[Limits of cardiac functional adaptation in "top level" resistance athletes]. / Limiti dell'adattamento funzionale cardiaco in atleti "top level" di resistenza.

BACKGROUND: Sports activity, particularly when performed at high level, provokes cardiovascular adjustments depending on the type of sport and on the level of the load. METHODS: We evaluated 15 athletes from the Italian national team during a non-agonistic period of cross country skiing, with non-invasive tests including exercise test, color Doppler echocardiography, Holter monitoring, physical examination and standard rest electrocardiogram. RESULTS: Physical examination, rest electrocardiogram, exercise testing and echocardiography were all within the range of the expected values for this type of subjects. Holter monitoring recorded during the periods of agonistic activity revealed significant hypokinetic arrhythmias such as severe bradycardia, pauses, I and II degree atrioventricular blocks, and complete atrioventricular block in 2 cases; these features were not observed on Holter monitoring recorded during the non-agonistic period. CONCLUSIONS: The perfect health status of subjects and their racing results may bring about physiological functional adjustments, but these observations suggest the need for a follow-up to evaluate possible pathologic outcomes.

[Thrombolysis & arrhythmias]. / Trombolisi e aritmie.

In this study, we assessed one particular aspect of the arrhythmogenic phenomena that occur during reperfusion secondary to thrombolysis, that is the therein involved metabolic mechanisms. The employed experimental model (isolated Langendorff-perfused rat heart) allowed us to distinguish which factor involved during ischemia, low coronary flow or low oxygen tension, is primarily involved during arrhythmogenesis. This was made possible by comparing two settings characterized by the same oxygen supply, but with different coronary flows and PO2 values, i.e., ischemia and hypoxemia. As expected, the contractile dysfunction was higher during reoxygenation at the end of hypoxemia than during reperfusion at the end of ischemia (p < 0.05). However, the incidence of arrhythmias was similar in both cases. Therefore, whereas the contractile dysfunction appears to be more sensitive to coronary flow, the incidence of arrhythmias appears to be more sensitive to the total oxygen supply to the heart. This implies that the mechanisms underlying the development of contractile dysfunction and arrhythmogenesis follow different paths.

Effects of oral pirenzepine on heart rate variability and baroreceptor reflex sensitivity after acute myocardial infarction.

OBJECTIVES: Our aims were 1) to assess whether oral pirenzepine could increase indexes of cardiac vagal activity in postinfarction patients, and 2) to compare the effects of this agent with those of transdermal scopolamine. BACKGROUND: Depression of vagal tone and reflexes predicts a poor arrhythmic outcome after myocardial infarction. Interventions for shifting the sympathovagal balance toward vagal dominance are now of increased clinical interest. Intravenous pirenzepine increases RR interval variability in normal volunteers, a finding that could have therapeutic implications if confirmed in postinfarction patients after oral administration of the drug. METHODS: In a single-blind placebo-controlled crossover trial, short-term RR interval variability and baroreceptor reflex sensitivity were evaluated in 20 patients an average of 19 +/- 6 days after infarction. Analysis was performed during control conditions and during administration of placebo, oral pirenzepine and transdermal scopolamine. RESULTS: Compared with placebo, at a dose of 25 mg twice daily, pirenzepine significantly increased all time and frequency domain measures of RR interval variability and augmented baroreceptor reflex sensitivity by 60% (mean +/- 1 SD 10.4 +/- 5.9 vs. 6.5 +/- 3.2 ms/mm Hg, p = 0.0007). Pirenzepine and scopolamine showed a similar vagomimetic effect, but the overall incidence of adverse effects was lower with pirenzepine (1 [5%] of 20 vs. 10 [50%] of 20). CONCLUSIONS: In patients with a recent myocardial infarction, oral pirenzepine proved equal to transdermal scopolamine in significantly increasing indexes of cardiac vagal activity. These data suggest that oral pirenzepine may have a therapeutic potential for preventing malignant ventricular arrhythmias after infarction.

Effect of thrombolysis on heart rate variability and life-threatening ventricular arrhythmias in survivors of acute myocardial infarction.

OBJECTIVES: The aim of the present study was to determine the influence of early thrombolysis on ventricular tachyarrhythmias (clinical and inducible) and heart rate variability in survivors of myocardial infarction at high risk for life-threatening ventricular arrhythmias. BACKGROUND: A greater electrical heart stability may be important in improving survival in patients treated with thrombolysis. Few data are available about the influence of fibrinolysis on postinfarction arrhythmic events and other prognostic variables, such as inducible ventricular tachycardia and heart rate variability. METHODS: The study group comprised 51 consecutive patients who underwent electrophysiologic study within 30 days of infarction, owing to the presence of two or more of the following criteria: left ventricular ejection fraction < 40%, late potentials and repetitive ventricular ectopic beats. Thirty patients underwent thrombolysis within 6 h of the onset of symptoms (Group A), and 21 received conventional treatment (Group B). Inducibility of sustained monomorphic ventricular tachycardia was tested in both groups, and the standard deviation of all normal RR intervals during 24-h Holter monitoring was calculated. All patients were prospectively evaluated for occurrence of arrhythmic events. RESULTS: The two groups were similar with regard to left ventricular ejection fraction (mean +/- 1 SD 38 +/- 6% [Group A] vs. 36 +/- 8% [Group B]). Ventricular tachycardia was induced in 6 (20%) of 30 Group A patients versus 14 (67%) of 21 Group B patients (p = 0.002). The standard deviation of normal RR intervals was higher in Group A than in Group B (113 +/- 36 vs. 90 +/- 39 ms, p = 0.05). In patients with anterior infarction, the standard deviation of normal RR intervals was higher in 19 patients with thrombolysis than in 16 patients with conventional treatment (118 +/- 41 vs. 74 +/- 24 ms, p = 0.0002). During a mean follow-up period of 23 +/- 11 months, 4 (13%) of 30 Group A patients had an arrhythmic event versus 9 (43%) of 21 Group B patients (p = 0.04). CONCLUSIONS: After myocardial infarction, in high risk patients, thrombolysis significantly reduced the occurrence of arrhythmic events independently of left ventricular function. This effect may be related to both an improvement in electrical heart stability, as elucidated by electrophysiologic study, and a favorable action on the cardiac sympathovagal balance.

Influence of transdermal scopolamine on cardiac sympathovagal interaction after acute myocardial infarction.

In 41 survivors of acute myocardial infarction (AMI) a prospective study was performed in 2 sequential phases. In phase 1, the role of baroreflex sensitivity and heart rate variability as predictors of inducible and spontaneous sustained ventricular tachyarrhythmias was evaluated. In phase 2, the effects of transdermal scopolamine on baroreflex sensitivity, spectral and nonspectral measures of heart rate variability were investigated. At a mean follow-up of 10 +/- 3 months after AMI, 5 of 41 patients (12%) developed a late arrhythmic event. Of these, all (100%) had inducibility of sustained monomorphic ventricular tachycardia at programmed stimulation compared with 3 of 36 patients (8%) without events (p < 0.0001). At multivariate analysis, baroreflex sensitivity had the strongest relation to both inducibility of sustained monomorphic ventricular tachycardia (p < 0.0001) and occurrence of arrhythmic events (p < 0.0001). Of 41 patients, 28 (68%) consented to undergo phase 2 of the investigation. Baroreflex sensitivity significantly (p < 0.00001) increased after transdermal scopolamine as well as heart rate variability indexes. Of these, the mean of SDs of normal RR intervals for 5-minute segments (p < 0.0001) and the total power (p < 0.0001) had the most significant improvement after scopolamine. The present investigation confirms that assessment of autonomic function is an essential part of arrhythmic risk evaluation after AMI. Transdermal scopolamine, administered to survivors of a recent AMI, reverses the autonomic indexes that independently predict arrhythmic event occurrence. On the basis of these data, transdermal scopolamine could be a potential useful tool in the prophylaxis of life-threatening ventricular arrhythmias after AMI.

Prediction of late arrhythmic events after acute myocardial infarction from combined use of noninvasive prognostic variables and inducibility of sustained monomorphic ventricular tachycardia.

A combined use of noninvasive techniques and electrophysiologic study in the prediction of arrhythmic events was prospectively evaluated in 303 surviving patients of acute myocardial infarction (AMI). The most powerful combination of noninvasive prognostic variables in identifying patients suitable for invasive strategies was also assessed. Patients who had > or = 2 variables among left ventricular ejection fraction < 0.4, ventricular late potentials and repetitive ventricular premature complexes (VPCs) were considered eligible for programmed ventricular stimulation. After 15 +/- 7 months of follow-up, 19 patients (6%) had an arrhythmic event. Left ventricular dyskinesia (p < 0.00001) and ejection fraction < 0.4 (p < 0.000001), late potentials (p < 0.001), filtered QRS duration > or = 106 ms (p < 0.00001), VPCs/hour > 6 (p < 0.05), paired VPCs (p < 0.01), > or = 2 runs of unsustained ventricular tachycardia (VT) per monitoring (p < 0.001), heart rate variability index < or = 29 (p < 0.00001) and mean RR interval < or = 750 ms (p < 0.01) were found to be significant univariate predictors of events. At multivariate analysis, only low left ventricular ejection fraction, prolonged filtered QRS duration, reduced heart rate variability index and detection of > or = 2 runs of unsustained VT per monitoring had an independent relation to late arrhythmic events. Of 67 eligible patients, 47 (70%) consented to undergo programmed stimulation. A positive electrophysiologic study was found to be the strongest independent predictor of events among patients preselected by noninvasive techniques. With a good sensitivity (81%), a combined use of noninvasive tests and electrophysiologic study selected a group of post-AMI patients at sufficiently high risk (event rate 65%) to be considered candidates for interventional therapy. The combination of > or = 2 variables among left ventricular ejection fraction < 0.4, filtered QRS duration > or = 106 ms and > or = 2 runs of unsustained VT was superior to the other ones in identifying high-risk subjects (positive and negative predictive values for arrhythmic events of 44 and 99%, respectively). On the basis of the data, this scheme appears to be the most appropriate for selecting patients suitable for electrophysiologic testing and invasive strategies after AMI.

Late arrhythmic events and patency of the infarct-related coronary artery in survivors of acute myocardial infarction.

In the present study we evaluated the influence of intravenous thrombolysis and patency of the infarct-related coronary artery on both markers of ventricular electrical instability and incidence of late arrhythmic events after acute myocardial infarction (AMI). Ninety one patients surviving a first AMI who consecutively performed coronary angiography were enrolled in the present study; 44 patients (48%) received thrombolysis, 47 patients (52%) were treated conventionally. Of 91 patients, 90 (99%) had signal-averaged electrocardiogram (SAECG), and 40 (44%) programmed ventricular stimulation. No significant difference was observed between thrombolytic-treated and control group in late potential rate, SAECG determinants and ventricular arrhythmia inducibility. Of 91 patients, 40 (44%) had occlusion of the infarct-related artery: of these, 15 (37%) had late potentials compared with 5 of 51 patients (9%) with a patent artery (p < 0.01). Mean left ventricular ejection fraction was not significantly different between the two groups (0.50 +/- 0.15 vs 0.55 +/- 0.12; p = NS). No significant difference was present between the two groups of patients with regard to inducibility of sustained ventricular tachyarrhythmias, however an odds ratio of 3.5 was observed in the group with a closed vessel.(ABSTRACT TRUNCATED AT 250 WORDS)

[The electrocardiographic anomalies and 2D-echocardiographic findings during the recovery phase of the stress test in the postinfarct patient]. / Anomalie elettrocardiografische e reperti ecocardiografici 2D durante la fase di recupero del test ergometrico nel post-infarto.

BACKGROUND: The appearance or the increase of repolarization abnormalities in the EKG during post exercise (ET) recovery phase (R) is considered a marker of ischemia. METHODS: In order to evaluate the real meaning of these changes we compared the EKG data with eventual modifications of left ventricular kinesis analyzed by 2D-ECHO. 10 male patients with previous myocardial infarction, mean age 50 +/- 4.8 y, underwent exercise testing on a treadmill (Bruce's protocol) and continuous 2D-ECHO observation from the end of exercise along the whole R. Patients were divided in two groups: Group A (6 patients) and Group B (4 patients), all free of symptoms. RESULTS: Group A showed ischemic EKG markers during exercise which increased during R; Group B showed ischemic EKG markers only during R. The 2D-ECHO showed in Group A an impairment of left ventricular kinesis at peak exercise without increase or extension during R (WMSI at rest 1.32; peak ET 1.60; R 1.60); in Group B the kinetic alterations appeared only in R (WMSI at rest 1.33, peak ET 1.42; R 1.80), strictly related to EKG markers. CONCLUSIONS: The data suggest : 1) that the increase of EKG abnormalities already present during exercise do not seem to imply more severe ischemia; 2) that EKG changes appearing during R are markers of ischemia which occur in the R.

Regional flow responses to exercise.

Both neural and humoral systems participate in the control of blood flow to various organs. Exercise places the greatest demands on the circulation. At rest, in humans, skeletal muscle receives somewhere between 15% and 20% of cardiac output, while during maximal exercise, this percentage reaches a value of 80% to 90%. The active human muscles have a high-flow capacity that exceeds the capacity of the heart to pump blood. Measurements in single human muscle have indicated that blood flow may be inhomogenous, that is, probably depending on variations of the vasomotor tone of the muscle mediated by humoral and neural factors. Exercise raises cardiac output and coronary blood flow, which rise linearly with increases in heart rate. In normal young men, coronary blood flow averages 280 ml/min/100 g of the left ventricle and reaches as high as 390 ml/min during moderately severe exercise, requiring about 85% of maximal heart rate. In nonexercising organs, the blood flow decreases at about 20% to 40% of the resting values, being the net result of competing vasoconstrictor and vasodilator drives.

Influence of thrombolysis on signal-averaged electrocardiogram and late arrhythmic events after acute myocardial infarction.

The influence of intravenous thrombolysis on both prevalence of ventricular late potentials and incidence of late arrhythmic events was evaluated in 174 consecutive patients surviving a first acute myocardial infarction; 106 patients (61%) received thrombolysis (group A) and 68 (34%) had conventional therapy (group B). In group A, 18 patients (17%) had late potentials compared with 23 (34%) in group B (p less than 0.05); mean left ventricular ejection fraction was not different (0.50 +/- 0.09 vs 0.50 +/- 0.10; p = not significant [NS]). Of 63 patients who underwent coronary arteriography because of postinfarction ischemia, 28 (44%) had a closed infarct-related artery; of these, 11 (39%) had late potentials compared with 3 of 35 (9%) with a patent artery (p less than 0.01). Mean left ventricular ejection fraction was not significantly different between the 2 groups (0.49 +/- 0.09 vs 0.53 +/- 0.09; p = NS). At a mean follow-up of 14 +/- 8 months, 8 of 161 patients (5%) had a late arrhythmic event; 6 of 8 (75%) with and 28 of 153 (18%) without events had late potentials (p less than 0.001). In group A, 4 of 99 patients (4%) had events compared with 4 of 62 (6%) in group B (p = NS, relative risk 1.6). Of 24 patients with anterior wall AMI and left ventricular dyskinesia, 6 events occurred. In this group of patients, a higher rate of events was observed (25%); 3 of 16 (19%) treated with thrombolysis had an event compared with 3 of 8 (37%) treated conventionally (p = NS, relative risk 2.6).(ABSTRACT TRUNCATED AT 250 WORDS)

Functional evaluation 10 days and 3 weeks after acute myocardial infarction: comparative significance and prognostic value.

Early functional evaluation after non-complicated acute myocardial infarction (AMI) is widely recommended because of its prognostic value in the short term. In fact it seems to have a prognostic value within 15-20 days of the AMI, but in this period the patient is particularly controlled and is often still hospitalized. To evaluate the real significance of an early functional evaluation within 10 days of the AMI (mean 8.6 days +/- 1.2) as compared to an identical functional evaluation performed at 3 weeks after AMI (mean 20.16 days +/- 5.38) 25 patients with uncomplicated myocardial infarction were studied. Significant statistical differences were found between the first (ET1) and second (ET2) functional evaluations: they concern the maximal heart rate reached (P less than 0.001), the maximal pressure-rate product (P less than 0.05), the percentage increment of heart rate (P less than 0.01) and the total work performed (P less than 0.001). Agreement between ET1 and ET2 was found in 19 cases; 12 patients showed markers of ischaemia both at ET1 and ET2, while seven were free from ischaemia at both times. In six cases a disagreement between ET1 and ET2 was found: in particular, three cases had ischaemic ET1 and nonischaemic ET2; the reverse was seen in the other three. During follow-up (mean 215.4 days +/- 85.5), the total number of new events (reinfarctions, angina or surgery) among the 25 patients was eight; none occurred within the first 30 days after the AMI.(ABSTRACT TRUNCATED AT 250 WORDS)

Gas exchange and metabolic transients in heart transplant recipients.

In human heart transplant recipients (HTR) an impairment of the cardiac function was expected to reduce peak oxygen consumption and the kinetics of the adjustment of respiratory gas exchange at the onset of rectangular work loads. In nine patients (males, 23-59 yr) 1 to 8 months after cardiac transplantation average peak VO2 (VO2p) was 1.1 L.min-1 +/- 0.3 (SD), i.e. 45% of that of the controls, the corresponding VCO2p value being 1.4 L.min-1 +/- 0.3 (SD). Mean VEp was 62.9 L.min-1 +/- 20.3 (SD), mean HRp was 136 beats.min-1 +/- 11 (SD), i.e. 45 beats.min-1 higher than preexercise values. Mean [Lab]p was 7.7 mM +/- 1.7 (SD), indicating that at the heaviest load the HTR were performing work at or above their maximum aerobic power. During the initial 60-90 sec of the transition from rest to graded rectangular exercise HR did not change from the resting value, increasing thereafter almost linearly with time. The half time (t1/2) of the VE on-response was 112 sec +/- 30 (SD) (controls values: 59 sec +/- 16), that of the VCO2 on- was 95 sec +/- 18 (SD) (58 sec +/- 11), and that of the VO2 on- was 78 sec +/- 24 (SD) (38 sec +/- 6). In spite of the slow kinetics of the VO2 on- response, no massive accumulation of lactate was found in the early phase of exercise. The limitation of the peak exercise in HTR appears to be imposed by a reduced maximal cardiac performance. The slow readjustment of the latter, as expected from the sluggish heart rate response, however, does not impair substantially the work load transients nor reduce the anaerobic threshold.

The effects on exercise tolerance of a new transdermal therapeutic system containing nitroglycerine, in patients with stable angina pectoris.

In two randomized, double blind, placebo-controlled, within patient, studies, the effects of 4 doses of a new transdermal therapeutic system containing nitroglycerin (TTS-NTG) were studied in a total of 15 patients with stable exercise-induced angina pectoris. A single 24-hour application of TTS-NTG 10 cm2, TTS-NTG 20 cm2 and TTS placebo (1st study: 6 patients) and of TTS-NTG 40 cm2, TTS-NTG 80 cm2 and TTS placebo (2nd study: 9 patients) was applied on 3 different days, and a symptom-limited cycloergometric exercise test was performed 3, 12 (only in the 2nd study) and 24 hours after the application of each treatment. In comparison with placebo, the doses tested in the 1st study induced, at the 3rd hour post-dosing, a decrease in standing systolic blood pressure and an improvement in exercise tolerance which, however, were not statistically significant while the effects at the 24th hour were similar to those of placebo. In the 2nd study, in comparison with placebo, both TTS-NTG doses induced, 3 hours post-dosing, a significant decrease in both lying and standing systolic (P less than 0.01) blood pressure at rest, and a significant (P less than 0.01) improvement in exercise tolerance throughout the 24 hours of application. It is concluded that, in patients with exercise-induced angina pectoris due to coronary artery disease, a single application of TTS-NTG 40 cm2 or 80 cm2 results in a 24-hour increase in exercise tolerance.

Arrhythmias in sport.

The presence of arrhythmias in athletes is not infrequent. Bradyarrhythmias are more frequent in sportsmen than in the general population. This fact is often due to a 'relative vagal hypertony', owing to a training effect. Tachyarrhythmias are also present in sportsmen in almost the same percentage as in sedentary people. Any of several types of tachyarrhythmia can be seen. Abnormal heart conditions can be demonstrated in many athletes with symptomatic tachyarrhythmias. These arrhythmias frequently occur during exercise and in the early phase of recovery. An organic disorder was present in 26 of 32 athletes who were investigated with an exercise test, Holter monitoring and an electrophysiological test because of the presence of tachyarrhythmias. In six cases we were not able to find any cardiac disease. In 75% of these cases the arrhythmias had a strong relation with exercise. During follow-up (1-5 years; mean 2.88 years) some arrhythmias recurred in spite of medical treatment, in 12 of the 32 subjects, while the other 20 were free of symptoms and arrhythmias. In our opinion it is not possible to ascribe to sport, per se, the direct responsibility for these arrhythmias.

[Assessment of coronary stenosis by myocardial scintigraphy with thallium-201 after dipyridamol infusion]. / Evidenziazione di stenosi coronariche mediante scintigrafia miocardica con tallio-201 dopo infusione di dipiridamolo.

After a 4 minute i.v. dipyridamole infusion (0.14 mg/Kg/min) serial Thallium-201 scans were obtained in 45 patients, without myocardial necrosis, undergoing coronarography. Twelve patients had effort angina, 6 rest angina, 14 effort associated with rest angina, 13 had atypical chest pain. Thirty-two patients had a 50% or greater stenosis of 1 or more coronary artery (8 had three vessels disease, 7 two vessels, 17 one vessel); 13 patients had no significant coronary stenosis ("control group"). The test induced electrocardiographic signs of ischemia in 18 patients, all with significant coronary stenosis, 15 of them experienced angina too. Sensitivity of Thallium-201 for detecting coronary artery stenosis was 94% (30 of 32) and specificity was 85% (11 of 13). In the group of the 17 patients with one vessel disease we obtained a sensitivity and specificity of 100% (17 of 17). We conclude that Thallium-201 myocardial imaging after pharmacologic vasodilatation with dipyridamole is a highly sensitive and specific test for detecting coronary artery stenoses without necessary overt ischemia. In fact dipyridamole, as consequence of its important coronary vasodilatation, produces differences in myocardial perfusion with relative perfusion defects detectable with Thallium-201 imaging.

[Myocardial revascularization in patients with severe ventricular impairment. Short-term follow-up]. / L'intervento di rivascolarizzazione miocardica nei pazienti con severa compromissione ventricolare. Follow-up a breve termine.

To assess the influence of aorto-coronary bypass grafting on surgical risk and short-term survival of patients with marked impairment of left ventricular (LV) function, we evaluated--among 435 patients who underwent coronary bypass surgery between January 1981 and December 1982--22 cases with: LV ejection fraction (EF) less than or equal to 0.35 (mean 0.27 +/- 0.06), LV end-diastolic pressure greater than or equal to 15 mmHg (mean 19.9 +/- 6.9 mmHg.), presence of three or more dysfunctional (hypokinetic or akinetic) segments on biplane LV angiography, three vessels disease in 90.1%. All patients but two had angina refractory to medical therapy. Operative mortality rate was 4.5%. Perioperative non fatal infarction rate was 9.1%. There were three late deaths. Mean duration of follow-up was 10.5 +/- 8.3 months with a survival of 81.8%. In the survivors we observed: dramatic improvement in respect to angina (94.5% are asymptomatic) and quality of life; exercise performance improvement (75% of patients have a functional impairment less than or equal to 30% at treadmill test); significant improvement in global and segmental LV function (mean echocardiographic EF 0.37 +/- 0.10, p less than 0.001). Because of relative low surgical risk and encouraging short-term results, aortocoronary bypass grafting can be performed even in patients with important LV disfunction, when associated with severe angina.

[Drug therapy combinations in angina pectoris]. / Associations médicamenteuses dans l'angine de poitrine.

The critical level of myocardial oxygen consumption at which anginal pain will occur can be assessed in patients with coronary artery disease. We studied the results of exercise ECG in patients with effort angina, administered placebo, nitrate derivatives, betablockers, and calcium inhibitors, alone and in different associations. Nitrate derivatives and calcium inhibitors appeared to be more effective than betablockers. The study demonstrated the utility of the association of betablockers with other drugs with a more effective anti-anginal action but without the hypotensive or antiarrhythmic effects of betablockers which are often very desirable in the treatment of coronary artery disease.