Measurement of plasma brain natriuretic peptide level as a guide for cardiac overload.

OBJECTIVES: We examined whether measurement of the plasma BNP concentrations might be useful for the early diagnosis of the existence and severity of disease in patients with heart disease in daily clinical practice. METHODS AND RESULTS: The plasma BNP and ANP concentrations in 415 patients with heart disease and hypertension and 65 control subjects were measured. Patients with heart disease had higher plasma BNP and ANP concentrations than did those with hypertension or control subjects. Among the etiology of cardiac diseases, specifically dilated cardiomyopathy and hypertrophic cardiomyopathy, was associated with the highest plasma BNP concentrations, whereas dilated cardiomyopathy was associated with the highest plasma ANP concentrations. Plasma BNP concentrations showed an increase as the severity of the heart disease, as graded according to the NYHA classification of cardiac function, increased. In both patients with heart disease and hypertension, the plasma BNP values were higher in those who had abnormalities in their echocardiogram and electrocardiogram as compared to those without any abnormalities. The plasma BNP levels also showed a significant correlation with left ventricular wall thickness and left ventricular mass. On the other hand, the plasma ANP levels showed significant correlations with left ventricular dimension. Receiver operative characteristic analysis revealed that plasma BNP levels showed substantially high sensitivity and specificity to detect the existence of heart diseases. CONCLUSION: Measurements of the plasma BNP concentrations is useful to detect the existence of the diseases, and abnormalities of left ventricular function and hypertrophy in patients with heart disease in daily clinical practice.

Left cervical aortic arch with aortic coarctation and saccular aneurysm.

Cervical aortic arch is a very rare malformation and is occasionally accompanied by other cardiovascular anomalies. A 48-year-old male patient had a left cervical aortic arch with aortic coarctation and saccular aneurysm distal to the coarcted segment. The major clinical manifestations were upper body hypertension with a 50-mmHg discrepancy between the upper and lower limbs and a loud continuous murmur in the upper chest and back. Magnetic resonance angiography successfully depicted the anomalous aorta, and the aortic coarctation and aneurysm were surgically resected and the thoracic aorta was reconstructed. The discrepancy in blood pressure diminished after the operation, but antihypertensive medication was continued to satisfactorily control the hypertension.

Screening for cardiac dysfunction in asymptomatic patients by measuring B-type natriuretic peptide levels.

Early diagnosis and treatment of heart failure lead to improved survival; pre-clinical detection would thus be beneficial. A non-invasive biochemical testing method would indeed be ideal to screen for the condition. In the present study, we sought to determine whether circulating levels of B-type natriuretic peptide (BNP) correlate with cardiac function in asymptomatic subjects. 294 consenting asymptomatic subjects were examined. BNP levels in elevated patients (> 18.4 pg / ml) showed significant correlation with echocardiographic parameters of the systolic and diastolic functions (EF r = -0.51, FS r = -0.50, E/A r = 0.42, p < 0.01). Moderate correlation with the CTR on chest X-ray was also seen (r = 0.23, p < 0.01). Multiple regression analysis showed numerous echocardiographic and hemodynamic parameters including those of systolic and diastolic function in addition to left ventricular wall thickness, blood pressure and serum creatinine levels to be significantly associated with raised BNP levels. Elevated BNP levels reflect cardiac function (both systolic and diastolic) in the asymptomatic population. Detection of cardiac dysfunction by the non-invasive biochemical test may prove useful in early pre-clinical diagnosis of heart failure.

Elevated B-type natriuretic peptide levels after anthracycline administration.

BACKGROUND: Cardiotoxicity leading to congestive heart failure is a complication of the anthracyclines. Biochemical methods to diagnose and monitor cardiac function after anthracycline administration would be most useful. We examined the diagnostic role of B-type natriuretic peptide (BNP), a potent biochemical marker of left ventricular dysfunction, in patients administered anthracyclines. METHODS: Twenty-seven consecutive patients receiving anthracyclines were investigated by serial measurements of BNP levels and other cardiac neurohormones (A-type natriuretic peptide, renin, aldosterone, angiotensin II, norepinephrine, and epinephrine) and myocardial markers (creatine kinase-MB and myosin light chain). Echocardiography was done to assess systolic (ejection fraction) and diastolic (mitral inflow A/E ratio) functions. RESULTS: Of the examined cardiac biochemical markers, BNP levels alone showed marked elevations to abnormal levels after anthracycline administration. Most patients showed transient increases (peak at 3 to 7 days). Patients with persistent elevations showed a poor prognosis. A/E ratio also correlated with increases in BNP levels in selected patients, which may suggest that raised BNP levels are reflective of induced diastolic dysfunction. CONCLUSIONS: Our studies suggest the possible use of BNP levels to assess the cardiac state after anthracycline administration. BNP levels most likely reflect cardiac tolerance to the cardiotoxic agent. Serial BNP profiles also suggest persistent elevations to be associated with potentially decompensatory states in contrast to tolerable transient increases. Diagnosis of degree of cardiac tolerance by response to drug administration may be analogous to use of stress testing (exercise) to help define underlying left ventricular dysfunction.

[Gene Polymorphism of 5, 10-methylenetetrahydrofolate reductase as a coronary risk factor].

Hyperhomocysteinemia has been identified as a possible risk factor for coronary artery disease. The association of the alanine/valine (A/V) polymorphism of 5, 10-methylenetetrahydrofolate reductase (MTHFR), one of the key enzymes catalyzing re-methylation of homocysteine, with coronary artery disease was examined in 362 Japanese males with a diagnosis of coronary artery disease confirmed with coronary angiography. The A/V polymorphism was analyzed with PCR followed by Hinf I digestion. The screening of 778 male volunteer controls revealed that the frequency of V allele in Japanese was 0.33, comparable to that in the French Canadian population. The VV genotype, which correlates with increased plasma homocysteine levels due to reduced activity and increased thermolability of this enzyme, was significantly more frequent in patients with coronary artery disease (15.7%, n = 362) than in controls (10.2%, n = 778; p = 0.0067). The association of the VV genotype with coronary artery disease was further increased in patients with > or = 99% stenotic lesion (p = 0.0010). In these patients, the frequency of the VV genotype was significantly higher in patients with triple-vessel disease (26%) than in patients with single- or double-vessel disease (15% and 14%, respectively). The fasting plasma homocysteine levels in VV subjects were higher than those in AV or AA subjects. The VV genotype of MTHFR associated with increased plasma homocysteine levels may represent an important genetic risk factor for coronary artery disease, especially with the occurrence of myocardial infarction.

Genetic polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR) as a risk factor for coronary artery disease.

BACKGROUND: Epidemiological studies have identified hyperhomocyst(e)inemia as an independent risk factor for coronary artery disease (CAD). Recently, the alanine/valine (A/V) polymorphism of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, one of the key enzymes catalyzing remethylation of homocysteine, has been reported. The VV genotype correlates with increased plasma homocyst(e)ine levels as a result of the reduced activity and increased thermolability of this enzyme. In this study, we examined the distribution of the MTHFR genotypes in Japanese men and the association between the VV genotype and CAD. METHODS AND RESULTS: The diagnoses of CAD of all the studied patients were confirmed by coronary angiography. The MTHFR genotype was analyzed by PCR followed by HinfI digestion. In 778 healthy male subjects, the frequency of the V allele was 0.33, comparable to that in a French Canadian population. In 362 patients with CAD, the VV genotype was significantly more frequent than in control subjects (16% versus 10%, P=.0067). The association of the VV genotype with CAD was further increased in patients with > or = 99% stenotic lesions (18%, P=.0010), whereas no significant association with the VV genotype was observed in patients without a > or = 99% stenosis. When the genotype frequency was compared among patients with different numbers of stenotic coronary arteries, the frequency of the VV genotype was significantly higher in patients with triple-vessel disease (26%) than in patients with single- or double-vessel disease (15% and 14%, respectively). CONCLUSIONS: The VV genotype of MTHFR was also common in the Japanese population and was significantly associated with CAD. The frequency of this genotype in particular was correlated with the severity of disease. The VV genotype associated with a predisposition to increased plasma homocyst(e)ine levels may represent a genetic risk factor for CAD.

Angiotensin converting enzyme polymorphism is associated with severity of coronary heart disease and serum lipids (total cholesterol and triglycerides levels) in Japanese patients.

BACKGROUND: Much past research has concerned the relationship between coronary heart disease and the angiotensin converting enzyme (ACE) genotype, with many lines of evidence demonstrating polymorphism to be an independent risk factor for myocardial infarction. Interestingly, however, association of ACE polymorphism and severity of coronary artery stenosis according to racial background has recently been proposed. OBJECTIVE: To clarify the relationship between the ACE genotype and severity of coronary artery stenosis in Japanese patients. METHODS: In 36 consecutive patients undergoing coronary catheterization, comparative examination of coronary angiography findings with the ACE genotype was conducted. RESULTS: The severity of coronary artery stenosis indeed showed a relationship with the ACE genotype, with more severe coronary artery stenosis associated with the deletion (D) allele (P < 0.05). The serum lipids, total cholesterol and triglycerides levels, were also elevated in patients with the D allele (P < 0.05). CONCLUSION: We have provided further evidence that ACE polymorphism is associated with severity of coronary heart disease in a Japanese population. A possible relationship between serum lipids and the ACE genotype is also suggested.

Stenotic bicuspid aortic valve associated with a ventricular septal defect in an adult presenting with congestive heart failure: a rare observation.

This report is concerned with an adult presenting with stenotic bicuspid aortic valve associated with a ventricular septal defect (VSD). The association between aortic regurgitation (AR) and VSD has often been described, but that between a stenosed aortic valve and VSD has been rarely observed, although bicuspid aortic valves and ventricular septal defects are probably the two most common congenital heart defects. The development of congestive heart failure in the presented case was considered to be due to an increase in the left to right shunt through the VSD. This was attributable to a progressive elevation in left ventricular pressure as a result of the development, with age, of stenosis of the bicuspid aortic valve.

Right ventricular inflow obstruction due to giant hematoma formed by chronic constrictive pericarditis.

A 26-year-old man having chronic constrictive pericarditis with rare complications is described. Right ventricular inflow obstruction was caused by an intracavity giant mass which was surrounded by thick calcified pericardium. The mass consisted of old bloody fluid with some calcified tissue. The findings of auscultation closely mimicked those of tricuspid valvular stenosis.

Treatment of infective endocarditis with granulocyte colony-stimulating factor.

Granulocyte colony-stimulating factor (G-CSF) is a glycoprotein hormone which stimulates the proliferation and differentiation of a subset of granulocyte precursors and enhances some functional activities of mature neutrophils. We tested the effects of G-CSF on a patient with intractable infective endocarditis. The white blood cell count was increased 3-fold and the inflammatory reactions such as C-reactive protein and erythrocyte sedimentation rate were completely normalized without any side effects. This is the first report describing the use of G-CSF for infective endocarditis. Administration of G-CSF might be suitable for treating intractable infections which cannot be controlled by antibiotics alone.

[Aortic pulse wave velocity in patients with coronary atherosclerosis--a comparison with coronary angiographic findings].

This study was conducted to investigate the relationship between aortic pulse wave velocity (PWV) and coronary atherosclerosis. We measured PWV in 105 subjects (84 males and 21 females; age 59 +/- 0.5) who received coronary angiographic examination (CAG). PWV was measured by simultaneous recording of pulse waves from the left carotid and the left femoral arteries, electrocardiogram and phonocardiogram. The subjects were classified into 4 groups according to the number of major coronary arteries having stenosis, that is, N group with normal CAG, 1 vessel disease (VD) group, 2VD group and 3VD group. The PWV value was significantly greater only in 3VD group (n = 10, age 63 +/- 3.6, PWV 10.0 +/- 0.88 m/sec) than that in N group (n = 18, age 53 +/- 2.0, PWV 8.0 +/- 0.34 m/sec). No significant difference was observed between PWV value in N group and that in all patients with coronary artery stenosis (n = 87, age 60 +/- 2.0, PWV 8.9 +/- 0.2 m/sec). To further investigate the relationship between PWV values and CAG findings, we used a CAG score which means the sum of the points assigned to each coronary artery segment (American Heart Association) according to the severity of stenosis (0, 1, 2, 3, and 4 for normal, less than 49% stenosis, 50 to 74% stenosis, 75 to 99% stenosis, and complete occlusion, respectively). The PWV values significantly correlated with the CAG score and also with age by a simple regression analysis. Multivariate analysis, however, revealed that PWV values did no longer correlate with CAG score. PWV values still significantly correlated with age.(ABSTRACT TRUNCATED AT 250 WORDS)