Direct and autonomically mediated effects of oral quinidine on RR/QT relation after an abrupt increase in heart rate.

OBJECTIVES: This study evaluates the direct and autonomically mediated effects of oral quinidine on ventricular repolarization in humans. BACKGROUND: Interactions between quinidine-related vagolytic properties and autonomic modulation on ventricular repolarization are unknown. The relative role of the two components, if present, might improve our understanding of the therapeutic and proarrhythmic mechanisms of quinidine on the ventricular tissue. METHODS: Rate-related changes in the QT interval were investigated after an abrupt increase in heart rate in 15 patients during atrial pacing. In the control study, the QT interval was measured at six paced cycle lengths (600, 540, 500, 460, 430 and 400 ms) both in the basal state and after autonomic blockade (intravenous propranolol, 0.2 mg/kg, and intravenous atropine, 0.04 mg/kg); oral quinidine was then administered at a daily dosage of 1,200 mg for 3 to 4 days, after which the QT duration was reassessed using the same method in a second study. RESULTS: During the control study, the mean slope of the regression curve estimating the correlation between pacing cycle length and QT duration was significantly lower after autonomic blockade (0.14 +/- 0.05) than in the basal state (0.27 +/- 0.10, p < 0.05). Quinidine exhibited a prominent but opposite effect on the mean slope of the regression curves in basal conditions (from 0.27 +/- 0.10 to 0.20 +/- 0.07, p < 0.05) and after withdrawal of autonomic modulation (from 0.14 +/- 0.05 to 0.19 +/- 0.05, p < 0.05), thus annulling the differences observed between the two states in the control study. CONCLUSIONS: A quinidine-induced increase in QT duration as cycle length is prolonged is consistent with a reverse use dependence effect on ventricular repolarization. This effect is not evident in the basal state owing to interaction of quinidine-related vagolytic effect with the autonomic tone. Reverse use dependence and vagolytic activity on ventricular tissue indicate two potentially undesirable effects that could play a role in the lack of efficacy or proarrhythmic effect of quinidine.

Atrial septal aneurysm: echopolycardiographic study.

Atrial septal aneurysm (ASA) with diagnosis during life is a rarely reported anomaly, especially when not associated with other congenital or acquired valvular cardiopathies. Among 4,000 routine echocardiograms, 23 cases of ASA were found (8 men and 14 women, aged 19 to 79 years). Three patients had coronary artery disease, 2 had dilated cardiomyopathy, 2 had systemic hypertension, 11 had mitral valve prolapse and 5 had no other identifiable cardiovascular diseases. Echocardiography revealed various motion patterns of ASA. No phonomechanocardiographic findings were related to the presence of ASA, and no correlation between echographic and phonocardiographic findings was found.

a 49-year-old woman with dyspnoea, palpitations and syncope.

Pulmonary hypertension is rarely described in association with Sjögren's syndrome. The authors report the case of a patient in which pulmonary hypertension was the inaugural clinical manifestation of primary Sjögren's syndrome. Clinical assessment, differential diagnosis, etiopathological implications, and therapeutic approach are discussed.

Clinical feasibility of low energy internal atrial cardioversion with a three-electrode configuration in patients with unsuccessful conventional configurations.

Low energy internal cardioversion is a safe and highly effective method for atrial fibrillation termination. We will describe 6 patients in whom the conventional 2-electrode systems with the defibrillation leads positioned in the right atrium and in the coronary sinus or left pulmonary artery failed to terminate the arrhythmia despite the use of maximal available energies. A 3-electrode configuration including right atrium, coronary sinus and left pulmonary artery was used in order to encompass as much atrial mass as possible between the cathode and the anode. The atrial fibrillation was successfully interrupted in 4 out of 6 patients. The creation of a 3-electrode configuration may be a further technical expedient in order to increase the success rate of internal cardioversion when usual manoeuvres like lead repositioning, reversion of polarity, or addition of antiarrhythmic drugs are ineffective.

Diagnosis of mitral valve diseases using indirect (esophageal) left atrial pulse.

The diagnostic usefulness of the indirect (esophageal) left atrial pulse (ESO) has been analyzed in: 1) 25 patients (pts) with mitral insufficiency (MI), 2) 18 pts with mitral stenosis, 3) 29 pts with combined valvular disease, 4) 10 normal subjects. In addition, in 1) and 4), the ESO was recorded under the following dynamic conditions: a) during isometric exercise (handgrip), b) after inhalation of amyl nitrite, c) after intravenous infusion of methoxamine. The ESO tracing demonstrated estimates of the severity of the disease. Under dynamic conditions no modification from the resting morphology was obtained in the control group, whereas in MI the following modifications were observed: a) increased, progressive, positive elevation of the systolic phase of the ESO during the handgrip and the administration of the methoxamine; b) tendency to return to normal morphology after amyl nitrite.

Mechanographic evaluation of left atrial activity in mitral valve prolapse.

Twenty-five patients suffering from mitral valve prolapse were studied to demonstrate any diagnostic modifications of the indirect (esophageal) left atrial pulse (ESO). Valvular prolapse is demostrated on the ESO by a sudden change in slope of the curve after the "x" point, in coincidence with a midsystolic click. Late systolic mitral insufficiency, when associated with prolapse is illustrated on the ESO tracing in two ways: a) an abnormally tall "v" wave; b) a late systolic plateau which begins immediately after the click and continues beyond the second heart sound. After the infusion of methoxamine or isometric exercise the ESO is usually of the a) conformation, while after the inhalation of amyl nitrite the tracing tends to be of the b) type. The "c" wave is at times altered but not always. This alteration is characterized by a greater amplitude and sharper peak. Based on the physiopathogenesis of the alterations of the ESO, it can be stated that they are specific, and sensitive enough to be both qualitative and quantitative.

Two-dimensional echocardiography in post traumatic tricuspid incompetence.

Four patients with post traumatic tricuspid incompetence underwent complete two-dimensional echocardiographic study. Systolic intra-atrial protrusion of the anterior tricuspid leaflet beyond the valvular ring, with total loss of coaptation with the other leaflets, was documented in all patients. These abnormalities were not evident in all transducer locations suggesting the possibility of false negative echocardiograms. An echocardiogram showing a marked systolic excursion of a tricuspid leaflet into the right atrium beyond the level of the tricuspid ring together with the total loss of coaptation does not necessarily mean the rupture of the subvalvular apparatus.

[Spectral analysis of a "sea gull cry" murmur (author's transl)]. / Analisi spettrale di un rumore "a grido di gabbiano".

"Precordial honk" is a loud, high pitched, musical and usually intermittent systolic noise. The concept of extracardiac origin and "inocence" of this finding is superseded and today its valvular origin during mitral prolapse, mitral or tricuspidal insufficiency - due to rheumatic or ischaemic disease - or during cardiomiopathy is demonstrated. The acoustic characterization of this finding was based on phonocardiographic registration. All the authors describe the "precordial honk" as a high frequency murmur without specifying the acoustic characteristics of the phenomenon. A spectral analysis technique applied to the acoustic cardiac signal (Fourier analysis) has been employed in order to study the "precordial honk" of a 15-year-old boy with mitral valve prolapse. This made possible to show that this sound had only one fundamental frequency at 300 Hz. without harmonics; a "sea gull cry" murmur (as the cry of many birds is) justifying the name given by clinicians. The spectral analysis of phonocardiography signal allow to study, more precisely, the cardiac acoustic phenomenon.

[Technical and methodological aspects concerning the application of Fourier's analysis to phonocardiography (author's transl)]. / Aspetti tecnici e metodologici dell'introduzione in fonocardiografia dell'analisi di Fourier.

The frequency spectrum analysis (Fourier's analysis) has recently been applied to phonocardiography. Using this mathematical approach instead of the current empirical analysis, it is possible to obtain -- on a less subjective basis -- more precise pathophysiological and diagnostic information from the acoustic cardiac phenomena. On the other hand, this refinement of the method of analysis stresses the need for better technical and methodological solutions, in order to reach the standardization of both the transduction and the recording of the acoustic signal at higher level of sensibility, fidelity and reproducibility. With this in mind, and on the basis of their experience, the Authors suggest the adoption of devices with specific technical characteristics, and propose a suitable method of application of Fourier's analysis to the phonocardiogram.

Bedside evaluation of sinus bradycardia: usefulness of atropine test in discriminating organic from autonomic involvement of sinus automaticity.

In 55 patients with persistent sinus bradycardia who underwent an electrophysiologic study of sinus node, both in the basal state and after autonomic blockade (propranolol, 0.2 mg/kg, and atropine, 0.04 mg/kg), an atropine test (0.02 mg/kg) was performed the following day. The 49 patients in whom sinus rate could be evaluated after atropine were subdivided into two groups--group I, 24 patients (age: 54 +/- 13 years) with normal intrinsic sinus automaticity (normal intrinsic heart rate and intrinsic corrected sinus node recovery time) and group II, 25 patients (age: 62 +/- 9 years) with abnormal intrinsic sinus automaticity. In group I, atropine increased sinus rate from 53.7 +/- 4 to 87.9 +/- 17 bpm (delta %: 65.5 +/- 33) and in group II from 51.6 +/- 5 to 73.9 +/- 14 bpm (delta %: 43.1 +/- 26). The discriminant threshold of sinus rate after atropine and its percent increase, obtained by discriminant analysis, was 80 bpm and +52%, respectively, with a misleading classification of 32% and 36%, respectively. The overall predictive accuracy of sinus rate after atropine was higher than the percent change in sinus rate (73% and 65%, respectively). These data evidence that the atropine test is not very helpful in discriminating between an organic and an autonomic involvement of sinus automaticity in patients with sinus bradycardia.

Phonometric approach to the analysis of cardiac acoustic phenomena.

The use of phonocardiography is limited by the lack of standardization of acoustical signal pick-up and of the filters. Moreover, quantitative evaluations are not possible. This limits the analysis of acoustic phenomena and makes confrontation between different laboratories impossible. To avoid these drawbacks we have developed a method based on phonometric principles. Heart sounds of twenty for normal subjects were recorded by an air-coupled microphone with the standard 6 ml cavity. The response curve of the microphone is flat from .2 to 8000 Hz. The signal was measured and stored on an analogic tape recorder together with the ECG. For each subject the 3 weighting networks (A, B and C, according to the American National Standard Institute) and the linear recording (SPL) were used and the peak value of every record was written down in dB-peak. The amplitude spectra were obtained through the FFT algorithm. Normal heart sounds reached a high frequency limit of 170 Hz. with a maximum amplitude of 67 dB SPL, 24 dB A, 42 dB B and 59 dB C. Each spectral pattern can provide a useful reference to compare with pathological acoustical findings.

Phonometric study of the human first heart sound.

The first heart sound was studied in 20 normal subjects. The phonocardiogram (PCG) was recorded from apical and mid-precordial areas using microphone with a flat response curve from 0.2 to 8,000 Hz. It was stored, together with a simultaneous electrocardiogram, on an FM analog tape recorder (linear frequency response from 0 to 4,000 Hz), fitted with a filter with weighting curve B according to the American National Standard Institute. A linear (SPL) recording was also made. The signal was fed through a digital converter into a minicomputer and the frequency distribution of the first heart sound was analyzed using Fast Fourier Transform. These data were stored and the average spectra were calculated for both B and SPL. The SPL spectra from both apex and mid-precordium showed a maximum intensity of about 80 dB between 12-20 Hz, decreasing progressively to a constant level of 35 dB between 110-120 Hz. The spectra obtained from both areas using filter B showed a maximum intensity of 40-50 dB between 20-60 thereafter. It is important to emphasize that the dB values in B and SPL are absolute, since they refer to a standard reference weighting. It appears that the SPL recording is more valuable in that it allows the study of all components of the PCG signal. The spectra obtained in this study will be used as a standard for future research in various pathological conditions.

Effects of ibopamine on peripheral hemodynamics: a strain gauge plethysmographic study in patients with congestive heart failure.

Peripheral hemodynamics were studied using strain gauge plethysmography in patients with congestive heart failure after administration of ibopamine (SB-7505), the orally active 3,4-diisobutyryl ester of N-methyldopamine, a dopaminergic agonist, and of sulpiride, a specific dopaminergic antagonist. 50 mg of sulpiride were administered parenterally in 12 patients 3 h after a single oral dose of 150 mg of ibopamine. Ibopamine increased significantly resting arterial blood flow and venous capacity and decreased peripheral resistance. Sulpiride was found to significantly counteract the activity of ibopamine.

Long-term reliability of single lead atrial synchronous pacing systems using closely spaced atrial dipoles: five-year experience.

To assess the long-term capability of single atrioventricular (AV) lead VDD pacing systems using close atrial dipoles to assure reliable atrial guided pacing, the safety and efficacy of 86 VDD units implanted in 73 patients at a single center since November 1988 was reviewed. All patients suffered from advanced AV block with normal sinoatrial function. Sixty five patients received a LEM/CCS Twinal 30/30S system, four patients received a Vitatron-Saphir system, and four patients received a Medtronic Thera VDR 8348 system. All patients underwent provocative tests in search of myopotential interference, and Holter recordings; in a group of patients who underwent pacemaker replacement a comparison was made between implant and replacement measurements. The mean follow-up duration was 27.3 months. A high percentage of successfully VDD paced patients and a low incidence of pacemaker malfunction, regularly solved by pacemaker reprogramming, was reported. Atrial signal amplitudes comparable to those measured at implant were found at replacement in all patients. These data support the long-term reliability of single AV lead VDD pacing systems with closely spaced atrial dipoles, as well as stable atrial sensing by floating bipolar atrial electrodes and effective atrial synchronous ventricular pacing over time.

Italian multicenter study on a single lead VDD pacing system using a narrow atrial dipole spacing.

Since November 1988, 514 patients with advanced atrioventricular (AV) block and normal sinoatrial function have received the single lead VDD pacing system Twinal 30 Lem/CCS in 30 Italian centers. At implantation, particular attention was paid to the correct positioning of the atrial dipole in the mid- to mid-high right atrium and to the atrial electrogram characteristics. The follow-up included a chest X ray, to be performed before discharge of the patient from the hospital, telemetric evaluations of the endoatrial potential, provocative tests for interferences by myopotentials, 24-hour ambulatory EGG recordings, and where possible, exercise stress tests. The mean follow-up duration was 15.2 months, ranging from 1 to 42 months. A very low percentage of chronic atrial fibrillation, loss of atrial sensing, and system replacement was reported, most of the patients (93.5%) being paced in VDD mode. All investigations indicated an excellent overall system performance, stable AV synchrony, and infrequent myopotential interference, and a low complication rate throughout the follow-up period.

Cardiomechanical effect of k-strophanthoside administered to healthy volunteers by the rectal route.

Eight healthy volunteers were given k-strophanthoside (Strofopan) 1 mg rectally in order to evaluate changes in the cardiac function. Cardiomechanical measurements were performed by the polygraphic method before administering the drug and 1, 2, 3, 4, 5 and 6 h later. Three of the eight subjects continued to receive k-strophanthoside 1 mg daily for a further 6 days. Similar evaluations were made at the same times on day 3 and on day 7 of treatment. All indices considered varied to a statistically significant extent and showed the maximum effect at about the 4th h. The most evident changes were observed in the ICT and the PEP/LVET ratio. Here, the maximum variations were 46.3% and 29.5%, respectively, as compared with baseline values (P less than 0.01). When treatment was given for 7 days, the baseline values measured on day 3 and day 7 before administration showed a moderate and constant decrease in all parameters as compared with the first baseline value. This proves that k-strophanthoside administered rectally possesses steady-state activity with time. From a comparison of the changes in the same parameters as observed in a previous investigation after administering digoxin 0.50 mg orally there is reason to conclude that the effects obtained after administering k-strophanthoside 1 mg rectally were of the same magnitude.

AV delay and exercise stress tests: behavior in normal subjects.

In normal subjects the atrioventricular (AV) conduction is accelerated during exertion. The relationship between heart rate and AV delay is usually described as "linear". Looking at the increasing importance given to an appropriate AV synchrony in permanent dual chamber and P synchronous pacing we present the results of an investigation performed to study the correlation between AV conduction time and heart rate under stress conditions, and disclose some new aspects of this matter, which will possibly be useful for a further improvement of pacemaker technology.

Peripheral hemodynamic effects of ibopamine in patients with congestive heart failure. A placebo-controlled, double-blind study.

Under double-blind conditions, 150 mg of ibopamine (di-isobutyric ester of N-methyldopamine) or placebo were given orally to 11 patients with congestive heart failure; after 3 hours, 50 mg of sulpiride were administered intramuscularly. Peripheral hemodynamics were evaluated at the level of the forearm using strain-gauge plethysmography. Ibopamine increased arterial blood flow and venous capacity and decreased arterial peripheral resistance; these effects were counteracted by sulpiride. No significant changes were observed after placebo and sulpiride. These findings confirm the vasodilating effects of ibopamine on peripheral hemodynamics and its utility in patients for the treatment of congestive heart failure.