A) Right ventricle (RV) in pulmonary hypertension
RV failure is the main cause of death in patients with pulmonary arterial hypertension (PAH),
and the ability of the RV to adapt to the progressive increase in pulmonary vascular
resistance associated with changes to the pulmonary vasculature in PAH is the main
determinant of a patient's functional capacity and survival.
The response of the right ventricle (RV) to the increase in afterload produced by the
pulmonary vascular changes characteristic of PAH is the key factor in the development of
symptoms and in determining survival. Structurally, rising systolic and diastolic ventricular
pressures increase diastolic and systolic stretch on the RV wall, which leads initially to an
increase in muscle mass (adaptive hypertrophy) due to increased protein synthesis and an
increase in cardiomyocyte size through the addition of sarcomeres. However, the RV cannot
maintain adaptive hypertrophy in the face of sustained pressure overload, and eventually
there is a transition to dilatation. At this stage there is no further increase, or even a
decrease, in RV contractility, despite a further increase in load. One consequence of RV
dilatation is an increase in wall tension, which increases myocardial oxygen demand and
simultaneously decreases RV perfusion, leading to further compromised contractility and
dilatation.
The exact mechanisms leading to the development of RV failure in patients with PAH are still
unclear. Several mechanisms have been hypothesized: RV myocardial ischaemia, microvascular
endothelial cell dysfunction, and myocyte apoptosis. In severe end-stage PAH, the RV changes
its shape from the normal conformation to a more spherical one, and RV wall stress increases
because RV wall thickness does not increase proportionally.
Given the importance of the RV in PAH, preservation and improvement of its function should be
important aspects of therapy; however, there are currently few data specifically related to
this aspect of treatment response.
B) Vasodilator therapy and RV in pulmonary hypertension Although RV failure is the main cause
of death in patients with pulmonary arterial hypertension (PAH), there is insufficient data
about the effects of PAH treatment on RV geometry and function mainly because the RV
assessment has been hampered by its complex crescentic shape, large infundibulum, and its
trabecular nature. . This is specifically true for vasodilator therapies. Such therapies may
affect the RV via direct cardiac-specific effects or indirect effects by reducing RV load. In
a meta-analysis of clinical studies of PAH-specific therapies, active treatment was
associated with a reduction in pulmonary vascular resistance which was accompanied by a
decrease in pulmonary artery pressure, and an increase in stroke volume, but without an
increase in contractility, suggesting that current PAH therapies have predominantly pulmonary
vasodilating effects and have limited cardiac-specific effects. In a study of epoprostenol
therapy, beneficial effects on RV structure and function (RV dilatation, curvature of the
interventricular septum and maximal tricuspid regurgitant jet velocity) compared with placebo
were reported following 12 weeks of treatment, with change in 6-min walk distance between
baseline and 12 weeks being inversely related to the change in diastolic eccentricity index
and pericardial effusion size. Such improvements may contribute to the clinical improvement
and prolonged survival observed with epoprostenol in other studies.
Other evidence of improvements in RV parameters has come from descriptive studies using a
number of PAH-specific therapies; however, these generally include a small number of
patients, and this, together with the fact that such studies evaluated different parameters
(both in terms of functional parameters and measures of RV size/mass), makes the assessment
of results difficult. longer term studies of epoprostenol have not shown a positive treatment
effect on RV size/mass although without a comparator arm it is not possible to determine
whether long-term therapy slowed down the rate of RV hypertrophy or dilatation.
Overall, therefore, the effects of PAH-specific therapies on RV function remain to be fully
investigated.
C) Treprostinil Treprostinil is a tricyclic benzindene analogue of prostacyclin, and has as
such similar anti-platelet and vasodilatory actions, including acute pulmonary vasodilation.
Treprostinil, a stable prostacyclin analog, has similar pharmacologic effects to
epoprostenol, However, in contrast to epoprostenol, treprostinil is chemically stable at room
temperature and neutral 'power of hydrogen' (pH) and has a longer half-life (elimination
half-life of 4.5 h with distribution half-life of 40 min, compared with 2 to 3 min for
epoprostenol) permitting continuous subcutaneous infusion (16). Treprostinil has been shown
in a large multicenter randomized controlled trial to improve exercise capacity, clinical
state, functional class, pulmonary hemodynamics, and quality of life in patients with
pulmonary arterial hypertension.
D) Assessment of RV with cardiac magnetic resonance imaging Currently, the most widely used
noninvasive techniques are echocardiography and cardiac magnetic resonance imaging), and a
number of potential indicators assessed using these methods have been proposed. Cardiac
magnetic resonance imaging provides a higher spatial resolution, and is not limited by
factors affecting echocardiography (e.g. acoustic window). Cardiac magnetic resonance imaging
allows for the visualisation and measurement of complex three-dimensional geometry and it is
therefore particularly suited to the complex morphology of the RV. Precise, noninvasive
assessment of cardiac volumes and function is possible, without the need for geometric
approximations, while assessments such as flow measurements in the heart and great vessels
using techniques such as cine phase-contrast provide more comprehensive data on cardiac
function than echocardiography.