In a 72‑year‑old man with preserved left ventricular ejection fraction (~60 %), grade 1 diastolic dysfunction, normal filling pressures, excellent exercise capacity (Bruce stage 4) and low‑normal B‑type natriuretic peptide (BNP), is a stress echocardiogram indicated and should N‑terminal pro‑B‑type natriuretic peptide (NT‑proBNP) replace BNP for monitoring?

Stress Echocardiography and NT-proBNP in Grade 1 Diastolic Dysfunction

A stress echocardiogram is specifically indicated for your clinical scenario, and NT-proBNP offers superior diagnostic utility compared to BNP for monitoring patients with preserved ejection fraction and grade 1 diastolic dysfunction.

Stress Echocardiography: Strongly Recommended

Your clinical profile—grade 1 diastolic dysfunction with excellent exercise capacity (Bruce stage 4) and normal filling pressures at rest—places you in the exact patient population for whom diastolic stress testing is most appropriate. 1

Why Stress Echo Is Indicated

• Grade 1 diastolic dysfunction represents delayed myocardial relaxation with normal left atrial pressure at rest, making it impossible to determine whether exertional symptoms arise from cardiac dysfunction or non-cardiac causes without provocative testing 1

• Patients with grade 1 diastolic dysfunction cannot augment myocardial relaxation with exercise as normal subjects do, so they can only achieve required cardiac output by raising left ventricular filling pressures—this elevation is detectable only during stress 1

• Resting echocardiography that shows normal filling pressures does not explain exertional symptoms, which is the precise indication for diastolic stress testing according to ASE/EACVI guidelines 1

• Exercise diastolic parameters correlate better with exercise capacity than resting parameters, and the E/e′ ratio during exercise provides superior prognostic information 1

What the Test Will Show

• Normal subjects maintain an E/e′ ratio of 6-8 from rest through peak exercise because e′ velocity increases proportionally with E velocity 1

• In grade 1 diastolic dysfunction, e′ velocity remains unchanged or increases minimally with exercise while E velocity rises, causing the E/e′ ratio to increase significantly (often to >15) and indicating elevated filling pressures 1

• An exercise E/e′ ratio >15 correlates strongly with invasively measured pulmonary capillary wedge pressure and left atrial pressure, providing objective evidence of exercise-induced cardiac limitation 1

Common Pitfall to Avoid

• Do not assume that excellent exercise capacity (Bruce stage 4) excludes the need for stress testing—patients with grade 1 diastolic dysfunction may achieve high workloads but only at the expense of markedly elevated filling pressures that cause symptoms 1

NT-proBNP: Superior to BNP in Your Scenario

NT-proBNP is the preferred biomarker over BNP for chronic assessment in patients with preserved ejection fraction and grade 1 diastolic dysfunction.

Why NT-proBNP Is Better

• NT-proBNP has a longer half-life than BNP, providing more stable measurements that are less influenced by acute hemodynamic fluctuations, making it superior for chronic outpatient monitoring 2

• In patients with preserved LVEF and grade 1 diastolic dysfunction with normal E/e′ ratio (~8), BNP levels are typically low-normal because BNP reflects current hemodynamic stress rather than structural changes alone 2

• Patients with HFpEF exhibit significantly lower BNP concentrations than those with reduced ejection fraction, with values often falling in a "gray zone" of 100-400 pg/mL despite diastolic dysfunction 2

• In a cohort with BNP 100-400 pg/mL and normal LVEF, BNP did not predict heart failure outcomes (P=0.78), whereas the E/e′ ratio was predictive (P=0.0032), demonstrating BNP's limited utility in this setting 2

Specific NT-proBNP Thresholds

• NT-proBNP >125 pg/mL is considered indicative of cardiac dysfunction in non-acute outpatient evaluation 2, 3

• However, NT-proBNP may remain in the normal or low-normal range when filling pressures are not markedly elevated (E/e′ ~8), so a low value does not exclude diastolic dysfunction 2

• Age-adjusted thresholds should be applied: for patients >75 years, use >1800 pg/mL as the rule-in threshold 3, 4

Diagnostic Performance Data

• NT-proBNP has 99% sensitivity and 98% negative predictive value at the 300 pg/mL threshold for excluding acute heart failure, but specificity is only moderate (60-76%) 3, 4

• In asymptomatic hypertensive patients with diastolic dysfunction, mean NT-proBNP was 213 pg/mL versus 58 pg/mL in controls (P=0.008) 5

• NT-proBNP levels correlate strongly with E/e′ ratio (r=0.761, P=0.001), and an NT-proBNP threshold of 269 pg/mL predicts E/e′ >15 with 90% sensitivity and 73% specificity 6

Practical Algorithm for Your Situation

1. Proceed with stress echocardiography using either treadmill or supine bicycle protocol 1

2. Acquire mitral inflow velocities, mitral annular tissue Doppler velocities, and peak TR velocity at baseline, during each exercise stage, and in early recovery 1

3. Calculate E/e′ ratio at peak exercise or early recovery—an increase to >15 (from your baseline of ~8) indicates exercise-induced elevation of filling pressures and confirms cardiac etiology of any exertional symptoms 1

4. Measure baseline NT-proBNP (not BNP) for future comparison and risk stratification 2, 3

5. Interpret NT-proBNP in context: values >125 pg/mL suggest cardiac dysfunction, but normal values do not exclude grade 1 diastolic dysfunction with normal resting filling pressures 2, 3

6. Use serial NT-proBNP measurements (changes >50% are clinically significant) to track disease progression or treatment response over time 3

Critical Interpretation Factors

• Your low-normal BNP is expected given your normal filling pressures at rest (E/e′ 8) and preserved LVEF (60%) 2

• Obesity (if present) can artificially lower both BNP and NT-proBNP by 20-30%, potentially masking cardiac dysfunction 3, 4

• Renal function affects NT-proBNP interpretation—always document serum creatinine with every measurement 3, 4