What is grade 2 diastolic dysfunction?

Grade 2 Diastolic Dysfunction

Grade 2 diastolic dysfunction, also known as pseudonormalization, represents a moderate stage of left ventricular diastolic impairment characterized by elevated left ventricular filling pressures with impaired relaxation that appears "normalized" on basic mitral inflow patterns. 1

Definition and Hemodynamic Characteristics

Grade 2 diastolic dysfunction occurs when the left ventricle has impaired relaxation but elevated left atrial pressure (LAP) compensates for this, creating a mitral inflow pattern that superficially resembles normal filling. This pseudonormal pattern is clinically concerning because severe diastolic dysfunction can be easily missed if only basic mitral inflow is assessed. 1

The key hemodynamic feature is moderately increased filling pressure with the left atrium generating higher pressures to maintain adequate ventricular filling despite impaired ventricular relaxation. 1

Diagnostic Criteria

According to the 2016 ASE/EACVI guidelines, Grade 2 diastolic dysfunction is diagnosed when:

For patients with reduced or preserved ejection fraction:

• Mitral E/A ratio is between 0.8-2.0 (the "indeterminate zone")
• At least 2 of 3 additional parameters meet cutoff values: 1
  • E/e' ratio >14
  • LA maximum volume index >34 mL/m²
  • TR jet velocity >2.8 m/sec

Alternative supportive findings include:

• Pulmonary vein S/D ratio <1
• Ar-A duration ≥30 msec (in hypertrophic cardiomyopathy) 1

Clinical Presentation

Grade 2 diastolic dysfunction represents disease progression from Grade 1 (impaired relaxation with normal filling pressures). Patients typically have underlying structural heart disease such as:

• Hypertensive heart disease with LV hypertrophy 1
• Heart failure with preserved ejection fraction (HFpEF) 1
• Diabetic cardiomyopathy 2, 3
• Chronic kidney disease 4, 5

The pseudonormal pattern reflects the transition from early to more advanced diastolic disease, where the left atrium must work harder to maintain cardiac output.

Echocardiographic Appearance

The mitral inflow pattern shows:

• E/A ratio that appears "normal" (0.8-2.0) but is actually abnormal given the clinical context
• The E velocity is elevated due to increased LAP, not improved relaxation
• Tissue Doppler shows reduced e' velocities (septal <7 cm/sec, lateral <10 cm/sec), confirming impaired relaxation 1

Figure 13 from the guidelines illustrates this perfectly: A patient with hypertensive heart disease, normal EF, LV hypertrophy, and moderately enlarged left atrium showing pseudonormal LV filling pattern consistent with elevated filling pressures and Grade II diastolic dysfunction. 1

Clinical Significance and Prognosis

Grade 2 diastolic dysfunction carries important prognostic implications:

• Associated with increased mortality in multiple populations including sepsis 2, post-myocardial infarction 6, and chronic kidney disease 5
• In diabetic patients with sepsis, Grade 2 dysfunction showed significantly elevated NT-pro-BNP levels (mean 503 pg/ml) 2
• Represents a critical transition point where elevated filling pressures begin causing symptoms and complications
• Can progress to Grade 3 (restrictive filling) if underlying disease worsens 1

Important Clinical Pitfalls

Beware of LA stunning after cardioversion: Markedly reduced mitral A velocity can create an apparent "restrictive" pattern (E/A >2) despite normal filling pressures. In this scenario, use mitral deceleration time rather than E/A ratio for assessment. 1

**Young patients (<40 years):** E/A ratios >2 may be normal findings, so other signs of diastolic dysfunction must be present before diagnosing Grade 2 dysfunction. 1

Post-hemodialysis assessment: The 2016 guidelines could not assess diastolic function in 37% of hemodialysis patients post-dialysis, highlighting the importance of timing echocardiography appropriately. 4

Progression Pattern

The natural history follows a predictable pattern:

• Grade 1 → Impaired relaxation, normal filling pressures
• Grade 2 → Impaired relaxation, elevated filling pressures (pseudonormalization)
• Grade 3 → Restrictive filling, markedly elevated pressures (E/A >2.5, DT <150 msec, IVRT <50 msec) 1