How is Heart Failure Diagnosed?
The initial approach to a patient with suspected heart failure relies heavily on a thorough medical history and careful clinical exam. However, signs and symptoms of heart failure are non-specific—they might be caused by a number of other conditions—so further testing is often necessary to make a conclusive diagnosis. A complete blood count, chemistry panel, and urinalysis, as well as a chest X-ray, are generally part of this workup. Blood testing for natriuretic peptides (BNP or N-terminal prohormone of brain natriuretic peptide [NT-proBNP]), an electrocardiogram, and an echocardiogram are also standard parts of an initial assessment.22,47,66
Electrocardiography and Imaging
An electrocardiogram (ECG) can be used to measure electric abnormalities, enlargement of the heart chambers, and arrhythmia. It is recommended as part of an initial evaluation of individuals with suspected heart failure.3,47,66
An echocardiogram is among the most useful diagnostic tests for heart failure.66 Echocardiography is an ultrasound technique that displays real-time images of the heart 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 (which help visualize blood flow through the heart), it represents an important diagnostic approach for patients with heart failure.3 Echocardiography is also an important technique to estimate and monitor changes in left ventricular ejection fraction.
Other imaging techniques may also be used to evaluate the size and thickness of the heart chambers, detect myocardial damage, or detect pulmonary edema, including chest radiography (X-rays), computed tomography (CT or CAT scans), and magnetic resonance imaging (MRI).3,19,67,68 In particular, MRI is useful in helping determine the cause of heart failure and establishing prognosis. It can also help guide treatment.69
B-type natriuretic peptide (BNP), a peptide hormone released mostly by cells of the ventricle (cardiomyocytes) in response to heart muscle stretch or injury, is a valuable biomarker both for diagnosing acute heart failure and predicting clinical outcomes.70-73 BNP normally functions to signal the kidneys to release sodium and water into the urine to lower blood volume, and thus, blood pressure. Serum levels of BNP, and its precursor fragment (NT-proBNP), rise proportionally with risk for cardiovascular disease.71 In one prospective cohort study of 380 people in Sweden, having a low BNP was one of the best predictors of survival to age 90 in men.74
Cardiac troponins (cTnI and cTnT) are regulatory proteins associated with muscle fibers in the heart that 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, such as from a heart attack.75 Cardiac troponins may also leak from cells during chronic diseases, such as heart failure.76 Measuring serum cTnT using a high-sensitivity assay (hs-cTnT) can be used in heart failure diagnosis and risk assessment.77-79 A recent meta-analysis of 16 studies with over 67,000 subjects found that there is a strong association between heart failure and cardiac troponins, and that its measurement was predictive of a heart failure event.80
In addition to these biomarkers, other markers of inflammation, oxidative stress, vascular dysfunction, and myocardial problems can mark heart failure.81,82 Measurements of soluble ST2, a member of the interleukin 1 receptor family and marker of cardiac distress,83 and galectin-3, a protein that plays a role in inflammation, cancer, and heart disease,84 can predict hospitalization and death. Monitoring multiple biomarkers may be useful to target heart failure therapies in the future, but further research is needed.
Additional tests that may help diagnose and monitor heart failure include thyroid function tests, especially thyroid-stimulating hormone (TSH), as hyperthyroidism and untreated hypothyroidism can cause heart failure. Standard blood tests to measure electrolyte levels and assess liver and kidney function (such as a chemistry panel and complete blood count [CBC]) may also be useful.47,66
Cardiovascular risk markers, such as homocysteine, insulin-like growth factor 1, C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6), may also be assessed,30 although they are not specific for heart failure and may be more relevant for prognosis than diagnosis.85
Iron and Heart Failure
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 (primary hemochromatosis) or following multiple blood transfusions, leading to cell death via oxidative stress. This phenomenon, called iron-overload cardiomyopathy, 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.86-88
The prevalence of iron deficiency in heart failure with reduced ejection fraction (HFrEF) may be as high as 50%. Mechanisms leading to this deficiency include poor absorption, gastrointestinal losses, and diminished bioavailability. Iron deficiency is associated with an increased risk of cardiovascular morbidity and mortality.89 Individuals with heart failure may develop iron deficiency as their condition progresses. In an analysis of studies including more than 1,500 heart failure patients, 50% of subjects were found to be iron deficient.90 Also, a 2013 study on 552 subjects with chronic heart failure found that iron deficiency was strongly associated with reduced quality of life.91
Iron supplementation in heart failure patients with iron deficiency is associated with improved symptoms, functional capacity, quality of life, and reduced hospital admissions.92-94 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 the direct effects of depleted iron stores in others.95 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. More severe anemia is associated with more severe heart failure, and iron deficiency is associated with a reduced exercise capacity.96
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.97 Recognition and management of anemia is an important component of heart failure care.95,98-100 Several blood tests can be useful for screening for anemia and may help guide treatment, including ferritin, TIBC, vitamin B12, folate, and reticulocyte (immature red blood cell) count.
The role of iron supplementation in heart failure patients remains controversial. Iron Repletion Effects on Oxygen Uptake in Heart Failure (IRONOUT-HF), a randomized, double-blind, placebo-controlled trial involving supplementation of 150 mg of oral iron polysaccharide twice daily in patients with HFrEF, found no clinical effect after supplementation, even when iron stores were repleted, suggesting poor oral iron absorption in HFrEF patients. A recent re-analysis of the trial did not support iron supplementation in iron deficient patients with HFrEF.89 Additional research may be needed to clarify the role of iron supplementation in patients with heart failure.