Mário Cerqueira-Gomes

The effect of dietary sodium restriction on neurohumoral activity and renal dopaminergic response in patients with heart failure

This work evaluates the effect of a low‐sodium diet on clinical and neurohumoral parameters and on renal dopaminergic system activity in heart failure (HF) patients.

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.

Influence of non-steroidal anti-inflammatory drugs on renal function and 24h ambulatory blood pressure-reducing effects of enalapril and nifedipine gastrointestinal therapeutic system in hypertensive patients.

Objective: To evaluate the influence of non-steroidal anti-inflammatory drugs (NSAIDs; aspirin and indomethacin) on the renal and antihypertensive effects of enalapril and nifedipine gastrointestinal therapeutic system (GITS) in patients with essential hypertension. Design and methods: In a crossover study, 18 patients on an unrestricted-salt diet were randomly assigned to receive either enalapril (20-40 mg/day) or nifedipine-GITS (30-60mg/day) for 4-8 weeks, followed by aspirin (100 mg/day for 2 weeks) and then indomethacin (75 mg/day for 1 week). Blood pressure was measured by 24 h ambulatory monitoring. Results: Enalapril and nifedipine-GITS significantly reduced blood pressure compared with placebo. Aspirin did not alter the antihypertensive effect of either drug. Indomethacin attenuated (by 45%) the antihypertensive effect of enalapril throughout the 24 h period of evaluation, but did not interfere with the effect of nifedipine. Furthermore, indomethacin significantly reduced the fractional excretion of sodium and plasma levels of prostaglandins in a similar way when added to either the enalapril or the nifedipine regimen. Conclusions: Vasodilatory prostaglandins are probably involved in the antihypertensive effects of enalapril but not of nifedipine, and this interaction seems to be independent of any indomethacin-induced decrease in renal sodium excretion. Nifedipine may be an appropriate drug to treat hypertensive patients requiring concomitant therapy with NSAID.

Effect of a heart failure clinic on survival and hospital readmission in patients discharged from acute hospital care

Ambulatory care by physicians especially devoted to the management of heart failure (HF) has been reported to have beneficial effects. The aim of this work was to assess the effect of outpatient management at a HF clinic, as compared with care by the usual assistant physician, on prognosis of HF patients. In this non‐randomised study, we prospectively followed 339 patients after a hospitalisation index for HF, in order to compare prognosis between two groups of HF patients according to the ambulatory assistance setting: either a specific outpatient clinic (n‐157) or the usual assistant physician (n‐182). The outcomes assessed were all‐cause death or cardiac‐cause rehospitalisation during the first month after discharge and survival over the longer term. The risk of dying or being readmitted during the first month after discharge was significantly lower in patients followed at the HF clinic (adjusted odds ratio 0.23; 95% CI 0.12–0.46). Patients followed in the HF clinic also had an independent significantly lower hazard of dying during a longer‐term follow up of average length 373 days (adjusted hazard ratio 0.52; 95% CI 0.34–0.81). The results support the fact that a multidisciplinary and permanently available medical staff might be of relevance in improving outcomes in HF patients.

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.

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.

Evaluation of the Sympathetic Nervous System Using Heart Rate Variability and Plasma Hormones in Hypertensive Patients Treated with Cilazapril and Atenolol

In a double-blind placebo-controlled parallel study, we assessed basal and post-therapeutic sympathetic activity both in supine and standing positions in mildly to moderately hypertensive patients by two different methods: frequency domain indices of heart rate variability (HRV) and plasma levels of both noradrenaline (NA) and its metabolite, 3,4-dihydroxyphenylglycol (DOPEG). Patients were evaluated on placebo and after 8 weeks of treatment with either cilazapril, 2.5-5 mg/day (13 patients) or atenolol, 50-100 mg/day (14 patients). Twenty-four-hour blood pressure was similarly reduced (p < 0.01) by both cilazapril and atenolol. Heart rate decreased with atenolol by 14 beats per min (p < 0.001) but did not change with cilazapril. When compared to the placebo, cilazapril did not modify sympathetic activity indices of HRV but did significantly reduce NA and DOPEG levels in both the supine and standing (p < 0.05) positions. As expected, atenolol reduced (p < 0.05) sympathetic activity indices of HRV but did not modify NA levels in either position. Moreover, while on placebo, patients showed no significant correlations between values of NA or DOPEG, nor in any of the HRV indices. We conclude that: (1) the antihypertensive effects of cilazapril and atenolol are similar, but in these patients, sympathetic activity indices showed divergent results both before and after therapy; (2) this may be due to different aspects of sympathetic activators, assessed independently by different methods, and (3) these discrepancies must be taken into account when evaluating autonomous nervous system parameters.

RENAL DOPAMINERGIC MECHANISMS IN RENAL PARENCHYMAL DISEASES, HYPERTENSION, AND HEART FAILURE

The recovery of renal function in renal transplant recipients is accompanied by an enhanced ability to synthesize dopamine (DA), which may contribute to maintain sodium homeostasis. Patients suffering from chronic renal parenchymal disease, a well-recognized form of salt sensitive (SS) hypertension, have a reduced ability to produce DA that correlates well with deterioration of renal function. In patients afflicted with IgA nephropathy, but normal renal function, urinary excretion of DA correlated positively with BP responses to changes from 200 to 20 mmol/day salt intake. In black salt resistant (SR) normotensives (NT) and SR hypertensives, under low salt intake (40 mmol/day), but not SS-NT and SS-HT, the saline infusion induced increments of DA and DOPAC urinary excretion correlated significantly with increments of sodium urinary excretion and sodium fractional excretion. Patients afflicted with heart failure (HF) have a reduced delivery of L-DOPA to the kidney, accompanied by an increase in DA/L-DOPA urinary ratios. This suggests that HF patients have an increased ability to take up or decarboxylate L-DOPA. Sodium restriction resulted in a significant decrease in urinary L-DOPA, DA and DOPAC in HF patients, suggesting that the system responds to sodium. It is concluded that activity of renal dopaminergic system may be altered in SS subjects, despite the level of their BP, and an enhanced delivery of L-DOPA to the kidney may be beneficial in edema formation states.

Predictors of Myocardial Dysfunction in Human Immunodeficiency Virus-Infected Patients

BACKGROUND Some of the most frequent manifestations of heart involvement in human immunodeficiency virus (HIV) infection include right and left ventricular dysfunction. The pathogenesis remains obscure. METHODS AND RESULTS This prospective clinical and echocardiographic study involved 181 patients at all stages of HIV infection. We tested a set of clinical variables using a backward logistic regression model to assess their ability to independently predict the presence of ventricular dysfunction. The presence of pulmonary infections (all etiologies mixed) was the only variable independently associated with isolated right ventricular dysfunction (odds ratio = 4.08; P = .02). Signs suggestive of pulmonary arterial hypertension were present in 71% of the patients with right ventricular dilation. History of previous opportunistic infections (all etiologies mixed) (odds ratio = 10.9; P = .0026) and time since the diagnosis of acquired immunodeficiency syndrome more than 12 months (odds ratio = 6.6; P = .03) were the only two independent predictors of left ventricular dysfunction. CONCLUSIONS Isolated right ventricular dysfunction may be secondary to pulmonary hypertension caused by repetitive pulmonary infections and not to primary myocardial disease. The aggressive treatment of opportunistic infections may become an important element of heart failure prophylaxis in HIV infection because they may be associated with left ventricular dysfunction.

Influence of sublingual captopril on plasma catecholamine levels during hypertensive emergencies and cold immersion

Experimental evidence of captopril-induced inhibition of sympathetic activity, mediated by decrease in angiotensin II production, is presented. The blood pressure, plasma catecholamine, plasma renin activity, and plasma aldosterone responses to a single dose of sublingual captopril in 23 patients with hypertensive emergencies were evaluated. The major correlation found was between the captopril-induced decrease in blood pressure and the decrease in plasma norepinephrine levels (r = 0.57, p less than 0.01). In another 11 hypertensive patients with normal or high renin levels, captopril lowered by 65 percent the increase in plasma norepinephrine induced by cold immersion of the forearm. In both circumstances, plasma renin and aldosterone levels changed in accordance with the expected inhibition of angiotensin converting enzyme activity. These data suggest that, in selected circumstances in hypertensive patients, captopril exhibits a depressive influence on sympathetic activity along with the inhibition of the renin-angiotensin system.