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in PAH should enroll patients in different stages of the disease, so that we could
have solid evidence over the entire spectrum of the disease.
The current strategy to preserve RV function in PAH is by attempting to reducethe RV afterload. This strategy is effective when loading conditions can be normal-
ized, as it is the case with lung transplantation or with pulmonary endarterectomy in
PAH and chronic thromboembolic pulmonary hypertension (CTEPH), respectively
[ 41 ]. However, in a subset of patients, it was noted that RV dysfunction might prog-
ress despite a reduced PVR with targeted medical therapies. A deterioration of RV
function was associated with poor outcome, irrespective of any changes in PVR [ 41 ].
Similarly, Eisenmenger syndrome [ 42 ] and congenital pulmonary stenosis [ 43 ]
patients usually present a severe increase in RV chronic pressure-overloaded and a
relatively good prognosis explained by adaptive remodeling of the RV to those bur-
densome hemodynamic conditions [ 44 , 45 ]. The beneficial effects of ExT on RV
function were not always mirrored by a reduction in RV afterload. As illustrated in
Table 17.2, except for one [ 30 ], all studies showed an improvement of cardiac perfor-
mance despite the presence of persistent RV pressure-overload [ 24 , 25 , 27 , 29 , 31 ,
32 ]. Measures of RV overload ranged from PVR, PAP, RV peak systolic pressure
(RVSP), pulmonary artery acceleration time (PAAT), acceleration time to ejection
time ratio (AT/ET) and, less frequently, arterial elastance (Ea). This unrelated change
between RV afterload and RV function in response to ExT further strengthen the
hypothesis that other factors, beyond afterload, are important modulators of RV func-
tion in PAH [ 46 , 47 ]. More importantly, ExT seems to influence some of those factors
and, consequently, might be used to increase tolerance to an increased afterload.
3.2 Exercise Training, Right Ventricular Hypertrophy
and Remodeling
RV hypertrophy is a compensatory mechanism that modulates RV function within
the homeostatic range. Following the law of Laplace, increased RV wall thickness
(concentric hypertrophy) lowers RV wall stress and, together with changes in mus-
cle properties, improves pumping effectiveness [ 18 ]. This compensatory stage is
called “adaptive remodeling”. However, if the disease progresses, the hypertrophic
process will be halted and CO falls [ 18 ]. In an attempt to restore CO, the RV dilates
(eccentric hypertrophy) and heart rate (HR) increases, leading to RV uncoupling and
reduced output in advanced stages of disease [ 48 ]. Thus, while RV dilatation might
be beneficial in the acute phase (Frank-Starling mechanism), it will lead to increased
RV wall stress, energy exhaustion, reduced RV function and failure in the long term
[ 18 ]. This failing stage is called “maladaptive remodeling” [ 18 ]. As shown in
Table 17.2, RV hypertrophy was not changed with ExT in 11 studies, which together
with the improved RV function, suggests that ExT was capable to promote adaptive
RV remodeling (or delay maladaptive remodeling). Further corroborating this
notion, it was reported in one study that ExT prevented the RV to develop a spherical
D. Moreira-Gonçalves et al.