Version August 2025
INTRODUCTION —
Heart failure (HF) is a common clinical syndrome caused by a variety of cardiac diseases [1]. Evaluation of the etiology and severity of HF is discussed here. Initial evaluation of suspected HF and the management and prognosis of HF are discussed separately. (See "Heart failure: Clinical manifestations and diagnosis in adults" and "Overview of the management of heart failure with reduced ejection fraction in adults" and "Prognosis of heart failure" and "Treatment and prognosis of heart failure with preserved ejection fraction".)
Evaluation of patients with HF should also include evaluation for concurrent conditions as appropriate, such as sleep-disordered breathing. (See "Sleep-disordered breathing in heart failure".)
DEFINITION —
HF is a common clinical syndrome with symptoms caused by impaired ability of one or both ventricles to pump at a normal pressure due to a structural or functional cardiac disorder [2]. It is characterized by specific symptoms, such as dyspnea and fatigue, and signs, such as fluid retention. There are many ways to assess cardiac function. However, there is no diagnostic test for HF, since it is largely a clinical diagnosis that is based upon a careful history and physical examination. (See "Heart failure: Clinical manifestations and diagnosis in adults".)
Classification of HF severity — The history, including assessment of New York Heart Association (NYHA) functional class, and physical examination in conjunction with the diagnostic tests reviewed below should both establish the primary cause of the HF and provide a reasonable estimate of its severity.
The classification system that is most commonly used to quantify the degree of functional limitation imposed by HF is one first developed by the NYHA. This system assigns patients to one of four functional classes, depending on the degree of effort needed to elicit symptoms (table 1):
●Class I – Patients with heart disease without resulting limitation of physical activity. Ordinary physical activity does not cause HF symptoms such as fatigue or dyspnea.
●Class II – Patients with heart disease resulting in slight limitation of physical activity. Symptoms of HF develop with ordinary activity but there are no symptoms at rest.
●Class III – Patients with heart disease resulting in marked limitation of physical activity. Symptoms of HF develop with less than ordinary physical activity but there are no symptoms at rest.
●Class IV – Patients with heart disease resulting in inability to carry on any physical activity without discomfort. Symptoms of HF may occur even at rest.
Stages in the development of HF — There are several stages in the evolution of HF, as outlined by the American College of Cardiology Foundation/American Heart Association guidelines [2]:
●Stage A – At high risk for HF but without structural heart disease or symptoms of HF.
●Stage B – Structural heart disease but without signs or symptoms of HF. This stage includes patients in NYHA functional class I with no prior or current symptoms or signs of HF.
●Stage C – Structural heart disease with prior or current symptoms of HF. This stage includes patients in any NYHA functional class (including class I with prior symptoms).
●Stage D – Refractory HF requiring specialized interventions. This stage includes patients in NYHA functional class IV with refractory HF.
This staged system, in contrast to the NYHA classification, emphasizes the progressive nature of HF and defines the appropriate therapeutic approach for each stage.
The long-term prognosis can also be estimated. The peak VO2 is a helpful predictor of prognosis, but functional class and exercise capacity, the magnitude of the reduction in left ventricular ejection fraction (LVEF) with systolic dysfunction, serum B-type natriuretic peptide concentrations, and a variety of other factors are also important. (See "Predictors of survival in heart failure with reduced ejection fraction".)
Etiology
Categories of disease — HF is caused by a variety of disorders, including diseases affecting the pericardium, myocardium, endocardium, cardiac valves, vasculature, or metabolism [2]. The discussion here will focus primarily on myocardial causes of HF. There are two basic pathophysiologic myocardial mechanisms that cause reduced cardiac output and HF: systolic and diastolic dysfunction. Systolic and diastolic dysfunction each may be due to a variety of etiologies. Effective management is often dependent upon establishing the correct etiologic diagnosis. As an example, coronary revascularization may be beneficial in patients with ischemic cardiomyopathy who have evidence of hibernating myocardium. (See "Epidemiology of heart failure" and 'Testing for coronary artery disease' below.)
The challenge of finding the correct etiology in patients with HF is illustrated by studies that have compared the clinical (pre-transplant) diagnosis and morphologic diagnosis (based upon pathologic examination of the explanted heart) in heart transplant recipients. In two series, each spanning two decades, 17 and 13 percent of patients were misdiagnosed prior to transplantation, particularly patients with nonischemic cardiomyopathy (30 and 22 percent with clinical misdiagnosis) [3,4]. Conditions that were missed clinically included cardiac sarcoidosis, myocarditis, arrhythmogenic right ventricular cardiomyopathy (in both series), and hypertrophic cardiomyopathy and noncompaction (in one series [4]).
Heart failure with reduced ejection fraction — HF with reduced EF (HFrEF; LVEF ≤40 percent) is also known as systolic HF or HF due to systolic dysfunction.
The most common causes of systolic dysfunction are coronary (ischemic) heart disease, idiopathic dilated cardiomyopathy (DCM), hypertension, and valvular disease. Effective therapy of hypertension has led to a changing pattern in which coronary disease has become more prevalent as a cause of HF [5,6]. In one review, coronary disease and hypertension accounted for 62 and 10 percent of cases, respectively [5]. (See "Epidemiology of heart failure".)
As compared with all patients presenting with HF, patients who present with initially unexplained DCM have a different distribution of etiologies. After a complete evaluation of 1278 such patients, the relative frequency of the different causes was as follows [7]:
●Idiopathic – 50 percent
●Myocarditis – 9 percent
●Ischemic heart disease – 7 percent
●Infiltrative disease – 5 percent
●Peripartum cardiomyopathy – 4 percent
●Hypertension – 4 percent
●HIV infection – 4 percent
●Connective tissue disease – 3 percent
●Substance use disorders– 3 percent
●Doxorubicin – 1 percent
●Other – 10 percent
Heart failure with preserved ejection fraction — HFpEF is also known as diastolic HF and refers to HF in patients with an LVEF ≥50 percent [2].
Diastolic dysfunction can be caused by many of the same conditions that lead to systolic dysfunction. The most common causes are hypertension, ischemic heart disease, diabetes, hypertrophic obstructive cardiomyopathy, and restrictive cardiomyopathy. However, many patients with symptoms suggestive of HF (shortness of breath, ankle edema, or paroxysmal nocturnal dyspnea) who have intact LV systolic function may not have diastolic dysfunction, but have other etiologies that can account for their symptoms, including obesity, lung disease, or occult coronary ischemia [8]. (See "Heart failure with preserved ejection fraction: Clinical manifestations and diagnosis".)
Heart failure with midrange ejection fraction — Patients with LVEF between 41 and 49 are categorized as HF with mid-range ejection fraction (HFmrEF), and share characteristics with both HFpEF and HFrEF. (See "Treatment and prognosis of heart failure with mildly reduced ejection fraction".)
DETERMINING THE CAUSE AND SEVERITY OF HEART FAILURE OR CARDIOMYOPATHY
Diagnostic approach — The approach to determining the cause and severity of HF or cardiomyopathy includes the history, physical examination, and diagnostic tests. Initial tests include an electrocardiogram (ECG), initial blood tests, echocardiogram, and assessment for coronary artery disease.
Clinical presentation — Symptoms of HF include those due to excess fluid accumulation (dyspnea, ankle or abdominal swelling) and those due to a reduction in cardiac output (fatigue, weakness) that is most pronounced with exertion. (See "Heart failure: Clinical manifestations and diagnosis in adults", section on 'Symptoms and associated conditions'.)
The history and clinical presentation may be helpful in identifying the etiology of HF. As examples:
●Classic exertional angina usually indicates ischemic heart disease.
●Acute HF after an antecedent flu-like illness suggests viral myocarditis.
●Long-standing hypertension or alcohol use suggests hypertensive or alcohol-induced cardiomyopathy.
●A diagnosis of amyloidosis should be strongly considered in patients who have a family history of unexplained cardiomyopathy or amyloidosis, low voltage on ECG, LV hypertrophy by echocardiography (especially without hypertension), and a history of heavy proteinuria. It should be appreciated, however, that mild proteinuria can be seen with HF alone. (See "Predictors of survival in heart failure with reduced ejection fraction", section on 'Albuminuria'.)
●HF may be provoked or worsened by drugs, including antiarrhythmic agents such as disopyramide and flecainide; calcium channel blockers, particularly verapamil; beta blockers; and nonsteroidal antiinflammatory drugs [9].
●Acute pulmonary edema occurring during or shortly after infusion of blood products suggests transfusional volume overload.
Physical examination — The physical examination can provide evidence of the presence and extent of cardiac filling pressure elevation, volume overload, ventricular enlargement, pulmonary hypertension, and reduction in cardiac output. (See "Heart failure: Clinical manifestations and diagnosis in adults", section on 'Physical examination'.)
Findings that suggest particular causes of HF include:
●Primary valvular dysfunction should be considered in a patient with a cardiac murmur. (See "Auscultation of cardiac murmurs in adults".)
●The presence of hypertension suggests hypertension as a cause of HF and/or as an exacerbating factor.
●Extracardiac findings may suggest specific types of cardiomyopathy, such as the following:
•The presence of periorbital purpura (nearly pathognomonic for AL amyloid cardiomyopathy) or peripheral neuropathy (a nonspecific finding seen in some patients with AL or mutant transthyretin amyloid cardiomyopathy). (See "Cardiac amyloidosis: Epidemiology, clinical manifestations, and diagnosis", section on 'Clinical manifestations'.)
•The classic triad of cirrhosis, diabetes mellitus, and skin pigmentation ("bronze diabetes") suggests late stage hemochromatosis, but most patients with iron overload present at an earlier stage without these findings. (See "Clinical manifestations and diagnosis of hereditary hemochromatosis", section on 'Clinical manifestations'.)
INITIAL TESTS
Electrocardiogram — The ECG may show findings that favor the presence of a specific cause of HF and can also detect arrhythmias such as asymptomatic premature ventricular complex/contraction (PVC; also referred to as premature ventricular beats or premature ventricular depolarizations), runs of nonsustained ventricular tachycardia, or atrial fibrillation, which may be the cause of or exacerbate HF. (See "Arrhythmia-induced cardiomyopathy".)
Patients with dilated cardiomyopathy frequently have first degree atrioventricular block, left bundle branch block, left anterior fascicular block, or a nonspecific intraventricular conduction abnormality.
Potentially diagnostic findings on ECG include the following:
●Evidence of ischemic heart disease, including evidence of prior or acute myocardial infarction or ischemia.
●LV hypertrophy due to hypertension; a pseudoinfarct pattern may also be present representing significant posterior forces of the increased LV mass.
●Low limb lead voltage on the surface ECG with a pseudo-infarction pattern (loss of precordial R wave progression in leads V1-V6) can suggest an infiltrative process such as amyloidosis.
●Low limb lead voltage with precordial criteria for LV hypertrophy is most suggestive of idiopathic dilated cardiomyopathy. A widened QRS complex and/or a left bundle branch block pattern is also consistent with this diagnosis.
●Heart block, that may be complete, and various types of intraventricular conduction defects are observed in patients with cardiac sarcoidosis.
●The presence of a persistent tachycardia such as atrial fibrillation with a rapid ventricular response may result from or lead to HF, since this arrhythmia can cause cardiomyopathy (tachycardia-mediated cardiomyopathy).
Initial blood tests — Recommended initial blood tests for patients with symptoms and signs of HF include [2]:
●A complete blood count, which may suggest concurrent or alternate conditions. Anemia or infection can exacerbate pre-existing HF. (See "Evaluation and management of anemia and iron deficiency in adults with heart failure".)
●Serum electrolytes (including calcium and magnesium), blood urea nitrogen, and creatinine may indicate associated conditions. Hyponatremia generally indicates severe HF, though it may occasionally result from excessive diuresis [10]. Kidney function impairment may be caused by and/or contribute to HF exacerbation. Baseline evaluation of electrolytes and creatine is also necessary when initiating therapy with diuretics and/or angiotensin converting enzyme inhibitors.
●Liver function tests, which may be affected by hepatic congestion.
●Fasting blood glucose and lipid profile to detect underlying diabetes mellitus and lipid disorders. (See "Heart failure in patients with diabetes mellitus: Epidemiology, pathophysiology, and management" and "Screening for lipid disorders in adults".)
●Thyroid stimulating hormone, since hyperthyroidism or hypothyroidism can precipitate HF. (See "Cardiovascular effects of hyperthyroidism" and "Cardiovascular effects of hypothyroidism".)
Echocardiography — Echocardiography should be performed in all patients with new onset HF and can provide important information about ventricular size and function. For example, patients with idiopathic dilated cardiomyopathy typically have both left and right ventricular enlargement (four-chamber dilation) with decreased left systolic ventricular function. (image 1 and figure 1 and movie 1 and movie 2 and movie 3). (See "Echocardiographic recognition of cardiomyopathies".)
The sensitivity and specificity of two-dimensional echocardiography for the diagnosis of systolic dysfunction are as high as 80 and 100 percent, respectively [10]. A number of other important findings also can be detected:
●Although regional wall motion abnormalities are compatible with coronary artery disease, they are not specific for ischemia since they also occur in 50 to 60 percent of patients with idiopathic dilated cardiomyopathy [11].
However, regional wall motion assessment using dobutamine stress echocardiography may increase the ability to distinguish among ischemic and nonischemic cardiomyopathies. The presence of six or more akinetic segments, for example, was 80 percent sensitive and 96 percent specific for ischemic dilated cardiomyopathy in one report [12].
●Pericardial thickening suggestive of constrictive pericarditis.
●Valvular structure and function in valve disease.
●Interatrial and interventricular shunts.
●Abnormal myocardial texture in infiltrative cardiomyopathies, with LV hypertrophy and a "sparkling" pattern being suggestive of cardiac amyloidosis (movie 4 and movie 5 and movie 6). (See "Echocardiographic recognition of cardiomyopathies".)
●Right ventricular size and function in right HF.
●Estimation of pulmonary capillary wedge pressure (PCWP) via the ratio (E/Ea or E/E') of tissue Doppler of early mitral inflow velocity (E) to early diastolic velocity of the mitral annulus (Ea or e'). An E/e' ratio >15 suggests a PCWP >15 mmHg when e' is the mean of medial and lateral mitral annulus early diastolic velocities [13]. Use and limitations of this method are discussed separately. (See "Echocardiographic evaluation of left ventricular diastolic function in adults", section on 'Tissue Doppler imaging'.)
•However, the E/e' ratio may not be a reliable indicator of PCWP in patients with acute decompensated HF. In a series of 106 patients with acute decompensated HF and LVEF ≤30 percent, the E/e' ratio did not correlate with PCWP [14]. One limitation of this study is that patients with significant mitral valve disease were not excluded.
•One limitation of use of the E/e' ratio is that it does not predict PCWP in patients with significant mitral valve disease (either mitral stenosis or mitral regurgitation). In patients with mitral valve disease, a preliminary report indicates that the ratio of isovolumetric relaxation time to the time interval between the onset of E and Ea (TE-Ea) correlates with PCWP [15].
●A short deceleration time (≤125 ms) is an independent predictor of poor prognosis in patients with LV dysfunction, regardless of the presence or absence of symptoms [16].
●Right atrial and pulmonary artery pressures, determined by the peak velocity of tricuspid regurgitation on Doppler echocardiography. These findings correlate with the pulmonary artery wedge pressure, regardless of the etiology of HF or severity of tricuspid regurgitation; they can be used to assess changes in LV filling pressures resulting from therapy [9].
●Limited data suggest that the cardiac output can be measured accurately by pulsed-wave Doppler from the LV outflow tract, even in the presence of a low output state or tricuspid regurgitation (image 2) [17].
Echocardiography in conjunction with dobutamine is also useful in predicting recovery of cardiac function [18,19]. (See "Prognosis of heart failure".)
Testing for coronary artery disease — In virtually all patients with newly diagnosed HF, we obtain a test to evaluate for the presence of coronary artery disease (CAD).
Reduced systolic function — In patients with HFrEF, CAD is the most common cause of LV dysfunction. The approach to testing is determined by the likelihood of CAD, as follows:
●Determine the likelihood of CAD – The first step in our approach to testing is to determine the likelihood that CAD is the cause of the patient’s LV dysfunction. This assessment is done by evaluating for risk factors and signs of CAD that include:
•Age >40 for males or age >50 years for females
•History of hypertension, diabetes, stroke, peripheral arterial disease, chronic kidney disease, or hyperlipidemia
•History of tobacco use
•Family history of early CAD
•Symptoms consistent with angina
•Regional wall motion abnormalities and/or signs of infarction in a coronary artery distribution
•History of ventricular arrhythmias or cardiac arrest
●Is there another cause for HFrEF? – In patients with new-onset HFrEF, other causes of HFrEF may be evident. The presence of a diagnosis known to cause LV dysfunction may decrease the likelihood of CAD.
●Approach to testing for CAD – Our approach to testing is based on the likelihood of CAD, as follows:
•Presence of risk factors or signs of CAD – In patients with newly diagnosed HF who have established risk factors for CAD or signs of CAD, we obtain a test for CAD. Similar to other patients who undergo testing for CAD, patients with a high likelihood of CAD should undergo initial testing with invasive coronary angiography, while patients with low to moderate likelihood of CAD should undergo initial testing with a noninvasive test.
•Absence of risk factors or signs of CAD – In patients with new-onset HF, no risk factors for CAD, and no signs of CAD (eg, focal hypokinesis), the approach to testing is determined by the presence or absence of a diagnosis that is more likely to explain HFrEF:
-No diagnosis that likely causes HFrEF – If the risk of CAD is low, but there is no other diagnosis that explains HFrEF, we obtain a noninvasive study to evaluate for CAD.
-Other causes of HFrEF have been identified – If the risk of CAD is low and there is the patient has a diagnosis that is likely to cause HFrEF, we may not evaluate for CAD.
The approach to choosing an optimal stress imaging study or coronary computed tomographic angiography (CCTA) and the details on invasive coronary angiography are discussed separately. (See "Complications of diagnostic cardiac catheterization" and "Selecting the optimal cardiac stress test".)
The American Heart Association/American College of Cardiology/Heart Failure Society of America guidelines support the use of stress imaging and invasive or noninvasive coronary arteriography to test for CAD in patients with HF [2].
The role of viability testing for the management of patients with ischemic cardiomyopathy is discussed elsewhere. (See "Treatment of ischemic cardiomyopathy", section on 'Additional imaging'.)
●Interpretation of results – Due to the high prevalence of mild CAD in many populations, the presence of nonobstructive CAD on testing does not fully establish CAD as the cause of HF. The presence of asymptomatic angiographic coronary artery disease in patients with abnormal LV function does not prove causality unless there is evidence of prior infarction, hibernating myocardium, or no other explanation for LV dysfunction [20,21].
The approach to revascularization in this population is discussed separately. (See "Treatment of ischemic cardiomyopathy".)
●Rationale – This approach to testing for CAD in newly diagnosed HF is based on the high frequency with which CAD causes HF and the need to definitively exclude CAD, which is a potentially treatable cause of HF. While stress imaging studies or CCTA are accurate studies for the exclusion of CAD, invasive coronary angiography is the gold standard. In addition, invasive coronary angiography performed via the radial artery has a low risk of complications.
There are limited data that compare various tests for CAD in patients with HF. In one trial that included patients with newly diagnosed HFrEF, patients were randomly assigned to initial testing with CCTA or invasive coronary angiography [22]. After 12 months of observation, 23 percent of patients assigned to CCTA underwent coronary angiography (77 percent avoided invasive coronary angiography) and there were similar rates of cardiac death, myocardial infarction, cardiac arrest, cardiac hospitalization, and procedural complications. However, not all patients in this trial underwent coronary angiography. Further details on the diagnostic characteristics of CCTA can be found elsewhere. (See "Clinical use of coronary computed tomographic angiography", section on 'Diagnostic accuracy'.)
Preserved systolic function — In patients with preserved systolic function, the approach to testing for CAD is similar to the approach in patients with reduced systolic function and is discussed separately. (See "Heart failure with preserved ejection fraction: Clinical manifestations and diagnosis", section on 'Testing for coronary artery disease'.)
ADDITIONAL TESTS —
If a cause of HF is not determined from the above assessment, the initial evaluation can help guide further testing.
Blood tests — If it is determined that dilated cardiomyopathy is responsible for HF and the cause is not apparent after the initial evaluation, several other blood tests may be warranted (see "Causes of dilated cardiomyopathy"). As noted above, thyroid disease should be considered in the initial evaluation.
Other studies that may be undertaken in selected patients depending upon the results of initial evaluation and include the following [2]:
●Screening for human immunodeficiency virus. (See "Overview of cardiac and vascular diseases in patients with HIV", section on 'Heart failure attributed to HIV'.)
●Iron studies (ferritin and transferrin saturation) are helpful to screen for hereditary hemochromatosis (HH). Prior to increased screening, cardiac disease was the presenting manifestation in up to 15 percent of patients with HH. Thus, the absence of other characteristic findings of HH does not preclude the diagnosis. (See "Clinical manifestations and diagnosis of hereditary hemochromatosis", section on 'Cardiac iron overload'.)
●Antinuclear antibodies and other serologic tests for lupus and other rheumatologic diseases.
●Viral serologies and antimyosin antibody if myocarditis is suspected.
●Evaluation for pheochromocytoma.
●Thiamine, carnitine, and selenium levels.
●Genetic testing and counseling (eg, in patients suspected of familial cardiomyopathy after obtaining a detailed family history). (See 'Evaluation for genetic causes of cardiomyopathy' below.)
●Serum and urine protein electrophoresis in patients with suspected plasma cell disorders.
Cardiovascular magnetic resonance — Cardiovascular magnetic resonance (CMR) imaging can be used to identify late gadolinium enhancement patterns suggestive of myocardial infarction or various causes of cardiomyopathy such as hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, sarcoidosis, cardiac amyloidosis, and myocarditis (which were among the diagnoses that were missed in some series). (See 'Etiology' above and "Clinical utility of cardiovascular magnetic resonance imaging" and "Cardiac imaging with computed tomography and magnetic resonance in the adult".)
Endomyocardial biopsy — Endomyocardial biopsy is recommended in clinical scenarios in which its diagnostic and prognostic value is felt to outweigh the procedural risks. The diagnostic value of endomyocardial biopsy depends upon the anticipated yield of the procedure and also the availability of effective therapy. The indications, potential benefit, and risks of endocardial biopsy in identifying the etiology of dilated cardiomyopathy are discussed in detail separately. (See "Endomyocardial biopsy".)
In summary, endomyocardial biopsy is recommended in patients with fulminant HF (unexplained new-onset HF of less than two weeks duration with hemodynamic compromise) and in patients with early atrioventricular block, arrhythmias, or refractory HF (unexplained new-onset HF of two weeks to three months’ duration with a dilated LV). (See "Endomyocardial biopsy", section on 'EMB recommended'.)
Endomyocardial biopsy is suggested in other specific clinical scenarios when other evaluation is inconclusive. (See "Endomyocardial biopsy", section on 'EMB suggested in selected cases'.)
Evaluation for genetic causes of cardiomyopathy — In patients in whom a cause of cardiomyopathy (eg, ischemic, valvular) cannot be established by other forms of testing, we evaluate for a genetic etiology of cardiomyopathy.
Initial evaluation — The initial evaluation for genetic cardiomyopathies includes a complete family history and review of all relevant clinical data for signs characteristic of specific cardiomyopathies:
●Family history – For all patients in whom a genetic cause of cardiomyopathy is suspected or in whom a clear cause of cardiomyopathy has not been identified, we recommend a thorough family history that includes assessment for signs or symptoms of cardiomyopathy among at least three generations of relatives. The family history should include evaluation for the presence of:
•Unexplained HF before age the age of 60
•Sudden death without a history of ischemia or treatment with an implantable cardioverter-defibrillator
•History of heart transplantation or mechanical circulatory support
In addition, the family history should include an analysis of the pedigree (eg, cause of death). Referral to a center with expertise in genetic cardiomyopathies may be helpful in obtaining and reviewing family history and pedigree information.
This approach is consistent with professional guidelines [2,23].
●Signs characteristic of inherited cardiomyopathies – The patient's clinical findings may suggest the presence of a specific genetic cardiomyopathy (eg, enlarged right ventricle and arrhythmias consistent with arrhythmogenic right ventricular cardiomyopathy [ARVC], severe hypertrophy and LV outflow tract obstruction consistent with hypertrophic cardiomyopathy [HCM]). The evaluation for each genetic cardiomyopathy requires experience and knowledge of these conditions. A description of the clinical features characteristic of each genetic cardiomyopathy is beyond the scope of this topic; further details are available in the following topics:
•(See "Arrhythmogenic right ventricular cardiomyopathy: Anatomy, histology, and clinical manifestations".)
•(See "Restrictive cardiomyopathies", section on 'Clinical features'.)
•(See "Mitochondrial myopathies: Clinical features and diagnosis", section on 'Clinical features'.)
Additional evaluation — Following the initial evaluation, the approach to genetic testing depends on the clinical scenario:
●Findings suspicious for a genetic cardiomyopathy – In patients in whom the clinical findings or family history suggest the presence of a specific disease or of an inherited disorder, genetic testing is typically required.
•Clinical findings suggest a specific disease – In patients in whom a specific disease is suspected, we pursue appropriate diagnostic testing for that disease.
•Family history suggests an inherited cardiomyopathy – In patients whose family history suggests the presence of an inherited cardiomyopathy but not a specific disease, we obtain genetic testing. If the provider or patient has uncertainty regarding the findings expected from testing, consultation with a genetic counselor may be appropriate. (See "Genetic counseling: Family history interpretation and risk assessment" and "Secondary findings from genetic testing".)
Among the relatives who may have a pathogenic gene variant, testing typically begins with the relative who is the most clearly affected [2]. The results of testing in this individual determine whether testing of other family members is indicated (see 'Family screening' below). This approach is consistent with professional guidelines [2,23].
In patients who will undergo genetic testing, we test for the presence of pathogenic gene variants using a broad panel of genes known to cause cardiomyopathy. However, this approach is not shared by all experts. Some experts advocate for targeted gene testing restricted to genes likely to cause the suspected disease, while others advocate for broader testing of a panel of genes that commonly cause genetic cardiomyopathy. The diverse presentation and clinical findings among the genetic cardiomyopathies favors a broad approach to testing, while the desire to minimize false positive results and contain costs related to broader testing recommend the targeted approach. There are limited data on the relative efficacy of these approaches to testing, but broad testing may have a higher true positive rate than does targeted testing. In a study that included 3147 patients suspected of a cardiomyopathy (nonarrhythmic or arrhythmic) and who underwent broad genetic testing, broad testing yielded a genetic diagnosis in 22 percent of patients, while disease-specific testing yielded a genetic diagnosis in 20 percent of patients.
●No findings to suggest a genetic cardiomyopathy – In patients without clinical findings or family history suggestive of a specific disorder, we do not routinely obtain genetic testing. This approach is consistent with professional guidelines; however, the yield of genetic testing is unclear [2,23]:
•In a series that reported the results of genetic testing in patients with no clear cause for dilated cardiomyopathy, a genetic cause for disease was detected in 10 to 20 percent of patients [24].
•In a cohort of 1015 patients with DCM or LV systolic dysfunction who were referred for genetic testing, 37 percent of patients had a positive gene test for a disease known to cause cardiomyopathy. After screening multiple factors, the factors that were independently associated with a gene positive test were:
-Family history of DCM (odds ratio [OR] 2.3)
-Low ECG voltage in the limb leads (OR 3.6)
-Presence of skeletal myopathy (OR 3.4)
-Absence of hypertension (OR 2.3)
-Absence of left bundle branch block (OR 3.6)
The presence of each additional factor increased the probability of a gene positive test result by approximately 20 percent. The overall diagnostic accuracy of a score composed of the factors above was high in a separate cohort used for validation of the criteria (area under the curve 0.74; 95% CI 0.71-0.78).
Family screening — We agree with society guidelines that recommend screening first-degree relatives of patients with cardiomyopathy (including all types for which the guidelines recommend detailed family history). These guidelines are supported by evidence that cardiomyopathy is frequently familial and that affected family members are frequently asymptomatic [2]. Progressive disease may occur within a relatively short period of time in initially asymptomatic family members with abnormal ECG or echocardiographic findings [25-27]. (See "Approach to diagnosis of asymptomatic left ventricular systolic dysfunction".)
The following screening is recommended for first-degree relatives of patients with cardiomyopathy [2]:
●Clinical screening for cardiomyopathy in asymptomatic first-degree relatives is recommended whether genetic testing has been undertaken and whether a genetic cause was identified by genetic testing. Screening should include the following:
•History (with special focus on HF symptoms, arrhythmias, presyncope, and syncope)
•Physical examination (with special attention to the cardiac and skeletal muscle systems)
•ECG
•Echocardiogram
•Creatine kinase MM fraction (at initial evaluation only)
•Signal-averaged ECG in ARVC only
•Holter monitoring in HCM and ARVC
•Exercise treadmill testing in HCM
•CMR imaging in ARVC
●Asymptomatic first-degree relatives with negative clinical or genetic screening should be rescreened at regular intervals or at any time that symptoms or signs of cardiac dysfunction appear. The frequency of recommended rescreening varies with cardiomyopathy type:
•HCM – Every three years until 30 years old, except yearly during puberty
•DCM – Every three to five years beginning in childhood
•ARVC – Every three to five years after age 10
•LV noncompaction – Every three years beginning in childhood
•Restrictive cardiomyopathy – Every three to five years beginning in adulthood
More frequent screening is recommended if a mutation is present in the family.
SOCIETY GUIDELINE LINKS —
Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Heart failure in adults" and "Society guideline links: Cardiomyopathy".)
SUMMARY AND RECOMMENDATIONS
●Diagnostic approach – Clinical assessment of the patient with heart failure (HF) or cardiomyopathy includes history, physical examination, initial blood tests, ECG, chest radiograph, and echocardiography. (See 'Diagnostic approach' above and "Heart failure: Clinical manifestations and diagnosis in adults".)
●Initial blood tests – For patients with newly diagnosed HF, we obtain a complete blood count, serum electrolytes, creatinine, blood urea nitrogen, liver function tests, fasting glucose, hemoglobin A1c, and thyroid function tests. (See 'Initial blood tests' above.)
●Echocardiography – Echocardiography should be performed in all patients with new-onset HF. Echocardiography has a high sensitivity and specificity for the diagnosis of myocardial dysfunction, and may also establish the etiology of HF. (See 'Echocardiography' above.)
●Testing for coronary artery disease – In all patients with newly diagnosed HF, we obtain a test to evaluate for coronary artery disease (CAD). (See 'Testing for coronary artery disease' above.)
•Risk factors or signs of CAD – In patients with newly diagnosed HF who have established risk factors for CAD or signs of CAD, we typically obtain a coronary angiogram as the initial test to evaluate for CAD.
•No risk factors or signs of CAD – In patients with new-onset HF and no risk factors or signs of CAD, we obtain either a coronary angiogram, stress imaging study, or coronary computed tomographic angiography (CCTA) as the initial test for CAD.
●Additional testing – Beyond an initial evaluation, echocardiography, and assessment for coronary artery disease, additional tests may be warranted to establish the etiology of cardiomyopathy. (See 'Additional tests' above and "Causes of dilated cardiomyopathy".)
•Blood tests – In patients without a clear cause for HF, we obtain iron studies, testing for human immunodeficiency virus, anti-nuclear antibodies, and trace element levels. Additional blood tests typically require suspicion for a specific cause. (See 'Blood tests' above.)
•CMR – Cardiovascular magnetic resonance (CMR) imaging may be helpful in distinguishing ischemic heart disease from cardiomyopathy and in identifying the type of cardiomyopathy. (See 'Cardiovascular magnetic resonance' above and "Clinical utility of cardiovascular magnetic resonance imaging", section on 'CMR characterization of myocardial diseases'.)
•Endomyocardial biopsy – Endomyocardial biopsy should be reserved for patients with established indications. (See 'Endomyocardial biopsy' above.)
•Genetic testing – In patients in whom a cause of cardiomyopathy (eg, ischemic, valvular) cannot be established by other forms of testing, we evaluate for a genetic etiology of cardiomyopathy. (See 'Evaluation for genetic causes of cardiomyopathy' above.)
