[SFAAT: the study of nonrheumatic chronic atrial fibrillation in the Trieste area. Results of an enrollment study]. / SFAAT: studio della fibrillazione atriale cronica non reumatica nell'area triestina. Risultati dell'arruolamento.

BACKGROUND: Chronic atrial fibrillation unassociated with rheumatic valvular heart disease (NRAF) considerably increases the risk of thromboembolism. Recent studies have provided new evidence concerning the risk-benefit ratio of anticoagulant therapies in patients with AF. OBJECTIVE: To evaluate the incidence of primary end points (ischemic stroke, systemic embolism, bleeding complications to oral anticoagulant or antiplatelet therapy) and secondary end points (death, TIA) in patients with NRAF. METHODS AND RESULTS: Between November 1992 and June 1993, 694 patients with chronic NRAF were enrolled in the Trieste Area Study on Nonrheumatic Atrial Fibrillation (TASAF), an ongoing prospective community study with a follow-up period of 2 years. The preliminary results of the enrolled study population show: an elevated mean age (71 +/- 9 years), the prevalence of males (383/694), high prevalence of overt or previous heart failure (23%), of mitral regurgitation confirmed at echocardiography (30%) and of previous myocardial infarction (11%). Many of the enrolled patients had a history of hypertension (58%). With regard to the etiology of the underlying heart disease, the following should be emphasized: a high incidence of cardiac hypertrophy (with or without history of hypertension) (28%) and of degenerative cardiopathy (20%); unclassifiable cardiopathy (14%); and lone AF (13%). Echocardiographic findings: left ventricular dysfunction (17%); mitral annular calcification (27%); and good mean left ventricular function (EF 0.50 +/- 0.15). Retrospectively there were 96 clinically documented embolic events in 78 subjects while in 34 patients there were 38 episodes suspected for embolism or TIA. Nine patients suffered 1 recurrence of embolism; three patients suffered 2 recurrences; one patient had 3 recurrences; and 4 patients had one suspected recurrence of TIA. In 35 cases the embolic events clustered around the time of the onset of the arrhythmia. In the other 99 subjects the embolic complication appeared after the onset of AF: range 1-266 months. The group of patients with true embolic events in comparison with patients without embolism or with suspected embolism or TIA had same variables predictive of thromboembolic complications: arrhythmia duration (p = 0.09) and previous myocardial infarction (p = 0.03); in contrast mitral annular calcification (p = 0.06), history of hypertension (p = 0.09) and cardiac hypertrophy (with or without hypertension) (p = 0.07) demonstrated only a slight trend of statistical significance. Comparing the clinical characteristics and echocardiographic findings of patients without embolism with those of patients with tru embolism, or suspected embolism, or TIA the variables predictive of thromboembolic events were: arrhythmia duration (p = 0.007), history of hypertension (p = 0.01), cardiac hypertrophy (with or without hypertension (p = 0.02) and mitral annular calcification (p = 0.01), at the same time, age showed only a trend of statistical significance (p = 0.06). Among the 616 patients without a history of embolism only 3% were treated with oral anticoagulant agents and 28% with antiplatelet therapy, while among the 78 subjects with documented embolism only 28% were receiving anticoagulant therapy and 58% were receiving antiplatelet agents. CONCLUSIONS: NRAF is an important risk factor for thromboembolism. Some clinical characteristics and echocardiographic findings increase the risk. Physicians still hesitate to use oral anticoagulants and antiplatelet agents in their patients for the prevention of embolic complications.

[Unusual electrocardiographic changes on exercise testing in patients with angina pectoris]. / Aspetti inusuali dell'elettrocardiogramma da sforzo in pazienti con angina pectoris.

We describe three patients with angina pectoris and uncommon electrocardiographic aspects during exercise test. These cases demonstrate the wide variability of the electrocardiographic changes and symptoms during exercise test and may by considered an example of myocardial response to spasm-related ischemia.

[Dynamic electrocardiogram in chronic atrial fibrillation treated with digitalis]. / L'elettrocardiogramma dinamico nella fibrillazione atriale cronica trattata con digitale.

To assess heart rate variability in chronic atrial fibrillation, 60 patients (20 men, 40 women: mean age 63 +/- 8 years: NYHA 2.0 +/- 0.5) with various cardiac conditions were investigated with 24-hour Holter monitoring during daily life. Twenty-five healthy subjects (5 men, 20 women: mean age 55 +/- 9) were considered as the control group. All patients had "controlled" heart rate (50-90 bpm) on basal ECG, normal hematological and thyroid hormone values, and took digoxin alone (mean dosage 0.22 +/- 0.05 mg). Mean digoxin plasma levels were 0.88 +/- 0.48 ng/ml. Maximum, minimum and average heart rate were quite good during the night but too high during the daytime and far higher than those observed in healthy subjects. In fact, up to 82% of patients (at 9 a.m.) had a maximum heart rate higher than 115 bpm. Pauses between 2.0 and 3.0 sec occurred in 40 out of 60 patients (66%). No patients had pauses longer than 4.0 sec. In our experience, patients in chronic atrial fibrillation "controlled" with digoxin alone showed a daytime heart rate which was often too high. We suggest 24-hour Holter monitoring to detect subgroups that may be treated successfully with digoxin associated with calcium-antagonists or beta-blockers.

Individual responses to transdermal nitrates after chronic administration in angina pectoris.

The aim of this study was to investigate whether, and to which extent, sustained treatment with transdermal nitroglycerin plasters may lead to the development of tolerance in patients with effort-induced angina pectoris. Ten patients, all men, mean age 62.7 years, took part in a double-blind, cross-over, acute study, comparing the transdermal therapeutic system of nitroglycerin 10 mg/24 hours with placebo. Patients were then treated for 1 month with the active drug in single-blind condition, and finally they took part in a further acute study identical to the first. Cycloergometric exercise tests were carried out 4 hours after dosing. In comparison with placebo, the active drug significantly (P less than 0.01) increased ischaemic threshold (ST depression = 1 mm) after both acute (from 299 +- 92 to 413 +- 120 sec) and chronic treatment (416 +- 107 sec). The same results were obtained for exercise duration to peak exercise (acute study: from 336 +- 65 to 482 +- 90 sec; chronic treatment: 466 +- 118 sec). The final acute study confirmed the stability of angina, showing that the improvement in exercise tolerance after chronic treatment was entirely due to the pharmacological effect of the drug. In terms of single patient response to the active treatment, 7 of the 10 patients showed an improvement in exercise tolerance after both acute and chronic treatment, while in 3 patients no antianginal effect was observed. These results suggest that nitrate tolerance cannot be considered an inevitable finding in patients chronically treated with transdermal patches.

Acute effects of felodipine in exertional angina pectoris.

To investigate the antianginal efficacy, duration of action and tolerability of 2 doses of the new calcium antagonist felodipine, 15 patients (14 men and 1 woman, mean age 62 years) with stable exertional angina pectoris and angiographically demonstrated coronary artery disease were randomly given felodipine, 5 and 10 mg, and placebo on 3 different days. A bicycle ergometer exercise test was performed 3 and 10 hours after dosing. In comparison with placebo, felodipine 5 and 10 mg significantly increased resting heart rate and decreased resting systolic and diastolic blood pressure 3 hours after administration (p less than 0.001). Ten hours after administration, only supine systolic blood pressure was still significantly lower (p less than 0.001). Anginal (time to mild chest pain) and ischemic (time to 1 mm ST depression) thresholds, as well as duration of exercise and total work at peak exercise, were higher in comparison with placebo at 3 and 10 hours (p less than 0.001). In comparison with the lower dose, 10 mg felodipine induced a decrease in supine (p less than 0.05) and sitting (p less than 0.01) systolic blood pressure at rest and an increase in total work to anginal threshold (p less than 0.01), as well as in total work and duration of exercise at peak exercise (p less than 0.05). These results suggest that a single administration of felodipine, 5 and 10 mg, may improve exercise capacity over a 10-hour period in patients with stable exercise-induced angina due to atherosclerotic heart disease.

Exercise-induced intermittent angina and ST-segment elevation in Prinzmetal's angina.

A patient with primary angina showed intermittent ST elevation (with and without chest pain), during two exercise tests performed on consecutive days; the same ST changes were also seen during the recovery phase. The electrocardiographic changes recorded in this patient may be considered an example of myocardial response to spasm-related ischemia.

Mechanism of action and efficacy of verapamil and beta-blockers in exercise-induced ventricular tachycardia.

To determine the antiarrhythmic efficacy of beta-blockers (beta-B) and verapamil (V) in exercise-induced ventricular tachycardia (Ex-VT), nine patients with reproducible Ex-VT (in two consecutive exercise tests) were studied by means of electrophysiologic study (EPS) in basal conditions and serial exercise testing after beta-B (metoprolol 25 mg tid to 100 mg qid; oxprenolol 40 mg tid) and/or V (80-160 mg tid). Ejection fraction was normal in four cases and depressed in five. Of these nine patients, four developed Ex-VT during chronic amiodarone treatment, which was continued. During EPS, VT was induced at a critical atrial pacing rate in one case, and with the extrastimulus technique in four. Ventricular tachycardia was not inducible with either technique in four patients. Five of the six patients on beta-B and none of the seven on V developed Ex-VT, although they achieved the same or higher work-loads as compared to the basal exercise tests. In the case with rate-dependent VT, beta-B and V prevented VT at work-loads, sinus rates and double products significantly higher than those obtained in basal conditions. In the others, maximal heart rate and double product were lower on beta-B and showed a wide variability on V. V and beta-B appeared to be highly effective in preventing Ex-VT, in patients with normal heart as well as in those with greatly depressed ejection fraction. Both of the drugs appeared to suppress re-entry or triggered activity in the patient with rate-dependent Ex-VT.(ABSTRACT TRUNCATED AT 250 WORDS)

[Natural history of patients with isolated atrial fibrillation]. / La storia naturale dei pazienti con fibrillazione atriale isolata.

Sixty three patients (pts) (aged less than or equal to 50 years) with a history of "lone" atrial fibrillation (AF) and normal heart size at radiological examination were followed-up for a mean period of 95 months (range 1-360). The arrhythmia remained paroxysmal in 43 pts, became chronic in 13, while in 7 could not be reverted to sinus rhythm at the time of first observation. Clinical examination was normal in 58 pts; in 23 echocardiography disclosed mild abnormalities. In 2 pts auscultation revealed a mid-systolic apical click, i n one a mid-systolic murmur and in 2 click and murmur together. These findings were correlated to slightly pathological echocardiographic patterns. M-mode and B-mode echocardiography yielded normal results in 35 pts and showed minor pathological findings in 28 (16 with paroxysmal AF and 12 with chronic AF). Thyroid hormones, tested in 58 pts, were within normal limits in 53, showed decreased T4 in 2 and increased T3 in 3 (2 of whom in treatment with amiodarone). During the follow-up period, no patient had a deterioration of the clinical status from the cardiovascular point of view. However, one patient suffered an episode of cerebral embolism, with rapid resolution, and one a cerebral transient ischemic attack. In conclusion "lone" AF has a favourable prognosis and systemic anticoagulation is not indicated, particularly in the absence of left atrial dilatation.

[Hemodynamic and anti-angina effects of transdermal nitroglycerin after acute and chronic administration. Additive effect of sublingual isosorbide dinitrate]. / Effetti emodinamici ed antianginosi della nitroglicerina transdermica dopo somministrazione acuta e cronica. Effetto additivo dell'isosorbide dinitrato sublinguale.

To evaluate the acute and chronic anti-anginal efficacy of a Transdermal Therapeutic System, releasing 10 mg of nitroglycerin over 24 hours (TTS 10), and possible additional effects of isosorbide dinitrate 5 mg (ISDN) sublingually (s.l.), ten patients with stable exercise-induced angina pectoris and pathological coronary angiography were studied. The protocol of the trial consisted of an initial acute study, carried out in double-blind conditions and following a cross-over design, to compare TTS 10 and placebo. Cycloergometric exercise tests were performed on the first and second day, 3 hours after dosing. After a 30 minute rest period, a sublingual 5 mg dose of ISDN was given and 15 minutes later a further exercise test was carried out. Subsequently, patients received TTS 10 in single-blind conditions for 16 days. On the 15th and 16th day, stress test was repeated, 3 hours after the application of active plasters and, 30 minutes later, a further exercise test was performed, 15 minutes after a sublingual dose of ISDN 5 mg or placebo, given in double-blind conditions and in randomized sequence. After acute and chronic administration, TTS 10 significantly improved exercise tolerance in comparison with placebo. During the first acute study, ISDN 5 mg s.l., led to a significant reduction in systolic BP, a reflex increase in heart rate and a further improvement in exercise tolerance, whether patients were on placebo or TTS.(ABSTRACT TRUNCATED AT 250 WORDS)

[Gingival hyperplasia caused by nifedipine]. / Iperplasia gengivale da nifedipina.

In a 66-year-old patient a relationship between the development of gingival hyperplasia and nifedipine treatment was suggested. The hyperplasia was clinically and histologically similar to the gingival hyperplasia induced by diphenylhydantoin. The nifedipine-induced gingival hyperplasia may be probably caused by alterations in calcium metabolism. The withdrawal of the drug results in a complete remission of the disease.

[Recurrent alveolitis caused by amiodarone]. / Alveolite ricorrente da amiodarone.

More recently a few cases of pulmonary toxicity due to amiodarone administration and reversed following drug discontinuation and corticosteroid therapy have been reported. An unusual case of recurrence of amiodarone pulmonary toxicity is described. After receiving amiodarone 1.200 mg/week for 6 month a 54-year-old woman showed clear signs of pulmonary alveolitis with ray signs of diffuse pulmonary infiltrates. The pulmonary symptoms recurred after discontinuing corticosteroidis 17 months after amiodarone was stopped and were associated with a persistent amiodarone level in broncho alveolar lavage. Only after 20 months the complete resolution of pulmonary symptoms was achieved.

Effect of a new transdermal therapeutic system containing nitroglycerin on exercise capacity in patients with angina pectoris.

In a double-blind, within-patient, randomized, placebo-controlled, acute study, the effects at rest and on exercise capacity of two doses of a new transdermal therapeutic system (TTS), releasing respectively 10 and 20 mg of nitroglycerin (NTG) over 24 hours, were assessed in 15 outpatients with stable exercise-induced angina pectoris. A symptom-limited exercise test was performed 4 and 24 hours after the application of each system. In comparison with placebo, both TTS-NTG doses induced a statistically significant (p less than 0.01) increase in total duration of exercise, in exercise duration to 1 mm ST segment depression, in maximal workload and in total work performed, at both 4 and 24 hours after dosing. Furthermore, both TTS-NTG doses induced a significant rise in the pressure-rate product, both 4 and 24 hours after dosing (p less than 0.01 and p less than 0.05, respectively). No statistical difference was found between the two doses of active drug in any of the above-mentioned evaluation parameters. The only unpleasant side effect was the typical nitrate headache, which occurred in 11 of 15 patients. In conclusion, a single application of TTS-NTG, 20 cm2 or 40 cm2, may improve exercise capacity over a 24-hour period in patients with stable exercise angina due to atherosclerotic heart disease.

[TTS-nitroglycerin and slow-release metoprolol: efficacy in patients with stable exercise-induced angina]. / TTS-nitroglicerina e metoprololo retard: efficacia nei pazienti con angina da sforzo stabile.

The antianginal efficacy of slow-release metoprolol (SRM) alone and associated to a transdermal therapeutic system containing nitroglycerin (TTS-TNG), was investigated in 10 patients with chronic, stable exertional angina and angiographic evidence of obstructive coronary artery disease, by means of a double blind, cross-over trial. Each patient performed a symptom-limited exercise test 4 and 24 hours after single blind placebo on day 1, and double blind SRM (200 mg) alone or SRM plus TTS-TNG, on days 3 and 5, in a randomized sequence. The protocol of Redwood was employed. Compared to the beta-blocker alone, the combined administration of SRM and TTS-TNG was associated to a significant increase in mean exercise duration 4 hours (528 +/- 180 vs 412 +/- 110 sec.; p less than 0.001) and 24 hours (432 +/- 115 vs 391 +/- 100 sec.; p less than 0.05) after drug administration. A significant increase in mean total work performance 4 hours (4626 +/- 1070 vs 3272 +/- 803 kgm; p less than 0.01) and 24 hours (3445 +/- 1045 vs 2941 +/- 773 kgm; p less than 0.01) after drug administration was observed as well. During placebo all the tests were stopped due to angina associated with ST depression greater than or equal to 1 mm. Conversely, the test was terminated due to fatigue by 8 patients at 4 hours and 5 patients at 24 hours after combined therapy, and respectively by 5 and 1 patient after SRM alone. No side effects were observed after the administration of SRM alone, whereas 5 patients complained of mild headache after SRM and TTS-TNG.(ABSTRACT TRUNCATED AT 250 WORDS)

May early exercise testing after myocardial infarction predict the extent of coronary artery disease?

To determine whether exercise testing performed soon after myocardial infarction may predict the degree of coronary artery disease, 78 patients performed stress testing and coronary angiography 15 +/- 5 and 64 +/- 35 days, respectively, after myocardial infarction. Out of 34 patients with a positive test, 22 (65%) demonstrated a multivessel disease, and 37 (84%) out of 44 patients with a negative test had normal coronary angiograms or single vessel disease (p = .0006). In addition to stress testing, no clinical parameter considered (infarct location, heart failure and cardiomegaly) was predictive of the extent of coronary artery disease.

[Clinical and hemodynamic implications of anterior ST segment depression in inferior myocardial infarct]. / Implicazioni cliniche ed emodinamiche del sottoslivellamento anteriore del tratto ST nell'infarto inferiore.

The finding of ST segment depression (reduced ST) in the anterior leads during acute inferior myocardial infarction is a common clinical sign. Nevertheless, its significance is not yet well established. To evaluate the significance of this finding, 58 patients with acute inferior myocardial infarction, who has an electrocardiogram within 8 hours from the onset of the disease, were divided into 2 groups: group A (14 patients with anterior reduced ST less than 1 mV) and group B (44 patients with reduced ST greater than or equal to 1 mV in one or more anterior leads). All patients subsequently underwent coronary angiography and left ventriculography, mean 50 days after acute myocardial infarction. reduced ST was not predictive of left anterior descending coronary artery disease. On the contrary, a significantly higher rate of 2-3 vessel disease (p less than 0.05) and of critical stenosis or occlusion of the right or circumflex coronary artery (p less than 0.05) was found in group B. Peak CK level was significantly higher (p less than 0.01) in this group as well. No significant difference was found in ejection fraction and anterior wall motion abnormalities, whereas a higher number of patients in group B showed a depressed function of the postero-basal segment (p less than 0.05). During 6 months follow-up, 2 patients in group A and 24 in group B experienced cardiac events (angina, reinfarction, heart failure, coronary artery by-pass grafting, cardiac death) (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Compliance with cardiac rehabilitation in the elderly.

To evaluate the compliance of the elderly with cardiac rehabilitation (CR) after myocardial infarction, 370 consecutive patients greater than or equal to 65 years of age, admitted to our Coronary Care Unit over a period of 2 years, were examined: 48 died in the hospital, 34 were transferred to other wards and 29 were unable to perform a submaximal exercise test before discharge. Out of the remaining 259 patients, 43 began the CR and 32 completed it with a good outcome. Eleven patients interrupted the CR because of associated diseases. A social investigation was carried out on 83 of the 259 patients discharged from our ward. In addition to associated diseases and an extremely low exercise tolerance (41% of cases), the lack of participation was due to socioeconomic problems (9.5%), to lack of motivation (52.3%) and to inadequate information (38.1%). Nevertheless, 76% of patients indicated that they attained their previous way of life in a relatively short period of time. It is concluded that: CR is useful in patients who complete it; low compliance is due mainly to medical problems and lack of motivation; better information might slightly increase the compliance in our Center; most patients can, in any case, reach their previous way of life. It is debatable whether CR is advisable in old age, or should be directed towards selected groups of patients.

[Early exercise test after myocardial infarct: prognostic stratification]. / La prova da sforzo precoce dopo infarto del miocardio: stratificazione prognostica.

Exercise testing in myocardial infarction before discharge has been used for treatment and exercise prescription in the post-hospital phase. Aim of this study was to investigate the prognostic significance, within one year after the infarction, of submaximal exercise testing before discharge. 428 patients performed the test 14.5 days after the acute episode and were followed for 12 months. The following variables were examined: heart rate, blood pressure, rate-pressure product at maximum exercise, total work and reasons for stopping the test (fatigue, submaximal HR, BP greater than or equal to 200/110, hypotension, ischemic or arrhythmic response). Two events were considered: 1) non fatal reinfarction; 2) cardiac death. Two methods of multivariate analysis (Cox's model regression analysis and discriminant analysis) were used. None of the considered variables was found to be predictive of non fatal reinfarction. According to Cox's model total performed work and hypertensive response were found to be predictive of cardiac death, while using discriminant analysis only total work had a predictive value (discriminant function: L = 0.00094 X total work performed + 1.48643; p less than 0.01). In detail, the higher the total work, the better the probabilities of survival, while in patients who stopped the test because of hypertension, the probabilities of cardiac death were lower. Exercise testing performed in uncomplicated myocardial infarction before hospital discharge provides, the basis for a more rational management of patients in the post-infarction phase, and contributes to identify a subset of high-risk patients.