[7] Hypertension, obesity, metabolic syndrome, and sedentary lifestyle have been identified as important risk factors for diverse types of heart disease including HFpEF.

Endothelial cells also are responsible for the production of E-selectin, which recruits lymphocytes into the tissue beneath the endothelium that subsequently release transforming growth factor beta, encouraging fibrosis and thus ventricular stiffening.

Cardiac macrophages are thought to play an important role in the development of fibrosis as they are increased in HFpEF and release pro-fibrotic cytokines, such as IL-10.

[11] Conditions, such as hypertension, that encourage increased left ventricular afterload can lead to structural changes in the heart on a gross, as well as a microscopic level.

It is thought that increased pressure, in concert with a pro-inflammatory state (insulin resistance, obesity), encourage ventricular stiffening and remodeling that lead to poor cardiac output seen in HFpEF.

[citation needed] Cardiac senescence, or cellular deterioration that occurs as part of normal aging, closely resembles the manifestations of HFpEF.

[17] Animal studies show that even at a young age, a decline in estrogen leads to changes in expression of fibrosis related genes in the heart.

These causes include:[citation needed] Structural changes that occur with HFpEF are often radically different from those associated with heart failure with reduced ejection fraction (HFrEF).

This leads to increased left ventricular mass and is typically accompanied by a normal, or slightly reduced, end diastolic filling volume.

While early stage HFrEF is associated with a significant disruption of extracellular matrix proteins initially, as it progresses fibrotic replacement of myocardium may occur, leading to scarring and increased interstitial collagen.

Histological evidence supporting diastolic dysfunction demonstrates ventricular hypertrophy, increased interstitial collagen deposition and infiltration of the myocardium.

The term diastolic dysfunction is sometimes erroneously applied in this circumstance, when increased fluid volume retention causes the heart to be over-filled (high output cardiac failure).

[39] Combined with the characteristic deficit in stroke volume observed in HFpEF patients, many individuals display poor exercise tolerance.

[42] Patients with HFpEF, in addition to cardiac abnormalities, display changes in (endothelial) microvascular function, skeletal muscle metabolism and in fat distribution and character throughout the body.

Techniques such as catheterization are invasive procedures and thus reserved for patients with co-morbid conditions or those who are suspected to have HFpEF but lack clear non-invasive findings.

[citation needed] A patient is said to have diastolic dysfunction if they have signs and symptoms of heart failure but the left ventricular ejection fraction is normal.

A second approach is to use an elevated BNP level in the presence of normal ejection fraction to diagnose diastolic heart failure.

Concordance of both volumetric and biochemical measurements and markers lends to even stronger terminology regarding scientific/mathematical expression of diastolic heart failure.

Fick may be[clarification needed] readily and inexpensively inverted to cardiac output and ejection fraction to mathematically describe diastole.

[47] Newer echocardiographic techniques such as speckle tracking for strain measurement, particularly for the left atrium,[48] are becoming increasingly utilised for the diagnosis of HFpEF.

Frequently this involves administration of diuretics to relieve complications associated with volume overload, such as leg swelling and high blood pressure.

[citation needed] Commonly encountered conditions that must be treated for and have independent recommendations for standard of care include atrial fibrillation, coronary artery disease, hypertension, and hyperlipidemia.

Specifically, cardiac resynchronization, administration of beta blockers and angiotensin converting enzyme inhibitors are applied to good effect in HFrEF but are largely ineffective at reducing morbidity and mortality in HFpEF.

Ability to perform daily tasks, hemodynamic status, kidney function, electrolyte balance, and serum natriuretic peptide levels are important parameters.

Behavioral management is important in these patients and it is recommended that individuals with HFpEF avoid alcohol, smoking, and high sodium intake.

[5] MRAs (spironolactone, finerenone) are recommended for appropriately selected patients with symptomatic HFpEF (LVEF >= 45%, elevated BNP level or heart failure admission within 1 year, eGFR > 30 mL/min/1.73 m2, creatinine < 2.5 ml/dL, potassium < 5.0 mEq/L).

[57] Evidence from a meta-analysis demonstrated significant reductions in all-cause mortality with beta-blocker therapy, though overall effects were driven largely by small, older trials of patients post-myocardial infarction.

[49] Some evidence suggests that vasodilating beta blockers, such as nebivolol, can provide a benefit for patients with heart failure regardless of ejection fraction.

[49] Likewise, treatment with angiotensin converting enzyme inhibitors, such as enalapril, ramipril, and many others, may be of benefit due to their effect on preventing ventricular remodeling but under control to avoid hypotension.

[61] In patients with HFpEF, SGLT2 inhibitors carry a class 2a recommendation according to the 2022 ACC/AHA/HFSA Guideline for the Management of Heart Failure as a potentially beneficial treatment for reducing HF hospitalizations and CV mortality.