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Heart Failure

Diagnosis of Heart Failure

Physical Signs and Symptoms

Key symptoms of heart failure include (Foley 2012):

  • Fatigue and difficulty breathing (dyspnea), which can lead to decreased capacity for physical activity (exercise intolerance). In mild heart failure, difficulty breathing may be present only during physical activity, while in advanced heart failure it may be difficult for patients to breathe even at rest.
  • Fluid retention, which may result in peripheral or pulmonary edema (Hunt 2005). However, not all people with heart failure will exhibit both exercise intolerance and edema.
  • Frequent nighttime urination (nocturia).
  • In advanced heart failure, symptoms of wheezing, abdominal discomfort, anorexia and weight loss may occur.

Some signs that may suggest heart failure include changes in heart size (e.g. cardiomegaly) and/or rhythm, impaired lung function, evidence of low blood oxygen, and abdominal swelling. These signs are typically progressive with the severity of heart failure, and some may not be apparent in mild heart failure, but emerge as heart failure advances to moderate or severe stages (Foley 2012).

Diagnostic Tools

Exercise testing. Exercise testing (treadmill test or the six-minute-walk test) can be used to monitor changes in exercise tolerance and may be combined with measurements of gas exchange or blood oxygen saturation to provide quantitative indications of cardiovascular function (Shoemaker 2012; Pollentier 2010; Hunt 2009).

Cardiovascular function parameters. Heart failure may be associated with a wide spectrum of structural and functional abnormalities in the left ventricle, which can be assessed by measuring the left ventricle ejection fraction (Hunt 2009). The left ventricular ejection fraction measures the fraction of the blood that leaves the left ventricle and enters systemic circulation with each heartbeat. It represents the efficiency at which the left ventricle empties itself. A normal ejection fraction is 55-70% (ie, a normally functioning heart will eject 55-70% of the total blood in the left ventricle with each heartbeat). Ejection fractions between 40% and 55% may indicate cardiac damage, and <40% supports a diagnosis of heart failure or significant heart muscle damage (American Heart Association 2012). It is important to note that heart failure can occur in patients with a normal ejection fraction (Hunt 2009; American Heart Association 2012). This measurement must, therefore, be interpreted in conjunction with other diagnostic tests.

Biomarker Testing

  • Brain natriuretic peptide (BNP), also called B-type natriuretic peptide, is currently one of the most measured biomarkers both for diagnosing heart failure and predicting clinical outcomes (Weber 2006; Nagarajan 2011; van Kimmenade 2012). BNP is a peptide hormone released mostly by cells of the ventricle (cardiomyocytes) in response to heart muscle stretch or injury (Weber 2006; Di Angelantonio 2009). It normally functions to signal the kidneys to release sodium and water into the urine to lower the blood volume and, thus, blood pressure. Serum levels of BNP and its precursor fragment (NT-proBNP) can both be quantified and rise proportionally with the level of risk for cardiovascular disease (Di Angelantonio 2009).
  • Cardiac troponins (cTnI and cTnT) are regulatory proteins associated with muscle fibers in the heart, and they can be released into circulation upon cardiomyocyte damage or death. Quantitation of serum cardiac troponins is the gold standard for detecting acute damage to the heart muscle (Nagarajan 2012), such as from a heart attack. Cardiac troponins may also “leak” from cells during chronic diseases, such as heart failure (Nagarajan 2011), and measurement of serum cTnT using a high-sensitivity assay (hs-cTnT) can be used in heart failure diagnosis and risk assessment (Wang 2000; Nishio 2007; McQueen 2013).

Additional tests that may help in the diagnosis and monitoring of heart failure include thyroid function tests (especially thyroid-stimulating hormone [TSH]), as hyperthyroidism and untreated hypothyroidism can be a primary or contributory cause to heart failure, and standard blood tests for electrolyte levels and to assess liver and kidney function (ie, chemistry panel and complete blood count [CBC]) (Hunt 2005).

Cardiovascular risk markers such as homocysteine, insulin-like growth factor 1, C-reactive protein, tumor necrosis factor-alpha (TNF- α), and interleukin-6 (IL-6) may also be assessed (Kenchaiah 2004), although they are not specific for heart failure and may be more relevant for prognosis rather than diagnosis (van Kimmenade 2012).

Iron and Heart Failure

Iron plays a dualistic role in heart failure; both iron overload and iron deficiency are associated with heart failure, but in different circumstances. Iron can accumulate in cardiac muscles in hereditary iron metabolism diseases (eg, primary hemochromatosis) or following multiple blood transfusions, leading to cell death via oxidative stress. This phenomenon is called iron-overload cardiomyopathy and is a major cause of heart failure in people with iron overload disorders. A blood test called transferrin saturation can be used to screen for iron overload. Physicians may test for iron excess in heart failure patients with a personal or family history of iron metabolism diseases, or if iron overload is suspected for another reason (Kremastinos 2011; Gujja 2010; Murphy 2010).

On the other hand, individuals with heart failure may develop iron deficiency as their condition progresses. In an analysis of studies including more than 1500 heart failure patients, 50% of subjects were found to be iron deficient (Klip 2013). Also, a 2013 study on 552 subjects with chronic heart failure found that iron deficiency was strongly associated with reduced quality of life (Comin-Colet 2013). Iron supplementation in heart failure patients with iron deficiency is associated with improved symptoms, functional capacity, quality of life, and reduced hospital admissions (Filippatos 2013; Kapoor 2013; Avni 2012). The specific mechanisms by which iron deficiency negatively impacts heart failure outcomes are not clearly defined, but may be due to iron-deficiency related anemia in some cases, and to the direct effects of depleted iron stores in others (Jankowska 2010). An iron and total iron binding capacity (TIBC) test can be used to screen for iron deficiency.

Anemia is fairly common among individuals with heart failure and is associated with poor outcomes. Iron deficiency is a prominent cause of anemia in many situations, but anemia can occur independently of iron deficiency in heart failure. Excluding iron deficiency, other possible causes of anemia in heart failure include impaired production of erythropoietin (a hormone that controls red blood cell production), kidney problems, and problems with fluid retention (Westenbrink 2007). Recognition and management of anemia is increasingly recognized as an important component of heart failure care, but the best treatment strategies are still being investigated as of the time of this writing (Shah 2013; Pereira 2013; Kilicgedik 2012; Jankowska 2010). Several blood tests can be useful for screening for anemia and may help guide treatment, including ferritin, total iron binding capacity (TIBC), vitamin B12, folate, and reticulocyte (immature red blood cell) count.

Electrocardiography and Imaging

An electrocardiogram (ECG) can be used to measure electric abnormalities, enlargement of heart chambers, and arrhythmia. It is an important tool in screening for cardiac abnormalities that can contribute to heart failure (Hunt 2009).

An echocardiogram is among the most useful diagnostic tests for heart failure (Hunt 2005). Echocardiography is an ultrasound technique that displays real-time images of the heart and can be used to visualize abnormalities in the heart muscle or valves, quantitate changes in the size of heart chambers, or detect abnormalities in blood flow. When combined with Doppler flow studies, it represents an important diagnostic approach for patients with heart failure (Hunt 2009). Echocardiography is also an important technique to estimate and monitor changes in the left ventricular ejection fraction. Other imaging techniques may also be used to evaluate the size of heart chambers, detect myocardial damage, or detect pulmonary edema; these include chest radiography (“X-rays”), computed tomography (CT or “CAT” scans), and magnetic resonance imaging (MRI) (Hunt 2009; Mangalat 2009).

Classification and Staging of Heart Failure

A variety of approaches have been used to quantify the degree of functional limitation imposed by heart failure.  The most widely used scale is the New York Heart Association Functional Classification (NYHA), which classifies patients with cardiac disease into one of four classes based on their degree of comfort at different levels of physical activity.

NYHA Functional Classification (N.Y. Criteria Committee 1964)

  • Class I. Patients with cardiac disease that have no limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, breathlessness, or chest pain.
  • Class II. Patients with cardiac disease resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, breathlessness, or chest pain.
  • Class III. Patients with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less-than-ordinary activity causes fatigue, palpitation, breathlessness, or chest pain.
  • Class IV. Patients with cardiac disease resulting in an inability to carry on any physical activity without discomfort. Symptoms of heart failure or chest pain may be present even at rest. If any physical activity is undertaken, discomfort increases.

Due to the fact that the NYHA classification system is subject to significant inter-observer variability, a second approach to heart failure classification, which is intended to complement the NYHA classification system, has been developed by the American College of Cardiology Foundation/American Heart Association (ACCF/AHA) Task Force on Practice Guidelines (Jessup 2009; Brozena 2003). This system takes into consideration both the development of heart failure and its progression (Jessup 2009). The ACCF/AHA staging system identifies 4 stages involved in the development and progression of heart failure. The first 2 stages (A and B) are not considered overt heart failure, but have risk factors that predispose to heart failure and are an attempt to help healthcare providers with the early identification of at-risk patients (Hunt 2005).

American College of Cardiology Foundation/American Heart Association Staging (Hunt 2005)

At Risk for Heart Failure

  • Stage A. At high risk for heart failure, but without structural disease or symptoms of heart failure
  • Stage B. Structural heart disease, such as left ventricular hypertrophy/dysfunction, but without signs or symptoms of heart failure

Heart Failure

  • Stage C. Structural heart disease with prior or current symptoms of heart failure
  • Stage D. Treatment-resistant heart failure requiring specialized intervention