[Neuro-hormonal mechanisms in heart failure -- from physiopathology to treatment]. / Mecanismos neuro-hormonais na insuficiência cardíaca--da fisiopatologia ao tratamento.

This review updates some recent advances of a new and exciting developments in basic and clinical cardiology: a) the role, in the congestive heart failure (CHF), of the neurohumoral systems (NHS) which act to maintain circulatory homeostatic equilibrium, and b) the therapeutic implications of such a role. Six NHS, acting in CHF, have presently been identified: three of them induce vasoconstriction and sodium retention (sympathetic nervous systems, renin-angiotensin-aldosterone system and arginine-vasopressine system); the remaining three offset or balance the former ones, acting, therefore as "counterregulators" (prostaglandins--PGE2 and PGI2--, dopaminergic system and atrial natriuretic factor). Each one of these NHS influences the "compensatory" mechanisms of heart failure, acting on the target-organs both by direct effects and by interaction with other NHS; consequently, in heart failure, all the NHS are stimulated with the respective increase in the plasma levels of their active agents. In asymptomatic stages of ventricular dysfunction the stimulation of the vasodilator-and-natriuretic systems appears to be predominant and able to maintain circulatory equilibrium. However, as the heart dysfunction increases and becomes symptomatic, the vasoconstrictor and sodium-retaining forces appear to predominate; this phenomenon becomes increasingly apparent as the functional class becomes more advanced. The hyperstimulation of these last systems has an extremely important role in the pathophysiology and clinical manifestations of congestive heart failure, as well as in its prognosis. Therefore, the attempts to correct these neurohormonal imbalance in patients with heart failure has a sound rational basis, not only to improve the symptoms and the exercise capacity but also to increase the survival of these patients. At the present time, amongst the potential pharmacological interventions acting on NHS in CHF, the blockade of the RAA system with ACE-inhibitors is generally accepted as the most feasible, the safest and the most effective therapeutic tool. In fact, its application has broadened from an earlier use in severe CHF to other symptomatic stages of cardiac failure, including the milder forms. In addition, preliminary data strongly suggest its unique usefulness in asymptomatic phase of ventricular dysfunction. Looking back at the medical therapy of heart failure, in can be concluded that we are starting a new era. Throughout 200 years (since the introduction of digitalis) the therapeutic goal in CHF has been the improvement of symptoms. With the developments of the present decade, a new and exciting goal is being offered to these patients, called by Packer "the second frontier", that is, the prolongation of their lives.

[Efficacy and safety of diltiazem in the treatment of arterial hypertension in the elderly]. / Eficácia e segurança do Diltiazem no tratamento da hipertensão arterial no idoso.

A multicentric, non-comparative study was made to evaluate the efficacy and safety of diltiazem 180 mg in the elderly, with dose titration in subjects above the age of 60 years. The blood pressure measurements were done by ambulatory blood pressure monitoring (ABPM). We achieved a reduction of at least 10 mmHg in systolic blood pressure in 52.2% and in diastolic blood pressure in 42.5% of the patients. The estimated differences between the initial values and those after treatment are 30% (CI95%: 22-38%) for diurnal blood pressure load, 22% (CI95%: 14-29%) for nocturnal blood pressure load, 13 mmHg (CI95%: 10-16 mmHg) for median systolic BP, and 8 mmHg (CI95%: 6-10 mmHg) for median diastolic BP. In 62.5% of the subjects the daily dose of diltiazem was increased to 240 mg (180 mg in the morning and 60 mg at night). All the cardiovascular parameters evaluated showed a significant decrease at the end of the study. A significant change was not recorded in the laboratory parameters and the adverse event average was minimal. The results showed that diltiazem in monotherapy is effective in the control of hypertension in the elderly and can improve compliance to the treatment.

Diltiazem effects on left ventricular function preliminary results of 12 patients evaluated by calibrated apexcardiogram.

Diltiazem is a calcium channel blocker whose effects on left ventricular function (LVF) are controversial. We studied 12 patients with ischemic heart disease (IHD) before starting and 15 and 30 days after having initiated Diltiazem 60 mg t.i.d. LVF was accessed by means of the normalized indexes of the calibrated apexcardiogram: nS for systolic LVF evaluation and nA for diastolic LVF evaluation. Recent works have shown that these indexes have a good correlation with invasive parameters of LVF. We verified that nS did not change and nA decreased significantly (p < 0.05) after Diltiazem. We preliminary concluded that Diltiazem has no deleterious effect on LV systolic function and improves LV diastolic function, by decreasing nA, a parameter which correlates well with LV end diastolic pressure.

Phonomechanocardiographic parameters in patients with atrial septal defect.

The purpose of the present study was to noninvasively evaluate left (LV) systolic and diastolic function in patients with atrial septal defect (ASD) using the phonomechanocardiogram. We studied 40 patients with atrial septal defect, 16 males and 24 females, ages ranging from 6 to 56 years (mean 21.1 years), consecutively observed before surgery in our institution, during a four year period. We measured the systolic time intervals (Q-A2c, Q-S1, ICT, PEP, LVETc, PEP/LVET), the Apex Cardiographic (ACG) diastolic parameters A2-Oc and A/H and the hemodynamic variables Qp/Qs, Pulmonary Vascular Resistance (PVR) and Left Ventricular End Diastolic Pressure (LVEDP). We compared the data with 74 normal individuals using the Student t-test and linear regression analysis. We found significant Q-S1 lengthening (81.2 +/- 16.4 ms, p < 0.001); PEP, ICT and A2-Oc were significantly reduced (101.2 +/- 21.7 ms, p < 0.001, 20.0 +/- 5.3 ms, p < 0.05 and 117.1 +/- 26.3 ms, p < 0.001, respectively) and A/H was significantly increased (17.4 +/- 12.1%, p < 0.005). Except for the case of Q-S1, where there was a weak positive linear correlation with Qp/Qs (r = 0.37), we found no correlation between the other parameters and Qp/Qs or PVR. Sixty-seven percent of the patients had Q-S1 prolongation and a Q-S1 > 76.2 ms identified left-right shunts > 2 with a positive predictive value of 82%; 62% of the patients had a reduced A2-Oc and a A2-Oc < 110 ms identified shunts > 2 with a positive predictive value of 90%.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of left ventricular function after acute myocardial infarction. Two-dimensional echocardiography versus radionuclide angiography. Study of 50 patients.

Two-dimensional echocardiography and gated blood radionuclide angiography was performed in 50 patients (mean age 51.3 years; 48 men and 2 women) after acute myocardial infarction, before discharge from the hospital. The aim of this study was to compare the wall motion score, determined by two-dimensional echocardiography (2DE), with the ejection fraction obtained by radionuclide angiography (RNA). The correlation between the results obtained by 2DE and RNA was good (r = 0.75; p less than 0.0001). We conclude that 2DE is a powerful diagnostic tool for the evaluation of left ventricular function.

[Role of digitalis in the pharmacologic treatment of cardiac insufficiency]. / O lugar do digitálicos na terapêutica farmacológica da insuficiência cardíaca.

The use of digoxin in some patients with heart failure is controversial. Although many patients taking digoxin have no clinical deterioration after discontinuance of the drug, there is a group who demonstrate clinical deterioration on digoxin withdrawal (patients with enlarged hearts, S3 gallop and supraventricular dysrhythmias). The risk of digitalis administration is high in some patients with increased sensitivity to the drug--renal failure, thyroid disfunction, ischemic heart disease, chronic obstruction lung disease and geriatric patients. It seems reasonable that on 1989 the use of digitalis on heart failure should be preferred on patients with supraventricular arrhythmias, enlarged hearts and S3 gallop.

[Neuro-hormonal mechanisms in heart insufficiency--from physiopathology to treatment]. / Mecanismos neuro-hormonais na insuficiência cardíaca--da fisiopatologia ao tratamento.

This review updates some recent advances of a new and exciting developments in basic and clinical cardiology: a) the role, in the congestive heart failure (CHF), of the neurohormonal systems (NHS) which act to maintain circulatory homeostatic equilibrium, and b) the therapeutic implications of such a role. Six NHS, acting in CHF, have presently been identified: three of them induce vasoconstriction and sodium retention (sympathetic nervous systems, renin-angiotensin-aldosterone system and arginine-vasopressine system); the remaining three offset or balance the former ones, acting, therefore as "counterregulators" (prostaglandins--PGE2 and PGI2--, dopaminergic system and atrial natriuretic factor). Each one of these NHS influences the "compensatory" mechanisms of heart failure, acting on the target-organs both by direct effects and by interaction with other NHS; consequently, in heart failure, all the NHS are stimulated with the respective increase in the plasma levels of their agents. In asymptomatic stages of ventricular dysfunction the stimulation of the vasodilator-and-natriuretic systems appears to be predominant and able to maintain circulatory equilibrium. However, as the heart dysfunction increases and becomes symptomatic, the vasoconstrictor and sodium-retaining forces appear to predominate; this phenomenon becomes increasingly apparent as the functional class becomes more advanced. The hyperstimulation of these last systems has an extremely important role in the pathophysiology and clinical manifestations of congestive heart failure, as well as in its prognosis. Therefore, the attempts to correct these neurohormonal imbalance in patients with heart failure has a sound rational basis, not only to improve the symptoms and the exercise capacity but also to increase the survival of these patients. At the present time, amongst the potential pharmacological interventions acting on NHS in CHF, the blockade of the SRA system with ACE-inhibitors is generally accepted as the most feasible, the safer and the most effective therapeutic tool. In fact, its application has broadened from an earlier use in severe CHF to other symptomatic stages of cardiac failure, including the milder forms. In addition, preliminary data strongly suggest its unique usefulness in asymptomatic phases of ventricular dysfunction. Looking back at the medical therapy of heart failure, it can be concluded that we are starting a new era. Throughout 200 years (since the introduction of digitalis) the therapeutic goal in CHF has been the improvement of symptoms. With the developments of the present decade, a new and exciting goal is being offered to these patients, called by Packer "the second frontier", that is, the prolongation of their lives.

A double-blind trial comparing mianserin and maprotiline in depressed inpatients.

The antidepressant effects and side effects of mianserin and maprotiline were assessed in a double-blind trial in 62 inpatients (34 men and 28 women; mean age, 43.6 years) with primary depressive illness. For the first week of the trial, 32 patients received 30 mg/day of mianserin and 30 patients received 75 mg/day of maprotiline; for the next three weeks, the dosage of each drug was doubled. According to scores on the Hamilton Psychiatric Rating Scale for Depression, administered on days 0, 7, 14, 21, and 28, the antidepressant effects of the two drugs were virtually identical. Results of electrocardiographic and vectorcardiographic recordings and other measurements indicated that by day 28 the QRS duration was significantly longer (P less than 0.05) in the maprotiline group. On days 14 and 28, mean systolic blood pressure was significantly higher (P less than 0.05) in the maprotiline group. By day 28, the incidence of anticholinergic side effects--constipation and dry mouth--was significantly higher (P less than 0.05) in the maprotiline group. Although maprotiline's effects on heart functions never reached clinical significance, its anticholinergic side effects could be bothersome, especially to older patients.