Baseline characteristics including blood and urine metal levels in the Trial to Assess Chelation Therapy 2 (TACT2).

Background: The reduction in cardiovascular disease (CVD) events with edetate disodium (EDTA) in the Trial to Assess Chelation Therapy (TACT) suggested that chelation of toxic metals might provide novel opportunities to reduce CVD in patients with diabetes. Lead and cadmium are vasculotoxic metals chelated by EDTA. We present baseline characteristics for participants in TACT2, a randomized, double-masked, placebo-controlled trial designed as a replication of the TACT trial limited to patients with diabetes.

Coronary Steal Syndrome Secondary to Large Coronary to Pulmonary Artery Fistulas.

Coronary artery fistulas represent rare congenital or acquired defects in the coronary circulation. We describe a case of bilateral coronary to pulmonary artery fistulas resulting in coronary artery steal syndrome in a patient with a history of valve-sparing aortic repair surgery.

Chelation Therapy in Patients With Cardiovascular Disease: A Systematic Review.

Background EDTA is an intravenous chelating agent with high affinity to divalent cations (lead, cadmium, and calcium) that may be beneficial in the treatment of cardiovascular disease (CVD). Although a large randomized clinical trial showed benefit, smaller studies were inconsistent. We conducted a systematic review of published studies to examine the effect of repeated EDTA on clinical outcomes in adults with CVD.

Impact of baseline renal dysfunction on cardiac outcomes and end-stage renal disease in heart failure patients with mitral regurgitation: the COAPT trial.

Aims: Baseline renal dysfunction (RD) adversely impacts outcomes among patients with heart failure (HF) and severe secondary mitral regurgitation (MR). Heart failure and MR, in turn, accelerate progression to end-stage renal disease (ESRD), worsening prognosis. We sought to determine the impact of RD in HF patients with severe MR and the impact of transcatheter mitral valve repair (TMVr) on new-onset ESRD and the need for renal replacement therapy (RRT).

Direct oral anticoagulants in patients with atrial fibrillation and bioprosthetic valve replacement: A meta-analysis.

Objectives: This systematic review and meta-analysis compares direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) in patients with atrial fibrillation and bioprosthetic valve replacement or repair (BVR).

Background: The optimal anticoagulation therapy for patients with atrial fibrillation and a history of bioprosthetic valve replacement or repair (BVR) is not well understood.

Methods: We performed a systematic literature review to identify clinical studies that compared anticoagulation therapies for patients with atrial fibrillation and BVR.

In-hospital outcomes after transcatheter edge-to-edge mitral valve repair in patients with chronic kidney disease: An analysis from the 2010-2016 National inpatient sample.

Objectives: To assess the outcomes following transcatheter edge-to-edge mitral valve repair (TMVr) in patients with chronic kidney disease (CKD).

Background: Percutaneous TMVr is beneficial in high surgical risk patients with severe mitral regurgitation (MR). However, those with CKD are not well studied.

Differential Outcomes With Edetate Disodium-Based Treatment Among Stable Post Anterior vs. Non-Anterior Myocardial Infarction Patients.

Background: The Trial to Assess Chelation Therapy (TACT) found that chelation therapy significantly reduced clinical events in patients with a history of myocardial infarction (MI). The initial report of TACT included the observation of an interaction between edetate disodium infusions and MI location, as well as diabetes. Thus, we examined in greater detail the effect of edetate disodium chelation therapy as a function of MI location and diabetes.

Potential Role of Metal Chelation to Prevent the Cardiovascular Complications of Diabetes.

Context: For decades, there has been epidemiologic evidence linking chronic toxic metal exposure with cardiovascular disease, suggesting a therapeutic role for metal chelation. Given the lack of compelling scientific evidence, however, the indications for metal chelation were never clearly defined. To determine the safety and efficacy of chelation therapy, the National Institutes of Health funded the Trial to Assess Chelation Therapy (TACT).

Chelation therapy to prevent diabetes-associated cardiovascular events.

Purpose Of Review: For over 60 years, chelation therapy with disodium ethylene diamine tetraacetic acid (EDTA, edetate) had been used for the treatment of cardiovascular disease (CVD) despite lack of scientific evidence for efficacy and safety. The Trial to Assess Chelation Therapy (TACT) was developed and received funding from the National Institutes of Health (NIH) to ascertain the safety and efficacy of chelation therapy in patients with CVD.

Recent Findings: This pivotal trial demonstrated an improvement in outcomes in postmyocardial infarction (MI) patients.

Effect of high-dose oral multivitamins and minerals in participants not treated with statins in the randomized Trial to Assess Chelation Therapy (TACT).

Importance: In a prespecified subgroup analysis of participants not on statin therapy at baseline in the TACT, a high-dose complex oral multivitamins and multimineral regimen was found to have a large unexpected benefit compared with placebo. The regimen tested was substantially different from any vitamin regimen tested in prior clinical trials.

Objective: To explore these results, we performed detailed additional analyses of participants not on statins at enrollment in TACT.

Enhanced vasculotoxic metal excretion in post-myocardial infarction patients following a single edetate disodium-based infusion.

Unlabelled: Toxic metals have been associated with cardiovascular mortality and morbidity. We have hypothesized that enhanced excretion of vasculotoxic metals might explain the positive results of the Trial to Assess Chelation Therapy (TACT). The purpose of this study was to determine whether a single infusion of the edetate disodium- based infusion used in TACT led to enhanced excretion of toxic metals known to be associated with cardiovascular events.

Heavy Metals, Cardiovascular Disease, and the Unexpected Benefits of Chelation Therapy.

This review summarizes evidence from 2 lines of research previously thought to be unrelated: the unexpectedly positive results of TACT (Trial to Assess Chelation Therapy), and a body of epidemiological data showing that accumulation of biologically active metals, such as lead and cadmium, is an important risk factor for cardiovascular disease. Considering these 2 areas of work together may lead to the identification of new, modifiable risk factors for atherosclerotic cardiovascular disease. We examine the history of chelation up through the report of TACT.

Chelation therapy to treat atherosclerosis, particularly in diabetes: is it time to reconsider?

Introduction: Case reports and case series have suggested a possible beneficial effect of chelation therapy in patients with atherosclerotic disease. Small randomized trials conducted in patients with angina or peripheral artery disease, however, were not sufficiently powered to provide conclusive evidence on clinical outcomes.

Areas Covered: The Trial to Assess Chelation Therapy (TACT) was the first randomized trial adequately powered to detect the effects of chelation therapy on clinical endpoints.

CHA2DS2-VAS(C) and CHADS2 Scores Predict Adverse Clinical Events in Patients With Pacemakers and Sinus Node Dysfunction Independent of Atrial Fibrillation.

Background: CHA2DS2-VASc and CHADS2 scores were derived and validated for stroke-risk stratification in patients who have a diagnosis of atrial fibrillation (AF). We hypothesized that these scores would predict adverse cardiovascular events even in the absence of AF.

Methods: The CHA2DS2-VASc and CHADS2 scores for 2010 patients with sick sinus syndrome who underwent pacemaker implantation and were enrolled in the Mode Selection Trial (MOST) were calculated.

Metal pollutants and cardiovascular disease: mechanisms and consequences of exposure.

Introduction: There is epidemiological evidence that metal contaminants may play a role in the development of atherosclerosis and its complications. Moreover, a recent clinical trial of a metal chelator had a surprisingly positive result in reducing cardiovascular events in a secondary prevention population, strengthening the link between metal exposure and cardiovascular disease (CVD). This is, therefore, an opportune moment to review evidence that exposure to metal pollutants, such as arsenic, lead, cadmium, and mercury, is a significant risk factor for CVD.

Analysis of early out-of hospital mortality after transcatheter aortic valve implantation among patients with aortic stenosis successfully discharged from the hospital and alive at 30 days (from the placement of aortic transcatheter valves trial).

In high-risk or inoperable patients with severe symptomatic aortic stenosis, transcatheter aortic valve implantation (TAVI) is a proven alternative to standard (i.e., medical) therapy or surgical aortic valve replacement.

Chelation therapy and cardiovascular disease: connecting scientific silos to benefit cardiac patients.

Medical practitioners have treated atherosclerotic disease with chelation therapy for over 50 years. Lack of strong of evidence led conventional practitioners to abandon its use in the 1960s and 1970s. This relegated chelation therapy to complementary and alternative medicine practitioners, who reported good anecdotal results.

Predictors of poor outcomes after transcatheter aortic valve replacement: results from the PARTNER (Placement of Aortic Transcatheter Valve) trial.

Background: Transcatheter aortic valve replacement (TAVR) is a less invasive option for treatment of high-risk patients with severe aortic stenosis. We sought to identify patients at high risk for poor outcome after TAVR using a novel definition of outcome that integrates quality of life with mortality.

Methods And Results: Among 2137 patients who underwent TAVR in the PARTNER (Placement of Aortic Transcatheter Valve) trial or its associated continued access registry, quality of life was assessed with the Kansas City Cardiomyopathy Questionnaire-Overall Summary Scale (KCCQ-OS; range 0-100, where a higher score equates to a better quality of life) at baseline and at 1, 6, and 12 months after TAVR.

EDTA chelation therapy alone and in combination with oral high-dose multivitamins and minerals for coronary disease: The factorial group results of the Trial to Assess Chelation Therapy.

Background: Disodium ethylenediaminetetraacetic acid (EDTA) reduced adverse cardiac outcomes in a factorial trial also testing oral vitamins. This report describes the intent-to-treat comparison of the 4 factorial groups overall and in patients with diabetes.

Methods: This was a double-blind, placebo-controlled, 2 × 2 factorial multicenter randomized trial of 1,708 post-myocardial infarction (MI) patients ≥50 years of age and with creatinine ≤2.

The effect of an EDTA-based chelation regimen on patients with diabetes mellitus and prior myocardial infarction in the Trial to Assess Chelation Therapy (TACT).

Background: The Trial to Assess Chelation Therapy (TACT) showed clinical benefit of an EDTA-based infusion regimen in patients aged ≥50 years with prior myocardial infarction. Diabetes mellitus before enrollment was a prespecified subgroup.

Methods And Results: Patients received 40 infusions of EDTA chelation or placebo.