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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.amjmed.2009.06.033 Byline: Prakash C. Deedwania (a)(b), Joel A. Lardizabal (c) Keywords: Arrhythmia; Atrial fibrillation; Cardiomyopathy; Heart failure Abstract: Chronic heart failure and atrial fibrillation are 2 major disorders that are closely linked. Their coexistence is associated with adverse prognosis. Both share several common predisposing conditions, but their interaction involves complex ultrastructural, electrophysiologic, and neurohormonal processes that go beyond mere sharing of mutual risk factors. Rate control approach remains the standard therapy for atrial fibrillation in heart failure because current strategies at rhythm control have so far failed to positively impact mortality and morbidity. This is largely because of the shortcomings of current pharmacologic anti-arrhythmic agents. Surgical and catheter-based therapies are promising, but long-term data are lacking. The role of non-anti-arrhythmic therapeutic agents also is being explored. Further progress toward improved understanding the complex relationship between atrial fibrillation and heart failure should improve management strategies. Author Affiliation: (a) Department of Medicine, University of California, San Francisco School of Medicine, San Francisco, Calif (b) Department of Cardiology, Veterans Affairs Medical Center, Fresno, Calif (c) Division of Cardiology, University of California, San Francisco School of Medicine, Fresno Medical Education Program, Fresno Article Note: (footnote) Funding: None., Conflict of Interest: Dr Lardizabal does not have any relationship with industry and financial associations that might pose a conflict of interest. Dr Deedwania was a consultant and speaker and has been on the Advisory Board of Sanofi-Aventis., Authorship: Both authors were significantly involved in all steps of the writing process, including the conception, design, drafting and critical revision of the manuscript, as well as final approval for its submission.

Diabetes is defined by its association with hyperglycemia-specific microvascular complications; however, it also imparts a two- to fourfold risk of cardiovascular disease (CVD). Although microvascular complications can lead to significant [...]

OBJECTIVE--The Treating to New Targets study showed that intensive lipid-lowering therapy with atorvastattn 80 mg/day provides significant clinical benefit beyond that afforded by atorvastatin 10 mg/day in patients with stable [...]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.amjmed.2005.05.018 Byline: Prakash C. Deedwania (a), Vivian A. Fonseca (b) Keywords: Diabetes; Metabolic syndrome; Glucose intolerance; Cardiovascular disease Abstract: As the prevalence of diabetes continues to increase worldwide, diabetes-related macrovascular morbidity and mortality are becoming major health care problems. Epidemiologic evidence suggests this relationship begins early in the progression from normal glucose tolerance to frank diabetes. This report reviews this epidemiologic evidence linking early stages of glucose dysregulation with cardiovascular disease and discusses the results of major clinical trials demonstrating that lifestyle or pharmacologic intervention can reduce the incidence of diabetes in high-risk individuals. These observations indicate that early identification and aggressive treatment of subjects with impaired fasting glucose or impaired glucose tolerance have the potential to reduce both the incidence of diabetes and its related cardiovascular disease. Three clinical trials are being conducted to test whether early pharmacotherapy can reduce or delay the incidence of diabetes, and their results may well begin to shift the treatment paradigm toward earlier intervention. Author Affiliation: (a) Division of Cardiology, Department of Medicine, Veterans Affairs Central California Health Care System, University of California San Francisco Medical Education Program, Fresno, Calif (b) Diabetes Program, Tulane University Medical Center, New Orleans, La Article History: Received 4 February 2005; Revised 4 May 2005; Accepted 4 May 2005

Beta-blockers are underutilized in many patients. Barriers include perceived and real contraindications and frequently cited adverse effects. Misperceptions abound about the benefits and risks of these drugs in patients with [...]

Current management of patients after an acute myocardial infarction (AMI) reflects a variety of approaches ranging from conservative to aggressive. Although each method is appropriate in certain subgroups, their application frequently lacks a scientific basis. Current, clinically relevant, evidence-based practice guidelines are needed for secondary prevention for survivors after an AMI. To meet this need, the California Cardiology Working Group was assembled to evaluate the available data from clinical trials and other published studies and develop evidence-based, cost-effective guidelines for clinicians to use as a basis for patient management after an AMI. The group consisted of 18 members, including cardiologists from academic institutions and physicians working in cardiac intensive care, private practices, and managed care settings, representing a broad spectrum of expertise pertaining to patients who have had an AMI. The members had expertise in cardiac intensive care, interventional cardiology, nuclear cardiology, lipid disorders, echocardiography, and cardiac rehabilitation. The intended audience for these practice guidelines includes all physicians who treat survivors of MI. A literature review of all relevant clinical trials and other published data about the natural history after AMI and the effects of current therapeutic modalities are discussed herein. Case histories served as models for application of the literature-based data. The recommendations for management were reached by consensus vote based on the scientific evidence. When more than 1 management option applied, this was recognized in the recommendations. The recommendations accompany the text.

Although silent ischemia is common in patients with stable coronary artery disease (CAD), controversy surrounds the issue regarding the most appropriate method for detection. Routinely performed exercise tolerance testing provides important prognostic information. However, ambulatory electrocardiographic monitoring (AEM) has the distinct advantage of enabling evaluation of silent ischemia during daily life. Although numerous AEM studies have found a greater occurrence of silent ischemia than symptomatic ischemia in patients with stable angina pectoris, the independent prognostic value of AEM findings has not been definitively established. Several recent studies have addressed the question of whether AEM supplies additional information beyond that obtained from exercise testing. The results of these studies revealed that myocardial ischemia during daily life that is detected by AEM provides additional and independent prognostic information in patients with stable CAD who have evidence of ischemia during exercise testing. (Am J Cardiol 1994;73:15B-18B)

The role of myocardial oxygen demand in the pathogenesis of silent ambulatory myocardial ischemia was evaluated by reviewing and assessing the methods and results of recent studies. The performance of simultaneous ambulatory electrocardiographic and blood pressure monitoring in 25 men with proven coronary artery disease (CAD) revealed significant increases in heart rate and blood pressure (p < 0.001) preceding most silent ischemic events. By plotting the mean heart rate obtained at 5-minute intervals during the 30 minutes before an ischemic event, the ischemic heart rate was shown to be significantly higher (95 [+ or -] 15 vs 74 [+ or -] 11 beats per minute [bpm]; p < 0.01) than the nonischemic heart rate. The evaluation of heart rate changes during ambulatory ischemia (in patients with CAD and ischemia induced by an exercise test using gradual work load increments) showed a significant heart rate increase (> 10 bpm) at 1-5 minutes preceding the onset of ST-segment depression. Heart rate increases during exercise testing according to the gradual work load increments of the National Institutes of Health protocol were compared with the heart rate preceding ischemic events during daily life monitored by ambulatory electrocardiography and were found to be closely related. In contrast, heart rate increases that occurred during exercise testing using the standard Bruce protocol were higher and correlated less with those preceding ischemia in dally life. Heart rate and blood pressure increased significantly in most silent ischemic episodes, indicating that increased myocardial oxygen demand plays a significant role in the pathogenesis of myocardial ischemia during daily life.

To assess the effects of oral bepridil therapy (10-14 days) on cardiac performance and myocardial energetics in the presence of depressed left ventricular function, systemic and coronary hemodynamic effects and neurohumoral effects were evaluated in 7 patients with coronary artery disease and reduced ejection fraction at control, submaximal, and maximal pacing rates during atrial pacing stress. After bepridil therapy, arterial, right atrial, and left ventricular filling pressures as well as systemic vascular resistance and left ventricular stroke work index did not change, suggesting no deleterious effects of bepridil on cardiac performance in patients with reduced ejection fraction. Rate--pressure product, myocardial oxygen consumption, coronary sinus blood flow, myocardial lactate extraction, and catecholamine balance remained unchanged. Development of angina during pacing showed a variable response to bepridil. We conclude that despite its potential negative inotropic effect, bepridil does not exert deleterious effects on hemodynamics or left ventricular performance. The mechanism for its beneficial antianginal effect may be due to favorable redistribution of myocardial blood flow to ischemic zones; no clear effect on anginal threshold or sympathetic tone could be demonstrated in these patients. (Am J Cardiol 1992;69:31D-36D)

* Silent myocardial ischemia has been shown to occur far more frequently than anginal episodes in patients with coronary artery disease. Both an increase in myocardial oxygen demand and abnormalities of coronary vasomotor tone appear to play a significant role in the genesis of silent ischemia. Recent data show that in excess of 40% of patients with stable angina have frequent episodes of silent ischemia. The presence of silent ischemia predicts an increased risk of coronary events and cardiac death. Based on these data, it has been proposed that anti-ischemic therapy should be directed toward control of total ischemic burden. Although several recent studies have demonstrated efficacy of various antianginal drugs in reducing the number and duration of silent ischemic episodes, none has demonstrated beneficial effect on the associated adverse prognosis. (Arch Intern Med. 1991;151:2373-2382

The predictive value of several exercise test parameters in identifying stable angina patients at risk of silent myocardial ischemia during daily life were examined. A total of 97 patients with coronary artery disease, stable angina and ambulatory electrocardiographic data were evaluated. Of the 86 patients with a positive exercise test, 39 (group 1) had [is greater than or equal to] 1 episodes of ST-segment depression and 47 (group 2) did not develop ST changes during ambulatory electrocardiographic monitoring. Comparison of the exercise test parameters between the 2 groups revealed early onset of ischemia during exercise tests as the single most significant (p (Am J Cardiol 1990;66:1151-1156), Angina pectoris is the pain and choking feeling caused by episodes of reduced blood flow to the heart (ischemia). Silent myocardial ischemia occurs when the blood flow is reduced, yet no pain is felt. Silent myocardial ischemia is an indicator of problems and poor survival rates among patients with stable coronary artery disease. Although exercise stress tests are good predictors of heart risk, there is evidence that patients with stable coronary artery disease and a positive exercise test (changes in the electrocardiogram during exercise) are at especially high risk. Patients with prolonged episodes of reduced blood flow detected by ambulatory electrocardiographic monitoring (continuous blood pressure monitoring over a 24-hour period) are also at risk. Routine ambulatory monitoring to detect ischemia is impractical and expensive. To find predictors of silent ischemia that could be identified from the exercise test alone, 97 men with stable angina were evaluated. It was found that the most important measure was how long it took for transient ischemia to develop during the exercise test. Of the 39 patients who had had one or more episodes of silent ischemia during ambulatory monitoring, 95 percent developed ischemia within six minutes of beginning the exercise test. There was less success with predicting the duration of ischemia, perhaps resulting from different causes of the condition during testing and daily life. A combination of two formulas was found to provide a reliable means of predicting the presence of silent ischemia: the time to onset of exercise-induced ischemia and peak double product (a measure of heart muscle oxygen consumption). This method can detect those at increased risk, and unnecessary expensive tests can be avoided. Women were not tested, therefore it is not known if the results apply equally to them. (Consumer Summary produced by Reliance Medical Information, Inc.)

Congestive heart failure (CHF) is the inability of the heart to pump blood effectively, and is characterized by symptoms of weakness, shortness of breath, abdominal discomfort, and edema (fluid retention). This heart disease has been treated with angiotensin-converting enzyme (ACE) inhibitors, which prevent the formation of angiotensin, a factor that constricts blood vessels. Angiotensin also activates the production and release of the adrenal hormone aldosterone, which regulates sodium, chloride, and potassium metabolism. ACE inhibitors were shown to improve circulatory and clinical characteristics of severe CHF, and are also used to treat mild to moderate CHF. These agents also improve the function of the heart ventricles and the quality of life in patients with CHF. Combined therapy with the ACE inhibitor captopril and diuretics, which increase the excretion of water, is an effective alternative treatment to digoxin, which increases heart contraction, in patients with mild to moderate CHF. Other ACE inhibitors, specifically enalapril maleate and lisinopril, are combined with digoxin and diuretics to treat moderate to severe CHF. Captopril and enalapril were shown to improve survival in some patients. All ACE inhibitors have a similar mechanism of action, but differ in their absorption, distribution, metabolism, and excretion from the body. ACE inhibitors with a long duration of action may cause prolonged hypotension (low blood pressure), which may adversely affect organ function and the blood supply to tissues. Agents with a short duration of action produce only transient hypotension that rarely affects organ function. (Consumer Summary produced by Reliance Medical Information, Inc.)

The prevalence and patterns of silent myocardial ischemia were evaluated in 105 stable angina patients receiving conventional antianginal drug therapy. During 2,520 hows of electrocardiographic monitoring, silent ischemia was detected in 45 (43%) patients. A total of 188 ischemia episodes was observed; 163 (87%) were silent and accounted for a total ischemia duration of 5,771 minutes. There was no difference in Un baseline clinical characteristics between the patients with and without ambulatory silent ischemia. However, patients with silent ischemia on ambulatory electrocardiographic monitoring had earlier onset of Ischemia during exercise testing. The highest density of silent Ischemia events ocurred between 6 A.M. and 6 P.M. Comparison of the class or combination of antianginal agents used by the 2 groups revealed no difference. However, in patients with silent ischemia the mean duration per event was shorter for those receiving 2 (p (Am J Cardiol 1990;65:1090-1096), Angina pectoris is a chest pain that occurs when heart muscle is temporarily unable to receive adequate oxygen supply, that is, becomes transiently ischemic. Recently, studies conducted using ambulatory monitoring of patients during daily activities have shown that not all transient ischemic episodes cause pain. Furthermore, this 'silent' ischemia is a significant predictor of poor prognosis. Since most therapeutic regimens for angina have been designed to control symptoms, it is important to evaluate the effectiveness of these regimens in the control of silent ischemia as well. A total of 2,520 hours of electrocardiographic monitoring was performed on 105 patients, all receiving conventional treatment for stable angina. A total of 163 silent ischemic episodes were observed in 45 patients. There were no distinguishing characteristics among those patients who experienced the silent episodes, but it was found that the patients who had the silent episodes also experienced an earlier onset of ischemia during exercise testing. No differences were found in treatment between those with silent ischemia and those without, but there were some differences within the group of patients with silent ischemia. Patients taking beta blockers and patients taking several more than one antianginal drug experienced silent episodes of shorter duration than other patients. The results clearly indicate that silent ischemia is quite common among patients with stable angina pectoris. It is not yet known, however, whether more aggressive treatment designed to reduce silent ischemia will also reduce the generally less favorable prognosis associated with these events. (Consumer Summary produced by Reliance Medical Information, Inc.)

In order to determine the mechanisms of transient myocardial ischemia, in which blood supply to the heart muscle is temporarily interrupted, 25 patients with coronary artery disease and chronic stable angina were continuously monitored for heart rate and blood pressure over a total period of 650 hours. Ninety-two episodes of ischemia were recorded, 92 percent of which were not felt by the subjects. Increases in heart rate and systolic blood pressure (blood pressure following contraction of the heart) usually preceded the onset of transient ischemia, implicating an increased oxygen requirement by the heart in causing the event. However, some episodes showed no increases in these measures, suggesting that other mechanisms that cause constriction of the arteries also play a role. Although the predominance of one over the other may vary by patient, a combination of these factors is very likely. There is no doubt that transient myocardial ischemia occurs in a circadian, or 24-hour, rhythm. During the waking hours it is usually associated with physical activity. There is a surge in heart rate and blood pressure in the morning, resulting in increased demand for oxygen. Epinephrine, a hormone that causes constriction of the circulatory system, is at peak levels at this time, also increasing oxygen demand. However, it has been accepted that at night coronary artery spasm, rather than oxygen demand, causes transient ischemia. This study suggests that oxygen demand is the cause in both instances. Although the exact mechanism is unidentified, there are increases in heart rate and blood pressure before night-time ischemia, suggesting that disturbances of sleep and dreams, along with changes in posture, may be factors. If oxygen demand is the cause of transient myocardial ischemia, the ideal drug therapy would be a long-acting beta blocker for 24-hour protection, as suggested by recent studies. (Consumer Summary produced by Reliance Medical Information, Inc.)

The treatment of high-risk hypertensive patients with diabetes presents clinicians with challenges and opportunities. The coexistence of hypertension and diabetes dramatically and synergistically increases the risk of microvascular and macrovascular complications. Perhaps most important among these is the increased risk of cardiovascular events in this patient population, an observation that can be best appreciated by the increased number of deaths attributed to cardiovascular-related diseases in diabetic patients aged 45 to 65 years. Consequently, aggressive therapy in this population offers the promise of significantly reducing excess cardiovascular deaths. Despite this opportunity for reducing mortality in these high-risk patients, several challenges to treatment remain. While aggressive blood pressure reduction has been documented to reduce the rate of events in these patients, questions remain as to the level to which blood pressure should be reduced. The recent guidelines from the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure emphasized the importance of treating patients with hypertension and diabetes as if they already have target organ damage. Low blood pressure targets of 130/85 mm Hg, with an optimal goal of 120/80 mm Hg, can reduce the risk of events in hypertensive patients with diabetes, regardless of the pharmacological means used. However, there are physiologic and clinical rationale for renin angiotensin system blockade, with angiotensin-converting enzyme inhibition as the preferential therapy in these patients. In this regard, preliminary data with the new class of angiotensin II receptor blockers suggest that these agents may offer benefits equivalent to those observed with angiotensin-converting enzyme inhibitors while offering better tolerance. Arch Intern Med. 2000;160:1585-1594

Despite some indications to the contrary, evidence continues to accumulate that controlling cholesterol levels with drug therapy in older persons is a worthwhile goal. Older persons with hypercholesterolemia have an [...]

The efficacy of a moderate statin dosage for primary prevention of cardiovascular disease events in patients age 40-75 years with type 2 diabetes and no other risk factors was clearly [...]