What is diastolic dysfunction?

Diastolic Dysfunction: Pathophysiology, Assessment, and Clinical Significance

Diastolic dysfunction is characterized by impaired ventricular filling due to delayed relaxation, reduced compliance, or increased stiffness of the left ventricle, resulting in elevated filling pressures that can lead to symptoms of heart failure despite preserved ejection fraction. 1, 2

Definition and Pathophysiology

Diastolic dysfunction refers to abnormalities in the mechanical function of the heart during diastole, affecting the ventricle's ability to fill properly. It involves:

• Impaired relaxation: Delayed or incomplete relaxation of the ventricle during early diastole, often due to abnormal calcium reuptake by myocytes 2
• Reduced compliance: Increased stiffness of the ventricular wall, limiting the ability to fill at normal pressures 2
• Increased chamber stiffness: Leading to elevated filling pressures even with normal or near-normal end-diastolic volumes 1

The hemodynamic consequences include:

• Elevation of ventricular filling pressures
• Increased left atrial pressure
• Elevated pulmonary venous and pulmonary capillary pressures
• Eventually, increased pulmonary artery and right heart pressures 2

Causes and Risk Factors

Diastolic dysfunction commonly occurs in:

• Hypertension (causing LV hypertrophy and increased afterload)
• Aging (decreased elastic properties, increased myocardial stiffness)
• Coronary artery disease and myocardial ischemia
• Hypertrophic or restrictive cardiomyopathies
• Diabetes mellitus
• Obesity
• Valvular heart disease 1, 2

In hypertrophic cardiomyopathy, diastolic dysfunction results from multiple factors affecting both ventricular relaxation and chamber stiffness, including:

• Systolic contraction load from outflow tract obstruction
• Nonuniformity of ventricular contraction and relaxation
• Delayed inactivation from abnormal intracellular calcium reuptake
• Severe hypertrophy increasing chamber stiffness
• Diffuse myocardial ischemia 1

Classification and Grading

Diastolic dysfunction is typically graded as:

1. Grade I (Mild): Impaired relaxation pattern

   • E/A ratio < 1 (E < A)
   • Normal filling pressures
   • Reduced mitral annular velocity e' 2

2. Grade II (Moderate): Pseudonormal filling pattern

   • E/A ratio > 1 (E > A)
   • Elevated left atrial pressures
   • E/e' ratio > 14
   • Left atrial volume index > 34 ml/m² 2

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) 2

Diagnostic Assessment

Echocardiography is the primary tool for assessing diastolic function. Key parameters include:

• Mitral annular velocity (e'): Reduced values (<7 cm/s septal, <10 cm/s lateral) indicate diastolic dysfunction 2
• E/e' ratio: >14 indicates elevated filling pressures 2
• Left atrial volume index: >34 ml/m² indicates chronic elevated pressures 2
• Tricuspid regurgitation velocity: >2.8 m/s suggests pulmonary hypertension 2

According to the 2016 ASE/EACVI guidelines, diastolic function assessment should focus on these four key variables 1, 2.

Clinical Significance

Diastolic dysfunction is the primary pathophysiology in Heart Failure with Preserved Ejection Fraction (HFpEF), which:

• Accounts for approximately 40% of patients presenting with clinical heart failure 1
• Has high prevalence in elderly patients and women 2
• Is associated with lower mortality (8% annual) compared to systolic heart failure (19% annual) but substantial morbidity 3

Clinical manifestations include:

• Dyspnea (especially with exertion)
• Exercise intolerance
• Pulmonary congestion
• Signs of elevated filling pressures
• Normal or near-normal heart size on imaging 2

Diastolic dysfunction can be exacerbated by exercise, as the shortened diastolic filling period and potential myocardial ischemia further impair diastolic filling, leading to increased pulmonary venous pressure and dyspnea 1.

Exercise and Stress Testing

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

In healthy subjects, the E/e' ratio doesn't change significantly with exercise due to proportional increases in both mitral inflow and annular velocities. However, an increase in E/e' ratio and/or systolic pulmonary artery pressure with exercise indicates elevated LV end-diastolic pressure 1.

Understanding diastolic dysfunction is essential for proper diagnosis and management of patients with heart failure symptoms, particularly when systolic function appears preserved.