Cardiovascular · Year 1 · from Cardiovascular

Case 2: Heart Failure with Preserved Ejection Fraction (HFpEF)

Patient Presentation

Demographics: 72-year-old female

Chief Complaint: Shortness of breath with exertion and leg swelling

History of Present Illness: A 72-year-old female with long-standing hypertension, type 2 diabetes, obesity (BMI 34), and atrial fibrillation presents with 2 months of worsening dyspnea on exertion. She becomes short of breath climbing one flight of stairs. She reports leg swelling that worsens throughout the day and occasional difficulty lying flat. She denies chest pain. She has been compliant with her medications but notes her blood pressure has been difficult to control.

Physical Examination:

• Vital Signs: BP 158/92 mmHg, HR 88 bpm (irregular), RR 18/min, SpO2 96% on room air, BMI 34
• General: Obese, mild respiratory effort
• Cardiovascular:
• JVP 10 cm H2O
• Irregularly irregular rhythm
• S4 gallop, no S3
• PMI not displaced
• No murmurs
• Lungs: Fine bibasilar crackles
• Abdomen: Obese, mild hepatomegaly
• Extremities: 2+ pitting edema to mid-shins

Workup

• NT-proBNP: 890 pg/mL (elevated for age/sex, but less marked than HFrEF)
• Labs:
• HbA1c 7.6%
• Cr 1.2, eGFR 52
• Na 138, K 4.2
• ECG: Atrial fibrillation, rate 88, LVH by voltage criteria
• Echocardiogram:
• LV ejection fraction 58% (preserved)
• Concentric LVH (wall thickness 1.4 cm)
• Grade II diastolic dysfunction
• E/e' ratio 16 (elevated filling pressures)
• LA enlargement (48 mL/m2)
• Normal LV cavity size

Diagnosis

Heart Failure with Preserved Ejection Fraction (HFpEF) - NYHA Class II-III

Heart Failure Correlation:

Pathophysiology of Diastolic Dysfunction:

1. Concentric Hypertrophy:

• Chronic hypertension increases afterload
• LV adds sarcomeres in parallel (wall thickening)
• Maintains normal wall stress (Law of LaPlace)
• But reduces chamber compliance

1. Impaired Relaxation:

• Hypertrophied myocytes have abnormal calcium handling
• Reduced SERCA activity slows calcium reuptake
• Prolonged relaxation time
• Especially problematic with tachycardia (shortened diastole)

1. Increased Passive Stiffness:

• Myocardial fibrosis from chronic pressure overload
• Altered titin isoforms increase stiffness
• Reduced compliance: small volume changes cause large pressure changes

1. Elevated Filling Pressures Despite Normal EF:

• Stiff ventricle requires high pressure to fill adequately
• E/e' ratio reflects elevated LVEDP
• Transmitted to LA (enlargement, AF)
• Transmitted to pulmonary veins (congestion)

Contributing Comorbidities:

• Hypertension: Primary driver of LVH and diastolic dysfunction
• Diabetes: Myocardial stiffening, microvascular disease
• Obesity: Increased blood volume, systemic inflammation
• Atrial fibrillation: Loss of atrial kick, rapid rates worsen filling
• CKD: Volume overload, neurohormonal activation

Why EF Is "Preserved" but Heart Still Fails:

• EF measures systolic function (emptying)
• HFpEF has normal emptying but abnormal filling
• Reduced stroke volume from inadequate diastolic filling
• Inability to augment cardiac output with exercise

Pressure-Volume Loop:

• Steepened EDPVR (end-diastolic pressure-volume relationship)
• Higher pressures for same filling volume
• Normal ESPVR (contractility preserved)

Treatment

Congestion Management:

1. Diuretics:

• Loop diuretics for volume control
• Careful titration - HFpEF patients are preload-dependent
• Avoid over-diuresis (hypotension, renal dysfunction)

SGLT2 Inhibitor:

• Empagliflozin or dapagliflozin
• EMPEROR-Preserved and DELIVER trials showed benefit in HFpEF
• First medication class proven to improve outcomes in HFpEF

Comorbidity Management (Essential):

1. Blood Pressure Control:

• Target <130/80 mmHg
• Reduces ongoing LV remodeling

1. Rate Control for AF:

• Beta-blocker or diltiazem
• Avoid tachycardia (reduces filling time)

1. Diabetes Management:

• Optimize glycemic control
• SGLT2 inhibitors have dual benefit

1. Weight Loss:

• Significant symptomatic benefit with weight reduction

1. Treat Sleep Apnea:

• High prevalence in HFpEF
• CPAP may improve symptoms

Lifestyle:

• Sodium restriction (<2g/day)
• Daily weights to detect fluid accumulation
• Exercise training improves functional capacity

Clinical Pearl

HFrEF vs HFpEF - Key Distinctions:

Neurohormonal Activation in Both: Both HFrEF and HFpEF involve sympathetic and RAAS activation, but the myocardial response differs. Understanding that HFpEF is not simply "mild" heart failure but a distinct pathophysiologic entity explains why therapies proven in HFrEF (ACE-I, beta-blockers, MRA) have not shown clear mortality benefit in HFpEF.

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