Inspiratory muscle dysfunction with restrictive lung disease in congenital heart disease: linked to IL-6 and associated with exercise intolerance

Background: In adult patients with congenital heart disease (ACHD) inspiratory muscle dysfunction may underlie restrictive lung function impairment and may be linked to increased levels of IL-6 and TNF alpha and associated with exercise intolerance. The present study used a multimodal approach to evaluate the characteristics of inspiratory muscle function in ACHD patients while exploring its link to IL6 and TNF-alpha and association with exercise intolerance.

Methods: 30 ACHD (21 men, 35 ± 12 years) and 30 controls healthy controls matched for age, gender and body mass index underwent spiro-manometry and diaphragm ultrasound. 6 minute walking distance (6 MWD) test and NYHA functional class were used to quantify exercise intolerance. IL6 and TNF α were measured using enzyme-linked immunosorbent assays.

Results: ACHD patients showed reductions in forced vital capacity (FVC), maximum inspiratory (PIMax) and expiratory (PEMax) pressures compared with controls. On ultrasound, ACHD patients showed a reduced diaphragm thickening ratio (2.3 ± 0.5 vs. 2.8 ± 0.9, p < 0.01) and reduced diaphragm excursion velocity during a voluntary sniff maneuver (5.7 ± 2.2 vs. · 7.6 ± 2.0 cm/sec, p < 0.01). Not only indices of heart function (systemic ventricular function and NT-pro-BNP − 0.52; p < 0.01-) but also FVC (r = 0.53; p < 0.01) and PI Max (r = 0.43; p = 0.02) correlated with exercise intolerance. Lung and inspiratory muscle function were interrelated with heart function such that NT-pro-BNP correlated inversely with FVC (r = − 0.54; p < 0.01) and PIMax (r = − 0.37; p = 0.06). Circulating pro-inflammatory cytokines were markedly increased and IL-6 correlated inversely and strongest (r = 0.76; p < 0.0001) with exercise intolerance and with dyspnoea, heart function and lung and inspiratory muscle function.

Conclusions: Our findings suggest that in ACHD patients, there is relevant diaphragm dysfunction and that this is associated with restrictive lung function impairment and exercise intolerance and may be mediated in part, by increased levels of IL-6.