Masson's pseudoangiosarcoma, alias intravascular papillary endothelial hyperplasia, in dissecting aortic aneurysm caused by cystic medionecrosis.

This report describes a 25-year-old man who died due to extensive cystic medionecrosis of the aortic wall complicated by both an acute and an ancient dissection. The very unusual finding of an intravascular papillary endothelial hyperplasia, also known as Masson's pseudoangiosarcoma, in the dissected wall is reported given its resemblance to a hemangiosarcoma.

Left atrial and appendage mechanical function after pharmacological or electrical cardioversion in patients with chronic atrial fibrillation: a multicenter, randomized study.

BACKGROUND: Transient atrial and appendage dysfunction occurs after cardioversion of atrial fibrillation. It has been suggested that one component of early dysfunction is related to the method of restoration of sinus rhythm and it is less severe in patients undergoing pharmacological than electrical cardioversion. The aim of this study was to compare left atrial chamber and left atrial appendage mechanical function before and after 48 hours from electrical or pharmacological cardioversion in patients with chronic atrial fibrillation. METHODS: We studied the effects of the mode of cardioversion on Doppler left atrial and appendage function in 19 patients with persistent atrial fibrillation (> or = 4 weeks), who were randomized to pharmacological (quinidine) or electrical cardioversion (protocol: 200, 300, 360 J) after pre-treatment with verapamil. Transthoracic and transesophageal echocardiography were performed before and 48 hours after the restoration of sinus rhythm. To determine left atrial and appendage mechanical dysfunction, the peak A wave velocities were obtained from transmitral flow velocity profiles recorded in the apical 4-chamber view, and peak emptying and filling appendage velocities were measured by the transesophageal approach with the sample volume placed at the orifice of the left atrial appendage. All the patients were pre-treated with verapamil before cardioversion in order to achieve a satisfactory control of heart rate. RESULTS: Mean peak A wave velocities were 0.52 +/- 0.12 m/s in the patients treated electrically and 0.54 +/- 0.08 m/s in those treated pharmacologically (p = NS). Before and after electrical cardioversion, the peak filling velocities of the left atrial appendage were 0.42 +/- 0.17 and 0.43 +/- 0.17 m/s respectively, and the peak emptying velocities 0.30 +/- 0.14 and 0.36 +/- 0.17 m/s respectively; before and after pharmacological treatment, the peak filling velocities were 0.38 +/- 0.1 and 0.43 +/- 0.1 m/s respectively, and the peak emptying velocities were 0.30 +/- 0.13 and 0.43 +/- 0.24 m/s respectively (p = 0.08). CONCLUSIONS: Even a long period of atrial fibrillation does not lead to a marked depression of global left atrial and left atrial appendage function 48 hours after the restoration of sinus rhythm by means of electrical or pharmacological cardioversion. There is no evidence that electrical cardioversion causes greater post-cardioversion atrial and/or appendage dysfunction than pharmacological treatment after 48 hours. Pre-treatment with verapamil may have reduced the dysfunction (probably because of a reduction in mechanical remodeling during atrial fibrillation).

[Congenital quadricuspid aortic valve]. / Valvola aortica quadricuspide congenita.

A case of a 17-year-old asymptomatic man is reported. The patient had no other cardiac congenital abnormalities. Transthoracic echocardiography revealed a rare quadricuspid aortic valve malformation without aortic regurgitation.

Mortality and cause of death in patients with chronic non-rheumatic atrial fibrillation after a two-year follow-up.

BACKGROUND: Non-rheumatic atrial fibrillation (NRAF) is a very common arrhythmia but its role in the prognosis and cardiovascular mortality is controversial. In particular, cause and predictors of death are not completely known. METHODS: We analyzed the cause of death and the possible predictors of cardiovascular mortality in 664 outpatients (mean age 72 +/- 9 years old) enrolled in the "Trieste Area Study on Non-Rheumatic Atrial Fibrillation" (TASAF), a prospective community study, after a follow-up of 27 +/- 9 months. The mean duration of the arrhythmia at enrollment was 59 months (range 1-360 months). Only 42 patients (6.3%) were on anticoagulants by general practitioners and 205 (30.8%) were on antiplatelet drugs. RESULTS: Of these patients, 110 (16.5%) died: 28 (25.5%) due to a cerebral or peripheral thromboembolism, 10 (8.2%) of sudden death, 46 (42.7%) of expected cardiac death and 25 (22.7%) of non-cardiac causes. In one patient, the cause of death was uncertain. Sixty-nine patients underwent postmortem examination. In univariate analysis, left ventricular dysfunction (p = 0.03) and an enlarged left atrium (p = 0.03) proved to be directly related to increased cardiovascular mortality. Both in univariate and Cox proportional hazards model analysis, aging (odds ratio 1.09, IC 95% 1.05-1.12, p = 0.00001), history of heart failure (odds ratio 1.27, IC 95% 1.01-1.60, p = 0.036), cardiomegaly (odds ratio 1.35, IC 95% 1.01-1.81, p = 0.040), diabetes mellitus (odds ratio 1.35, IC 95% 0.99-1.84, p = 0.058) and previous myocardial infarction (odds ratio 1.56, IC 95% 1.20-2.03, p = 0.0007) were all independent risk factors for cardiovascular mortality. A history of cerebral or systemic embolism (23 versus 12%, p = 0.09) and, above all, one or more recurrences before enrollment (11 versus 2.3%, p = 0.04), were associated with embolic mortality. CONCLUSIONS: Patients with NRAF have an increased risk of cardiovascular death. Aging, the presence of diabetes, cardiomegaly on chest x-ray, heart failure and a previous myocardial infarction were independent risk factors for cardiovascular mortality. A history of embolism at enrollment significantly conditioned the embolic mortality rate but above all, embolic events during follow-up determined a very high percentage of total deaths (25.5% of all causes). A proper anticoagulant therapy should strongly be advised to all patients with no contraindications.

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.

[A longitudinal study on left atrial thrombosis in patients with non-rheumatic atrial fibrillation treated with anticoagulants]. / Studio osservazionale sulla trombosi atriale sinistra nei pazienti con fibrillazione atriale non reumatica trattati con anticoagulante.

BACKGROUND: Although atrial thrombosis is common in patients with non-rheumatic atrial fibrillation (NRAF) (6-27%), there are no studies about the effect that anticoagulant or antiplatelet drugs have on it. AIM OF THE STUDY: We have investigated the role of anticoagulant therapy, followed by family physicians, on left atrial thrombosis detected via transesophageal echocardiography (TEE) in patients with NRAF. METHODS: Sixty patients enrolled in the TASAF (Trieste Area Study on non-rheumatic Atrial Fibrillation) (60% males, mean age 72 +/- 7 years, 17% with lone atrial fibrillation, duration of arrhythmia 111 +/- 79 months), in whom we found a left atrial and/or left atrial appendage thrombus via TEE, were anticoagulated. The thrombus was in the left atrial appendage in 57 patients and in the left atrium in the others. In 28 of them it was mobile and in 50, the left atrial appendage flow was low or absent. Lastly, in 46 patients we found spontaneous echocontrast and a bilobate appendage was present in 8 of them. At follow-up, we repeated the TEE to evaluate the effect of the therapy on the atrial thrombosis. RESULTS: Only 53 patients received anticoagulant therapy (45 correctly), while 7 were treated with antiplatelet drugs by their family physicians. After a mean follow-up of 16 months, all patients underwent a repeat TEE and the thrombus was no longer evident in 35 cases (58%). The thrombosis disappeared in 26 (58%) of the 45 patients who correctly took anticoagulant therapy and in 5 of the 8 who were not adequately anticoagulated. Moreover, we didn't observe the thrombus in 4 of the 7 patients who were treated with antiplatelet drugs. There was no significant statistical difference between the benefits of anticoagulants and antiplatelet therapy in dissolving left atrial thrombosis. During follow-up, we recorded only one embolic event in the retina. None of the patients on antiplatelet drugs complained of any side effects, whereas in 5 of the 53 on anticoagulant therapy, we recorded one fatal intracranial hemorrhage, one gastric hemorrhage and three minor complications. CONCLUSIONS: Left atrial thrombosis in NRAF disappears in anticoagulated patients in an high percentage of cases (the therapy probably acts on more recent thrombi). Moreover, this therapy decreases the incidence of embolic events, although it increases the risk of hemorrages. Since the management of this preventive treatment in general medicine is very difficult, we hope that our health organization will establish Anticoagulation Clinics for the centralized management of this therapy.

D-dimer and anticoagulation in patients with mechanical prosthetic heart valves. A 2-year follow-up.

The best anticoagulation level in patients with mechanical heart valve prostheses is still being debated. D-dimer, which detects the presence of cross-linked fibrin degradation products, has been demonstrated to be a useful marker of coagulation activation. This study was designed to verify whether heart valve prostheses in anticoagulated patients are associated with abnormalities in D-dimer plasma levels, and if so, whether such levels are related to the anticoagulation level and/or whether they could be predictive of acute vascular or hemorrhagic events. In 132 patients with single and 10 with double mechanical valve replacement, international normalized ratio (INR) and D-dimer plasma levels were determined. The INR levels of the previous 8 months were reviewed to assess the time that each patient spent in the therapeutic range. The D-dimer plasma levels were compared with those obtained from 102 matched control subjects. The patients were then followed up for 2 years to record acute vascular and hemorrhagic events. For the entire group, D-dimer plasma levels in patients were the same as those in the control group. Patients with double valve replacement had higher D-dimer plasma levels than either monovalvular implant patients or control subjects. Patients who had spent < 75% of the time within the assigned anticoagulation range had higher values for D-dimer plasma levels (median, 270 vs 198 ng/mL, P = .02). The major determinants of D-dimer plasma levels were age (R2 = .07, P = .009) and the percentage of time spent below the predetermined INR level (R2 = .09, P = .001). During follow-up, 19 acute vascular and 16 hemorrhagic events occurred. High D-dimer tertile was the only parameter predicting the occurrence of thromboembolic events. In patients with mechanical heart valve prostheses, the D-dimer plasma level depended on the thoroughness of anticoagulation. Patients in the upper tertile of D-dimer values have an approximately 5-fold risk of vascular thromboembolic events. D-dimer determination can therefore be useful in detecting patients who are at a higher risk of severe vascular events.

[Ischemic heart disease and postoperative mortality in major vascular surgery. An up-to-date diagnostic approach]. / Cardiopatia ischemica e mortalità operatoria in chirurgia vascolare maggiore. Un moderno approccio diagnostico.

BACKGROUND: The aim of this study is to evaluate the efficacy the dobutamine stress echocardiography in predicting the perioperative cardiac risk of patients undergoing major vascular surgery. METHODS: Seventy-seven consecutive and not selected patients, undergoing a surgical treatment requiring aortic cross clamping, were assessed also with a transthoracic dobutamine stress echocardiography. With electrocardiographic and echocardiographic monitoring ventricular ischemia or wall motion abnormalities, 5 micrograms/kg per min of chlorhydrate dobutamine for 5 minutes were infused, followed by other 10 micrograms/kg per min increased up to 40 micrograms/kg per min. During the last 4 minutes 0.25 mg of atropin were infused increasingly up to 1 mg. RESULTS: Of all these patients, 26 had a stress ischemia but only 4 cases underwent a coronary angiography and only 2 of these underwent a preventive myocardial revascularization. Due to poor cardiac conditions pointed out with the dobutamine stress, 3 patients were not treated surgically. With an aggressive intra- and perioperative monitoring 73 patients underwent a surgical treatment: they were 28 aorto-bifemoral, 3 aorto-aortic grafts, 1 aorto-bisiliac thoraco-abdominal interposition graft, and 20 aorto-bifemoral, 4 aorto-femoral, 1 aorto-aortic thoraco-abdominal, 1 aorto-renal by-pass and 7 aorto-iliac-femoral thromboendoarterectomies. In the postoperative period 4 cardiac ischemic complications and 2 deaths (2.5%) were observed. CONCLUSIONS: According to our personal opinion, stress echocardiography can be considered a test with a excellent feasibility and safety rate, not expensive and with a good reproducibility and reliability. It allowed to predict the cardiac risk in our patients suggesting not only the surgical but also the anesthesiologic and the perioperative therapeutic management.

[Stratification of the thromboembolic risk in patients with non-rheumatic atrial fibrillation: assessment of left atrial dysfunction]. / La stratificazione del rischio tromboembolico nei pazienti con fibrillazione atriale non reumatica: il contributo della disfunzione auricolare sinistra.

BACKGROUND: Patients with non rheumatic atrial fibrillation (NRAF) have an increased risk for thromboembolic complications. Recent evidence suggests that left atrial appendage function (contraction, filling dynamics) may provide clues to the thrombogenic potential of this structure. The aim of this study was to identify left atrial spontaneous echocontrast and thrombus between patients with NRAF and their relationship with left atrial appendage function. METHODS: Transthoracic (TTE) and biplane or multiplane transesophageal echocardiography (TEE) were performed in 143 patients with chronic NRAF enrolled in the Trieste Area Study on non rheumatic Atrial Fibrillation (TASAF), an ongoing prospective community study with a follow-up period of 2 years. The maximal and minimal areas of the left atrial appendage were measured during three cardiac cycles and the peak emptying and filling velocities profile were obtained by pulsed wave Doppler at the orifice of the left atrial appendage. The left atrium and appendage were inspected for thrombus and spontaneous echocontrast. RESULTS: Left atrial appendage thrombus was present in 37 patients (26%) and spontaneous echocontrast in 60 patients (42%), 45% of patients with spontaneous echocontrast had thrombus. Univariate analysis identified positive correlation of thrombus with duration of atrial fibrillation (p = 0.05), hypertension (p = 0.01), left atrial area (p = 0.005), mitral annular calcification (p = 0.01), left ventricular dysfunction (p = 0.03) and a non significant correlation with the mitral valve prolapse (p = 0.08) in the TTE. The presence of mitral regurgitation did not demonstrate a protective effect (p = 0.73) against thrombosis. The variables of left atrial appendage function identifying a subgroup of patients with increased risk of thrombus formation were: shortening fraction of the area in the horizontal and vertical sections (p = 0.0001 and p = 0.002 respectively), the peak filling and emptying velocity in horizontal (p = 0.0001 equal for both) and vertical sections (p = 0.0001 equal for both). In summary these patients have a larger left atrial maximal area (p = 0.004) and a lower flow velocity profile (p < 0.00001) and more intense spontaneous echocontrast (p < 0.00001) than the others. Spontaneous echocontrast was correlated with left ventricular dysfunction (p = 0.008), left atrial area (p = 0.02) and there was a non-significant correlation with mitral annular calcification (p = 0.09) and lower left ventricular shortening fraction (p = 0.06). Transesophageal echocardiography variables have identified the subgroup of patients with an increased risk of echocontrast formation. This was positively associated with a low flow velocity profile (p = 0.0001), a left atrial appendage low shortening fraction in horizontal section (p = 0.001) and in vertical section (p = 0.05) and a low peak filling velocity in horizontal section (p = 0.003) and in vertical section (p = 0.004) and a low peak emptying velocity in horizontal section (p = 0.003) and in vertical section (p = 0.001). Prophylactic therapy with anticoagulant or antiplatelet agents has little benefits in our experience. CONCLUSIONS: Spontaneous echocontrast and low flow profile velocity (low peak emptying and filling velocity) and increased area of left atrial appendage were strongly associated with left atrial and/or appendage thrombus in patients with NRAF. The assessment of left atrial appendage function by TEE is an important component of the comprehensive evaluation of potentially increased risk of thrombus formation.

[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.

[Isolated double orifice mitral valve]. / Doppio orificio mitralico isolato.

A 58-year old woman with paroxysmal atrial fibrillation and isolated double orifice mitral valve is presented. This congenital abnormality is usually discovered by autopsy or surgery. In this case it was diagnosed by echocardiography.

[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.

[Perception threshold of angina and transient myocardial ischemia in ambulatory electrocardiography]. / Soglia di percezione dell'angina ed ischemia miocardica transitoria nell'elettrocardiogramma dinamico.

AIM OF THE STUDY: We studied the predictive value of prolonged angina perception threshold in identifying patients with stable coronary artery disease at risk of silent myocardial ischemia during daily life. METHODS AND RESULTS: 71 patients with documented coronary artery disease (previous myocardial infarction or stenotic lesion > 60% at angiography) underwent a symptom-limited exercise test and out-of-hospital Holter monitoring after drug withdrawal. A second exercise test was performed before disconnecting the dynamic EKG in order to validate the ST-depression recorded during ambulatory monitoring. 23 patients (32.4%) (Group A) had angina perception threshold > 60 sec after onset of ischemia (ST > 1 mm), while in 48 (67.7%) the delay in the perception of angina was shorter than 60 sec (Group B). The demographic, clinical and angiographic variables did not influence the angina perception threshold; however, this parameter was the most powerful predictor of ambulatory ischemia among the two groups (4.8 vs 2.8 p < 0.02), and in particular of the painless episodes (3.8 vs 1.8 p < 0.002). Moreover, the silent ischemic time was longer in patients of group A (4362 vs 1774 sec p < 0.017). Finally, the event-free survival was similar in the two groups of patients during the 2 years of follow-up (cardiac death 1 vs 3, nonfatal myocardial infarction 1 vs 1, aorto-coronary bypass 2 vs 7, PTCA 2 vs 2, unstable angina 0 vs 2), total events 6 vs 15 p = ns. CONCLUSIONS: These results demonstrate that the patients at risk for silent ischemia during ambulatory monitoring may be identified simply by evaluating their angina perception threshold during exercise test; however, silent ischemia does not have an adverse prognostic value.

[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)

Efficacy of continuous and intermittent transdermal treatment with nitroglycerin in effort angina pectoris: a multicentric study. The Collaborative Nitro Group.

Eighty-eight patients (84 men and 4 women; mean age 59.3 years) with stable exercise-induced angina pectoris were enrolled in this within-patient, placebo-controlled study aimed at comparing the efficacy of the continuous and intermittent (12 hour on, 12 hour off) application of transdermal nitroglycerin. Eighty-one patients completed the study. After a 1-week placebo run-in period, during which the stability of angina was assessed on a bicycle ergometer, the patients received continuous treatment (two 10 mg/24 hour patches twice daily, at 8 a.m. and 8 p.m.), intermittent treatment (two 10 mg/24 hour patches at 8 a.m. and two placebo patches at 8 p.m.) and placebo (two placebo patches twice daily, at 8 a.m. and 8 p.m.), each given for one week in a double-blind randomised sequence, according to a 3 x 3 latin-square design. A cycloergometric exercise test was performed at the end of each period of treatment, 4 and 10 hours after the application of the morning patch. In comparison with placebo, both schedules of the active treatment induced a significant increase in both the ischemic (duration of exercise to 1 mm ST segment depression) and the angina threshold (duration of exercise to mild angina) at the 4th and at the 10th hours after-dosing. A significant difference was also found between continuous and intermittent treatment at the same times of observation, in favour of the intermittent schedule. The limited number of anginal attacks recorded during placebo prevented any clinical evaluation of the treatments. This study shows that the efficacy of transdermal nitroglycerin is more pronounced when it is given following an intermittent schedule.(ABSTRACT TRUNCATED AT 250 WORDS)

Prognostic value of total ischemic burden in patients with stable ischemic heart disease.

Patients with stable coronary artery disease commonly have transient myocardial ischemia with or without experiencing angina, but the prognostic implications of this "total ischemic burden" is still a matter of debate. We studied 112 consecutive patients with coronary artery disease, normal left ventricular function at rest and exercise-induced myocardial ischemia, a 24-hour ambulatory EKG was performed after drug withdrawal. The mean exercise duration was 572 +/- 192 seconds, with an ischemic threshold (ST depression = 1 mm) of 390 +/- 190 seconds). By Holter monitoring 30 patients had no ischemia and 82 (73%) had a total of 332 episodes of ST segment changes, the majority of which were asymptomatic (242/332, 73%). Among 82 patients with transient myocardial ischemia, 44 (54%) had only asymptomatic episodes. Nine patients (11%) complained of angina coincident to ST changes. Twenty-nine patients (35%) had both painful and painless ST segment alterations. All patients were prospectively followed-up while on conventional medical therapy. During a mean follow up of 25 +/- 10 months cardiac events occurred in 31 patients; there were 5 cardiac deaths, 3 non-fatal myocardial infarctions, 2 hospitalization for unstable angina and 21 revascularization procedures (PTCA or CABG). By multivariate analysis the number of stenotic vessels on coronary angiography was predictive of the events during the follow-up (p = 0.03), while other demographic, clinical, ergometric and angiographic variables were not influential. Event-free survival was similar for all subsets of transient myocardial ischemia (silent, symptomatic, or none).(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.

[Evaluation of exercise test reproducibility in patients with ischemic cardiopathy]. / Valutazione della ripetibilità del test da sforzo in pazienti con cardiopatia ischemica.

We evaluated the repeatability of some measurements taken during the bicycle ergometer exercise test (exercise duration, heart rate and pressure rate product at angina and ST segment depression times) in 166 consecutive non-selected ambulatory patients with proven ischemic heart disease. One hundred and sixty-six patients with history of angina and/or myocardial infarction performed three exercise tests within seven days of wash-out. Eighty-six (58.1%) of these experienced angina and ischemic ST segment depression during all three tests (group 1), and 80 (48.2%) finished at least one test without angina or ST segment depression (group 2). The degree of angina (according to Canadian Cardiovascular Society classification) was higher in the first group than in the second one; on the contrary, exercise duration as well as pressure rate product at ischemic threshold, heart rate and pressure rate product at the onset of angina were significantly lower (0.001 less than p less than 0.05) in the former group. In group 1, we analyzed ergometric parameter measurement "repeatability" during the three consecutive exercise tests. The analysis of variance for repeated measurements showed that exercise duration and pressure rate product values at ischemic threshold did not vary significantly in the three tests, while other ergometric parameters showed a greater variability (0.001 less than p less than 0.05). Age, previous myocardial infarction or rest angina, the number of critically stenotic coronary vessels and the ejection fraction did not condition the repeatability of the test. In conclusion, in our population of non-selected ischemic patients only 52% developed angina and ischemic ST segment depression during all three exercise tests performed.(ABSTRACT TRUNCATED AT 250 WORDS)