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3 Exercise Training and the Right Heart in Pulmonary
Arterial Hypertension
The primary cause of death in patients with PAH is right heart failure, which is pre-
ceded by RV dysfunction [ 18 ]. Right heart failure can be reversed by interventions
that normalize RV afterload such as lung transplantation and pulmonary endarterec-
tomy but there is no specific therapy directly targeting RV. If available, such strategy
could have tremendous clinical implications because RV function is a major inde-
pendent prognostic determinant of PAH patients [ 18 ]. Aerobic exercise training was
shown to improve cardiac function and reverse ventricular remodeling in clinically
stable individuals with left heart failure and left ventricular (LV) systolic dysfunc-
tion [ 19 ]. Despite the intimately related function of both ventricles, there are strik-
ing differences about how they respond and adapt to physiological or pathological
stimuli [ 20 – 22 ]. In addition, the response of pulmonary and systemic circulation to
exercise is also very different. Together, these distinctive features preclude any rec-
ommendation of ExT to PAH patients based on the evidence from LV failure. While
the data derived from clinical studies is scarce [ 23 ], the first insights about the
impact of ExT in RV function and remodeling came from pre-clinical studies.
3.1 Exercise Training and Right Ventricular Function
A detailed characterization of training programs, animal models and changes induced
by ExT in PAH is provided in Tables 17.1, 17.2 and Fig. 17.1. Overall, studies differ
in terms of MCT’s concentration, animals’ weigh, age and species, exercise intensity
and duration, and time point of the disease when ExT was initiated. The majority of
the studies argue that ExT can prevent RV systolic [ 24 – 32 ] and diastolic dysfunction
[ 25 , 27 , 29 ] while a minority shows no change (nor beneficial nor deleterious) [ 30 ,
33 , 34 ], and two studies report aggravation [ 33 , 35 ]. RV function was assessed by a
variety of invasive and non-invasive parameters such as cardiac output (CO), stroke
volume (SV), fractional shortening (FS), myocardial acceleration during isovolumic
contraction (AIV), isovolumic relaxation time (IVRT), tricuspid annular plane maxi-
mal systolic velocity (E’), tricuspid annular plane systolic excursion (TAPSE), end-
diastolic pressure (EDP), time constant of ventricular pressure decay (Tau),
end-diastolic (EDPVR) and end-systolic pressure- volume relationship (ESPVR).
Those studies reporting enhancement of RV function have in common the use of
higher exercise intensities [ 25 , 27 – 30 , 32 ], suggesting that the benefit may be inten-
sity-dependent. Similarly, it is accepted that training- related cardiac adaptations to
the LV are dependent on training intensity [ 36 – 38 ]. Regarding the RV, this hypothe-
sis was specifically evaluated in one study, where high intensity interval training
(HIIT), but not continuous aerobic training, was able to improve RV cardiac index
[ 30 ]. Likewise, it is interesting to note that free wheel running that is characterized
by intermittent, high intensity but short bouts of running throughout the day [ 39 ],
D. Moreira-Gonçalves et al.