Lone atrial fibrillation: prognostic differences between paroxysmal and chronic forms after 10 years of follow-up.

BACKGROUND: Lone atrial fibrillation (LAF) is defined by the presence of atrial fibrillation unassociated with other evidence of organic heart disease. There are conflicting data concerning the prognostic importance, rate of embolic complications, and survival in subjects affected by this arrhythmia. METHODS AND RESULTS: One hundred forty-five patients younger than 50 years at the time of the first diagnosis were identified; 96 had paroxysmal and 49 had chronic LAF. They were followed up with clinical and echocardiographic controls, and we recorded every thromboembolic complication and death. During the follow-up (10 +/- 8 years) among patients with paroxysmal LAF, 1 (1%) had an ischemic stroke, 2 a transient ischemic attack, and 1 a myocardial infarction. In the group with chronic LAF, 1 patient had moderate heart failure, 2 myocardial infarction, and 1 transient ischemic attack. In this group, 8 embolic complications in 7 (16.3%) patients were observed. One patient with intestinal embolism died during surgery; 2 (6.1%) patients died suddenly. CONCLUSIONS: The prognosis of young patients with paroxysmal LAF appears to be excellent, whereas patients with chronic LAF are at increased risk of embolic complications and higher mortality rates. Our results suggest that LAF is not always a benign disorder, as suggested by previous studies. Subgroups with substantially increased risk for thromboembolic events caused by LAF should be better identified.

[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.

Electrocardiography of myocarditis revisited: clinical and prognostic significance of electrocardiographic changes.

To clarify the clinical and prognostic value of the ECG, an ECG review was undertaken in 45 consecutive patients with a histologic diagnosis of active myocarditis (29 men and boys and 16 women and girls; age, 36.8 +/- 15 years; idiopathic myocarditis, 39 cases). In patients (21) with symptoms of recent onset (less than or equal to 1 month) AV block and repolarization abnormalities were the prevailing ECG features at the time of admission, and a pseudoinfarction pattern (Q waves plus ST-segment elevation) frequently heralded a rapidly fatal course ("fulminant myocarditis"). Left atrial enlargement and atrial fibrillation, left ventricular hypertrophy and LBBB, which prevailed in patients who had symptoms for longer periods, corresponded to the most severe degree of left ventricular dysfunction during the initial hemodynamic and echocardiographic evaluation. The overall mortality rate after 58 +/- 24 months from the time of diagnosis was 29%. Abnormal QRS complexes and LBBB were markers of poor survival, independently of initial indexes of left and right ventricular function, both of which indicate an increased propensity for sudden cardiac death.

[Lack of tolerance after administration of delayed-action isosorbide-5-mononitrate for 3 days in patients with exercise-induced silent ischemia: control with placebo]. / Assenza di tolleranza dopo somministrazione di isosorbide-5-mononitrato a lento rilascio per tre giorni in pazienti con ischemia silente da sforzo: controllo con il placebo.

In order to assess the development of tolerance we analyzed in a placebo-controlled study the effect of monotherapy with isosorbide-5-mononitrate (IS-5-MN) 60 mg in a controlled release formulation (Durules) once-a-day. The IS-5-MN was evaluated after the first dose and after once-a-day therapy for three days in 11 ambulatory patients (10 males, 1 female, aged 54 +/- 9 years) with stable exercise-induced silent myocardial ischaemia and significant coronary stenoses. The drug was given at 8 o'clock in the morning, and a bicycle ergometer exercise test was performed after 4 hours. The ST segment depression was evaluated by a computer-assisted system. Standing blood pressure decreased during all three periods of active treatment with IS-5-MN, (in comparison with placebo p < 0.001 and p < 0.01, p < 0.01 respectively). Heart rate did not change significantly. Compared with placebo baseline values, ischaemic threshold increased during the first day of treatment (188 sec, p < 0.0001 at 4 hours), and to a lesser extent both in second (103 sec, p < 0.003) and third day (116 sec, p < 0.003). The total exercise time increased during all three days of active therapy but significantly so only during the first day. The exercise stress test performed in the 5th day during placebo demonstrated a high reproducibility of ischaemic-threshold (235 vs 241 sec, p: ns), implying that the improvement during the active treatment with IS-5-MN was not due to a "training effect". Headache in 2 patients was the only significant side-effect.(ABSTRACT TRUNCATED AT 250 WORDS)

[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.

The use of associated propafenone in patients with amiodarone-resistant ventricular tachycardia.

To clarify the risk-benefit ratio involved in association of antiarrhythmic drugs, a combined therapy of amiodarone and propafenone was tested by means of continuous electrocardiographic monitoring, analysis of levels of the drug in the plasma and programmed electrical stimulation in a selected group of 10 patients who had left ventricular dysfunction and spontaneous relapses of sustained ventricular tachycardia despite treatment with amiodarone. Induction of sustained ventricular tachycardia, possible in each case during treatment with amiodarone, was suppressed after addition of propafenone in 2 patients (responders), who had the best ejection fractions of the entire group (greater than 45%). Worsening of spontaneous tachycardias developed in 4 cases during the combined therapy. These ventricular arrhythmias, although generally at a low rate, sometimes had the potential to degenerate into ventricular fibrillation and disappeared after both discontinuation of propafenone or increase of its dosage (1 patient). Of the six cases undergoing chronic combined treatment, only the responders to premature electrical stimulation were completely protected from recurrences of arrhythmia. Three cases, on the other hand, needed permanent endocardial pacing for symptomatic bradyarrhythmias. The combination of treatment with amiodarone and propafenone, although potentially useful in limiting dosages of and toxicity from amiodarone, is frequently associated with undesirable, and occasionally has severe, side-effects. The best candidates for this pharmacological association seem to be patients without severely depressed left ventricular function who have a greater probability of not presenting the inducibility of ventricular tachycardia after the addition of propafenone to the regimen for treatment.

[Hemodynamic effects of molsidomine in chronic congestive heart failure]. / Effetti emodinamici della molsidomina nello scompenso cardiaco congestizio cronico.

Acute haemodynamic effects of molsidomine, antianginal drug with vasodilator properties, were evaluated in 12 male patients with chronic congestive heart failure in New York Heart Association functional class 3 or 4 (mean age 56 +/- 7 years; ischemic heart disease in 8 cases, dilated cardiomyopathy in 3 cases, heart disease of combined aetiology in 1 case). After sublingual molsidomine (4 mg: 6 cases; 8 mg: 6 cases) the following haemodynamic changes were observed: mean right atrial pressure - 35% (p less than 0.01), left ventricular filling pressure -30% (p less than 0.01), total pulmonary resistance -33% (p less than 0.01), pulmonary arteriolar resistance -32% (p less than 0.01), cardiac index -6% (p less than 0.05), stroke volume index -12% (p less than 0.05), stroke work index +18% (p less than 0.01), heart rate -6% (p less than 0.01), double product -10% (p less than 0.01) (Fig. 3). Peak haemodynamic effect was reached between 30 and 90 minutes, lasting till 180 minutes. Molsidomine acutely reduced preload, did not show side effects and was well tolerated. These results suggest that molsidomine might be used in the treatment of chronic congestive heart failure, especially if characterized by an increased right and left ventricular filling pressure.

Hemodynamic evaluation of ibopamine in patients with refractory congestive heart failure.

Ibopamine (SB-7505), the orally active 3,4-diisobutyryl ester of N-methyldopamine, was investigated at doses ranging from 1.09 to 2.34 mg/kg in 12 patients suffering from refractory congestive heart failure. In 7 patients ibopamine produced favorable effects, increasing cardiac index (+35%), stroke volume index (+27%), stroke work index (+30%) and decreasing systemic vascular resistances (-15%), total pulmonary resistances (-20%), pulmonary arteriolar resistances (-28%), whereas in 5 patients it was ineffective. Transient adverse reactions occurred in 3 patients.

Vasodilators in left ventricular failure.

Vasodilator drugs are generally classified according to their prevalent site of action: arteriolar vasodilators (e.g. phentolamine, hydralazine, nifedipine) which reduce peripheral resistance and, therefore, increase stroke volume and cardiac output; venodilators (e.g. nitrates), which decrease filling pressure, redistributing intravascular blood volume from the central to the peripheral reservoirs and therefore relieve signs and symptoms of congestion; "balanced" vasodilators (e.g. nitroprusside, prazosin, captopril) which present both effects. Vasodilator therapy is indicated in heart failure caused by impaired contractility (congestive cardiomyopathy, ischemic heart disease) and volume overload (mitral and aortic regurgitation, ventricular septal defect). Hemodynamic studies of acute pharmacological effects are necessary for a correct drug choice, even if they are not always predictive of the long-term efficacy. Non-invasive studies (in particular echocardiography) don't seem actually adequate for vasodilator therapy evaluation. Finally it is not known if vasodilator treatment influence prognosis of chronic heart failure (especially survival), but there is evidence that it can lessen symptoms and increase effort tolerance.

[Captopril therapy in chronic congestive heart failure]. / Il captopril nella terapia dello scompenso cardiaco congestizio cronico.

Acute and chronic effects of captopril (C) were studied in 14 patients (12 males, 2 females; mean age 56 +/- 15 years) with chronic congestive heart failure (CCHF) refractory to digitalis and diuretics. All patients underwent hemodynamic evaluation before and after increasing doses of C (6.25-100 mg). Nine patients were evaluated during long term therapy by means of clinical examination, exercise testing, chest-X-ray and echocardiography. After C the following acute haemodynamic changes were observed. Mean right atrial pressure: -25% (p less than 0.01), left ventricular filling pressure: -22% (p less than 0.01), mean systemic arterial pressure: -15% (p less than 0.01), systemic vascular resistance: -31% (p less than 0.01), cardiac index: +36% (p less than 0.01). Of the 9 patients who were evaluated during long term C treatment, 7 (group A, mean follow up 6.4 +/- 4.2 months) improved in 1 or 2 NYHA functional classes and showed an increased exercise tolerance during the first 3-6 months of therapy. In this period, however, two sudden deaths and one drop-out were observed. Moreover, after the seventh month two patients of this group deteriorated clinically. Two patients (group B) developed a progressively weight gain during the first 15 days of C treatment. In the majority of our patients with refractory CCHF, captopril improves cardiac performance in the acute phase and in the first 3-6 months of therapy. Controlled studies and longer follow up are needed to understand better the long term effects of C in CCHF patients.