US 2013 02374.39A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2013/0237439 A1 Stolen et al. (43) Pub. Date: Sep. 12, 2013 (54) SYSTEMIS AND METHODS USING Publication Classification BOMARKERPANEL, DATA (71) Applicants: Craig M. Stolen, New Brighton, MN (51) Int. Cl. (US); Timothy E. Meyer, North Oaks, GOIN33/68 (2006.01) MN (US); Milan Seth, Minneapolis, MN (52) U.S. Cl. (US); Francis G. Spinale, Blythewood, CPC .................................. G0IN33/6893 (2013.01) SC (US); Nicholas David Wold, Arden USPC .............................................. 506/9; 435/7.92 Hills, MN (US) (72) Inventors: Craig M. Stolen, New Brighton, MN (US); Timothy E. Meyer, North Oaks, (57) ABSTRACT MN (US); Milan Seth, Minneapolis, MN (US); Francis G. Spinale, Blythewood, SC (US); Nicholas David Wold, Arden Embodiments of the disclosure are related to systems and Hills, MN (US) methods for utilizing biomarker panel data with respect to (73) Assignees: MEDICAL UNIVERSITY OF medical devices and methods, amongst other things. In an SOUTH CAROLINA, CHARLESTON, embodiment, the disclosure can include a method of predict SC (US); CARDIAC PACEMAKERS, ing the likelihood of response to CRT therapy. The method INC., ST. PAUL, MN (US) can include quantifying levels of one or more biomarkers in a (21) Appl. No.: 13/756,129 biological sample of a patient, analyzing the quantified levels to determine response to CRT therapy, wherein a panel of (22) Filed: Jan. 31, 2013 biomarkers includes at least two selected from the group Related U.S. Application Data consisting of CRP, SGP-130, SIL-2R, STNFR-II, IFNg, BNP (60) Provisional application No. 61/593,037, filed on Jan. sST2, MMP-2, MMP-9, TIMP-1, TIMP-2, TIMP-4. Other 31, 2012. embodiments are also included herein. Patent Application Publication Sep. 12, 2013 Sheet 1 of 7 US 2013/02374.39 A1 Quantifying Levels of Biomarkers Analyzing the Quantified Levels FIG. 1 Quantifying Levels Of Biomarkers Placing the Patient into a Category FIG. 2 Patent Application Publication Sep. 12, 2013 Sheet 2 of 7 US 2013/02374.39 A1 Quantifying Levels of Biomarkers Analyzing the Quantified Levels Adjusting Therapy FIG. 3 Patent Application Publication Sep. 12, 2013 Sheet 3 of 7 US 2013/02374.39 A1 350 Patient With DOCumented Heart Failure 352 Curren F Medications and Guideline 354 Met? Biomarker Up-Titrate? Add 368 Panel Medications. Using Analysis AHA IACC Guidelines 370 Follow-Up 372 Up-Tirate HF tandard of 360 Care Met? 358 Medications 362 Schedule Patient for CRT Device Follow-Up Referral for Implant Advanced HF Biomarker Treatment Panel Analysis FIG. 4 Patent Application Publication Sep. 12, 2013 Sheet 4 of 7 US 2013/02374.39 A1 Z2 Patent Application Publication Sep. 12, 2013 Sheet 5 of 7 US 2013/02374.39 A1 0// ?ETTONLNOO 06/G9/09/GG/ èJETTONLNOO G0/ Patent Application Publication Sep. 12, 2013 Sheet 6 of 7 US 2013/02374.39 A1 872 WENTRICULAR CHANNEL INTERFACE MCROPROCESSOR CHANNEL NTERFACE SHOCK PULSE GENERATOR TELEMETRY INTERFACE FIG. 7 US 2013/0237439 A1 Sep. 12, 2013 SYSTEMS AND METHODS USING from the group consisting of CRP, SGP-130, sIL-2R, STNFR BOMARKERPANEL, DATA II, IFNg, BNP, sST2, MMP-2, MMP-9, TIMP-1, TIMP-2, TIMP-4. In some embodiments, the method can include 0001. This application claims the benefit of U.S. Provi quantifying levels of one or more of a panel of biomarkers in sional Application No. 61/593,037, filed Jan. 31, 2012, the a biological sample of a patient, and using the quantified content of which is herein incorporated by reference in its levels to place the patient into one of a set of categories, the set entirety. of categories including CRT therapy responders, wherein the panel of biomarkers includes at least two selected from the TECHNICAL FIELD group consisting of CRP, SGP-130, SIL-2R, STNFR-II, IFN 0002 This disclosure relates generally to medical devices y, BNP, sST2, MMP-2, MMP-9, TIMP-1, TIMP-2, TIMP-4. and methods, and more particularly, to systems and methods 0008. An embodiment can include a method of identifying for utilizing biomarker panel data with respect to medical patients that are unlikely to respond to CRT therapy. The devices and methods, amongst other things. method can include quantifying levels of one or more of a panel of biomarkers in a biological sample of a patient, and BACKGROUND OF THE INVENTION analyzing the quantified levels to determine likelihood of 0003 Implantable medical devices (IMDs) are commonly response to CRT therapy, wherein the panel of biomarkers used to provide treatment to patients. Some types of implant includes at least two selected from the group consisting of able medical devices deliver electrical stimuli to a target CRP, SGP-130, sIL-2R, STNFR-II, IFNg, BNP, sST2, MMP tissue via a lead wire (“stimulation lead') or catheter having 2, MMP-9, TIMP-1, TIMP-2, TIMP-4. one or more electrodes disposed in or about the target tissue. 0009. An embodiment can include a method of determin In the context of cardiac rhythm management devices, the ing prognosis of a patient receiving CRT therapy. The method electrical stimulican be delivered in the form of pacing pulses can include selecting a patient that is receiving CRT therapy, to pace the heart and/or relatively high energy defibrillation quantifying levels of one or more of a panel of biomarkers in shocks or cardioversion shocks to terminate arrhythmias. a biological sample of the patient, and analyzing the quanti 0004. The American College of Cardiology/American fied levels to determine prognosis, wherein the panel of biom Heart Association Guidelines for the Evaluation and Manage arkers includes at least two selected from the group consisting ment of Chronic Heart Failure in the Adult defines heart of CRP, SGP-130, sIL-2R, STNFR-II, IFNg, BNP sST2, failure as a “complex clinical syndrome that can result from MMP-2, MMP-9, TIMP-1, TIMP-2, TIMP-4. any structural or functional cardiac disorder that impairs the 0010. An embodiment can include a method of treating a ability of the ventricle to fill with oreject blood'. Heart failure patient. The method can include quantifying levels of one or has various adverse hemodynamic and circulatory conse more of a panel of biomarkers in a biological sample of the quences. Signs and symptoms of heart failure include sys patient, analyzing the quantified levels, and adjusting therapy temic and pulmonary fluid accumulation, reduced activity for the patient based at least in part on the analysis results, levels and exercise tolerance, and poor kidney and cerebral/ wherein the panel of biomarkers includes at least two selected cognitive function, amongst others. Over time, patients with from the group consisting of CRP, SGP-130, sIL-2R, STNFR heart failure typically experience further declines in cardiac II, IFNg, BNP, sST2, MMP-2, MMP-9, TIMP-1, TIMP-2, pump function which is accompanied by increased fluid accu TIMP-4. In some embodiments, the method can include mulation, continued decline in activity/exercise tolerance, selecting a patient that is receiving CRT therapy, quantifying further decline in kidney and cerebral/cognitive function. levels of one or more of a panel of biomarkers in a biological 0005 Cardiac resynchronization therapy (CRT) is used to sample of the patient, analyzing the quantified levels to deter treat the delay in ventricular contractions of the heart that mine an expected response to CRT therapy, comparing the occur in some people with advanced heart failure. A delay expected response to CRT therapy to the patient’s actual between the contraction of the right and left ventricles often response to CRT therapy, and adjusting parameters of the occurs with heart failure, leading to biomechanically ineffi CRT therapy if the patients actual response to CRT therapy is cient heart contractions and reduced cardiac output. Cardiac worse than the expected response to CRT therapy, wherein the resynchronization therapy aims to address this problem panel of biomarkers includes at least two selected from the through stimulation of multiple chambers of the heart in order group consisting of CRP, SGP-130, SIL-2R, STNFR-II, IFNg, to resynchronize contraction of the right and left ventricles. BNP, sST2, MMP-2, MMP-9, TIMP-1, TIMP-2, TIMP-4. 0006 Biomarkers, or biological markers, are substances 0011. An embodiment can include a method of monitoring that can be used as an indicator of a biological state. Biom a patient receiving CRT therapy. The method can include arkers can include Small molecules, proteins, nucleic acids, quantifying levels of one or more of a panel of biomarkers in carbohydrates, lipids, and combinations thereof. a biological sample of the patient, and analyzing the quanti fied levels to determine status. In some embodiments the SUMMARY OF THE INVENTION method can include quantifying levels of one or more of a 0007 Embodiments of the disclosure are related to sys panel of biomarkers in a biological sample of the patient, and tems and methods for utilizing biomarker panel data and analyzing the change in quantified levels overtime to perform related medical devices and methods, amongst other things. one or more selected from the group consisting of analyzing An embodiment can include a method of predicting the like response to therapy changes and monitoring disease progres lihood of response to CRT therapy. The method can include S1O. quantifying levels of one or more of a panel of biomarkers in 0012. An embodiment can include an assay kit including a biological sample of a patient, analyzing the quantified probes to quantify levels of one or more of a panel of biom levels to determine likelihood of response to CRT therapy, arkers in a biological sample of a patient, wherein the panel of wherein the panel of biomarkers includes at least two selected biomarkers includes at least two selected from the group US 2013/0237439 A1 Sep.