Active B-Type Natriuretic Peptide Measured by Mass Spectrometry and Response to Sacubitril/Valsartan.

BACKGROUND: B-type natriuretic peptide (BNP) immunoassays (BNPia) do not differentiate active and inactive forms. Inactive NT-proBNP is used to track heart failure (HF) during treatment with sacubitril/valsartan, which inhibits BNP degradation. Mass spectrometry (MS) may better assess effects of HF treatment on biologically active BNP1-32. METHODS AND RESULTS: We developed a MS assay with immediate protease inhibition to quantify BNP1-32 over a linear range, using labeled recombinant BNP standard. In 4 healthy volunteers, BNP1-32 by MS (BNPMS) increased from below the 5 pg/mL detection limit to 228 pg/mL after nesiritide. In patients with HF, BNPMS was measured in parallel with BNP and NT-proBNP immunoassays before and during sacubitril/valsartan treatment. BNPMS was 4.4-fold lower than BNPia in patients with HF. Among patients not taking sacubitril/valsartan and without end-stage renal disease, BNPMS correlated with BNPia (rs = 0.77, P < .001) and NT-proBNP (rs = 0.74, P < .001). After a median of 8 weeks on sacubitril/valsartan, active BNPMS levels decreased by 50% (interquartile range -98.3% to 41.7%, n = 22, P = .048) and correlated with NT-proBNP (rs = 0.64, P < .001), but not with BNPia (rs = 0.46, P = .057). CONCLUSIONS: Active BNP measured by MS accounts for only a small amount of BNP measured by immunoassays. Although decreased BNP production was anticipated to be masked by inhibition of degradation, levels of active BNP decreased during chronic sacubitril/valsartan treatment.

The presence of fatty infiltration in the infraspinatus: its relation with the condition of the supraspinatus tendon.

PURPOSE: We aim to determine the prevalence of fatty infiltration and tears in the infraspinatus and to identify any associated risk factors. METHODS: Shoulder magnetic resonance imaging scans from 2006 to 2009 were reviewed. Arthrograms, inflammatory arthropathies, neoplasms, and fractures were excluded. Rotator cuff tears were graded in 4 categories: no tear, partial tear, and complete tear with and without retraction. Fatty infiltration was graded by radiologists using the modified Goutallier classification. Supraspinatus muscle atrophy (size) was measured by use of the ratio of the cross-sectional area of the muscle to the supraspinatus fossa on a sagittal T1-weighted sequence. RESULTS: Three hundred seventy-seven scans were included. The prevalence of infraspinatus tears was as follows: no tear, 74.8%; partial tear, 17.5%; complete tear, 3.2%; and complete tear with retraction, 4.5%. Fatty infiltration of grade 2 or higher was found in 18.1% of the infraspinatus without tears, 39.4% with partial tears, 66.7% with a complete tear, and 82.4% with a complete tear with retraction. In the infraspinatus without tears, increasing fatty infiltration was correlated with the severity of a concomitant supraspinatus tear. Fatty infiltration of grade 2 or higher in the infraspinatus without tears was found in 7.8% of shoulders with an intact supraspinatus, 18.6% with a partial supraspinatus tear, 23.5% with a complete supraspinatus tear, and 54.6% with a retracted complete supraspinatus tear. Supraspinatus muscle atrophy was correlated with infraspinatus fatty infiltration. CONCLUSIONS: Increased infraspinatus fatty infiltration was correlated with the severity of an infraspinatus tear. However, substantial fatty infiltration of the infraspinatus was seen even in the absence of a tear, and it was correlated with a worsening severity of a concomitant supraspinatus tear and atrophy. Concern over tear progression and increasing fatty infiltration of the infraspinatus may impact the management of isolated supraspinatus tendon tears. LEVEL OF EVIDENCE: Level IV, prognostic case series.