Context:Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome associated with diastolic function abnormalities. It remains unclear which factors, if any, can predict the transition from asymptomatic diastolic dysfunction to an overt symptomatic phase.Materials and Methods:Patients hospitalized with suspected heart failure between January 2012 and November 2014 with a transthoracic echocardiogram demonstrating preserved systolic function were screened (n = 425). Patients meeting the American College of Cardiology Foundation/American Heart Association definition for HFpEF (n = 40) were matched in a 1:1 fashion to individuals admitted for hypertensive urgency with diastolic dysfunction and neither pulmonary edema nor history of heart failure (n = 40). The clinical records and echocardiograms of all eighty patients included in this retrospective study were reviewed.Results:Patients with HFpEF had higher body mass index (BMI), creatinine, beta-blocker use, and Grade 2 diastolic dysfunction when compared to the hypertensive control population. Echocardiographic analysis demonstrated higher right ventricular systolic pressures, left ventricular mass index, E/A, and E/e’ in patients with HFpEF. Similarly, differences were observed in most left atrial (LA) parameters including larger LA maximum and minimum volume indices, as well as smaller LA-emptying fractions in the heart failure group. Multivariate logistic regression analysis revealed LA minimum volume index (odds ratio [OR]: 1.23 [1.09–1.38], P = 0.001) to have the strongest association with heart failure hospitalization after adjustment for creatinine (OR: 7.09 [1.43–35.07], P = 0.016) and BMI (OR: 1.11 [0.99–1.25], P = 0.074).Conclusion:LA minimum volume index best correlated with HFpEF in this patient cohort with diastolic dysfunction.
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. Interestingly, it also showed a particularly large reduction in CVD events and all-cause mortality in the prespecified subgroup of patients with diabetes. The TACT results may support the concept of metal chelation to reduce metal-catalyzed oxidation reactions that promote the formation of advanced glycation end products, a precursor of diabetic atherosclerosis.
Summary
In this review, we summarize the epidemiological and basic evidence linking toxic metal accumulation and diabetes-related CVD, supported by the salutary effects of chelation in TACT. If the ongoing NIH-funded TACT2, in diabetic post-MI patients, proves positive, this unique therapy will enter the armamentarium of endocrinologists and cardiologists seeking to reduce the atherosclerotic risk of their diabetic patients.
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