What is diastolic dysfunction?

Diastolic Dysfunction

Diastolic dysfunction is a cardiac abnormality characterized by impaired ventricular filling due to delayed relaxation, impaired left ventricular filling, and/or increased myocardial stiffness, resulting in elevated filling pressures despite normal or near-normal ejection fraction. 1

Definition and Pathophysiology

Diastolic dysfunction represents a mechanical abnormality in cardiac function where the heart's ability to fill properly during diastole is compromised. This occurs through several mechanisms:

• Delayed relaxation: Impaired active relaxation of the myocardium
• Increased chamber stiffness: Reduced compliance of the ventricle
• Impaired ventricular filling: Difficulty in filling the ventricle adequately at normal pressures

The pathophysiological changes lead to elevated left atrial and pulmonary capillary wedge pressures, which can result in symptoms of pulmonary congestion even with preserved systolic function 1, 2.

Contributing Factors

Several conditions and processes contribute to the development of diastolic dysfunction:

• Myocardial stiffness factors:

  • Progressive myocardial fibrosis
  • Accumulation of extracellular proteins
  • Structural changes in extracellular matrix
  • Myocyte hypertrophy 1

• Common underlying conditions:

  • Hypertension (leading cause)
  • Aging
  • Diabetes mellitus
  • Coronary artery disease
  • Obesity
  • Hypertrophic or restrictive cardiomyopathy
  • Valvular heart disease 1, 2

Classification

According to the European Society of Cardiology, diastolic dysfunction is classified into three grades:

1. Grade I (Mild): Impaired relaxation pattern

   • E/A ratio < 1 (E < A)
   • Normal filling pressures
   • Reduced mitral annular velocity (e')

2. Grade II (Moderate): Pseudonormalized filling pattern

   • E/A ratio > 1 (E > A)
   • Elevated left atrial pressures
   • E/e' ratio > 14
   • Left atrial volume index > 34 ml/m²

3. Grade III (Severe): Restrictive filling pattern

   • E/A ratio > 2.5
   • Deceleration time < 150 ms
   • Isovolumetric relaxation time < 50 ms
   • Severely reduced septal and lateral e' velocities (3-4 cm/s) 1

Diagnostic Assessment

The American Society of Echocardiography (ASE) and European Association of Cardiovascular Imaging (EACVI) recommend focusing on four key echocardiographic parameters:

Parameter	Normal	Abnormal
Mitral annular velocity e'	>7 cm/s (septal), >10 cm/s (lateral)	<7 cm/s (septal), <10 cm/s (lateral)
E/e' ratio	<14	>14
Left atrial volume index	<34 ml/m²	>34 ml/m²
Tricuspid regurgitation velocity	<2.8 m/s	>2.8 m/s

Diastolic stress echocardiography is valuable for detecting impaired diastolic function reserve in patients with:

• Unexplained dyspnea
• Subclinical diastolic dysfunction
• Suspected HFpEF with borderline diastolic abnormalities at rest 1

Clinical Presentation

Patients with diastolic dysfunction commonly present with:

• Exertional dyspnea
• Orthopnea
• Paroxysmal nocturnal dyspnea
• Fatigue and reduced exercise tolerance
• Peripheral edema
• Chest pain (with or without coronary artery disease)

Important demographic patterns include:

• Higher prevalence in women with more pronounced symptoms
• Increased incidence in elderly patients, often with delayed diagnosis due to attribution of symptoms to aging 1, 3

Clinical Significance

Diastolic dysfunction has important prognostic implications:

• It is present in approximately 50% of patients with normal systolic function and 100% of patients with depressed systolic function in conditions like aortic stenosis 4
• Diastolic heart failure has a lower annual mortality rate (approximately 8%) compared to heart failure with systolic dysfunction (19%), but still carries substantial morbidity 2
• Diastolic dysfunction may precede systolic dysfunction in many cardiac conditions 4

Management Considerations

There is no specific therapy to directly improve diastolic function, but management focuses on:

1. Treating underlying conditions:

   • Control of hypertension
   • Relief of myocardial ischemia
   • Regression of ventricular hypertrophy

2. Pharmacological options:

   • Beta-blockers: Lower heart rate and increase diastolic filling time
   • ACE inhibitors/ARBs: Improve relaxation and cardiac distensibility
   • Calcium channel blockers: May improve relaxation
   • Diuretics: For episodes of fluid overload (used cautiously) 1, 2

3. Addressing specific causes:

   • Aortic valve replacement in aortic stenosis
   • Reduction of circulating blood volume in decompensated states 4

Important Caveats

• Limited evidence from clinical trials for treatment of isolated diastolic dysfunction exists, as most trials have focused on established heart failure 1
• Diagnosis requires three conditions: (1) presence of heart failure signs/symptoms, (2) normal or slightly reduced LV ejection fraction (>50%), and (3) presence of increased diastolic filling pressure 2
• The correlation between non-invasive measures (like E/e') and invasively measured filling pressures is modest (correlation coefficient r=0.56), indicating limited predictive value 1
• Early recognition and appropriate therapy is crucial to prevent progression to diastolic heart failure and death 2