What is the likely cause of pulmonary congestion in a patient with a normal left ventricular ejection fraction (~56%), controlled blood pressure, and cardiomegaly?

Heart Failure with Preserved Ejection Fraction (HFpEF)

This patient most likely has heart failure with preserved ejection fraction (HFpEF), which is the primary cause of pulmonary congestion in patients with normal left ventricular systolic function (EF ≥50%) and cardiomegaly. 1

Primary Diagnosis: HFpEF

The clinical triad of pulmonary congestion, preserved EF (56%), and cardiomegaly strongly indicates HFpEF, which affects approximately 3 million people in the US and presents with objective evidence of cardiogenic pulmonary congestion despite normal systolic function. 2 According to the 2023 ACC Expert Consensus, cardiomegaly is listed as a major Framingham criterion for heart failure diagnosis, and the Universal Definition of HF requires symptoms/signs caused by structural/functional cardiac abnormalities with either elevated natriuretic peptides or objective evidence of cardiogenic pulmonary or systemic congestion. 1

Key Pathophysiologic Mechanism

The underlying etiology is diastolic dysfunction with impaired left ventricular relaxation, leading to elevated left ventricular end-diastolic pressure that transmits backward to cause pulmonary venous congestion. 1, 3 This occurs despite preserved systolic contractility (normal EF), as the stiff, non-compliant ventricle cannot adequately fill during diastole without generating high filling pressures. 4

Specific Etiologies to Investigate

While HFpEF is the syndrome diagnosis, you must systematically exclude specific cardiac mimics that require disease-directed therapy:

Infiltrative/Restrictive Cardiomyopathy

• Cardiac amyloidosis (particularly transthyretin amyloidosis) presents with increased LV wall thickness, preserved EF, and cardiomegaly. 1
• Look for: carpal tunnel syndrome, lumbar spinal stenosis, low-voltage ECG despite thick walls, and "sparkling" myocardium on echo. 1
• Confirm with technetium pyrophosphate scan and monoclonal protein screen. 1

Hypertrophic Cardiomyopathy

• Presents with LV hypertrophy, preserved EF, and diastolic dysfunction causing pulmonary congestion. 1
• Assess for asymmetric septal hypertrophy, systolic anterior motion of mitral valve, and family history. 1

Valvular Heart Disease

• Mitral stenosis or regurgitation can cause left atrial pressure elevation and pulmonary congestion with preserved LV systolic function. 1
• Aortic stenosis causes concentric LV hypertrophy with diastolic dysfunction. 1

Pericardial Disease

• Constrictive pericarditis or restrictive physiology can mimic HFpEF with elevated filling pressures and congestion. 1
• Evaluate with CMR or invasive hemodynamics if suspected. 1

Hypertensive Heart Disease

• Chronic hypertension is the most common risk factor for HFpEF development, causing concentric LV hypertrophy and diastolic dysfunction. 1, 4
• Even with "okay" BP currently, prior uncontrolled hypertension may have caused irreversible structural changes. 4
• Restrictive hemodynamic patterns can develop in severe hypertensive heart disease. 4

High-Output Heart Failure

• Hyperthyroidism, severe anemia, or arteriovenous fistulas can cause high-output failure with pulmonary congestion despite preserved EF. 1, 5
• Look for: tachycardia, widened pulse pressure, warm extremities, and thyroid symptoms. 5

Critical Diagnostic Algorithm

Step 1: Confirm HFpEF diagnosis with elevated natriuretic peptides (BNP >35 pg/mL ambulatory or >100 pg/mL hospitalized; NT-proBNP >125 pg/mL ambulatory or >300 pg/mL hospitalized). 1

Step 2: Perform comprehensive echocardiography assessing:

• LV wall thickness and mass (increased suggests hypertensive heart disease, infiltrative disease, or HCM) 1, 4
• Diastolic function parameters (E/e' ratio, left atrial volume index) 1
• Valvular function 1
• Estimated pulmonary artery systolic pressure 1

Step 3: Evaluate for specific cardiac mimics based on clinical red flags:

• If increased LV wall thickness + carpal tunnel/spinal stenosis: Order technetium pyrophosphate scan for amyloidosis 1
• If asymmetric septal hypertrophy: Consider genetic testing for HCM 1
• If significant valvular disease: Refer to cardiology/cardiac surgery 1
• If pericardial thickening: Consider CMR or invasive hemodynamics 1

Step 4: Exclude noncardiac mimics:

• Kidney disease (check creatinine, urinalysis for proteinuria) 1
• Liver disease (check liver function tests, abdominal ultrasound) 1
• Pulmonary disease (chest imaging, spirometry, arterial blood gas) 1

Common Pitfalls

Pitfall 1: Assuming all patients with preserved EF and congestion have "simple" HFpEF without investigating for treatable specific etiologies like amyloidosis or valvular disease. 1

Pitfall 2: Missing the diagnosis because natriuretic peptide levels are lower in HFpEF compared to HFrEF for a given elevation in LV end-diastolic pressure, especially in obese patients. 1

Pitfall 3: Overlooking concentric LV geometry (increased relative wall thickness) as a marker of increased risk for acute pulmonary edema episodes in these patients. 6

Pitfall 4: Failing to recognize that "controlled" blood pressure does not exclude prior hypertensive damage causing diastolic dysfunction and HFpEF. 4

Specialist Referral Indications

Immediate heart failure specialist consultation is warranted for diagnostic dilemmas, management of special/unusual cardiomyopathies, and optimization of guideline-directed medical therapy. 1 Multidisciplinary collaboration may include electrophysiologists, interventional cardiologists, endocrinologists, nephrologists, and pulmonologists depending on identified comorbidities. 1