The trial to assess chelation therapy 2 (TACT2): Rationale and design.

BACKGROUND: Intravenous edetate disodium-based infusions reduced cardiovascular events in a prior clinical trial. The Trial to Assess Chelation Therapy 2 (TACT2) will replicate the initial study design. METHODS: TACT2 is an NIH-sponsored, randomized, 2x2 factorial, double masked, placebo-controlled, multicenter clinical trial testing 40 weekly infusions of a multi-component edetate disodium (disodium ethylenediamine tetra-acetic acid, or Na2EDTA)-based chelation solution and twice daily oral, high-dose multivitamin and mineral supplements in patients with diabetes and a prior myocardial infarction (MI). TACT2 completed enrollment of 1000 subjects in December 2020, and infusions in December 2021. Subjects are followed for 2.5 to 5 years. The primary endpoint is time to first occurrence of all-cause mortality, MI, stroke, coronary revascularization, or hospitalization for unstable angina. The trial has >;85% power to detect a 30% relative reduction in the primary endpoint. TACT2 also includes a Trace Metals and Biorepository Core Lab, to test whether benefits of treatment, if present, are due to chelation of lead and cadmium from patients. Design features of TACT2 were chosen to replicate selected features of the first TACT, which demonstrated a significant reduction in cardiovascular outcomes in the EDTA chelation arm compared with placebo among patients with a prior MI, with the largest effect in patients with diabetes. RESULTS: Results are expected in 2024. CONCLUSION: TACT2 may provide definitive evidence of the benefit of edetate disodiumbased chelation on cardiovascular outcomes, as well as the clinical importance of longitudinal changes in toxic metal levels of participants.

Trends in the care of patients with acute myocardial infarction at a university-affiliated Veterans Affairs Medical Center.

BACKGROUND: Acute cardiac care of the veterans at Veterans Administration (VA) hospitals has been thought of as poor in quality. We examined the use of life-saving, evidence-based medical therapy in patients admitted with acute myocardial infarction to the University of Arkansas for Medical Sciences-affiliated VA Medical Center in Little Rock and compared the use of this therapy with other hospitals in Arkansas and in the rest of the nation. METHODS: Use of life-saving medical therapy in 117 patients admitted with acute myocardial infarction from January 2002 to December 2002 was compared with the National Registry of Myocardial Infarction database for the identical period. RESULTS: Heparin/low-molecular-weight heparin and glycoprotein IIb/IIIa inhibitors were used in 88% and 66% of patients, respectively. Aspirin, beta adrenergic-blocking agents, angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs), and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) were used in 92%, 93%, 62%, and 79% of the patients, respectively. The use of these therapies was better than in similar patients in Arkansas (P < .001) and the United States as a whole (P < .01). Calcium-channel blockers were used in 16% of the patients. At a mean follow-up period of 1.5 years, use of beta blockers and aspirin had decreased, whereas the use of statins and ACE inhibitors/ARBs was unchanged. CONCLUSION: This study shows that patients with acute myocardial infarction admitted to this university-affiliated VA Medical Center receive evidence-based life-saving medical therapy more often than in the rest Arkansas or in the entire United States. More important, patients at this federal institution continue to receive life-saving medical therapy during follow-up. Better use of evidence-based therapy may be related to affiliation of this VA Medical Center with a teaching institution where board certified cardiologists are involved in short- and long-term care of these patients.

Dietary recommendations in the prevention and treatment of coronary heart disease: do we have the ideal diet yet?

To respond to the question of the best "heart-healthy" diet, we reviewed the effects of common diets on lipids, their efficacy, advantages, and limitations. The high-protein, low-carbohydrate diet is effective for weight loss over the short term, but its long-term benefits remain unproved. The very low-fat diet decreases levels of total and low-density lipoprotein cholesterol and, with lifestyle modifications, may slow progression of coronary atherosclerosis. The high-protein and very low-fat diets are difficult to follow over the long term. The American Heart Association diet, which is rich in fruits, vegetables, and nuts, decreases blood pressure and may be acceptable to most patients. However, it is rich in carbohydrates and may not be suitable for patients who are obese and/or have high levels of triglycerides. In such patients, diet based on foods with a low glycemic index may be an alternative. There is also immense interest in the Mediterranean diet, which is acceptable to most patients, may decrease some biomarkers of coronary atherosclerosis, and may decrease cardiovascular events and death. Despite these options, there is no "fits all" dietary recommendation for prevention of coronary heart disease. Importantly, dietary discretion is only 1 part of lifestyle changes, such as exercise and smoking cessation.

The national cholesterol education program diet vs a diet lower in carbohydrates and higher in protein and monounsaturated fat: a randomized trial.

BACKGROUND: In the United States, obesity is a major clinical and public health problem causing diabetes, dyslipidemia, and hypertension, as well as increasing cardiovascular and total mortality. Dietary restrictions of calories and saturated fat are beneficial. However, it remains unclear whether replacement of saturated fat with carbohydrates (as in the US National Cholesterol Education Program [NCEP] diet) or protein and monounsaturated fat (as in our isocaloric modified low-carbohydrate [MLC] diet, which is lower in total carbohydrates but higher in protein, monounsaturated fat, and complex carbohydrates) is optimal. METHODS: We randomized 60 participants (29 women and 31 men) to the NCEP or the MLC diet and evaluated them every 2 weeks for 12 weeks. They were aged 28 to 71 years (mean age, 44 years in the NCEP and 46 years in the MLC group). A total of 36% of participants from the NCEP group and 35% from the MLC group had a body mass index (calculated as weight in kilograms divided by the square of height in meters) greater than 27. The primary end point was weight loss, and secondary end points were blood lipid levels and waist-to-hip ratio. RESULTS: Weight loss was significantly greater in the MLC (13.6 lb) than in the NCEP group (7.5 lb), a difference of 6.1 lb (P = .02). There were no significant differences between the groups for total, low density, and high-density lipoprotein cholesterol, triglycerides, or the proportion of small, dense low-density lipoprotein particles. There were significantly favorable changes in all lipid levels within the MLC but not within the NCEP group. Waist-to-hip ratio was not significantly reduced between the groups (P = .27), but it significantly decreased within the MLC group (P = .009). CONCLUSIONS: Compared with the NCEP diet, the MLC diet, which is lower in total carbohydrates but higher in complex carbohydrates, protein, and monounsaturated fat, caused significantly greater weight loss over 12 weeks. There were no significant differences between the groups in blood lipid levels, but favorable changes were observed within the MLC diet group.

Metabolic syndrome: dietary interventions.

PURPOSE OF REVIEW: Metabolic syndrome affects almost a quarter of the adult American population and its incidence is rising in the rest of the world. Its treatment involves both pharmacologic and nonpharmacologic interventions. In this review the authors focus on foods with potential benefits for this disease. RECENT FINDINGS: Metabolic syndrome is associated with the risk of diabetes, and thus cardiovascular disease. In recent years, many scientific studies have evaluated the role of different foods and diets in the treatment of the components of metabolic syndrome, especially atherogenic dyslipidemia. SUMMARY: It is imperative to identify strategies that favorably impact this deadly syndrome. Here the authors review how different nutrients in food can modify metabolic syndrome, potentially altering its natural history, and related consequences. Although there is no "all-inclusive" diet yet, it seems plausible that a Mediterranean-style diet exhibits most of the desired attributes.

How to prevent unnecessary coronary interventions: identifying lesions responsible for ischemia in the cath lab.

PURPOSE OF REVIEW: Coronary angiography is limited by the inability to identify intermediate coronary lesions responsible for ischemia. In the catheterization laboratory three techniques can be used for the evaluation of the physiologic significance of intermediate or borderline significant coronary stenoses: (1) pressure wire-derived coronary fractional flow reserve (FFR), (2) Doppler wire-derived measurement of coronary flow reserve (CFR), and (3) intravascular ultrasound (IVUS). RECENT FINDINGS: All of these techniques have been validated for assessing the functional significance of intermediate stenoses, but also have inherent limitations. SUMMARY: Overall, measurement of FFR appears to be the best method for interrogating intermediate coronary lesions. This review discusses the strengths and limitations of each of these techniques.

ST-segment elevation myocardial infarction, severe anemia and nonobstructive coronary disease: case report and brief comment.

When the metabolic demand of the heart exceeds its oxygen supply, myocardial ischemia or infarction (MI) may occur. One of the causes of this condition is severe anemia. The type of MI associated with cases of supply-demand myocardial mismatch is usually a non-ST elevation infarction (Non-STEMI), and is most commonly seen in patients with underlying coronary artery disease. We present a case report of ST segment elevation MI (STEMI), which we believe was secondary to severe anemia, occurring in the absence of angiographically significant coronary artery stenosis or thrombosis. Coronary artery spasm was not seen. In our review of the literature we found no similar cases (MEDLINE 1966-2002).

Can we prevent in-stent restenosis?

Nowadays stent placement has replaced balloon angioplasty as the most commonly performed percutaneous coronary interventional procedure, mainly because of its better acute and chronic outcome. As a result, in-stent restenosis (ISR) has become a widespread problem. The incidence of ISR varies from 10% to 50% and depends on the absence or presence of several risk factors, such as small vessel size, longer lesions, and diabetes. Intravascular ultrasound studies have demonstrated that ISR is mainly caused by neointimal proliferation; consequently, this pathologic process has become the target of many preventive and therapeutic approaches. This article provides an overview of such management strategies, highlighting the rather disappointing experiences with mechanical and systemic drug therapies; the relative merits and disadvantages of intracoronary radiation; and the exciting yet realistic promise, embodied by the recent advancements in drug-eluting stent technology, of potentially eradicating ISR in the near future.

Nonplatelet-mediated effects of aspirin.

Aspirin has nonplatelet-mediated effects that contribute to its efficacy in the primary and secondary prevention of coronary events. These include antiarrhythmic effects, as shown in animal studies, and antiatherosclerotic effects related to increase in nitric oxide synthesis/activity and reduction in inflammatory mediators. Epidemiological studies have also shown primary antiinflammatory properties. Aspirin is known to inhibit vascular smooth muscle cell proliferation and to produce an endothelial stabilizing effect. Other observed outcomes from the administration of this compound include a modest anticoagulant activity, angiogenesis reduction and a decrease in oxidant stress. We believe that these results complement the antiplatelet effect and make this agent unique in the management of ischemic heart disease.