Improvement in identification of multivessel disease after acute myocardial infarction following stress-recovery analysis of ST depression in the heart rate domain during exercise.

The demonstration of extensive coronary artery disease (CAD) after acute myocardial infarction (AMI) has important prognostic implications. Exercise-induced ST segment depression is commonly used for detecting the presence of CAD and evaluating its extension. However, even though there have been many attempts to increase its diagnostic yield, the accuracy of the electrocardiographic signal for identifying multivessel disease (MVD) is relatively low, particularly in post-MI patients. The aim of this study was to evaluate the ability of a simple index, combining information on the amount and kinetics of ST depression in the heart rate domain during exercise and recovery, to identify MVD after AMI. Seventy patients (mean age 53.4 years) underwent a bicycle, symptom-limited exercise stress test and coronary angiography 2-3 weeks and 6 weeks respectively, after uncomplicated AMI while cardioactive therapy was discontinued. After obtaining a computer-derived measurement of ST levels based on incremental averaging of normal complexes, the area subtended to baseline and limited by the ST trend against heart rate during both exercise (A1) and recovery (A2) was calculated. The difference (A1-A2) was defined as the 'Stress-Recovery Index' (SRI) and dichotomized, by means of receiver-operating characteristics curve analysis, at 5 mm x beats.min-1 to define an increased risk of MVD. The SRI of patients with MVD was significantly lower than that of patients with single vessel disease. The sensitivity of SRI < -5 mm x beats.min-1 (65%) for predicting MVD was significantly higher than that obtained by other conventional parameters, without appreciable loss of specificity (81%).(ABSTRACT TRUNCATED AT 250 WORDS)

Abrupt complement activation and transient neutropenia in patients with acute myocardial infarction treated with streptokinase.

BACKGROUND: Whether and to what extent complement is activated in acute myocardial infarction (AMI) and how it contributes to inflammation of the ischemic area are not yet clear. Fibrinolytic agents used for thrombolysis are known to activate complement in vitro and may contribute to its activation in vivo. The aim of this study was to measure the extent of complement activation in AMI patients, some treated and some not treated with streptokinase. In addition, because abrupt complement activation in vivo is usually associated with leukocyte margination, plugging of cells in the microcirculation, and hypotension, we correlated complement activation with leukocyte numbers and mean arterial pressure. METHODS AND RESULTS: Forty AMI patients were studied: 20 were treated with streptokinase (1.5 million IU IV over 60 minutes), and 20 were not given any fibrinolytic agent. The extent and severity of AMI were not significantly different in both groups. Blood samples were drawn on arrival at the hospital, during streptokinase infusion, and then daily for 1 week. Time-matched samples were also drawn from patients not treated with streptokinase. We measured plasma levels of anaphylatoxin C4a, C3a, and C5a by radioimmunoassay and membrane attack complexes SC5b-9 by enzyme immunoassay. Leukocytes and arterial pressure also were measured when samples were obtained. C4a, C3a, and SC5b-9 levels increased about 10-fold (P < .0001) during infusion of streptokinase. There were no significant increases in complement catabolic products in AMI patients not treated with streptokinase. There was a significant transient leukopenia (mean +/- SEM, -29.5 +/- 7.0%; P = .001) and decreases in systolic and diastolic pressures (systolic, -29.3 +/- 3.2%, P < .0001; diastolic, -27.5 +/- 3.4%, P < .0001) after 15 minutes of streptokinase infusion in coincidence with the peak of anaphylatoxins in plasma. CONCLUSIONS: Streptokinase treatment of AMI causes abrupt activation of the complement system, whereas no significant complement activation can be detected in plasma of AMI patients not treated with fibrinolytic agents. Complement activation causes a transient leukopenia, as reported for such other clinical conditions as dialysis and cardiopulmonary bypass, and possibly contributes to the hypotension observed during streptokinase treatment.

Determination of agreement between cardiopulmonary and standard ECG stress testing in coronary artery disease.

The agreement between the results of standard ECG (CX) and cardiopulmonary (CPX) exercise stress tests performed in randomized sequence was evaluated in 40 patients with known coronary artery disease but who were not taking cardioactive therapy. Systolic blood pressure and heart rate were significantly higher during CPX only at low workload (less than 100 W). Exercise time and rate-pressure product at both peak exercise and ischaemic threshold were not significantly different between the two tests, even though their variability exceeded the value of 20%, which is generally accepted as the cut-off point for defining CX parameters as reproducible. However, the metabolic response to exercise, assessed by means of blood lactate kinetics analysis, was highly reproducible between the two tests. We conclude that the provocative role of exercise testing is not altered by the gas exchange analysis technique used in CAD patients. However, the common indexes of myocardial as well as of global physical performance may be influenced, thus requiring caution in comparing data with those derived from CX or from reference values.

[Late ventricular potentials in the post-infarct patient. A follow-up at 4 years]. / I potenziali tardivi ventricolari nel post-infarto. Follow-up a 4 anni.

We performed a prospective study to evaluate the prognostic significance and the natural history of late ventricular potentials (LPs) in 209 patients (165 males and 44 females; mean age 59.8 +/- 10 years) who survived acute myocardial infarction. Signal-averaged electrocardiograms (SA-ECGs) were performed before hospital discharge (16 +/- 5 days) and after four years (mean follow-up 42 +/- 7 months). SA-ECGs were processed using a 40 Hz high-pass bidirectional filter. Duration of "filtered" QRS (normal value < 120 msec), duration of the low-amplitude signals (n.v. < 39 msec) and last 40 msec voltage of the QRS complex (n.v. > 20 microV) were measured. LPs were defined as the presence of two or more abnormal values. In addition, 24-hour Holter monitoring was performed in all patients, and left ventricular ejection fraction (LVEF) was determined by scintigraphy in 120 (57.4%). Sixty patients (28.7%) had LPs before hospital discharge (group 1), and 149 (71.3%) had normal SA-ECGs (group 2). During the follow-up period there were 10 arrhythmic events, 7 of which were sudden deaths, and three cases of sustained ventricular tachycardia. SA-ECG was repeated in 141 patients (68%). The mean values of SA-ECG's parameters did not change significantly between the two controls, and the correlation was good for all of them. Despite this, spontaneous normalization of SA-ECGs occurred in 21 patients (60%) and the subsequent appearance of LPs was seen in 13 (12%); in these latter, the SA-ECG's parameters measured before hospital discharge were "borderline" and significantly different from those who did not change. The sensitivity of SA-ECG as a predictor of arrhythmic events was 80% and the specificity 74%. Patients with arrhythmic events had a longer filtered QRS (126 +/- 33 vs 103 +/- 12 msec; p < 0.001), longer duration of the low-amplitude signals (57 +/- 23 vs 32 +/- 11 msec; p < 0.001), lower voltages (17 +/- 8 vs 36 +/- 24 microV; p < 0.001), and, moreover, higher peak CK values, lower LVEF and higher value of Lown modified class. In conclusion, SA-ECG confirms its value in identifying patients at risk of arrhythmic events after myocardial infarction. SA-ECG recordings taken before the discharge can be used to predict serial changes during follow-up.

Radionuclide assessment of left ventricular function in patients with myocardial infarction and diabetes mellitus.

The aim of this study was to compare left ventricular function, assessed by radionuclide angiocardiography, in 54 diabetics and 194 non-diabetics with acute myocardial infarction (AMI). The most meaningful results concern the inferior AMI group, whose left ventricular ejection fraction (LVEF) and regional wall motion were significantly lower in diabetics than in non-diabetics (LVEF was 44.2 +/- 11 vs. 51.6 +/- 9%, P less than 0.005; the regional wall motion score was 0.46 +/- 1 vs. 1.56 +/- 1, P less than 0.01, respectively), while no significant difference was observed in the anterior AMI group. However, in the group as a whole, the LVEF was 41 +/- 13% in diabetics and 47 +/- 13% in non-diabetics (P less than 0.01), the number of abnormally contracting segments was 2.0 +/- 0.9 and 1.5 +/- 1, respectively, and the wall motion score was 0.2 +/- 1.1 and 1.0 +/- 1.4, respectively (P less than 0.01). These data could be explained by an underlying cardiac dysfunction in diabetes, in addition to AMI. The more marked difference between diabetics and non-diabetics in inferior AMI might be related to the smaller infarct size in this group.

Clinical correlation between diabetic and non diabetic patients with myocardial infarction.

We have studied 130 patients with diabetes mellitus and 455 patients without. All the patients were consecutively admitted to our Coronary Care Unit with their first myocardial infarction. We have observed a higher incidence of heart failure, in-hospital mortality, atrial fibrillation, conduction abnormalities, and post-infarction angina among diabetics. Nevertheless, diabetic patients do not show evidence of larger infarcts than those without diabetes. In our patients the higher mortality among diabetics is related to an increased occurrence of left ventricular failure. Moreover, post-infarction ischemic episodes are more common compared with non diabetics. Since infarcts in diabetics do not seem to be more extensive than in non diabetics, we suggest, in accordance with others, that the poorer outcome among diabetic patients with AMI could be related to an underlying cardiac dysfunction of diabetics in addition to coronary artery diseases.

Prognostic significance and evolution of late ventricular potentials in the first year after myocardial infarction: a prospective study.

We performed a prospective study of the high-frequency components of the terminal portion of the QRS complex in 220 patients who survived acute myocardial infarction. Signal-averaged electrocardiograms (SA-ECGs) were performed before hospital discharge (16 +/- 6 days) and then serially at regular intervals over the following year. SA-ECGs were processed using a 40 Hz high-pass bidirectional filter. Duration of "filtered" QRS (D-normal value less than 120 ms), duration of the low-amplitude signals (D40 - n.v. less than 39 ms) and last 40 ms voltage of the QRS complex (V40 - n.v. greater than 20 microV) were measured. Late potentials (LPs) were defined as the presence of two or more abnormal values. In addition, 24-hour Holter monitoring was performed in 208 patients and left ventricular ejection fraction (LVEF) was determined by scintigraphy in 111. Sixty-two patients (group 1) had LPs, 158 had normal SA-ECGs (group 2). Spontaneous normalization of SA-ECGs occurred in 20% of patients after 6 months, although the mean values of D, D40 and V40 did not change significantly and the reproducibility was very good for all the indexes during all the follow-up controls. Three patients had sudden death and three presented again with spontaneous, sustained ventricular tachycardia. Five of 62 (8%) group 1 patients had an arrhythmic event compared with one of 158 patients (0.6%) in group 2. The sensitivity of SA-ECGs as a predictor of arrhythmic events was 83% with a specificity of 73%. Patients with subsequent arrhythmic events had longer filtered QRS (133 +/- 19 vs 104 +/- 16 ms; P less than 0.001), longer duration of the low-amplitude signals (54 +/- 15 vs 33 +/- 14 ms; P less than 0.01), and lower voltages in the last 40 ms of the filtered QRS (11 +/- 3 vs 36 +/- 25 microV; P less than 0.02) and, moreover, higher peak CK values and lower LVEF than those without such events. In conclusion, SA-ECGs provide important prognostic information in identifying patients at risk of arrhythmic events after myocardial infarction although dynamic changes of LPs are observed during the first year after myocardial infarction.

Effects of propafenone on directly measured sinoatrial conduction time.

Electrophysiologic investigation of the effects of antiarrhythmic drugs on sinoatrial conduction time (SACT) is conditioned by the inadequacies of indirect methods employing premature or asynchronous atrial stimulation. Direct recording of sinus node electrogram (SNE) is unaffected by the limitations of the indirect methods and is particularly useful when the effect of a drug on SACT is to be studied. In the present study the effect of propafenone on SACT directly (D) measured from SNE in 12 patients (7 male and 5 female subjects, 61 +/- 10 years) with normal sinus node function (NSNF) was investigated. DSACT, sinus node cycle length (SCL) and corrected sinus node recovery time (CSNRT) were evaluated before and 20 min after i.v. administration of 1 mg/kg propafenone. The following results (mean +/- SD) were obtained: in control condition SCL was 854 +/- 143 ms; CSNRT 316 +/- 82 ms; DSACT 88 +/- 20 ms. After propafenone SCL was 849 +/- 119 ms; CSNRT 340 +/- 93 ms; DSACT 97 +/- 15 ms (p less than 0.05). DSACT ranged from 60 to 105 ms and from 60 to 120 ms, respectively, before and after propafenone. In conclusion, in patients with NSNF propafenone 1. does not affect sinus node automatism and 2. prolongs significantly DSACT, which, however, remains within the upper normal limit.

[Flecainide and anti-arrhythmia therapy]. / Flecainide e terapia antiaritmica.

Flecainide is a benzenacetamide synthesised about a decade ago and only recently introduced into the treatment of arrhythmias. Its electrophysiological properties place it in Class IC of the anti-arrhythmia drugs. Flecainide has proved useful in the treatment of supraventricular arrhythmias, atrial fibrillation (especially in patients with Wolff-Parkinson-White disease), in reciprocating supraventricular tachycardias and in focal atrial tachycardias. The drug is also extremely effective in ventricular ectopias with a success rate of over 90%. Flecainide is therefore destined to be widely used in the treatment of arrhythmias and is indicated for both supraventricular and ventricular forms, particularly those resistant to other treatment. In addition the biological availability and long half life of Flecainide make it suitable for even very prolonged treatment.

[Intra-sinus echo: demonstration using direct intracavitary recording of the sinus potential]. / Echo intrasinusal: démonstration par enregistrement direct du potentiel sinusal par voie endocavitaire.

The authors searched for intra-sinusal echos during electrophysiological investigation of 53 patients (41 men, 12 women, average age: 61 +/- 12 years). Cycles of sinus echos were recorded in 8 patients (15 per cent). The period during which sinus echos could be recorded was 125 ms (average 40.6 +/- 34 ms). Indirect assessment of sinus node function in patients with sinus echos was normal (corrected sinus node recovery time, estimated atrio-sino atrial conduction times using Narula's technique). A valid and reproducible direct recording of the sinus node potential was only possible in one patient. In this case the echo cycles were provoked by stimulation periods of between 440 and 320 ms (echo zone of 120 ms). All the echos obtained were preceded by a sinus node potential with a different duration and morphology to that observed during basal sinus cycles (respective sino-atrial conduction times 105 and 115 ms). In this patient we were also able to induce sinus echos after a single extrastimulus during the spontaneous rhythm. the echo zone was 130 ms and with a shorter coupling interval (310 ms) two successive sinus echos were recorded. The demonstration of intrasinusal echos by direct recording of the sinus node potential supports the experimental data of Allessie and Bonke on isolated right atrial tissues of the rabbit. Improvements in the technique of endocavitary direct recording of the sinus node potential in man should complete this data by showing the possibility of sinoatrial tachycardias due to reentry.

[Sinus node electric activity in prolonged atrial pauses in subjects with the sick sinus syndrome]. / Attivitá elettrica sinusale durante pause atriali "prolungate" in soggetti con malattia del nodo del seno.

Sinus node electrogram (SNE) was recorded in 15 patients with sick sinus syndrome (SSS) in which prolonged atrial pauses were observed. The aim of this study was clarify the physiopathological mechanisms underlying atrial pauses as well as to evaluate the sensitivity of sinoatrial conduction time (SACT) directly measured on SNE and of SACT estimated with the indirect Strauss method with respect to the detection of SSS. The following results were obtained: Sinus electrical activity was recorded during atrial pauses (greater than or equal to 2 basic sinus cycle length) in all the 9 patients in which the pauses spontaneously occurred and in the 2 patients in whom the pauses of 2860 and 3190 msec were induced by atrial pacing. In one of these latter two patients, moreover, a complete electrical desynchronization was observed. In the remaining 4 patients in whom, pauses (greater than or equal to 3 sec) were induced by carotid sinus massage of in 3 no sinus electrical activity was detected on SNE while in 1 advanced sinus node desynchronization was observed. Direct sinoatrial conduction time was abnormally prolonged in 6 patients with SSS and indirect sinoatrial conduction time in 9 patients.

Mexiletine action on the specialized tissues of the human heart.

Electrophysiological properties of mexiletine (3 mg/kg i.v.) were studied in fifteen patients with various degrees of abnormalities in the specialized conduction system. Sinus cycle length was decreased in all patients; sinus node recovery time was increased in all patients, but the increment was not statistically significant. Atrial and atrioventricular (AV) nodal refractoriness were not modified. The relative refractory period of the His-Purkinje system was reduced in patients with normal intraventricular conduction on the surface electrocardiogram; no changes were noted in five patients with intraventricular conduction delay. In two patients, in whom AV nodal refractory period curves showed antegrade dual AV nodal pathways, mexiletine increased refractoriness of the fast pathway. This report points out that the drug is effective against arrhythmias sustained by a reentry mechanism, not only in the ventricles, but also in the AV node.

[The sinus node electrogram in the evaluation of atrial pauses]. / L'elettrogramma del nodo del seno nella valutazione delle pause atriali.

The aim of this study was to establish the electrophysiological mechanism of atrial pauses, defined as a sudden lengthening of atrial cycle greater than or equal to 10% of its basal value. The sinus node electrogram (SNE) was recorded during electrophysiological study in 20 subjects. Satisfactory recordings of 64 pauses were obtained, 25 of which were spontaneous, 16 were induced by short periods of atrial pacing (AP) in normal subjects, whereas 23 atrial pauses were induced with the premature stimulation method. The basal sinus cycle and the one during the spontaneous pauses were measured from the upstroke slope on the SNE. The electrically induced pauses of the sinus cycle were measured from the artifact of the stimulus to the upstroke slope of the SNE of the first post-pacing beat. We have found that: 1-spontaneous atrial pauses correspond to a moderate slowing of the sinus cycle and to a depression of the sinoatrial conduction occasionally up to a second degree sinoatrial block. Only in subjects with sick sinus disease, the atrial pauses are induced by depression of the sinus automatism; 2-in normal subjects the AP results in a sinoatrial conduction delay; 3-the single extrastimulus regularly produces a moderate increase of the sinoatrial conduction time with variable but minimal effects on the sinus node automatism.

[Direct measurement of sinoatrial conduction time in man. Correlation with sinus cycle length]. / Valutazione diretta del tempo di conduzione senoatriale nell'uomo. Suoi rapporti con la lunghezza del ciclo sinusale.

Recent reports have shown that it is possible to record sinus node potential (SNP) using a transvenous electrode catheter technique in animals and in man. We applied similar techniques to record sinoatrial activity in 24 normal subjects and in 6 patients with sick sinus syndrome. We used bipolar recordings, with one interelectrode distance of 1 cm, low-pass filters of 0.1-50 Hz and high-amplification (up to 100 microV/cm). Validation of the source of the sinus node electrograms (SNE) was obtained by using ad hoc criteria. Like SNE recorded in animals, human SNE shows a smooth, low-frequency upstroke slope that begins before and merges into atrial activation. Sinus node potential is separated from preceding T wave by an isoelectric plateau. In 24 subjects with normal sinus node function, the directly recorded sinoatrial conduction time (D-SACT) was 82.9 +/- 17.9 msec. Correlation with the SACT estimated by Narula's method was excellent (r = 0,84). In 12 patients with sinus arrhythmia on SNE, SACTs were directly measured as were the associated P-P intervals. When SACT at each sinus cycle length (SCL) was plotted against SCL for all subjects grouped together, the average change of SAT per 100 msec change of SCL was 15 msec. In 6 patients with sick sinus syndrome, D-SACT was 150.4 +/- 67.4 msec. When SACT at each SCL was plotted against SCL, the average change of SACT per 100 msec change of SCL was 39 msec. In the same patients the SACT estimated by Narula's method was 129 +/- 17 msec.

[Activity of a new long-acting anti-arrhythmic drug on ventricular extrasystole. Study with Holter continuous electrocardiographic monitoring]. / Attività di un nuovo antiaritmico "long-acting" sull'extrasistolia ventricolare. Studio con il monitoraggio elettrocardiografico continuo di Holter.

Therapeutic effectiveness of a new long-acting antiarrhythmic preparation was evaluated in 31 patients with sustained premature ventricular beats. After an observation period, a 24 hours Holter monitoring was performed. A group (21 patients) was treated with dihydrochinidine 250 mg twice a day; another group (11 patients) was treated with 500 mg twice a day. In the latter group was determined basal chinidinemia on the first and third day. A 24 hours Holter monitoring was repeated on the fourth day. In the first group we reached a 77.4% reduction of the arrhythmia: not enough, however, to agree with established statements. We reached a larger reduction (84.7%) with higher doses (1000 mg daily). This drug was well tolerated in both groups.

Baroreceptor control of atrioventricular conduction in man.

Although human baroreflexes are known to exert a powerful physiological control on heart rate, little information exists on the physiological control they exert on the atrioventricular conduction system. In 11 normotensive subjects with normal atrioventricular conduction, we altered baroreceptor activity by injection of pressor and depressor drugs (phenylephrine and trinitroglycerin) and recorded mean arterial pressure (MAP, catheter measurements), R-R interval, and pre-His and post-His intervals (A-H and H-V, His bundle recording). With the subjects in sinus rhythm, increasing MAP by 21+/- 1 mm Hg caused a marked lengthening (250 +/- 28 msec), and decreasing MAP by 17 +/- 2 mm Hg a marked shortening (142 +/- 16 msec) of the R-R interval. There was little change in the A-H interval and no change at all in the H-V interval. However, when the R-R interval was kept constant in these subjects by atrial pacing, a similar increase and decrease in MAP caused, respectively, a marked lengthening (49 +/- 6 msec) and shortening (19 +/- 3 msec) of the A-H interval, although the H-V interval remained unaffected. Thus physiological ranges of baroreceptor activation have a marked influence on the atrioventricular node but apparently not on the ventricular portion of the atrioventricular conduction system. This influence is unmasked when pacing prevents the baroreceptor influence on the sinoatrial node.

[A study of atrio-ventricular conduction in subjects with the Lown-Ganong-Levine syndrome (author's transl)]. / Studio della conduzione atrio-ventricolare in soggetti con sindrome di Lown-Ganong-Levine

Eight subjects with the Lown-Ganong-Levine syndrome were studied by means of His bundle recordings during sinus rhythm and during atrial pacing. During sinus rhythm in all cases, the A-H interval was lesser than the mean value observed in 10 control subjects. Atrial pacing at rates up to 190/min produced three types of responses. Four patients showed an initial increment in A-H interval, followed by a plateau response at higher rates. One patient showed an initial increment and a plateau response in A-H interval at low and intermediate rates, followed by a sudden and conspicuous increment at higher rates, indicating conduction of impulse through the A-V node, due to refractoriness of the by-pass tract. Three patients showed a progressive increase in A-H interval similar to that of normal subjects but to a lesser degree. The possible mechanisms for the different types of response are discussed.