Diagnosing Cardiomyopathy: History, Examination, and Testing

"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.

Whether a patient comes for clinical evaluation due to a concerning murmur or a cardiac arrest, the diagnostic journey typically starts on a predictable trajectory.

Taking a Clinical History

"A proper clinical evaluation should start with a comprehensive cardiac history, a family history including 3 generations, and a comprehensive physical examination," notes the American Heart Association (AHA) guideline for diagnosis of hypertrophic cardiomyopathy.

But the same could be said for all types of cardiomyopathy.

Just how detailed should the family history be? One study suggested that a simple question about any first-degree relative (parent, sibling, or child) with cardiovascular disease was just as good as asking more detailed questions about premature (age <55 years for men and <65 years for women) disease in family members or using a more formal risk assessment tool, although this was in a middle-age and older primary prevention population.

However, more detailed questions "might still be particularly important in younger individuals, who do not yet present with traditional risk factors," noted an accompanying editorial. "In this scenario, the information derived from the [family history] of CVD [cardiovascular disease] is likely more valuable because there is a higher likelihood of genetic factors leading to higher risk of future CVD events."

For hypertrophic and dilated cardiomyopathy, first-, second-, and third-degree relatives have approximately 50%, approximately 25%, and approximately 12.5% risk of inheriting the genetic risk for the disease, respectively, according to one review in discussing screening of athletes. "Using generally descriptive terms (e.g., 'abnormally enlarged or thickened heart') can help probe for family members with suspicious phenotypic manifestations of disease but no formal diagnosis," the authors of the editorial pointed out.

While time may limit how detailed a pedigree is attainable, detailed questions that can be useful include: "Is there a history of sudden death or childhood death? What age?...Does anyone have a pacemaker?"

Other aspects of history-taking recommended in the AHA guidelines are asking about the severity and triggers of dyspnea and fatigue, as well as the patient's chest pain, exercise capacity, physical activity, and sexual activity, weight gain or loss or early satiety, and palpitations or (pre)syncope.

Physical Examination

General aspects of the physical exam, according to the AHA guidelines, should include evaluation of the following:

• Peripheral edema or ascites

• Blood pressure (supine and upright)

• Pulse

• Jugular venous pressure at rest and following abdominal compression

• Kussmaul's sign, which can indicate restrictive cardiomyopathy

• Presence of extra heart sounds and murmurs

• Size and location of point of maximal impulse

• Presence of right ventricular heave

• Respiratory rate, rales, or pleural effusion

• Temperature of lower extremities

To help diagnose hypertrophic cardiomyopathy, the AHA also recommended looking for physical findings of outflow tract obstruction, both at rest and with "provocative" maneuvers, like the Valsalva maneuver or standing from a squatting position.

For restrictive cardiomyopathies due to cardiac amyloidosis, family history of neuropathy and personal history of carpal tunnel syndrome or enlarged tongue can provide clues for diagnosis.

Diagnostic Tests

Blood tests recommended by the AHA guidelines in the initial evaluation for patients who may have heart failure should include complete blood count, urinalysis, serum electrolytes (including calcium and magnesium), blood urea nitrogen, serum creatinine, glucose, fasting lipid profile, liver function tests, and thyroid-stimulating hormone. Screening for iron overload should include serum ferritin and transferrin saturation.

For individuals with dyspnea or who are acutely hospitalized, BNP or N-terminal pro-B-type natriuretic peptide (NT-proBNP) is also recommended. Cardiac troponin I or T "should be routine" in acute cases, while other biomarkers of myocardial injury or fibrosis can be considered as well.

Standard imaging across the board for the cardiomyopathies includes chest x-ray, electrocardiography (ECG), and echocardiography, with strain imaging in the case of suspected cardiac amyloidosis. Cardiac MRI also has many uses for diagnosing cardiomyopathies, and as in hypertrophic cardiomyopathy, can be used to risk-stratify for implantable cardioverter-defibrillator use.

Workup recommendations for cardiac amyloidosis as a cause of restrictive cardiomyopathy then involves serum or urine electrophoresis and immune fixation to look for monoclonal protein, with or without an abnormal free light chain assay. Patients go for fat pad aspiration (with bone marrow biopsy if monoclonal antibody was detected). If Congo red-positive deposits are found, patients need amyloid typing and then DNA mutation analysis with mass spectroscopy or, if not available, with immunohistochemistry or immunoelectron microscopy. Otherwise, an endomyocardial biopsy can be used to look for those deposits.

Transthyretin (TTR) amyloidosis is diagnosed using nuclear pyrophosphate scans, and cardiac MRI is also helpful in diagnosing amyloidosis (both for AL and ATTR amyloid).

For restrictive cardiomyopathy overall, ruling out constrictive pericarditis is a priority, as the two can appear similar, notes a review in the New England Journal of Medicine. Echo-based two-dimensional and Doppler imaging can help in the differential diagnosis, but, as the review notes, cardiovascular magnetic resonance imaging (CMR) and many other modalities have been used as well: "No technique is totally reliable, and in some patients the only way of making the differential diagnosis is to perform pericardiectomy." CMR isn't available due to factors like cost, presence of implanted devices, or severe renal insufficiency.

The baseline evaluation for hypertrophic cardiomyopathy should also include genetic testing, which is also gaining utility in other forms of cardiomyopathy.

Stress testing is called for if symptomatic, if left ventricular outflow tract obstruction is suspected, or to determine baseline functional capacity, according to the guidelines.

For dilated cardiomyopathy suspected to be cardiac sarcoidosis, there was "moderate consensus" on cardiac MRI or positron emission tomography imaging with fluorodeoxyglucose imaging. Endomyocardial biopsy can help confirm cardiac sarcoidosis, but absence does not rule it out. Suspected cardiac sarcoidosis with cardiac symptoms, an abnormal ECG, or cardiomegaly should prompt transthoracic echocardiogram, Holter monitoring, and subsequent advanced imaging.

For suspected myocarditis, no biomarkers are specific identifiers, but troponin testing is recommended in guidelines along with ECG and transthoracic echo. CMR was deemed reasonable.

Endomyocardial biopsy was also recommended for myocarditis presenting as acute heart failure with shock or high-grade heart block or symptomatic ventricular tachycardia. However, as a review in Radiology: Cardiothoracic Imaging noted, "it is not frequently performed due to the invasive nature of the procedure and associated risks, as well as low sensitivity compared with cardiac explant at autopsy. Endomyocardial biopsy is usually only indicated if there is clinical evidence that the results will have a meaningful effect on therapeutic decisions."

Read Part 1 of this series: Cardiomyopathy: What are the Signs, What are the Symptoms?

Up next: Pathophysiology and Epidemiology