Changes in n-terminal pro-brain natriuretic peptide over time in relation to indices of coronary microvascular dysfunction in chronic coronary syndrome

Background Coronary microvascular dysfunction (CMD) is prevalent in heart failure with preserved ejection fraction (HFpEF). CMD has been suggested as a promising therapeutic target in HFpEF. However, a cause and effect between CMD and the development of HFpEF is not established. Although not equal to heart failure, changes in N-terminal pro-brain natriuretic peptide (NT-proBNP) over time can act as a proxy for heart failure development. Purpose To investigate the association between thermodilution-derived indices of CMD and changes in NT-proBNP over time in an all-comer population of patients with chronic coronary syndrome (CCS). Methods Measurements of corrected Index of microcirculatory resistance (IMR), resting microvascular resistance (BRI), and microvascular resistance reserve (MRR) were determined in the LAD using thermodilution technique during coronary angiography in consecutive CCS-patients. Adenosine-infusion was used to achieve hyperemia. NT-proBNP was quantified at study inclusion and at follow-up. The association between changes in NT-proBNP over time and each coronary flow index was analysed using linear regression and construction of summary plots. Skewed variables were log-transformed. Linear mixed models and estimated marginal means were used to adjust for differing number of days between samples at inclusion and follow-up. Results Final analyses included 314 patients with available NT-proBNP at inclusion and follow-up from a cohort of 410 all-comer CCS-patients without previous heart failure undergoing elective coronary angiography. Median age was 68 years (IQR 60-73) and 76% were male. Median NT-proBNP at inclusion and follow-up were 109 (IQR 50-223) and 121 (IQR 58-341), respectively. Median time between NT-proBNP samples was 5.3 years (IQR 3.2-6.5). Patients with increasing NT-proBNP during follow-up were older (68 vs. 64 years) and had a lower prevalence of concomitant betablocker use (56% vs. 74%) compared to those with decreasing NT-proBNP. Change in NT-proBNP over time was not associated with any of the coronary flow indices in linear regression (Table 1). There were no interactions with NT-proBNP between inclusion and follow-up for elevated IMR (cut-off 25; p=0.703), decreased BRI (cut-off 49; p=0.068) or decreased MRR (cut-off 3; p=0.367; Figure 1). Patients with low MRR (≤3) had higher levels of NT-proBNP at inclusion and follow-up after adjusting for number of days between samples (Figure 1). Conclusion In CCS-patients without previous heart failure, NT-proBNP is associated with decreased MRR (≤3.0) in the LAD. Neither coronary microvascular resistance at hyperaemia or rest, nor endothelial-independent microvascular vasodilatory capacity, in the LAD, are associated with an increase in NT-proBNP over time in CCS-patients without previous heart failure. This may indicate that presence of CMD is not causing a more rapid development of HFpEF.