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Advances in Heart Failure
Mind-Body Medicine in Chronic Heart Failure
A Translational Science Challenge
Sitaramesh Emani, MD; Philip F. Binkley, MD, MPH
T
patients with congestive heart failure. Does the current value
or future potential of heart/brain medicine in fact justify the
creation of a new transdisciplinary and translational scientific
field of study and realm of clinical practice?
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he connection between the mind and body has often been
regarded by Western medicine as something ascribed to
the mystical and a topic residing outside the scope of
scientific thought. However, it has been a long-term integral
tenet in the medical practice of many other cultures.1 It could
be argued that the reliance of Western thought on the concept
of dualism in which Plato, Aristotle, and other classical
philosophers separated the body as a physical entity from the
mind as a “spiritual” force has ultimately discouraged health
care professionals from serious consideration of what has
appeared to be a vague and even mysterious connection
between the mind and body.2 Nevertheless, a growing body
of research has progressively identified the mechanistic
building blocks that demystify the reciprocal mind-body
interaction and show that it is clearly a physical rather than
mystical connection. Descriptions of neurovisceral changes in
which readily demonstrated structural alterations in the brain,
heart, and other organ systems arise in response to stress and
a variety of emotional states provide further demonstration of
the true organic mind-body connection. Perhaps the most
abundant mechanistic data pertain to the brain-heart interaction under both conditions of health and a variety of cardiovascular disease states. The increasing body of evidence for
these important interactions has in fact led to the call for
dedicated integrated fields such as neurocardiology or behavioral cardiology.3–5
It is therefore important to examine the current state of our
understanding of mind-body interactions including the experimental evidence identifying the physiological basis for these
interactions and their impact on clinical outcomes. As will be
shown, there is a significant overlap between the pathophysiologic mechanisms of congestive heart failure and the major
effectors of mind-body connections. This provides the basis
for potential new therapies that incorporate mind-body medicine. However, it must be determined whether our current
understanding of the mechanisms governing mind-body interactions is sufficient to proceed with routine application of
mind-body therapies in patients with heart failure. Further,
are patients with heart failure amenable to interventions that
act on the “heart-mind” axis in the same way as those without
heart failure? This review will examine this understanding in
an effort to determine whether current evidence justifies
incorporation of mind-body medicine in the treatment of
The Mechanistic Building Blocks Governing
Mind-Heart Interactions
The Autonomic Nervous System
The autonomic nervous system is probably the earliest and
most closely studied effector limb of the mind-heart interaction. As early as 1915, Eppinger and Hess3 proposed that
behaviors may differ between individuals because of a
predominance of sympathetic or parasympathetic activity.
This predominance determined the physiological as well as
behavioral responses to environmental stimuli and could
predispose individuals to disease states such as hypertension
or asthma. As discussed in excellent reviews by Samuels,5,6
the impact of stress and intense emotion on cardiovascular
function was submitted to credible scientific thought and
investigation in 1942 by Walter Cannon7 in a report reviewing what has been called “Voodoo Death.” This report
described episodes of sudden death recounted from a variety
of cultures which were apparently secondary to profound fear
or emotion often inspired by superstitious beliefs. Cannon
speculated that death resulted from enhanced sympathetic
nervous system and adrenal responses to intense emotional
stress and a belief in a power over which the victim had no
control. The events discussed in his article are in fact early
descriptions of what has come to be known as sudden
unexpected death, and a myriad of evidence has supported the
major role of the sympathetic nervous system in mediating
these episodes.5,6
Foundation evidence for the role of the autonomic nervous
system in stress-induced sudden cardiac death has been
provided by a variety of animal models. A wide range of
stressors have been shown to be associated with sudden
death.5,8,9 In general, interventions that interrupt release of
intracardiac but not circulating norepinephrine prevent stressinduced sudden death.
Autonomically mediated mind-body interactions constitute
one of the fundamental links between emotional states and
cardiovascular disease in human beings.9 –11 Perhaps the most
Received March 11, 2010; accepted August 16, 2010.
From The Ohio State University Division of Cardiovascular Medicine and the Dorothy Davis Heart and Lung Research Institute, Columbus, Ohio.
Correspondence to Philip F. Binkley, MD, The Ohio State University, 473 W 12th Ave, Columbus, OH 43210-1252. E-mail [email protected]
(Circ Heart Fail. 2010;3:715-725.)
© 2010 American Heart Association, Inc.
Circ Heart Fail is available at http://circheartfailure.ahajournals.org
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DOI: 10.1161/CIRCHEARTFAILURE.110.951509
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dramatic example of this connection is in the so-called
“broken heart syndrome” or Takotsubo cardiomyopathy.3,5,12
This syndrome of acute and generally reversible heart failure
with a characteristic pattern of ventricular contraction abnormalities appears due in part to increased sympathetic activity
producing either direct myocardial damage or contractile
dysfunction resulting from diffuse coronary vasospasm. A variety of other stress and distress related conditions have been
similarly shown to be characterized by significant abnormalities
of the autonomic nervous system. Prominent among these is
depression, which has been shown to be associated with sympathetic and parasympathetic imbalance and accordingly an
environment that can promote coronary artery disease, congestive heart failure, and sudden death.10,13–22
Although sustained increases in sympathetic activity are
known to adversely affect cardiovascular function, inappropriately enhanced activity of the parasympathetic nervous
system may be similarly damaging. ECG recordings obtained in
some rat models of stress show that sudden death is mediated by
profound bradycardia progressing to asystole.5,6,8 This suggests
that extreme stress may produce an “autonomic storm”
characterized by excessive activation of both the sympathetic
and parasympathetic nervous systems. Such malignant parasympathetic activity has been shown to play a role in human
disease. In a study by Luu et al,23 62% of deaths in patients
with advanced heart failure awaiting cardiac transplantation
were due to profound bradycardia, suggesting malignant
vagotonia as a cause of death.
The autonomic control of mind-body interactions has
special relevance to patients with heart failure who characteristically have marked parasympathetic/sympathetic imbalance.24,25 Can stress produce autonomic imbalance that in fact
leads to the occurrence or progression of ventricular failure?
In turn, can the autonomic imbalance in heart failure that
parallels that found in stress states in fact promote distress?
The significant coincidence of congestive heart failure and
depression13,26 and data indicating that depression may precede the appearance of congestive heart failure27,28 suggest
that this may be the case. Mind-body interactions that
interrupt this reciprocal autonomic dysfunction may therefore
benefit both conditions.
How Are Emotions and Stress Connected to
the Heart?
The autonomic nervous system is classically regarded as an
“involuntary” system regulated by hypothalamic centers and
thus beyond direct conscious control.5,29,30 Nevertheless, it
appears that conscious effort can alter cardiovascular function
acting through the so-called involuntary autonomic nervous
system.5,30,31 However, the question remains how an involuntary
nervous system may mediate the cardiovascular responses that
characterize conscious mind-heart interactions and the physiological response to various mental states. Increasing understanding of the relationship of cortical function to autonomic control
centers provides insight into possible mechanisms for volitional
control of cardiovascular function.5,29,32–39
Recognition of the role of cortical control of autonomic
function dates to at least 1869 when John Hughlings Jackson40,41 observed significant cardiovascular changes during
major motor seizure activity. He reasoned that cortical centers
governed not only voluntary motor movements but vasomotion and visceral motor activity. Over the years, a variety of
stimulation, ablation, and neuroanatomic studies have defined
cortical regions that have projections to centers having direct
control over sympathetic and parasympathetic activity.40
These cortical regions include the insular cortex, the somatic
and motor sensory cortex, the medial prefrontal cortex, and
the anterior cingulate cortex. As an example, the insular
cortex has been shown to have a “representation of the
autonomic nervous system5” as well as “viscerotopic sensory
inputs,”29 including those from the cardiovascular system.
Studies in animal models using both insular cortex stimulation and localized destructive lesions and studies in humans
who have had insular strokes suggest that the right posterior
insular cortex modulates cardiovascular sympathetic control
and the left posterior insular cortex modulates parasympathetic function.29,37–39,42– 47 In these models and in human
subjects, stimulation of the left insular cortex produced ST
changes, widening of the QRS complex, complete heart block
leading to asystolic death, and contraction band necrosis (see
below).42– 44 The cardiovascular regulatory capacity of the
insular cortex suggests one pathway for volitional cardiovascular control that may be operative in mind-heart interactions.
Similarly, the anterior cingulated cortex (ACC) has been
shown to serve as an interface between cognitive and emotional inputs with projections to autonomic control centers.40,48 It therefore plays a critical role in adaptive responses
to the internal and external environment and has been shown
to mediate these responses through autonomic pathways. The
ACC is functionally, anatomically, and histologically designed to integrate the emotional and cognitive activity of the
mind with the physiological responses of the cardiovascular
system as well as other organ systems.
Functional imaging studies in humans have demonstrated
that cortical centers such as the ACC and prefrontal cortex
constitute a network integrating emotional and cognitive
components of the mind with autonomic cardiovascular
control.49 Integrative body-mind training has been shown to
increase parasympathetic activity, increase electroencephalographic theta waves originating from these regions, and
increase blood flow to these central nervous system centers.
Therefore, changes in cognitive and emotional state produce
changes in autonomic cardiovascular control producing what
some authors have called “brain-body harmony.”49 These
functional changes can be accompanied by structural central
nervous system changes as evidenced by destructive lesions
in the ACC in patients with depression who have had a
myocardial infarction.50
Data for more than a century have confirmed that cortical
centers integrating emotional responses and cognitive states,
which constitute in part what is regarded as the “mind,” have
a direct connection to autonomic function. Autonomic control
is not simply based on reflex responses but is tightly linked to
cortical function. It would therefore be surprising if positive
and negative emotional and cognitive states did not have an
impact on cardiovascular function and the evolution of
cardiovascular diseases. The cortical influence over auto-
Emani and Binkley
nomic centers supports the belief that cardiovascular function
and disease risk can be altered through conscious efforts.
Inflammatory and Neuroimmune Pathways
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Both cardiovascular disease and mental distress are associated with activation of proinflammatory mechanisms. The
commonality of these mechanisms identifies inflammatory
pathways as a major mediator of reciprocal mind-heart
interactions. In addition, inflammation and autonomic activity are closely tied promoting states of neuroimmune activation that are operative in governing both psychological and
cardiovascular function.
Although the end-organ effects of proinflammatory cytokines are well recognized, the immune system also serves as
a communication network between the central nervous system and other organ systems.51–54 Cytokines produced and
released in the periphery can diffuse into the central nervous
system, where they in many ways function as neurotransmitters.51,55–59 Importantly, proinflammatory cytokines, either
from the periphery or produced within the central nervous
system, can stimulate the production of norepinephrine and
sympathetic activity.60,61 However, beyond the role of circulating cytokines which must diffuse through the blood-brain
barrier to the central nervous system, Tracey and other have
shown that proinflammatory cytokines convey signals
through the peripheral nervous system constituting a system
of rapid communication from the periphery to the central
nervous system.54 It is apparent that cytokine signaling via the
Vagus nerve can occur with cytokine concentrations that fall
well below the circulating levels required to cross the
blood-brain barrier.54,62– 64
In response to peripheral signaling by cytokines, the
autonomic nervous system can in turn activate both proinflammatory and antiinflammatory mechanisms. Bierhaus
et al65 showed that stress-induced increases in catecholamines
and cortisol rapidly increase NF-␬␤ expression in peripheral
blood monocytes that subsequently increase cytokine production. Further, NF-␬␤ production could be inhibited by ␣- and
␤-adrenergic blockade demonstrating the role of sympathetic
activation in triggering proinflammatory states.
The description of a “cholinergic antiinflammatory reflex”
exemplifies the orchestration of the mind-body communication network integrating inflammation and autonomic function.54,66 Studies by Tracey et al54,55,66 have shown that
stimulation of the efferent Vagus nerve reduces both cytokine
production and release by cells of the reticuloendothelial
system. The inflammatory reflex consists of stimulation of
vagal afferent fibers by cytokines, as discussed above, resulting in an augmentation of central parasympathetic outflow
via the Vagus nerve and consequent reduction of cytokine
production and release. This system constitutes a servocontrol
mechanism that keeps inflammation in check preventing the
deleterious effects of excessive proinflammatory stimulation.
Conversely, reduced parasympathetic activity, as occurs in
disease states such as congestive heart failure, can result in a
failure to inhibit proinflammatory cytokine production enhancing the risk of end-organ inflammatory damage and has
been shown to be a possible cause of increased proinflammatory cytokines in human subjects.67
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The evidence is clear that unrestrained proinflammatory
stimulation is associated with cognitive and mood changes. A
variety of animal models have shown that acute or chronic
stress results in increased proinflammatory cytokine production accompanied by behavioral changes and cognitive impairment.55,68,69 These studies parallel investigations in human subjects that show a significant association between
distress and depression and immune activation.70,71 Similar to
animal studies, administration of cytokines to human subjects, such as interferon-␣, or stimulation of the immune
system through vaccination results in depressed mood and
activation of the central nervous system in regions known to
affect cognitive function and mood.72–74
Studies by Kiecolt-Glaser and Glaser73,75–77 exemplify the
connection between chronic stress conditions in human subjects and increases in proinflammatory cytokines. Aging care
givers of patients with dementia were followed over a 6-year
period with measurement of circulating concentrations of
interleukin-6 (IL-6). Progressive increases in IL-6 concentrations were seen in all patients over time, but the rate of
increase was significantly higher in members of the care giver
cohort, who were under increased stress.76 Similar increases
in IL-6 were seen in other stress states such as marital
discord.73,77 These and similar studies demonstrate one pathway by which acute or chronic stress can lead to immune
system activation with resultant inflammatory cardiovascular
damage. Especially considering the apparent role of inflammation in the pathogenesis of congestive heart failure,78,79
these data suggest an intriguing link between stress and the
evolution of ventricular dysfunction. Preliminary data from
Ferketich et al80 support this link in a study in which patients
with symptomatic reduction in ventricular systolic function
were screened for symptoms of depression using the Beck
Depression Inventory (BDI). In these patients, there was a
significant linear correlation between BDI score and concentration of tumor necrosis factor-␣. It can be safely said that
the coincidence of depression and heart failure likely creates
a proinflammatory environment that can promote the progression of both disorders.
A variety of effectors of both the proinflammatory cascade
and autonomic nervous system likely play a role in patients
with congestive heart failure. As an example, nitric oxide,
which is dysregulated in congestive heart failure, plays a role
in modulating autonomic function and in mediating inflammation.81 Reduction in nitric oxide production in congestive
heart failure has been associated with abnormalities in autonomic balance.82– 87 Recent studies of a loss of function
polymorphism of the promoter for nitric oxide synthase
demonstrate that it is indeed tightly linked to autonomic
function in patients with congestive heart failure.88 Therefore,
nitric oxide exemplifies a family of mediators of both
inflammatory and autonomic pathways that regulates mindbody interactions and that is especially relevant in patients
with congestive heart failure.
Environmental Factors Contributing to
Mind-Heart Interactions
Although mind-body interactions are often considered a
self-contained, closed-loop process, there is evidence that
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Figure. Proposed remodeling of mind-heart interactions leads to progressive increases in neuroimmune activation in response to
stress. In a state such as depression, there is increased sympathetic activity, decreased parasympathetic activity, and activation of
proinflammatory pathways. In response to stress, there is further activation of the sympathetic nervous system and proinflammatory
pathways and further withdrawal of parasympathetic activity. This results in an environment that promotes sudden cardiac death and
vascular and myocardial injury.
external factors, such as infectious agents, may play a role in
governing these interactions. A progression of studies has
shown a role for Epstein-Barr virus (EBV) infection in
mediating altered mood through cytokine stimulation.75,89 –93
An early viral protein, dUTPase, produced even during
incomplete replication of EBV, has been shown to stimulate
peripheral blood mononuclear cells to produce IL-6 and other
cytokines. A strong association between the titer of dUTPase
antibody and concentration of circulating IL-6 was found in
the above noted study of caregiver stress. Therefore, reactivation of EBV, which is a common latent infection, appears
to result in stimulation of production of IL-6 and other
proinflammatory cytokines that can mediate both depression
and cardiovascular injury. This provides a model by which an
external infectious agent may modulate mind-body interactions through promotion and even initiation of the inflammatory “network of communication.”
Neurovisceral Regulation: Anatomic Consequences
of Mind-Heart Interactions
Anatomic and structural changes in the heart and the brain
accompany states of mental stress as well as different states of
concentration and meditation. These anatomic changes solidify the physical connection between the mind and body
further demonstrating the reality of these interactions.
In the myocardium, psychological stress has been demonstrated to produce classic changes of contraction band necrosis. Studies of hypothalamic stimulation in animal models
demonstrated ECG changes resembling those seen in humans
with central nervous system hemorrhage or infarction followed by arrhythmic death. Examination of the myocardium
in these animals demonstrated what may be interpreted as
contraction band necrosis resembling the lesions seen in
ischemic infarction.5,6,94,95 Similar lesions have been pro-
duced without central nervous stimulation but with psychic
stress.5,96 Studies in human subjects have reported these
myocardial lesions in patients with psychiatric illness or
subarachnoid hemorrhage.97,98 The finding of increased troponin levels in patients with intracerebral hemorrhage and the
demonstration of wall motion abnormalities in patients without coronary artery disease who have had an insular stroke
further speak to the structural myocardial damage that can be
mediated by the central nervous system.38,39
Conversely, structural changes in the central nervous
system have been shown to accompany differing psychological states. Chronic depression has been associated with
decreased hippocampal volume, which is related to the
duration of depression.99,100 In contrast to the damage and
volume loss that may accompany stress, practitioners of
various forms of meditation have increased cortical thickening, especially in centers involved with attention and sensory
processing including the prefrontal cortex and the right
insular cortex.101,102 Corresponding to these observations,
functional magnetic resonance studies have shown increased
activity in specific regions of the brain in subjects who have
practiced mediation for differing periods of time as compared
with control subjects.102
Associated with these anatomic changes is evidence for a
remodeling of mind-body interactions, which evolves with
repeated or sustained stress. This remodeling may “prime”
the systems governing mind-body interactions to produce an
exaggerated responses to stressful stimuli (Figure). The
existence of this remodeling process is supported by studies
showing that subjects with early life trauma have significant
increases in baseline and stress-induced neuroimmune activation.71 A variety of investigations have shown that episodes
of depression are not isolated but demonstrate a pattern of
repetition suggesting evolution of pathways that progres-
Emani and Binkley
sively facilitate depressed mood.10 Indeed, many of the same
mediators of mind-heart and mind-body interactions are
operative in central nervous system structural remodeling.
Chief among them are cytokines that are known to act as
neural trophic factors but which can over time mediate
apoptosis and reduction of tissue volume.55
It may be speculated that remodeling of mind-heart interactions results in an increasing magnitude of stress responses
that lead to permanent detrimental end organ damage. As an
example, if repeated stress produces even small areas of
contraction band necrosis over time, could this ultimately
result in ventricular systolic dysfunction and dilation? Further, would such remodeling of mind-heart interactions make
patients less susceptible to the potential beneficial effects of
interventions such as biofeedback, meditation, or other mindbody therapies?
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Interventions Targeting Mind-Heart Interactions
A rich mechanistic foundation for mind-body and mind-heart
interactions has now been established. This then raises the
question as to whether there are volitional modifications of these
interactions that can prevent and treat disease states. There is
now a wealth of clinical, mechanistic and outcome trials that
attempt to address this issue although the quality of these
investigations is highly variable.103 Relatively few of these
specifically address prevention or treatment of congestive
heart failure, although many have addressed risk factors for
cardiovascular diseases in general, and may lead to further
observations in the setting of ventricular failure. The mind-body
interventions that have been explored include biofeedback methods, meditation techniques, and relaxation therapies.
Biofeedback
Biofeedback interventions can be broadly defined as those in
which the subject learns to consciously regulate a given
physiological “target” variable.104 Often, the ability to regulate this specific variable is accompanied by modification of
other elements of the mind-heart interaction.
One of the most detailed studies of biofeedback is an
investigation by Moser et al105 performed in patients with
advanced congestive heart failure. Participants were randomized to either biofeedback intervention or to control conditions. The biofeedback cohort successfully increased skin
temperature, and compared with control subjects, significantly increased cardiac output, reduced systemic vascular
resistance, and decreased respiratory frequency. The mechanism by which the biofeedback intervention produced these
changes in hemodynamic variables is not certain but may
have resulted from biofeedback associated alterations in
autonomic vascular control.
Similarly, short-term studies of slow breathing in patients
with congestive heart failure have shown immediate changes
in baroreflex sensitivity measured by the interaction of heart
rate and blood pressure variability.106 For the congestive heart
failure group as a whole, there was a decrease in systolic and
diastolic blood pressure during slow breathing. This and other
studies suggest that there is the capacity to consciously
regulate autonomically governed mind-heart interactions
through alteration of baroreflex function.104,107–109
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Meditation and Relaxation Techniques
Meditation and relaxation techniques have been investigated
as other methods to beneficially alter mind-body interactions.
Meditation techniques may be broadly classified in three
categories. First are those techniques that require concentration on a specific external object or internal sensation (such as
breathing) in preparation for focused reflection, exclusion of
unwanted thoughts, or a quiet state of awareness.103,110,111
Transcendental meditation may be the most commonly recognized form of this category of meditation. Second are those
that rely on increased awareness or mindfulness of the
external and internal environment and exclusion of conscious
interpretations or evaluations of events and sensations in these
environments. Third is compassion mediation which incorporates stages of the above practices with the ultimate goal of
eliminating negative evaluations and fostering positive attitudes
toward the self and progressively to others in one’s surroundings.110 All of these require self-monitoring and progressive
practice to achieve a desired state of awareness.
Other techniques rely on eliciting the relaxation response,
which shares many features of the above mediation techniques. In essence, relaxation techniques consist of focused
attention, a passive nonevaluative approach to thoughts,
relaxation of muscle tone, and a nondistracting environment.112–114 The hallmark of the relaxation response is a
reduction in sympathetic nervous system activity.
Only a relatively small number of outcome studies have
examined the above or related mind-body interventions in
patients with congestive heart failure. However, a number of
studies have investigated both cardiovascular and clinical
outcomes following programs of meditation or relaxation
techniques. For example, it is estimated that there have been
more than 600 studies published examining the impact of
transcendental meditation on cardiovascular disease.115 A
review of selected studies of these techniques in patients
without heart failure provides proof of concept that they may
be effective in altering mind-heart interactions in patients
with ventricular failure.
Barnes et al116 examined blood pressure and noninvasively
measured cardiac output in adults without known cardiovascular disease who practiced transcendental meditation. Compared with a control group using relaxation methods, those
practicing transcendental meditation had decreases in systolic
and diastolic blood pressures, increases in cardiac output, and
decreases in systemic vascular resistance during meditation.
Similar results have been reported in adolescents with blood
pressures in the upper percentiles of normal.117,118 The
capacity to alter vascular tone and blood pressure may extend
to perhaps all forms of meditation. A 6-week trial of yoga and
meditation demonstrated significant reductions in heart rate
and blood pressure and evidence for endothelium-dependent
vasodilation in the intervention group.119
It is probable that mediation exerts its effect on vascular
control through autonomic mechanisms. This has been specifically examined by measurement of heart rate variability
and noninvasive measures of the preejection period (a surrogate for sympathetic activity) in a study of mindfulness
meditation.119 In subjects practicing this form of meditation,
there was coactivation of the sympathetic and parasympa-
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thetic nervous systems, a relative unusual event. This demonstrates the profound effect of this form of meditation on
autonomic function which has been suggested in other studies
and for other forms of meditation.49,120,121
In addition to their influence on autonomic function,
meditation and related techniques appear to influence the
immune component of mind-body interactions. In a recent
study, investigators measured markers of immune function in
healthy women stratified by their expertise in the practice of
hatha yoga122 and found that experienced practitioners had
lower levels of IL-6 and that novices had a greater odds of
having detectable C-reactive protein. Similar results have
been reported in a study of compassion mediation, in which
expert practitioners were found to have lower social stressinduced levels of IL-6.110
These representative studies demonstrate that the various
elements governing mind-body and mind-heart interactions
can be consciously influenced by practices such as meditation. Even the immune system, which may appear to be far
beyond the influence of conscious thought, can be regulated
through conscious effort and meditative practices. The studies
that have targeted patients with congestive heart failure
suggest that this may be the case in at least selected patients
with ventricular dysfunction.
Can Mind-Body Interventions Alter the Course of
Congestive Heart Failure?
Does the fact that meditation and relaxation techniques
modify mind-body interactions in non– heart failure populations imply that these techniques can serve as effective
complementary therapies in patients with ventricular dysfunction? As the severity of ventricular dysfunction
progresses, is the remodeling of mind-body interactions
advanced to the degree that they are irreversible? In severely
ill patients, including those with heart failure, heart rate and
blood pressure do not correlate with the severity of anxiety.123
This implies that the underlying disease process of congestive
heart failure may have already established a fixed autonomic
set point which is not readily altered by meditation or
relaxation therapies.
Among the relatively small studies that have specifically
addressed patients with heart failure, Jayadevappa et al111
examined 23 African American subjects hospitalized for
heart failure who were randomly assigned to a program of
transcendental meditation or health education. After 6
months, the transcendental mediation group had a significant
increase in the 6-minute walk distance as well as improvement in depression scores and measures of quality of life. In
addition, the meditation group was found to have a reduction
in hospitalizations over the 6-month study period. Yeh et
al124,125 used Tai Chi as a specific meditative style in heart
failure patients in 2 different studies and found significant
improvement in 6-minute walk distances, improved quality of
life, and reduction of brain natriuretic peptide. A prospective
study of body scan mediation in patients with heart failure
demonstrated improved quality-of-life scores, improved measures of exercise performance, and reduction in plasma
norepinephrine.126
Related to meditation techniques are stress management
therapies designed to provoke the relaxation response. In a
study of patients with New York Heart Association class II
and III symptoms, cognitive therapy and stress management
improved exercise stress duration as well depression scores
and were associated with significant weight loss.127 Guided
imagery offers another approach to elicit the relaxation
response and has been examined in a small uncontrolled pilot
study of patients with heart failure but only demonstrated
trends to improved quality-of-life measures and no change in
exercise capacity.128 Other relatively small studies ranging
from 14 to 83 participants have examined a variety of
relaxation therapies in patients with congestive heart failure
and have found only changes in subjective measures of
perceived wellness but not more objective physiological
measures.129 –132
The recently published SEARCH trial enrolled a comparatively large number of patients with relatively severe left
ventricular dysfunction.133 Participants in the treatment arm
were enrolled in a program of instruction in mindfulnessbased stress reduction, coping skills, and participation in
expressive support group discussions. At 12 months, the
participants in the intervention program reported a perception
of symptomatic improvement and had improved scores on
anxiety, depression, and quality-of-life scales. This study
represents one of the strongest demonstrations that mindbody interventions can produce a positive impact in at least a
subset of patients with congestive heart failure and provides
a foundation for future investigations (Table).
Summary and Conclusions
Evidence shows that there is a genuine physical and reciprocal connection between the mind and the body defined by
physiological pathways and organic structural remodeling of
the elements of these interactions. Further, interventions and
practices such as biofeedback, relaxation therapies, and meditation clearly alter at least acutely if not chronically the
effector systems governing mind-body and mind-heart interactions. Less clear is the role these interventions may play in
the immediate or future management of patients with ventricular failure. There is at this time a paucity of studies that
directly address these questions in patients with congestive
heart failure. Is it possible that mind-heart intervention techniques can reverse the remodeling of many of these pathways,
including the known aberrations of autonomic balance that
evolve early in the course of ventricular failure and that may
contribute to the progression of the disease process?25 Can
mind-body and mind-heart interactions address the significant
depression and anxiety that are prevalent in patients with
congestive heart failure and reverse the neuroimmune activation
operative in both conditions?9,13,27,28,55,69,80
The evidence-based medicine to address these questions is
lacking. As can be seen from the literature discussed in this
review, the clinical studies of mind-heart interventions are
often uncontrolled and underpowered owing to small sample
sizes. This has been recognized as a major limitation faced by
a large number of studies investigating mind-body interventions.103,134 In an era of translational investigation, this
appears to be a field ideally suited to the evolving scientific
Emani and Binkley
Table.
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Representative Studies Examining Mind-Body Interventions in Congestive Heart Failure
Intervention
Author and
Reference No.
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n
(Treatment Arm)
Biofeedback
Moser et al105
Follow-Up
Outcomes With Intervention
Prospective
Randomized
controlled
40 (20)
Immediate
Increased cardiac output and decreased systemic vascular
resistance
No changes in catecholamine levels or O2 consumption
Biofeedback
Swanson et al109
Prospective
Randomized
controlled
29 (15)
6 weeks
Improved 6MWD for subgroup with ejection fraction
⬎30% (n⫽9 vs 8)
No significant change in HRV or QoL
Slow breathing
Bernardi et al106
Prospective
NR
Self-matched
and controlled
102 (81)
Immediate
Increased baroreflex sensitivity and BP decrease in heart
failure patients pre intervention vs postintervention
(self-matched)
No significant difference between heart failure and control
populations
Transcendental
Meditation
Jayadevappa et al111
Prospective
Randomized
controlled
23 (13)
6 mo
Improved 6MWD, depression scores, and QoL
Meditation
Curiati et al126
Prospective
Randomized
controlled
19 (10)
14 wk
Reduced NE levels and improved QoL
Left ventricular ejection fraction not significantly changed
Tai Chi
Yeh et al124,125
Prospective
Randomized
controlled
30 (15)
12 wk
Improved QoL, 6MWD, decreased brain natriuretic peptide
Stress management
Kostis et al127
Prospective
Randomized
controlled
19 (7)
12 wk
Improved exercise time, QoL, depression, and weight loss
6MWD not statistically improved
Stress management
Luskin et al132
Prospective
Incomplete
Randomization
controlled
33 (14)
10 wk
Improved 6MWD, depression, perceived stress, and
emotional distress
HRV not statistically improved
Mindfulness-based
stress reduction
Sullivan et al
(SEARCH Trial)133
Prospective
NR
217 (117)
12 mo
Improved symptoms, anxiety, depression, and QoL
No differences in death and rehospitalization
Klaus et al128
Prospective
NR
Self-matched
8
6 wk
No statistically significant improvements in exercise or
dyspnea measures
QoL measures trended towards but not significant for
improvement
Progressive muscle
relaxation training
Yu et al129
Prospective
Randomized
controlled
121 (59)
14 wk
Trend toward symptom improvement
Relaxation response
Chang et al130
Prospective
Randomized
controlled
83 (33)
Approx 4 mo
Improved spiritual QoL
Trend toward improved emotional QoL
Physical QoL and exercise capacity not improved by
relaxation response
Guided imagery
Type
NR indicates nonrandomized; 6MWD, 6-minute walk distance; QoL, quality of life; HRV, heart rate variability; and NE, norepinephrine.
methods that connect fundamental scientific discovery to
clinical practice.
It is possible that these interventions will constitute important therapies complementary to current standard care. As an
example, a population-based study examining the impact of
spirituality on autonomic function and cardiovascular disease
found that an increase in the aggregate score of spirituality
measures highly correlated with autonomic control.3 This is
relevant to patients with congestive heart failure, who, with
progressive severity of disease, lose diurnal variation of
parasympathetic/sympathetic balance, which in effect represents a lack of what has been defined as autonomic control.135–138 Therefore, is it possible that mind-body interventions can restore normal autonomic control in patients with
congestive heart failure? Could these interventions increase
responsiveness to pharmacological treatment?
The role that mind-heart interventions will play in the
future treatment of patients with congestive heart failure is
yet to be defined. Although there is the clear indication that
the field of behavioral cardiology is one that is likely to
continue its evolution and play a significant role in the
advancement of patient care, it is also clear that this must be
preceded by further studies confirming benefit and defining
this field of practice.134 Further, although complementary and
alternative therapies are embraced by many patients, they
require commitment of time and to lifestyle change.139
Nevertheless, the reality of the mind-heart connection cannot
be ignored, and cardiovascular specialists must continue to
engage in the understanding, translational research, and
application of this field.
Translational science must now meet the challenge to build
on the intriguing studies that have established the mechanistic
722
Circ Heart Fail
November 2010
basis for mind-heart interactions. There are a wide variety of
investigations that must follow. The authors suggest a few:
●
●
●
●
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●
Investigate the capacity of mind-heart interactions to increase susceptibility to pharmacological therapy and to
cardiac resynchronization therapy.
Test whether the response to drug administration coordinated with mind-heart interventions is augmented compared with standard dosing regimens.
Test the capacity of mind-heart interventions to alleviate
comorbid conditions such as sleep disorders that commonly accompany ventricular failure are themselves influenced by states of stress and anxiety.140
Evaluate the capacity of mind-heart interventions to improve ventricular function through interruption of the
cascade of autonomic and proinflammatory pathways activated by depression and stress.141,142
Investigate the response to mind-body interventions in the
context of different genetic backgrounds similar to the
pharmacogenetic impact on drug response. Conversely,
evaluate the impact of mind-heart interventions on gene
function based on preliminary studies showing the plausibility of “mind/gene” interactions.143,144
These constitute just a few of the exciting possibilities for
translational research in mind-heart medicine and adapting
this field to the overall clinical and investigative approach to
patients with congestive heart failure. It is hoped that the field
of translational cardiovascular medicine will explore research
questions such as these and others to allow mind-heart
interventions to take a place in the growing armamentarium
of heart failure therapies.
Sources of Funding
Dr Philip F. Binkley is supported by the James H. and Ruth J. Wilson
Professorship.
Disclosures
None.
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KEY WORDS: Vagus nerve 䡲 sympathetic nervous system
nervous system 䡲 inflammation 䡲 autonomic function
䡲
autonomic
Mind-Body Medicine in Chronic Heart Failure: A Translational Science Challenge
Sitaramesh Emani and Philip F. Binkley
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Circ Heart Fail. 2010;3:715-725
doi: 10.1161/CIRCHEARTFAILURE.110.951509
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