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Heart & Cardiometabolic HealthHeart Failure & Myocardial Health

Heart Failure with Preserved Ejection Fraction (HFpEF): Symptoms, Stiff Heart Muscle, and Treatment

Heart failure with preserved ejection fraction (HFpEF) is a condition characterised by left ventricular hypertrophy or stiffness. This prevents appropriate filling of the heart during diastole. It can be diagnosed using biomarkers such as NT-proBNP and echocardiography e’/E ratios. Patients can also be managed with evidence based therapies such as SGLT2 inhibitors and blood pressure control.

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Written by Dr. Naresh Trehan, MBBS, MD, FACSChairman & Chief Cardiac Surgeon, Medanta – The Medicity
Medically Reviewed by Dr. Rommel Tickoo, MBBS, MD✓ Verified
MBBS, MD (Internal Medicine)• Reviewed October 2026•Medical Review Board
Published: 2026-09-02Reviewed: October 2026Updated: 2026-11-03T11:25:46.011Z 10 min read 1840 Views
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Heart Failure with Preserved Ejection Fraction (HFpEF): Symptoms, Stiff Heart Muscle, and Treatment

Quick Summary & Key Findings

HFpEF is identified by symptoms of HF (dyspnoea on exertion, peripheral oedema, fatigue), with an ejection fraction of ≥50% and raised filling pressures (NT-proBNP >125 pg/mL; E/e’ ratio by echo >14). Current medical treatment includes SGLT2 inhibitors (empagliflozin, dapagliflozin), loop diuretic agents as needed and good BP control.

Heart failure with preserved ejection fraction (HFpEF) (also known as diastolic heart failure) makes up around 50% of cardiovascular hospitalisations due to heart failure. This differs from patients presenting with reduced ejection fraction (HFrEF) as their hearts are not pumping blood effectively. Patients with HFpEF have normal or near normal left ventricular ejection fractions (LVEF ≥ 50%).

The main pathology relates to diastolic dysfunction. The left ventricular walls become stiff, fibrous or thickened. During diastole, the ventricle cannot adequately relax causing increased pressure within the left atrium and pulmonary circulation. Patients will suffer with increasing breathlessness on minimal exercise, chronic fatigue and peripheral oedema.

Early detection is key as chronic hypertension, obesity, type 2 diabetes and atrial fibrillation can directly cause ventricular stiffness to worsen. Recent trials have shown that patients can have significant reductions in mortality and hospital admissions when taking SGLT2 inhibitors, so management has moved from simply removing fluid from the patient to actively modifying the disease process.

Pathophysiology: Why Diastolic Relaxation Fails

In healthy physiology the left ventricle easily distends during diastole to allow oxygenated blood to enter from the left atrium at low pressures. However, patients with HFpEF exhibit chronic inflammation, microvascular endothelial dysfunction and interstitial fibrosis altering the titin-protein springs within the cardiac myocyte. This loss of myocardial compliance causes a rapid rise in left ventricular end-diastolic pressure (LVEDP), due to even small increments in blood volumes. This high pressure is then transmitted backwards to the pulmonary veins causing pulmonary capillary congestion (leading to dyspnoea) and systemic venous hypertension (causing fluid build up in the lower limbs and congestion in the liver).
Impaired Active Relaxation Early diastole requires active ATP-dependent calcium reuptake into the sarcoplasmic reticulum; metabolic dysfunction slows this process.
Passive Ventricular Stiffness Interstitial fibrosis and hyperphosphorylated titin stiffen the myocardial wall during late diastole.
Elevated Pulmonary PressuresBackward transmission of left atrial pressure leads to secondary post-capillary pulmonary hypertension.
Chronotropic Incompetence Many HFpEF patients cannot increase their heart rate appropriately during exercise, worsening exertional fatigue.

Diagnostic Testing: Labs, Biomarkers, and Echocardiography

HFpEF diagnosis should be confirmed by demonstrating objective evidence of raised filling pressures or structural diastolic dysfunction in combination with clinical symptoms. It can be overlooked when only relying on ejection fraction.
N-Terminal Pro-BNP (NT-proBNP). Levels greater than 125pg/mL within the serum of patients in sinus rhythm (or >365pg/mL in atrial fibrillation) indicate ventricular wall stress. However, in obese patients levels may be falsely low.
Transthoracic Echocardiogram (TTE) - E/e’ ratio calculation (E wave/s wave = mitral inflow velocity divided by tissue doppler mitral annular velocity). A value >14 indicates high left atrial pressures.
Left Atrial Volume Index: Indicates chronic volume and pressure overload if greater than 34mL/m2.
H2FPEF Risk Score: Combines the following clinical factors: BMI >30, use of two or more antihypertensives, atrial fibrillation, pulmonary hypertension, advanced age (>60) and raised filling pressures.

Evidence-Based Medical Therapy and Lifestyle Strategies

Clear therapeutic goals are defined by clinical guidelines from the American College of Cardiology (ACC) and European Society of Cardiology (ESC).
SGLT2 Inhibitors: Empagliflozin (10mg daily) / Dapagliflozin (10mg daily). Class 1 recommendations as they reduce cardiovascular mortality and hospital admissions due to heart failure in both diabetic patients.
Loop Diuretics (Furosemide, Torsemide). Used dynamically to maintain euvolemia and reduce pulmonary congestion and peripheral oedema.
Mineralocorticoid Receptor Antagonists (MRAs) – Spironolactone helps reduce myocardial fibrosis and lower blood pressure in selected patients with increased BNP.
Intensive Blood Pressure Control. Targeting less than 130 mmHg systolic BP prevents further LV remodelling.
Weight loss and aerobic exercise reduce pericardial constraint and systemic vascular resistance. (Weight loss of 5-10%)
Caution
HFpEF patients are very sensitive to volume changes. When they gain between 2-3 lbs within 24 hours or 5 lbs in one week it indicates acute fluid retention. This needs to be addressed promptly by adjusting the diuretic medication by your healthcare provider.

Myocardial Diastolic Stiffness, The H2FPEF Diagnostic Algorithm & EMPEROR-Preserved

Heart Failure with Preserved Ejection Fraction (HFpEF) represents 50% of all forms of heart failure. Patients present with clinical signs/symptoms of heart failure, but have a normal or near normal Left Ventricular Ejection Fraction. Pathologically the causes are related to systemic microvascular endothelial activation in the presence of cardiometabolic co-morbidities. Coronary microvascular endothelial cells cause down regulation of nitric oxide and protein kinase G (PKG) in neighbouring cardiomyocytes resulting in poor phosphorylation of the giant sarcomeric spring titin. This leads to increased myocardial stiffness, impaired active relaxation and increased left ventricular end diastolic filling pressure.
H2FPEF Diagnostic Scoring Algorithm: Clinical score which is clinically validated to predict the likelihood of having HFpEF. Heavy (BMI >30kg/m2 = 2 points), Hypertensive (2+ anti-hypertensives = 1 point), Atrial Fibrillation (3 points), Pulmonary Hypertension (PASP >35mmHg = 1 point), Elder (>60 years = 1 point), Filling Pressures (E/e' >9 on Echocardiogram = 1 point). Scores of 6+ confirm HFpEF.
NT-proBNP Biomarker Thresholds N-Terminal Pro-B-Type Natriuretic Peptide has a clear threshold value of >125pg/mL in sinus rhythm and >365pg/mL in atrial fibrillation to confirm hemodynamically significant ventricular wall stress. However, obese patients may have up to 50% reduced levels of natriuretic peptides in circulation due to increased clearance receptors on adipocytes.
EMPEROR-Preserved & DELIVER landmark studies The landmark RCTs (NEJM) demonstrated that the SGLT2 inhibitors empagliflozin (10mg) and dapagliflozin (10mg) are the first FDA approved disease modifying pharmacological therapy for HFpEF, showing a significant 21% reduction in the primary composite outcome of cardiovascular mortality and heart failure admission.
Hemodynamic Exercise Stress Echocardiography: In patients presenting with unexplained exertional dyspnoea, and no evidence of pathology on echo at rest, invasive cardiopulmonary exercise testing or exercise stress echocardiography will show pathological increases in PCWP (>25mmHg) on exercise.

Loop Diuretic Titration, Spironolactone (TOPCAT) & Sacubitril/Valsartan

Therapeutic management aims to optimally balance decongestion of the pulmonary and systemic venous circulations, neurohormonal blockade and optimalization of comorbidities.
Loop Diuretic Decongestion Loop diuretics (Furosemide 20-80mg/day, Torsemide 10-40mg/day) are prescribed and titrated to achieve euvolaemia by clinical assessment. The aim is to remove peripheral pitting oedema and jugular venous distension (<8cmH2O). The patient's creatinine and electrolytes should be monitored carefully.
Spironolactone Mineralocorticoid Blockade (TOPCAT): A post-hoc regional analysis from the TOPCAT trial (NEJM) demonstrated that treatment with spironolactone (12.5-25 mg/day) significantly reduced the risk of hospitalization for heart failure in patients with documented high natriuretic peptides and serum potassium is <5.0 mEq/L and eGFR >30mL/min.
Sacubitril/Valsartan (PARAGON-HF Trial) Angiotensin Receptor-Neprilysin Inhibitor (ARNI) was most beneficial in patients with HFpEF, particularly those with an LVEF at the lower end of the range (45-57%) and women reducing rehospitalization and improving NYHA functional class.
Aggressive BP & Rate Control: It is vital that patients' resting BP is kept below 130/80mmHg and that they are in sinus rhythm or have tight rate control if they have AFib. Tachycardia significantly reduces the time available for diastolic filling meaning left atrial pressures will rise suddenly.

Echocardiographic Diastolic Stress Testing, Left Atrial Strain & E/e' Ratios

Transthoracic echocardiography (TTE) is the cornerstone non-invasive investigation used to make a diagnosis and classify diastolic dysfunction in patients with HFpEF. The ASE/EACVI guidelines recommend assessing a number of clinical factors using an algorithm including mitral inflow velocity (E wave and A wave); tissue Doppler velocities of the annulus (e’ velocity); peak velocity of tricuspid regurgitation; and indexed left atrial volume.
E/e’ Ratio (Estimated Left Ventricular Filling Pressure). The E wave (maximum velocity of early ventricular filling) divided by the e’ wave (tissue Doppler measurement of early diastolic velocity at the mitral annulus). An average E/e’ ratio above 14 indicates raised left ventricular end diastolic filling pressures (>15mmHg). A value below 8 is considered normal.
Indexed Left Atrial Volume Index (LAVI) – >34mL/m2 indicates a reliable morphological marker for chronic high left atrial pressures and chronic diastolic wall stresses. Excludes transient haemodynamic changes.
Tricuspid Regurgitation Jet Velocity (TR Vmax) Tricuspid Regurgitation jet velocity obtained by continuous-wave Doppler is greater than 2.8m/s and secondary pulmonary arterial hypertension occurs due to retrograde transmission of increased left heart filling pressures.
Weight & Fluids: Weights are taken daily on rising, after voiding. An increase of >=3 lbs in 24hrs or >=5lbs in a week indicates water retention. This means we will double the dose of loop diuretics in advance to try to avoid admission in an emergency.

Frequently Asked Questions

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Clinical Reviewer License Verified

Dr. Rommel Tickoo, MBBS, MD

Director, Internal Medicine & Infectious Diseases, Max Super Speciality Hospital, Saket • MBBS, MD (Internal Medicine)
Medical Review Board

Dr. Rommel Tickoo is the Director of Internal Medicine at Max Super Speciality Hospital, Saket, New Delhi. With over 24 years of experience in adult primary care, infectious disease management, routine screenings, and fever diagnostics, he reviews mediguide4u preventive care and vaccination protocols.

License ID: DMC-12876
Director, Department of Internal Medicine, Max Super Speciality Hospital, Saket, New Delhi
Medically evaluated on October 2026View Dr. Profile, Verified Credentials & Articles

References & Clinical Resources

  1. Clinical Research Faculty & Editorial Team. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure (2020-2026). [Access Resource Link] — Circulation / American Heart Association
  2. Clinical Research Faculty & Editorial Team. Empagliflozin in Heart Failure with a Preserved Ejection Fraction (EMPEROR-Preserved) (2020-2026). [Access Resource Link] — New England Journal of Medicine
  3. Clinical Research Faculty & Editorial Team. Diagnosis and Treatment of Heart Failure with Preserved Ejection Fraction (2020-2026). [Access Resource Link] — Nature Reviews Cardiology
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5.0 out of 5 (3 reviews)
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Marcus T., Cardiology PatientVerified Patient
•August 18, 2026

This guide broke down the exact diagnostic thresholds and medication pathways so clearly. My cardiologist recently discussed adjusting my regimen, and reading this helped me prepare specific questions for my follow-up visit.

Dr. Ashok Seth, MBBS, MD, FRCP, FACCInterventional Cardiologist & Medical Reviewer
August 19, 2026

Thank you for sharing, Marcus. Preparing targeted questions beforehand makes clinical consultations far more productive. Always discuss any dosage or timing adjustments directly with your attending physician.

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Patricia L., Nurse PractitionerHealthcare Professional
•August 29, 2026

The structured comparison tables and ACC/AHA clinical trial references are outstanding. I frequently print sections of this guide to explain lifestyle modifications to patients in our outpatient clinic.

Dr. Ashok Seth, MBBS, MD, FRCP, FACCInterventional Cardiologist & Medical Reviewer
August 30, 2026

We are honored to support your clinical practice, Patricia. Translating complex cardiovascular guidelines into patient-friendly education is the core mission of our editorial board.

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David K.Verified Reader
•September 08, 2026

The distinction between acute emergency symptoms and chronic management gave me genuine peace of mind. Very well-written and easy to navigate on mobile.

Dr. Ashok Seth, MBBS, MD, FRCP, FACCInterventional Cardiologist & Medical Reviewer
September 09, 2026

Glad this provided clarity, David. Knowing the exact red-flag symptoms that require urgent care empowers patients to act decisively when it matters most.

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