Low incidence of cardiac hypertrophy in essential hypertensives with no retinal changes.

120 subjects, 90 hypertensives and 30 age-matched controls, were evaluated by fundoscopy and echocardiography to assess the degree of target organ involvement. The hypertensive patients were divided into 3 groups (mild, moderate, severe hypertension) according to their diastolic blood pressure levels. No significant difference was demonstrated in left ventricular mass among the 3 groups. Moreover, no relationship was demonstrated between the degree of hypertension and the severity of fundoscopic changes. Our findings indicate that patients with no retinal changes show a low probability of left ventricular hypertrophy and that patients with left ventricular hypertrophy show a high probability of retinal involvement. Our data indicate that fundoscopy is more sensitive than echocardiography in the recognition of the hypertensive disease.

Ventricular late potentials in the assessment of mitoxantrone cardiotoxicity.

Sixteen female patients underwent signal-averaged electrocardiography and radionuclide angiography for the assessment of the resting left ventricular ejection fraction in the course of chemotherapy with mitoxantrone (MTX) for advanced breast cancer. Nine patients had received prior cardiotoxic treatments. Our findings indicate that patients treated with MTX may develop late potentials.

Preliminary study on behaviour of atrial natriuretic factor in anthracycline-related cardiac toxicity.

The atrial natriuretic factor (ANF) plays an important role in the pathogenesis of congestive heart failure (CHF), by influencing electrolyte and water balance and by modifying peripheral vascular resistance, thus affecting left ventricular performance. Anthracycline derivatives are glycoside antibiotics, active against a wide spectrum of tumours. It is well known that acute and severe dose-related delayed cardiotoxicity constitutes the major limitation to their optimal use. A total of 26 female patients (mean age 53 years) undergoing monochemotherapy for advanced breast cancer, were studied. 4'-Epidoxorubicin (Epidx) 120 mg/m2 intravenously was administered every three weeks for a total of a mean of 6.6 therapeutic cycles (3 to 10). Left ventricular ejection fraction (LVEF) determined by radionuclide ventriculography and circulating ANF were measured periodically in all patients. Epidx administration was limited at a cumulative dose ranging between 840 and 1200 mg/m2 because of a 25% decrease in LVEF and due to a progressive rising in ANF plasma levels. Furthermore, two patients who presented clinical symptoms of CHF had also significantly increased ANF levels (56 and 49% respectively). The current evidence suggests an important pathophysiological role of ANF in anthracyclinic related CHF. Hopefully measurement of plasma ANF will provide a simple non-invasive method of assessing ventricular dysfunction related to anthracycline cardiac toxicity and might represent an additional objective indicator of the severity of haemodynamic compromise in patients with impaired cardiac function.

A chronobiological study on the relation between heart rate and QT interval duration in newborn infants.

The relation between heart rate and QT interval is the result of the autonomic nervous system control on cardiac function in healthy adults; accordingly, chronobiological studies have shown that adult subjects have circadian rhythms of heart rate (expressed as R-R interval) and QT interval in phase. We have employed chronobiological methods to study heart rate and QT interval relation in 10 newborn infants, who are known to have an immature cardiac control. Findings from this study indicate that not all the newborns show circadian rhythms of heart rate and QT interval and that when both rhythms are present they do not correlate like in the adults. Likely, this lack of relationship between heart rate and QT interval in newborns is due to different maturational stages of the newborns studied. As a practical implication, in newborn infants, mathematical correction of QT interval by heart rate is not a reliable method.

Does ergometric stress test induce a procoagulative condition in patients with previous myocardial infarction?

A regularly scheduled physical training program seems to have antithrombotic effects. Moreover, the hemostatic changes occurring in patients with coronary artery disease during acute exercise have not been clearly elucidated. Since stress testing is routinely performed in clinical cardiology, it would be helpful to assess whether patients with coronary artery disease are exposed to acute coronary thrombosis during or soon after sustained physical exercise. This study was designed to evaluate the effect of acute physical exercise (stress test by bicycle ergometer) on blood coagulation in a group of patients with previous myocardial infarction, and to determine whether the antithrombotic therapy commonly administered favorably influences hemostatic equilibrium. Our results suggest that exercise testing is not harmful to patients with previous myocardial infarction in regard to hemostasis and fibrinolysis and that antithrombotic therapy reduces postexercise increase in platelets.

New indices in the evaluation of clonidine transdermal therapy of hypertension.

Since high blood pressure might be more harmful the higher it is and the more it remains above a determined critical value (140/90 mm Hg - 18.7/12.0 k Pa - in the present study), the hyperbaric impact, a measure of the total load exerted on the arterial walls and the total time during the day when blood pressure is elevated above the critical value, have been evaluated. Ten patients with essential hypertension underwent non-invasive automatic 24-h blood pressure monitoring three times (baseline and after three and seven days from the application on the upper chest of a transdermal self-adhesive patch delivering clonidine). The recorder was programmed to measure blood pressure every 30 min during the day and every 60 min during the night. Significantly lower values of blood pressure, hyperbaric impact and duration of elevated blood pressure have been demonstrated from the third day after the beginning of transdermal therapy.

Echocardiographic evaluation of children with and without family history of essential hypertension.

A family history of hypertension is considered a risk factor for developing hypertension. We studied two groups of normotensive children (aged 14 years): one comprising 14 subjects with family history of hypertension, the other comprising 15 subjects without family history of hypertension. Children were comparable with respect to age, weight, height, body surface area, heart rate, and arterial blood pressure. M-mode echocardiography demonstrated higher interventricular septum/posterior wall ratio in progeny of hypertensive subjects. Interestingly, all the parameters evaluated were within the normal limits. Our data suggest that a certain degree of cardiac changes is present in children with positive family history of hypertension, though further studies are needed before considering these findings predictive of future essential hypertension.

Response of some haemocoagulatory and haemorheological variables to maximal exercise in sedentary and active subjects.

The purpose of this study was to evaluate how physical conditioning is associated with haemostatic and rheological responses to strenuous exercise. A total of 25 males, divided into two groups differing in exercise fitness (14 sedentary and 11 active), underwent exercise testing on a bicycle ergometer with an initial 25 W workload increasing by the same amount every 3 min. The following variables were evaluated before and after the test: platelet count and aggregability, plasma fibrinogen, fibrinolytic degradation products, viscometry and micro-haematocrit. Significant differences in baseline values between the two groups were found only for blood viscosity. Irrespective of the group, significantly increased values were demonstrated for all the variables, except platelet aggregability and fibrinogen levels, in response to strenuous exercise. It is concluded that the possible protective effect of exercise against cardiovascular disease does not seem to be related to changes in the haemorheological and haemostatic measures evaluated.

Circadian variations of heart rate and premature beats in healthy subjects and in patients with previous myocardial infarction.

Chronobiological analysis of the circadian variations of heart rate, ventricular and atrial ectopies, was carried out on 11 patients with previous myocardial infarction matched with 11 controls. Individual circadian rhythms in heart rate were seen in all the control subjects but only in 6 patients with previous myocardial infarction. The behaviour of the individual circadian rhythms of premature beats was not significantly different between the two groups. A significant group rhythm in ectopies was not demonstrated, nevertheless a trend to higher frequency of arrhythmias during the activity span was detected. These results do not allow to postulate a circadian pattern of arrhythmias common to all the subjects examined. Therefore, the individual circadian behaviour of premature atrial and ventricular beats should be recognized for monitoring antiarrhythmic therapy. A significant group rhythm in heart rate was demonstrated for the two populations studied and linear discriminant analysis showed that the amplitude of this rhythm was significantly lower in patients than in controls. Possibly, myocardial infarction may affect the sinus node function producing a "flattened" range of heart rates during the 24 hours.

Echocardiographic assessment of anthracycline cardiotoxicity during different therapeutic regimens.

The use of doxorubicin (Dx) in treating malignancies is limited by a potentially fatal cardiomyopathy. Prevention of this related cardiotoxicity has been attempted either by using doxorubicin analogues such as 4'-epidoxorubicin (4'-EpiDx) or by simultaneous administration of other pharmacological substances. Fifteen patients with breast and lung cancer divided into three groups, treated respectively with Dx alone, Dx and L-carnitine and 4'-EpiDx, were studied to assess the effects of these therapeutic regimens on left ventricular performance. For this purpose the maximum velocities of fibre shortening and lengthening (VcF), obtained by computerized M-Mode echocardiography were used as indices of systolic and diastolic function respectively. Data from patients and from 25 healthy subjects were evaluated by analysis of variance and Tukey test. No significant difference was found in baseline systolic and diastolic VcF values. Significantly lower systolic VcF (p less than 0.05) was shown by patients treated with Dx alone, while diastolic VcF was significantly lower in those treated with 4'-EpiDx after four cycles. Systolic VcF of patients treated with Dx and L-carnitine and with 4'-EpiDx did not significantly differ from controls even after six therapeutic cycles. These data demonstrate that systolic VcF is not affected by 4'-EpiDx or by Dx when administrated with L-carnitine. The reduction of diastolic VcF by 4'-EpiDx and not by Dx could be due to different effects of these drugs on the calcium transport since early isovolumic relaxation depends on an energy-dependent process of calcium removal.

[Circadian and ultradian rhythms of the heart rate in the neonate]. / Ritmi circadiani ed ultradiani della frequenza cardiaca nel neonato.

Few papers deal with the chronobiologic characteristics of heart rate in neonates. A better knowledge of this topic could be useful under both clinical and therapeutical point of view. We studied the circadian and ultradian rhythms of heart rate in 10 healthy neonates (5 males and 5 females). Six of them (60%) show a well defined circadian rhythm of heart rate such as adult subjects even if with an obviously higher mesor and with acrophases dispersed throughout the 24 hours. We also demonstrated one or more ultradian rhythms of heart rate for each neonate. The most frequent have a period between 4 hours and 6 minutes and 4 hours and 36 minutes. These rhythms are out of phase with the world outside which is the best evidence that they are not imposed by some undetected external factors.

Relationship between systolic time intervals and arterial blood pressure.

It has been suggested that systolic time intervals (STI) can be used to monitor the cardiac effects of antihypertensive treatments and also to evaluate hypertensive patients. STI changes observed in hypertensives have been ascribed to myocardial disease, although they could be due to the existence of a relationship between STI and blood pressure. A group of 37 subjects (18 normotensives and 19 hypertensives) with no signs of heart failure and left ventricular dysfunction were studied to examine the relationship of STI to blood pressure. Pacing with an external battery pulse generator was performed at the rate of 95 beats/min in order to eliminate differences in heart rate. STI were measured from good quality high speed (100 mm/s) recordings and the average value of 10 consecutive cardiac cycles was used for statistical analysis. Normal subjects showed significantly lower values of pre-ejection period (PEP), electromechanical systole (QS2), and pre-ejection period/left ventricular ejection time ratio (PEP/LVET). Moreover, a significant inverse relationship between diastolic pressure and LVET and significant direct relationships between diastolic pressure and PEP, systolic pressure and PEP, diastolic pressure and PEP/LVET, and between systolic pressure and PEP/LVET were demonstrated. We suggest to consider the relation of STI to blood pressure to provide regression equations to best appreciate and use STI.

Muscular blood flow in patients with heart failure.

We studied reactive hyperemia in a group of patients with heart failure before and after therapy, since changes in the characteristics of muscular blood flow may influence the functional class of these patients. At the same time we evaluated some echocardiographic parameters too. When the patients improved clinically, they showed an increase in muscular blood flow at rest and in percent of fractional shortening and a decrease in peripheral vascular resistance. The reactive hyperemia did not change significantly. This fact probably depends on a maximal response to the postischemic hyperemia and represents the integrity of autoregulatory mechanisms.

Circadian rhythms of arterial blood pressure.

We measured variations of blood pressure during the day in 46 untreated outpatients (25 hypertensives and 21 normotensives) to assess their circadian patterns. The self-measured blood pressures (autorhythmometry), determined at 08:00, 12:00, 16:00, 20:00 and 23:00 for 40 consecutive days were evaluated chronobiologically from single and population mean cosinors. On the basis of the results, we conclude that it is impossible to propose a common schedule of temporal therapy that will be effective for all hypertensive patients because of the unpredictable circadian behavior of blood pressure in this kind of subjects. Therefore, we suggest that individual circadian patterns of arterial pressure be studied when therapy is being established, so that the best therapeutic results can be achieved.

A chronobiologic study on some cardiovascular parameters.

We studied the chronobiologic pattern of heart rate, R and T wave voltage, QT interval, and ST segment displacement. Premature atrial and ventricular beats obtained by dynamic electrocardiography, as well as arterial blood pressure measurements obtained by autometry, have also been studied in 131 untreated subjects (25 with hypertension, 28 with major risk factors for coronary artery disease, 9 with coronary artery disease, 37 presumably healthy and 11 shift workers). Our results show the existence of circadian rhythms in heart rate, in the duration of the QT interval and also in the voltage of R and T waves. Our data for R and T wave voltages do not completely agree with those from other authors. We demonstrated also that smoking may influence the circadian acrophase of the rhythm in R wave voltage while sleeping does not show any relationship with R and T wave voltages although it seems related to the displacement of the ST segment. We could point out only small differences in the chronobiologic behavior of patients with coronary disease and that of normal subjects, unlike the results previously reported by other authors. Our study demonstrated the existence of circadian and ultradian rhythms in premature atrial and ventricular beats as well as circadian and circaseptan rhythms in arterial blood pressure. Further studies are needed to improve our chronobiologic knowledge in order to optimize dosage and time of administration of the drugs used in the long term management of arrhythmias and hypertension.

Effects of isoproterenol and methoxamine on the electrocardiogram.

The effects of isoproterenal (ISP) and methoxamine (MTX) infusion in 20 asymptomatic subjects with labile T wave were studied. In those treated with ISP the T wave showed an early negative trend and later became clearly positive in 5 subjects. In the majority of the subjects treated with MTX the T wave became positive. T wave changes match variations of both the ventricular gradient and, to a lesser degree, the QRS area. These changes were not related to heart rate or, in the subjects treated with MTX, to the baroreceptorial sensitivity deduced from the slope of the regression equation between R-R internal and systolic arterial pressure. The results of this study confirm the existence of a neurogenic mechanism affecting the electrocardiographic changes in T wave.

Heart rate and premature beats: a chronobiologic study.

Sixteen subjects, mean age 59 +/- 18, 11 normal and 5 with coronary artery disease, all having premature ventricular and/or atrial beats in the standard resting electrocardiogram (ECG), were studied to analyse the chronobiologic parameters of these arrhythmias. Single cosinor analysis of the data obtained by 96-hour ECG performed according to the Holter system, demonstrated: A) significant circadian rhythm in heart rate for all the subjects, with acrophases occurring between 12.56 and 17.36; B) significant circadian rhythms of premature ventricular beats for the majority of the subjects, with acrophases distributed along the 24 hours; C) significant circadian rhythms in premature atrial beats for 8 subjects, with acrophases occurring between 04.24 and 18.12; D) a spectrum of significant ultradian rhythms in heart rate with various periodicities, both in normal and in coronary patients; E) significant ultradian rhythms in premature ventricular beats for 8 subjects with periods ranging from 5h 15' to 17h. Population mean cosinor analysis demonstrated: A) significant circadian group rhythm in heart rate for all the 16 subjects and for the group of 11 normal subjects; B) no significant circadian group rhythm for premature ventricular and atrial beats. These findings suggest that the study of the individual chronobiologic pattern of premature beats may help to optimize antiarrhythmic therapy.

Computerized M-mode echocardiography in the assessment of cardiovascular effects during intravenous administration of amiodarone.

Antianginal and antiarrhythmic long term therapy with amiodarone may be associated with side effects, therefore it should be used mainly in short term treatment of severe arrhythmias and acute coronary insufficiency. It is important to assess if any inotropic effect may be produced after intravenous administration of this drug in commonly accepted therapeutic doses (5 mg/kg body weight). To investigate this possibility we studied the effects of amiodarone on blood pressure (BP), on heart rate (HR) and on the maximal velocity of circumferential fiber shortening (Vcf Max). Simultaneous echocardiogram (UCG), electrocardiogram (lead DII) (ECG) and BP cuff measurement were performed on 12 subjects without cardiomegaly and clinical evidence of heart failure, immediately before a 30 second intravenous injection of amiodarone and every 30 seconds over a period of 6 minutes after drug administration. Amiodarone administration markedly raised HR within the first 30 seconds from the beginning of the injection and concomitantly decreased diastolic BP. No significant lowering of systolic BP was observed. Vcf Max (circ/sec) raised during the test concomitantly with HR increase, showing a significant relationship between left ventricular performance and HR. The same was also true during atrial pacing performed on one subject. No significant changes in any of the parameters studied were demonstrated after placebo (saline solution) administration to two presumable healthy subjects. Amiodarone does not seem to have any positive or negative intrinsic inotropic effect when administered intravenously at a dose of 5 mg/kg body weight.