Sabino Scardi

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.

Afterload reduction with nifedipine in aortic insufficiency.

The acute hemodynamic effects of nifedipine were assessed in 12 patients with severe aortic insufficiency during control conditions and 30 minutes after administration of nifedipine (20 mg sublingually). Left ventricular end-diastolic pressure decreased from 19 +/- 8 (mean +/- standard deviation) to 9 +/- 5 mm Hg (probability [p] less than 0.0001), mean aortic pressure from 98 +/- 12 to 80 +/- 9 mm Hg (p less than 0.00001), systemic vascular resistance from 1,135 +/- 280 to 794 +/- 176 dynes . s. cm-5 (p less than 0.0002) and rate-pressure product from 11,732 +/- 1,727 to 10,022 +/- 1,103 mm Hg beats/min (p less than 0.01). Forward cardiac index increased by 24 percent, from 3.8 +/- 1.1 to 4.4 to 0.8 liters/min per m2 (p less than 0.04). Left ventricular end-diastolic volume, ejection fraction and total stroke work index did not change significantly. Regurgitant fraction, measured in five patients, changed parallel with systemic vascular resistance. Left ventricular function was maintained while both preload and afterload were decreased. Regurgitant flow was moderated and myocardial oxygen demand decreased. This hemodynamically favorable condition, due to nifedipine, is clinically important and suggests the need for further therapeutic trials.

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.

Efficacy of continuous and intermittent transdermal treatment with nitroglycerin in effort angina pectoris: a multicentric study

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)

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.

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.

Hypertrophic cardiomyopathy associated with myotonic muscular dystrophy (Steinert's disease)

A 52-year-old man with myotonic dystrophy and first degree atrioventricular block, right bundle branch block and left anterior hemiblock was shown by echocardiographic examination to have hypertrophy of the posterior segment of the septum and of the anterior left ventricular wall. Myocardial involvement in this patient may represent the full expression of a genetic defect involving both skeletal and myocardial striated tissue.

Corrected Transposition of the Great Vessels and Situs Inversus Viscerum in a 65-Year-Old Oligosymptomatic Woman

Corrected transposition of the great vessels (atrioventricular discordance and ventricular discordance) is a rare congenital heart disease and is very singular if it is associated with situs inversus viscerum. This is the case in a 65-year-old woman in NYHA functional class II. The NMR image shows the liver (L) on the …

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.

Effect of isosorbide-5-mononitrate 80 mg slow release on hemodynamic variables and exercise performance in men with coronary artery disease

Abstract The anti-ischemic effect of a single 80-mg dose of isosorbide-5-mononitrate slow release (IS-5-MN SR) was investigated in 20 patients with documented coronary artery disease and stable, reproducible, exercise-induced ischemia with or without angina. At 7 AM, patients received—following a randomized, double-blind, crossover design—either the active drug or placebo. Bicycle exercise tests were performed at 5 and 10 hours after dosing without concomitant anti-ischemic treatment. Compared with placebo, IS-5-MN SR significantly decreased standing systolic and diastolic blood pressures, both at 5 hours ( P P P P P P