Geert Kleinnibbelink

General Discussion 10 203 10.2 – Relation between acute cardiac responses to exercise and subsequent cardiac remodelling It is well established that chronic exercise will lead to physiological cardiac remodelling such as chamber enlargement and hypertrophy. 34, 35 The substrate for cardiac remodelling is the repetitive exposure to haemodynamic stress during acute bouts of exercise. Therefore, by implication, the acute cardiovascular changes in haemodynamics may be related to this chronic remodelling. Although acute and chronic exercise responses are highly relevant research topics, relatively little research has assessed the association between acute cardiac responses and chronic cardiac remodelling. Hulshof et al . studied the direct relationship between acute changes in cardiac haemodynamics and chronic remodelling. 36 They demonstrated that uncoupling of the LV strain-volume loop is related to reverse LV remodelling in a cohort of 30 patients undergoing aortic valve replacement due to a severe stenosis. In line with this work, we tested the hypothesis whether baseline acute cardiovascular responses to exercise are related to chronic cardiac remodelling ( Chapter 3 ). We included 21 participants of whom 15 completed a 12-week training programme. In order to increase RV afterload 37, 38 , the training programme was performed under hypoxic conditions (FiO 2 14.5%) to induce RV remodelling after a relatively short period of training. Indeed, we succeeded in inducing RV remodelling after 12 weeks hypoxic exercise training. At baseline, we performed stress echocardiography, at low-to- moderate intensity exercise, to explore cardiac responses to acute exercise. Interestingly, we found that augmentation in RV fractional area change to acute exercise was related to the increase in RV size following exercise training ( Figure 1A ). This association between the pre-training augmentation in RV fractional area change to acute hypoxic exercise and RV remodelling after 12 weeks of hypoxic training substantiates that acute cardiac responses of the RV to exercise are related to subsequent RV remodelling. It has been hypothesized that repetitive exposure to high volumes of exercise may lead to maladaptive remodelling of the RV with a phenotype similar to that seen in patients with arrhythmogenic RV cardiomyopathy. 23, 39-42 There is a lack of empirical, prospective data to explore this theory. The concept explored in this thesis, i.e. exploring cardiac responses to exercise and their relation with subsequent cardiac remodelling, may be a potential strategy for future studies aiming to better understand this cardiac (patho)physiology.