NT-proBNP thresholds insufficient to diagnose HF in ambulatory patients with chronic dyspnea
For every 100 patients in whom heart failure (HF) with preserved ejection fraction is suspected due to dyspnea, using currently recommended N-terminal pro-B-type natriuretic peptide (NT-proBNP) thresholds could result in approximately 39 patients being misdiagnosed.
Measuring plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) is not an effective method to diagnose heart failure with preserved ejection fraction (HFpEF), an international study found.
To better understand the diagnostic performance of NT-proBNP in the ambulatory/outpatient setting, researchers assessed patients with chronic dyspnea and diagnosed HFpEF or noncardiac dyspnea by exercise catheterization. Researchers then derived and tested optimal NT-proBNP cut points to rule HFpEF in or out. The cut points were also tested in three additional validation cohorts for whom HFpEF was diagnosed by resting catheterization only, previous hospitalization for HF, or exercise echocardiography. Results were published by Circulation on Jan. 22.
The current recommended threshold to rule out HF, a NT-proBNP level of less than 125 pg/mL, had 82% sensitivity (95% CI, 77% to 88%) in patients with a body mass index (BMI) of less than 35 kg/m2. This sensitivity decreased to 67% (95% CI, 58% to 77%) in patients with a BMI of 35 kg/m2 or more. The lower rule-out NT-proBNP threshold of less than 50 pg/mL had 97% sensitivity (95% CI, 95% to 99%) in patients with a BMI less than 35 kg/m2 but slightly lower sensitivity in those with a BMI of 35 kg/m2 or greater (86%; 95% CI, 79% to 93%). The diagnostic thresholds were confirmed in validation cohorts.
When researchers tested consensus age- and BMI- stratified rule-in thresholds, they found these only demonstrated 65% specificity (95% CI, 57% to 72%). A rule-in NT-proBNP threshold of at least 500 pg/mL had 85% specificity (95% CI, 78% to 91%) in those with a BMI less than 35 kg/m2, with 100% specificity at a BMI of 35 kg/m2 or greater. Good specificity was seen with lower rule-in thresholds (≥220 pg/mL) in patients with a BMI of 35 kg/m2or greater. Findings were consistent in the additional validation cohorts, and NT-proBNP provided no incremental discrimination among patients with a history of atrial fibrillation (AF). At least 98% of patients with AF and dyspnea were found to have HFpEF in the cohorts.
The study is the first to provide evidence-based evaluation of NT-proBNP decision thresholds for ambulatory patients with chronic exertional dyspnea without overt congestion, the authors wrote. Findings showed that “in patients with chronic unexplained dyspnea, current rule-in and rule-out NT-proBNP diagnostic thresholds lead to unacceptably high error rates, with important interactions by obesity and AF status,” they said.
Overall, “for every 100 patients with suspected ambulatory HFpEF and intermediate pretest probability, application of existing NT-proBNP diagnostic thresholds would result in 24 patients with HFpEF being incorrectly labeled as having [noncardiac dyspnea], and 15 patients with [noncardiac dyspnea] would be incorrectly diagnosed with HFpEF,” the researchers wrote.
No patients from South America or Africa were included in the study, and the authors noted that external validity in these populations is warranted. Cohorts were predominately of White or Asian race, with underrepresentation of Black individuals.