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Diastolic Heart Failure

Disease Details

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Description: Diastolic heart failure, also known as heart failure with preserved ejection fraction (HFpEF), occurs when the heart's left ventricle is unable to relax properly and fill with blood, leading to insufficient blood flow to meet the body's needs.
Type: Diastolic heart failure, also known as heart failure with preserved ejection fraction (HFpEF), is typically not classified as a single gene-inherited disease. Instead, it is a complex condition that results from multiple factors, including hypertension, diabetes, obesity, and aging. Genetic predispositions can play a role, but there is no specific pattern of genetic transmission as seen in Mendelian inherited diseases.
Signs And Symptoms: Clinical manifestations of HFpEF are similar to those observed in HFrEF and include shortness of breath including exercise induced dyspnea, paroxysmal nocturnal dyspnea and orthopnea, exercise intolerance, fatigue, elevated jugular venous pressure, and edema.Patients with HFpEF poorly tolerate stress, particularly hemodynamic alterations of ventricular loading or increased diastolic pressures. Often there is a more dramatic elevation in systolic blood pressure in HFpEF than is typical of HFrEF.
Prognosis: The progression of HFpEF and its clinical course is poorly understood in comparison to HFrEF. Despite this, patients with HFrEF and HFpEF appear to have comparable outcomes in terms of hospitalization and mortality. Causes of death in patients vary substantially. However, among patients in more advanced heart failure (NYHA classes II-IV), cardiovascular death, including heart attacks and sudden cardiac death, was the predominant cause in population-based studies.Until recently, it was generally assumed that the prognosis for individuals with diastolic dysfunction and associated intermittent pulmonary edema was better than those with systolic dysfunction. However, in two studies in the New England Journal of Medicine in 2006, evidence was presented to suggest that the prognosis in diastolic dysfunction is the same as that in systolic dysfunction.
Onset: Onset of diastolic heart failure can be insidious, often developing gradually over time. It is typically seen in older adults and is associated with conditions like hypertension, diabetes, and obesity. Symptoms include shortness of breath, fatigue, and difficulty exercising.
Prevalence: The prevalence of diastolic heart failure, also known as heart failure with preserved ejection fraction (HFpEF), varies widely but is estimated to account for approximately 50% of all heart failure cases. This condition is more common in older adults, particularly women, and those with hypertension, obesity, and diabetes. The exact prevalence can vary based on the population studied and diagnostic criteria used.
Epidemiology: Diastolic heart failure, also known as heart failure with preserved ejection fraction (HFpEF), primarily affects older adults and is more common in women than men. It accounts for about 50% of all heart failure cases. Risk factors include hypertension, obesity, diabetes, and atrial fibrillation. The prevalence of diastolic heart failure increases with age, and it is particularly frequent in individuals over the age of 65.
Intractability: Diastolic heart failure, also known as heart failure with preserved ejection fraction (HFpEF), is challenging to manage but not considered intractable. It requires comprehensive treatment strategies that include lifestyle modifications, control of comorbid conditions, and medication to manage symptoms and improve quality of life. While there is currently no definitive cure, ongoing medical advancements continue to improve patient outcomes.
Disease Severity: Diastolic heart failure, also known as heart failure with preserved ejection fraction (HFpEF), is a condition where the heart's ventricles become stiff and cannot relax properly, leading to inadequate filling of blood. Severity can vary widely:

1. **Mild:** Patients may have symptoms only with exertion and mild effects on daily activities.
2. **Moderate:** Symptoms occur with minimal exertion and there might be some limitations in daily activities.
3. **Severe:** Symptoms are present even at rest, significantly impacting daily life quality and activities.

The severity is typically assessed through clinical evaluation, imaging (e.g., echocardiography), and functional capacity tests.
Healthcare Professionals: Disease Ontology ID - DOID:9775
Pathophysiology: Diastolic heart failure, also known as heart failure with preserved ejection fraction (HFpEF), occurs when the heart's left ventricle is unable to relax properly during the diastolic phase (when the heart is filling with blood). This results in increased filling pressures and insufficient blood flow to meet the body's needs, despite a normal ejection fraction.

Pathophysiology:
1. **Impaired Ventricular Relaxation:** The left ventricle becomes stiffer and less compliant, often due to myocardial hypertrophy or fibrosis.
2. **Increased Filling Pressures:** The reduced compliance of the left ventricle leads to elevated diastolic pressures, which can cause pulmonary congestion and subsequent symptoms like shortness of breath.
3. **Preserved Ejection Fraction:** Despite the filling issues, the stroke volume and ejection fraction of the heart remain within normal ranges.
4. **Vascular Stiffness:** Often associated with systemic hypertension, which contributes to the increased workload on the heart and further complicates the relaxation process.
5. **Endothelial Dysfunction and Inflammation:** Chronic endothelial dysfunction and ongoing inflammatory processes can exacerbate myocardial stiffness and impair relaxation.

Management typically involves controlling blood pressure, managing fluid overload, and addressing comorbid conditions such as diabetes and atrial fibrillation.
Carrier Status: Diastolic heart failure, also known as heart failure with preserved ejection fraction (HFpEF), is not a condition that involves carrier status. Instead, it is a type of heart failure where the heart's lower chambers (ventricles) are stiff and do not relax properly, leading to inadequate filling with blood. Since diastolic heart failure is a complex medical condition influenced by factors such as age, hypertension, obesity, diabetes, and coronary artery disease, the concept of being a "carrier" does not apply.
Mechanism: Diastolic heart failure, also known as heart failure with preserved ejection fraction (HFpEF), occurs when the heart's ventricles are unable to relax and fill properly during the diastolic phase. This results in insufficient blood filling the heart and, consequently, reduced blood being pumped out to the body. The underlying mechanisms and molecular pathways involved include:

1. **Mechanism:**
- **Impaired Relaxation and Reduced Compliance:** The primary mechanical issue in diastolic heart failure is the inability of the ventricles to relax fully, leading to reduced ventricular compliance. This means the ventricles become stiffer and less able to expand and fill with blood during diastole.
- **Increased Left Ventricular End-Diastolic Pressure (LVEDP):** Due to impaired relaxation, the pressure within the left ventricle remains elevated, which can lead to increased pressure in the left atrium and pulmonary veins, potentially causing pulmonary congestion and symptoms such as shortness of breath.
- **Altered Myocardial Structure:** The ventricles often exhibit abnormal myocardial structure, including increased myocardial fibrosis and hypertrophy (thickening of the ventricular walls), contributing to diastolic dysfunction.

2. **Molecular Mechanisms:**
- **Fibrosis:** Excessive deposition of extracellular matrix proteins, particularly collagen, leads to myocardial fibrosis, which stiffens the ventricular walls and impairs relaxation. Transforming growth factor-beta (TGF-β) and other fibrogenic cytokines play crucial roles in this process.
- **Inflammation:** Systemic and local inflammatory processes contribute to the development of diastolic dysfunction. Pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukins, may promote myocardial fibrosis and hypertrophy.
- **Oxidative Stress:** Reactive oxygen species (ROS) can damage myocardial cells and promote fibrosis and hypertrophy. Oxidative stress is linked to the activation of signaling pathways such as nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs).
- **Calcium Handling Abnormalities:** Proper cardiac muscle relaxation depends on the appropriate handling of intracellular calcium. In diastolic heart failure, there may be dysregulation of calcium handling proteins such as SERCA2a (sarcoplasmic/endoplasmic reticulum calcium ATPase), leading to impaired relaxation.
- **Titin Isoform Shifts:** Titin, a protein contributing to myocardial elasticity, exists in different isoforms. A shift toward stiffer isoforms of titin can reduce ventricular compliance and impair diastolic filling.
- **Endothelial Dysfunction:** Dysfunctional endothelium can lead to reduced nitric oxide (NO) bioavailability, contributing to vascular stiffness and increased afterload, further exacerbating diastolic dysfunction.

Understanding these mechanisms is essential for developing targeted therapies to manage diastolic heart failure effectively.
Treatment: Despite increasing incidence of HFpEF effective inroads to therapeutics have been largely unsuccessful. Currently, recommendations for treatment are directed at symptom relief and co-morbid conditions. Frequently this involves administration of diuretics to relieve complications associated with volume overload, such as leg swelling and high blood pressure.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. There are particular factors unique to HFpEF that must be accounted for with therapy. Randomized clinical trials addressing the therapeutic adventure for these conditions in HFpEF have found conflicting or limited evidence.Specific aspects of therapeutics should be avoided in HFpEF to prevent the deterioration of the condition. Considerations that are generalizable to heart failure include avoidance of a fast heart rate, elevations in blood pressure, development of ischemia, and atrial fibrillation. Considerations more specific to HFpEF include avoidance of preload reduction. As patients display normal ejection fraction but reduced cardiac output they are especially sensitive to changes in preloading and may rapidly display signs of output failure. This means administration of diuretics and vasodilators must be monitored carefully.HFrEF and HFpEF represent distinct entities in terms of development and effective therapeutic management. 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. Many of these therapies are effective in reducing the extent of cardiac dilation and increasing ejection fraction in HFrEF patients. It is unsurprising they fail to effect improvement in HFpEF patients, given their un-dilated phenotype and relative normal ejection fraction. Understanding and targeting mechanisms unique to HFpEF are thus essential to the development of therapeutics.Randomized studies on HFpEF patients have shown that exercise improves left ventricular diastolic function, the heart's ability to relax, and is associated with improved aerobic exercise capacity. The benefit patients seem to derive from exercise does not seem to be a direct cardiac effect, but rather is due to changes in peripheral vasculature and skeletal muscle, which show abnormalities in HFpEF patients. A two-year exercise trial on otherwise-healthy middle-aged adults having HFpEF showed improved cardiac function, and regular exercise was recommended to prevent future risk of HFpEF.Regularly assessment of patients allows determination of progression of the condition, response to interventions, and need for alteration of therapy. 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.
Compassionate Use Treatment: Diastolic heart failure, also known as heart failure with preserved ejection fraction (HFpEF), is a challenging condition to treat. There are no specific drugs approved exclusively for HFpEF, so doctors sometimes consider compassionate use or off-label treatments. Here are some options:

1. **Sacubitril/Valsartan**: Although primarily approved for heart failure with reduced ejection fraction (HFrEF), it's being investigated for HFpEF.

2. **SGLT2 Inhibitors (e.g., Empagliflozin, Dapagliflozin)**: Originally developed for diabetes, studies have shown potential benefits in reducing heart failure hospitalizations.

3. **Aldosterone Antagonists (Spironolactone, Eplerenone)**: These are sometimes used off-label due to their potential to reduce heart failure hospitalizations.

4. **Relaxin**: This hormone has been explored in experimental studies for its effects on heart function and vasodilation in HFpEF patients.

5. **Gene Therapy**: Experimental approaches targeting specific genetic factors involved in diastolic dysfunction are being studied.

6. **Stem Cell Therapy**: Investigated as a potential treatment to regenerate heart tissue and improve diastolic function, though still in experimental stages.

These treatments should be discussed with a healthcare provider to assess their appropriateness based on individual patient conditions and current research findings.
Lifestyle Recommendations: Lifestyle recommendations for managing diastolic heart failure include:

1. **Diet**: Adopt a heart-healthy diet rich in fruits, vegetables, whole grains, and lean proteins. Reduce sodium intake to help control blood pressure and fluid retention.

2. **Exercise**: Engage in regular, moderate physical activity such as walking, swimming, or cycling, as tolerated and recommended by a healthcare provider.

3. **Weight Management**: Maintain a healthy weight to reduce the strain on the heart. Obesity can exacerbate heart failure symptoms.

4. **Smoking**: Quit smoking and avoid exposure to secondhand smoke, as smoking can worsen heart failure and overall cardiovascular health.

5. **Alcohol**: Limit alcohol consumption as excessive drinking can lead to worsened heart function.

6. **Stress Management**: Implement stress-reducing techniques such as mindfulness, yoga, or meditation to help manage blood pressure and overall heart health.

7. **Regular Medical Follow-up**: Keep regular appointments with a healthcare provider to monitor heart function and manage symptoms effectively.

8. **Medication Adherence**: Take prescribed medications as directed to manage blood pressure, fluid buildup, and any other related conditions.

9. **Fluid Restriction**: Follow any fluid restriction guidelines provided by a healthcare provider to prevent fluid overload.
Medication: In diastolic heart failure, also known as heart failure with preserved ejection fraction (HFpEF), the heart's ventricles do not relax properly, affecting their ability to fill with blood. Management primarily aims at controlling symptoms and addressing underlying conditions. Medications commonly used include:

1. **Diuretics**: Help reduce fluid overload and alleviate symptoms such as swelling and shortness of breath.
2. **Beta-blockers**: Aid in reducing heart rate and blood pressure, which can improve heart function.
3. **Calcium channel blockers**: Help in relaxing the heart muscles and blood vessels.
4. **ACE inhibitors/ARBs**: Address high blood pressure and can help in preventing the progression of heart failure.
5. **Aldosterone antagonists**: Help in reducing fluid retention and potentially improve heart function.

The specific treatment plan often depends on the patient's individual health profile and associated conditions.
Repurposable Drugs: Current evidence suggests that some existing drugs may show potential for repurposing in diastolic heart failure (heart failure with preserved ejection fraction, or HFpEF). These include:

1. **Statins**: Primarily used to lower cholesterol, statins have shown potential benefits in improving endothelial function and reducing inflammation.
2. **Metformin**: Commonly used for diabetes, metformin may improve endothelial function and reduce left ventricular mass.
3. **Spironolactone**: An aldosterone antagonist, originally used for its diuretic properties, has shown some promise in reducing heart stiffness and improving diastolic function.
4. **Sacubitril/Valsartan (Entresto)**: Although primarily used for systolic heart failure, it has shown some promise in patients with HFpEF for reducing heart failure hospitalizations.

Research is ongoing, and clinical judgments should be based on individual patient circumstances and the most current evidence.
Metabolites: Diastolic heart failure, also known as heart failure with preserved ejection fraction (HFpEF), is a condition where the heart's ventricles do not relax properly and hence do not fill adequately with blood during the diastolic phase. Metabolites involved in diastolic heart failure can indicate biochemical alterations associated with the condition. Commonly studied metabolites in this context include:

1. **Lactic Acid:** Elevated levels can be found due to impaired oxygen delivery and utilization.
2. **Amino Acids (e.g., branched-chain amino acids):** Changes in levels can reflect alterations in muscle metabolism.
3. **Fatty Acids:** Dysregulation in fatty acid metabolism is often observed.
4. **Glucose and Glycated Products:** Alterations in glucose metabolism and increased levels of advanced glycation end-products (AGEs) may be present.
5. **Ketone Bodies:** Shifts towards ketone body metabolism can occur as an adaptive response.

These metabolites help in understanding the metabolic shifts and potential targets for therapeutic intervention in diastolic heart failure.
Nutraceuticals: There is no current, established use of nutraceuticals specifically for the treatment of diastolic heart failure. It's important to follow evidence-based medical treatments and consult healthcare providers for appropriate management.
Peptides: In the context of diastolic heart failure, natriuretic peptides such as B-type Natriuretic Peptide (BNP) and N-terminal pro-B-type Natriuretic Peptide (NT-proBNP) are important biomarkers. These peptides are released in response to ventricular volume expansion and pressure overload, conditions commonly seen in heart failure. Elevated levels of BNP and NT-proBNP are useful in diagnosing diastolic heart failure and assessing the severity of the disease.