Treatment for Diastolic Dysfunction

Heart failure is the leading cause of hospital stays for those over the age of 65.  The need for therapeutic and diagnostic methods for this condition will only increase as the elderly population continues to grow.  Diastolic dysfunction with preserved left ventricular function is a condition where abnormal stiffening of the heart ventricles leads to abnormal filling of the ventricles during their relaxation period.  As the condition advances, fluid extravasates into the lungs, and the situation is elevated to diastolic heart failure (DHF).   DHF is associated with aging, hypertension, coronary heart disease and infiltrative cardiomyopathy.  While many medications exist for the treatment of contractile systolic heart dysfunction, there are no FDA approved medications for diastolic dysfunction.  Moreover, many cases of drugs that help in systolic dysfunction are inactive in diastolic dysfunction. 

Diastolic heart failure currently accounts for nearly 50% of all heart failure patients, with high levels of mortality (a five year rate of 25-35%) and morbidity (over half the patients are readmitted within a year).  With the elderly population expected to grow, cardiovascular drugs that treat diseases like heart failure, hypertension, and hyperlipidemia will be in demand as an alternative to risky surgical procedures and lifestyle changes.  These compounds have strong growth potential in the next decade or two, especially with the fact that most patients will need to continue treatment for the rest of their lives.

For physician, it can be difficult to distinguish diastolic from systolic heart failure based on physical findings or symptoms.  The signs and symptoms of heart failure are nonspecific and usually can be attributed to other causes like pulmonary disease, anemia, hypothyroidism, depression, and obesity.  In addition, diagnostic criteria for diastolic dysfunction are still being debated.  In reality, DHF diagnosis is a matter of ruling out other possible causes in patients seeming to have heart failure but who have normal heart size and ejection fraction.  Cardiac catheterization is effective at diagnosing DHF, but the invasive nature of the procedure diminishes its appeal.  Doppler echocardiography is currently used for confirming diastolic heart failure, but that delays treatment.  Using an available kit, medical staff can quickly determine elevated beta-natriuretic peptide levels, indicating heart failure in patients; however, this test does not differentiate between systolic and diastolic heart failure.

Description/Details

Scientists at the University of Illinois at Chicago (UIC) have demonstrated for the first time that diastolic dysfunction with preserved ejection fraction associated with hypertension, the most common risk factor, has a unique molecular mechanism.  Furthermore, data indicates that administration of cardiac metabolic modifiers and compounds that behave in a similar manner can help in ameliorating this disease.  Also, UIC Scientists have suggested a potential chemical structure by which these compounds may be exerting their effects.

The invention further provides a method of modulating (i.e., reducing) myofilament calcium sensitivity in a subject, using cardiac metabolic modifiers, such as Ranolazine, to treat heart failure with preserved ejection fraction.  Ranolazine is an FDA-approved compound currently marketed by Gilead for treatment of chronic angina pectoris.  UIC scientists have identified other potential drug candidates for this application.

Applications

  • Treatment for diastolic dysfunction

Benefits

  • The compound (Ranolazine) is already FDA-approved, so the proposed treatment for diastolic dysfunction can be readily marketed.
  • Fewer steps will be needed for ultimately reaching it to the patients because the drug has already been tested for any adverse effects such as toxicity etc.
  • A wider adoption of the drug (because of expanded use in myriad cardiac conditions) will help bring down the cost of drug for patients who suffer from cardiac ailments and have to be treated using Ranolazine.

Inventor Name

Samuel Dudley

Reference #

DD010
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