Sympathetic nerve activity reactivity is associated with cardiac fibrosis in humans

Abstract

Abstract Background Hypertension causes cardiac remodelling and left ventricular hypertrophy (LVH) in some individuals but not others [1-3]. 90% of people with heart failure preserved ejection fraction (HFpEF) have hypertension. One possible mechanism is increased sympathetic drive resulting in cardiac fibrosis. Resting sympathetic nerve activity (SNA) is associated with cardiac remodelling in both animals and humans and progressively increases from hypertension to LVH to HFpEF. However, humans are not in a constant rested state, and are frequently exposed to multiple physiological stressors throughout the day, resulting in surges in SNA. Amplified SNA reactivity to stressors may contribute to cardiac remodelling more than elevated resting SNA levels, as intermittent β-adrenergic receptor stimulation with isoprenaline in mice has been shown to cause more severe cardiac fibrosis when compared to a sustained isoprenaline administration [4]. Purpose To determine whether resting SNA and/or SNA reactivity to a physiological stressor (cold pressor test) were associated with cardiac fibrosis in humans. Methods Nineteen (10M, 9F; 48 ± 13 years; BMI: 25.9 ± 3.2 kg/m²) participants with varying ambulatory blood pressures (SBP: 126±13 mmHg, DBP: 83±8 mmHg, SBP range: 111-153 mmHg, DBP range: 68-96 mmHg), provided written informed consent. Blood pressure (Finometer), heart rate (ECG) and muscle SNA (peroneal microneurography) were recorded simultaneously during a 5-minute baseline, and a 2-minute rest, 3-minute cold pressor test (3-4°C) and 5-minute recovery. Cardiac extracellular volume (ECV) was measured using magnetic resonance imaging (1.5T Avanto, Siemens) as an index of cardiac fibrosis. Simple linear regressions were conducted between baseline SNA and ECV, and change in SNA from rest to peak cold pressor test and ECV using SPSS. Results Resting SNA was not associated with ECV. However, the absolute change in SNA burst incidence (bursts/100 heartbeats) and burst frequency (bursts/minute, Figure 1) from rest to peak cold pressor test, were positively associated with ECV, showing that the greater the SNA response to a stressor, the higher the ECV. Specifically, for every 1 burst/100 heartbeat increase in burst incidence (from rest to peak cold pressor test), ECV increased by 0.120%, and for every 1 burst/minute increase in burst frequency (from rest to peak cold pressor test), ECV increased by 0.128%. Conclusion SNA reactivity but not resting SNA level was found to be a predictor of ECV, where the greater the SNA response to a stressor, the higher the ECV. This indicates that intermittent surges in SNA may be more important for promoting cardiac fibrosis than the overall level of resting SNA in humans.Figure 1.