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.

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.

Myocardial infarction following sublingual administration of isosorbide dinitrate.

A 78-year-old with healed septal necrosis suffered a recurrent myocardial infarction of the anterior wall following the administration of isosorbide dinitrate 5 mg sublingually. After detailing the course of events, we discuss the role of paradoxical coronary spasm and hypotension-mediated myocardial ischemia occurring downstream to significant coronary arterial stenosis in the pathophysiology of acute coronary insufficiency.

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.

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)

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.

[Oxprenolol in the treatment and prevention of cardiac arrhythmias]. / L'oxprenololo nel trattamento e nella profilassi delle aritmie cardiache

Authors have analyzed the antiarrhythmic effect of oxprenolol, a beta blocking agent, in the treatment of various types of arrhythmias and in the prophylaxis of recurrences of auricular flutter and fibrillation. The results obtained in a group of 68 cases of different arrhythmias may be summarized in the following way: a) the drug efficiently reduces the ventricular rate in sinus tachycardia and in atrial flutter and fibrillation with high ventricular rate, even if resistant to treatment with digitalis; b) in patients with asynchronous pacemaker oxprenolol leads to disappearance or an important reduction of competitive rhythms; c) in supraventricular paroxysmal tachycardias the results are positive in the majority of cases (while on the contrary in 2 cases of ventricular tachycardias the drug was not effective). A group of 116 cases with auricular flutter or fibrillation (in which sinus rhythm had been restored with quinidine or cardioversion has been analyzed to study the prophylactic activity of oxprenolol in these arrhythmias. The cases have been divided at random into two groups and have been treated with quinidine (g 0.80 p.d.) or with an association of oxprenolol (mg 60 p.d.) and quinidine (g 0,60 p.d.). The observation period varied from a minimum of 1 month to a maximum of 3 years and 3 months. The curves showing the percentage of persistance of sinus rhythm in the two groups were very similar and after 3 years and 3 months 100% of patients observed presented a recurrence of arrhythmias.

[Prognostic evaluation of silent ischemia during exercise in patient with recent infarction. Italian multicenter study. SMISS Group]. / Evaluation du pronostic de l'ischémie silencieuse à l'effort chez des patients avec infarctus récent. Etude italienne multicentrique. Groupe SMISS.

AIM: The aim of the Multicenter Silent Ischemia Study (SMISS), co-ordinated by the Italian Working Group on Cardiac Rehabilitation, was to evaluate prospectively, the prognostic significance of silent myocardial ischemia during exercise testing in patients with proven ischemic cardiac disease. METHODS: Over a period of six months 4389 consecutive patients performing a maximal symptom-limited exercise testing, after drug withdrawal, were enrolled in the 73 ergometric laboratories. All patients were followed up after 12 months, at which time electrocardiogram, examination and clinical history were reassessed. Here we report the results of 1111 patients group with the recent myocardial infarction (inferior 3 months). The follow-up was completed in 1031 (93%) patients. RESULTS: The results of exercise testing were normal in 666 (64.6%) patients; angina alone in 33 (3.2%) patients; silent ischemia in 234 (22.7%) patients; symptomatic ischemia in 98 (9.5%) patients. In 270 patients (26.1%) new events occurred: angina (19.7%); myocardial infarction (3.1%; PTCA (4%); CABG (6%); cardiac death (1.4%). The total events were more common in the patients with exercise induced angina (48.5%) and in those who had exercise induced-symptomatic ischemia (48%), in respect of patients with silent ischemia (29.5%) and of those who had normal testing (20.7%) (p = 0.0001). Myocardial infarction rate was higher in patients with symptomatic ischemia (7.1%) that for those of all other groups (silent ischemia: 1.3%, angina: 3%, normal 3.2%) (p = 0.05). Moreover, the patients with symptomatic ischemia had higher incidence of CABG (p = 0.0001). The mortality rate was low among all patients and did not show differences among the groups. Only among the 31 patients (3%) with blood pressure fall was mortality higher that in patients with a normal blood pressure increase. By multivariate logistic analysis the angina induced by exercise maintained its prognostic significance for all the events, but also other variables were significant: poor exercise tolerance and, between clinical variables angina before myocardial infarction. CONCLUSION: The results showed, in patients who underwent to exercise testing after drug withdrawal, a low incidence of cardiac death and of myocardial infarction on 12 month follow-up; the patients with induced-exercise symptomatic schema had a greater risk for all cardiac events, except for death.

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).

[New operative models for the management of anticoagulant prophylaxis]. / Nuovi modelli operativi per la gestione della profilassi anticoagulante.

Anticoagulant therapy has proven to be effective for patients at risk for thromboembolic disease. Nevertheless, in daily clinical practice the oral anticoagulant therapy (OAT) is underused because it is still considered dangerous and difficult to manage, particularly in patients with chronic non-rheumatic atrial fibrillation. In the most important published studies about this topic we found that only 7-55% of patients with atrial fibrillation were treated with antiplatelet drugs, while 9.9-48.4% took anticoagulant prophylaxis; so, despite a favourable temporal trend after large trials have shown a positive prophylactic effect with antithrombotic drugs, they are underused. It has been estimated that in our country 500,000-600.00 potential patients could have indication for this treatment. Nevertheless, the traditional management of oral anticoagulation is fraught with difficulties such as patients' compliance, reliability of laboratory, global management of the treatment. Undoubtedly, this prophylaxis is very heavy for the patient and the physician often don't like this treatment for its dangerous potential, frequent difficulties of the management, obstacles in the communication among laboratory, physician and patient. Other common problems usually are the distance from patient's home-laboratory, its working hours, means of transportation. It is important a suitable organization and a control of the factors contributing to obtain favourable results for assuring a good cost/benefit ratio of OAT. The relationship among patient-physician-laboratory play a fundamental role. Alternative models are therefore prospected: anticoagulation clinic, computerised decision support software or portable coagulometer. Actually available instruments give us immediately the patients' INR and represent a new option and a promising strategy to monitor these large cohort of patients. Thus the management of OAT can be done by family physicians or by anticoagulant clinic or by patients themselves, after a suitable training period permitting a partial or total self management. These new strategies have improved therapeutic control of oral anticoagulation and in addition to the health advantages both also have economic benefits.

[Impact of chronic atrial fibrillation on cardiovacular mortality]. / Impatto della fibrillazione atriale cronica sulla mortalità cardiovascolare.

The largest cohort studies and a number of other epidemiological or clinical studies have found an increased risk of total, cardiovascular and stroke mortality in patients (both men and women of every age) with chronic non-rheumatic atrial fibrillation (AF) compared to heterogeneous individuals in normal sinus rhythm. These studies suggested that AF increases the probability of death without changing the mode of death. Many excess deaths due to non-rheumatic AF occur soon after the diagnosis of the arrhythmia. Non-rheumatic AF is complicated by the heterogeneity of the underlying heart disease and accompanying medications. Prognosis in non-rheumatic AF is dependent upon the age of the patients and the underlying cardiac conditions but non-rheumatic AF is a potent risk factor for stroke. Stroke in patients with non-rheumatic AF is generally more severe and induces higher mortality. A recent Framingham study has shown that an increased mortality rate persists when adjusted for age, hypertension, smoking, myocardial infarction, congestive heart failure, and stroke or transient ischemic attacks. These results demonstrate that non-rheumatic AF is independently associated with a 50 to 90% increase in the risk of death. Also the excess mortality observed in patients with chronic lone AF supports the independent role of the arrhythmia. The higher incidence of a chronic arrhythmia and the known complications of this condition pose serious problems for health care as our population ages. Passive acceptance of non-rheumatic AF is not correct. In all patients with non-rheumatic AF, restoring and maintaining sinus rhythm for as long as possible needs to be taken into serious consideration. New antiarrhythmic drugs and new strategies for the management of non-rheumatic AF are accumulating. When the arrhythmia is chronic, correct anticoagulant prophylaxis is a must, as several randomized trials have demonstrated a significant reduction in thromboembolic stroke incidence and related mortality with an acceptable hemorrhagic risk by using warfarin.

[Barriers to cardiovascular prevention]. / Gli ostacoli alla prevenzione cardiovascolare.

Data from observational and clinical trials provide a solid basis for the formulation of recommendations for the prevention of coronary artery disease. Numerous obstacles to the implementation of risk reduction interventions have been identified. These include: the patients, physician and health care organization, financial and social barriers, current government social and health policies, and direct and indirect costs. The strategies to overcome these barriers include the development of predictable clinical guidelines for the management of risk factors, the requirement of expertise in risk factor management in training and certification, the implementation of model programs for risk factor management that have been shown to be effective including those utilizing non physician professionals, the inclusion of risk factor management as a key indicator of the level of care in quality assistance programs and the cost-effectiveness of preventive interventions, physician and nursing education programs, referral clinics with subspeciality services, quality programs and standards, legislation and regulation, implementation of patient compliance. In conclusion, the improvement of risk factor management will require an efficient health care system and a coordinated effort by primary care physicians, other professionals (such as cardiovascular physicians and specialized nurses) and government policy.

[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.