Metabolic syndrome is characterized by a combination of obesity, hypertension, 
insulin resistance, dyslipidemia, and impaired glucose tolerance. This 
multifaceted syndrome is often accompanied by a hyperdynamic circulatory state 
characterized by increased blood pressure, total blood volume, cardiac output, 
and metabolic tissue demand. Experimental, epidemiological, and clinical studies 
have demonstrated that patients with metabolic syndrome have significantly 
elevated cardiovascular morbidity and mortality rates. One of the main and 
frequent complications seen in metabolic syndrome is cardiovascular disease. The 
primary endpoints of cardiometabolic risk are coronary and peripheral arterial 
disease, myocardial infarction, congestive heart failure, arrhythmia, and 
stroke. Alterations in expression and/or functioning of several key proteins 
involved in regulating and maintaining ionic homeostasis can cause cardiac 
disturbances. One such group of proteins is known as ryanodine receptors 
(intracellular calcium release channels), which are the major channels through 
which Ca(2+) ions leave the sarcoplasmic reticulum, leading to cardiac muscle 
contraction. The economic cost of metabolic syndrome and its associated 
complications has a significant effect on health care budgets. Improvements in 
body weight, blood lipid profile, and hyperglycemia can reduce cardiometabolic 
risk. However, constant hyperadrenergic stimulation still contributes to the 
burden of disease. Normalization of the hyperdynamic circulatory state with 
conventional therapies is the most reasonable therapeutic strategy to date. 
JTV519 (K201) is a newly developed 1,4-benzothiazepine drug with antiarrhythmic 
and cardioprotective properties. It appears to be very effective in not only 
preventing but also in reversing the characteristic myocardial changes and 
preventing lethal arrhythmias. It is also a unique candidate to improve 
diastolic heart failure in metabolic syndrome.