Altered calcium uptake by the sarcoplasmic reticulum following cardiac transplantation in humans

Abnormalities in the diastolic properties of the heart have been described following human cardiac transplantation and may reflect, at least in part, decreased Ca2+ uptake by the sarcoplasmic reticulum. This possibility was evaluated by obtaining serial myocardial biopsies in 13 patients who underwent cardiac transplantation for severe heart failure. Oxalate-supported Ca2+ uptake by the sarcoplasmic reticulum was measured in homogenates of 83 ventricular biopsies from transplanted hearts. Biopsies from seven subjects with normal cardiac function and morphology served as controls. In the transplanted hearts, there was a tendency for Ca2+ uptake rate to decline with time so that 4-5 months postoperatively, it was significantly lower (4.5 +/- 0.5 nmoles Ca2+/mg/min) compared to controls (5.6 +/- 0.5 nmoles Ca2+/mg/min, p less than 0.01). Plasma norepinephrine levels fell from the high preoperative values (689 +/- 50 pg/mL) towards normal (215 +/- 7 pg/mL) within 30 days after transplantation. Subsequently, however, there was a tendency for norepinephrine levels to increase (369 +/- 55 pg/mL at 4 months). In four patients for which serial observations were available, there was an inverse relationship between myocardial Ca2+ uptake and plasma norepinephrine levels. These results indicate the feasibility of obtaining reproducible serial measurements of Ca2+ uptake in human cardiac biopsies. The decline in sarcoplasmic reticulum function following cardiac transplantation may be, in part, the biochemical basis for the reported impairment in diastolic relaxation.     

B-type natriuretic peptide level in the diagnosis of asymptomatic diastolic dysfunction.

OBJECTIVE: Brain natriuretic peptide (BNP) reflects the left ventricular pressure and volume overload. It is known that it increases in systolic dysfunction proportionally with left ventricular pressure increase. The BNP levels are well correlated with NYHA classification and prognosis. Our aim was to evaluate the predictive value of BNP in patients with diastolic dysfunction but normal systolic dysfunction demonstrated by echocardiography. METHODS: Fifty patients (mean age: 48.5+/-6.75 years; 29 males, 21 females) were included in this cross-sectional, case-controlled study. Systolic dysfunction was the exclusion criterion. The following parameters were used to evaluate diastolic function: isovolumetric relaxation time, transmitral early to late filling flow velocities (E/A) ratio, deceleration time E, pulmonary vein Doppler findings and color mitral flow propagation velocity. Diastolic dysfunction was determined in 30 hypertensive patients (Group 1), whereas 20 patients who had normal diastolic flow patterns on echocardiography (Group 2). Blood samples were taken for serum BNP level measurements. RESULTS: The BNP levels were 12.0+/-4.97 pg/ml in individuals with normal filling pattern and 66.17+/-17.56 pg/ml in individuals with abnormal filling patterns (p<0.001). The accuracy of BNP in detection of diastolic dysfunction was assessed with receiver-operating characteristic (ROC) analysis. The area under the ROC curve for BNP test accuracy in detection any abnormal diastolic dysfunction was 0.969 (95% CI, 0.909 to 1.029; p<0.001). A BNP value of 37.0 pg/ml had sensitivity of 80%, specificity of 100%, a positive predictive value of 100%, a negative predictive value of 23% and accuracy of 88% in identifying asymptomatic prolonged relaxation pattern. We found a strong correlation between left ventricular mass index and plasma BNP levels (r=0.62, p<0.05). CONCLUSION: Estimation of BNP values could be accepted as a fast and reliable blood test in the diagnosis of asymptomatic diastolic dysfunction.     

Validity of N-terminal propeptide of the brain natriuretic peptide in predicting left ventricular diastolic dysfunction diagnosed by tissue Doppler imaging in patients with chronic liver disease

BACKGROUND AND AIMS: Left ventricular diastolic dysfunction has been reported in patients with liver cirrhosis. Although conventional Doppler echocardiography has been used to assess diastolic filling dynamics, this technique is limited in diagnosing left ventricular diastolic dysfunction. The aim of the study was to validate the N-terminal propeptide of the brain natriuretic peptide (NT-proBNP) in predicting left ventricular diastolic dysfunction diagnosed by tissue Doppler imaging in patients with chronic liver disease. METHODS: In 64 patients, left ventricular diastolic dysfunction was classified using tissue Doppler imaging and serum levels of NT-proBNP were measured. RESULTS: Left ventricular diastolic dysfunction was found in 25 of 31 (80.6%) patients with severe liver fibrosis/cirrhosis versus 2 of 8 (25.0%) patients with moderate and 6 of 25 (24.0%) patients with mild liver fibrosis (P<0.001). Mean NT-proBNP levels were 407.1+/-553.4 pg/ml in patients with severe fibrosis/cirrhosis as compared with 60.8+/-54.9 pg/ml and 55.4+/-41.4 pg/ml in patients with mild and moderate fibrosis (P=0.001). NT-proBNP was most accurate in predicting advanced left ventricular diastolic dysfunction with an area under the receiver-operating characteristic curve of 0.90 (95% confidence interval, 0.77-1.0; P<0.001). A cutoff value of greater than 290 pg/ml was highly predictive of advanced left ventricular diastolic dysfunction. CONCLUSION: NT-proBNP is a useful marker in detecting advanced left ventricular diastolic dysfunction in patients with chronic liver disease. Patients with severe liver fibrosis/cirrhosis and NT-proBNP levels exceeding 290 pg/ml should undergo further cardiac evaluation.     

Correlation between N-terminal pro B-natriuretic peptide and ultrasonic backscatter: implications for diastolic dysfunction in hypertension

OBJECTIVE: This study was designed to determine how N-terminal pro brain-natriuretic peptide (NT-proBNP) levels correlate with cyclic variation of integrated backscatter (CVIBS) as a reflection of abnormal diastolic function in hypertension. PATIENTS: Forty essentially hypertensive patients were studied. CVIBS values were obtained from the septal wall in the parasternal long-axis view. Twelve had normal diastolic function, 18 had impaired relaxation, and 10 had pseudonormal pattern. RESULTS: Patients with normal diastolic function had a mean NT-proBNP concentration of 34 +/- 17 pg/ml and a mean CVIBS value of 7.1 +/- 0.9 dB; those with impaired relaxation had a mean NT-proBNP concentration of 71 +/- 25 pg/ml and a mean CVIBS value of 6.7 +/- 1.1 dB. Patients with pseudonormal pattern had the highest NT proBNP levels (206 +/- 75 pg/ml) and lowest CVIBS values (5.7 +/- 0.9 dB). An NT-proBNP value of 62 pg/ml had a sensitivity of 83% and a specificity of 91%; a CVIBS value of 7.2 dB had a sensitivity of 83.3% and a specificity of 66.7% for detecting diastolic dysfunction. An NT-proBNP value of 120 pg/ml had a sensitivity of 76% and a specificity of 96%; a CVIBS value of 6.1 dB had a sensitivity of 87.5% and a specificity of 75% for detecting severe diastolic dysfunction. A close correlation was found between the NT-proBNP and CVIBS values (r: 0.54, P < 0.05). CONCLUSION: Combinative use of NT-proBNP and CVIBS can detect the presence of diastolic abnormalities on echocardiography. A good correlation was found between the NT-proBNP and CVIBS values in detecting diastolic dysfunction in essentially hypertensive patients.     

Utility of B-natriuretic peptide levels in identifying patients with left ventricular systolic or diastolic dysfunction

PURPOSE: Although echocardiography is important for making the diagnosis of left ventricular dysfunction, its cost and lack of availability limit its use as a routine screening test. B-Natriuretic peptide levels accurately reflect ventricular pressure, and preliminary studies with a rapid assay have found that levels are sensitive and specific for diagnosing heart failure in patients with dyspnea. We hypothesized that B-natriuretic peptide levels obtained through the use of a rapid assay should correlate with echocardiographic abnormalities of ventricular function. SUBJECTS AND METHODS: We studied 400 patients who were referred for echocardiography at the San Diego Veteran's Healthcare System between June and August 2000 to evaluate ventricular function. B-natriuretic peptide levels were measured by a point-of-care immunoassay; cardiologists assessing left ventricular function were blinded to the assay results. Patients were grouped into those with normal ventricular function, systolic dysfunction only, diastolic dysfunction only, and both systolic and diastolic dysfunction. RESULTS: Mean (+/- SD) B-natriuretic peptide concentration was 416 +/- 413 pg/mL in the 253 patients diagnosed with abnormal left ventricular function, compared with 30 +/- 36 pg/mL in the 147 patients with normal left ventricular function. Patients with both systolic and diastolic dysfunction had the highest levels (675 +/- 423 pg/mL). The area under the receiver operating characteristic (ROC) curve for B-natriuretic peptide levels to detect any abnormal echocardiographic finding was 0.95 (91% confidence interval: 0.93 to 0.97). B-Natriuretic peptide levels were unable to differentiate systolic vs. diastolic dysfunction. In patients with symptoms of heart failure and normal systolic function, B-natriuretic peptide levels >57 pg/mL had a positive predictive value of 100% for diastolic abnormalities. CONCLUSIONS: A simple, rapid test for B-natriuretic peptide levels can reliably predict the presence or absence of left ventricular dysfunction on echocardiogram. For some patients, a normal level may preclude the need for echocardiography.     

Serum concentrations of tumour necrosis factor-alpha (TNF-alpha) and soluble TNF-alpha receptor p55 in patients with hypothyroidism and hyperthyroidism before and after normalization of thyroid function

BACKGROUND: Tumour necrosis factor-alpha (TNF-alpha) is a cytokine with numerous immunological and metabolic activities. Receptors for TNF-alpha have been demonstrated in thyroid follicular cells and TNF-alpha and its receptors have been implicated in the cytotoxic mechanisms that characterize the thyroid destruction in autoimmune thyroid disease. In patients with Graves' disease, serum levels of TNF-alpha have been reported to be elevated and administration of TNF-alpha to humans has been shown to induce hormonal alterations resembling those seen in the nonthyroidal illness syndrome. OBJECTIVE: To evaluate serum concentrations of TNF-alpha and the soluble receptor for TNF-alpha (sTNFR-I) in a group of patients with thyroid dysfunction before and after normalization of thyroid function with appropriate therapy. DESIGN: We studied 20 patients with hypothyroidism (18 women and 2 men, mean age +/- SD, 48.8 +/- 16.1 years) and 20 patients with hyperthyroidism (14 women and 6 men, age 44.6 +/- 15.9 years). Patients were assessed at the time of diagnosis and again after normalization of thyroid function tests with appropriate therapy. A group of 20 healthy subjects (15 women and 5 men, age 44.9 +/- 15.1 years) were also studied as a control group. SETTING: All subjects were ambulatory and were studied as outpatients during visits to the endocrinology clinic. MEASUREMENTS: Serum concentrations of free T4 (FT4), total T3, TSH, TNF-alpha and sTNFR-I were measured in all subjects. TNF-alpha and sTNFR-I were measured using a quantitative enzyme immunoassay. RESULTS: In patients with hypothyroidism serum concentrations of TNF-alpha (3.17 +/- 1.18 pg/ml) and sTNFR-I (1273 +/- 364 pg/ml) were significantly higher than those found in controls (2.42 +/- 0.76 pg/ml, P < 0.05, and 971 +/- 235 pg/ml, P < 0.01, respectively). Normalization of thyroid function with l-thyroxine therapy did not significantly modify TNF-alpha or sTNFR-I levels. There were no differences in pre- and post-therapy values of TNF-alpha and sTNFR-I in patients with autoimmune (n = 14) or nonautoimmune (n = 6) hypothyroidism. Before therapy, patients with hyperthyroidism showed elevated serum concentrations of TNF-alpha (3.36 +/- 1.21 pg/ml; P < 0.01) and sTNFR-I (2274 +/- 579 pg/ml; P < 0.001) in relation to the control group. Treatment of hyperthyroidism was accompanied by a normalization of TNF-alpha levels (2.46 +/- 0.89 pg/ml; P < 0.001) and by a significant decrease in sTNFR-I concentrations (1369 +/- 475 pg/ml; P < 0.001). Post-therapy levels of TNF-alpha and sTNFR-I showed a significant correlation with loss of weight (r = 0.674, P < 0.01, and r = 0.629, P < 0.01, respectively) in hypothyroid patients. No correlation between these parameters was found in the group of patients with hyperthyroidism. CONCLUSIONS: In summary, these results confirm the relevance of activation of the TNF-alpha system in patients with thyroid dysfunction, as high plasma concentrations of TNF-alpha and sTNFR-I have been demonstrated in patients with hypothyroidism or hyperthyroidism. Treatment of hyperthyroidism is accompanied by a significant reduction in the previously elevated concentrations of both TNF-alpha and sTNFR-I. However, these changes are not seen when normalizing thyroid function in patients with hypothyroidism.     

Doppler echocardiography-derived index of myocardial performance (TEI index): comparison with brain natriuretic peptide levels in various heart disease.

Plasma brain natriuretic peptide (BNP) has diagnostic and prognostic value in heart failure. Cardiac dysfunction varies from systolic or diastolic dysfunction alone to the combination of both. In the present study, Doppler echocardiographic parameters, including the Doppler echocardiography-derived index (TEI index), were compared with plasma BNP levels in 74 patients with various heart diseases. Blood sampling was performed before an echocardiographic examination was conducted. The TEI index was defined as the summation of isovolumic contraction and relaxation time divided by ejection time. In patients with left ventricular (LV) systolic dysfunction (ejection fraction <50%), the TEI index and BNP were increased significantly compared with patients with normal LV systolic function (p<0.05). Patients with a TEI index > or =0.45 showed significantly increased BNP levels compared with patients with a TEI index <0.45, irrespective of LV systolic function (241.4+/-451.2 vs 65.9+/-81.8pg/ml; p<0.05). The TEI index was significantly higher in patients with a BNP > or =73pg/ml than in patients with BNP <73pg/ml (0.57+/-0.24 vs 0.46+/-0.17; p<0.05). Other echocardiographic parameters did not correlate significantly with levels of plasma BNP. Of the echocardiographic parameters, a simple Doppler index (TEI index) that combines systolic and diastolic function can detect LV dysfunction in patients with high levels of plasma BNP in various heart diseases.     

BNP as a marker of diastolic dysfunction in the general population: Importance of left ventricular hypertrophy

BNP is a marker of systolic left ventricular dysfunction (LVSD) and heart failure. To assess BNP for the detection of diastolic dysfunction in the general population, we examined 1678 subjects within an age- and sex-stratified survey (MONICA Augsburg). BNP was measured using a commercially available RIA (Shionogi). BNP increased in subjects with diastolic dysfunction (mean 20.3+/-4.7 pg/ml vs. control 9.6+/-0.5 pg/ml, p<0.001), but to a lesser extent than in subjects with LV hypertrophy (LVH, mean 37.3+/-49.1 pg/ml, p<0.001 vs. control) or LVSD (mean 76.2+/-23.2 pg/ml, p<0.001 vs. control). Individuals with sole diastolic abnormality displayed BNP concentrations at the control level (mean 9.7+/-1.7 pg/ml). In univariate analysis, age, BMI, systolic blood pressure, left atrial size, LV mass index, diastolic dysfunction and EF displayed a significant correlation with BNP (p<0.001). However, LV mass index displaced diastolic dysfunction as a significant predictor of BNP in multivariate analysis. Upon ROC analysis, sensitivity and specificity for the detection of diastolic dysfunction by BNP were only 61% and 55%, respectively. Nevertheless, a normal BNP test virtually excluded the presence of diastolic dysfunction and concomitant LVH (NPV 99.9%). Increased BNP concentrations in subjects with diastolic dysfunction are strongly related to LVH. Population-wide screening for diastolic dysfunction with BNP cannot be recommended although a normal BNP test usually excludes diastolic dysfunction and LV hypertrophy.     

Utility of B-natriuretic peptide as a rapid, point-of-care test for screening patients undergoing echocardiography to determine left ventricular dysfunction

BACKGROUND: Although echocardiography is an important tool for making the diagnosis of left ventricular (LV) dysfunction, the cost of this procedure limits its use as a routine screening tool for this purpose. Brain natriuretic peptide (BNP) accurately reflects ventricular pressure, and preliminary studies have found it to be highly sensitive and highly specific in diagnosing congestive heart failure in the emergency department. We hypothesized that BNP might therefore be useful as a screening tool before echocardiography in patients with suspected LV dysfunction. METHODS: Subjects included patients referred for echocardiography to evaluate the presence or absence of LV dysfunction. Patients with known LV dysfunction were excluded from analysis. BNP was measured by a point-of-care immunoassay (Biosite Diagnostics, San Diego, Calif). The results of BNP levels were blinded from cardiologists making the assessment of LV function. Patients were divided into those with normal ventricular function, abnormal systolic ventricular function, abnormal diastolic function, and evidence of both systolic and diastolic dysfunction. RESULTS: Two hundred patients in whom LV function was unknown were studied. In the 105 patients (53%) whose ventricular function was subsequently determined to be normal by echocardiography, BNP levels averaged 37 +/- 6 pg/mL. This was significantly less than in those patients with either ultimate diastolic dysfunction (BNP 391 +/- 89 pg/mL (P <.001) or systolic dysfunction (BNP 572 +/- 115 pg/mL (P <.001). A receiver-operator characteristic curve showing the sensitivity and specificity of BNP against the echocardiography diagnosis revealed the area under the curve (accuracy) was 0.95. At a BNP level of 75 pg/mL was 98% specific for detecting the presence or absence of LV dysfunction by echocardiography. CONCLUSIONS: A simple, rapid test for BNP, which can be performed at the bedside or in the clinic, can reliably predict the presence or absence of LV dysfunction on echocardiogram. The data indicate that BNP may be an excellent screening tool for LV dysfunction and may, in fact, preclude the need for echocardiography in many patients.     

Brain natriuretic peptide blood levels in the differential diagnosis of dyspnea.

STUDY OBJECTIVES: In dyspneic patients without left ventricular enlargement, it may be difficult to differentiate between obstructive lung disease and diastolic heart failure. Determination of plasma brain natriuretic peptide (BNP) levels, known to increase with ventricular stretch, may be of clinical relevance in this situation. We compared the discriminant power of BNP blood levels and of echocardiography in patients with either chronic obstructive lung disease or diastolic heart failure. PATIENTS: Twenty-six New York Heart Association class III dyspneic patients with normal left ventricular systolic function were enrolled: 17 patients with chronic obstructive lung disease and 9 patients with unequivocal diastolic heart failure. RESULTS: Echocardiographic data were unable to accurately differentiate between the two groups, whereas BNP levels were significantly and markedly higher in patients with diastolic heart failure when compared to those with obstructive lung disease (224 +/- 240 pg/mL vs 14 +/- 12 pg/mL, p < 0.0001). CONCLUSIONS: These preliminary results warrant a prospective, large-scale evaluation of the value of BNP assay for determining diastolic dysfunction, a common cause of dyspnea in elderly patients, and differentiating it from other diagnoses such as obstructive lung disease.     

Bedside tests of B-type natriuretic peptide in the diagnosis of left ventricular diastolic dysfunction in hypertensive patients

AIMS: To investigate the value of B-type natriuretic peptide (BNP) in diagnosing left ventricular diastolic dysfunction in patients with hypertension. METHODS: The left ventricular diastolic function and plasma BNP levels were assessed prospectively in 135 hypertensive patients. RESULTS: The plasma BNP in patients with (n=61) and without (n=74) diastolic dysfunction was 122+/-105 and 18+/-16 pg/ml, respectively (p<0.001). Increased BNP levels were associated with systolic blood pressure (p<0.05), left ventricular mass index (p<0.001), the E/A ratio of transmitral flow (p<0.01) and the isovolumic relaxation time (p<0.01). A receiver-operator characteristic curve showing the sensitivity and specificity of BNP against the echocardiography diagnosis of diastolic dysfunction revealed an area under the curve (accuracy) of 0.904 (p<0.01). Using a cut-off value of >40 pg/ml, the sensitivity and specificity of plasma BNP in diagnosing left ventricular diastolic dysfunction were 79% and 92%, respectively. CONCLUSIONS: The plasma BNP levels in patients with hypertension are closely related to left ventricular hypertrophy and filling impairment. Plasma BNP may be used to facilitate the diagnosis of left ventricular diastolic dysfunction.     

B-type natriuretic peptide and cardiac dysfunction in Duchenne muscular dystrophy

Serum levels of B-type natriuretic peptide have moderate utility for detection of early ventricular dysfunction in adults and in experimental muscular dystrophy. To determine if B-type natriuretic peptide levels are useful in the detection of early left ventricular dysfunction in Duchenne muscular dystrophy patients, measurements were obtained in 21 patients being evaluated by echocardiography for left ventricular dysfunction. Two patients with clinical evidence of heart failure were excluded (mean B-type natriuretic peptide level of 352 pg/ml). Age range of the remaining 19 patients was 9-21 yrs. Fractional shortening was abnormal (<30%) in 14/19 and early diastolic tissue Doppler velocities were abnormal in 13/16. In these patients B-type natriuretic peptide levels were clearly normal (<30 pg/ml) in 15/19 and only mildly elevated (30-80 pg/ml) in 4/19. The 4 patients with mildly elevated B-type natriuretic peptide had significantly lower fractional shortening (12.6+/-5.9 versus 19.8+/-5.3, p<0.05). In conclusion, B-type natriuretic peptide levels are normal in the majority of Duchenne muscular dystrophy patients with asymptomatic left ventricular dysfunction and only mildly elevated when fractional shortening is markedly reduced.     

Elevated serum TNF-alpha level as a link between endothelial dysfunction and insulin resistance in normotensive obese patients.

AIMS: The aim of the study was to analyse the role of tumour necrosis factor-alpha (TNF-alpha) in insulin resistance and endothelial dysfunction in patients with different types of obesity. PATIENTS AND METHODS: Fasting serum TNF-alpha immunoreactive concentration (enzyme-linked immunosorbent assay, ELISA) and bioactivity (L929 cell cytotoxicity assay), endothelin-1 and C-peptide levels (radioimmunoassay, RIA) were measured in 15 patients with android- and 13 patients with gynoid-type obesity and 15 lean healthy controls with normal glucose tolerance and blood pressure. RESULTS: Significantly (P<0.01) higher TNF-alpha concentration (8.92 +/- 0.44 pg/ml) and bioactivity (3.12 +/- 0.48 U/ml) were found in patients with android obesity as compared to patients with gynoid obesity (7.01 +/- 0.30 pg/ml, 0.97 +/- 0.11 U/ml) and to the lean controls (6.88 +/- 0.26 pg/ml, 0.88 +/- 0.08 U/ml). Serum endothelin-1 (5.38 +/- 0.30 pg/ml) and C-peptide levels (4.82 +/- 0.71 ng/ml) were also significantly higher (P < 0.01) in patients with android-type obesity than in controls (3.89 +/- 0.43 pg/ml, 1.46 +/- 0.25 ng/ml, respectively). In patients with gynoid-type obesity, only the C-peptide levels proved to be significantly higher (2.84 +/- 0.29 ng/ ml). Endothelin-1 levels, although were found to be slightly higher, did not differ statistically from in controls (4.56 +/- 0.31 pg/ml). There were significant positive linear correlations only in patients with android-type obesity between TNF-alpha, body mass index (BMI), serum endothelin-1 and C-peptide levels. CONCLUSIONS: TNF-alpha may be one of the factors contributing to insulin resistance and vascular dysfunction in patients with android obesity.     

Impact of obstructive sleep apnea on right ventricular global function: sleep apnea and myocardial performance index

BACKGROUND: Obstructive sleep apnea (OSA) is characterized by repetitive upper airway obstructions during sleep, and it might cause cardiovascular complications such as heart failure, arrhythmias, myocardial infarction, systemic and pulmonary hypertension. OBJECTIVES: To determine right ventricular diameters and myocardial performance index (MPI) reflecting ventricular global function in uncomplicated OSA patients. METHODS: 49 subjects without hypertension, diabetes mellitus, or any cardiac or pulmonary disease referred for evaluation of OSA had overnight polysomnography and complete echocardiographic assessment. According to the apnea-hypopnea index (AHI), subjects were divided into three groups: group 1: control subjects (AHI <5, n = 20), group 2: patients with mild OSA (AHI: 5-14, n = 11), and group 3: moderate-severe OSA (AHI > or = 15, n = 18). Right ventricular free wall diameter was measured by M mode, and right ventricular MPI was calculated as (isovolumic contraction time + isovolumic relaxation time)/pulmonary ejection time. RESULTS: There were no differences of age, body mass index, heart rates, systolic and diastolic blood pressures among the groups (p > 0.05). Right ventricular end-diastolic and end-systolic diameters were not statistically different between the groups, and were within normal limits. Also, right ventricular free wall diameter was not significantly different between the groups of control, mild OSA and moderate-severe OSA (6.7 +/- 0.9, 6.9 +/- 1.0, 7.1 +/- 1.1 mm, p > 0.05). Right ventricular diastolic dysfunction was shown only in group 3 patients. Right ventricular MPI was statistically higher in group 3 (0.62 +/- 0.18) than in group 2 patients (0.50 +/- 0.10), and group 1 patients (0.48 +/- 0.08, p < 0.001). CONCLUSIONS: It was suggested that patients with moderate-severe OSA had a right ventricular global dysfunction, in addition to the presence of a diastolic dysfunction.     

Relation between stage of left ventricular diastolic dysfunction and QT dispersion

OBJECTIVE: In 30-40% of patients with clinical heart failure diastolic dysfunction is present although systolic function is normal. Evaluation of diastolic functions are important for the patient's early diagnosis, treatment and prognosis. QT dispersion is an important parameter that reflects heterogeneity of ventricular repolarization and predicts ventricular arrhythmia and sudden death. According to several studies, QT dispersion is significantly increased in patients with diastolic dysfunction due to ischemic heart disease and left ventricular hypertrophy compared to the patients without diastolic dysfunction. However, a study about the relation between the stage of left ventricular diastolic dysfunction and QT dispersion is not present. The aim of this study was to investigate the correlation between the stage of left ventricular diastolic function determined by transthoracic echocardiography and QT dispersion. METHODS AND RESULTS: In our study the left ventricular diastolic functions of 80 patients were evaluated by transthoracic echocardiography. Eighty patients were divided to four stages each containing 20 patients. Stage 0 was defined as normal, stage 1 as prolonged relaxation pattern, stage 2 as pseudonormal pattern and stage 3 as restrictive pattern. We measured QT dispersion (QT D) and corrected QT dispersion (QTc D) values according to Bazzet's formula in their ECGs. QT D and QTc D were found 20+/-8 ms vs. 26+/-1 ms in normal patients, 25+/-8 ms vs. 37+/-9 ms in the patients with prolonged relaxation pattern, 28+/-10 ms vs. 38+/-11 ms in the patients with pseudonormal pattern and 38+/-13 ms vs. 41+/-14 ms in the patients with restrictive pattern. A significant direct relation was found between the stage of left ventricular diastolic function and QT, QTc dispersion (p<0.01). Furthermore, when classified according to the aetiology of the left ventricular diastolic dysfunction (stage 1, 2, 3) QT D and QTc D were 24+/-6 ms vs. 32+/-9 ms in the patients with left ventricular hypertrophy (LVH), and 32+/-9 ms vs. 41+/-12 ms in the patients with ischaemic heart disease (IHD). The differences between the two groups were statistically significant (p<0.01). CONCLUSIONS: These findings show that QT D and QTc dispersion values increase in relation to increasing left ventricular diastolic functional stage that is determined by echocardiography and that the patients with ischaemic heart disease have much more increased QT values than the patients with left ventricular hypertrophy.     

Proinflammatory cytokines (IL-6, TNF-alpha) and cardiac troponin I (cTnI) in serum of young people with ventricular arrhythmias

In the most cases the origin of ventricular arrhythmias is ischaemic, necrosis focus or presence of the connective tissue in cardiac muscle. The aim of the study was to evaluate troponin I (cTnI), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) vs in young subject with ventricular arrhythmias. Into the study group included young people without organic heart diseases, dyselectrolitemia, with normal ECG which has not elevated levels of C-reactive protein (55 persons). The control group consisted of 22 healthy persons. The values of cTnI were not increased. The TNF-alpha concentrations were elevated in persons with ventricular arrhythmias (92 +/- 232 pg/mL vs. 2 +/- 1 pg/mL, p < 0.001). The IL-6 concentrations were slightly elevated without statistical significance (1.5 +/- 4.5 pg/mL i 0.1 +/- 0.04 pg/mL, p = 0.06). CONCLUSIONS: There was no evidence of myocardial injury in young people with ventricular arrhythmias (cTnI). We noted increase levels of proinflammatory cytokines. It might suggest that the background of ventricular arrhythmias is inflammation.     

Clinical significance of brain natriuretic peptide in patients with postmyocardial infarction

BACKGROUND: Risk stratification after acute myocardial infarction (AMI) includes the evaluation of left ventricular (LV) function. Natriuretic peptides, and particularly brain natriuretic peptide (BNP), emerged as a potential marker of ventricular function and prognosis after AMI. HYPOTHESIS: Brain natriuretic peptide levels are related to ventricular function, either systolic or isolated diastolic, and can give prognostic information in patients surviving AMI. METHODS: In all, 101 patients were enrolled. An echocardiographic (M-mode, two-dimensional, and pulsed Doppler) evaluation was performed and blood samples for BNP measurement were obtained. Clinical events were recorded during 12 months of follow-up. RESULTS: A negative correlation between BNP and LV ejection fraction was observed (r = -0.38; p < 0.001). The BNP levels were higher among patients with LV systolic dysfunction than in patients with isolated diastolic dysfunction (339.1 +/- 249.9 vs. 168.0 +/- 110.5 pg/ml, p = 0.001). The latter had higher levels of BNP than those with normal LV function (68.3 +/- 72.6 pg/ml, p < 0.001). The BNP accuracy to detect LV systolic dysfunction was good (area under the ROC curve [AUC] = 0.83) and increased when isolated diastolic dysfunction was also considered (AUC = 0.87). Brain natriuretic peptide had a very good accuracy in the prediction of death (AUC = 0.95) and the development of heart failure (AUC = 0.90). CONCLUSION: These results extend previous evidence relating BNP to systolic function after AMI. Furthermore, a relationship between BNP levels and diastolic function was found. Brain natriuretic peptide had a very good performance in detecting the occurrence of an adverse event. We conclude that BNP can detect high-risk patients and help select patients for more aggressive approaches.     

Left ventricular diastolic function in pregnancy in patients with arterial hypertension. A prospective study with M-mode echocardiography and Doppler echocardiography

INTRODUCTION: During pregnancy eminent cardiovascular changes occur. The aim of the following study was to investigate the course of hemodynamic parameters under increased volume load during pregnancy in women suffering from mild arterial hypertension. METHODS: Altogether 47 women (age: 25 +/- 4 years) with mild arterial hypertension detected during pregnancy underwent echocardiography at the 9th, 24th and 33rd week of gestation. Furthermore echocardiography was performed postpartum at weeks 1 and 8. The control group comprised 45 healthy pregnant women. In all patients left ventricular muscle mass index and systolic shortening fraction were measured. The following Doppler echocardiographic parameters were ascertained: peak early diastolic and peak late diastolic flow, VE/VA ratio, acceleration time, deceleration time and isovolumetric relaxation time. RESULTS: During pregnancy all patients had an increase of left ventricular muscle mass index and a decrease of fractional shortening. All patients developed a relevant diastolic dysfunction. While the control group developed signs of disturbed relaxation as reduction of peak early diastolic flow (0.89 +/- 0.07 versus 0.82 +/- 0.08 m/s*), VE/VA ratio and an increase of isovolumetric relaxation time (72 +/- 12 versus 123 +/- 7*) at the 33rd week of gestation (* p < 0.01), all pregnant women with mild arterial hypertension developed a diastolic dysfunction with signs of delayed relaxation already at the beginning of gestation. 26 pregnant women with arterial hypertension developed a restrictive diastolic filling pattern at 24 weeks of gestation. The other 21 pregnant women only showed restriction for a short time at the end of gestation. In healthy pregnant women, volume load results in a reversible physiologic left ventricular hypertrophia, a significant alteration of diastolic left ventricular function in terms of a disturbed relaxation pattern and a temporary decrease of systolic function. In comparison hypertensive pregnant women show a delayed relaxation at the beginning of pregnancy and 50% developed early signs of restrictive cardiomyopathy. These changes may predispose to critical complications during pregnancy.     

NT-proBNP in normoalbuminuric patients with Type 2 diabetes mellitus.

OBJECTIVE: To examine levels of NT-proBNP and its relation to hypertension, as well as diastolic function in normoalbuminuric patients with Type 2 diabetes. RESEARCH DESIGN AND METHODS: The study comprised 60 Type 2 diabetic patients without albuminuria. Thirty patients were normotensive and 30 had hypertension. Exclusion criteria were cardiac symptoms and an ejection fraction < 55%. Thirty age- and sex-matched normal subjects served as controls. Diastolic dysfunction was assessed with echocardiography, by means of mitral inflow and colour M-Mode flow propagation recordings. RESULTS: Overall NT-proBNP was significantly elevated in the Type 2 diabetes group, compared with the controls [54.5 pg/ml (5-162) vs. 32.7 pg/ml (5-74.3) P = 0.02]. NT-proBNP was significantly higher among hypertensive patients compared with both normotensive patients and controls but no difference was found between the normotensive patients and the controls [58.0 pg/ml (8.5-162), P < 0.05 vs. 50.8 pg/ml (5-131) P = 0.4]. Patients with concentric and eccentric hypertrophy had significantly higher NT-proBNP levels compared with the control group [81.0 pg/ml (5-147), P < 0.001 and 66.8 pg/ml (42-128), P < 0.001], whereas patients with left ventricular remodelling (enlarged relative wall diameter but normal left ventricular mass) were comparable with the control group [42.3 pg/ml (8.3-142) P = 0.55]. Patients with left atrial enlargement also had incremental NT-proBNP values. NT-proBNP was only moderately correlated to age (r = 0.33, P < 0.05) and left ventricular diastolic diameter (r = 0.41, P < 0.05), but unrelated to diastolic function. CONCLUSIONS: NT-proBNP is significantly increased in hypertensive, normoalbuminuric patients with Type 2 diabetes. These findings were related to left ventricular hypertrophy and increased left atrial and ventricular diameters.     

Plasma and pericardial fluid natriuretic peptide levels in postinfarction ventricular dysfunction

AIMS: In the present study we examined plasma and pericardial fluid ANP and BNP concentrations in postinfarction ventricular dysfunction. The association of peptide levels to left ventricular (LV) dysfunction and to the localization of the myocardial infarction (MI) was studied. METHODS AND RESULTS: Plasma and pericardial fluid samples were obtained from 37 patients undergoing coronary bypass surgery. According to the ECG and preceding coronary angiography, the patients were divided into three groups: previous anterior myocardial infarction (MI) (n=12), previous inferior/posterior MI (n=15) and no history of MI (n=10). When compared to the control group with no MI, the patients with anterior MI had elevated plasma ANP and BNP (134+/-13 vs. 81+/-15 pg/ml, P<0.01 and 95+/-10 pg/ml vs. 26+/-8 pg/ml, P<0.01, respectively) and pericardial fluid BNP (473+/-60 pg/ml vs. 57+/-8 pg/ml, P<0.001) levels. The plasma natriuretic peptide concentrations were not increased in the patients with inferior/posterior MI, but the pericardial fluid BNP concentrations were greater than in the patients with no history of MI (129+/-35 pg/ml vs. 57+/-8 pg/ml, P<0.05). Six of the 12 patients with previous anterior MI had LVEF> or =45%. Despite their normal LV systolic function, these patients had increased plasma and pericardial fluid BNP levels when compared to the group with no history of MI (68+/-18 pg/ml vs. 26+/-8 pg/ml, P<0.05 and 534+/-258 pg/ml vs. 57+/-8 pg/ml, P<0.01, respectively). CONCLUSIONS: Previous anterior myocardial infarction was associated with increased cardiac BNP production even if the LV systolic function was normal (LVEF> or =45%). The high pericardial fluid BNP concentrations in postinfarction patients suggest that the BNP synthesis and release are augmented in the ventricular myocardium independent from the LVEF.