# US 9,753,039 B2 · Prognosis of adverse events in patients with suspected chronic heart failure > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 9,753,039 B2 - Document ID: US9753039B2 - Status: Granted - Kind: B2 - Application number: 15/211,802 - Filed: 2016-07-15 - Published: 2016-11-03 - Granted: 2017-09-05 - Earliest claimed: 2012-04-12 - Assignees: B.R.A.H.M.S GmbH - Applicants: B.R.A.H.M.S. GmbH - Inventors: Joachim Struck; John GF Cleland - Web page: https://patentgrep.com/patent/US9753039B2 ## CPC - G01N 33/68: involving proteins, peptides or amino acids {(involving lipoproteins G01N33/92)} - G01N 33/6893: {related to diseases not provided for elsewhere} - G01N 2333/585: Calcitonins - G01N 2800/325: Heart failure or cardiac arrest, e.g. cardiomyopathy, congestive heart failure - G01N 2800/50: Determining the risk of developing a disease - G01N 2800/54: Determining the risk of relapse - G01N 2800/56: Staging of a disease; Further complications associated with the disease - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) ## Abstract The present invention is in the field of clinical diagnostics. Particularly the present invention relates to the prognosis of adverse events in patients with stable chronic heart failure or being suspected of having stable chronic heart failure by determination of the level of Procalcitonin (PCT). ## Claims ### Claim 1 A method for determining an enhanced risk of a patient with stable chronic heart failure or suspected of having stable chronic heart failure suffering an adverse event, comprising: (a) detecting and quantitating the level of procalcitonin (PCT), or a fragment thereof consisting of amino acids 1 to 116 or 2 to 116 or 3 to 116 of SEQ ID NO:1, in a sample of bodily fluid of said patient, wherein the detection and quantitation comprises a PCT detection assay wherein the sample is contacted with an antibody that specifically binds to PCT to form a detectable PCT:antibody complex, and detecting and quantitating the complex; and (b) comparing said level of PCT or fragments thereof to a statistically significant predetermined threshold level, wherein, when said level of procalcitonin or fragments thereof exceeds said threshold level, said patient is determined to have an enhanced risk of suffering an adverse event. ### Claim 2 (depends on 1) The method of claim 1, wherein the adverse event is selected from the group consisting of worsening or decompensation of heart failure, a cerebrovascular event, a cardiovascular event and mortality. ### Claim 3 (depends on 1) The method of claim 1, further comprising correlating said level of procalcitonin or fragments thereof with one or more clinical variables selected from a the group consisting of age, gender, diabetes, COPD (chronic obstructive pulmonary disease), symptoms, quality of life, NYHA (New York Heart Association functional classification of heart failure category), BMI (body mass index), heart rate and rhythm, systolic and diastolic blood pressure, edema and severity of ventricular dysfunction. ### Claim 4 (depends on 1) The method of claim 1, wherein the PCT assay has a lower detection limit below 0.05 ng/mL. ### Claim 5 (depends on 1) The method of claim 1, wherein said patient does not have acute or decompensated heart failure. ### Claim 6 (depends on 1) The method of claim 1, wherein said sample is selected from the group consisting of a blood sample, a serum sample, and a plasma sample. ### Claim 7 (depends on 1) The method of claim 1, wherein said threshold level is between 0.015 and 0.05 ng/ml, inclusive. ### Claim 8 (depends on 7) The method of claim 7, wherein said threshold level is between 0.015 ng/mL and 0.035 ng/mL, inclusive. ### Claim 9 (depends on 1) The method of claim 1, wherein the determination of an enhanced risk relates to the enhanced risk of suffering an adverse event within 7 years. ### Claim 10 (depends on 9) The method of claim 9, wherein the determination of an enhanced risk relates to the enhanced risk of suffering an adverse event within 5 years. ### Claim 11 (depends on 9) The method of claim 9, wherein the determination of an enhanced risk relates to the enhanced risk of suffering an adverse event within 4 years. ### Claim 12 (depends on 9) The method of claim 9, wherein the determination of an enhanced risk relates to the enhanced risk of suffering an adverse event within 2 years. ### Claim 13 (depends on 1) The method of claim 1, further comprising correlating said level of procalcitonin or fragments thereof with the level of one or more additional prognostic marker(s), wherein the combination of said level of procalcitonin or fragments thereof with said level of additional prognostic marker(s) increases the predictive value of said level of procalcitonin or fragments thereof or the level of said related marker for getting an adverse event. ### Claim 14 (depends on 13) The method of claim 13, wherein the additional prognostic marker is selected from a group consisting of troponin, myeloperoxidase, CRP (C-reactive protein), neopterin, GDF-15 (growth-differentiation factor 15), ST2 (interleukin-1 receptor-like protein ST2), cystatin-C, haemoglobin, creatinine and the following peptides in form of their mature peptides, precursors, pro-hormones and associated prohormone fragments: natriuretic peptides, adrenomedullin, endothelins, and vasopressin. ### Claim 15 (depends on 14) The method of claim 14, wherein one of said prognostic marker(s) is pre-proBNP (pre-pro-B-type natriuretic peptide) or fragments thereof in a sample obtained from said patient. ### Claim 16 A method for antibiotic treatment guidance in a patient with stable chronic heart failure or suspected of having stable chronic heart failure, said patient having an increased risk of suffering an adverse event, comprising: (a) detecting and quantitating the level of procalcitonin (PCT), or a fragment thereof consisting of amino acids 1 to 116 or 2 to 116 or 3 to 116 of SEQ ID NO:1, in a sample of bodily fluid of said patient, wherein the detection and quantitation comprises a PCT detection assay wherein the sample is contacted with an antibody that specifically binds to PCT to form a detectable PCT:antibody complex, and detecting and quantitating the complex; and (b) comparing said level of PCT or fragments thereof to a statistically significant predetermined threshold level, wherein, when said level of procalcitonin or fragments thereof exceeds said threshold level, said patient is determined to have an enhanced risk of suffering an adverse event, and the need for antibiotic treatment is indicated. ### Claim 17 (depends on 16) The method of claim 16, further comprising administering an antibiotic when the level of PCT or fragments thereof of at least 12 amino acids in length in a sample of a bodily fluid of a patient with stable chronic heart failure or suspected of having stable chronic heart failure is between 0.015 and 0.05 ng/ml, inclusive. ### Claim 18 (depends on 1) The method of claim 1, wherein (a) includes detecting and quantitating the level of a fragment of PCT consisting of amino acids 2 to 116 or 3 to 116 of SEQ ID NO:1, in a sample of bodily fluid of said patient, wherein the detection and quantitation comprises a PCT detection assay wherein the sample is contacted with an antibody that specifically binds to PCT to form a detectable PCT:antibody complex, and detecting and quantitating the complex. ### Claim 19 (depends on 16) The method of claim 16, wherein (a) includes detecting and quantitating the level of a fragment of PCT consisting of amino acids 2 to 116 or 3 to 116 of SEQ ID NO:1, in a sample of bodily fluid of said patient, wherein the detection and quantitation comprises a PCT detection assay wherein the sample is contacted with an antibody that specifically binds to PCT to form a detectable PCT:antibody complex, and detecting and quantitating the complex. ### Claim 20 (depends on 14) The method of claim 14, wherein one of said prognostic marker(s) is NT pro-BNP (SEQ ID NO:2) or BNP (SEQ ID NO:3).