What are the causes and evaluation approaches for heart failure, including initial and serial assessments?

Causes of Heart Failure and Evaluation Approach

Primary Causes of Heart Failure

Coronary artery disease is the dominant cause of heart failure, accounting for approximately two-thirds of cases with left ventricular systolic dysfunction, making ischemic evaluation essential in every heart failure workup. 1

Major Etiologies by Frequency

• Ischemic heart disease represents approximately 40% of heart failure cases globally and is the single most common etiology 2
• Hypertension accounts for 17-31% of cases, with higher prevalence in heart failure with preserved ejection fraction (HFpEF) 2
• Idiopathic dilated cardiomyopathy comprises approximately 30% of cases, with up to 30% having a genetic basis 2
• Valvular heart disease (excluding primary valvular disease requiring separate guidelines) 1
• Myocardial toxins including anthracyclines, trastuzumab, high-dose cyclophosphamide, and alcohol 1
• Myocarditis and infectious causes 1

Critical Geographic and Demographic Variations

• Eastern Europe and Middle East show highest rates of ischemic etiology, while Africa shows lowest rates 2
• Elderly patients and women more commonly present with HFpEF, particularly with systolic hypertension and myocardial hypertrophy 3, 2
• Patients in low- and middle-income countries present with more advanced heart failure at younger ages and are more often women 4

Initial Evaluation: The Algorithmic Approach

Step 1: History - Specific Risk Factors to Identify

The evaluation must systematically identify treatable and reversible causes, as some conditions leading to left ventricular dysfunction can be reversed with targeted therapy. 1

Personal History Must Include:

• Hypertension, diabetes mellitus, dyslipidemia, tobacco use 1
• Coronary, valvular, or peripheral vascular disease 1
• Rheumatic fever, heart murmur, congenital heart disease 1
• Mediastinal irradiation (heart failure may occur years after exposure) 1
• Sleep-disordered breathing symptoms 1
• Cardiotoxic agent exposure: ephedra, anthracyclines, trastuzumab, cyclophosphamide 1
• Current and past alcohol consumption (quantify precisely) 1
• Illicit drug use 1
• Sexually transmitted disease exposure 1
• Thyroid disorder, pheochromocytoma 1
• Collagen vascular disease 1

Family History Must Include:

• Atherosclerotic disease (myocardial infarctions, strokes, peripheral arterial disease) 1
• Sudden cardiac death 1
• Myopathy or skeletal myopathy 1
• Conduction system disease requiring pacemaker 1
• Tachyarrhythmia 1
• Unexplained cardiomyopathy 1

Step 2: Initial Laboratory Evaluation (All Patients)

The following tests are mandatory for initial evaluation: 1

• Complete blood count 1
• Urinalysis 1
• Fasting lipid profile 1
• Liver function tests 1
• Serum electrolytes (including calcium and magnesium) 1
• Blood urea nitrogen and serum creatinine 1
• Fasting glucose 1
• Thyroid-stimulating hormone 1

Step 3: Cardiac Imaging - Echocardiography is the Diagnostic Standard

Comprehensive echocardiographic evaluation is essential because patients commonly have multiple cardiac abnormalities contributing to heart failure, and it serves as the baseline for serial comparison. 1

Echocardiography Must Assess:

• Left ventricular ejection fraction (defines HFrEF ≤40% vs HFpEF ≥50%) 2, 5
• Chamber size and ventricular mass 1
• Valvular abnormalities 1
• Cardiac hypertrophy 1
• Diastolic filling patterns 1
• Severity of structural remodeling 1

Alternative Imaging When Indicated:

• Magnetic resonance imaging for chamber size, ventricular mass, right ventricular dysplasia, pericardial disease, myocardial viability, and scar tissue identification 1
• Computed tomography for similar assessments 1
• Radionuclide ventriculography for highly accurate left and right ventricular ejection fraction when echocardiography is inadequate 1

Step 4: Electrocardiography and Chest Radiography

• 12-lead ECG identifies prior myocardial infarction, left ventricular hypertrophy, conduction abnormalities (left bundle-branch block), and arrhythmias 1
• Chest radiography estimates cardiac enlargement, pulmonary congestion, and detects pulmonary disease 1

Critical caveat: Neither chest x-ray nor ECG should form the primary basis for determining the specific cardiac abnormality due to low sensitivity and specificity 1

Step 5: Biomarker Assessment

B-type natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP) measurement is useful when clinical uncertainty exists, as it has high negative predictive value for ruling out heart failure. 1, 5

BNP/NT-proBNP Utility:

• Supports diagnosis when clinical uncertainty exists 1
• Establishes prognosis and disease severity in outpatients 1
• Guides optimal medical therapy dosing in select euvolemic outpatients 1
• Supports diagnosis in hospitalized patients with acute decompensation 1
• Determines prognosis in hospitalized patients 1

Important limitation: Serial measurement to reduce hospitalizations or mortality has not been established as useful 1

Step 6: Selective Additional Testing

Order these tests only when clinical suspicion warrants: 1

• Serum ferritin for hemochromatosis screening 1
• HIV testing 1
• Antinuclear antibody assays for rheumatologic diseases 1
• Rheumatoid factor 1
• Metanephrine measurements for pheochromocytoma 1
• Cardiac troponin for myocardial injury assessment 1

Serial Evaluation Strategy

Renal Function and Electrolyte Monitoring

Serial monitoring must include renal function testing and serum electrolytes, as these guide diuretic therapy and detect medication-related complications. 1

Repeat Echocardiography Indications

Obtain repeat echocardiography when: 1

• Change in clinical status occurs 1
• Patient experiences or recovers from a clinical event 1
• Treatment that might significantly affect cardiac function has been administered 1

Biomarker Trends

• Measurement of BNP/NT-proBNP establishes prognosis in outpatients with chronic heart failure 1
• Other biomarkers of myocardial injury or fibrosis may be considered for additional risk stratification 1

Critical Clinical Pitfalls to Avoid

Do not dismiss heart failure based solely on absence of peripheral edema or pulmonary rales—these signs may be absent in early stages or well-treated patients. 5

Do not overlook that patients with very low ejection fraction may be asymptomatic, while those with preserved left ventricular systolic function may have severe disability—the poor correlation between ejection fraction and symptoms is well-established. 1, 5

Never use heart failure as the sole diagnosis—the underlying cause must always be identified, as specific etiologies require targeted treatments beyond standard heart failure management. 3

Remember that heart failure may occur years after exposure to anthracyclines or mediastinal irradiation, requiring careful historical inquiry about remote exposures. 1

Do not confuse NYHA functional class with ACC/AHA stage—functional class changes with treatment, but stage progression is essentially unidirectional. 5