Retroconduction selective recognition in wide-dipole floating atrial sensing. The Multicenter Study Group.

Effective discrimination of retrogradely conducted P waves would allow distinguishing sinus tachycardia from supraventricular tachycardias due to AV or nodal reentry, and would prevent pacemaker-mediated tachycardia in AV sequential pacing. This might be especially relevant in VDD implants, where retroconduction could be induced by escape ventricular stimulation. In order to analyze the respective waveform properties, anterograde and retrograde atrial signals were recorded by a wide floating electrode dipole, on the implantation of a permanent single-pass lead for VDD pacing. Generally, bipolar recording did not allow reliable discrimination, while the signal nature could be readily diagnosed from the main features of the unipolar atrial electrograms. The unipolar waveform recorded under sinus rhythm in high right atrium, close to the superior vena cava opening (proximal EGM), started with a negative deflection in 88% of the patients. In 7% of the patients, the first deflection of the signal was positive in some cardiac cycles only, and, on the average, the amplitude of the positive phase was not higher than 5% of the signal peak-to-peak amplitude. Conversely, under retroconduction, the starting deflection attained higher positive values in 98% of the patients, being stably over 15% of the peak-to-peak amplitude in 86% of the Furthermore, in 69% of the cases, the lag time between the onset of the negative deflection of proximal and distal (mid-low atrium) unipolar EGM changed unambiguously when retroconduction occurred, exceeding the range of variation observed in each patient during sinus activity. The combined evaluation of unipolar EGM shape and lag time allowed specific retroconduction recognition in 95% of the patients. We suggest that this approach may yield useful information for the discrimination of retrograde atrial signals, provided that the recording dipole is sufficiently long and the proximal electrode is properly positioned in the high right atrium.

Tolerance to the repolarization effects of rac-sotalol during long-term treatment.

AIMS: To establish whether tolerance to the QT effect could ensue during maintenance treatment with rac-sotalol. METHODS: The effect of rac-sotalol on QT interval duration was studied in 10 patients after single oral administration (160 mg) and after 6-day multiple oral dosing (80 mg two or three times daily). In order to separate the pure Class III effect from the bradycardia-related QT prolongation, heart rate/QT relationship was preliminarly assessed in each patient after the administration of a pure beta-adrenoceptor blocker (propranolol, 80 mg orally). Repolarization changes were quantified as percent difference between the measured QT and the expected QT on the basis of the individual heart rate/QT relationship. RESULTS: In all patients QT interval prolongation was linearly correlated with rac-sotalol log plasma concentration. The maximal QT prolongation and peak plasma concentration were not significantly different following acute and chronic administrations (QT effect: +18.1+/-6.3% vs +14.2+/-3.3%; peak concentration: 1.64+/-0.49 mg l(-1) vs 1.83+/-0.66 mg l(-1)). Line slopes were also unchanged following chronic treatment (21.8+/-8.9 vs 21.1+/-9.2). In four cases a significant rightward shift of the line occurred during repeated administrations, consistent with the appearance of pharmacodynamic tolerance. The inconstancy of this change in responsiveness may either be ascribed to a genetically determined individual susceptibility or to a variable interplay between Class III effect, gradual QT prolongation due to long-term beta-adrenoceptor blockade and tolerance development. CONCLUSIONS: During maintenance treatment with rac-solatol, partial loss of repolarization effects occurred in some patients suggesting pharmacological tolerance.

Pharmacodynamic variability of flecainide assessed by QRS changes.

The effect of flecainide on the QRS interval was studied in 10 patients who were receiving long-term oral treatment (50 to 150 mg twice daily) for arrhythmias that were refractory to other drugs. Total and free drug plasma levels and QRS durations were measured at intervals after the morning administration. Free drug plasma levels were linearly correlated with QRS duration in each patient and the slope of the line was widely variable in the population studied. Even after the data from one patient with an unusually high slope (0.454) was excluded from the analysis, the slope range was 0.0284 to 0.144. Pharmacodynamic variability could not be explained by heart rate changes, active metabolites, electrolyte disturbances, or free drug concentration. None of the pharmacokinetic parameters measured (average steady-state concentration, fluctuation of maximum and minimum concentrations, time to peak concentration, final half-life, and protein binding) showed an intersubject variability greater than 4.4 times. Our findings suggest that the determination of flecainide free plasma concentration may not be sufficient to forecast electrophysiologic effects in individual patients.

[Myocardial infarct before 45 years of age: significance of the coronarographic study in asymptomatic patients]. / Infarto miocardico sotto i 45 anni: significato dello studio coronarografico in pazienti asintomatici.

The aim of our study was to evaluate the significance of coronary arteriography in young asymptomatic patients after myocardial infarction. Among a total of 586 consecutive patients who underwent left ventriculography and coronary angiography because of coronary heart disease during the period from January 1984 to June 1986, we selected 51 patients (8.7%) under 45 years of age (range 28-45 years) and without angina, dyspnea or electrocardiographic signs of myocardial ischemia during bicycle ergometric stress test. These patients, 50 males (98.0%) and 1 female (2.0%) were angiographically evaluated from 1 to 12 months after a first myocardial infarction. Coronary occlusions greater than or equal to 70% were found in 44 patients (86.3%): 36 of them (70.6%) had single-vessel disease, 6 (11.8%) double-vessel disease and only 2 (3.9%) triple-vessel disease; no coronary obstructions greater than or equal to 50% of the left main coronary artery were found. Among the 7 patients without critical stenoses (13.7%) 3 had "normal" coronary arteries, 3 noncritical stenoses and one presented an anomalous origin of the left circumflex artery from the right sinus of Valsalva. Only 1 patient underwent surgery. In conclusion, in young asymptomatic patients after a myocardial infarction coronary arteriography may identify a small group either without or with minor atherosclerotic involvement of the coronary tree, while the presence of a localized disease is confirmed in most patients. Therefore, in this selected subgroup, coronary angiography has a limited usefulness in defining high-risk patients possibly requiring surgical treatment.