Diastolic Heart Failure

Aka: Diastolic Heart Failure, Diastolic Dysfunction, Heart Failure with Preserved Ejection Fraction, HFpEF

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II. Definitions

  1. Heart Failure with Preserved Ejection Fraction (HFpEF or Diastolic Heart Failure)
    1. Signs and symptoms of Congestive Heart Failure with elevated BNP (or filling pressure) AND
    2. Left ventricular ejection fraction >50% (some include EF >40% as mildly reduced)

III. Epidemiology

  1. Incidence and Prevalence
    1. Prevalence: 5 Million in U.S.
    2. Incidence: 650,000 per year in U.S.
    3. HFpEF accounts for 30-60% of Congestive Heart Failure (increasing by 1% per year)
    4. Lifetime risk may approach 10%
  2. Age
    1. Prevalence increases with age (esp. over age 55 years)
      1. Age 50 to 59 years: Prevalence 8 in 1000
      2. Age 80 to 89 years: Prevalence 79 in 1000 men (66 per 100 women)
  3. Gender
    1. Higher overall Prevalence in elderly women
    2. Higher morbidity and mortality in men (possibly due to comorbid Coronary Artery Disease)
  4. Race
    1. More common in non-hispanic black patients (and higher age-adjusted mortality)

IV. Pathophysiology

  1. Hypertrophic heart with impaired relaxation
    1. Stiff, less compliant left ventricle that does not adequately fill
  2. Heart meets metabolic needs
    1. But cost is a higher diastolic pressure
    2. Transmits pressures to lung vasculature (with reduced Lung Compliance)
    3. Results in pulmonary congestion
    4. Ultimately leads to right-sided Heart Failure
  3. Mechanisms
    1. Abnormal renal Sodium metabolism
    2. Decreased compliance of myocardial wall as well as arterial wall
    3. Decreased diastolic ventricular filling

V. Causes

  1. See Heart Failure Causes
  2. Common causes of Diastolic Dysfunction
    1. Hypertension
      1. Longstanding Uncontrolled Hypertension is the most common underlying etiology
      2. Causes Left Ventricular Hypertrophy
    2. Coronary Artery Disease
    3. Aortic Stenosis
  3. Other causes of Diastolic Dysfunction
    1. Cardiomyopathy (e.g. Amyloidosis, Sarcoidosis)
    2. Hypertrophic Cardiomyopathy
    3. Glycogen Storage Disease
    4. Hypereosinophilic Syndrome
    5. Hemochromatosis
    6. Constrictive Pericarditis or Pericardial Effusion
    7. Other Valvular disease

VI. Risk Factors

  1. Shared risks with HFrEF
    1. Advanced age
    2. Hypertension
    3. Ischemic Heart Disease
    4. Valvular heart disease
    5. Atrial Fibrillation (comorbid in up to 50% with HFpEF)
    6. Tobacco Abuse
  2. Other Key Factors most prevalent in HFpEF
    1. Female gender
    2. Obesity (comorbid in up to 80% with HFpEF)
    3. Diabetes Mellitus
    4. Sedentary lifestyle
  3. Exacerbating Factors
    1. Tachycardia
    2. Increased ventricular load (volume overload)
    3. Exercise
    4. Increased salt intake
    5. NSAIDs
    6. Hyperthyroidism
    7. Infection or fever
    8. Anemia

VII. Presentations: Typical patient

  1. Elderly women with systolic Hypertension and Left Ventricular Hypertrophy
  2. Comorbid Obesity or Diabetes Mellitus or Metabolic Syndrome

VIII. Symptoms

  1. Dyspnea on exertion
  2. Fatigue
  3. Generalized weakness
  4. Orthopnea or paroxysmal nocturnal Dyspnea
  5. Peripheral Edema

IX. Signs

  1. Symptoms and signs overlap with Systolic Dysfunction
    1. S3 Gallup Rhythm (LR+ 4.4)
    2. Jugular Venous Distention (LR+ 7.4)
    3. Displaced apical impulse (LR+ 16)
    4. Madhok (2008) BMC Fam Pract 9:56 [PubMed]
  2. Establish Congestive Heart Failure diagnosis clinically
  3. Evaluate for Systolic Dysfunction
  4. Rule out other causes
    1. Significant valvular disease
    2. Pericardial disease (e.g. pericardial constriction)
    3. Inducible Myocardial Ischemia
  5. Document elevated left ventricle end diastolic pressure
    1. Often impractical to perform

X. Labs: Initial

  1. See Systolic Dysfunction
  2. Complete Blood Count
  3. Comprehensive metabolic panel (serum Electrolytes, renal and hepatic function)
  4. Lipid profile
  5. Iron studies (e.g. Serum Iron, TIBC)
  6. Thyroid Stimulating Hormone (TSH)
  7. B-Type Natriuretic Peptide (BNP)
    1. Does not distinguish from Systolic Dysfunction
    2. BNP <100 or NT-BNP <300 excludes Acute Heart Failure in the Emergency Department (LR- 0.1)
    3. Martindale (2016) Acad Emerg Med 23(3); 223-42 [PubMed]

XI. Diagnosis

  1. See Framingham Heart Failure Diagnostic Criteria
  2. See H2FPEF Score
  3. Transthoracic Echocardiogram
    1. See Echocardiogram in Congestive Heart Failure
    2. Left Ventricular Ejection Fraction >50%
    3. E-A Wave Ratio abnormal (evaluates for Diastolic Dysfunction)
      1. Definitions
        1. E Wave: Peak velocity diastolic mitral valve flow
        2. A Wave: Atrial contraction
      2. Interpretation
        1. Normal E-A Ratio: 1.5
        2. Early Diastolic Dysfunction: E-A Ratio <1
        3. Moderate Diastolic Dysfunction: E-A=1.5
        4. Severe Diastolic Dysfunction: E-A Ratio >2
    4. Other measures
      1. Left ventricular mass
      2. Valvular Disease
      3. Left atrial size
      4. Measurement of Tau abnormal
  4. Coronary Angiography
    1. Indicated if Angina or ischemia on other testing

XII. Differential Diagnosis

  1. See Secondary Cardiomyopathy
  2. See Generalized Edema Below the Diaphragm
  3. See Dyspnea Causes

XIII. Management: General

  1. See Congestive Heart Failure Exacerbation Management
  2. Goals
    1. Increase Exercise capacity and physical functioning
    2. Improve diastolic function
  3. Aggressively manage Hypertension
    1. Controlling Blood Pressure is the single most important factor
  4. Manage other Coronary Risk Factors
    1. Hyperlipidemia
    2. Obesity
    3. Tobacco Abuse
    4. Diabetes Mellitus
    5. Encourage regular aerobic Exercise (Exercise training is effective)
      1. Fukuta (2016) Eur J Prev Cardiol 23(10: 78-85 [PubMed]
  5. Reduce exacerbating factors
    1. Control Myocardial Ischemia
      1. Revascularization as indicated
    2. Maintain sinus rhythm and prevent Tachycardia
    3. Manage Atrial Fibrillation
      1. Treat causative conditions (e.g. Hyperthyroidism)
      2. Atrial Fibrillation Rate Control
      3. Atrial Fibrillation Anticoagulation
    4. Optimize comorbidities (e.g. COPD, Anemia, Obesity)
    5. Screen and treat for Obstructive Sleep Apnea
  6. Other measures
    1. Sodium restriction does not appear to significantly benefit Heart Failure patients
      1. Colin-Ramirez (2023) Circ Heart Fail 16(1):e009879 +PMID: 36373551 [PubMed]
  7. Cardiology Consultation indications
    1. Unclear HFpEF diagnosis
    2. Refractory volume status or symptoms
    3. Associated end-organ dysfunction
    4. Advanced Heart Failure symptoms

XIV. Management: Medications

  1. Precautions
    1. HFpEF patients are sensitive to excessive Preload reduction (e.g. Diuretics, nitrates)
    2. Risk of weakness, Dizziness, Syncope
    3. Monitor Electrolytes, Renal Function and volume status (esp. when adding or titrating medications)
  2. Preferred medications in Diastolic Dysfunction
    1. Angiotensin Receptor Blockers (ARB)
      1. Some guidelines recommend ARB over ACE, but evidence is limited and dated
        1. Yusuf (2003) Lancet 362(9386): 777-81 [PubMed]
        2. Cleland (2006) Eur Heart J 27(19): 2338-45 [PubMed]
      2. Have not reduced mortality or hospitalizations
        1. Heran (2012) Cochrane Database Syst Rev (4):CD003040 [PubMed]
      3. Medications: ARB
        1. Candesartan start 4-8 mg/day
        2. Losartan start 25-50 mg/day
        3. Valsartan start 20-40 mg/day
      4. Medications: ARB/Neprilysin Inhibitor - Entresto (Sacubitril/Valsartan)
        1. Entresto start 24/26 mg orally twice daily
        2. Has been FDA approved for HFpEF, but evidence is weak
        3. (2021) Presc Lett 28(2): 9
        4. Sible (2016) Cardiol Rev 24(1):41-7 [PubMed]
    2. ACE Inhibitor
      1. Improves myocardial relaxation and compliance
      2. Lowers Preload and Afterload
    3. Diuretics
      1. Thiazide Diuretics
        1. Preferred agent for Hypertension
      2. Loop Diuretics (e.g. Furosemide, Bumetanide, Torsemide)
        1. Diuretics may decrease Dyspnea and acute exacerbations
          1. Loop Diuretics are indicated for Fluid Overload (highest symptom burden in exacerbations)
          2. Target symptom baseline and dry weight
        2. If not Fluid Overloaded, Loop Diuretics may lower Preload and increase symptoms
          1. Risk of Hypotension, Prerenal Failure
      3. Aldosterone Antagonists (e.g. Spironolactone)
        1. Medications
          1. Eplerenone 25 mg/day
          2. Spironolactone 12.5 to 25 mg/day
        2. Efficacy
          1. Likely beneficial in HFpEF and FDA approved for HFpEF
          2. Appears to reduce HFpEF hospitalizations
          3. Kosmas (2018) Ann Transl Med 6(23): 461+PMID:30603649 [PubMed]
          4. Jhund (2024) Lancet 404(10458): 1119-31 [PubMed]
    4. Beta Blockers
      1. Not included in AHA/ACC Heart Failure management guidelines
      2. Consider in comorbid Coronary Artery Disease, Atrial Fibrillation and Left Ventricular Hypertrophy
      3. Effects: Maximizes diastolic filling and decreases pulse
      4. No difference in mortality or hospitalizations
        1. van Veldhuisen (2009) J Am Coll Cardiol 53(23): 2150-8 [PubMed]
        2. Yamamoto (2013) Eur J Heart Fail 15(1): 110-8 [PubMed]
  3. Other medications to consider
    1. SGLT2 Inhibitors: Jardiance (Empagliflozin) or Farxiga (Dapagliflozin)
      1. Consider as first-line therapy in comorbid HFpEF and Diabetes Mellitus
        1. Avoid if eGFR <25 ml/min
      2. Appears effective in reducing hospitalizations even in non-Diabetic patients with HFpEF (NNT 35 in 2 years)
        1. However, best effect is in reduced Ejection Fraction (even mild reduction of 40-50% EF)
        2. May reduce risk of comorbid Atrial Fibrillation
        3. Anker (2021) N Engl J Med [PubMed]
        4. Zolniker (2020) Circulation 141(15): 1227-34 [PubMed]
      3. Agents
        1. Jardiance (Empagliflozin) start 10 mg/day
        2. Farxiga (Dapagliflozin) start 10 mg/day
  4. Medications to use with caution
    1. Nondihydropyrimidine Calcium Channel Blockers
      1. Example: Verapamil
      2. Improves diastolic function overall
      3. Avoid in Left Ventricular Dysfunction
      4. No survival benefit in Diastolic Dysfunction
    2. Dihydropyramidine Calcium Channel Blockers
      1. Example: Amlodipine
      2. Indications: Heart Rate control, Angina
      3. No survival benefit in Diastolic Dysfunction
      4. Limit use to when Beta Blocker is contraindicated
    3. Vasodilators (Nitrates, Hydralazine)
      1. Indications: Preload reduction and Angina
      2. No survival benefit in Diastolic Dysfunction
      3. Limit use to when ACE Inhibitor is contraindicated
      4. Associated with decreased Exercise tolerance
        1. Redfield (2015) N Engl J Med 373(24): 2314-24 [PubMed]
  5. Medications to avoid
    1. Digoxin
      1. Avoid except in Atrial Fibrillation
      2. No effect on mortality, but may increase hospitalizations
        1. Hashim (2014) Am J Med 127(2): 132-9 [PubMed]

XV. Prevention

  1. Control Cardiac Risk Factors
  2. Consider Cardiac Rehabilitation

XVI. Complications

  1. Mortality from Diastolic Heart Failure is equivalent to Systolic Heart Failure mortality

XVII. Prognosis

  1. HFpEF mortality approaches that of HFrEF in some studies (75%)
    1. Shah (2017) J Am Coll Cardiol 70(20): 2476-86 [PubMed]
  2. Hospitalizations
    1. Mortality at one year after first HFpEF admission: 25%
    2. Mortality at five years after first HFpEF admission
      1. Age over 60 years: 24%
      2. Age over 80 years: 54%
  3. Factors associated with worse prognosis
    1. Higher NT-BNP levels
    2. Advanced age
    3. Diabetes Mellitus
    4. Prior Myocardial Infarction
    5. Chronic Obstructive Pulmonary Disease
    6. Chronic Kidney Disease
      1. Creatinine Clearance >60 ml/min/1.73 m2: Survival >80% 4 year
      2. Creatinine Clearance <20 ml/min/1.73 m2: Survival <20% 4 year

XVIII. References

  1. (2017) Presc Lett 24(4):20
  2. Senni (1997) Mayo Clin Proc 72:453-60 [PubMed]
  3. (1995) Circulation 92:2764-84 [PubMed]
  4. (1999) J Card Fail 5:357-82 [PubMed]
  5. Barzin (2025) Am Fam Physician 112(4): 435-40 [PubMed]
  6. Borlang (2011) Eur Heart J 32(6): 670-9 [PubMed]
  7. Gazewood (2017) Am Fam Physician 96(9): 582-8 [PubMed]
  8. Zile (2002) Circulation 105:1387-93 [PubMed]
  9. Zile (2002) Circulation 105:1503-8 [PubMed]

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