Abstract: The invention provides a compound of formula (I): or a salt thereof, wherein A, B, R1, R2, R3 and X have any of the values described in the specification, as well as compositions comprising a compound of formula I. The compounds are useful as therapeutic agents for treating diastolic dysfunction.

Abstract: This invention relates to reducing the risk of arrhythmias as a result of an acute cardiovascular disorder or injury such as a myocardial infarction by using mitochondrial-targeted antioxidants to improve cardiac function.

Abstract: Diagnostic methods relating to a cardiac ventricular dysfunction are provided. In some embodiments, the diagnostic method is a method of diagnosing diastolic dysfunction in the absence of systolic dysfunction in a subject. The method comprises assaying a sample obtained from the subject for evidence of activation of renin-angiontensin system (RAS), evidence of oxidative stress, a level of adiponectin, or a combination thereof, wherein, when there is a lack of evidence of RAS activation, a lack of evidence of oxidative stress, a reduction in the level of adiponectin, or a combination thereof, as compared to a control subject, the subject is diagnosed with diastolic dysfunction in the absence of systolic dysfunction. Also provided are methods of diagnosing a type of cardiac ventricular dysfunction, methods of determining a therapeutic regimen for a subject suffering from a cardiac ventricular dysfunction, and methods of treating diastolic dysfunction in the absence of systolic dysfunction.

Abstract: Provided herein are methods of determining a subject's need for anti-coagulation therapy. In exemplary embodiments, the method comprises measuring a level of derivatives of reactive oxygen metabolites (DROMs) in a biological sample obtained from the subject. In exemplary embodiments, the method comprises measuring a level of C-reactive protein (hs-CRP).

Abstract: The invention provides methods of determining risk for stroke in a patient, as well as methods of determining a subject's need for anti-coagulation therapy. In exemplary embodiments, the method comprises measuring a level of derivatives of reactive oxygen metabolites (DROMs) in a biological sample obtained from the subject, wherein an increased level of DROMs, relative to a control level, is indicative of the subject's need for anticoagulation therapy. Further provided are methods of decreasing risk of stroke in a subject, methods of determining the efficacy of a therapeutic agent, methods of monitoring a subject's risk of stroke, and kits.

Abstract: The invention provides a method of treating diastolic dysfunction, e.g., diastolic dysfunction with preserved ejection fraction, in a subject. The method comprises administering to the subject in an amount effective to treat the diastolic dysfunction a cardiac metabolic modifier, as described herein. In some embodiments, the diastolic dysfunction is characterized by (i) a lack of increased late INa in cardiomyocytes, (ii) an increase in myofilament calcium sensitivity, or (iii) a combination thereof. In some embodiments, the subject does not suffer from a cardiac injury or a structural heart disease, as described herein. Further provided are a method of treating heart failure with preserved ejection fraction in a subject, a method of treating acute decompensated heart failure, a method of modulating myofilament calcium sensitivity in a subject, and a method of treating a condition associated with or caused by increased myofilament calcium sensitivity.

Abstract: Diagnostic methods relating to a cardiac ventricular dysfunction are provided. In some embodiments, the diagnostic method is a method of diagnosing diastolic dysfunction in the absence of systolic dysfunction in a subject. The method comprises assaying a sample obtained from the subject for evidence of activation of renin-angiontensin system (RAS), evidence of oxidative stress, a level of adiponectin, or a combination thereof, wherein, when there is a lack of evidence of RAS activation, a lack of evidence of oxidative stress, a reduction in the level of adiponectin, or a combination thereof, as compared to a control subject, the subject is diagnosed with diastolic dysfunction in the absence of systolic dysfunction. A method of diagnosing a type of cardiac ventricular dysfunction, a method of determining a therapeutic regimen for a subject suffering from a cardiac ventricular dysfunction and methods of treating diastolic dysfunction in the absence of systolic dysfunction are also provided.

Abstract: Provided herein are methods of identifying a subject at risk for arrhythmias, heart failure or sudden cardiac death. In exemplary aspects, the method comprises the step of determining a level of splicing factor hLuc7a, splicing factor RBM25 and/or PERK in a biological sample obtained from the subject, wherein an increased level, compared to a control level, indicates a risk for arrhythmia or heart failure. The invention also provides methods of diagnosing hypertrophic cardiomyopathy (HCM), or a risk therefor, in a subject. The method comprises the step of determining a level of E28D, RBM25, PRPF40A, or LUC7L3, or a combination thereof, in a biological sample obtained from the subject, wherein an increased level is indicative of the subject having HCM or a risk therefor. Diagnostic kits comprising binding agents for the markers are furthermore provided.

Abstract: Provided herein are methods of treating a medical condition in which RAS activation is increased. The method comprises the step of administering to a subject a c-Src inhibitor in an amount effective to treat the medical condition. The invention also provides a method of treating or preventing a cardiac arrhythmia. The method comprises the step of administering to the subject a c-Src inhibitor in an amount effective to treat or prevent the cardiac arrhythmia. The invention additionally provides a method of delaying the onset of sudden cardiac death. The method comprises the step of administering to the subject a c-Src inhibitor in an amount effective to delay the onset of SCD. Methods of augmenting gap junction function and methods of increasing Connexin 43 levels in a subject in need thereof are further provided.

Abstract: Methods and compositions for treating and screening drugs for conditions are provided.

Abstract: The present invention relates to novel isoforms in or near the 5? untranslated region (upstream of the start codon) and the 3? untranslated region (down stream of the start codon) which correlates with an increased risk of heart disease. These isoforms are various spliced variants of the wild-type sodium channel mRNA. Preferably, the isoforms that correlate with heart disease are E1B1 (SEQ ID NO. 1), E1B2 (SEQ ID NO. 2), E1B3 (SEQ ID NO. 3), E1B4 (SEQ ID NO. 4), E2B1 (SEQ ID NO. 5), E2B2 (SEQ ID NO. 6), E28B (SEQ ID NO. 7), E28C (SEQ ID NO. 8), and E28D (SEQ ID NO. 9).