Short- and long-term reproducibility of time and frequency domain heart rate variability measurements in normal subjects.

OBJECTIVE: To obtain data relating to the reproducibility of the time and frequency domain measurements obtained from 10-min ECG recordings. METHODS: Eighteen normal volunteers underwent evaluations of time and frequency domain heart rate variability 2 weeks and 7 months after baseline analysis. The time domain parameters were mean NN, the standard deviation of NN intervals, the percentage of successive NN intervals > 50 ms and the root mean square successive difference of NN intervals. The frequency domain evaluations (total power, low frequency, and high frequency) were made by means of both the Fast Fourier Transform algorithm (FFT) and the autoregressive method (AR) from 10-min ECG recordings made under three different conditions: rest, controlled respiration, and after a passive head-up tilt test. Reproducibility was evaluated by means of the interclass correlation coefficient (ICC), comparing baseline values with the results obtained at the second week and the seventh month. Time domain evaluation were also made from 10-min ECG. RESULTS: All of the time domain measurements had an ICC > or = 0.75, except for the standard deviation of NN intervals, which had an ICC of 0.57. The frequency domain parameters obtained by means of either FFT or AR showed similar reproducibility. Low frequency was reproducible under all three conditions, total power only at rest, and high frequency only during controlled respiration. CONCLUSION: The reproducibility of frequency domain parameters depends on the analysed condition. These results are of primary importance when the effects of drugs or other interventions on heart rate variability are under investigation.

Effect of respiratory rate on the relationships between RR interval and systolic blood pressure fluctuations: a frequency-dependent phenomenon.

OBJECTIVE: The aims of this study were to determine the relationships between oscillations in systolic blood pressure and heart period at different breathing frequencies and to investigate the role of sympathetic contribution to this relationship. METHODS: Fourteen healthy volunteers underwent three randomized periods of controlled breathing at 6, 10 and 16 breaths/min. ECG (RR), respiratory signal (RESP) and systolic blood pressure (SBP) were continuously recorded. The component of RR and SBP oscillations related to respiration (RRResp and SBPResp) was defined by means of uni- and bivariate spectral analysis. The squared coherence (K2) and phase between RR and RESP, and RR and SBP (RR-SBP) were also assessed. When the K2 of RR-SBP in the respiratory band was > 0.5, we considered the phase and calculated the closed-loop gain between the two signals. Seven subjects were also studied after chronic metoprolol treatment. RESULTS: Although the mean values of RR and SBP did not differ between the three periods of breathing, the higher the respiratory rate, the smaller the RRResp and SBPResp. The phase was always negative (SBPResp changes preceded RRResp changes), thus suggesting a baroreflex link. The higher the respiratory rate, the lower the gain and phase. Pharmacological beta-adrenoceptor blockade increased the gain and shifted the phase, but the relationships found at baseline between the respiratory rate and both the gain and phase remained unchanged. CONCLUSIONS: The effect of breath rate on the relationship between heart rate and systolic pressure variabilities is a frequency-dependent phenomenon that is also independent of the sympathetic drive.

Diastolic dysfunction and baroreflex sensitivity in hypertension.

The determinants of diastolic dysfunction in patients with systemic hypertension are not completely known. To evaluate the possible role of age, arterial blood pressure, and baroreflex heart rate response impairment in causing diastolic dysfunction, we studied 61 patients (42 male; mean+/-SD age, 43.9+/-12 years) with newly recognized and therefore previously untreated systemic hypertension. Diastolic dysfunction was evaluated by means of Doppler echocardiography (and diagnosed as such when the early to atrial peak velocity ratio corrected to heart rate was <1), arterial blood pressure by 24-hour ambulatory monitoring, and baroreflex heart rate response by means of the spectral technique (alpha index) during paced (0.27 Hz) and spontaneous breathing (in a supine position and during tilt). Nineteen patients had diastolic dysfunction, the most powerful predictor of which was age (r=-0.63, P<0.001). The patients with diastolic dysfunction had significantly lower values for spectral baroreflex gain in the high-frequency band than those without (5.2+/-3 versus 8.4+/-5 ms/mm Hg during paced breathing, P<0.05; 7. 4+/-4 versus 13.3+/-7 ms/mm Hg in a supine position, P<0.05; 4.3+/-4 versus 5+/-2 ms/mm Hg during tilt, P

Effects of nadolol and its combination with atrial pacing on rate-enhanced ventricular premature complexes.

To explore the role of heart rate in the genesis of ventricular premature complexes whose incidence increases when the length of the preceding cardiac cycle decreases, we analyzed the effect of nadolol alone and together with atrial pacing in 4 patients. Nadolol lengthened the RR cycle and suppressed ventricular premature complexes; atrial pacing, restoring the baseline RR cycle lengths, led to the reappearance of ventricular premature complexes, suggesting the major role of heart rate.

Beta-blocker effects on respiratory sinus arrhythmia and baroreflex gain in normal subjects.

STUDY OBJECTIVE: The results of studies on the effect of beta-adrenergic blockade on respiratory sinus arrhythmia (RSA) are discordant. The aim of this study was to verify whether chronic beta-adrenergic blockade is capable of increasing RSA, and therefore vagal outflow, and to analyze whether the mechanism of action is central or peripheral. PARTICIPANTS AND DESIGN: Twenty normal subjects (28+/-2 years old) were randomized to receive a hydrophilic (nadolol) beta-blocker, a lipophilic (metoprolol) beta-blocker, and placebo. MEASUREMENTS: After 1 week of therapy, a spectral analysis was made of the variability in heart rate and systolic BP during controlled breathing at 16 breaths/min. The high-frequency component was calculated for the RR interval (measure of RSA) and systolic pressure, and the squared coherence and phase functions were assessed between RR and systolic pressure fluctuations in the respiratory band; a negative phase means that RR changes follow systolic pressure changes. The gain in the relationship between the two signal fluctuations was also calculated. RESULTS: Both beta-blockers increased the mean (+/-SD) RR interval (placebo=808+/-21, nadolol=1,054+/-30, metoprolol=1,031+/-27 ms; p<0.0001), RSA (placebo=542, nadolol=1,177, metoprolol=1,316 ms2; p=0.002), and the gain (placebo=13.6+/-1.5, nadolol=21.9+/-2.8, metoprolol=24.5+/-3.6 ms/mm Hg; p<0.002), and both modified the phase function (placebo=-21.1+/-5.3, nadolol=-1.8+/-4.9, metoprolol=-2.9+/-4.2 degree; p<0.0001). No difference was found between nadolol and metoprolol. CONCLUSIONS: Chronic beta-adrenergic blockade enhanced both RSA and baroreflex gain and reduced the phase between the RR interval and systolic pressure oscillations. Since no difference was found between the hydrophilic and the lipophilic beta-blockers, these changes seem to be due to a peripheral effect.

Propionyl-L-carnitine: a new compound in the metabolic approach to the treatment of effort angina.

The effects of propionyl-L-carnitine on exercise tolerance of 12 patients with stable exertional angina were assessed in a double-blind, placebo-controlled, cross-over protocol using serial exercise tests. Compared to placebo, propionyl-L-carnitine significantly increased total work from 514 +/- 199 to 600 +/- 209 W (P less than 0.05) (17%) and prolonged exercise time and time to ischemic threshold from 515 +/- 115 to 565 +/- 109 sec (P less than 0.05) (10%) and from 375 +/- 102 to 427 +/- 93 sec (P less than 0.01) (14%), respectively. ST segment depression at the highest common work level was significantly reduced from 0.19 +/- 0.08 to 0.15 +/- 0.08 mV (P less than 0.05) (21%). No significant changes in heart rate, systolic blood pressure, and rate-pressure product at rest, at the highest common work level, on appearance of the ischemic threshold, or at peak exercise were observed after propionyl-L-carnitine treatment. No side effects were observed under propionyl-L-carnitine treatment. This study shows that propionyl-L-carnitine can significantly improve exercise tolerance in patients with stable angina. Our data seem to confirm that propionyl-L-carnitine most likely exerts its protective action via the metabolic pathway.

Assessment of cardiac vagal activity in patients with hyperthyroidism.

Previous studies suggested that in patients with hyperthyroidism an autonomic imbalance and in particular a lower than normal vagal activity might be present. To verify this hypothesis we have evaluated the respiratory sinus arrhythmia (RSA, a measure of cardiac vagal activity) in ten hyperthyroid patients and in ten normal subjects. RSA was calculated from the power of the spectral component of the heart rate variability in high frequency band (HF-RR) during both spontaneous (supine and passive head-up tilt) and controlled breathing (supine). During controlled breathing the phase relation between heart rate and respiratory has been computed. The hyperthyroid patients showed a higher heart rate in all three conditions (P<0.001) and higher spontaneous respiratory rate in supine position (centered frequency of HF-RR: 0.342+/-0.015 vs 0.262+/-0.016 Hz; P<0.001). No difference was found in hyperthyroid patients compared to controls in terms of the HF-RR power in normalized units both during spontaneous breathing (supine, 43+/-8.3 vs 39.7+/-6.7%; tilt 18.8+/-5.9 vs 19.3 vs 4.1%; mean+/-SE) and controlled breathing (45.4+/-7.1 vs 48.9+/-6.9%). No difference was found also in terms of the phase relationship between the heart rate and the respiratory signals (77.5+/-32.3 vs 77.5+/-28.1, degrees). Hyperthyroid patients seem not to have an impaired cardiac vagal activity.

Effect of intermittent subdiastolic pressure in thigh cuffs on human arterial baroreflex.

BACKGROUND: We investigated the effects of subdiastolic variations of the pressure inside the thigh cuffs on cardiovascular oscillations and arterial baroreflex sensitivity in humans. METHODS: During 10 min of controlled breathing at low (0.1 Hz) and high (0.25 Hz) frequencies, 30 healthy subjects underwent variations of the pressure inside the thigh cuffs (from 0 to 40 mmHg) at 0.25 and 0.1 Hz respectively; the periods of controlled breathing without cuff pressure modulation were used as a control. The frequency responses of cardiovascular signals were assessed using spectral analysis, and baroreflex sensitivity by the sequence method. RESULTS: Cuff pressure modulation at 0.25 Hz did not affect the RR interval, arterial pressure, or baroreflex sensitivity; at 0.1 Hz it did not change the RR interval and arterial pressure, but engaged (0.76 +/- 0.2 of coherence) and increased the low frequency oscillations of the RR interval (from 5.6 +/- 1 to 6.1 +/- 0.9 ln ms2, p < 0.05) and improved baroreflex sensitivity by 25% (from 14.2 +/- 9 to 17.7 +/- 10 ms/mmHg, p < 0.01). CONCLUSIONS: Subdiastolic thigh cuff pressure modulation at 0.1 Hz improved the low frequency oscillations of heart rate and baroreflex sensitivity. This approach represents a new and simple non-pharmacological strategy for acutely improving baroreflex sensitivity in humans.

Whole-body bioelectrical impedance analysis in patients with chronic heart failure: reproducibility of the method and effects of body side.

BACKGROUND: Fluid imbalance and malnutrition have an important role in the clinical setting of chronic heart failure (CHF). Recently, tetrapolar bioelectrical impedance analysis has been suggested as an attractive method which may be used in the clinical assessment of the body composition. The aim of this study was to determine the effects of body side on whole bioelectrical impedance analysis parameters and test-retest reliability, prior to its use in a large cohort of patients. METHODS: In 114 consecutive patients with CHF (mean age 65 +/- 10 years, left ventricular ejection fraction 31 +/- 9%, NYHA functional class 2.6 +/- 0.9) we measured the total body resistance, the reactance and the derived angle phase using a single-frequency (50 KHz) tetrapolar plethysmograph device. The evaluations were performed on the left and right sides of the body, in a random order, on two different occasions 30 min apart. The effects of body side were analyzed by the Student's t-test and the test-retest reliability was computed by using the coefficient of variation and intraclass correlation coefficient. RESULTS: In both evaluations, the mean resistance value of the right side was significantly lower (almost 10 ohms) than that of the left side, the reactance was not different, and as a consequence the angle phase was significantly higher (almost 0.1 degrees) in the right than in the left side. The test-retest reliability for all the measurements considered was very high (the intraclass correlation coefficient ranged from 0.95 to 0.99 and the coefficient of variation from 1.7 to 4.3%). CONCLUSIONS: In CHF, the body side is important for the whole-body assessment of the resistance and the angle phase, but not for reactance. In addition, all these measurements are characterized by an excellent test-retest reliability and, consequently, do not necessitate a substantial increase in the sample size for the detection of small differences in experimental studies.

Influence of hydrophilic and lipophilic beta-blockers on heart rate, ventricular repolarization and their interrelationship in normal subjects.

BACKGROUND: It has been hypothesized that hydrophilic and lipophilic beta-blockers have different antiarrhythmic properties because only the latter seem to reduce the rate of sudden death in post-myocardial infarction patients as well as animal models which seem to be independent of their effect on autonomic nervous system modulation. The aim of this study was to evaluate the different effects of a hydrophilic (nadolol) and lipophilic (metoprolol) beta-blocker on ventricular repolarization in normal subjects. METHODS: Seventeen normal subjects entered this randomized, single-blind cross-over study designed to compare the effects of nadolol (80 mg/day) and slow-release metoprolol (200 mg/day) on dynamic ventricular repolarization. The RR intervals, the QT evaluated at the apex (QT apex) and at the end (QT end) of the T wave before and after correction for heart rate, the standard deviation of QT apex and QT end, and the slope of the QT/RR linear relationship (QTa-slope and QTe-slope) were studied using the ELATEC system (ELA Medical, Mountrouge, France), and an evaluation was made of their reproducibility and the effects of each beta-blocker. RESULTS: The most reproducible parameters were QT apex, corrected QT apex and the QTe-slope. Nadolol was associated with a greater adrenergic blockade than metoprolol (lengthening of RR interval +25 +/- 7 and +17 +/- 8% respectively, p = 0.0003) and a lower effect on ventricular repolarization (reduction of corrected QT apex -0.6 +/- 3 and -2.5 +/- 2.1% respectively, p < 0.01; reduction of QTe-slope -5 +/- 16 and -15 +/- 15% respectively, p = 0.03). CONCLUSIONS: At the dosages used in the study, metoprolol showed lower adrenergic blockade but greater effect on ventricular repolarization than nadolol.

[Cardiopulmonary sensitivity and chemosensitivity]. / Sensibilità cardiopolmonare e chemosensibilità.

The autonomic control of the cardiovascular system plays an important role in maintaining the arterial pressure at the levels necessary for adequate tissue perfusion. In cardiovascular diseases, the impairment of the basic reflex mechanisms that are responsible for the moment-to-moment regulation could increase sympathetic activity and is correlated with an adverse outcome. The objective of the present review was to provide information about the methodological aspects exploring cardiopulmonary and chemoreceptor reflexes. Different techniques are available and all of them include assessment of reflexes through the activation or deactivation of either the cardiopulmonary baroreceptors or chemoreceptors. Intravenous saline load, head-down tilt, passive legs raising, head-out water immersion and the application of a lower body positive pressure are the principal methods utilized for activating cardiopulmonary baroreceptors; on the contrary deactivation could be achieved by acutely induced hypovolemia by furosemide or blood donation, inflation of a congestion cuff on the thighs or application of a negative pressure on the lower body. The transient exposure to a hypoxic or a hypercapnic gas mixture is frequently used to determine the peripheral and central chemoreflexes, respectively. The reflexes are quantified by the gain between output (i.e. heart rate, sympathetic activity, vascular resistance, ventilation) and input (oxygen saturation, end-tidal CO2 or changes in central venous pressure). One important limitation in assessing the cardiopulmonary baroreflex by using currently available techniques is that the involvement of the arterial baroreflex cannot be avoided. In addition, chemoreflexes cannot be interpreted unless the breathing rate is controlled. To date, several techniques are available for the quantification of cardiopulmonary baroreceptor and chemoreceptor reflexes and could provide new information on the abnormal autonomic mechanisms contributing to the pathophysiology of several cardiovascular diseases.

[Is it possible to predict the anti-arrhythmic effect of beta blockers based on various relations between premature ventricular beat and the preceding cardiac cycle?]. / E possibile predire l'effetto antiaritmico dei betabloccanti in base al riconoscimento di differenti relazioni tra battiti prematuri ventricolari ed il precedente ciclo cardiaco?

The aim of our study was to correlate betablocker effects on premature ventricular beats (PVBs) with different patterns between PVB frequency and cardiac cycle. The computer program we used correlates each PVB to the preceding cycle length in a 24-hour electrocardiogram recording. The arrhythmic patterns obtained were defined as tachycardia-dependent, indifferent and bradycardia-dependent. We selected 51 patients (39 males, 12 females, mean age 52 years) with different cardiac diseases, all in sinus rhythm, with > 25 PVBs/h, characterized by PVB stability and reproducible pattern in 2 Holter monitoring recorded at a 3-5 day interval. A tachycardia-dependent pattern (TDP) was demonstrated in 20 patients; 22 patients showed an indifferent pattern (IP) and 9 a bradycardia-dependent pattern (BDP). A third Holter monitoring was performed 4-5 days after nadolol administration (80 mg/day). Nadolol caused a 87.7% PVB suppression in TDP patients (p < 0.001), a 34.8% PVB reduction in IP patients (p < 0.01) and a 36.3% increase in BDP patients (NS). The different effect of nadolol on these groups was highly significant (chi 2 30.9; p < 0.0001). These results indicate that pattern definitions is useful in identifying PVB subsets which are likely to be improved, or not, by betablockers.

Efficacy and duration of the effect of gallopamil sustained release in patients with chronic stable effort angina.

This double-blind, placebo-controlled, cross-over study was designed to evaluate the effects and duration of action of gallopamil sustained release (SR) in patients with stable effort angina. Exercise tests were performed 3, 8, and 12 hours after the last administration of placebo or gallopamil SR. Blood samples for plasma gallopamil concentration were taken just before each exercise test. Statistical analysis was performed using an analysis of variance for multiple comparisons with evaluation of interaction between sequence and period according to a cross-over design. Compared to placebo, gallopamil SR significantly prolonged exercise time from 412 +/- 100 to 481 +/- 71 s (p less than 0.02; 17%), from 416 +/- 88 to 484 +/- 67 s (p less than 0.01; 16%), and from 364 +/- 88 to 440 +/- 85 s (p less than 0.02; 21%) at 3, 8 and 12 hours respectively after administration. Time to -1 mm ST segment depression was also significantly prolonged from 263 +/- 56 to 336 +/- 76 s (p less than 0.001; 28%), from 262 +/- 81 to 356 +/- 70 s (p less than 0.001; 36%), from 231 +/- 65 to 291 +/- 76 s (p less than 0.001; 26%), respectively. No significant relationship between plasma levels and anti-ischemic activity was observed. In conclusion, our data show that gallopamil slow-release is effective in improving exercise tolerance of patients with chronic angina and that its therapeutic effect persists, substantially unchanged, up to 12 hours after administration.

Sleep suppression of ventricular arrhythmias: a predictor of beta-blocker efficacy.

It has been reported that the frequency of premature ventricular contractions in some patients tend to decrease during the hours of sleep when modifications in autonomic tone and bradycardia occur. The aim of this study was to evaluate whether the phenomenon of sleep suppression may be a sensitive and specific parameter for predicting the antiarrhythmic effect of beta-blockers on premature ventricular contractions. The presence of sleep suppression was evaluated in 45 patients (mean age 50 +/- 17 years) with frequent premature ventricular contractions at two baseline Holter recordings. Sleep suppression was defined as > 50% reduction in the number of nighttime as opposed to day-time premature ventricular contractions. Three groups of patients were identified: those with sleep suppression at both Holter recordings (group 1); those with sleep suppression at only one Holter recording (group 2); and those without sleep suppression at either Holter recording (group 3). A third Holter was performed 5 days after nadolol administration. In group 1, nadolol led to a mean reduction in the number of premature ventricular contractions of 90% (> 70% in 21/23 patients). In group 2, the mean reduction was 76% (> 70% in three out of six patients). In group 3, there was a mean increase in the number of premature ventricular contractions of 33%. The positive predictive accuracy of sleep suppression in relation to the antiarrhythmic efficacy of nadolol is very high (88%) when sleep suppression is present during two baseline Holter recordings. Sleep suppression is a sensitive parameter for identifying the premature ventricular contractions likely to benefit from beta-blocker administration.

Holter-guided identification of premature ventricular contractions susceptible to suppression by beta-blockers.

To evaluate whether the identification of the different types of relations between premature ventricular contractions (PVCs) and the preceding sinus cycle length is capable of predicting the effect of beta-blockers on the PVCs themselves, 55 patients (43 men, 12 women, mean age 52.6 +/- 15.6 years) with different cardiac diseases, and >30 PVCs/hr characterized by stability and the same relation at two Holter monitoring periods were studied. The relation was tachycardia enhanced (the shorter the preceding cycle length, the higher the incidence of PVCs) in 23 patients (group 1); indifferent (no correlation between the preceding cycle length and PVC incidence) in 21 (group 2); and bradycardia enhanced (the longer the preceding cycle length, the higher the incidence of PVCs) in 11 (group 3). A third Holter monitoring was performed 6 days after nadolol administration (80 mg/day) to evaluate its effect on the three types of PVCs. Incidence in all patients (-88;p<0.001). In group 2, it caused a reduction in the majority of patients (-60%;p<0.05) but an increase in five. In group 3, it caused a reduction in only half of the patients (-45%) and a 91% increase in the remainder. The difference in the effect of nadolol in the three groups was highly significant (X2=27.5;p<0.0001). The relation between the incidence of PVCs and the preceding cycle length is a useful means of identifying subsets of patients with PVCs who will benefit from beta-blockers.

The effect of nadolol on heart rate and the standard deviation of the RR intervals.

The aim of this study was to evaluate the effect of nadolol in modifying the standard deviation of RR intervals (SDRR) and the coefficient of variance (CV) in 47 patients characterized by symptomatic, frequent (> 30 h-1) and reproducible premature ventricular contractions (PVCs). Sixteen patients had suffered a previous myocardial infarction (Group 1), 22 had various non-ischaemic cardiac diseases (Group 2) and nine had no heart disease (Group 3). All patients underwent two 24 h Holter recordings during the washout period, and a third Holter recording was taken 5 days after the administration of nadolol (80 mg.day-1). The RR cycle length (RR), SDRR and CV were evaluated for each 24 h period, as well as for six daytime (1000-1600h) and six night-time hours (0000-0600h). In all three groups, nadolol was highly effective in lengthening RR. However, the effect on SDRR was different in the three groups; 24-h SDRR tended to be reduced in all three groups (but the reduction was significant only in Group 1) due to a certain RR homogeneity. On the other hand, daytime SDRR tended to increase (but the increase was significant only in Group 3). CV is concomitantly affected by heart rate and SDRR, therefore it may be more sensitive in evaluating the effect of beta-blockers. The reduction in CV post-nadolol means that the bradycardia-induced effect is associated with an inadequate increase, or even a reduction in SDRR, whereas the absence of any CV changes (found only in Group 3) is the result of a concomitant increase in both RR cycle length and SDRR.(ABSTRACT TRUNCATED AT 250 WORDS)

[Double-blind randomized placebo-controlled study of the effects of slow release and immediate release forms of propafenone in patients ventricular extrasystole symptoms]. / Studio in doppio cieco, randomizzato, controllato con placebo, degli effetti di due formulazioni di propafenone a rilascio ritardato e di quello a rilascio immediato sulle extrasistoli ventricolari sintomatiche. Gruppo degli Investigatori.

This is a multicenter, randomized, double-blind, placebo-controlled, cross-over and double-dummy study aimed at testing the efficacy and tolerability of two slow-release propafenone (Pr SR) preparations and compare them with the effect of instant release propafenone (Pr IR). The study was performed in 83 patients with frequent (> 30 premature ventricular contractions/hour) and stable (< 35% variability in two 24-hour ECG monitoring periods) symptomatic premature ventricular contractions. Patients were preliminarily studied in wash-out from antiarrhythmic drugs. After a period of placebo administration, all patients underwent three consecutive periods during which they received Pr IR at the dosage of 150 mg x 3, Pr SR at the dosage of 225 mg x 2, Pr SR at the dosage of 325 mg x 2. The periods lasted 10-14 days each and the sequence was randomly assigned. Twenty-four-hour ECG monitoring periods were obtained at the end of the placebo as well as at the last day of each treatment period. Treatment efficacy was evaluated by intention to treat analysis in 80 patients and by protocol in 61. Treatment was considered efficacious when premature ventricular contraction reduction > or = 75%, couplet reduction > or = 90% and non sustained ventricular tachycardias were completely suppressed. Pr IR 150 mg x 3 was efficacious in 42% of patients, Pr SR 325 mg x 2 in 45.9% and Pr SR 225 mg x 2 in 32%. Tolerability was considered good in the majority of patients. These results show that among the different types studied, Pr SR 325 mg x 2 should be considered the treatment of choice for premature ventricular contractions.

Evaluation of pentisomide on stable ventricular premature beats. Comparison with placebo.

Pentisomide, a new class I anti-arrhythmic drug, was compared to placebo in 50 hospitalized patients with frequent (greater than 30 h-1) and stable ventricular premature beats (VPB) (variation less than 50% between two preliminary and one placebo 24-h Holter recordings). All patients underwent a single-dose acute oral testing followed by a short-term testing with 300 mg t.i.d. for 4 days and then by a 4-day placebo period. For the studied population, a 56.4% reduction of simple VPB and a 98.8% decrease of couplets and runs were the minimum required to define the drug efficacy and to exclude spontaneous variability, using the linear regression analysis. Pentisomide was found effective in 27 (54%) of the 50 patients after the acute test and in 23 (46%) after the short-term test. The drug induced a mild increase of PR and QRS intervals, while QTc, heart rate, blood pressure and ejection fraction showed no significant variations. Subjective tolerability was excellent.

Objective evaluation of gallopamil in patients with chronic stable angina. Exercise testing, Holter monitoring, cross-sectional echocardiography and plasma levels.

In this double-blind, randomized placebo-controlled study the effects of two dosages of gallopamil on exercise tolerance were evaluated in 12 patients with stable effort angina. After a pre-study screening aimed at assessing the reproducibility of the exercise response, the patients entered the study which consisted of three 7-day consecutive periods during which placebo or gallopamil 50 mg t.i.d. or gallopamil 75 mg t.i.d. were administered according to a randomized sequence. 24-hour Holter monitoring and cross-sectional echocardiography were performed on the 6th and 7th day of each treatment period, respectively. On the 7th day of each treatment period, patients underwent an exercise test 2 and 8 h after the last administration of gallopamil or placebo. Blood samples for plasma gallopamil concentrations were taken just before each exercise test. The results were analysed using a three-way analysis of variance; intergroup differences were evaluated by the Newman-Keuls test. At 2 h, 11 patients with placebo and three with gallopamil experienced angina; both dosages of gallopamil significantly prolonged exercise time and -1 mm time and also reduced ST segment depression and the rate-pressure product at submaximal workload. No significant change in the rate-pressure product was observed either on the appearance of 1 mm ST depression or at peak exercise. At 8 h, 11 patients with placebo and gallopamil 50 mg t.i.d. and 10 with gallopamil 75 mg t.i.d. experienced angina; although exercise time was significantly prolonged by both dosages of gallopamil, the increase in -1 mm time and reduction of ST segment depression at submaximal workload did not reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)