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"Medical Journeys" is a set of clinical resources reviewed by physicians, meant for the medical team as well as the patients they serve. Each episode of this 12-part journey through a disease state contains both a physician guide and a downloadable/printable patient resource. "Medical Journeys" chart a path each step of the way for physicians and patients and provide continual resources and support, as the caregiver team navigates the course of a disease.

The signs and symptoms that bring a patient with heart failure with reduced ejection fraction (HFrEF) to the clinic for diagnosis are varied, and none incontrovertibly point to diagnosis.

Typical symptoms of dyspnea, orthopnea, paroxysmal nocturnal dyspnea, fatigue, and ankle swelling can arise from a number of different diagnoses. Right-sided heart failure symptoms like abdominal bloating and early satiety are even less specific.

The clinical picture that emerges from history taking and the physical exam is the cornerstone of assessment that can point to underlying causes, effective treatment, and even need for referral for advanced HF care.

Figuring out why the clinical deterioration occurred in cases of acute HF hospitalization is important, according to the American Heart Association/American College of Cardiology . The document calls for assessment of factors including the following:

• Concurrent illness, such as ongoing myocardial ischemia, pulmonary emboli, or systemic infection

• Initiation of a medication that could have been detrimental in the setting of HF, such as nonsteroidal anti-inflammatory drugs

• Chronic right ventricle pacing, such as a newly implanted pacemaker or medications that might have led to bradycardia and pacing (for example, amiodarone)

• Nonadherence to a medication or dietary regimen

• Ongoing substance abuse

• Social determinants of health, such as housing stability, food security, and transportation availability

Elevated cardiac filling pressures lead to clinical congestion that can be assessed with greater specificity by elevated jugular venous pressure, positive abdominojugular reflux, an S₃ gallop rhythm on auscultation, laterally displaced apical impulse, and a to the Valsalva maneuver. Less specific signs include weight loss or gain, lung rales, peripheral edema, ascites, cool or mottled extremities, and a pulse pressure-to-systolic blood pressure ratio of 0.25 or less.

Dyspnea upon leaning forward, dubbed bendopnea, is also suggestive of heart failure but less typical, present in 28% of patients in one of patients referred for right-heart catheterization.

"As a result of compensatory upregulation in lymphatic drainage, patients with chronic HFrEF may lack lung rales or peripheral edema, even when pulmonary capillary wedge pressure is elevated," a noted.

In the PARADIGM-HF trial population, 21% of patients had one sign of congestion, 7% had two, and 2% had three or more signs of congestion. And the more of these signs present, the higher the risk of cardiovascular death or HF hospitalization -- independent of symptoms, natriuretic peptides, and validated risk scores.

Diagnostic Tests

If the history and physical exam lead to suspicion of HF, the next step is diagnostic testing, initially with biomarkers and cardiac imaging and then confirmatory invasive imaging.

U.S. guidelines call for laboratory evaluation to include a complete blood count, urinalysis, serum electrolytes, blood urea nitrogen, serum creatinine, hemoglobin A1c, lipid profile, liver function tests, iron studies, and thyroid-stimulating hormone. Those tests are usually done on the initial evaluation, and may need to be repeated with changes in clinical condition or treatment.

Particularly for patients presenting with dyspnea, measurement of B-type natriuretic peptide (BNP) or N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) can support diagnosis or exclusion of HF.

While a "widening array of biomarkers including markers of myocardial injury, inflammation, oxidative stress, vascular dysfunction, and matrix remodeling have been shown to provide incremental prognostic information over natriuretic peptides," the guidelines concluded that they "remain without evidence of an incremental management benefit." These include , , , and .

All patients should also get a 12-lead electrocardiogram (ECG) on the initial encounter to optimize management, according to the guidelines. Clinical indications that may necessitate repeated ECG include suspicion for arrhythmia, ischemia or myocardial injury, conduction, or other cardiac abnormalities.

In terms of imaging, chest x-ray has a class I recommendation to assess heart size and pulmonary congestion and to detect alternative cardiac, pulmonary, and other diseases that may cause or contribute to the patient's symptoms in cases of suspected or new-onset HF. Chest x-ray has 81% sensitivity overall for the diagnosis of acute HF. In the (ADHERE), 18.7% of HF patients had no signs of congestion on chest radiography in the emergency department. The JAMA review notes that "individual signs tend to be more specific than sensitive," citing 64-79% sensitivity of cardiomegaly but 95% specificity or greater for peribronchial cuffing, Kerley B lines, alveolar edema, and bilateral pleural effusions.

To confirm HFrEF diagnosis, transthoracic echocardiography is needed to assess cardiac structure and affirm left ventricular systolic dysfunction with a left ventricular EF (LVEF) of 40% or less. If echocardiography is inadequate, the guidelines give a class I recommendation for alternatives to assess LVEF, such as cardiac magnetic resonance (CMR), cardiac CT, and radionuclide imaging.

There's usually more to it, though, as determining the cause and other comorbidities often necessitates specific diagnostic testing and evaluation. About half of HFrEF cases have ischemic etiology, so many newly diagnosed patients need evaluation for coronary artery disease, with coronary angiography as the gold standard.

The JAMA review, though, noted that not all patients may head for coronary angiography, since advanced age or multiple severe comorbidities should be considered prior to referral and it might not be needed for patients who are not candidates for or who chose not to have revascularization. In addition, the review said, noninvasive CT angiography "may be considered in patients with low pretest probability for coronary atherosclerosis." Stress testing has lower sensitivity and specificity.

Depending on the clinical suspicion, diagnostic studies may also be needed for cardiac amyloidosis, sarcoidosis, hemochromatosis, infectious causes like COVID-19 or Chagas disease, thyroid disorders, acromegaly, connective tissue disorders, or various cardiomyopathies.

Genetic Testing

Many cardiomyopathies have an inherited component, so genetic screening has taken on an increasing role alongside taking a thorough family history. In one , taking a detailed three-generation family history for "idiopathic" cardiac disease patients in the hospital turned up a familial diagnosis in nearly one-third.

Guidelines call for detailed three-generation family history for all cardiomyopathy patients. This should include asking patients about family members who have had cardiomyopathy, an enlarged or weak heart, recurrent syncope, sudden death, unexplained death from drowning or a single-vehicle crash, a pacemaker or atrial fibrillation on its own before age 65, and any type of skeletal muscle disease, like Duchenne.

U.S. heart failure guidelines also give a class I recommendation to cascade screening of first-degree family members of select patients with genetic or inherited cardiomyopathies.

Read Part 1 of this series: Heart Failure: A Look at Low Ejection Fraction

Read Part 2 of this series: Exploring Heart Failure With Preserved Ejection Fraction

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