Background and aims: Aortic stenosis (AS) is the most common valve disease in Europe. It is associated with adverse myocardial remodelling and impaired exercise capacity, reflecting limited ability to increase cardiac output during physical exertion. Resting measures of AS do not fully capture functional limitations and despite practical recommendations, cardiopulmonary exercise testing (CPET) remains underused in this patient population. In patients with severe AS, important knowledge gaps remain regarding how circulating biomarkers reflect structural myocardial remodelling, how exercise capacity and systolic blood pressure (SBP) change before and after surgical aortic valve replacement (AVR), and how structured postoperative exercise training influences functional recovery. This thesis aimed to improve pre- and postoperative evaluation of patients with severe AS by exploring exercise physiology methods, focusing on CPET and circulating biomarkers.

Methods: Four studies were conducted within two prospective cohorts of patients with severe AS referred for AVR at a tertiary centre in Sweden.

In paper I, associations between circulating biomarkers and diffuse myocardial fibrosis assessed by myocardial biopsies and by imaging were explored.

In paper II, maximal and submaximal CPET variables were evaluated before and one year after AVR surgery.

In paper III, SBP responses during incremental CPET were analyzed before and after AVR, including categorization of SBP responses and work-load indexed SBP-slopes.

In paper IV, a randomized controlled trial assessed the effect of a 12-week aerobic exercise training intervention compared to usual care on CPET-derived functional outcomes following AVR.

Results: In Paper I (n=36), circulating biomarkers showed distinct associations with DMF assessed by cardiac magnetic resonance imaging (CMR) and histopathology. Biomarkers related to extracellular matrix turnover (Galectin-3, MMP-2) and myocardial stress (Troponin-I, NT-proBNP) were most strongly linked to CMR-derived measures (T1-time, extracellular volume), while NT-proBNP correlated with biopsy-derived collagen volume fraction. These findings indicate that biochemical markers reflect complementary aspects of myocardial remodelling.

In paper II (n=30), maximal exercise capacity was relatively preserved preoperatively (mean peak VO₂ ≈95% of predicted). One year after AVR, maximal workload increased modestly (+8%), peak VO₂ showed no significant group-level change, and submaximal aerobic capacity (VO₂ at ventilatory threshold) increased significantly (+9%). Improvements in peak VO₂ were heterogeneous and inversely related to baseline values. We found a strong significant correlation between submaximal oxygen uptake efficiency slope (OUES) and peak VO₂ (r = 0.89, p<0.05). 

In Paper III (n=45), an exercise-induced drop in SBP was uncommon preoperatively (<10%). Following AVR, SBP responses showed overall improvement, with no postoperative SBP drops observed. Among patients achieving maximal effort at preoperative and postoperative assessments (n=31), the SBP/Watt slope increased by approximately 48%.

In Paper IV (n=12), patients randomized to supervised aerobic exercise training demonstrated significant improvements in maximal workload (+28%) and peak VO₂ (+23%) after 12 weeks of intervention, whereas no significant changes were observed in the control group. Submaximal CPET variables showed non-significant trends toward improvement.

Conclusion: This thesis demonstrates that CPET-derived functional and hemodynamic responses provide clinically relevant information beyond traditional resting measures in severe AS. Circulating biomarkers were related to DMF. By capturing complementary aspects of myocardial remodelling and cardiopulmonary function before and after valve replacement, these methods support a more integrated approach to patient evaluation and postoperative management.