Methods of prognosis and treatment for heart failure with preserved ejection fraction using urinary protein levels
AssigneeThe Trustees of the University of Pennsylvania
InventorsLei ZHAO, Julio CHIRINOS, Ashok DONGRE
Life of this patent
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Abstract
Methods of prognosis and treatment of subjects with heart failure with preserved ejection fraction (HFpEF) based on urinary protein levels are described herein. Such methods may include obtaining a urine sample of a subject (e.g., a HFpEF patient), measuring urinary protein levels in the sample, analyzing the urinary protein levels, e.g., to identify elevated levels, and determining whether the subject is at risk of death or heart failure hospital admission (DHFA) based on the analysis, and may further include treating the subject based on the risk determination.
Claims166
A method for determining a risk of death or heart failure hospital admission (DHFA) in a subject comprising:
- measuring, or having measured, one or more urinary protein levels in the subject's urine;
- analyzing, or having analyzed, the one or more urinary protein levels;
- and determining the risk of DHFA in the subject based on the analysis of the one or more urinary protein levels.
The method of any preceding claim, further comprising obtaining, or having obtained, a urine sample from the subject, from which the one or more urinary protein levels are measured.
The method of any preceding claim, wherein analyzing the one or more urinary protein levels comprises comparing the one or more urinary protein levels to a threshold.
The method of any preceding claim, wherein the HFpEF is hypercontractile HFpEF.
The method of any preceding claim, wherein the HFpEF is hypocontractile HFpEF.
The method of any preceding claim, further comprising treating the subject with a therapy based on the subject's risk of DHFA.
The method of any preceding claim, wherein the subject has symptomatic heart failure and a left ventricular ejection fraction (LVEF) greater than or equal to 45%.
The method of any preceding claim, wherein the one or more urinary protein levels in the subject's urine are measured using liquid chromatography-mass spectrometry (LC-MS).
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of one or more collagen derived proteins.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of one or more pancreatic alpha amylases.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of one or more urinary proteins selected from the group consisting of ANGPTL2, AMY2A, DNASE1, ALDH1A1, and AMY2B.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of ANGPTL2.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of DNASE1.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of ALDH1A1.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of SLC2A5.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of prostasin.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of one or more proteins selected from the group consisting of DNASE1, AMY2A, ANGPTL2, EGF, ZG16B, ALDH1A1, ICOSLG, PLAU, HSP60, AMY2B, B4GALT1, SLC2A5, and COL15A1.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of one or more proteins selected from the group consisting of ANGPTL2, AMY2A, DNASE1, ALDH1A1, AMY2B, PLAU, HSP60, ZG16B, ICOSLG, and PGKA.
A method of treating heart failure with preserved ejection fraction (HFpEF) in a subject in need thereof, comprising:
- measuring, or having measured, one or more urinary protein levels in the subject's urine;
- analyzing, or having analyzed, the one or more urinary protein levels;
- determining, or having determined, the risk of death or heart failure hospital admission (DHFA) in the subject based on the analysis of the one or more urinary protein levels;
- and
- treating the subject with a HFpEF therapy.
The method of any preceding claim, further comprising obtaining, or having obtained, a urine sample from the subject, from which the one or more urinary protein levels are measured.
The method of any preceding claim, wherein analyzing the one or more urinary protein levels comprises comparing the one or more urinary protein levels to a threshold.
The method of any preceding claim, wherein the HFpEF is hypercontractile HFpEF.
The method of any preceding claim, wherein the HFpEF is hypocontractile HFpEF.
The method of any preceding claim, wherein the HFpEF therapy is selected from the group consisting of a beta blocker, an angiotensin-converting enzyme (ACE) inhibitor, an angiotensin receptor blocker (ARB), an angiotensin receptor-neprilysin (ARN) inhibitor, a mineralocorticoid receptor antagonist (MRA), a SGLT2 inhibitor, a diuretic, a GLP-1 agonist, a calcium sensitizer, a soluble guanylate cyclase stimulator, and ivabradine, or any combination thereof.
The method of any preceding claim, further comprising, following treatment:
- measuring, or having measured, one or more post-treatment urinary protein levels in the subject's urine;
- analyzing, or having analyzed, the one or more post-treatment urinary protein levels;
- and
- determining, or having determined, the post-treatment risk of DHFA in the subject based on the analysis of the one or more urinary protein levels.
The method of any preceding claim, wherein the subject has symptomatic heart failure and a left ventricular ejection fraction (LVEF) greater than or equal to 45%.
The method of any preceding claim, wherein the one or more urinary protein levels in the subject's urine are measured using liquid chromatography-mass spectrometry (LC-MS).
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of one or more collagen derived proteins.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of one or more pancreatic alpha amylases.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of one or more urinary proteins selected from the group consisting of ANGPTL2, AMY2A, DNASE1, ALDH1A1, and AMY2B.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of ANGPTL2.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of DNASE1.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of ALDH1A1.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of SLC2A5.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of prostasin.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of one or more proteins selected from the group consisting of DNASE1, AMY2A, ANGPTL2, EGF, ZG16B, ALDH1A1, ICOSLG, PLAU, HSP60, AMY2B, B4GALT1, SLC2A5, and COL15A1.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of one or more proteins selected from the group consisting of ANGPTL2, AMY2A, DNASE1, ALDH1A1, AMY2B, PLAU, HSP60, ZG16B, ICOSLG, and PGKA.
The method of any preceding claim, wherein if the subject is determined to be at risk of DHFA, then administering a first HFpEF therapy, and if the subject is determined to not be at risk of DHFA, then administering a second HFpEF therapy.
The method of any preceding claim, wherein if the subject is determined to be at high risk of DHFA, then administering a first HFpEF therapy, and if the subject is determined to be at low risk of DHFA, then administering a second HFpEF therapy.
A method for assessing the severity of HFpEF in a subject comprising:
- measuring, or having measured, one or more urinary protein levels in the subject's urine;
- analyzing, or having analyzed, the one or more urinary protein levels;
- and
- determining the severity of HFpEF in the subject based on the analysis of the one or more urinary protein levels.
A method for monitoring the severity of HFpEF in a subject who is suffering from or has been diagnosed with HFpEF, comprising:
- measuring, or having measured, one or more urinary protein levels in the subject's urine;
- analyzing, or having analyzed, the one or more urinary protein levels;
- and
- determining the severity of HFpEF in the subject based on the analysis of the one or more urinary protein levels.
A method for identifying therapeutic options for a subject at risk of death or heart failure hospital admission (DHFA), comprising:
- (a) obtaining, or having obtained, a urinary sample from the subject;
- (b) measuring, or having measured, one or more urinary protein levels in the sample;
- (c) analyzing, or having analyzed, the urinary protein levels in the sample;
- (d) selecting at least one urinary protein based on the analysis;
- and
- (e) selecting a drug or drug combination, wherein the drug or drug combination has a functional effect on the at least one urinary protein selected in (d).
The method of any preceding claim, wherein the drug or drug combination is selected from the group consisting of a beta blocker, an angiotensin-converting enzyme (ACE) inhibitor, an angiotensin receptor blocker (ARB), an angiotensin receptor-neprilysin (ARN) inhibitor, a mineralocorticoid receptor antagonist (MRA), a diuretic, a GLP-1 agonist, a calcium sensitizer, a soluble guanylate cyclase stimulator, ivabradine, a SGLT2 inhibitor, and aficamten, or a pharmaceutically acceptable salt thereof, or any combination thereof.
A method of treating heart failure with preserved ejection fraction (HFpEF) in a subject in need thereof, comprising:
- measuring, or having measured, one or more urinary protein levels in the subject's urine;
- analyzing, or having analyzed, the one or more urinary protein levels;
- determining, or having determined, the severity of HFpEF in the subject based on the analysis of the one or more urinary protein levels;
- and
- treating the subject with a HFpEF therapy.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the levels of one or more collagen derived proteins.
The method of any preceding claim, wherein the one or more collagen derived proteins comprises COL15A1 and/or COL6A1.
The method of any preceding claim, wherein the one or more urinary protein levels comprise the levels of one or more pancreatic alpha amylases.
The method of any preceding claim, wherein the one or more pancreatic alpha amylases comprises AMY2A.
The method of any preceding claim, wherein the one or more pancreatic alpha amylases comprises AMY2B.
The method of any preceding claim, wherein the one or more urinary protein levels comprise levels of one or more proteins selected from the group consisting of ANGPTL2, AMY2A, DNASE1, ALDH1A1, and AMY2B.
The method of any preceding claim, wherein the one or more urinary protein levels comprise the level of ANGPTL2.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of DNASE1.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of ALDH1A1.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of MBD1 and/or IGHA2.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of ANGPTL2, AMY2A, SLC2A5, or combinations thereof.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of SLC2A5.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of prostasin.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of one or more proteins selected from the group consisting of MBD1, IGHA2, albumin, IGLV3-25, MAGEA4, KIF3A, APCS, Haptoglobin, COL15A1, COL6A1, ZG16B, ICOSLG, XPNPEP2, attractin, ALDH1A1, PGKA, PLAU, EGF, AMY2A, ATP1B1, SERPINA5, MELTF, HSP60, B4GALT1, CPE, AMY2B, SLC2A5, PROZ, DNASE1, ATP5F1A, MAN1A1, IGFALS, SLC12A3, prostasin, QPCT, HMCN1, C11orf54, LRRC19, ANGPTL2, and X6R868.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of one or more proteins selected from the group consisting of MBD1, IGHA2, albumin, IGLV3-25, MAGEA4, KIF3A, APCS, and Haptoglobin.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of one or more proteins selected from the group consisting of COL15A1, COL6A1, ZG16B, ICOSLG, XPNPEP2, attractin, ALDH1A1, PGKA, PLAU, EGF, AMY2A, ATP1B1, SERPINA5, MELTF, HSP60, B4GALT1, CPE, AMY2B, SLC2A5, PROZ, DNASE1, ATP5F1A, MAN1A1, IGFALS, SLC12A3, prostasin, QPCT, HMCN1, C11orf54, LRRC19, ANGPTL2, and X6R868.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of one or more proteins selected from the group consisting of DNASE1, AMY2A, ANGPTL2, EGF, ZG16B, ALDH1A1, ICOSLG, PLAU, HSP60, AMY2B, B4GALT1, SLC2A5, and COL15A1.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of one or more proteins selected from the group consisting of MBD1, IGHA2, ANGPTL2, AMY2A, DNASE1, AMY2B, ALDH1A1, PLAU, HSP60, ZG16B, ICOSLG, EGF, PGKA, C11orf54, ATP5F1A, SLC2A5, prostasin, ATP1B1, COL6A1, B4GALT1, and X6R868.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of one or more proteins selected from the group consisting of ANGPTL2, AMY2A, DNASE1, ALDH1A1, AMY2B, PLAU, HSP60, ZG16B, ICOSLG, and PGKA.
The method of any preceding claim, wherein the HFpEF therapy is selected from the group consisting of a beta blocker, an angiotensin-converting enzyme (ACE) inhibitor, an angiotensin receptor blocker (ARB), an angiotensin receptor-neprilysin (ARN) inhibitor, a mineralocorticoid receptor antagonist (MRA), a diuretic, a GLP-1 agonist, a calcium sensitizer, a soluble guanylate cyclase stimulator, ivabradine, a SGLT2 inhibitor, and aficamten, or a pharmaceutically acceptable salt thereof, or any combination thereof.
A method of determining a risk of death or heart failure hospital admission (DHFA) in a subject, comprising determining a risk of DHFA in the subject based on one or more urinary protein levels.
The method of any preceding claim, further comprising measuring or having measured the one or more urinary protein levels in the subject's urine.
The method of any preceding claim, wherein the subject is suffering from and/or has been diagnosed with heart failure with preserved ejection fraction (HFpEF).
The method of any preceding claim, wherein the subject is suffering from and/or has been diagnosed with symptomatic heart failure.
The method of any preceding claim, wherein the subject is suffering from and/or has been diagnosed with NYHA Class II, III, or IV heart failure.
The method of any preceding claim, wherein determining the risk of DHFA comprises determining whether the one or more urinary protein levels are above or below a threshold.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the levels of one or more collagen derived proteins.
The method of any preceding claim, wherein the one or more collagen derived proteins comprises COL15A1 and/or COL6A1.
The method of any preceding claim, wherein the one or more urinary protein levels comprise the levels of one or more pancreatic alpha amylases.
The method of any preceding claim, wherein the one or more pancreatic alpha amylases comprises AMY2A.
The method of any preceding claim, wherein the one or more pancreatic alpha amylases comprises AMY2B.
The method of any preceding claim, wherein the one or more urinary protein levels comprise levels of one or more proteins selected from the group consisting of ANGPTL2, AMY2A, DNASE1, ALDH1A1, and AMY2B.
The method of any preceding claim, wherein the one or more urinary protein levels comprise the level of ANGPTL2.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of DNASE1.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of ALDH1A1.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of MBD1 and/or IGHA2.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of ANGPTL2, AMY2A, SLC2A5, or combinations thereof.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of SLC2A5.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of prostasin.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of one or more proteins selected from the group consisting of MBD1, IGHA2, albumin, IGLV3-25, MAGEA4, KIF3A, APCS, Haptoglobin, COL15A1, COL6A1, ZG16B, ICOSLG, XPNPEP2, attractin, ALDH1A1, PGKA, PLAU, EGF, AMY2A, ATP1B1, SERPINA5, MELTF, HSP60, B4GALT1, CPE, AMY2B, SLC2A5, PROZ, DNASE1, ATP5F1A, MAN1A1, IGFALS, SLC12A3, prostasin, QPCT, HMCN1, C11orf54, LRRC19, ANGPTL2, and X6R868.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of one or more proteins selected from the group consisting of MBD1, IGHA2, albumin, IGLV3-25, MAGEA4, KIF3A, APCS, and Haptoglobin.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of one or more proteins selected from the group consisting of COL15A1, COL6A1, ZG16B, ICOSLG, XPNPEP2, attractin, ALDH1A1, PGKA, PLAU, EGF, AMY2A, ATP1B1, SERPINA5, MELTF, HSP60, B4GALT1, CPE, AMY2B, SLC2A5, PROZ, DNASE1, ATP5F1A, MAN1A1, IGFALS, SLC12A3, prostasin, QPCT, HMCN1, C11orf54, LRRC19, ANGPTL2, and X6R868.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of one or more proteins selected from the group consisting of DNASE1, AMY2A, ANGPTL2, EGF, ZG16B, ALDH1A1, ICOSLG, PLAU, HSP60, AMY2B, B4GALT1, SLC2A5, and COL15A1.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of one or more proteins selected from the group consisting of MBD1, IGHA2, ANGPTL2, AMY2A, DNASE1, AMY2B, ALDH1A1, PLAU, HSP60, ZG16B, ICOSLG, EGF, PGKA, C11orf54, ATP5F1A, SLC2A5, prostasin, ATP1B1, COL6A1, B4GALT1, and X6R868.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of one or more proteins selected from the group consisting of ANGPTL2, AMY2A, DNASE1, ALDH1A1, AMY2B, PLAU, HSP60, ZG16B, ICOSLG, and PGKA.
A method of treating heart failure with preserved ejection fraction (HFpEF) in a subject in need thereof, comprising:
- determining one or more urinary protein levels in the subject;
- and
- if the one or more urinary protein levels are above a threshold, then administering to the subject a first HFpEF therapy, and
- if the one or more urinary protein levels are below a threshold, then administering to the subject a second HFpEF therapy.
A method of treating heart failure with preserved ejection fraction (HFpEF) in a subject in need thereof, wherein the subject has been administered a first HFpEF therapy, comprising:
- determining one or more urinary protein levels in the subject;
- and
- if the one or more urinary protein levels are above a threshold, then administering to the subject a second HFpEF therapy.
A method of treating heart failure with preserved ejection fraction (HFpEF) in a subject in need thereof, wherein the subject has been administered a first HFpEF therapy, comprising:
- determining one or more urinary protein levels in the subject;
- and
- if the one or more urinary protein levels are below a threshold, then administering to the subject a second HFpEF therapy.
The method of any preceding claim, wherein the second HFpEF therapy comprises a different drug than the first therapy.
The method of any preceding claim, wherein the first HFpEF therapy comprises a first drug at a first dosage and the second therapy comprises the first drug at a second dosage.
The method of any preceding claim, wherein the first HFpEF therapy is selected from the group consisting of a beta blocker, an angiotensin-converting enzyme (ACE) inhibitor, an angiotensin receptor blocker (ARB), an angiotensin receptor-neprilysin (ARN) inhibitor, a mineralocorticoid receptor antagonist (MRA), a diuretic, a GLP-1 agonist, a calcium sensitizer, a soluble guanylate cyclase stimulator, and ivabradine, or a pharmaceutically acceptable salt thereof, or any combination thereof.
The method of any preceding claim, wherein the first HFpEF therapy is a SGLT2 inhibitor.
The method of any preceding claim, wherein the first HFpEF therapy is aficamten or a pharmaceutically acceptable salt thereof.
The method of any preceding claim, wherein the second HFpEF therapy is selected from the group consisting of a beta blocker, an angiotensin-converting enzyme (ACE) inhibitor, an angiotensin receptor blocker (ARB), an angiotensin receptor-neprilysin (ARN) inhibitor, a mineralocorticoid receptor antagonist (MRA), a diuretic, a GLP-1 agonist, a calcium sensitizer, a soluble guanylate cyclase stimulator, and ivabradine, or a pharmaceutically acceptable salt thereof, or any combination thereof.
The method of any preceding claim, wherein the subject is suffering from and/or has been diagnosed with heart failure with preserved ejection fraction (HFpEF).
The method of any preceding claim, wherein the subject is suffering from and/or has been diagnosed with symptomatic heart failure.
The method of any preceding claim, wherein the subject is suffering from and/or has been diagnosed with NYHA Class II, III, or IV heart failure.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the levels of one or more collagen derived proteins.
The method of any preceding claim, wherein the one or more collagen derived proteins comprises COL15A1 and/or COL6A1.
The method of any preceding claim, wherein the one or more urinary protein levels comprise the levels of one or more pancreatic alpha amylases.
The method of any preceding claim, wherein the one or more pancreatic alpha amylases comprises AMY2A.
The method of any preceding claim, wherein the one or more pancreatic alpha amylases comprises AMY2B.
The method of any preceding claim, wherein the one or more urinary protein levels comprise levels of one or more proteins selected from the group consisting of ANGPTL2, AMY2A, DNASE1, ALDH1A1, and AMY2B.
The method of any preceding claim, wherein the one or more urinary protein levels comprise the level of ANGPTL2.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of DNASE1.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of ALDH1A1.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of MBD1 and/or IGHA2.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of ANGPTL2, AMY2A, SLC2A5, or combinations thereof.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of SLC2A5.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of prostasin.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of one or more proteins selected from the group consisting of MBD1, IGHA2, albumin, IGLV3-25, MAGEA4, KIF3A, APCS, Haptoglobin, COL15A1, COL6A1, ZG16B, ICOSLG, XPNPEP2, attractin, ALDH1A1, PGKA, PLAU, EGF, AMY2A, ATP1B1, SERPINA5, MELTF, HSP60, B4GALT1, CPE, AMY2B, SLC2A5, PROZ, DNASE1, ATP5F1A, MAN1A1, IGFALS, SLC12A3, prostasin, QPCT, HMCN1, C11orf54, LRRC19, ANGPTL2, and X6R868.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of one or more proteins selected from the group consisting of MBD1, IGHA2, albumin, IGLV3-25, MAGEA4, KIF3A, APCS, and Haptoglobin.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of one or more proteins selected from the group consisting of COL15A1, COL6A1, ZG16B, ICOSLG, XPNPEP2, attractin, ALDH1A1, PGKA, PLAU, EGF, AMY2A, ATP1B1, SERPINA5, MELTF, HSP60, B4GALT1, CPE, AMY2B, SLC2A5, PROZ, DNASE1, ATP5F1A, MAN1A1, IGFALS, SLC12A3, prostasin, QPCT, HMCN1, C11orf54, LRRC19, ANGPTL2, and X6R868.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of one or more proteins selected from the group consisting of DNASE1, AMY2A, ANGPTL2, EGF, ZG16B, ALDH1A1, ICOSLG, PLAU, HSP60, AMY2B, B4GALT1, SLC2A5, and COL15A1.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of one or more proteins selected from the group consisting of MBD1, IGHA2, ANGPTL2, AMY2A, DNASE1, AMY2B, ALDH1A1, PLAU, HSP60, ZG16B, ICOSLG, EGF, PGKA, C11orf54, ATP5F1A, SLC2A5, prostasin, ATP1B1, COL6A1, B4GALT1, and X6R868.
The method of any preceding claim, wherein the one or more urinary protein levels comprises the level of one or more proteins selected from the group consisting of ANGPTL2, AMY2A, DNASE1, ALDH1A1, AMY2B, PLAU, HSP60, ZG16B, ICOSLG, and PGKA.
The method of any preceding claim, wherein the subject is determined to be at risk of HFpEF before the onset of HFpEF.
The method of any preceding claim, wherein the subject is suffering from and/or has been diagnosed with hypertrophic cardiomyopathy (HCM) and is considered at risk for HFpEF.
The method of any preceding claim, wherein the subject is suffering from and/or has been diagnosed with NYHA Class I heart failure and is considered at risk for HFpEF.
The method of any preceding claim, wherein the subject is a HFpEF patient who is resistant to guideline-directed medical therapy.
The method of any preceding claim, wherein the subject is a HFpEF patient who is intolerant to guideline-directed medical therapy.
Dependencies are inferred from the claim text.