a higher prevalence of hypertension and diabetes. The plasma B-type natriuretic peptide (BNP) levels and blood urea nitrogen (BUN) levels were lower, while the serum hemoglobin and sodium levels were higher in high-BMI patients. The prevalence of atrial fibrillation was lower in high-BMI patients. Predictors for all-cause death or CHF hospitalization based on univariate analysis were age, prior CHF hospitalization, estimated glomerular filtration rate, plasma BNP levels, BUN levels, and serum hemoglobin and sodium levels. According to multivariate analysis, a high BMI was still associated with better outcomes., Conclusions: High BMI was associated with better clinical outcomes in Japanese CHF patients.

Background: Inflammatory processes in the atria during systemic inflammation remain unclear, so this study tested the hypothesis that macrophages infiltrate the atrial myocardium mainly through the atrial endocardium with the contribution of fractalkine., Methods and Results: Sprague-Dawley rats were injected with lipopolysaccharide (LPS) to simulate inflammation in the atria. Inflammation was immunohistologically assessed by the presence of macrophages. Macrophage infiltration was diffuse throughout the atrial myocardium after LPS injection. At an earlier phase after LPS injection, the number of macrophages dramatically increased, mainly in the atrial endocardium, and the expression of fractalkine protein was markedly increased by treatment with LPS in the atrial endocardium. The LPS-induced increase in atrial macrophage infiltration was significantly suppressed by neutralizing the fractalkine protein (P<0.01)., Conclusions: In an experimental model of atrial inflammation, macrophages infiltrated the myocardium mainly through the atrial endocardium with the contribution of fractalkine. Inhibition of macrophage infiltration by suppressing chemokine expression could be a novel therapeutic approach to controling acute inflammation in the atria.

Background: Calcium-channel blockers (CCBs) are highly effective in suppressing coronary spasm and are widely used as the standard therapy for coronary spastic angina, but it is unclear if CCB treatment completely suppresses the symptoms., Methods and Results: The clinical course of the symptoms caused by coronary spasm was investigated in patients taking CCBs: 90 patients were evaluated and 80 patients were followed. The mean follow-up period was 1,796+/-1,169 days. There were no cardiac deaths, but 3 patients were admitted to the hospital, 1 because of the onset of non-Q wave myocardial infarction and 2 because of repeat anginal attacks. In those 2 patients, medical therapy was discontinued at their discretion. In the follow-up analysis, we found that the incidence of symptoms caused by repeat anginal attacks was 37.0% (27/73) in the first year and was increasing every year., Conclusions: CCBs are strongly recommended for improving the prognosis of coronary spasm, but in many cases they do not suppress completely symptoms.

Background: Approximately half of the patients with chronic heart failure (CHF) show preserved systolic function, but less is known about CHF with preserved ejection fraction (EF)., Methods and Results: In a retrospective analysis, patients with CHF who had been admitted to hospital were divided into 2 groups: reduced EF (EF < or = 40%) and preserved EF (EF >40%). The rate of preserved EF was 53.5% and those with preserved EF were older, more likely to be female, and had a lower serum hemoglobin concentration than those in the reduced EF group. In the multivariate analysis, only older age was independently related to CHF with preserved EF. CHF patients with preserved EF who were successfully discharged from hospital and then followed at the outpatient clinic were reviewed and re-hospitalization for CHF was examined by Cox hazard univariate analysis, which showed that prior CHF hospitalization, absence of hypertension, and non-use of angiotensin-converting enzyme inhibitor (ACEI) and/or angiotensin-receptor blocker (ARB) were predictors. In the multivariate analysis, non-use of ACEI/ARB was the sole predictor for CHF re-hospitalization., Conclusions: CHF patients with preserved EF are older than those with reduced EF and use of ACEI/ARB prevents their re-hospitalization.

Background: Patients with congestive heart failure (CHF) are often re-hospitalized, worsening both their quality of life and prognosis. Although renal dysfunction reportedly increases the risk of CHF, the association between renal dysfunction and re-hospitalization for CHF remains unclear., Methods and Results: Patients with CHF and decreased renal function were reviewed. The estimated glomerular filtration rate (GFR) was calculated with the Modification of Diet in Renal Disease equation. Patients with decreased renal function (estimated GFR on admission <45 ml .min(-1) . 1.73 m(-2)) were re-hospitalized more frequently than were patients with preserved renal function (estimated GFR on admission >or=45). Patients with decreased renal function were older and had higher rates of anemia, worsening renal function during hospitalization, and previous hospitalization for CHF. Independent predictors of re-hospitalization for CHF identified with multivariate analysis were age, previous hospitalization for CHF, decreased renal function, and non-use of an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker., Conclusions: Renal dysfunction is an independent predictor of re-hospitalization for CHF, so careful follow-up is needed, even after discharge.

Background: Recent studies suggest that B-type natriuretic peptide (BNP) is an important predictor of cardiac events in hypertensive patients., Methods and Results: The relationship between the plasma BNP level and various clinical parameters was examined in 154 untreated hypertensive patients without heart failure or atrial fibrillation (mean age: 58.0+/-10.7; mean blood pressure: 164.5+/-15.2/99.1+/-9.7 mmHg; mean BNP: 32.7+/-36.7 pg/ml). First, the patients were divided into 2 groups based on BNP: normal (<18.5 pg/ml, mean 9.7+/-5.7, n=69); or elevated (>18.5 pg/ml, mean 51.4+/-40.4, n=85). The elevated BNP group had a significantly greater electrocardiographic voltage index (SV1+RV5; 3.7+/-1.2 vs 3.2+/-0.8 mV, p=0.0029), cardiothoracic ratio/chest radiography (CTR; 49.1 vs 46.9%, p=0.0037), left ventricular mass index (LVMI; 122.2+/-31.7 vs 103.1+/-26.4 g/m2, p=0.0005) and deceleration time (DT; 241+/-39 vs 208+/-30 ms, p=0.0001), as well as a smaller E-wave to A-wave (E/A ratio) (0.80+/-0.22 vs 0.96+/-0.28, p=0.0003), compared with the normal BNP group. There were no significant differences in casual blood pressure, body mass index, serum creatinine and ejection fraction between the 2 groups. Next, the patients were divided into 3 groups based on BNP: normal (<18.5, n=69), moderate (18.5 to 40, mean 27.0+/-5.7, n=43) and high (40<, mean 76.3+/-45.3, n=42). In the high BNP group, most clinical parameters indicated the most severe organ damage compared with other groups, including SV1+RV5, DT and LVMI. In all patients, logarithmic BNP was positively correlated with the age, pulse pressure, SV1+RV5, CTR, ventricular wall thickness, DT, LVMI and negatively correlated with hemoglobin, renin and E/A ratio. Using multiple regression analysis, renin and DT were significantly associated with BNP. No gender differences in the relationship between BNP and clinical parameters were found., Conclusions: Results suggest that BNP is a useful indicator for the initial assessment of the severity of essential hypertension, detecting both cardiac hypertrophy and diastolic dysfunction, and may also be valuable for risk stratification.

Background: Acute myocardial infarction (MI) sometimes occurs without painful symptoms and in such cases, prognosis is worsened by delays in diagnosis and revascularization. Renal insufficiency induces many types of neuropathy, but the relation between renal insufficiency and painless MI remains unclear., Methods and Results: Patients with MI and elevated creatine kinase levels were retrospectively analyzed. Renal insufficiency (serum creatinine concentration > or =1.5 mg/dl) and other characteristics (age, sex, body mass index, hypertension, smoking, diabetes mellitus, dyslipidemia, history of stroke, previous MI, hemodialysis, and atrial fibrillation) were compared between patients who had MI with painful symptoms (painful MI, n=131) and patients who had MI without painful symptoms (painless MI, n=18). Other variables compared were the time from symptom onset to admission, peak creatine kinase concentration, Killip class, site of MI, emergency coronary angiography, postprocedural Thrombolysis In Myocardial Infarction grade III flow, and in-hospital death. Univariate analysis identified older age, renal insufficiency, and previous MI as predictors of painless MI. Patients with painless MI showed higher rates of Killip class > or =II and in-hospital death and a longer time from symptom onset to admission. However, multivariate analysis identified only renal insufficiency as an independent predictor of painless MI., Conclusions: MI without painful symptoms frequently develops in patients who have renal insufficiency, so the possibility of painless MI should be evaluated in such patients to ensure early diagnosis and treatment.

Background: Angiotensin II receptor blockers (ARB) are now commonly used to treat hypertension because of their beneficial effects on cardiovascular remodeling. However, ARB treatment can not inhibit the left ventricular (LV) remodeling sufficiently, which may be related with aldosterone secretion. To inhibit the action of aldosterone during ARB treatment, the additional effects of an aldosterone blocker and spironolactone (SPRL) on LV hypertrophy in patients with essential hypertension was studied., Methods and Results: The patients with essential hypertension were randomly divided into 2 groups; 1 group was treated with an ARB, candesartan (8 mg/day), for 1 year (ARB group) and other group was treated with the ARB for the first 6 months and with the ARB plus SPRL (25 mg/day) for the next 6 months (combination group). Seventy patients who underwent echocardiography every 6 months were analyzed and were also classified into 4 subgroups of LV geometric pattern according to the LV mass index (LVMI) and the relative wall thickness (RWT). The ARB treatment and the addition of SPRL significantly reduced the blood pressure, however, both treatments did not affect the LV geometry in both groups. The ARB treatment in the subgroups of concentric LV remodeling (RWT>or=0.45 and LVMI<125) and concentric LV hypertrophy (RWT>or=0.45 and LVMI>or=125) significantly reduced RWT. However, ARB treatment in all subgroups did not affect LVMI. The addition of SPRL only in the concentric LV hypertrophy subgroup significantly reduced the LVMI, despite similar changes in blood pressure., Conclusions: These results indicated that the addition of SPRL treatment during the ARB treatment and conventional treatments is clinically useful to reduce the LVMI in hypertensive patients with concentric LV hypertrophy; however, does not improve the eccentric LV hypertrophy.

Background: Prevention of restenosis after coronary stenting is clinically important. We compared amlodipine and quinapril to determine which is more effective in preventing restenosis after stenting., Methods and Results: Immediately after successful coronary stenting of 101 lesions in 63 consecutive patients, the patients were randomly divided into 2 groups: 32 patients with 48 lesions were administered amlodipine 5 mg/day (group A), and 31 patients with 53 lesions were administered quinapril 10 mg/day (group Q). Lesions were assessed by quantitative coronary angiography (QCA) before and immediately after stenting and in the follow-up phase. Intravascular ultrasound (IVUS) could only be performed on 20 lesions in group A and 16 lesions in group Q throughout the follow-up period. We analyzed each lesion at 5 sites. In the follow-up phase, the minimal lumen diameter in group A was significantly larger than that in group Q (1.88 +/- 0.64 mm vs 1.52 +/- 0.53 mm, p<0.01). In the follow-up phase, the neointimal area (stent area-lumen area) in group A was significantly smaller than that in group Q (1.9 +/- 0.5 mm2 vs 2.7 +/- 0.8 mm2 at the middle portion of stent, p<0.01)., Conclusion: These QCA and IVUS findings suggest that amlodipine has beneficial effects in inhibiting neointimal hyperplasia in stented lesions compared with quinapril.

Abdominal aortic aneurysm (AAA) is commonly associated with coronary artery disease (CAD). Eleven patients underwent the combined operation of coronary artery bypass grafting (CABG) on the beating heart and AAA repair: 10 underwent off pump CABG and 1 patient required centrifugal pump and pulmonary assist with closed circuit because of unstable hemodynamics. All cases were discharged without severe complications and with patent coronary bypass grafts.

Ca2+ influx via the Na+/Ca2+ exchanger (NCX) may lead to Ca2+ overload and myocardial injury in ischemia-reperfusion. Direct evidence that increased cytoplasmic Ca2+ concentration ([Ca2+]i) is mediated by the reverse mode of the NCX is limited, so in the present study the [Ca2+]i dynamics and left ventricular pressure were monitored in perfused beating hearts. The effects of KB-R7943 (KBR), a selective inhibitor of the NCX in the reverse mode, were analyzed during low-Na+ exposure and ischemia-reperfusion. Hearts from Sprague-Dawley rats were retrogradely perfused and loaded with 4 micromol/L fura-2 to measure the fluorescence ratio as an index of [Ca2+]i. To evaluate KBR effects on the reverse mode exchanger, the increase in [Ca2+]i induced by low-Na+ exposure (Na+: 30 mmol/L, 10 mmol/L caffeine pre-treatment) was measured with and without 10 micromol/L KBR (n=5). In another series, the hearts were subjected to 10 min of low-flow ischemia with pacing, followed by reperfusion in the absence (n=6) or in the presence of 10 micromol/L KBR (n=6). Background autofluorescence was subtracted to estimate the ratio in the ischemia-reperfusion protocol. KBR significantly suppressed the increase in [Ca2+]i induced by low-Na+ (40.2 +/- 11.2% of control condition, p=0.014), as well as on increase in diastolic [Ca2+]i during ischemia (% increase from pre-ischemia in [Ca2+]i at 10 min: KBR, 17.9 +/- 6.4%; no KBR, 44.4 +/- 7.7%; p=0.024). After reperfusion, diastolic [Ca2+]i normalized more rapidly in KBR-treated hearts (% increase at 1 min: KBR, 4.5 +/- 7.0%; no KBR, 39.8 +/- 12.2%; p=0.03). Treatment with KBR also accelerated recovery of the rate-pressure product on reperfusion (1 min: KBR, 8,944 +/- 1,554 min(-1) mmHg; no KBR, 4,970 +/- 1,325; p<0.05). Thus, inhibition of the reverse mode exchanger by KBR reduced ischemic Ca2+ overload and possibly improved functional myocardial recovery during reperfusion in a whole heart model.

Stent implantation has decreased the incidence of restenosis after coronary intervention, but has not eliminated it. The contribution of the angiotensin-converting enzyme (ACE) genotype to the development of coronary artery disease and restenosis after coronary stenting was investigated in 67 Japanese patients in whom 103 lesions in which stents had been successfully implanted were assessed by quantitative coronary angiography, before, immediately after coronary stenting, and during follow-up. The distribution of the patients with the DD, ID, and II genotypes was 13%, 54%, and 33%, respectively. The prevalence of multivessel disease in the DD genotype was significantly higher (DD genotype: 78%; ID genotype: 58%; II genotype: 27%, chi2=8.13, p=0.016) and the late loss in the DD genotype (1.43+/-0.96 mm) was significantly greater (ID genotype: 0.78+/-0.98 mm and II genotype: 0.79+/-0.88 mm, p<0.05 vs DD genotype). However, there was no significant difference in the restenosis rate among the 3 genotypes. The present study in Japanese patients indicates that the DD genotype is associated with more extensive coronary artery disease and progression of the inward remodeling within the stented lesion, which is primarily caused by neointimal hyperplasia.

To investigate the effect of pre-treatment of a thrombus with a low dose of urokinase on establishing patency in a persistent infarct-related artery (IRA) during direct percutaneous coronary angioplasty (PTCA), the frequency of acute restenosis during direct PTCA, alone, or in combination with the intracoronary administration of urokinase, was examined in a consecutive nonrandomized series of patients with acute myocardial infarction (AMI). Two hundred and seventy-two successful PTCA patients (residual stenosis <50%) were divided into 2 groups: 88 patients received pre-treatment with intracoronary urokinase following PTCA (combination group); 184 received only direct PTCA without thrombolytic therapy (PTCA group). In the present study, after achievement of a residual stenosis of less than 50%, IRA was visualized every 15 min to assess the frequency of acute restenosis, which was defined as an acute progression of IRA with more than 75% restenosis after initially successful PTCA. In the patients with a large coronary thrombus, the frequency (times) of acute restenosis was significantly lower in the combination group than in the PTCA group (0.98+/-0.19 vs 2.92+/-0.32, p<0.0001). On the other hand, in the patients with a small coronary thrombus, the frequency of acute restenosis showed no difference in either group. The present study indicates that in patients with AMI, PTCA combined with pre-treatment of a low dose of urokinase is much more effective than PTCA alone, especially for those patients who have a large coronary thrombus.

Culprit lesions in acute coronary syndrome [acute myocardial infarction (AMI) and unstable angina pectoris (UAP)] were examined angiographically in 222 patients who had previously undergone coronary angiography (CAG). The observation period lasted 5 years after primary CAG in medically treated patients (group M, 127 cases) and after final follow-up CAG in patients treated by percutaneous transluminal coronary angioplasty (PTCA) (group B, 95 cases). There were 33 AMIs, including 5 deaths (22/127, 17.3%, in group M vs 11/95, 11.6%, in group B; p<0.01) and 189 UAPs (105/127, 82.7%, in group M vs 84/95, 88.4%, in group B; NS). High-grade stenoses (>75%) were found in 76 (59.8%) patients in group M, of which 41 lesions (54%) resulted in acute coronary syndromes (ACSs). In group M, ACSs resulted from insignificant stenosis (< or =50%) in 67 (53%) patients and from significant stenosis (>50%) in 60 (47%) patients. In group B, ACSs resulted from insignificant stenosis in 78 (82%) patients and from significant stenosis in 17 (18%) patients. Out of 95 PTCA sites, high-grade restenosis occurred in 3 lesions and ACSs (2 AMI, 14 UAP) in 16 (16.8%). We conclude that ACSs are more likely to develop from insignificant lesions than from significant lesions. High-grade stenoses are prone to become occlusive lesions and PTCA reduces this potential risk. Most target sites of PTCA that escaped restenosis were stable in the long term.

Low doses (< or = 100 pmol/kg) of endothelin-1 (ET-1) and endothelin-3 (ET-3) elicited a fall in mean arterial pressure (MAP) and a dose-related reduction in hindquarter vascular resistance in anesthetized rats. The depressor response to low doses of ET-1 or ET-3 was short-lived (about 10 sec) and reversible. High doses (> or = 200 pmol/kg) of ET-1 and ET-3 elicited a biphasic response; an initial fall in MAP followed by a gradual increase in MAP. The pressor response to large doses of ET-3 was less than that to large doses of ET-1. On the other hand, the depressor response to low doses of ET-3 was similar to that to low doses of ET-1. Both ET-1 and ET-3 at low doses exhibited primarily a vasodilatory activity. Pretreatment with NG-monomethyl-L-arginine (L-NMMA), a compound that inhibits nitric oxide (NO) production by endothelial cells, attenuated the hypotensive and hindquarter vasodilating effects of low doses of these isopeptides, indicating that the hindquarter vasodilating responses to these peptides depend upon the release of NO from endothelial cells. On the other hand, pretreatment with either aspirin or indomethacin did not alter the hypotensive or the hindquarter vasodilating effects of either ET-1 or ET-3, indicating that cyclooxygenase products may not be involved in the vasodepressive mechanisms of these peptides. L-NMMA attenuated the vasodilating effects of these peptides, but did not completely inhibit the response, suggesting that NO production by endothelial cells plays only a partial role in the vasodilation of ET in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

In order to assess myocardial hypertrophic activity during the process of hypertensive cardiac hypertrophy in the presence and absence of treatment with anti-hypertensive agents, we analyzed myocardial polyamine concentrations in spontaneous hypertensive (SHR) rats and control rats of Wistar Kyoto (WKY) strain. The anti-hypertensive agents studied were diltiazem, hydralazine and captopril, each of which was administered for 5 weeks. In comparison with WKY rats, SHR rats showed elevated blood pressure and enlarged hearts with higher myocardial spermidine concentration. Although blood pressure was lowered in the diltiazem-treated SHR rats, heart weight and myocardial spermidine concentration increased as in untreated SHR rats. In the hydralazine-treated group increases in both blood pressure and myocardial spermidine concentration were suppressed, while an increase in heart weight was not. In the captopril-treated group, increases in blood pressure, heart weight and spermidine concentration were all suppressed. Since spermidine level appears to be a sensitive indicator of hypertrophic activity in the heart, this study suggests that captopril exerts an inhibitory effect on hypertensive cardiac hypertrophy whereas diltiazem does not. It also suggests that hypertrophy may reach a certain plateau level earlier in the hydralazine-treated animals than in others.