Evaluating the clinical importance of exercise-induced pulmonary hypertension and biomarker correlations in systemic sclerosis

Background

Pulmonary arterial hypertension (PAH) is a major cause of morbidity and mortality in systemic sclerosis (SSc). Despite targeted therapies, outcomes for SSc-associated PAH (SSc-PAH) remain poor. Early disease detection is essential for improving outcomes, with exercise-induced pulmonary hemodynamics showing promise for early diagnosis. NT-proBNP has emerged as a valuable biomarker for screening SSc-PAH. Additionally, Interleukin-6 (IL-6) plays a significant role in the inflammatory and fibrotic processes in SSc-PAH by driving vascular damage and promoting fibroblast activation.

Our prospective study aimed to demonstrate a correlation between biomarkers determined immediately before exercise and the hemodynamic response measured during exercise Doppler echocardiography (ESE).

Methods

55 consecutive patients with previously diagnosed SSc (female 89%, mean age 56,7±13 years) were enrolled, with key exclusion criteria including resting PAH, definitive fibrosis on CT scan, and infeasible exercise tests. All patients underwent exercise stress echocardiography (ESE) with an incremental workload of 25 watts every two minutes. Key ESE parameters were recorded at baseline, 50 watts, and peak exercise, focusing on changes in pulmonary pressure (PASP), pulmonary vascular resistance (PVR), and right-ventricular pulmonary arterial coupling (TAPSE/PASP), as well as left ventricular filling pressures estimated by E/e’. Before ESE, lung ultrasounds were performed to count B-lines (indicating mild fibrosis), and blood samples were taken to determine NT-proBNP and IL-6 levels.

Results

During ESE, at peak exercise, PASP increased significantly (26±8mmHg vs 47±16mmHg, p<0,001, and PVR (1,36±0,3 WU vs 1,68±0,6 WU, p<0,05). TAPSE/PASP decreased (1,06±0,5vs vs. 0,6±0,4, p<0,05), and E/e’ increased significantly (8,2±2vs vs 9,8±4, p<0,05). The prevalence of stress-induced PAH was 37% in the population. NT-proBNP level was significantly correlated with resting LAVI (r 0,5, p<0,005), left atrial reservoir strain (r -0,4, p<0,05), and E/e’ (r 0,3, p<0,05). However, we did not find a relationship between exercise parameters and NT-proBNP level. IL-6 level only correlated with resting B-lines over the lung (r: 0,3, p<0,05)

Conclusion

Stress-induced PAH is common in SSc, even with normal resting parameters. NT-proBNP levels correlate with resting measures, particularly left ventricular diastolic dysfunction, but do not predict hemodynamic changes during exercise. IL-6 levels are associated only with the number of B-lines, indicating mild pulmonary fibrosisRelationship between biomarkers and ECHO