HFpEF Exacerbation with a Near-Normal BNP: When Labs Mislead

A 50-year-old African American woman with known HFpEF, hypertension, uncontrolled type 2 diabetes (HbA1c >14%), hyperlipidaemia, and major depressive disorder presented with worsening exertional dyspnoea, bilateral lower extremity oedema, abdominal swelling, orthopnoea, palpitations, and reduced urine output. She denied chest pain or fever. She reported taking her diuretics as prescribed, though chart review confirmed prior non-compliance — she had been hospitalised two weeks earlier for similar symptoms plus hyperglycaemia.

Crucially, during the prior admission two weeks before, her BNP was 11.2 pg/mL — profoundly below the threshold for heart failure — and acute coronary syndrome was excluded by serial ECGs and high-sensitivity troponin. She had been discharged on diuretics and compression stockings. The failure to recognise her presentation as HFpEF at that earlier admission underscores the diagnostic hazard of relying on BNP as a gatekeeper for heart failure diagnosis in this patient population.

On examination, the patient was tachypnoeic (RR 28/min), blood pressure ranging 92/50 to 146/86 mmHg (wide variability). Oxygen saturation was 97–99% on room air. BMI was 23 kg/m² — not obese by anthropometric measure — but the African American ethnicity, diabetes, and LV hypertrophy combination independently blunts natriuretic peptide production through distinct mechanisms. Bibasilar crackles, bilateral pedal oedema, and generalised anasarca were present. ECG showed poor R-wave progression in anterior leads and a prolonged QTc of 485 ms.

Figure 1

ECG — Poor R-Wave Progression and Prolonged QTc

Electrocardiogram demonstrating atypical R-wave progression in the anterior leads (blue circles) and a prolonged QTc interval (red marking, QTc 485 ms). Poor R-wave progression in HFpEF often reflects left ventricular hypertrophy with concentric remodelling rather than prior infarction. The prolonged QTc is an arrhythmia risk marker in this context; QTc-prolonging medications were appropriately avoided. Neither finding is specific to HFpEF but together support the diagnosis in the appropriate clinical context.

Chest X-ray demonstrated bilateral patchy pulmonary opacities and bilateral pleural effusions — a pattern far more consistent with congestive heart failure than infectious aetiology, given the absence of fever and negative blood cultures. CT angiography excluded pulmonary embolism (despite elevated D-dimer) but confirmed moderate bilateral pleural effusions, mild interstitial pulmonary oedema, and mild cardiomegaly.

Figure 2

Chest X-Ray — Bilateral Pleural Effusions on Admission

Anteroposterior chest radiograph showing bilateral pleural effusions (red arrows). In the context of a BNP of only 32 pg/mL, this radiographic finding was the first objective evidence that the clinical presentation reflected genuine volume overload rather than a non-cardiac cause of dyspnoea. Chest X-ray remains an indispensable diagnostic tool in suspected HFpEF precisely because it is not confounded by the factors that blunt natriuretic peptide levels — obesity, ethnicity, and metabolic disease.

Figure 3

CT Angiogram — Coronal View Showing Bilateral Pleural Effusions

Coronal CT angiogram of the chest demonstrating moderate bilateral pleural effusions (red arrows). CT provided anatomical confirmation of the pulmonary congestion pattern seen on plain X-ray while simultaneously excluding pulmonary embolism as an alternative explanation for the dyspnoea and elevated D-dimer. The presence of bilateral effusions — rather than unilateral — reinforces a cardiac hydrostatic mechanism rather than infection or malignancy.

Figure 4

CT Angiogram — Axial View Showing Bilateral Pleural Effusions

Axial CT view confirming moderate bilateral pleural effusions (red arrows) with mild interstitial pulmonary oedema and mild cardiomegaly. The radiological constellation — bilateral effusions, interstitial oedema, and cardiomegaly — is sufficient to diagnose decompensated heart failure clinically, even in the presence of a BNP value well within the normal range.

Transthoracic echocardiography confirmed EF 55–60%, normal LV and RV size and systolic function without regional wall motion abnormalities, mildly concentric LV hypertrophy, and estimated PASP 34 mmHg — all consistent with HFpEF. Nuclear cardiac stress testing was negative for myocardial ischaemia. The patient was admitted to the ICU for increased work of breathing and managed with IV bumetanide and oral spironolactone, with progressive clinical improvement. She was discharged on bumetanide, spironolactone, empagliflozin, and lisinopril, with beta-blocker added at cardiology follow-up.

Notably, BNP rose from 32 pg/mL on admission to 97.8 pg/mL at discharge despite clinical improvement — illustrating the paradoxical BNP dynamics seen in HFpEF when third-space fluids mobilise during decongestive therapy.

Figure 5

Discharge Chest X-Ray (Day 6) — Interval Improvement in Pleural Effusions

Follow-up anteroposterior chest radiograph on day of discharge demonstrating substantial decrease in bilateral pleural effusions (red arrows) compared to the admission film, confirming successful decongestive therapy. The radiographic response to diuresis — independent of BNP trends — is the most reliable marker of treatment efficacy in HFpEF with blunted natriuretic peptide production.

Discussion

Three overlapping biological factors converged to suppress BNP to 32 pg/mL despite florid HFpEF decompensation in this patient. First, African American patients exhibit systematically lower natriuretic peptide levels compared to other ethnicities, possibly related to salt-sensitive hypertension, higher rates of left ventricular hypertrophy, and altered clearance receptor activity. Second, left ventricular hypertrophy in HFpEF is associated with relatively reduced wall stress compared to HFrEF — the fundamental physiological signal for BNP secretion — so NP levels are lower in proportion to clinical severity. Third, established diuretic therapy (even when partially non-compliant) reduces myocardial stretch enough to further suppress NP production. In chronically managed HFpEF patients under age 75 on diuretic therapy, a BNP below 100 pg/mL does not exclude clinically significant decompensation. The paradoxical rise in BNP from 32 to 97.8 pg/mL as the clinical picture improved reflects mobilisation of third-space fluid back into the intravascular compartment, transiently increasing preload and wall stress — a well-recognised phenomenon that should not be misinterpreted as clinical deterioration.

This case is a clinical argument for comprehensive multi-modal assessment rather than biomarker-first diagnosis of HFpEF. The diagnostic pathway that identified the decompensation combined physical examination (JVD, bibasilar crackles, anasarca, S3 absent but not required), plain chest radiography, CT chest imaging, and echocardiography — all of which confirmed congestion without BNP support. Current ACC/AHA/HFSA guidelines appropriately acknowledge that BNP levels can be inconclusive and recommend that imaging and clinical evaluation should guide therapy in such patients. The H2FPEF and HFA-PEFF scoring systems, which incorporate echocardiographic and clinical variables beyond NP, are specifically designed to diagnose HFpEF when NP levels are borderline or misleadingly low. Clinicians should apply these composite scoring systems rather than dismissing HFpEF based on a normal BNP in high-risk populations.