Candesartan cilexetil is not associated with cough in hypertensive patients with enalapril-induced cough. Multicentre Cough Study Group.

The aim of this study was to evaluate the occurrence of dry cough during treatment with candesartan cilexetil, enalapril, or placebo in patients with hypertension and a history of angiotensin converting enzyme (ACE)-inhibitor-related cough. Patients with confirmed cough during an enalapril (10 mg) challenge period, followed by no cough during a placebo dechallenge period were randomized to 8 weeks of double-blind treatment with candesartan cilexetil (8 mg) (n = 62), enalapril (10 mg) (n = 66), or placebo (n = 26). Incidence and severity of dry cough was evaluated by the symptom assessment questionnaire, frequency of dry cough by a visual analog scale, and the possible impact on quality of life by the minor symptom evaluation (MSE) profile. The percentage of patients with cough was significantly lower with candesartan cilexetil (35.5%) than with enalapril (68.2%, P < .001), and did not differ between candesartan cilexetil and placebo (26.9%, P > .20). Patients coughed less frequently and with less severe cough with candesartan cilexetil than with enalapril, and similarly with candesartan cilexetil and placebo. Changes in the MSE profile were minor, although candesartan cilexetil had better scores for contentment than placebo (P = .03), and also tended to be associated with better sleep than enalapril (P = .08). In hypertensive patients with ACE-inhibitor-induced cough, the incidence, frequency, and severity of dry cough was significantly lower with candesartan cilexetil than with enalapril, and no different from that found with placebo.

Hypertrophy to failure.

Left ventricular hypertrophy (LVH) is a common consequence of hypertension, and an independent risk factor for cardiovascular morbidity and mortality. The presence and severity of LVH is best determined by echocardiography and expressed as left ventricular mass index or left ventricular wall thickness. Pathological LVH, in response to pressure or volume load on the heart, is characterised by myocyte hypertrophy and hypertrophy/hyperplasia of nonmyocyte cells within the myocardium. Angiotensin II and aldosterone are promoters of increased fibroblast activity and a significant increase in collagen fibres in the myocardium. Early diagnosis and treatment of hypertension has significantly decreased the incidence of LVH and subsequent heart failure in many countries, but the choice of antihypertensive therapy alters the rate of reversal of LVH and the subsequent development of heart failure. Angiotensin converting enzyme (ACE) inhibitors, beta-blockers and calcium channel blockers produce the most rapid reversal of hypertrophy. Meta-analysis of these many small trials suggests an advantage of ACE inhibitors over other groups of antihypertensive agents.

Interdisciplinary treatment of morbidity in benign chest pain.

This study tested the hypothesis that functional morbidity in benign chest pain can be modified independently of symptoms through interdisciplinary medical and cognitive-behavioral intervention. Analyses used data collected in a sixteen-week trial of interdisciplinary treatment for disability in benign chest pain. One hundred four chest pain patients having normal coronary arteriograms (NCA) (n = 14) or mitral valve prolapse (MVP) with no other known cardiac or arterial disease (n = 90) were assigned to individual treatment, group treatment, self-monitoring attention control, or a wait-list control group. Results indicate that interdisciplinary intervention, in group or individualized format, was successful for improving short-term and long-term (follow-up range = six to sixteen months) functional status, in both MVP and NCA patients. Correlation analysis indicated that functional improvements were not dependent on reductions in the frequency of symptoms. In fact, significant reductions in disability were obtained in those treated patients (13 of 43) who reported no reduction, or an actual increase, in the frequency of chest symptoms. These data indicate that disability in benign chest pain may be modified independently of symptoms by an integration of medical and cognitive-behavioral strategies.

A Canadian multicentre study of a 48 h infusion of milrinone in patients with severe heart failure.

Milrinone is a nonglycoside, nonsympathomimetic bipyridine with positive inotropic and systemic vasodilator properties. In order to evaluate the efficacy and safety of a short term infusion of milrinone, 105 patients with stable New York Heart Association (NYHA) class III or IV heart failure received a loading dose (50 micrograms/kg) and a 48 h continuous infusion (0.5 micrograms/kg/min). Administration of the loading dose resulted in a 28% decrease in pulmonary capillary wedge pressure (PCWP) (P less than 0.001), a 38% increase in cardiac index (P less than 0.001), and a 34% increase in stroke volume index (P less than 0.001) within 15 mins. Milrinone infusion maintained an average 27% and 24% reduction in PCWP during the first and second days, respectively (P less than 0.001). Cardiac index was 32% and 34% above baseline during the same intervals (P less than 0.001). There were no clinically significant changes in heart rate or mean arterial blood pressure during the study period. In a subset of 47 patients who underwent Holter monitoring before and during infusion, a significant increase in ventricular arrhythmias (premature ventricular complexes per hour, ventricular couplets per hour and ventricular runs greater than or equal to three) was demonstrated (P less than 0.0001). In general, milrinone was well tolerated. Of the 105 patients entered, one died of an acute myocardial infarction after premature termination of the infusion, and the infusion rate was decreased in two others because of supraventricular arrhythmias. In patients with severe heart failure, intravenous milrinone has significant beneficial hemodynamic effects. ECG monitoring for arrhythmias is recommended during milrinone infusion.

Doxazosin for the treatment of chronic congestive heart failure: results of a randomized double-blind and placebo-controlled study.

In this study we evaluated the effects of once-daily administration of oral doxazosin in patients with chronic congestive heart failure (CHF). After a stabilization period of at least 2 weeks with digitalis and diuretics, 73 patients with chronic CHF were randomized to receive additionally either doxazosin or placebo in double-blind fashion. Patients underwent weekly dose adjustments with increasing doses of doxazosin (1, 2, 4, 8, and 16 mg daily) or placebo for 5 weeks, and 67 were evaluated for 12 additional weeks on maximally tolerated doses of blinded study drugs. Treatment groups were evaluated with respect to symptoms of heart failure, indexes of quality of life and left ventricular function, frequency and type of arrhythmia, adverse events, and mortality rates. Doxazosin (11.9 +/- 0.9 mg) given once daily produced a favorable trend in the investigators' and patients' assessments of symptomatic change. Doxazosin was associated with a significantly higher level of voluntary submaximal exercise and a favorable trend on left ventricular ejection fraction (increase of 9.8% of the baseline value vs 2.7% with placebo; p = NS). During the 3-month steady-dosing period, patients treated with doxazosin had a significant (p less than 0.004) reduction in ventricular arrhythmias and significantly fewer morbid and mortal cardiac events (including episodes of worsening heart failure severe enough to prompt discontinuation of the study, myocardial infarction, and death). Doxazosin was well tolerated, producing no major side effects and only a slightly higher frequency of minor treatment-related side effects compared with placebo (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Nonbacterial thrombotic endocarditis complicating mitral valve prolapse presenting as Parinaud's syndrome--a case report.

Nonbacterial thrombotic endocarditis is the most common form of endocarditis found at autopsy. Systemic embolization may complicate this condition in patients with mitral valve prolapse. The authors report a case of mitral valve prolapse and nonbacterial thrombotic endocarditis in which the presenting feature was Parinaud's syndrome.

Primary pulmonary artery sarcoma mimicking pulmonary thromboembolism.

A 69-year-old woman presenting with dyspnea had a pericardial window created for fibrinous pericarditis. The patient subsequently developed pulmonary hypertension and a ventilation perfusion scan was compatible with pulmonary thromboembolism. A primary tumour of the pulmonary artery was suggested by angiography, computerized axial tomography and magnetic resonance imaging. Pathology confirmed a spindle cell pulmonary artery sarcoma.

Anasarca due to pulmonic valve regurgitation with low pulmonary vascular resistance.

A 57-year-old woman underwent pulmonic valvotomy for congenital pulmonic stenosis. She developed severe pulmonic insufficiency, secondary tricuspid regurgitation, and anasarca in spite of a normal pulmonary artery pressure. Insertion of a pulmonary valve prosthesis and tricuspid valve plication reversed all clinical symptoms and signs of this rare complication of pulmonary valvotomy.

Use of calcium ion entry blockers in family practice.

Verapamil, nifedipine, and diltiazem are drugs which decrease intracellular calcium in cardiac muscle, smooth muscle, and nodal cardiac cells. Unlike B-blockers, each drug acts at a different site on the cell membrane and has an important difference in overall action. Verapamil is used to treat angina, systemic hypertension, hypertrophic cardiomyopathy, and supraventricular and junctional tachyarrhythmias. Nifedipine is useful in angina, vasospastic disorders, and hypertension. A specific role for diltiazem is now being defined.

A placebo-controlled study to determine the efficacy of oral disopyramide phosphate for the prophylaxis of ventricular dysrhythmias after acute myocardial infarction.

1 To evaluate oral disopyramide phosphate in the prophylaxis of dysrhythmias occurring in acute myocardial infarction (MI) patients (presenting within 12 h of symptoms, age 21-70 years), a placebo-controlled, randomized double-blind, in hospital trial was conducted. After prognostic stratification (anterior and non-anterior MI at each of 4 regional hospitals) patients were randomly assigned to receive oral disopyramide phosphate (loading dose 150, 200, or 300 mg followed 6 h later by 100, 150, or 200 mg every 6 h for patients assessed to weigh less than 55, 55-85, or greater than 85 kg, respectively or matching placebo. The primary exclusion criteria were overt heart failure, systolic BP less than 100 mmHg, significant heart block or history of urinary retention. Active drug or placebo was continued for 7 days or until (a) detection of "warning arrhythmias' requiring i.v. lignocaine intervention (greater than 5 for 7 days or until (a) detection of "warning arrhythmias' requiring i.v. lignocaine intervention (greater than 5 premature ventricular contractions (PVCs)/min, R on T PVCs, multifocal PVCs, bigeminal PVCs, ventricular tachycardia or ventricular fibrillation) or (b) onset of exclusion criteria. In addition, plasma drug concentrations were determined and 24 h electrocardiographic tapes were obtained on day 1, and on one of days 4-7 but these results are not presented here. 2 Out of 121 patients entering the trial, 101 had confirmatory ECG and enzyme changes. Of these, 9 of 47 patients receiving disopyramide phosphate required lignocaine compared to 20 of 54 receiving placebo (19% v 37%; P = 0.047). Corresponding numbers for patients discontinuing trial medication for other non-fatal complications of MI were 5 and 3, and for those dying, were 3 (2 infarct extensions and 1 massive infarction), and 0, respectively. Respective numbers discontinuing trial medication for possible drug side effects (viz. urinary retention requiring catheterization) were 6 and 1 (P = 0.031). 3 In circumstances where i.v. therapy is deemed impractical, use of oral disopyramide phosphate given prophylactically in patients with acute MI may reduce the incidence of "warning arrhythmias' by a clinically significant extent.

Intracoronary nitroglycerin reversal of life-threatening ergonovine maleate-induced coronary artery spasm.

Ergonovine maleate was given to a patient suspected as a case of Prinzmetal's variant angina following demonstration of normal coronary arteries by angiography. Profound shock, heart block, and severe pain accompanied marked spasm of the left coronary artery. Direct infusion of nitroglycerin into the left coronary artery reversed the spasm when sublingual and intraaortic nitroglycerin failed to prevent further hemodynamic and clinical deterioration.

Pulmonary edema.

The physician who deals with pulmonary edema from a pathophysiologic basis will seldom make a diagnostic or therapeutic error. Recent additions to preload and afterload therapy have greatly helped in the emergency and ambulatory treatment of pulmonary edema due to left heart failure. Careful follow-up and patient self-monitoring are the most effective means of reducing hospitalization of chronic heart failure patients.

Relief of coronary artery spasm by nitroglycerin: time-dependent variability in drug action.

The arteriographic distinction between a fixed atheromatous obstruction and localized vasospasm in the coronary artery is often decided by the response of the lesion to nitroglycerin. We studied the time course of nitroglycerin in four patients with coronary artery spasm as revealed by selective angiography. Following complete dissolution of a 0.6 mg tablet of nitroglycerin sublingually a slight increase in heart rate occurred as early as two minutes, variable changes in overall vessel diameter were observed within four minutes, but the localized spasm remained fixed. It was not until six minutes had elasped that reinjection showed disappearance of spasm and uniform patency of the vessel in all cases. These observations stress the importance of waiting an appropriate period of time (at least six minutes) following complete absorption of sublingual nitroglycerin before any conclusion can be rationally drawn regarding the nature of a stenotic lesion as seen angiographically.

Management of stable angina pectoris.

A state of stable angina pectoris may persist for many years and can usually be managed medically by the family physician. Once contributing or alternate diagnoses have been dealt with, most patients will be rendered either pain-free or greatly improved by use of nitrate and/or ß-adrenoreceptor blockade. A few patients will not be sufficiently improved by medical therapy. These should be considered for aortocoronary saphenous vein bypass surgery.Risk factor modification and psychological support are also managed by the family physician in most instances.

Human lung homotransplantation.

Left lung homotransplantation was performed in a 31-year-old man in terminal irreversible respiratory failure due to advanced silicosis. Within 10 minutes of completion of transplantation, arterial pO(2) rose from 52 to 211 mm. Hg, pCO(2) dropped from 90 to 43 mm. Hg, and pH rose from 7.15 to 7.42. On assisted ventilation, arterial O(2) tension was maintained within normal limits for the first four days. Thereafter, arterio-alveolar difference for O(2) increased to 300 mm. and that for CO(2) to 25 mm. Xenon-133 ventilation perfusion ratios confirmed differences between the two lungs. Terminally, bronchopneumonia and hypoxemia were present. Surfactant content of the lung was within normal limits. Postmortem examination revealed bronchopneumonia, bronchial infarction, lymphatic engorgement and mild rejection. Future efforts should emphasize selection of non-infected donors, minimal reliance on steroids for immunosuppression, cardiopulmonary bypass during transplantation, and more definite criteria for rejection.