Population based study on the prevalence of the stages of heart failure.
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Age Distribution↗
Biomedical subjects
P Bettencourt
Publications and source records attributed to P Bettencourt.
Full-genome RNAi profiling of early embryogenesis in Caenorhabditis elegans.
A key challenge of functional genomics today is to generate well-annotated data sets that can be interpreted across different platforms and technologies. Large-scale functional genomics data often fail to connect to standard experimental approaches of gene characterization in individual laboratories. Furthermore, a lack of universal annotation standards for phenotypic data sets makes it difficult to compare different screening approaches. Here we address this problem in a screen designed to identify all genes required for the first two rounds of cell division in the Caenorhabditis elegans embryo. We used RNA-mediated interference to target 98% of all genes predicted in the C. elegans genome in combination with differential interference contrast time-lapse microscopy. Through systematic annotation of the resulting movies, we developed a phenotypic profiling system, which shows high correlation with cellular processes and biochemical pathways, thus enabling us to predict new functions for previously uncharacterized genes.
Animals↗
Heart failure, aging, and renal synthesis of dopamine.
The present study evaluates renal dopaminergic activity in 23 patients with heart failure (HF), 10 age-matched controls, and 10 young subjects during normal-salt (NS) intake and after 8 days of low-salt (LS) intake (patients with HF and age-matched controls only). LS intake produced a marked reduction in urine volume in patients with HF but failed to affect urine volume in age-matched controls. Urinary sodium and fractional excretion of sodium were markedly reduced by LS intake in patients with HF and age-matched controls. Daily urinary excretion of L-3,4-dihydroxyphenylalanine (L-dopa) and dopamine was lower in patients with HF than in age-matched controls. LS intake failed to alter L-dopa and dopamine urinary excretion in control subjects. In patients with HF, LS intake produced a significant decrease in urinary L-dopa excretion, but failed to alter the urinary excretion of dopamine. No significant differences were observed in urinary L-dopa, dopamine, and dopamine metabolite levels between aged controls and young healthy subjects. Urinary dopamine-L-dopa ratios in patients with HF on LS intake (24.5 +/- 7.1) were significantly greater than those with NS intake (11.6 +/- 1.3). Urinary dopamine-L-dopa ratios in old control subjects (LS, 9.7 +/- 1.3; NS, 9.3 +/- 1.1) did not differ from those in young healthy subjects (9.2 +/- 0.8). LS intake produced a marked increase in plasma aldosterone levels in both patients with HF (84.6 +/- 14.4 to 148.2 +/- 20.4 pg/mL; P = 0.0008) and controls (102.1 +/- 13.4 to 151.6 +/- 15.7 pg/mL; P < 0.04). Plasma norepinephrine levels were not significantly affected by LS intake in controls (5.1 +/- 1.62 to 6.3 +/- 1.6 pmol/mL; P = 0.22), but were significantly increased in patients with HF (5.8 +/- 0.8 to 7.1 +/- 0.9 pmol/mL; P = 0.04). In conclusion, patients with HF are endowed with an enhanced ability to take up (or decarboxylate) filtered L-dopa, which might counterbalance the reduced renal delivery of L-dopa, contributing to a relative preservation of dopamine synthesis. This may result as a compensatory mechanism, activated by stimuli leading to sodium reabsorption. Age seems to have no influence on renal dopamine production.
3,4-Dihydroxyphenylacetic Acid↗
Neurohormonal activation, the renal dopaminergic system and sodium handling in patients with severe heart failure under vasodilator therapy.
The benefits of tailoring therapy with vasodilators in patients with severe heart failure are well documented, but this may lead to neurohormonal activation and sodium retention. Renal dopamine has local natriuretic actions and interacts with other hormones involved in renal sodium handling. The aim of the present work was to determine the effects of arterial underfilling induced by vasodilator therapy on renal sodium handling, neurohormonal activation and the activity of the renal dopaminergic system in patients with severe heart failure. For this purpose we monitored haemodynamic parameters, plasma levels of type B natriuretic peptide (BNP), catecholamines, aldosterone, renin activity (PRA), sodium and creatinine, and urinary excretion of sodium, creatinine, L-DOPA, dopamine and its metabolites, before initiation of sodium nitroprusside therapy and every 6 h thereafter (for 42 h), and again after 5 days of angiotensin-converting enzyme (ACE) inhibition, in 10 male patients with severe heart failure. The results of nitroprusside therapy were a marked increase in cardiac index and a substantial decrease in systemic vascular resistance index. Plasma levels of BNP decreased significantly, while PRA, noradrenaline and aldosterone showed marked increases, resulting in a substantial reduction in urinary sodium excretion. Creatinine clearance was not affected. Urinary dopamine and dopamine metabolites increased in response to nitroprusside therapy. After 5 days of ACE inhibition, urinary sodium returned to baseline values, while urinary dopamine was markedly reduced. These results suggest that the renal dopaminergic system is activated in patients with severe heart failure by stimuli leading to sodium renal reabsorption.
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[Type B natriuretic peptide in the diagnosis of heart failure with preserved systolic function].
BACKGROUND: Heart failure (HF) with preserved left ventricular systolic function (LVSF) is observed in up to 50% patients with HF. There is no consensus on non-invasive diagnosis of this entity. OBJECTIVE: Evaluation of B-type natriuretic peptide (BNP) in the diagnosis of HF with preserved left ventricular systolic function. DESIGN: Prospective study. PATIENTS: One hundred and seventy-six consecutive patients with suspected HF were evaluated. Patients were classified as having HF with preserved LVSF, if they had symptoms and signs of HF, an ejection fraction greater than 40% and an abnormal Doppler pattern of the mitral inflow or atrial fibrilation and no other causes for the symptoms. All patients had a 12-lead EKG, chest roentgenogram, simple spirometry, M-mode and 2D echocardiogram with pulsed Doppler study of transmitral inflow and determination of plasma BNP levels. RESULTS: Of the 176 patients, 65 had ejection fraction greater than 40%. Of these patients 46 were classified as having HF with preserved LVSF and 19 as not having HF. Patients with HF and preserved LVSF were older, had a higher systolic blood pressure (SBP), less pathologic Q waves on ECG and higher left ventricular ejection fraction and plasma BNP than patients without HF. Multivariate analysis revealed that BNP and SBP were independently associated with the diagnosis of HF. The accuracy of BNP in the diagnosis of HF with preserved LVSF evaluated by the area under the receiver operating characteristic curve was 0.94. CONCLUSION: These results suggest that the measurement of BNP levels can help clinicians in the diagnosis of HF with preserved LVSF. Whether BNP levels might be used in clinical practice as a test for the diagnosis of HF with preserved LVSF is a question that merits further studies.
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Prognosis in patients with heart failure and preserved left ventricular systolic function.
BACKGROUND: It is recognized that heart failure patients with preserved left ventricular systolic function have better prognosis; nevertheless, there are some studies with conflicting results. Also, there is a paucity of data concerning the prognostic factors in this group of patients. OBJECTIVES: To determine possible variables with prognostic relevance in heart failure patients with preserved left ventricular systolic function (ejection fraction > 40%). METHODS: 157 consecutive ambulatory patients with heart failure were assessed; those patients with ejection fraction > 40% were included in the study (n = 46). All patients were evaluated by clinical interview and physical examination, ECG, echocardiogram (M-mode, 2D and pulsed Doppler of mitral flow), biochemical study and determination of type B natriuretic peptide (BNP). The patients were grouped according to the rhythm presented on ECG: Group I--patients with atrial fibrillation; Group II--patients in sinus rhythm Group II was further subdivided in two groups according to the presence or absence of restrictive left ventricular filling pattern. All patients had a clinical follow-up, with recording of events (death or hospitalization from cardiac cause). The mean follow-up time was 682.2 +/- 55 days. RESULTS: The mean age of the patients was 70.4 +/- 1.2 years; 54.3% were women; mean ejection fraction was 49.6 +/- 1%; mean BNP levels were 202.9 +/- 41.3 pg/ml. Mortality was 19.6% and the combined event death or hospitalization from cardiac cause) occurred in 26.1% of the patients. Among the clinical, demographic, biochemical, echocardiographic and neurohumoral parameters, only BNP levels had prognostic significance in the whole population. In Group II patients, BNP levels, heart rate and restrictive left ventricular filling pattern were identified as having prognostic significance. Kaplan-Meyer curve analysis showed that both BNP and restrictive left ventricular filling pattern seemed to be important prognostic markers. CONCLUSIONS: This preliminary study suggests thar neurohumoral activity (determined by plasma BNP levels) and a restrictive ventricular filling pattern may be important factors in prognostic stratification of heart failure patients with preserved left ventricular systolic function.
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Echocardiographic patterns and prognosis in heart failure.
BACKGROUND: There are many variables with prognostic value in patients with heart failure (HF). Those related to left ventricular function are among the most important. Recently, the evaluation of the patterns of ventricular filling by pulsed Doppler echocardiography has been studied as a variable with prognostic value. OBJECTIVES: To evaluate the prognostic value of echocardiography variables (diastolic and systolic) in patients with HF. These variables were analysed in respect to hospital admission for cardiovascular reasons or death. MATERIAL AND METHODS: We evaluated 157 consecutive patients with HF and included 110 patients who were in sinus rhythm. The mean age was 68.2 +/- 0.9 years. HF was ischemic in 52.7%. Patients underwent echocardiography examination within the week of reference. The patients were grouped according to left ventricular (LV) systolic dysfunction (LV ejection fraction < 40%). We also classified patients in two groups according to the presence of a restrictive pattern in diastolic transmitral flow profile. Finally, we classified all patients in four groups according to their systolic function and diastolic pattern: Group I--systolic dysfunction and restrictive ventricular filling pattern. Group II--systolic dysfunction without restrictive ventricular filling pattern. Group III--without systolic dysfunction with restrictive ventricular filling pattern. Group IV--without systolic dysfunction without restrictive ventricular filling pattern. The events were death or hospital admission. The mean follow up time was 625 +/- 55 days. We did a statistical analysis and for all tests a p value < 0.05 was considered statistically significant. RESULTS: We found impaired LV systolic function (systolic HF) in 73.6% and restrictive ventricular filling pattern in 45.5%. During the follow-up 41.8% died or were admitted to hospital. Patients with systolic HF had lower admission free survival rate. Patients with restrictive ventricular filling pattern had lower admission free survival rate than those without. Group I had lower admission free survival rate than Group II and Group IV. Group IV had a higher admission free survival than all other Groups. CONCLUSIONS: These results support and expand previous observations that diastolic function variables, such as the pattern of ventricular filling (namely the restrictive) have independent prognostic value in patients with HF.
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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.
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Predictors of prognosis in patients with stable mild to moderate heart failure.
BACKGROUND: A number of prognostic indexes have been developed to predict the outcome of patients with severe heart failure (HF). In patients with mild to moderate HF, however, there is no consensus regarding the usefulness of such indexes. The goal of this study is to determine the prognostic value of selected clinical variables in the latter group of patients. METHODS AND RESULTS: We prospectively evaluated the prognostic value of the functional capacity evaluation, the ventricular function, biochemical metabolic indicators, and brain natriuretic peptide (BNP) levels in 139 consecutive patients with mild to moderate HF. A clinical and echocardiographic examination (M-mode, 2D and pulsed Doppler of the mitral inflow); a 6-minute walk test; and a determination of serum sodium, uric acid, and BNP levels were performed. Death by any cause was predefined as the study end-point. Variables found to be related with survival in a univariate Cox regression analysis were NYHA class; ischemic origin for HF; left ventricular ejection fraction; deceleration time of the E wave; and 6-minute walk distance, serum sodium, uric acid, and BNP levels. In a multivariate analysis, ischemic origin of HF, 6-minute walk distance, deceleration time of the E wave, and BNP levels were found to be independent prognostic factors. The clustering of the independent prognostic factors was associated with the worse prognosis. CONCLUSIONS: These results suggest that the noninvasive evaluation used in this study and in our population of patients with mild to moderate HF allows the identification of individuals with the worst prognosis. The selected variables might prove to be very helpful in stratifying HF patients and identifying those that might benefit the most from a HF management program.
Activities of Daily Living↗
Evaluation of brain natriuretic peptide in the diagnosis of heart failure.
A diagnosis of heart failure (HF) can be difficult, especially in patients with mild symptomatology. The purpose of this study was to evaluate the significance of brain natriuretic peptide (BNP) in the diagnosis of HF with systolic or isolated diastolic ventricular dysfunction. One hundred patients and 9 controls were included in the study. Eighty-five patients were diagnosed with HF, based on clinical and echocardiographic findings. BNP levels were accurate for the diagnosis of HF, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.92. In addition, BNP levels showed an excellent accuracy for the diagnosis of isolated diastolic HF (AUC = 0.89). These data suggest that the measurement of BNP levels may be helpful in the diagnosis of HF and in selecting patients for further evaluation. Furthermore, BNP measurement can play an important role in the diagnosis of isolated diastolic HF.
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[Angiotensin converting enzyme inhibitors in the treatment of heart failure].
A brief revision of the clinical trials that support the use of ACE inhibitors in patients with heart failure is made in this paper. The use of ACE inhibitors in clinical practice, recommendations for it's use in specific population and perspectives of ACE inhibitors use in the future of heart failure are discussed.
Angiotensin-Converting Enzyme Inhibitors↗
Renal synthesis of dopamine in asymptomatic post-infarction left ventricular systolic dysfunction.
Left ventricular systolic dysfunction (LVSD) following acute myocardial infarction (AMI), by decreasing renal blood flow, may interfere with renal L-DOPA availability and, consequently, dopamine synthesis. Dopamine of renal origin exerts local natriuretic effects. We studied 17 post-AMI patients with asymptomatic LVSD (ejection fraction < 40%) and 14 without (ejection fraction > or = 40%), measuring 24-h urinary excretions of L-DOPA, dopamine and its metabolites, and plasma levels of the amines, amine derivatives and type-B natriuretic peptide (BNP). Baseline characteristics were well balanced between the two groups. No differences were observed in urinary volume and sodium and creatinine excretions. The group with asymptomatic LVSD presented lower urinary excretion of L-DOPA (66.8 +/- 10.1 versus 115.3 +/- 21.9 nmol x day(-1), P = 0.04), whereas plasma levels of L-DOPA were identical in both groups. Urinary dopamine was similar in the two groups (1124.2 +/- 172.4 versus 1049.0 +/- 146.4 nmol x day(-1), P = 0.86), resulting in higher urinary dopamine/L-DOPA ratios in patients with asymptomatic LVSD (20.4 +/- 3.0 versus 9.9 +/- 0.8, P < 0.001). Plasma levels of BNP were higher in the asymptomatic LVSD group (348.5 +/- 47.3 versus 146.8 +/- 21.9 microg x ml(-1), P = 0.003). Ejection fraction was negatively correlated with both plasma levels of BNP and urinary dopamine/L-DOPA ratios. Renal dopamine production is well preserved in patients with asymptomatic LVSD and increased neurohumoral activation, despite reduced urinary excretion of its precursor. This suggests that renal uptake and/or decarboxylation of L-DOPA is enhanced in this condition, as a compensatory mechanism, contributing to preservation of urinary sodium excretion.
Dopamine↗
Brain natriuretic peptide as a marker of cardiac involvement in hypertension.
Hypertensive patients with heart abnormalities have increased risk of cardiovascular events. Brain natriuretic peptide is a natriuretic peptide mainly of ventricular origin produced in response to pressure and stretch. We hypothesise that brain natriuretic peptide could be a useful marker of cardiac remodelling in hypertensive patients. We studied 36 consecutive community mild-to-moderate hypertensive patients and 11 well-matched normotensive controls with respect to clinical characteristics, brain natriuretic peptide, creatinine and echocardiography parameters (M-mode, 2-D arid transmitral pulsed Doppler). Brain natriuretic peptide levels were significantly higher in hypertensive patients than in controls [36.54 (IQR: 38.61) vs. 10.30 (IQR: 13.20) pg ml(-1), p<0.0001] and it was correlated with left ventricular mass index. Hypertensive patients with impairment of diastolic filling had significantly higher brain natriuretic peptide concentrations than patients with no abnormalities on echocardiography [61.16 (45.38) vs. 31.27 (18.10) pg ml(-1), p=0.001]. Multivariate analysis showed that only diastolic dysfunction and left ventricular mass index were significantly and independently related with brain natriuretic peptide concentrations in this population. In conclusion, impairment of diastolic function and left ventricular mass index are related to brain natriuretic peptide levels, thus giving the insight that this peptide can be a marker of ventricular remodelling in hypertensive patients.
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Treating diastolic heart failure: the role of ACE inhibitors.
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Angiotensin-Converting Enzyme Inhibitors↗
Angiotensin-converting enzyme inhibitors in heart failure: physicians' prescribing behavior.
BACKGROUND: Several studies document an underuse of angiotensin-converting enzyme inhibitors (ACEIs) in heart failure (HF) patients, despite their proven efficacy and good tolerability. Also, there is some evidence that the doses used in clinical practice are far lower than those used in clinical trials. METHODS AND RESULTS: To identify patterns of ACEI use in HF patients this study examined data collected on admission day regarding demographic, clinical, and medical care characteristics of 355 patients hospitalized because of decompensated HF who were treated with and without ACEIs. Additionally, measures of in-hospital outcome were compared among the two groups. Fifty-eight point six percent of patients were receiving ACEIs at admission and 80.6% were treated with ACEIs during hospitalization. The average ACEI does was low. No differences were observed in age and measures of severity of HF between ACEI-prescribed and nonprescribed patients. Patterns that could explain ACEI underuse included female sex, lower systolic blood pressure, worse renal function, left ventricular diastolic dysfunction, use of alternate drugs (eg, spironolactone), and overall less intense medical management. Patterns associated with the use of lower doses of ACEIs included older age, higher New York Heart Association functional class, and lower systolic blood pressure. In-hospital death rates were significantly higher for patients not treated with ACEIs. CONCLUSIONS: This study suggests that many patients eligible for ACEI treatment were deprived of the advantages of these drugs because of erroneous clinical strategies. Nevertheless, the patterns of ACEI use were similar to those reported by other studies. Clinical trials conducted to determine the risk/benefit ratio of ACEI use in patients with renal dysfunction and the utility of ACEIs in diastolic HF, as well as programs to educate care providers on proper use of ACEIs in HF patients, are strongly recommended.
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