# US 7,608,418 B2 · NT-proANP and NT-proBNP for diagnosing cardiac diseases

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- Number: US 7,608,418 B2
- Document ID: US7608418B2
- Status: Granted
- Kind: B2
- Application number: 11/945,309
- Filed: 2007-11-27
- Published: 2009-02-12
- Granted: 2009-10-27
- Earliest claimed: 2005-06-07
- Assignees: Roche Diagnostics Operations, Inc.
- Inventors: Georg Hess; Andrea Horsch
- Web page: https://patentgrep.com/patent/US7608418B2

## CPC

- G01N 33/6887: {from muscle, cartilage or connective tissue}
- G01N 33/6893: {related to diseases not provided for elsewhere}
- G01N 2333/58: Atrial natriuretic factor complex; Atriopeptin; Atrial natriuretic peptide [ANP]; Brain natriuretic peptide [BNP, proBNP]; Cardionatrin; Cardiodilatin
- G01N 2800/32: Cardiovascular disorders
- G01N 2800/325: Heart failure or cardiac arrest, e.g. cardiomyopathy, congestive heart failure
- 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

Described are methods for diagnosing a cardiac disease, particularly an acute cardiac event, in a patient presenting with symptoms of acute cardiac decompensation, comprising the steps of (a) measuring, typically in vitro, the level of NT-proBNP (N-terminal brain natriuretic peptide) or a variant thereof in a sample from the patient, (b) measuring, typically in vitro, the level of NIT-proANP (N-terminal atrial natriuretic peptide) or a variant thereof in a sample from the patient, (c) combining the information of the measured levels of NT-proANP and NT-proBNP, wherein an increased level of NT-proANP in presence of a non-increased or weakly increased level of NT-proBNP indicates the presence of an acute cardiac event, or wherein an increased level of NT-proANP in presence of a highly increased level of NT-proBNP indicates the presence of a chronic cardiac disease. The methods also allow distinguishing an acute cardiac event from decompensation of a chronic cardiac disease. Described also are corresponding kits and to methods of treatment of cardiac diseases.

## Claims

### Claim 1

A method for distinguishing an acute cardiac event from a chronic cardiac disease in a patient presenting with symptoms of acute cardiac decompensation, the method comprising the steps of
measuring in a sample from the patient, within 24 hours after occurrence of the symptoms, a level of NT-proANP or an isoform thereof having at least 80% sequence similarity,
measuring in a sample from the patient, within 24 hours after occurrence of the symptoms, a level of NT-proBNP or an isoform thereof having at least 80% sequence similarity, and
comparing the measured level of NT-proANP with the measured level of NT-proBNP as a means of distinguishing an acute cardiac event from a chronic cardiac disease, wherein
a level of NT-proANP of more than 3000 pg/ml and a level of NT-proBNP of less than 1000 pg/ml indicates the presence of an acute cardiac event, and wherein a level of NT-proANP of more than 3000 pg/ml and a level of NT-proBNP of more than 3000 pg/ml and indicates the presence of a chronic cardiac disease.

### Claim 2 (depends on 1)

The method according to claim 1 wherein measurements of NT-proANP and NT-proBNP are performed in parallel.

### Claim 3 (depends on 1)

The method according to claim 1 wherein the sample is selected from the group consisting of blood, plasma, and serum.

### Claim 4 (depends on 1)

The method according to claim 1 further comprising the step of measuring a level of NT-proANP in at least one additional sample.

### Claim 5 (depends on 1)

The method according to claim 1 further comprising the step of measuring a level of NT-proBNP in at least one additional sample.

### Claim 6 (depends on 1)

The method according to claim 1 wherein a time-course of NT-proANP and/or NT-proBNP is established.

### Claim 7 (depends on 1)

The method according to claim 1 further comprising the step of expressing the measured levels of NT-proANP and NT-proBNP as a ratio.

### Claim 8 (depends on 1)

The method according to claim 1 further comprising the step of measuring in a sample from the patient at least one biomarker selected from the group consisting of troponin T, creatine kinase (CK), creatine kinase muscle-brain (CK-MB), and myoglobin.

### Claim 9 (depends on 1)

The method according to claim 1 further comprising the step of measuring a diagnostic indicator selected from the group consisting of left ventricular ejection fraction, echocardiogram, angina pectoris, electrocardiogram, parameters of thyroid or kidney function, arterial hypertension, thallium scintigram, angiography, and cardiac catheterization.

### Claim 10

A method for recommending initiation of treatment of a patient for a cardiac disease, wherein the patient presents with symptoms of acute cardiac decompensation, the method comprising the steps of
measuring in a sample from the patient, within 24 hours after occurrence of the symptoms, a level of NT-proANP or an isoform thereof having at least 80% sequence similarity,
measuring in a sample from the patient, within 24 hours after occurrence of the symptoms, a level of NT-proBNP or an isoform thereof having at least 80% sequence similarity,
comparing the measured level of NT-proANP with the measured level of NT-proBNP as a means of distinguishing an acute cardiac event from a chronic cardiac disease, wherein
a level of NT-proANP of more than 3000 pg/ml and a level of NT-proBNP of less than 1000 pg/ml indicates the presence of an acute cardiac event, and wherein a level of NT-proANP of more than 3000 pg/ml and a level of NT-proBNP of more than 3000 pg/ml and indicates the presence of a chronic cardiac disease,
optionally initiating an examination of the patient by a cardiologist, and
recommending the initiation of treatment if the comparison step indicates the presence of a cardiac disease.
