Methods for treating or predicting risk of a ventricular tachyarrhythmia event

Abstract

Provided herein are methods that include (i) determining a level of soluble ST2 in a biological sample from a subject, (i) comparing the level of soluble ST2 in the biological sample to a reference level of soluble ST2 (e.g., a level of soluble ST2 in the subject at an earlier time point), and (iii) selecting, implanting, replacing, or reprogramming an implanted cardiac device, e.g., an ICD, CRT, or CRT-D device, for a subject having an elevated level of soluble ST2 in the biological sample compared to the reference level of soluble ST2, or selecting a subject for participation in, or stratifying a subject participating in, a clinical study of a treatment for reducing the risk of a ventricular tachyarrhythmia (VTA) event. Also provided are methods for evaluating the risk of a VTA event in a subject. Also provided are kits for performing any of these methods.

1 .- 42 . (canceled) 
     
     
         43 . A method of treating a subject to reduce the risk of a VTA event, the method comprising:
 determining a level of soluble ST2 in a biological sample from a subject;   comparing the level of soluble ST2 in the biological sample to a reference level of soluble ST2;   identifying a subject having an elevated level of soluble ST2 in the biological sample compared to the reference level of soluble ST2 as having an increased risk of a VTA event; and   implanting an implanted cardiac device into the identified subject, or replacing or reprogramming an implanted cardiac device in the identified subject.   
     
     
         44 . The method of  claim 43 , wherein the VTA event is ventricular tachycardia, ventricular fibrillation, or ventricular flutter. 
     
     
         45 . The method of  claim 43 , wherein the subject has heart failure. 
     
     
         46 . The method of  claim 43 , wherein the subject has an implanted cardiac defibrillator (ICD) or cardiac resynchronization therapy (CRT) device. 
     
     
         47 . The method of  claim 43 , wherein the reference level of soluble ST2 is a level of soluble ST2 in a healthy subject. 
     
     
         48 . The method of  claim 43 , wherein the risk of a VTA event is the risk of a VTA event within one year. 
     
     
         49 . The method of  claim 43 , wherein the biological sample comprises blood, serum, or plasma. 
     
     
         50 . The method of  claim 43 , further comprising:
 determining the level of one of more additional biomarkers selected from the group consisting of: atrial natriuretic peptide (ANP), proANP, N-terminal (NT)-proANP, brain natriuretic peptide (BNP), proBNP, NT-proBNP, cardiac troponin I, C-reactive protein, creatinine, and Blood Urea Nitrogen (BUN) in the biological sample;   comparing the level of the one or more additional biomarkers in the biological sample to a reference level of the one of more additional biomarkers; and   identifying a subject having an elevated level of the one or more additional biomarkers in the biological sample compared to the reference level of the one or more additional biomarkers as having an increased risk of a VTA event.   
     
     
         51 . The method of  claim 50 , wherein the one or more additional biomarkers are selected from the group consisting of BNP, proBNP, and NT-proBNP. 
     
     
         52 . A method of treating a subject to reduce the risk of a VTA event, the method comprising:
 determining a level of soluble ST2 in a first biological sample obtained from a subject at a first time point;   determining a level of soluble ST2 in a second biological sample obtained from the subject at a second time point;   comparing the level of soluble ST2 in the first biological sample to the level of soluble ST2 in the second biological sample;   identifying a subject having an elevated level of soluble ST2 in the second biological sample compared to the level of soluble ST2 in the first biological sample as having an increased risk of a VTA event; and   implanting an implanted cardiac device into the identified subject, or replacing or reprogramming an implanted cardiac device in the identified subject.   
     
     
         53 . The method of  claim 52 , wherein the VTA event is ventricular tachycardia, ventricular fibrillation, or ventricular flutter. 
     
     
         54 . The method of  claim 52 , wherein the subject has heart failure. 
     
     
         55 . The method of  claim 52 , wherein the subject has an implanted cardiac defibrillator (ICD) or cardiac resynchronization therapy (CRT) device. 
     
     
         56 . The method of  claim 52 , wherein the risk of a VTA event is the risk of a VTA event within one year. 
     
     
         57 . The method of  claim 52 , wherein the first time point and the second time point are within one year of each other. 
     
     
         58 . The method of  claim 52 , wherein the first and second biological sample comprise blood, serum, or plasma. 
     
     
         59 . The method of  claim 52 , further comprising:
 determining the level of one of more additional biomarkers selected from the group consisting of: atrial natriuretic peptide (ANP), proANP, N-terminal (NT)-proANP, brain natriuretic peptide (BNP), proBNP, NT-proBNP, cardiac troponin I, C-reactive protein, creatinine, and Blood Urea Nitrogen (BUN) in one or both of the first biological sample and the second biological sample;   comparing the level of the one or more additional biomarkers in one or both of the first biological sample and the second biological sample to a reference level of the one of more additional biomarkers; and   identifying a subject having an elevated level of the one or more additional biomarkers in one or both of the first biological sample and the second biological sample compared to the reference level of the one or more additional biomarkers as having an increased risk of a VTA event.   
     
     
         60 . The method of  claim 59 , wherein the one or more additional biomarkers is BNP, proBNP, or NT-proBNP. 
     
     
         60 .- 62 . (canceled) 
     
     
         63 . The method of  claim 43 , wherein the implanted cardiac device is an implanted cardiac defibrillator (ICD), a cardiac resynchronization therapy (CRT), or a cardiac resynchronization therapy defibrillator (CRT-D) device. 
     
     
         64 . The method of  claim 43 , wherein the subject has previously had at least one ventricular tachyarrhythmia event. 
     
     
         65 . The method of  claim 43 , wherein the subject is human. 
     
     
         66 . The method of  claim 52 , wherein the implanted cardiac device is an implanted cardiac defibrillator (ICD), a cardiac resynchronization therapy (CRT), or a cardiac resynchronization therapy defibrillator (CRT-D) device. 
     
     
         67 . The method of  claim 52 , wherein the subject has previously had at least one ventricular tachyarrhythmia event. 
     
     
         68 . The method of  claim 52 , wherein the subject is human.