Diagnosis and management of patients with heart failure.
Healthcare providers need to continually assess how to use resources in the most efficient way to manage the growing number of HF patients. Yearly costs attributable to HF in the U.S. are estimated at $32 billion, including the cost of healthcare services, medication, and lost productivity, and they are expected to triple by 2030. (5) Approximately 80 percent to 90 percent of costs are associated with chronic cases. (6) Not only are direct care costs high, but a study in Germany showed that indirect costs account for an additional 40 percent of overall HF-related expenditures. (7) New and emerging techniques in imaging and diagnostics, as well as value-based care delivery, are providing physicians with powerful tools to diagnose and manage HF more efficiently.
Definition of HF
HF is a complex clinical syndrome that results from any structural or functional impairment of ventricular filling or ejection of blood. The cardinal manifestations of HF are dyspnea and fatigue, which may limit exercise tolerance, and fluid retention, which may lead to pulmonary and/or splanchnic congestion and/or peripheral edema. Some patients have exercise intolerance but little evidence of fluid retention, whereas others complain primarily of edema, dyspnea, or fatigue. Because some patients present without signs or symptoms of volume overload, the term "heart failure" is preferred over "congestive heart failure." There is no single diagnostic test for HF because it is largely a clinical diagnosis based on a careful history and physical examination. However, both the natriuretic peptides and imaging studies are extremely useful in the diagnosis of patients suspected of heart failure. (8)
The clinical syndrome of HF may result from disorders of the pericardium, myocardium, endocardium, heart valves, or great vessels, or from certain metabolic abnormalities, but most patients with HF have symptoms due to impaired left ventricular (LV) myocardial function. Ejection fraction (EF) is considered important in classification of patients with HF because of differing patient demographics, co-morbid conditions, prognosis, and response to therapies (Table 1).
Ejection fraction is the fraction of blood ejected from a ventricle of the heart with each heartbeat. The LV is the heart's main pumping chamber that pumps oxygenated blood through the ascending (upward) aorta to the rest of the body, so EF is usually measured only in the left ventricle. An LV EF of 55 percent to 70 percent is considered normal. An LV EF of 50 percent or lower is considered reduced, and an EF of less than 40 percent is generally considered consistent with HF. (8)
Causes and classification of HF
The etiology of HF is diverse. There is no agreed single classification system for the causes of HF, with much overlap between potential categories (Table 2). Many patients will have several different pathologies that include both cardiovascular and non-cardiovascular causes at the origin of HF. Identification of these diverse pathologies should be part of the diagnostic workup, as they may offer specific therapeutic opportunities. (9)
There are two major classifications of HF: the American College of Cardiology Foundation/American Heart Association (ACCF/AHA) and the New York Heart Association (NYHA) classifications. (10) Both the ACCF/AHA stages of HF and the NYHA functional classifications provide useful and complementary information about the presence and severity of HF (Table 3). The ACCF/AHA stages of HF emphasize the development and progression of disease and can be used to describe individuals and populations, whereas the NYHA classes focus on exercise capacity and the symptomatic status of the disease. (8) Even though the ACCF/AHA classification is newer, the NYHA system appears to be used more frequently. Regardless of which system is used, progression in HF stages is associated with reduced five-year survival and increased plasma natriuretic peptide concentrations. (11)
Diagnostic evaluation of HF: natriuretic peptides
The diagnosis of HF can be difficult, especially in the early stages. (12) Many of the signs and symptoms are non-specific and may be particularly difficult to identify and interpret in patients such as obese individuals, the elderly, or patients with chronic lung disease. It is therefore critical to the diagnosis that an underlying cardiac cause can be established or ruled out. Patients with HF often present with a wide differential diagnosis, making diagnosis by clinical presentation alone challenging. Some of the signs and symptoms, such as dyspnea, orthopnea, and paroxysmal nocturnal dyspnea, are due to congestion, while some are due to lack of adequate cardiac output, including fatigue, weakness, and exercise intolerance.
This heterogeneity of presentation often results in delays in definitive diagnosis and treatment, and such delays are linked with poor prognosis. (13) Thus, together with HF's risk for death and hospitalization, the growing incidence and prevalence make it a priority.
The natriuretic peptides (NPs) are markers of hemodynamic stress on the heart, denoting the neurohumoral activation of the myocardium. B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NTproBNP) are the two brain NPs that are derived from the prohormone, proBNP. BNP and NT-proBNP are produced in a 1:1 ratio when the left ventricle is stretched due to hemodynamic pressure.
BNP and NT-proBNP are synthesized mainly in the ventricular myocardium in response to myocardial wall stress. BNP is a neurohormone that acts to relieve the symptoms associated with volume expansion and pressure overload by promoting natriuresis and diuresis, vasodilation, and the suppression of the renin angiotensin aldosterone system. BNP is termed brain natriuretic peptide because it was initially discovered in the porcine brain. Both BNP and NT-proBNP levels in the blood are used for screening and diagnosis of acute congestive heart failure (CHF) and may be useful to establish prognosis in HF, as both markers are typically higher in patients with worse outcomes. But the non-cleaved intact proBNP is also present in the circulation and represents a substantial part of the BNP and NT-proBNP immunoreactivity. (14) The optimal application of NP testing is in conjunction with a good history, physical exam, and knowledge of the differential diagnosis of an elevated NP value. NP values are proportional to morbidity and mortality. (Figure 1)
NPs in dyspnea testing in non-acute settings
Non-specific symptoms do not help clinicians discriminate between HF and other clinical issues. (15) Signs and symptoms of HF due to fluid retention may resolve quickly with diuretic therapy. Signs such as elevated jugular venous pressure and displacement of the apical impulse may be more specific, but they are harder to detect and have poor reproducibility. As noted above, signs and symptoms may be particularly difficult to identify and interpret in obese individuals, in the elderly, and in lung disease patients. (15)
A detailed history should always be obtained. HF is unusual in an individual with no relevant medical history (e.g., a potential cause of cardiac damage), whereas certain features, particularly previous myocardial infarction, greatly increase the likelihood of HF in a patient with appropriate symptoms and signs. At each visit, signs and symptoms of HF need to be assessed, with particular attention to evidence of congestion. In non-acute settings, the types of patients who would most benefit from NP testing include patients with symptoms of dyspnea, patients with known coronary artery disease, patients with diabetes, patients with hypertension, and patients older than 60 years of age (8,16-18) (Figure 2)
Testing in acute settings (24)
The workup of patients suspected of HF in acute settings is somewhat different from that which applies to those who present in non-acute settings. The majority of patients who present to the Emergency Department (ED) with HF are admitted to the hospital. This approach is largely due to the challenge of identifying ED patients at low risk for poor outcomes. Risk stratification of patients with acute HF is traditionally problematic, not only because of the patients' underlying HF, but also because of their multiple comorbidities. Further, even for patients who exhibit no objective markers of high risk, the subsequent inability to ensure close follow-up, provide bedside HF education, and address the importance of adherence to therapeutic recommendations makes direct ED discharge problematic.
Because most patients hospitalized for acute HF present to the ED, emergency medicine physicians have become the gatekeepers for patients suspected of acute HF. ED patients with acute HF can be largely assigned to either of two groups based on presentation blood pressure: hypertensive patients (>140 mm Hg) and normotensive patients (<140 mm Hg). Hypotension (<90 mm Hg) and cardiogenic shock are rare and make up less than five percent of ED presentations. (25-26) Therefore, patients arriving at the ED with dyspnea and/or chest pain or who are suspected of having heart failure should be tested with BNP or NT-proBNP and possibly imaging studies. (Figure 3)
In 2006, Januzzi et al published a very important paper which evaluated the use of NT-proBNP in 1256 patients with dyspnea suspected of HF. (28) This was a multi-center study to determine NT-proBNP cut-points for diagnosis or exclusion of acute HF and to evaluate the prognostic significance of elevated NT-proBNP in the setting of acute HF. The results of this study with regard to NT-proBNP are summarized in Table 4.
Using the single, age-independent rule-out cut-point of 300 ng/mL, the authors found that NT-proBNP had a negative predictive value (NPV) of 98 percent. In order to improve both sensitivity and specificity to rule-in HF, the authors found the age-related cut-points were better than any single value. This relationship between age and natriuretic peptide levels is likely consequent to age-related changes in LV compliance, (29) as well as decreasing glomerular filtration rate (GFR). (30) Although age stratification improved the ability of NT-proBNP to identify patients with high likelihood of acute HF, the authors found no need for age stratification to exclude the diagnosis of HF.
The optimal application of NP testing is in conjunction with a good history, physical exam, and knowledge of the differential diagnosis of an elevated NP value. The measurement of NPs has a direct impact on patient management. (31,32) When used in conjunction with other clinical information, measurement of NPs in an acute setting improves the care of acutely dyspneic patients and reduces time to discharge as well as total cost of treatment. NP levels typically decrease rapidly in patients responding favorably to therapy.
While the clinical utility of the NP has been well established, NP elevations can be observed in conditions other than HF and acute coronary syndrome (ACS) (Table 5), justifying the mandatory incorporation of all clinical data into the NP result interpretation. Importantly, these elevations of the natriuretic peptides should not be perceived as false positive results due to their associated strong prognostic values. (33-34)
Management of patients with HF
HF is sub-classified based on the left ventricular ejection fraction. HF with a reduced ejection fraction (HFrEF) is characterized by a left ventricular ejection fraction (LVEF) of less than 40 percent. Conversely, HF with preserved ejection fraction (HFpEF) is characterized by a normal LVEF and an impairment of cardiac relaxation with abnormal ventricular filling. Conventional therapies have been targeted to treat patients with HFrEF. These include angiotensin-converting enzyme inhibitors (ACEis) and, when ACEis are contraindicated, angiotensin receptor blockers (ARBs) and loop diuretics. These are considered first-line pharmacotherapy because they have repeatedly been shown to reduce death and hospitalizations significantly and improve exercise tolerance, functional capacity or status, LVEF, and quality of life. (8)
Even though the current drugs used to treat heart failure work reasonably well, there is still room for improvement by further reducing the mortality rate. For a period of 10 years, the FDA did not approve any new drugs for the chronic treatment of HF. In July 2015, the agency approved a new drug for the treatment of patients with HFrEF. This drug is currently marketed by Novartis under the brand name Entresto. (34) Entresto is actually a combination of two drugs: valsartan, which is an angiotensin II receptor blocker, and sacubitril, which is a neprilysin inhibitor. (35) This combination of drugs is also known as an angiotensin receptor blocker neprilysin inhibitor or ARNI.
The mechanism of action of Entresto is very interesting and has some profound effects on the natriuretic peptides. Valsartan blocks the angiotensin n receptor, causing vasodilation; reduces secretion of vasopressin; and reduces production and secretion of aldosterone, among other actions. The combined effect reduces blood pressure. Sacubitril is metabolized to a substance that inhibits neprilysin, which is responsible for the degradation of BNP, thereby causing a rise in the levels of BNP. Elevation of BNP levels increases the beneficial effects of removing extracellular fluid via natriuresis, diuresis, and vasodilation, inhibiting production of renin and aldosterone and stimulating growth of vascular myocytes. Neither sacubitril nor its metabolites seem to have any effect on NT-proBNP levels. (36)
What is the net effect on natriuretic peptides in patients being treated with Entresto? Despite significant clinical improvement, BNP levels will tend to increase in patients being treated with Entresto. This increase in BNP levels may be confusing to physicians who may have become accustomed to levels decreasing as the patient shows clinical improvement. Since Entresto has no effect on the degradation of NT-proBNP, the levels of this NP will show the usual decrease, which follows clinical improvement in the patient. (37,38)
Both BNP and NT-proBNP are readily available in the modern clinical laboratory. Therefore, which NP should physicians use in routine clinical practice? In patients not being treated with Entresto, both BNP and NT-proBNP provide useful information to assist in the diagnosis of patients suspected of having HF. It should be noted that BNP and NT-proBNP have better diagnostic utility as rule-out tests. In patients receiving Entresto therapy, NT-proBNP will decrease, mimicking clinical improvement in the patient. BNP will tend to increase in response to sacubitril administration despite clinical improvement. (8) Some recent publications demonstrate that the single measurement of BNP and/or NT-proBNP cannot provide a comprehensive biological and clinical picture for patients under Entresto. (14,39) However, despite these differences, the physician will ultimately make the choice. The therapeutic use of Entresto for the treatment of patients with HFrEF was supported in a recent update to the HF guidelines. (40) These guidelines strongly recommended treatment of patients with HFrEF with an ARNI in order to reduce morbidity and mortality in this group of patients.
The road ahead
As healthcare systems are in a transition from service-based to value-based models, concepts of prevention or early diagnosis become increasingly important; therefore the use of biomarkers (and advanced imaging) have gained significance. Participants in the expert panel agree that in the field of HF both have a central role in therapy guidance as in ACS.
To further establish new standards of HF care, new and innovative biomarkers guide differentiating diagnoses and therefore should be used as an early detection tool, as well as for monitoring and outpatient care. Biomarkers such as NT-proBNP can indicate diagnostic pathways, and a multi-biomarker panel could offer further diagnostic value.
Please visit mlo-online.com for references.
Jim Aguanno, PhD, serves as Senior Clinical Consultant for Siemens Healthineers.
Laurent Samson, PhD, serves as Associate Director, Global Commercial Marketing, for Siemens Healthineers.
RELATED ARTICLE: Use of high-sensitivity troponin T is associated with fewer adverse events in patients with chest pain.
Chest pain is one of the most common reasons why people seek emergency care at the hospital, and it is one of the main signs of acute coronary syndrome (ACS). The investigation of these patients usually includes a clinical examination, ECG, and blood sampling for analysis of the cardiac biomarker troponin. ACS is ruled out in most patients, who are then discharged with the diagnosis "unspecified chest pain."
In a 2016 study by Omstedt et al, it was found that approximately one percent of these discharged patients experienced a major adverse cardiac event (MACE) within the next 30 days. (1) Since the introduction of troponin as a biomarker for cardiac injury, the sensitivity of the assays has improved and their use has been more widespread. In recent years, the fifth-generation assay high sensitivity troponin T (hsTnT), has been widely implemented in hospitals in our native Sweden and elsewhere. There were no previous studies regarding the incidence of MACE in relation to the clinical use of this high-sensitivity assay in patients with unspecified chest pain.
We therefore conducted a registry-based cohort study of 65,696 patients, (2) all 18 years and older, who were discharged with "unspecified chest pain" (defined as code R07.1-4 per the International Classification of Diseases-10th edition) between July 2006 and November 2013, to investigate whether the implementation of hsTnT assays in Swedish hospitals resulted in reduced incidence of MACE in this patient group. MACE was defined as a hospital stay with myocardial infarction (Ml), unplanned revascularization, or all-cause mortality. Patients evaluated with the conventional assay were compared with patients evaluated with the new hsTnT assay. Patients were divided into two groups: those who were discharged directly from the emergency department (ED), and those who were discharged after an initial admission within the ED.
The hsTnT assay implemented in 16 Swedish hospitals was the current iteration of the cTnT assay. This new biomarker was compared to "conventional" assays.
Results and discussion
The majority of patients (57,701; 88 percent) were discharged directly from the ED, while the rest were discharged after an initial admission. When conventional assays were in use, cardiovascular risk factors and history of cardiovascular disease were more common in patients who were directly discharged. In directly discharged patients, 270 patients (0.9 percent) had a MACE within 30 days when conventional assays were in use compared to 185 patients (0.6 percent), analyzed with hsTnT (p < 0.001) (odds ratio: 0.7, 95 percent; confidence interval: 0.57 to 0.83). More of the admitted patients had a cardiovascular high-risk profile after the implementation of hsTnT. For these admitted patients, 199 (3.4 percent) experienced a MACE within 30 days with conventional assays, and 157 patients (7.2 percent) after the introduction of the hsTnT assay (p < 0.001). In contrast to the directly discharged patients, there was a significant increase in the number of MACE events after the introduction of hsTnT (odds ratio: 2.18, 95 percent; confidence interval: 1.76 to 2.72) among admitted patients.
Our study showed that patients with chest pain directly discharged from the ED had fewer MACEs and significantly less cardiovascular disease and risk factors after the implementation of a highsensitivity troponin assay, as opposed to patients analyzed with the conventional assays. However, patients discharged after an initial admission had a significantly higher incidence of MACE and more cardiovascular risk factors when analyzed with the newer, hsTnT assay. Previous studies regarding assays with higher sensitivity have shown that more at-risk patients are admitted, and they also report a significant increase in admitted ACS patients with troponin levels above the myocardial infarction (MI) cut-off. (3) Other studies have also shown that in patients with baseline hsTnT elevation with a negative conventional assay, there was an incremental increase in nonfatal Ml or death. We believe that this newer assay has detected more true at-risk patients in our study compared to the conventional assays, which would explain why the admitted patients had a higher incidence of MACE and a higher cardiovascular risk profile. We believe that our study reflects clinical reality, since it is performed on unselected patients who were healthy or with previous ACS.
The implementation of the hsTnT assay in Swedish hospitals was associated with fewer MACEs in patients with unspecified chest pain who were directly discharged from the ED. The opposite was observed for admitted patients. We believe that more true at-risk patients were identified and admitted with the newer assay and that it appears to have improved evaluations in the ED. Further, the hsTnT assay provides an opportunity to employ a one-hour algorithm in the ED, which uses the one-hour delta value of troponinT that has been introduced recently in some Swedish hospitals. Although these algorithms were not investigated in our study, they may provide an even quicker and safer rule-out ofACSintheED.
(1.) Omstedt A, Hoijer J, Djarv T, Svensson P. Hypertension predicts major adverse cardiac events after discharge from the emergency department with unspecified chest pain. Euro heart J Acute Cardiovasc Care. 2016;5(5):441-448.
(2.) Nejatian A, Omstedt A, Hoijer J, Hansson L0, Djarv T, Eggers KM, Svensson P. Outcomes in patients with chest pain discharged after evaluation using a high-sensitivity troponin T assay. J Am Coll Cardiol. 2017;69(21):2622-2630.
(3.) Eggers KM, Lindahl B, Melki D, Jernberg T. Consequences of implementing a cardiac troponin assay with improved sensitivity at Swedish coronary care units: an analysis from the SWEDEHEART registry. Euro heart journal. 2016;37(30):2417-2424.
Atosa Nejatian, MD, and Asa Omstedt, MD, are physicians at Karolinska University Hospital, Stockholm, Sweden. Per Svensson, MD, PhD, serves as a senior lecturer at Karolinska Institute.
CONTINUING EDUCATION TEST
DIAGNOSIS AND MANAGEMENT OF PATIENTS WITH HEART FAILURE and USE OF HIGH-SENSITIVITY TROPONIN T IS ASSOCIATED WITH FEWER ADVERSE EVENTS IN PATIENTS WITH CHEST PAIN
January 2018 (This form may be photocopied. It is no longer valid for CEUs after July 31, 2019.)
TEST QUESTIONS: Circles must be filled in, or test will not be graded. Shade circles like this: [??] Not like this: X.
1. What is the most common diagnosis for hospital admissions in the United States?
() a. gallbladder attack
() b. heart failure
() c. hip fractures
() d. kidney stones
2. What is the estimated mortality rate over three years for heart failure (HF) patients?
() a. 10 percent
() b. 30 percent
() c. 50 percent
() d. 80 percent
3. What are the associated healthcare costs of HF attributed to?
() a. healthcare services
() b. medication
() c. loss of productivity
() d. all of the above
4. HF can result from either a structural or functional impairment of the ventricular filling or ejection of blood.
() a. True
() b. False
() 5. According to the article by Aguanno and Samson, what two tests are extremely () helpful in the determination of HF?
() a. cardiac enzymes and natriuretic peptides
() b. cardiac enzymes and imaging studies
() c. natriuretic peptides and imaging studies
() d. none of the above
6. The measurable ejection fraction of blood comes from the
() a. left ventricle.
() b. right ventricle.
() c. right atrium.
() d. left atrium.
7. An ejection fraction less than ___ percent is consistent with heart failure.
() a. 90
() b. 70
() c. 40
() d. 20
8. The ACCF/AHA is the only organization working to classify HF.
() a. True
() b. False
9. Signs and symptoms of HF are difficult to diagnose, especially in
() a. obese individuals.
() b. the elderly.
() c. patients with lung disease.
() d. all of the above
10. Symptoms related to congestion include dyspnea, orthopnea, and paroxysmal nocturnal dyspnea, while symptoms related to inadequate cardiac output include fatigue, weakness, and exercise intolerance.
() a. True
() b. False
11. What peptides are produced when the left ventricle of the heart is stretched due to hemodynamic pressure?
() a. ANP and BNP
() b. ANP and NT-proBNP
() c. BNP and NT-proBNP
() d. BNP and proBNP
12. What should always be assessed in order to determine the likelihood of HF in a non-acute setting?
() a. daily blood work
() b. detailed history
() c. daily signs and symptoms
() d. none of the above
13. Which physicians have become the gatekeepers of patients with acute HF?
() a. specialist physicians
() b. primary-care physicians
() c. emergency physicians
() d. naturopathic physicians
14. The study performed by Januzzi et al concluded that the ideal application of NP testing should be used in conjunction with
() a. a good history.
() b. knowledge of the differential diagnosis of NP values.
() c. a physical exam,
() d. all of the above
15. Conventional therapies such as ACEis and ARBs are used to treat
() a. HFpEF.
() b. HFrEF.
() c. HSpER.
() d. all of the above
16. Entresto is a combination of
() a. valsartan and sacubitril.
() b. valsartan and ACEis.
() c. sacubitril and ACEis.
() d. sacubitril and ARBs.
17. The effects of Entresto show an
() a. increase in BNP and a decrease in NT-proBNP.
() b. decrease in BNP and an increase in NT-proBNP.
() c. increase in BNP and no effect on NT-proBNP.
() d. decrease in BNP and no effect on NT-proBNP.
18. What caridac marker did the study conducted by Nejatian, Omstedt, and Svensson assess?
() a. troponin-I
() b. high-sensitive troponin T
() c. lipoprotein a
() d. high-sensitive CKMB
19. The outcome of the study concluded that cardiac evaluations on patients were improved upon in the Emergency Department with the use of hsTnT testing.
() a. True
() b. False
Caption: Figure 1. Cleavage of the pre-proBNP molecule into BNP and NT-proBNP
Caption: Figure 2. How to interpret BNP and NT-proBNP values in non-acute Settings (15, 19-23)
Caption: Figure 3. How to interpret BNP and NT-proBNP values in acute settings (18, 27, 28)
Table 1. Ejection fraction in classification of patients with HF Type Classification EF% Description I Heart Failure [less than Also referred to as with Reduced or equal systolic HF. Randomized Ejection to] 40% controlled trials have Fraction (HFrEF) mainly enrolled patients with HFrEF and it is only in these patients that effective therapies have been demonstrated to date. II Heart Failure [greater Also referred to as with Preserved than or diastolic HF. Several Ejection equal different criteria have Fraction (HFpEF) to] 50% been used to further define HFpEF The diagnosis of HFpEF is largely one of excluding other potential non-cardiac causes of symptoms suggestive of HF. To date, effective therapy has not been identified. IIa HFpEF, 41 to 40% These patients fall into a Borderline borderline or intermediate group. Their characteristics, treatment patterns, and outcomes appear similar to those patients with HFpEF. IIb HFpEF, Improved >40% It has been recognized that a subset of patients with HFpEF previously had HFrEF. These patients with improvement or recovery in EF may be clinically distinct from those with persistently preserved or reduced EF. Further research is needed to better characterize there patients. Table 2. Common causes of heart failure Some Common Causes of HF Myocardial infarction Coronary artery disease Valvular disease Idiopathic cardiomyopathy Viral or bacterial cardiomyopathy Pulmonary embolism Myocarditis Pericarditis Arrhythmias Chronic hypertension Thyroid disease Pregnancy Septic shock Trauma Congenital heart disease Table 3. Classifications of heart failure ACCF/AHA Stage NYHA Functional Classification of HF A At high risk None for HF without structural heart disease or symptoms of HF B Structural I No limitation of physical heart disease activity; ordinary physical but without activity does not cause symptoms signs or of HF. symptoms of HF Structural I No limitation of physical heart disease activity; ordinary physical with prior or activity does not cause symptoms current of HF. C symptoms of HF II Slight limitation of physical activity; comfortable at rest but ordinary physical activity results in symptoms of HF. III Marked limitation of physical activity; comfortable at rest but less than ordinary activity causes symptoms of HF. IV Unable to carry on any physical activity without symptoms of HF or symptoms of HF at rest. D Refractory HF IV Unable to carry on any physical requiring activity without symptoms of HF specialized or symptoms of HF at rest. intervention ACCF = American College of Cardiology Foundation; AHA = American Heart Association; NYHA = New York Heart Association Table 4. Age dependent cut-points for diagnosing acute heart failure using NT-proBNP ICON NT-proBNP Age-Adjusted Cut Points to Suppress Age Strata Cut Point PPV NPV (pg/mL) [less than or equal to] 50 (n = 183) 450 76% 99% 50-75 (n = 554) 900 82% 88% [greater than or equalt o]75 (n = 513) 1800 92% 55% Overall Average 88% 66% PPV = Positive Predictive Value; NPV = Negative Predictive Value Table 5. * Heart muscle diseases * Valvular heart disease * Arrhythmia * Anemia * Critical illnesses * Stroke * Pulmonary diseases * Congenital heart diseases * Patients with chronic kidney disease
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|Title Annotation:||CE: CARDIAC BIOMARKERS|
|Author:||Aguanno, Jim; Samson, Laurent|
|Publication:||Medical Laboratory Observer|
|Article Type:||Cover story|
|Date:||Jan 1, 2018|
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