Showing papers in "Clinical Cardiology in 1997"

Biology of the endothelium

Abstract: The endothelium releases factors that control vascular relaxation and contraction, thrombogenesis and fibrinolysis, and platelet activation and inhibition. Maintaining the functional integrity of the endothelium, therefore, is critical for the preservation of blood flow and the prevention of thrombosis. This article reviews the primary endothelium-dependent substances that promote either relaxation (e.g., nitric oxide, prostacyclin) or contraction (e.g., endothelin) of blood vessels, including their physiology, mechanism of effect, and role in endothelial dysfunction. Risk factors for cardiovascular disease, such as hypertension, hypercholesterolemia, diabetes, vascular aging, and estrogen deficiency, are discussed in terms of their contributions to endothelial dysfunction, which may be the initial step in atherogenesis.

Endothelial function and oxidant stress.

Abstract: Both endothelial cells and vascular smooth muscle cells are capable of producing reactive oxygen species from a variety of enzymatic sources In disease states such as atherosclerosis and hypertension, vascular production of these reactive oxygen metabolites can increase substantially Increases in the production of superoxide anion can lead to decreases in ambient levels of nitric oxide via a facile radical/radical reaction that occurs more rapidly than the reaction of superoxide anion with superoxide dismutase This phenomenon alters endothelial regulation of vasomotion in a variety of disease conditions Recent evidence suggests that the major source of vascular superoxide ion and hydrogen peroxide is a membrane-bound, reduced nicotinamide-adenine dinucleotide (NADH)-dependent oxidase The activity of this enzyme system is regulated by angiotensin II and is elevated following prolonged exposure to nitroglycerin Alterations of vascular oxidant state caused by angiotensin II may contribute substantially to vascular pathology and may also provide a link between hypertension and atherosclerosis

Coronary risk factors, endothelial function, and atherosclerosis: A review

Abstract: The traditional risk factors for coronary heart disease, which include hypercholesterolemia, hypertension, cigarette smoking, diabetes mellitus, and high-fat diet, have all been associated with impairments in endothelial function. Impaired endothelium function may promote the development of atherosclerosis through its effects on vasoregulation, platelet and monocyte adhesion, vascular smooth muscle cell growth, and coagulation. Increased oxidative stress may be another mechanism by which endothelial dysfunction contributes to atherosclerosis, although controversy exists on this issue. Risk factor modification, particularly lowering elevated concentrations of low-density lipoprotein cholesterol, improves endothelial function. At least seven clinical studies have demonstrated improved endothelial function with cholesterol reductions in patients with markedly elevated or even borderline elevations in cholesterol concentrations, whether or not coronary heart disease is present. Other interventions that improve endothelial function include blood pressure reduction, smoking cessation, and administration of estrogen to postmenopausal women.

Depression and coronary heart disease: a review for cardiologists.

Abstract: Major depression is a common comorbid condition in patients with coronary heart disease (CHD). Although mild emotional distress may be a normal reaction to myocardial infarction or other manifestations of CHD, major depression should not be considered a normal reaction, nor should it be ignored. Major depression is a debilitating comorbid disorder that can seriously complicate recovery and increase the risks of further cardiac morbidity and mortality. Fortunately, it is one that can be successfully treated in the majority of cases. The purpose of this review is to present the evidence for the negative prognostic effects of depression in cardiac patients and to discuss methods for assessing and treating depression in these patients.

Alcohol, ischemic heart disease, and the french paradox

Abstract: Many studies have shown either an inverse relation between alcohol intake and ischemic heart disease or a U-shaped curve in which the equivalent of two drinks per day of any kind of alcohol is associated with a decreased incidence of coronary disease compared with no drinks, while higher doses result in an increased risk of infarction and stroke. Although the cardioprotective effects of most alcoholic beverages are probably due to an elevation of high-density lipoprotein as well as the ability of alcohol to prevent platelet aggregation and increased fibrinolysis, there is an increased favorable effect of red wine. The unique cardioprotective properties of red wine reside in the action of flavonoids which are absent in white wine (with the exception of champagne) and sparse in beer (with the exception of dark beers). The best researched flavonoids are resveritrol and quercetin, which confer antioxidant properties more potent than alpha-tocopherol. Grape juice has about half the amount of flavonoids by volume as does red wine.

Angiotensin-II-receptors: new targets for antihypertensive therapy.

Abstract: The renin-angiotensin system regulates blood pressure and sodium homeostasis through a series of coordinated substrate-enzyme interactions. These interactions result in the production of angiotensin II (AII), which exerts a number of diverse biologic effects mediated through AII cell-surface receptors. Dysregulation of this system is implicated in the pathogenesis of various forms of hypertension. Traditional therapy for hypertension has included angiotensin-converting enzyme inhibitors, which block the production of AII. However, a new class of drugs, AT1-receptor blockers, now offers a number of benefits by specifically blocking the effects of AII at its physiologically relevant receptor.

Circadian rhythmic fractal scaling of heart rate variability in health and coronary artery disease.

Abstract: Background: In clinical cardiology, heart rate variability is a putative index of autonomic cardiovascular function. Signs of reduced vagal activity are not only associated with an enhanced risk of sudden cardiac death, but such impaired heart rate variability became a new predictor of sudden cardiac death and other mortality in patients with a variety of diseased states. Hypothesis: It is postulated (1) that the time structure (chronome) of heart rate variability in clinical health includes a circadian rhythm and deterministic chaos, the latter gauged by the correlation dimension of RR intervals; and (2) that this chronome is altered in patients with coronary artery disease (CAD). Methods: From 24-h Holter records of 11 healthy controls and 10 patients with CAD, 500-s sections around 02:00, 06:00, 10:00, 14:00, 18:00 and 22:00 hours were analyzed for smoothed RR intervals sampled at 4 Hz. Correlation integrals were estimated for embedding dimensions from 1 to 20 with a 1.0-s time lag, using an algorithm modified from Grassberger and Procaccia. The Wilcoxon signed-rank test compares circadian end points assessed by cosinor between the CAD patients and age-matched controls. Results: A circadian rhythm characterizes the correlation dimension of healthy subjects peaking during the night (p «0.005). Patients with CAD have a lowered correlation dimension (p « 0.05) and an altered circadian variation which requires the consideration of an approximately 12-h (circasemidian) component. Conclusion: The results demonstrate the sensitivity of circadian rhythms for the detection of disease. A partial 24- to 12-h (circadian-to-circasemidian) frequency multiplication (or partial variance transposition) in CAD of the correlation dimension, apart from being a potential clue to the etiology of the disease, adds a new feature to a chronocardiology combining, with the fractal scaling, an assessment of circadian and circasemidian components as measures of predictable variability to be tested for use in diagnosis, prognosis, and as putative guides to treatment timing.

Coronary arteriovenous fistulas: collective review and management of six new cases--changing etiology, presentation, and treatment strategy.

Abstract: We considered it worthwhile to review the literature of the last decade (1985-1995) to answer the question whether the etiology and the clinical picture of coronary arteriovenous fistulas (CAVFs) have changed. Furthermore, new therapeutic modalities such as percutaneous transcatheter embolization have been developed. We tried to define the place of these techniques in the therapeutic arena. Clinical presentation and management of six patients with eight congenital CAVFs and 76 subjects with 96 congenital and acquire I CAVFs taken from a review of the recent literature are presented. Sixty-three review subjects (78%) were treated medically with one fatal case. Ligation of the fistula was achieved by surgical techniques in 10% of review subjects, while percutaneous transcatheter embolization (PTE) was performed in nine patients (12%). Percutaneous transcatheter embolization techniques are being increasingly used in the treatment of CAVFs. The etiology of CAVFs has a tendency to show alterations toward the acquired pathogenesis. In 64% of the review subjects the fistula was congenital in origin, and in 36% it had an acquired cause. Among the patients of the current review, the clinical presentations were 55% asymptomatic, 34% chest pain (anginal or atypical), and 13% congestive heart failure. The CAVFs of our six patients are all congenital in origin. In the current review, the clinical presentation showed a trend toward increasing chest complaints (34%) compared with the review (10%) published in the mid 1970s. This may be due to a higher mean age, and hence increased concurrent coronary artery disease due to aging compared with the review population of two decades ago.

Endothelial dysfunction in essential hypertension

Abstract: In the last decade, significant advances have occurred in our understanding of the presence and nature of endothelial dysfunction in a number of cardiovascular conditions, including hypertension. Endothelium-derived nitric oxide (NO) is recognized as an important mediator of endothelium-dependent vascular relaxation, and a defect in the endothelium-derived NO system--possibly decreased synthesis and/or release of NO by endothelial cells--is now known to cause the abnormal response to acetylcholine in hypertensive vessels and to account at least in part for the increased vascular resistance observed in hypertension. Extensive research by our laboratory and others to determine the nature of the defect in the NO system has found that the defect is not related to decreased availability of L-arginine, the NO precursor, or to a defect at the muscarinic receptor level or a specific G protein-dependent intracellular signal-transduction pathway; nor is it related to extracellular inactivation of NO by superoxide anion. These findings have contributed to our understanding of endothelial dysfunction in essential hypertension and have pointed out distinctions between the mechanisms leading to this vascular abnormality in hypertensive and hypercholesterolemic patients. While the exact nature of the NO system defect in hypertension is still to be clarified, the vasoconstrictive and proatherogenic effects of endothelial dysfunction probably contribute to the cardiovascular complications associated with elevated blood pressure. Continued research targeted at the identification of the precise mechanism(s) responsible for endothelial dysfunction in hypertension may lead to the development of novel therapeutic strategies to reduce the vascular complications associated with the hypertensive process.

Left atrial size is the major predictor of cardiac death and overall clinical outcome in patients with dilated cardiomyopathy: a long-term follow-up study.

Abstract: Hypothesis: This study was undertaken to determine whether echo-derived left atrial dimension and other echocardiographic, clinical, and hemodynamic parameters detected at the time of entry into the study may influence prognosis in patients with dilated cardiomyopathy during a long-term follow-up. Methods: This was a prospective cohort analysis of 123 patients with dilated cardiomyopathy. Clinical evaluation, chest x-ray, M-mode and two-dimensional echocardiogram, exercise test, 72-h ambulatory electrocardiogram monitoring, and cardiac catheterization study were performed in all patients. The study was divided into two phases: in the first phase, patients were divided into two groups according to the left atrial size (≥45 mm; <45 mm), with cardiac death as the end point. In the second phase, all patients were further divided into two groups according to their clinical course. A multivariate analysis was performed to determine independent correlated parameters of cardiac mortality and overall clinical outcome. Results: Cardiac mortality rate was 47.9%: 29% in the group without left atrial dilation and 54.3% in the group with dilated left atrium. Multivariate analysis revealed that left atrium ≥45 mm, New York Heart Association functional classes III/IV, and the presence of one or more episodes of ventricular tachycardia at Holter monitoring were independent predictors of cardiac mortality, while left atrium ≥45 mm, left ventricular end-diastolic pressure >17 mmHg, and exercise tolerance ≤ 15 min were independent predictors of poor clinical outcome. Conclusions: Our results revealed that left atrial size is the principal independent predictor of prognosis in patients with dilated cardiomyopathy in that patients with left atrial dilation had an increase in mortality and a worse clinical outcome compared with those without left atrial dilation.

Dofetilide in patients with left ventricular dysfunction and either heart failure or acute myocardial infarction: Rationale, design, and patient characteristics of the DIAMOND studies

Abstract: Background: Attempts to prolong life with antiarrhythmic drugs in patients at increased risk of sudden cardiac death have so far been disappointing or inconclusive. Hypothesis: The Danish Investigations of Arrhythmia and Mortality ON Dofetilide (DIAMOND) encompass two survival studies testing the prophylactic use of the selective potassium-channel blocker, dofetilide, in patients at high risk of sudden death. Methods: The first study includes patients admitted to hospital with congestive heart failure (CHF), the other includes patients with acute myocardial infarction (MI) within the previous 7 days. In both studies patients must have left ventricular systolic dysfunction (ejection fraction 35%) determined by echocardiography. Each of the two studies are planned to enroll 1500 patients. Consecutive hospitalized patients with MI or CHF are screened in 37 Danish hospitals. Eligible patients are randomized to receive dofetilide or matching placebo. All patients are continuously monitored by telemetry for the first 3 days of the study to detect possible arrhythmic events and to ensure resuscitation in case of serious arrhythmias. Minimum duration of follow-up is 12 months. Results: Between November 1993 and July 1996, a total of 5812 consecutive patients with CHF and 8688 consecutive patients with MI was screened for entry. Of these, 1518 patients were included in the CHF study and 1510 patients in the MI study. Overall 1-year mortality of randomized patients were 28 and 22%, respectively. Conclusion: DIAMOND will provide important data on the safety and efficacy of dofetilide in high-risk patients with left ventricular dysfunction and either CHF or MI, as well as evaluate tolerability in these populations.

Heart rate variability as a measure of autonomic nervous system function in anorexia nervosa

Abstract: Background and hypothesis: Alteration in sympathovagal balance may be a mechanism of increased cardiovascular mortality and sudden death of patients with anorexia nervosa. This study was undertaken to characterize cardiac autonomic control in patients with anorexia nervosa by means of heart rate variability analysis. Methods: Heart period variability by 24-h Holter recording was evaluated in 13 young women with anorexia nervosa, 10 constitutionally thin women, and 10 women of normal weight. Results: High-frequency power, a measure of parasympathetic modulation of heart rate, and all-time domain measures of heart rate variability were higher in patients with anorexia nervosa than in thin women and in those of normal weight. Thin women showed lower values of total power and of most components of power spectrum. Conclusions: Our data demonstrate an increased vagal tone in young women with anorexia nervosa. The marked increase in parasympathetic activity, not in response to an increase in sympathetic activity, could be detrimental and may contribute to the higher cardiovascular mortality of these patients.

Myocardial bridging in a young patient with sudden death.

Abstract: Systolic compression of a coronary artery is considered to be a benign phenomenon, although numerous case reports have suggested an association between bridging and sudden death or ischemia in certain patients without other abnormalities on cardiovascular evaluation. We present the case of a young patient with two episodes of spontaneous ventricular fibrillation and electrocardiographic evidence of ischemia, whose only primary abnormality on extensive workup was a long segment of left anterior descending systolic compression. This case adds to the growing body of anecdotal evidence that myocardial bridging may be associated with significant cardiac events.

Doppler echocardiography distinguishes between physiologic and pathologic "silent" mitral regurgitation in patients with rheumatic fever.

Abstract: Background: The diagnosis of rheumatic fever is based on physical findings (major) and supporting laboratory evidence (minor) as defined by the Jones criteria. Rheumatic carditis is characterized by auscultation of a mitral regurgitant murmur. Doppler echocardiography, however, may detect mitral regurgitation when there is no murmur (“silent” mitral regurgitation), even in normal individuals. Hypothesis: The hypothesis of this study was that physiologic mitral regurgitation can be differentiated from pathologic “silent” mitral regurgitation by Doppler echocardiography. Methods: The study group consisted of 68 patients (2–27 years) with normal two-dimensional imaging and Doppler evidence of mitral regurgitation but no murmur. Patients with rheumatic fever (n = 37) met Jones criteria (chorea in 20, arthritis in 17). Patients without rheumatic fever (n = 31) were referred for innocent murmur (n = 7), abnormal electrocardiogram (n = 13), and chest pain (n = 11). Echoes were independently reviewed by two cardiologists blinded to the diagnosis. Pathologic mitral regurgitation was defined as meeting the following four criteria: (1) length of color jet > 1 cm, (2) color jet identified in at least two planes, (3) mosaic color jet, and (4) persistence of the jet throughout systole. Jet orientation was also noted. Results: Using the above criteria, there was agreement in echo interpretation of pathologic versus physiologic mitral regurgitation in 67 of 68 patients (interobserver variability of 1.5%). Pathologic regurgitation was found in 25 (68%) patients with rheumatic fever but in only 2 (6.5%) patients without rheumatic fever (p<0.001). The specificity of Doppler for detecting pathologic regurgitation was 94% with a positive predictive value of 93%. The color mitral regurgitant jet was posteriorly directed in all 25 patients with rheumatic fever. Conclusion: Pathologic “silent” mitral regurgitation of rheumatic fever can be distinguished from physiologic mitral regurgitation using strict Doppler criteria, particularly when the jet is directed posteriorly. These data support the use of Doppler echocardiography as a minor criterion for evaluating patients with suspected rheumatic fever.

Symptomatic improvement and reduced hospitalization for patients attending a cardiomyopathy clinic

Abstract: Background: The major costs associated with the management of congestive heart failure (CHF) are inpatient costs. Outcome studies are therefore important to establish whether intensive outpatient care for heart failure can reduce these costs while at the same time improving outcomes in this disabling disorder. Hypothesis: Care delivered in a cardiomyopathy clinic might result in objective improvement in cardiac function and symptoms while reducing hospital admissions and emergency department visits. Methods: The outcomes of 21 patients treated for 6 months in a cardiomyopathy clinic are evaluated. New patients referred to the clinic with ejection fraction (EF) <0.45 were enrolled. The Minnesota Living with Heart Failure questionnaire was completed at initial and final visits. All patients underwent baseline and final echocardiogram, radionuclide left ventriculogram, and cardiopulmonary exercise testing. Patients were followed by a nurse practitioner and a cardiologist with maximization of standard treatment. Congestive heart failure-related hospitalizations and clinic and emergency room visits for both 6-month periods before and during the study were determined. Results: There was significant (p<0.05) improvement in these parameters: Heart failure score increased 23 points; New York Heart Association class decreased from 2.6 to 2.2; EF increased from 0.24 to 0.36; diastolic and systolic left ventricular dimensions decreased from 65 to 59 mm and from 57 to 50 mm, respectively. The number of clinic visits increased 5-fold, whereas there were 86% (14 to 2, p = 0.017) and 100% (8 to 0, p = 0.002) reductions in the number of CHF hospitalizations and emergency visits. There was one death during follow-up. Conclusion: Managing patients in a cardiomyopathy clinic may result in a better quality of life, with both symptomatic improvement and decreased hospitalizations.

Amiodarone in restoration and maintenance of sinus rhythm in patients with chronic atrial fibrillation after unsuccessful direct‐current cardioversion

Abstract: Background: When direct-current (DC) cardioversion is used, sinus rhythm can be restored, at least temporarily, in 80–90% of patients with atrial fibrillation. However, there is a small but significant group of patients with chronic atrial fibrillation in whom DC cardioversion has failed to restore sinus rhythm. The value of antiarrhythmic drug pretreatment before DC cardioversion is still controversial. Hypothesis: The aim of our study was to assess (1) the effecti veness of repeat DC cardioversion in patients with chronic atrial fibrillation after pretreatment with amiodarone, and (2) the efficacy of amiodarone in maintaining sinus rhythm after repeat cardioversion. Methods: Forty-nine patients with chronic atrial fibrillation after ineffective DC cardioversion were included in the study. Repeat DC cardioversion was performed after loading with oral amiodarone, 10–15 mg/kg body weight/day for a period necessary to achieve the cumulative dose of over 6.0 g. Results: Spontaneous conversion to sinus rhythm during amiodarone pretreatment was achieved in 9 of 49 patients (18%). Direct-current cardioversion was performed in 39 patients and sinus rhythm was achieved in 23 of these patients (59%). Mean heart rate decreased from 95 beats/min before to 68 beats/min after DC cardioversion (p<0.001). Systolic blood pressure significantly (p<0.05) decreased from 126 ± 23 to 108 ± 25 mmHg. Complications occurring in four patients just after electroconversion were well tolerated and of short duration. After 12 months, 52% of patients maintained sinus rhythm on low dose (200 mg/day) amiodarone therapy. Conclusion: Pretreatment with amiodarone and repeat DC cardioversion allows for restoration of sinus rhythm in about 65% of patients with chronic atrial fibrillation after first ineffective DC cardioversion. Direct-current cardioversion can be performed safely with the use of standard precautions in patients who are receiving amiodarone. At 12 months' follow-up, more than 50% of patients maintain sinus rhythm on low-dose amiodarone after successful repeat cardioversion.

A practical approach to torsade de pointes

Abstract: Summary: The term torsade de pointes refers to polymorphic ventricular tachycardia that occurs in the setting of an abnormally long QT interval. While the most common cause is treatment with QT prolonging drugs, torsade de pointes also occurs in the congenital long QT syndromes and in the setting of acquired heart block or severe electrolyte disturbance, notably hypokalemia. Among QT prolonging drugs that cause torsade de pointes, both antiarrhythmics and “noncardioactive” drugs have been recognized. The electrocardiographic features of torsade de pointes include labile QT intervals, prominent U waves, and a “pause-dependent” onset of the arrhythmia. Treatment consists of recognition of the syndrome, correction of underlying electrolyte abnormalities, and withdrawal of any offending drugs. Magnesium, isoproterenol, or cardiac pacing provides specific antiarrhythmic therapy in torsade de pointes.

Modification of the circadian pattern of ventricular tachyarrhythmias by beta-blocker therapy.

Abstract: Background: Sudden cardiac death exhibits a circadian variation and predominantly occurs during morning hours. Beta-adrenergic antagonists have shown to blunt this morning peak. However, previous reports studying the effects of beta blockers on the circadian variation did not analyze the underlying cause of sudden cardiac death. It thus remains unclear whether ventricular tachyarrhythmias are influenced by beta-blocker therapy. Hypothesis: This study tested the hypothesis that beta-blocking agents blunt the morning peak of life-threatening ventricular tachyarrhythmias. Methods: In 87 patients who were treated and monitored with an implantable cardioverter defibrillator, the circadian distribution of ventricular tachyarrhythmias terminated by appropriate shocks was analyzed and compared in those receiving beta blockers versus those not receiving beta-blocker therapy. Results: Tachyarrhythmic episodes in the absence of beta-blocker therapy (n = 344) exhibited a circadian variation with a distinct morning peak (16, 38, 28, and 18% of episodes at 0–6, 6–12, 12–18, and 18–24 h, respectively, p<0.001). In contrast, tachyarrhythmic episodes during beta-blocker therapy (n = 104) were equally distributed over time (22, 27, 24, and 27% of episodes at 0–6, 6–12, 12–18, and 18–24 h, respectively, p = 0.95). The circadian distribution of episodes was significantly different in patients with and those without beta blockade (p<0.05). Conclusion: Beta-adrenergic antagonists influence the circadian distribution of malignant ventricular tachyarrhythmias in patients with an implantable cardioverter defibrillator. The blunted morning peak of tachyarrhythmic events during beta blockade supports the hypothesis that a sympathetic surge is involved in the circadian pattern of malignant arrhythmias.

Variability in the measurement of intracoronary ultrasound images : Implications for the identification of atherosclerotic plaque regression

Abstract: Background and hypothesis: Serial coronary angiography cannot reliably detect the small changes in arterial dimensions. Measurement of arterial dimensions by intracoronary ultrasound (ICUS) may be a superior method to determine the extent of atherosclerotic burden since it directly images the diseased portion of the vessel. Methods: To quantify inter- and intraobserver variability of ICUS measurements, 27 images of atherosclerotic coronary lesions were measured by two study physicians and repeated 14 days later. Results: Interobserver correlation coefficients for external elastic lamina, lumen, and effective plaque area were 0.96, 0.99, and 0.91, respectively. Intraobserver correlation coefficients for external elastic lamina, lumen, and effective plaque area were 0.99, 0.99, and 0.97, respectively. To determine progression or regression in effective plaque area, a minimal difference of 2.77 mm2 (which represents a 23% change in plaque area) is needed. Conclusions: Direct visualization of the extent of atherosclerosis by ICUS can be accomplished with a low degree of inter- and intraobserver variability. ICUS may be a preferable alternative to angiography in atherosclerosis regression trials.

Postinfarction left ventricular pseudoaneurysm.

Abstract: Left ventricular wall rupture after myocardial infarction is a mechanical complication that may result in a pseudoaneurysm. Between January 1994 and October 1996, false or pseudoaneurysms were detected in 6 (0.0026%) of 2,600 consecutive patients (4 women, 2 men; mean age 59.4 years) undergoing cardiac catheterization at University Medical School, Debrecen, Hungary. All patients had a history of cardiovascular disease, with diagnosis of pseudoaneurysm confirmed by echocardiography. The average time from the occurrence of acute infarction to diagnosis was 37.0 days (range 3-80 days). All patients were in New York Heart Association functional class IV congestive heart failure; in four patients cardiogenic shock was present. Five patients underwent coronary angiography, which demonstrated multivessel disease and occlusion of the infarct-related artery (TIMI 0) without adequate collateral circulation (grade 0-1). Five patients had surgical repair of the false aneurysm, and, in three patients, concomitant coronary bypass grafting was performed. The 2-year mortality rate for all patients was 50%. Early diagnosis of false aneurysm is facilitated by echocardiography, and coronary angiography is required before surgery. Early surgical correction with coronary revascularization is advised.

Atrial fibrillation: a review of mechanism, etiology, and therapy.

Abstract: The prevalence of elderly individuals in the populations of developed countries is increasing rapidly, and atrial fibrillation (AF) is quite common in these elderly patients: currently, 11% of the U.S. population is between the ages of 65 and 85 years; 70% of people with AF are between the ages of 65 and 85 years. AF causes symptoms secondary to hemodynamic derangements that are the result of increased ventricular response and loss of atrial booster function. AF can lead to reversible impairment of left ventricular function, cardiac chamber dilatation, clinical heart failure, and thromboembolic events. AF requires treatment in order to prevent these potential complications. Type Ia, Ic, and III antiarrhythmics are capable of converting AF to normal sinus rhythm (NSR). Amiodarone has the greatest efficacy and safety for converting AF and maintaining NSR while digoxin and verapamil are ineffective in restoring NSR. Quinidine, flecainide, disopyramide, and sotalol have also been shown to maintain NSR after conversion of AF. Proarrhythmia is a definite concern with the latter four agents. Alternative therapy for AF includes anticoagulation with warfarin or aspirin for the prevention of thromboembolic events, and a variety of agents to control the ventricular response. All medications used to treat AF carry significant risks in the elderly, whether from proarrhythmia, overdosing because of compliance errors, or hemorrhage secondary to anticoagulation. Treatment of AF must be based on a careful risk-benefit evaluation. The physician must know the capability of the particular patient as well as drug mechanisms and effects in the elderly. The decision to convert patients from AF to NSR or to leave the patient in AF and control the ventricular response represents a complex intellectual challenge. Factors favoring one or the other of these two clinical strategies are discussed. Multicenter clinical trials, for example, the Atrial Fibrillation Follow-up Investigation Rhythm Management (AFFIRM) trial, are currently underway to assess various clinical strategies for maintenance of NSR following conversion from AF. Amiodarone is one of the drugs under investigation.

Conservative treatment for brucella endocarditis

Abstract: Endocarditis is the most devastating complication of brucellosis. The accepted treatment for Brucella endocarditis (BE) is a combination of valve replacement and antibiotics. Conservative antibiotic treatment alone is not recommended by most authors, as it is considered ineffective, risking fatality. We describe a patient with BE, in whom antibiotic treatment alone resulted in complete recovery. On reviewing the literature, we found 12 additional such cases. We compared this group of 13 patients with data from 49 published cases treated with a combination of surgery and antibiotics, with a favorable outcome. Absence of congestive heart failure or a prosthetic valve, relatively mild extravalvular cardiac involvement, and a somewhat shorter disease history until initiation of treatment were characteristic of the group treated conservatively in comparison with patients who underwent surgery. In selected patients with BE, conservative antibiotic treatment may be a valid alternative to surgery.

Non‐hodgkin's lymphoma of the heart in patients infected with human immunodeficiency virus

Abstract: Summary: A case of HIV-associated cardiac non-Hodgkin’s lymphoma (NHL) is described, and the epidemiologic and clinicopathologic features of 21 cases previously reported in the literature are analyzed. All patients were homosexual males, and the cardiac NHL was the first acquired immune de- ficiency syndrome-defining condition in the majority. Patients were referred with nonspecific clinical findings including dys- pnea and tachycardia, but rapid progression of cardiac dys- function was frequent after symptoms appeared. Echocardio- graphy constitutes the most useful noninvasive procedure in the diagnosis of cardiac NHL. Most of the patients had dis- seminated disease at initial presentation; pathologically, the lymphomas were of B lymphocyte origin and of high-grade subtypes. Prognosis of HIV-associated cardiac NHL is gen- erally poor, although clinical remission has been observed with combination chemotherapy. Cardiac lymphomas in HW- associated patients are typically high-grade and often dissem- inate early. Although the prognosis is poor, patients in whom dissemination has not occurred could have longer survival un- der \y

Amiodarone: the expanding antiarrhythmic role and how to follow a patient on chronic therapy.

Abstract: Amiodarone was introduced as an antiarrhythmic compound in the early 1970s and was approved in the U.S. for the treatment of refractory ventricular arrhythmias in late 1984. Since that time the drug has become the most widely studied antiarrhythmic compound with expanding potential indications, including maintaining stability of sinus rhythm, secondary prevention in the survivors of myocardial infarction, and prolongation of survival in certain subsets of patients with congestive heart failure. Intravenous amiodarone was introduced in the U.S. in 1995 for the control of recurrent destabilizing ventricular tachycardia or ventricular fibrillation resistant to conventional therapy. The level of comfort in its use has risen considerably in the recent past. This has stemmed from the reasonably decisive evidence that class I agents increase mortality in patients with structural heart disease. In contrast, amiodarone either reduces mortality or its effect is neutral; this is consistent with its low to negligible proarrhythmic actions. The drug does not aggravate heart failure and it may even increase left ventricular ejection fraction and improve exercise capacity. Above all, it is becoming increasingly evident from wider experience and from controlled clinical trials that the side-effect profile of the drug is not as compelling an issue as it appeared to be when first used in much higher doses. Therefore, the overall objective of amiodarone therapy is to use the lowest dose that produces a defined therapeutic end point without causing serious side effects. Careful clinical surveillance in conjunction with monitoring of certain laboratory parameters and indices of efficacy at regular intervals permits the drug to be used effectively in a large number of patients who fail to respond to, or are intolerant of other antiarrhythmic compounds. Many experienced clinicians have begun to consider the use of amiodarone as first-line therapy in certain disorders of rhythm, especially in patients with severely compromised ventricular function.

Isolated and Preclinical Impairment of Left Ventricular Filling in Insulin- Dependent and Non-Insulin-Dependent Diabetic Patients

Abstract: Summary Backgrourd: Diabetes mellitus can induce a pattern of myocardial pathology known as specific diabetic cardiomyopathy, even if this is not clearly specified. Hvpothesis: The aim of our study was to evaluate the presence of preclinical myocardial damage in insulin- and non-insulin-dependent diabetic patients and controls by assessment with Doppler echocardiography. Methods: Twenty insulin-dependent diabetic (IDDM) patients, I0 non-insulin-dependent diabetic (NIDDM) patients, and 12 healthy individuals (C) as controls, matched for age, gender, and without overt cardiovascular disease, were assessed in this study. Results: Systolic function parameters presented normal values in the three groups, with the exception of a slight reduction in ventricular volume indices in the NIDDM group. Diastolic function was clearly impaired in both groups of patients versus that in healthy controls. In particular, ventricular filling was impaired in the NIDDM compared with the IDDM patients, especially the peak early filling rate E (p

The vital role of papillary muscles in mitral and ventricular function: echocardiographic insights.

Abstract: The two left ventricular (LV) papillary muscles are small structures but are vital to mitral valve competence. Partial or complete rupture, complicating acute myocardial infarction, causes severe or even catastrophic mitral regurgitation, potentially correctable by surgery. Papillary muscle dysfunction is a controversial topic in that the role of the papillary muscle itself, in causing mitral regurgitation post infarction, has been seriously questioned; it is less confusing if this syndrome is attributed not only to papillary muscle but also to adjacent LV wall ischemia or infarction. Papillary muscle calcification is easily and frequently detected on echocardiography, but its clinical significance remains uncertain. Papillary muscle hypertrophy accompanies LV hypertrophy of varied etiology and may have a significant role in producing dynamic late-systolic intra-LV obstruction in hypertrophic cardiomyopathy and other hyperdynamic hypertrophied LV chambers. All the above abnormalities can be adequately assessed by 2-D echocardiography and the Doppler modalities. In selected cases, transesophageal echocardiography can provide additional valuable data by improving visualization of papillary muscles and mitral apparatus.

Plasma nitrite/nitrate level is inversely correlated with plasma low-density lipoprotein cholesterol level.

Abstract: Background: Plasma nitrite/nitrate (NOx) is a stable end product of the vasodilator nitric oxide (NO). However, there are few reports about plasma NOx levels in humans. Hypothesis: The purpose of this study was to assess the availability of plasma NOx for evaluating basal endogenously-synthesized or endothelium-derived NO, and to examine whether NOx levels are lowered in patients with coronary artery disease (CAD) or its risk factors. Methods: Plasma NOx levels were measured using an automated system based on the Griess reaction. NOx levels for a 24-h period reproducibly became lowest at 6 A.M. in restricted healthy volunteers, and became stable in inpatient volunteers at 6 A.M. within 4 days after admission. Results: Based on these findings, NOx levels at 6 A.M. in inpatients can be considered as the basal levels. In 40 inpatients suspected of CAD (28 men, 12 women; mean age 60 ± 11 years), the basal levels of NOx were not related to CAD and its risk factors, except for hypercholesterolemia. The NOx level of patients with hypercholesterolemia was significantly lower than that of patients with normal cholesterol (n = 16, 34 ± 16 μmol/l vs. n = 24, 49 ± 23 μmol/l, p < 0.03). Furthermore, the NOx levels correlated negatively with the total cholesterol and low-density lipoprotein cholesterol levels (r= –0.40, p < 0.01; r = –0.47, p < 0.003, respectively), but not with other lipid fraction levels. Conclusion: The results suggest that the quantity of basal endothelium-derived NO synthesis may be decreased in the presence of hypercholesterolemia.

Pulmonary hypertension: Newer concepts in diagnosis and management

Abstract: Pulmonary hypertension comprises a family of disorders occurring as a primary disease or as a complication of a large number of respiratory and cardiac diseases. Pulmonary hypertension is present when pulmonary artery pressure or mean pressure exceeds 30 mmHg or 20 mmHg, respectively. Underlying the hemodynamic changes that result in pulmonary hypertension, whether from hypoxia, acidosis, increased pulmonary blood flow, increased shear stress, or idiopathic causes, is a dysfunctional vascular endothelium. In this review, the role of the history and physical examination in the initial assessment is emphasized. Newer diagnostic modalities, such as subselective pulmonary angiography and ultrafast computed tomography scanning, are reviewed. Low-flow oxygen, anticoagulation, and calcium-channel blockade are presented as accepted therapeutic modalities. Inhaled nitric oxide and prostacyclin infusion are presented as newer therapies that may be useful given the limited availability of donor organs for hear-lung transplantation. Future therapeutic strategies are likely to develop from advances in vascular biology.

Plaque Disruption and Coronary Thrombosis: New Insight into Pathogenesis and Prevention

Abstract: Clinical and pathologic studies have confirmed that disruption or superficial erosion of atherosclerotic plaque is the major cause of coronary thrombosis, which is the primary mechanism responsible for acute coronary syndromes of unstable angina, acute myocardial infarction, and sudden cardiac death. Serial angiographic studies have shown that nearly 60-70% of acute coronary syndromes evolve from mildly to moderately obstructive atherosclerotic plaques. The risk of plaque disruption appears to be a function of both plaque vulnerability (intrinsic factors) and extrinsic triggers, and is determined largely by the size of the lipid-rich atheromatous core, the thickness of the fibrous cap covering the core, and the presence of ongoing inflammation within and underneath the cap. Hemodynamic or mechanical stresses may precipitate plaque disruption, particularly in places where the fibrous cap is weakest, such as the shoulders. The degree of thrombosis following plaque disruption depends on the thrombogenicity of the disrupted plaque, the disturbed local rheology, and the systemic thrombotic-thrombolytic milieu. Surges in sympathetic activity (such as those provoked by sudden vigorous exercise, emotional stress, or cold weather) may also trigger plaque disruption. These observations have led to the concept of plaque stabilization as a new strategy for the prevention of acute coronary syndromes. Plaque stabilization can be achieved through pharmacologic and lifestyle-modifying interventions that alter plaque composition and/or inflammatory activity within the plaque and thus reduce its vulnerability to disruption.

Myocardial Bridge as a Cause of Thrombus Formation and Myocardial Infarction in a Young Athlete

Abstract: We report here a young male athlete who had an acute myocardial infarction after strenuous exercise. Coronary angiography clearly demonstrated thrombus formation within a prominent myocardial bridge. Periarterial resection surgery was performed, which resulted in resolution of the angiographic “milking” effect of muscle bridge. Our observation. along with previous reports, suggests that myocardial bridges should be added to the list of known causes of sudden death or myocardial infarction in young persons after strenuous exercise. Thrombus formation within a myocardial bridge may be a potential mechanism whereby this anatomic curiosity may cause a tragic clinical event.