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Pathophysiology of right ventricular failure

Clifford R. Greyson, MD

Right ventricular failure may be defined as the inability of the tion may occur abruptly and catastrophically because of unique
right ventricle of the heart to provide adequate blood flow through aspects of right ventricular physiology. This review will focus on
the pulmonary circulation at a normal central venous pressure. the pathophysiology of acute right ventricular failure in the critical
Critical care specialists encounter right ventricular failure rou- care setting and summarize the limited management options
tinely in their practice, but until recently right ventricular failure available. (Crit Care Med 2008; 36[Suppl.]:S57–S65)
as a primary clinical entity received scant consideration. Indeed, KEY WORDS: right ventricle; pulmonary hypertension; Frank-
there is still not a single published practice guideline focused on Starling relation; contractile dysfunction; hypoxic pulmonary va-
right ventricular failure. Right ventricular failure is usually due to soconstriction; coronary ischemia; ventricular wall stress; central
a combination of right ventricular pressure overload and contrac- venous pressure; heart failure; cor pulmonale
tile abnormalities of the right ventricular free wall. Decompensa-

I n contrast to the left ventricle hypertension, and consequent right acutely decompensated left heart fail-
(LV) of the heart, the right ventri- ventricular dysfunction is seen rou- ure). Ultimately, many of these patients
cle (RV) receives little attention. tinely in critically ill patients (2). Sepsis end up in critical care units, where RV
Pulmonary disease specialists con- may cause right heart failure directly by failure may be the primary manifestation
centrate on disorders of the pulmonary inducing RV dysfunction (3). Pulmo- of their disease or a major complicating
circulation that affect right heart func- nary embolism is far more common factor in the management of their under-
tion directly but tend not to study disor- than generally appreciated, with an es- lying conditions. Altogether, RV failure is
ders of right heart function per se. At the timated 600,000 cases in the United estimated to account for 3% of all acute
same time, cardiovascular disease spe- States each year, and causes ⬎50,000 heart failure admissions and confers
cialists interested in heart failure have deaths annually, largely due to acute RV worse mortality rates than acutely de-
largely ignored the right heart as a dis- failure (4). RV failure occurs in the set- compensated left heart failure (12).
tinct area of investigation. Indeed, Amer- ting of idiopathic dilated cardiomyopa- While the function of the RV has long
ican Heart Association/American College thy, probably as a consequence of the been recognized, awareness of its impor-
of Cardiology practice guidelines for same mechanism causing LV dysfunc- tance has waxed and waned over the
management of heart failure barely men- tion and also as a consequence of pul- years. The importance of the RV was first
tion the RV and provide no guidance for monary hypertension secondary to ele- recognized by William Harvey in 1616
management of either acute or chronic vated left-sided filling pressures in (13), but in 1943 Starr et al. (14) con-
RV failure (1). Not a single professional ischemic LV cardiomyopathy (5). RV cluded that the RV functioned only as a
society has published a practice guideline failure may be an independent risk fac- passive conduit, since there were “no in-
concentrating on RV failure. tor for morbidity and mortality in pa- crements of venous pressure” following
Nevertheless, right heart failure re- tients with left heart failure (6). RV electrocautery ablation of the RV free wall
mains a major public health problem. failure is still a leading cause of death in dogs. A resurgence of interest in the
Respiratory failure causing hypoxic pul- and morbidity early after cardiac trans- RV followed reports by Cohn and col-
monary vasoconstriction, pulmonary plant (7) and following several other leagues (15) in 1974 that RV infarction
cardiothoracic procedures (8). Primary was common and difficult to manage,
pulmonary hypertension, while rela- that RV involvement in inferior myocar-
From the Department of Veterans Affairs Medical tively rare with only 300 new cases an- dial infarction conferred an eight-fold in-
Center and the University of Colorado Health Sciences nually in the United States, is difficult crease in mortality (16), that RV dysfunc-
Center, Denver, CO. to manage and results in RV failure (9). tion in acute pulmonary embolism is a
Supported, in part, by the Department of Veterans
Affairs and by grant R01 HL068606 from the National
By some estimates, 1 in 2000 of the predictor of mortality independent of sys-
Institutes of Health/National Heart, Lung, and Blood 10 –15 million people with chronic ob- temic hemodynamics (17), and that RV
Institute, Bethesda, MD. structive pulmonary disease will de- dysfunction is an independent predictor
Dr. Greyson has applied for a patent for protease velop RV failure, accounting for several of poor outcome in left heart failure (6).
inhibition for prevention or treatment of heart failure.
thousand new cases per year (10). Cor- Why have investigators only recently
For information regarding this article, E-mail: onary ischemia may cause RV failure, rediscovered the clinical importance of
Copyright © 2007 by the Society of Critical Care both directly (as in RV myocardial in- the RV of the heart? Limited understand-
Medicine and Lippincott Williams & Wilkins farction) (11) and indirectly (as in acute ing of the physiology of the RV by clini-
DOI: 10.1097/01.CCM.0000296265.52518.70 ventricular septal defect or from cians who view the RV merely as a weak

Crit Care Med 2008 Vol. 36, No. 1 (Suppl.) S57

LV has likely contributed to the problem. Table 1. Typical values for systemic and pulmonary pressure and resistance
Fortunately, along with the growing body
Pulmonary/RV/RA Systemic/LV/LA
of clinical data indicating a critical role
for RV function in health and disease has Pressure, mm Hg, average ⫾ range
come a stream of experimental data that Atrial mean 2–7 2–12
help to explain the disparate conclusions Ventricular systolic 15–28 90–140
from the past. In recognition of a Na- Ventricular diastolic 0–8 4–12
tional Institutes of Health working Vascular mean 10–16 65–105
Resistance, dyne䡠sec䡠cm⫺5䡠M2, average ⫾ SD
group’s conclusion that increased em- Vascular 123 ⫾ 54 2130 ⫾ 450
phasis on the pathophysiology of the
right heart is warranted (18), there is RV, right ventricle; RA, right atrium; LV, left ventricle; LA, left atrium.
now a National Institutes of Health spe- Data from Grossman and Baim (23), Davidson and Bonow (24), and others.
cial emphasis area concentrating on RV

Normal Physiology of the RV

The RV is not simply a weak LV. Mac-
roscopically, ultrastructurally, and bio-
chemically, the RV differs dramatically
from the LV. The normal RV seldom ex-
ceeds 2–3 mm wall thickness at end-
diastole, compared with 8 –11 mm for the
LV. A distinct pattern of conduction re-
sults in a bellows-like or peristaltic-like
contraction beginning near the apex of
the heart and moving in a wave toward
the outflow tract (19). The biochemical
composition of the RV and LV differs,
with the RV having a higher proportion of
the ␣-myosin heavy chain isoform that
results in more rapid but less energy-
efficient contraction (20). Recent data
suggest there may be dramatic differ-
ences in the response of the RV to adren-
ergic agents (21).
The coronary perfusion pattern of the
RV differs significantly from that of the
LV. Because tissue pressure in the LV Figure 1. Illustration of how the geometry of the right ventricle (RV) changes with contraction and is
rises during systole to systemic levels, affected by pressure overload. Top, the crescentic RV flattening in systole, leading to a large-volume
coronary perfusion of the LV is largely change with minimal change in RV free wall area. Bottom, how a shift of the interventricular septum
during acute pressure overload permits RV end-diastolic volume to increase with no change in
confined to the diastolic interval. Tissue
end-diastolic RV free wall area, a decrease in interventricular septal surface area, and a corresponding
pressure in the RV does not normally decrease in left ventricle (LV) end-diastolic volume. Because the RV free wall does not stretch, there
exceed aortic root systolic pressure, per- is no recruitment of RV function via the Frank-Starling mechanism, while at the same time there is
mitting continued coronary flow a loss of function via the Frank-Starling mechanism in the LV.
throughout the cardiac cycle; thus, under
typical hemodynamic conditions, coro-
nary flow to the RV is roughly balanced to blood momentum; the relatively high file of the LV results in a geometrically
between systolic and diastolic time peri- momentum of blood movement ejecting predictable relationship between LV sur-
ods (22). into the low-pressure pulmonary circula- face area and LV volume, the bellows-like
Ejection of blood into the highly com- tion results in RV ejection continuing contraction of the RV free wall (Fig. 1,
pliant, low-resistance pulmonary circula- after ejection from the LV has ended, and top) results in a much higher ratio of RV
tion results in dramatically different he- even during RV relaxation (25). volume change to RV free wall surface
modynamics. Table 1 shows differences The RV accommodates dramatic vari- area change and allows the RV to eject a
in normal hemodynamic measurements ations in venous return resulting from large volume of blood with little alter-
for the LV and the RV (23, 24). The nor- changes in volume status, position, and ation in RV wall stretch. This pattern of
mal RV generates less than one sixth the respiration while maintaining more or contraction is optimized for moving large
work of the LV while moving the same less constant cardiac output (26). In part and varying volumes of blood but is
volume of blood. Compared with the LV, this is because the thin RV is easily dis- poorly adapted to generating high pres-
a much lower proportion of RV stroke tensible, but to a larger extent it is a sure. For example, at end-systole, LV free
work goes to pressure generation, with a direct result of RV geometry. While the wall radius of curvature decreases, which
correspondingly higher proportion going more or less circular cross-sectional pro- facilitates further development of pres-

S58 Crit Care Med 2008 Vol. 36, No. 1 (Suppl.)

sure by decreasing wall stress, but RV free stretch (Fig. 1, bottom). Since an in- increments in afterload, the RV ulti-
wall radius of curvature increases at end- crease in volume is less effective at re- mately begins to dilate and recruit func-
systole (Fig. 1), resulting in higher stress cruiting the Frank-Starling effect in the tion via the Frank-Starling mechanism.
at peak pressure than would be developed RV than in the LV, an increase in RV Once all mechanisms of contractile re-
were the geometry more like the LV, and volume at the expense of LV volume may serve are exhausted, systemic pressure
consequently hinders further pressure have a net negative effect on overall car- begins to fall, with a dramatic, sudden,
development. diac output. and irreversible decrease in RV contrac-
Like the LV, the RV can use the Frank- The pericardium plays a major role in tile function. This sudden catastrophic
Starling mechanism to increase stroke modulating the interaction between the hemodynamic collapse was first demon-
work as a consequence of an increase in RV and the LV and in limiting RV dilation strated in 1954 by Guyton et al (39). Fig-
RV stretch (27). However, the relatively during volume or pressure overload. By ure 2, taken from Guyton’s report, shows
flat relationship between RV surface area limiting total cardiac volume, the effects a steady rise in RV-generated pressure
and RV volume described previously of interventricular interaction may be during progressive constriction of the
means that large changes in RV volume magnified, as described previously, and main pulmonary artery, until the RV can
are necessary before the Frank-Starling recruitment of RV function by the Frank- no longer compensate, at which point a
mechanism is recruited. Since relatively Starling mechanism may be impaired. sudden decline in systemic pressure and
large increments in RV volume result in Conversely, by preventing RV dilation cardiac output ensues.
relatively small increments in RV stretch, and reducing end-systolic RV free wall This catastrophic hemodynamic col-
minimal recruitment of function via the stress, contractile function may actually lapse occurs at the onset of, and is exac-
Frank-Starling mechanism occurs at base- be preserved in some cases (33). erbated by, RV ischemia (40, 41). As RV
line (28). Once the RV begins to dilate and systolic pressure increases, the dynamics
becomes more circular in contour, a Response of the RV to of RV coronary perfusion change, with a
steeper relationship between volume and Increased Pressure decline in coronary perfusion during the
stretch develops, and the Frank-Starling re- systolic interval (42). At very high RV
lation becomes more important (29). In both the LV and the RV, an increase pressure, RV coronary vasodilator reserve
Global function of the RV depends on in end-systolic pressure results in a cor- is lost entirely, and RV ischemia may en-
independent but coordinated contribu- responding increase in end-systolic vol- sue. Several investigators have found that
tions from both the RV free wall and the ume and a decrease in ejection fraction, improving RV coronary perfusion
interventricular septum. In an experi- through the well-known end-systolic through aortic constriction during acute
mental system, Damiano et al. (30) elec- pressure-volume relation (34, 35). If RV pressure overload has a modest ben-
trically isolated the RV from the left nothing else changed, an increase in pul- eficial effect on RV pressure, suggesting
atrium and LV to allow changing the in- monary artery pressure would result in a that RV failure during acute pressure
terval between RV and LV activation. Us- decrease in RV ejection fraction and overload is at least in part due to isch-
ing this approach, they were able to show stroke volume and a corresponding de- emia (40, 41, 43). However, enhancing
that the RV and the LV both make inde- crease in cardiac output. Thus, for the RV coronary flow using coronary vasodila-
pendent contributions to RV output. to maintain cardiac output when con- tors does not improve RV contractile
Despite the contribution of the inter- fronted with an increase in afterload or function (40, 44), and the effect is sub-
ventricular septum to RV output, under pressure, RV performance must increase stantially attenuated when the RV and the
normal circumstances RV function is rel- to generate the required increase in LV are mechanically uncoupled and cor-
atively independent of LV loading condi- stroke work. The RV could potentially onary perfusion is independently con-
tions. Chow and Farrar (31) supported compensate through either an increase in trolled (45), suggesting that aortic con-
dogs with an LV assist device to permit contractile state or the Frank-Starling striction may improve RV function
independently altering RV and LV loading mechanism. In a model of acute RV pres- indirectly through interventricular inter-
conditions; even after reducing LV intra- sure overload through pulmonary artery action. Thus, it is controversial to what
cavitary pressure to zero, normal RV banding in lambs (28, 36) and sheep (36), extent RV ischemia is responsible for the
pressure was maintained, indicating that increased stroke work during acute RV onset of RV contractile failure. Neverthe-
the RV free wall is able to generate sub- pressure overload was shown to be medi- less, once RV coronary perfusion pressure
stantial external work without assistance ated primarily through an increase in begins to fall due to systemic hypoten-
from interaction with the LV. However, contractility, with at most a small contri- sion, RV contractile failure progresses
functions of the RV and LV become more bution from the Frank-Starling mecha- rapidly and catastrophically.
directly intertwined (so-called “interven- nism using increased RV end-diastolic Figure 3 illustrates the catastrophic
tricular interdependence”) under a num- volume. The rapid increase in contractile downward spiral once RV compensatory
ber of pathologic conditions that either function in response to an increase in mechanisms are exhausted. This cata-
increase total cardiac volume (such as LV demand, called homeometric autoregula- strophic change is irreversible in the ab-
or RV heart failure) or decrease effective tion or the Anrep effect, appears to be sence of relief of RV outflow obstruction
intrapericardial volume (such as pericar- mediated through rapid alterations in because the fall in systemic pressure re-
dial effusion). In such cases, an increase calcium dynamics (37) and may occur sults in a loss of RV tissue perfusion, a
in RV volume results in a corresponding without a change of adrenergic state. As further decline in RV contractility, and a
decrement in LV volume (32), and be- pulmonary impedance rises, endogenous further decline in systemic pressure, in a
cause of interventricular septal shift, the or exogenous catecholamines may permit feed-forward downward spiral.
increase in RV volume can occur with no a further increase in RV pressure via an Right coronary ischemia, which is the
change in RV free wall surface area or increase in inotropy (38). With further primary cause of this rapid decompensa-

Crit Care Med 2008 Vol. 36, No. 1 (Suppl.) S59

teases, such as calpain to dysfunction, as
occurs in skeletal muscle subjected to
high loads (51), is suggested by recent
reports that calpain inhibitors may par-
tially attenuate the development of RV
contractile failure in acute pressure over-
load (52).
Acute pressure or volume overload in-
duces expression of B-type natriuretic
protein, various cytokines, growth fac-
tors, and calcium handling genes (53).
When RV pressure persists, changes in
cytoskeletal structure occur (54), with
longer term pressure overload resulting
in a shift in glucose and fat metabolism
akin to that seen in LV pressure overload
(55). Whether these changes are adaptive
or maladaptive is unknown.

RV Response to a Primary
Reduction in Contractility
Pulmonary vascular resistance is nor-
mally ⱕ10% of systemic vascular resis-
Figure 2. Main figure from the seminal investigation by Arthur Guyton and colleagues (39) showing tance, and mean pulmonary artery pres-
the limits of right (RT.) ventricle (RV) contractile function in the setting of increasing pulmonary sure is normally not much higher than
artery (PUL. ART.) outflow obstruction, with the resulting abrupt and catastrophic collapse in systemic
15 mm Hg. If LV filling pressure is low
hemodynamics once RV compensatory mechanisms are exhausted. The original figure legend reads
“Effect of increasing pulmonary arterial constriction on the mean pressures at different points in the
and pulmonary vascular resistance is nor-
circulatory system.” mal, active contraction of the RV, or even
the interventricular septum, is not nec-
essary to maintain cardiac output. For
tion, is probably not the only contributor example, to maintain a cardiac output of
to altered RV contractile function during 6 L/min with a normal left atrial pressure
acute pressure overload and may not play of 8 mm Hg requires a mean pulmonary
a significant role in right heart failure artery pressure of only 14 mm Hg; with
from pulmonary hypertension in a major- no contribution from the RV at all, this
ity of stable patients (46). While homeo- can be developed entirely by a modest
metric autoregulation and increased ad- increase in central venous pressure.
renergic tone both up-regulate RV Thus, a reduction in RV contractility
contractility during acute pressure over- may not by itself result in RV failure, and
load, there is evidence that pressure over- even very severe isolated RV ischemia
load down-regulates RV contractility dur- may be well tolerated because elevated
ing (47) and following (48, 49) acute RV central venous pressure provides suffi-
pressure overload even in the absence of cient driving force to maintain flow
ischemia. The mechanism of the down- across the pulmonary circulation. This
ward regulation is not known; however, was demonstrated in a report by Brooks
the severity of this element of contractile and colleagues (43), in which complete
dysfunction is directly related to end- right coronary occlusion had essentially
Figure 3. Illustration of the downward spiral of systolic wall stress and is exacerbated by no impact on RV developed pressure, car-
right ventricle (RV) function that ensues once RV end-systolic RV dilation, presumably be- diac output, or left ventricular developed
compensatory mechanisms are exhausted in the cause end-systolic RV dilation results in pressure, when pulmonary artery pres-
face of rising RV systolic pressure stress. With the RV wall thinning, increased RV radius of sure was normal. Congenital heart dis-
RV teetering on the edge of compensation, even a curvature, and increased wall stress at ease corrective procedures, such as the
small additional increment in pulmonary outflow the same RV systolic pressure (49). Fontan procedure, exploit this low-
resistance, or a small decrement in RV contrac- Shortly after acute RV pressure over- resistance state of the normal pulmonary
tile function, can precipitate an abrupt decline in
load ensues, ultrastructural changes con- circulation, bypassing the RV entirely
function through a feed-forward mechanism in-
sisting of focal myocyte necrosis can be (56).
volving decreased systemic pressure, decreased
RV coronary perfusion, RV ischemia, RV contrac- identified in the RV free wall (50). While However, in the setting of increased
tile dysfunction, and further reduction in cardiac some of these are potentially due to direct pulmonary vascular resistance or ele-
output. The decline is irreversible if pulmonary mechanical disruption of myofibrils or vated left atrial filling pressure, central
vascular impedance is not reduced or RV contrac- focal adrenergic overstimulation, the venous pressure may not be sufficient to
tility is not increased. possible contribution of activation of pro- maintain pulmonary arterial flow and RV

S60 Crit Care Med 2008 Vol. 36, No. 1 (Suppl.)

failure ensues. When Brooks and col- into account the fact that central venous ume depletion, and RV failure only be-
leagues (43) repeated right coronary ar- pressure may be elevated for reasons comes evident with repletion of volume).
tery occlusion in the setting of a modest completely unrelated to the function of Elevated central venous pressure is
increase in pulmonary artery pressure, the RV, RV failure may be defined as “the commonly, although not invariably, asso-
there was a profound reduction in cardiac clinical syndrome resulting from the ciated with other evidence of elevated
output and systemic pressure. In other right heart’s inability to provide adequate body water and salt in the form of periph-
words, under normal circumstances, the blood flow to the pulmonary circulation eral and visceral edema. The failing right
RV free wall’s contribution to circulation at a normal central venous filling pres- heart may dilate, leading to a parasternal
is not terribly important; impairments in sure.” heave, or decreased RV compliance may
RV contractile function may become clin- This definition of RV failure provides a lead to a right-sided third heart sound.
ically significant only when demand on practical means of identifying RV failure Virtually all other signs and symptoms of
the RV increases. clinically: RV failure is not present if right heart failure are a direct conse-
The consequence of these two facts, there is adequate cardiac output and cen- quence of the underlying etiology of RV
that global RV performance is not solely a tral venous pressure is normal. However, failure rather than RV failure per se and
result of RV free wall contraction and that if cardiac output is inadequate, central therefore may or may not be present de-
normal pulmonary vascular resistance is venous pressure is high, RV contractile pending on the etiology. For example, in
very low, is that RV failure does not occur dysfunction is apparent on imaging stud- RV failure due to primary pulmonary hy-
in the absence of elevated pulmonary ar- ies, and abnormalities of LV function are pertension, there may be a loud pulmo-
tery input impedance. This largely ex- not sufficient to explain the clinical syn- nary component to the second heart
plains why Starr et al. (14) found “no drome, RV failure must be present. sound, although this may be lost as RV
increment in venous pressure” and the Clinical RV failure may be due primar- failure worsens and pulmonary artery
hemodynamic consequences of RV infarc- ily to excessive contractile demand or to pressure falls. A tricuspid regurgitation
tion went unrecognized in many early impaired contractile function. However, murmur secondary to RV dilation or tri-
experimental preparations. in general both increased contractile de- cuspid valve incompetence may or may
In summary, RV pressure overload, if mand (pulmonary hypertension) and im- not be present. A large number of signs
sufficiently severe, will inevitably result paired contractile function will be and symptoms of RV failure have been
in RV failure; for all practical purposes, present to some extent. In either case, listed in other reviews (57), but none of
RV failure never occurs in the absence of once the normal compensatory mecha- them is particularly sensitive or specific.
RV pressure overload; and successful re- nisms of the RV (such as Anrep effect or Many patients endure a prolonged pe-
lief of pressure overload will usually ame- circulating catecholamines) have been riod of moderate RV failure before cata-
liorate RV failure, even if manipulation of exhausted, central venous pressure will strophic hemodynamic collapse. The in-
energy supply (e.g., coronary perfusion) begin to rise. Thus, some evidence of vestigation by Guyton et al. (39) provides
is unsuccessful at changing the threshold central venous pressure overload in con- insight into this unpredictable event.
at which RV failure occurs. junction with RV contractile dysfunction With the RV teetering on the edge of its
is universally present in the setting of reserve, any slight impairment in con-
Clinical Syndrome of RV Failure manifest RV failure. tractile function or slight increment in
Elevated central venous pressure ulti- demand (e.g., through an increase in pul-
Cardiovascular disease specialists have mately leads to RV dilation, which, if monary vascular resistance or through an
struggled with the definition of heart fail- modest, may be adaptive through the increase in pulmonary vein pressure) re-
ure for years. Current American College Frank-Starling mechanism. However, as sults in further reduction in RV output,
of Cardiology/American Heart Associa- central venous pressure continues to rise, further impairment of LV filling, impair-
tion guidelines define heart failure as “a further RV dilation becomes maladaptive, ment of RV coronary perfusion, further
complex clinical syndrome that can re- both through an increase of RV end- reduction in RV contractile function, and
sult from any structural or functional systolic wall stress and consequent im- rapid decompensation progressing to
cardiac disorder that impairs the ability pairment of contraction and through im- death.
of the ventricle to fill with or eject blood” pingement on the LV via the interventricular Absence of pulmonary congestion
(1). This very broad and nonspecific def- septum. Finally, output from the RV will with elevated central venous pressure is
inition was developed to accommodate fall due to ischemia, with progressive sys- often considered to be the most specific
the fact that LV dysfunction alone may temic hypotension, or output from the finding of isolated RV failure; however,
not result in clinical manifestations of LV will begin to fall through a direct severe RV failure may result in elevated
heart failure and that, conversely, clinical impediment to LV filling, and the down- left ventricular end diastolic pressure due
manifestations of heart failure may occur ward spiral previously described rapidly to interventricular septal shift, so at least
in the absence of demonstrable LV sys- ensues. in theory pulmonary venous pressure
tolic dysfunction. Similarly, RV dysfunc- No single sign, symptom, or labora- may be able to rise to the point of causing
tion alone does not usually result in clin- tory test can perfectly identify all episodes pulmonary congestion (58).
ical right heart failure, while clinical of RV failure. Nevertheless, it is probably
right heart failure may occur in the ab- fair to say that decompensated RV failure Clinical Conditions Resulting in
sence of preexisting RV contractile dys- is not present if jugular venous pressure Increased RV Pressure
function. is normal, regardless of any measured
An essentially universal feature of index of RV contractile function (al- Numerous clinical conditions can re-
clinical LV failure is an elevation of left though in some cases RV dysfunction sult in excessive RV pressure and/or in-
atrial pressure. By analogy, and taking may be occult during intravascular vol- creased pulmonary vascular resistance.

Crit Care Med 2008 Vol. 36, No. 1 (Suppl.) S61

Most common in the critical care unit are sary since hypoxemia may worsen as a filling pressure automatically requires a
acute increases in small-vessel pulmo- result of increased perfusion of poorly corresponding increase in mean pulmo-
nary vascular resistance due to hypoxia ventilated lung, and trials of these agents nary artery pressure to maintain the
and pulmonary vascular constriction have been disappointing (67). Scattered same cardiac output at the same pulmo-
(59), direct lung injury in acute respira- reports of beneficial acute effects of nary vascular resistance.
tory distress syndrome (2), and positive agents more commonly used in chronic During hemodynamically significant
pressure ventilation (60). Obstruction of pulmonary hypertension, such as bosen- RV infarction, right atrial function be-
the pulmonary artery circulation, such as tan and sildenafil (68), while encourag- comes much more important to maintain
with pulmonary embolism or direct pul- ing, have not yet been verified in well- cardiac output. Loss of atrioventricular
monary artery constriction or injury, controlled trials. An experimental report synchrony in the setting of RV infarct and
may result in sudden sustained increases that levosimendan might improve pul- inferior myocardial infarction may con-
in pulmonary artery pressure. Adult con- monary hemodynamics (69) showed tribute to cardiogenic shock; in such
genital heart disease is another potential promise in a small clinical study (70), but cases, synchronous atrioventricular pac-
cause of RV failure due to pressure over- this agent does not yet have an estab- ing may be helpful (11).
load, although such patients appear to lished indication for treatment of acute RV failure due to RV infarct may im-
have a better prognosis than those with RV failure. prove spontaneously over time (71). The
primary pulmonary hypertension (61). A reason for this is not entirely clear; how-
sudden increase in RV afterload may oc- Conditions Resulting in ever, some investigators have argued that
cur in cardiac grafts transplanted into a Decreased RV Contractile the RV is more tolerant of ischemia than
patient with long-standing heart failure Function the LV because of lower oxygen demand,
and pulmonary hypertension (7), and car- collateral coronary flow, or other reasons.
diopulmonary bypass may precipitate Decreased RV contractile function Alternatively, it may be that increased RV
acute pulmonary hypertension and RV may develop due to decreased energy sup- afterload in the setting of acute LV infarct
failure through poorly understood mech- ply (coronary ischemia) or other primary improves with resolution of LV abnor-
anisms (62). abnormalities of the contractile appara- malities, permitting the underlying con-
Acute pressure overload can occur tus. RV ischemia may develop as a conse- tractile abnormality of the RV to be better
suddenly or in the context of long- quence of severe pulmonary hypertension tolerated. Regardless, hemodynamically
standing RV pressure overload. Long- and/or decreased systemic pressure but significant RV infarct confers a high mor-
standing RV pressure overload may result more commonly occurs as a consequence tality, and reperfusion therapy directed at
in RV hypertrophy, and patients with of an acute coronary syndrome. The RV RV myocardial infarction has been shown
long-standing pulmonary hypertension usually receives its blood supply via the to be effective at reducing morbidity and
and Eisenmenger syndrome may tolerate right coronary artery. Since the right mortality (72).
astonishingly high, even suprasystemic, coronary artery is dominant (i.e., supplies Primary abnormalities of right heart
RV pressures with minimal evidence of the inferior wall of the heart) in approx- function may occur due to the long-term
RV failure (63). Conversely, relatively imately 90% of individuals, the over- consequences of pressure overload, as de-
modest increases in RV pressure may pre- whelming majority of clinically evident scribed here. In addition, toxic circulat-
cipitate sudden RV failure in patients RV infarcts occur in the setting of inferior ing factors may impair RV function de-
with no preceding pulmonary hyperten- myocardial infarction. RV ischemia may spite normal nutrient supply during
sion or when RV contractile reserve is occur in up to half of all inferior wall septic shock (3).
already depressed. Because the transition myocardial infarctions, although hemo-
from compensated to decompensated RV dynamic compromise due to RV dysfunc-
failure may be abrupt, it is often not pos- tion is apparent in a relatively small pro- Miscellaneous Causes of RV
sible to identify the specific event that portion of these (11). RV myocardial Failure
ultimately led to clinical deterioration in infarction is often unrecognized; the syn-
any given case. drome was not well appreciated until RV failure usually requires either a
Treatment of pulmonary hypertension Cohn and colleagues’ (15) report in 1974. large increase in RV afterload or a modest
per se in the critical care setting will not While isolated RV infarcts may occur, due increase in RV afterload coupled with a
be discussed in detail here. Few therapeu- either to thrombosis of a nondominant reduction in RV contractility. Although
tic interventions have proven to be of RCA or to an isolated RV septal branch, as volume overload, either from atrial septal
significant value. Thrombolysis and discussed previously, isolated decreases defect, tricuspid regurgitation, or pul-
thrombectomy for selected patients with in RV contractile function may be clini- monic regurgitation, is commonly con-
pulmonary embolism may or may not be cally silent if elevations in RV outflow sidered a cause of RV failure, in general
helpful (64 – 66). RV failure due to ele- pressure are not present. Conversely, this will not cause RV failure acutely in
vated left-sided filling pressures may re- since inferior myocardial infarction may the absence of increased pulmonary ar-
spond to left heart failure treatments, cause LV dysfunction and elevated LV fill- tery pressure. For example, resection of
such as diuresis, afterload reduction, pos- ing pressure, the combination of a simul- the tricuspid or pulmonic valves for iso-
itive inotropes, revascularization, and in- taneous decrease in RV contractile func- lated endocarditis frequently does not re-
tra-aortic balloon counterpulsation. Pul- tion and an increase in pulmonary artery sult in decompensated RV failure (73, 74).
monary hypertension from hypoxic input impedance (via an increase in LV Many patients tolerate high flows from
pulmonary vasoconstriction may respond and left atrial filling pressure) provides atrial septal defect without difficulty (75).
acutely to vasodilators, such as prostacy- the perfect substrate for development of However, conditions such as acute ven-
clin or nitric oxide, but caution is neces- acute RV failure, since an increase in LV tricular septal defect, which simulta-

S62 Crit Care Med 2008 Vol. 36, No. 1 (Suppl.)

neously increases pulmonary flow and tile function appears abnormal on im- interventricular septum. Digoxin has
pressure, may rapidly result in RV failure. aging studies. been suggested as an effective inotropic
Pulmonary hypertension and RV fail- agent in the setting of RV failure from
ure may be attributed to LV diastolic dys- Treatment of Refractory RV pulmonary hypertension, although the
function, but identifying the inciting Failure beneficial effects are modest, and it is
cause can be difficult. As the RV dilates, unknown whether they are sustained
there may be a shift of the interventric- In acute RV failure, the underlying (82). Other inotropic agents, such as nor-
ular septum toward the LV, resulting in cause of RV failure should be addressed to epinephrine and levosimendan, may be
impaired LV filling and a shift to a higher the extent possible. If treatment of the effective in part through their positive
point on the LV pressure-volume rela- underlying etiology is impossible or un- inotropic effects and in part through fa-
tion. Doppler echocardiography of the LV successful, attempts should be made to vorably modulating the interaction be-
may then become consistent with im- optimize RV loading conditions. Even in tween the RV and the pulmonary vascular
paired relaxation, but this is a manifesta- the setting of intrinsic RV contractile dys- system (so-called ventricular-vascular
tion of interventricular interaction rather function, the RV may have some compen- coupling) (47, 69, 70).
than a direct abnormality of LV myo- satory reserve through the Frank-Star- In a few cases, RV assist devices (83)
cardial function or material properties ling relation. Thus, volume loading may and even intra-aortic balloon counterpul-
(76). Thus, it may be difficult to deter- improve RV output. However, since RV sation devices placed in the pulmonary
mine whether abnormalities of LV dia- contractile failure is directly related to RV artery (84) have been used with variable
stolic function are primarily a cause or wall stress, excessive volume loading may success.
an effect of RV failure without some paradoxically worsen RV contractile func- As described previously, limited data
means for temporarily altering RV load- tion through RV dilation; the subsequent suggest that proteases may contribute to
ing conditions. impediment to LV filling through the in- ongoing, or even acute, RV contractile
Other causes of RV failure, such as RV terventricular septum or through peri- failure in some settings; however, evi-
dysplasia and infiltrative cardiomyopa- cardial restriction can result in worsened dence supporting this hypothesis has
thies, are relatively rare but should be total cardiac output, ultimately leading been developed only in animal models
considered when no other etiology for RV once again to the vicious cycle of RV (52, 85).
failure can be identified. hypoperfusion and further impairment of
RV contractility. Once central venous CONCLUSIONS
pressure has exceeded 10 –14 mm Hg,
Conditions Masquerading as RV further volume loading is usually detri- RV failure occurs when the RV is un-
Failure mental (77, 78). However, optimal load- able to provide adequate blood flow
ing conditions can be difficult to deter- through the pulmonary circulation at a
Several other settings may mimic RV mine. Invasive hemodynamic monitoring normal central venous pressure. The un-
failure but would not reasonably be con- (e.g., central venous or pulmonary artery derlying physiology of the RV explains
strued as an abnormality of right heart catheters) may be useful in testing vari- why its response to stress is fundamen-
function. First, elevated central venous ous interventions. For example, if cardiac tally different from the LV response to
pressure, along with clinical signs of RV output falls in response to an increment stress and provides a framework for un-
failure, may be present in the setting of in central venous pressure, volume re- derstanding the clinical manifestations of
pure volume overload (e.g., excessive duction with a diuretic agent or renal and the potential therapeutic approaches
postoperative volume repletion, acute re- replacement therapy may be indicated de- to RV failure. RV failure is inherently an
nal failure); in these cases, RV contractile spite systemic hypotension. Echocardiog- unstable condition, with a tendency to-
function is normal, and intravascular vol- raphy may be helpful in revealing ward abrupt and irreversible decompen-
ume reduction eliminates the secondary whether further RV volume loading is sation. Empirical therapy, such as vol-
findings without impairing overall car- having an adverse effect on LV geometry. ume loading, may be counterproductive
diac output and should not be considered Once any underlying cause of RV con- and precipitate sudden decompensation.
to be a result of RV failure. Second, direct tractile failure has been addressed and The complex interaction of the RV and
compression of the RV, from pericardial loading conditions optimized, attempts at the LV makes clinical assessment of RV
effusion, pericardial fibrosis, tumor, or improving RV contractile function may failure and its response to therapy diffi-
massive pleural effusion, may impair RV be attempted. Dobutamine has been cult; noninvasive imaging or invasive he-
filling, resulting in decreased RV output shown to have beneficial effects on RV modynamic monitoring may be necessary
simultaneously with increased central ve- contractile function in pulmonary hyper- to identify the etiology of RV failure and
nous pressure. Imaging studies are most tension without affecting pulmonary vas- determine optimal therapy. Further re-
helpful in eliminating these as causes of cular resistance (79). During RV infarc- search into the mechanism of RV con-
elevated central venous pressure. Lower tion, dobutamine has been shown to tractile dysfunction in the critical care
extremity edema, while commonly attrib- exert overall favorable hemodynamic ef- setting is necessary, since current thera-
uted to right heart failure, is often due to fects and is considered an agent of choice peutic options are extremely limited.
extrinsic compression of venous or lym- (78, 80); however, while dobutamine may
phatic return, renal failure, alterations in improve overall hemodynamics without
the renin-angiotensin system, or drug worsening RV ischemia, it likely does not
therapy. If central venous pressure is enhance function of ischemic segments 1. Hunt SA, Abraham WT, Chin MH, et al: ACC/
normal, edema is generally not attrib- of the RV (81) and instead improves func- AHA 2005 guideline update for the diagnosis
utable to RV failure even if RV contrac- tion of nonischemic regions of the RV or and management of chronic heart failure in

Crit Care Med 2008 Vol. 36, No. 1 (Suppl.) S63

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