In a patient with suspected Heart Failure with preserved Ejection Fraction (HFpEF) and low Stroke Volume Index (SVI), is squatting beneficial in increasing End-Diastolic Volume (EDV)?

Squatting in Suspected HFpEF: Effects on EDV and Clinical Implications for Low SVI

In patients with suspected HFpEF and low stroke volume index (SVI), squatting will increase end-diastolic volume (EDV), but this is generally NOT beneficial and may actually worsen symptoms by precipitating acute pulmonary congestion due to the stiff, non-compliant left ventricle characteristic of HFpEF. 1

Hemodynamic Effects of Squatting on EDV

• Squatting increases venous return and preload, which mechanically increases left ventricular end-diastolic volume (EDV) by augmenting blood flow back to the heart 1
• In patients with diastolic dysfunction (the hallmark of HFpEF), the left ventricular end-diastolic pressure (LVEDP) rises dramatically with acute volume loading because the stiff ventricle operates on the steep portion of its pressure-volume curve 1
• This increased preload from squatting can precipitate acute pulmonary congestion in patients with diastolic dysfunction, as the non-compliant ventricle cannot accommodate the additional volume without excessive pressure elevation 1

Why Increased EDV is Problematic in HFpEF with Low SVI

The Fundamental Pathophysiology

• HFpEF is characterized by impaired left ventricular diastolic dysfunction with blunted end-diastolic volume response that limits stroke volume and cardiac output 2
• Patients with HFpEF demonstrate "blunting of stroke volume despite an exaggerated increase in filling pressures with exercise," meaning that increased preload does not translate into improved stroke volume 3
• In HFpEF, stroke volume may be reduced despite preserved ejection fraction due to concentric LV hypertrophy and reduced end-diastolic volumes 3

Distinct Pathophysiology Based on LVEF Range

• Patients with HFpEF and LVEF 50-60% demonstrate reduced contractility, impaired ventriculo-arterial coupling, and higher extracellular volume fraction, suggesting more fibrosis 4
• Patients with HFpEF and LVEF >60% demonstrate a hypercontractile state with excessive LV afterload and diminished preload reserve, meaning they cannot effectively utilize additional preload 4
• During exercise stress, patients with LVEF >60% show attenuated increases in end-systolic volume and more exaggerated increases in LV filling pressures, with LV stroke volume actually decreasing under exertion 4

Clinical Implications for Low SVI in HFpEF

The Stroke Volume Problem

• Reduced arteriovenous O2 difference accounts for >50% of the reduction in peak VO2 in HFpEF and is a stronger independent predictor of peak VO2 than exercise cardiac output 3
• Impaired cardiac output reserve during exercise is attributable to modest blunting of stroke volume augmentation and chronotropic incompetence (occurring in up to 50% of HFpEF patients) 3
• Poor stroke volume reserve in elderly female hypertensives with HFpEF is due to simultaneous failure of LV preload reserve and arterial vasodilatory reserves 5

Why Additional Preload Doesn't Help

• Patients with depressed SV reserve show decreased arterial compliance during exercise and exhibit a lesser decrease in systemic vascular resistance with a drop in effective arterial volume 5
• The problem in HFpEF is not insufficient preload but rather the inability of the stiff ventricle to accommodate increased volume without excessive pressure elevation 1
• Elevated jugular venous pressure and pulmonary edema—not improved stroke volume—are the hallmarks of volume overload in these patients 1

Diagnostic Considerations

Assessing Filling Pressures

• Average E/e' ratio >14, left atrial maximum volume index >34 mL/m², and tricuspid regurgitation jet velocity >2.8 m/sec indicate elevated left atrial pressure regardless of posture 1
• Exercise E/septal e' >13, lower amplitude of changes in diastolic longitudinal velocities, and induced pulmonary hypertension (systolic pulmonary artery pressure ≥50 mmHg) are markers of adverse outcomes 3
• No single echocardiographic parameter is sufficiently accurate to be used in isolation to diagnose LV diastolic dysfunction; a comprehensive examination incorporating all relevant two-dimensional and Doppler data is recommended 3

Hemodynamic Classification

• Patients with HFpEF show heterogeneous distribution across hemodynamic subgroups based on SVI (<35 mL/m² vs ≥35 mL/m²) and E/E' (<15 vs ≥15) 6
• Patients with low SVI and high E/E' (Group D) represent the most severely compromised hemodynamic state 6

Management Approach for HFpEF with Low SVI

Avoid Volume Loading

• Do not attempt to increase stroke volume by augmenting preload through maneuvers like squatting or aggressive fluid administration 1
• Instead, focus on diuretics at the lowest effective dose to manage fluid retention and relieve congestion 7
• For acute symptoms with orthopnea, initial recommended dose is 20-40 mg IV furosemide (or equivalent) 7

Disease-Modifying Therapy

• Initiate SGLT2 inhibitors (dapagliflozin or empagliflozin) as first-line disease-modifying therapy, which reduce heart failure hospitalizations without relying on preload augmentation 7
• Consider spironolactone particularly in patients with LVEF in the lower preserved range (40-50%), as it may reduce heart failure hospitalizations 7

Address Peripheral Mechanisms

• Since reduced arteriovenous O2 difference is the primary mechanism of exercise intolerance in HFpEF, focus on supervised exercise training to improve skeletal muscle oxygen extraction and mitochondrial function 3
• Exercise training improves peak VO2 predominantly through peripheral adaptations (increased mitochondrial density, capillary density, blood flow redistribution) rather than cardiac output improvements 3

Common Pitfalls to Avoid

• Do not assume that increasing preload will improve stroke volume in HFpEF—the stiff ventricle cannot effectively utilize additional volume 1, 4
• Avoid excessive diuresis which may lead to hypotension and worsening renal function, but also avoid volume overload 7
• Do not treat HFpEF patients the same as those with reduced ejection fraction, as response to therapies differs significantly 7
• Recognize that arterial diastolic blood pressure may remain normal or even decrease despite severely elevated intracardiac filling pressures (LVEDP >20 mmHg) 1