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HomeCirculationVol. 146, No. 12State of the Science: The Relevance of Symptoms
in Cardiovascular Disease and Research: A Scientific Statement From the American
Heart Association
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* Abstract
* Symptom Traits and Caveats in CVD
* Acute Coronary Syndrome
* Heart Failure
* Valvular Heart Disease
* Stroke
* Peripheral Vascular Disease
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STATE OF THE SCIENCE: THE RELEVANCE OF SYMPTOMS IN CARDIOVASCULAR DISEASE AND
RESEARCH: A SCIENTIFIC STATEMENT FROM THE AMERICAN HEART ASSOCIATION
* Corrine Y. Jurgens
, PhD, RN, ANP, FAHA, Chair,
* Christopher S. Lee
, PhD, RN, FAHA, Vice Chair,
* Dawn M. Aycock
, PhD, RN, ANP-BC, FAHA,
* Ruth Masterson Creber
, PhD, MSc, RN, FAHA,
* Quin E. Denfeld
, PhD, RN, FAHA,
* Holli A. DeVon
, PhD, RN, FAHA,
* Linda R. Evers
, JD,
* Miyeon Jung
, PhD, RN, FAHA,
* Gianluca Pucciarelli
, PhD, RN, FAHA,
* Megan M. Streur
, PhD, RN, FNP,
* Marvin A. Konstam
, MD, FAHA and
* on behalf of the American Heart Association Council on Cardiovascular and
Stroke Nursing; Council on Hypertension; and Stroke Council
Corrine Y. Jurgens
Corrine Y. Jurgens
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,
Christopher S. Lee
Christopher S. Lee
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,
Dawn M. Aycock
Dawn M. Aycock
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,
Ruth Masterson Creber
Ruth Masterson Creber
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,
Quin E. Denfeld
Quin E. Denfeld
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,
Holli A. DeVon
Holli A. DeVon
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Linda R. Evers
Linda R. Evers
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Miyeon Jung
Miyeon Jung
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Gianluca Pucciarelli
Gianluca Pucciarelli
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Megan M. Streur
Megan M. Streur
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Marvin A. Konstam
Marvin A. Konstam
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and
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Originally published18 Aug
2022https://doi.org/10.1161/CIR.0000000000001089Circulation. 2022;146:e173–e184
* Other version(s) of this article
* YOU ARE VIEWING THE MOST RECENT VERSION OF THIS ARTICLE. PREVIOUS
VERSIONS:
* August 18, 2022: Ahead of Print
ABSTRACT
Symptoms of cardiovascular disease drive health care use and are a major
contributor to quality of life. Symptoms are of fundamental significance not
only to the diagnosis of cardiovascular disease and appraisal of response to
medical therapy but also directly to patients’ daily lives. The primary purpose
of this scientific statement is to present the state of the science and
relevance of symptoms associated with cardiovascular disease. Symptoms as
patient-reported outcomes are reviewed in terms of the genesis, manifestation,
and similarities or differences between diagnoses. Specifically, symptoms
associated with acute coronary syndrome, heart failure, valvular disorders,
stroke, rhythm disorders, and peripheral vascular disease are reviewed.
Secondary aims include (1) describing symptom measurement methods in research
and application in clinical practice and (2) describing the importance of
cardiovascular disease symptoms in terms of clinical events and other
patient-reported outcomes as applicable.
Symptoms are subjective experiences that may indicate disease or significant
change in health status. Symptoms have been linked to cardiovascular disease
(CVD) since Egyptian physicians and Hippocrates described fatigue and dyspnea,
respectively, as being related to the failing heart.1,2 In a contemporary view
of CVD, symptoms often are critical elements of the diagnosis, evaluation,
management, and certainly lived experience of illness. Symptoms also drive
health care use and are a major contributor to broad patient-reported outcomes
such as quality of life in chronic CVD.3,4 More commonly, research in CVD is
focused on major adverse cardiovascular events such as hospitalization or death
in response to cardiovascular therapies and less so on symptoms despite their
fundamental significance. The primary purpose of this scientific statement is to
present the state of the science and relevance of symptoms associated with CVD.
Symptoms as patient-reported outcomes are reviewed in terms of the genesis,
manifestation, and similarities or differences between diagnoses. Secondary aims
are to describe symptom measurement methods in research and to describe the
importance of symptoms in terms of clinical events and other patient-reported
outcomes as appropriate.
SYMPTOM TRAITS AND CAVEATS IN CVD
Although we frequently assume that symptoms are subjective experiences that
accurately reflect underlying bodily changes, several caveats must be taken into
consideration in the interpretation of symptoms in CVD (Table 1).
Table 1. Symptom Definition, Characteristics, Traits, and Caveats
DefinitionSubjective experiences that may indicate disease or change
thereinCharacteristicsIntensity, quality, duration, timing, distress,
interference with lifeTraitsLocalized (for example, substernal chest pain) or
generalized (for example, fatigue) experiences that can involve any of the
body’s senses5CaveatsBodily changes must be (1) different in intensity or
frequency and (2) sufficient in magnitude, newness, or significance compared
with normal bodily sensations to be detected as symptoms.5,6Bodily changes are
interpreted as a function of their attribution (for example, fatigue from heart
failure vs a normal aging process)7,8 and within cultural norms.9Bodily changes
may be misinterpreted (that is, symptoms can be experienced without underlying
change in pathogenesis, or change in underlying pathogenesis may not be
experienced as symptoms).External stressors may cause unawareness of major body
changes or hypervigilance to even small changes in health.10Symptoms may be
highly variable among patients with similar cardiovascular
disorders.10,11Symptoms of CVD commonly occur in clusters.12–14
CVD indicates cardiovascular disease.
Most notably, patients with CVD may experience symptoms in the absence of major
changes in underlying pathogenesis. The absence of symptoms also does not
necessarily confer the absence of change in underlying pathogenesis,
particularly in advanced CVD.15 Nevertheless, symptoms have relevance in CVD,
particularly in acute coronary syndrome (ACS), heart failure (HF), valvular
disorders, stroke, rhythm disorders, and peripheral vascular disease.
ACUTE CORONARY SYNDROME
CHEST PAIN AND ASSOCIATED SYMPTOMS
The most frequently reported symptom of ACS is chest pain. Chest pain has often
been described as substernal pressure or discomfort and may radiate to the jaw,
shoulder, arm, or upper back. The most common co-occurring symptoms with chest
pain are dyspnea, diaphoresis, unusual fatigue, nausea, and lightheadedness.16
Symptoms such as unusual fatigue and weakness have often been labeled as
atypical in ACS, but this labeling may be a function of men being the standard
for typical symptom presentation as opposed to true symptom frequency. In a
review of 7 studies assessing prodromal symptoms of ACS,17 chest
discomfort/pain, arm pain/discomfort, jaw pain, back/shoulder blade pain,
unusual fatigue, shortness of breath, sleep disturbance, dizziness, headache,
anxiety, and gastrointestinal complaints were reported in ACS. Patients with
persistent angina also experience higher rates of depression and anxiety.18 It
remains unknown how depression may affect the report of physical symptoms of
ischemic heart disease; however, shortness of breath and chest pain may be more
prevalent among depressed patients with ischemic heart disease.19
A central challenge in interpreting symptoms in ACS is the lack of consensus on
the duration of the prodromal phase, which in the literature ranges from 1 month
to 48 hours before an ACS event.16,17 Women reporting arm pain or discomfort and
unusual fatigue during initial ischemic heart disease evaluation are more likely
to have a cardiac event at any point in the next 90 days.20 However, few cardiac
symptoms are actually sensitive and specific for ischemic heart disease.
Consequently, women are at risk for additional morbidity such as sustaining an
ST-segment–elevation myocardial infarction secondary to misjudging or
attributing symptoms to a minor cause. Put simply, it can be challenging to
determine whether prodromal symptoms are specific to an ACS episode, as well as
their clinical relevance to patient outcomes.
SEX DIFFERENCES
More similarities in symptom presentation in ACS have been reported among women
compared with men, but salient differences have been found. For example, in the
EPIHeart study, there were no significant differences in the frequency or
location of chest pain by sex, but women reported significantly more severe pain
and more referred pain compared with men.21 In a large American cohort, women
were significantly more likely to experience nausea, shoulder pain, upper back
pain, and a greater number of ACS symptoms compared with men.16 Last, in the
VIRGO study (Variation in Recovery: Role of Gender on Outcomes of Young AMI
Patients), younger women with acute myocardial infarction were more likely to
present with a cluster of ≥3 symptoms (ie, epigastric symptoms, palpitation, and
pain or discomfort in the jaw, neck, arms, or shoulders) compared with men.12
On average, women with ACS are significantly older than men, with differences
ranging from 2 to 10 years.16,21,22 Ischemic heart disease is less prevalent
among women than men for every age group in the United States except 20 to 39
years of age.23 The incidence of myocardial infarction or fatal ischemic heart
disease is higher for women only after 85 years of age.23 Younger individuals
with ACS are more likely to be male, to smoke, and to have a family history of
premature CVD. Younger adults are also less likely to have extensive disease or
ST-segment–elevation myocardial infarction.24 There is a caveat in that the term
young varies across the literature, ranging from ≤40 to ≤55 years of age, and
there is no universally accepted cutoff.24 The contributions of chronological
(passage of time) and biological (functional decline) aging25 to symptoms
experienced by patients with ACS are unknown.
CLINICAL APPLICATION OF MEASUREMENT
A majority of ACS symptom measures are disease-specific and multidimensional,
and many are valid and reliable (Online Table).26 However, the availability of
multiple measures means that there is no standard instrument in use. A lack of
standard measures means that there could be a bias in favor of certain symptom
assessments and an inability to compare symptoms across cohorts. Moreover, lack
of harmonization of ACS symptom measurement in research hampers growth in
cumulative evidence. Therefore, little can be done to synthesize salient
findings about symptoms across ischemic heart disease/ACS studies and to
incorporate evidence-based information about symptoms into treatment guidelines
and patient education materials. In clinical practice, tracking symptoms over
time with respect to both severity and life interference with a valid and
reliable measure would help contribute to the limited evidence base compared
with the more typical arbitrary approaches to symptom appraisal. The Online
Table outlines the strengths, limitations, and content of and key references for
the various measures available for CVD.
HEART FAILURE
DYSPNEA
Dyspnea (aka‚ shortness of breath, breathing discomfort, or breathlessness) is a
hallmark of HF. Increased dyspnea is one of the most common reasons that adults
with HF seek hospitalization, and severe dyspnea is associated with a greater
risk of mortality.27 Dyspnea is often characterized in terms of provocation,
meaning dyspnea at rest, dyspnea on exertion, orthopnea, paroxysmal nocturnal
dyspnea, and bendopnea.28,29 It is important to account for dyspnea
heterogeneity in both clinical practice and research by using nuanced measures
and probing questions to capture this common and multifaceted symptom. Profiling
techniques have been helpful in pinpointing patients with different clinical
phenotypes of dyspnea in HF.30 Moreover, it is important to consider
non–HF-related causes when evaluating dyspnea, especially comorbid conditions
such as chronic obstructive pulmonary disorder.31
EARLY PHYSICAL SYMPTOMS
Early and subtle symptoms also can be harbingers of worsening HF and impending
hospitalization or death.27 For example, gastrointestinal-related symptoms such
as upset stomach, nausea and vomiting, and loss of appetite can be related to
intestinal congestion.32 Fatigue is rated as both the most common and the most
bothersome hallmark HF symptom.33 Fatigue has variable causes both related and
unrelated to HF pathophysiology and results in exercise intolerance, especially
with co-occurring dyspnea. Together, these symptoms may herald muscle wasting
and cachexia, which are indicators of HF progressing to more advanced stages.34
OTHER SYMPTOMS AND SYMPTOM CLUSTERS
Adults with HF commonly report insomnia and wake disturbances related to both HF
(eg, pulmonary congestion) and non-HF causes (eg, sleep apnea), as well as side
effects from medications (eg, nocturia).35 Pain is a common but often
unsolicited symptom in HF and can be attributable to cardiac causes (eg,
deconditioning) or noncardiac causes (eg, diabetic neuropathy).36 For some
patients with HF, pain increases toward the end of life and can be exacerbated
by physical limitations.37 In addition to physical symptoms, 25% to 30% of
adults with HF report mood disturbances, manifesting primarily as depressive and
anxiety symptoms, that are independently associated with poor clinical
outcomes.38 In HF, physical and affective symptoms frequently cluster together
regardless of cultural differences,39 and such symptom clusters are associated
with a gradient in clinical event risk.13,40
Cognitive dysfunction is common among patients with HF. It is likely
attributable to lowered cerebral blood flow resulting from HF and associated
with structural and functional changes to the brain.41 A central challenge in
dealing with cognitive dysfunction is that it is both a sign of HF and it
directly affects a patient’s ability to recognize and respond to other symptoms
when they occur.42 Accordingly, patients with HF who experience cognitive
dysfunction have higher 30-day and 1-year mortality.43 However, by definition,
cognitive dysfunction is not subjective and is therefore not a symptom.
SEX AND AGE DIFFERENCES
Women report higher physical symptom burden, higher depression and anxiety, and
lower quality of life.44–47 Symptoms reported more frequently by women are
similar to what occurs in ACS (eg, nausea, palpitations, epigastric
symptoms).44,46 Women also were more likely to report higher pain (other than
chest pain), nervousness, edema, and sweating.44 Differences may partly be
explained by a higher comorbid illness burden or diagnosis of HF at a later age
among women.
Older adults in general perceive less dyspnea compared with younger adults.48
Indeed, among adults with HF, older age is associated with problems recognizing
and interpreting dyspnea.49 In addition, physically frail adults with HF have
significantly worse dyspnea, sleep-wake disturbances, and depressive symptoms
compared with adults with HF who are not physically frail.50 Taken together,
both chronological age and biological age contribute to patient experience with
symptoms in HF.
CLINICAL APPLICATION OF MEASUREMENT
Several measures of symptoms in HF are commonly used and have evidence of
validity and reliability (Online Table). Although quality of life and health
status measures are most commonly used in HF, the number of symptoms indirectly
covered by such measures is limited. Current and future work in HF symptoms is
now focused on symptom patterns and clustering over time, which have received
limited attention in other CVDs.
VALVULAR HEART DISEASE
Valvular heart disease is a frequent cause of HF, with symptoms generally
indistinguishable from other HF causes. Rheumatic heart disease, although still
prevalent in low- and middle-income countries,51 has largely disappeared
elsewhere and has been replaced by population aging and cardiomyopathies as
predominant drivers of valve disease. In the absence of acute severe valve
dysfunction, patients generally have a prolonged asymptomatic period, followed
by a period of progressive symptoms,52 resulting from the valve lesion itself or
secondary myocardial remodeling and dysfunction. The staging of valvular heart
disease is based on a combination of valve findings, symptoms, and ventricular
function.53 Over time, left-sided valve dysfunction may result in pulmonary
hypertension with tricuspid regurgitation and right-sided HF. Functional
assessment may be aided by maximal exercise testing (ie, cardiopulmonary
exercise testing). The 6-minute walk test and quality-of-life questionnaires are
among the more common tools used to quantify benefit after valve intervention
and to compare different interventional approaches. Among the valve lesions,
there are subtle differences in terms of the role of symptoms in guiding the
timing of intervention (Table 2).56
Table 2. Valve Lesions and Salient Symptom Differences
Aortic stenosisAS may present with angina, syncope, or dyspnea, with none being
specific for this disease.52,54
All symptoms of AS portend progressive deterioration and limited survival.
Mortality correlates with the presenting symptom, with angina being the least
onerous; HF symptoms, notably dyspnea, carrying the worst prognosis; and syncope
being in between.55
Recommendation for delayed intervention in the absence of symptoms assumes that
sudden cardiac death (that is, without antecedent symptoms) is rare in adults
and is exceeded by surgical risk.53
Intervention in severe disease is considered before symptom onset attributable
to a decline in procedural morbidity and mortality and an estimated annual rate
of sudden death between 0.5% and 1%.53,54
Transcatheter aortic valve replacement has a favorable impact on symptoms and
functional capacity in inoperable patients. It is at least equivalent to
surgical intervention in high- to moderate-risk patients.56,57Aortic
regurgitationAcute AR, as with acute bacterial endocarditis or acute aortic
dissection, can be catastrophic, with acute pulmonary edema or cardiogenic
shock.
In chronic AR, after an often-protracted asymptomatic period, symptoms of HF
reflect advancing LV remodeling and dysfunction.
Early surgery is indicated when associated symptoms appear or in the presence of
reduced LVEF (≤55%) to avoid progressive, irreversible LV damage.52,53,58Mitral
stenosisWith incident rheumatic MS virtually abolished, more cases are now
recognized to be attributable to severe mitral annular calcification.
Left-sided HF, with progressive dyspnea and exercise intolerance, is a
manifestation of mitral flow obstruction, resulting in increased pulmonary vein
pressure and impaired LV filling.
Pulmonary hypertension, with associated RV dilation and dysfunction and symptoms
of edema, hepatic congestion, and ascites, is more evident and less reversible
with MS than with other valve lesions.
Unlike with aortic valve disease, relatively mild symptoms may be manageable
with diuresis and rate control.
Advancing valve pathology and symptoms, including increased dyspnea and
functional incapacity, call for mitral valvuloplasty or replacement.53 Such
intervention often results in dramatic symptom improvement and prevention of
progressive symptoms of pulmonary arterial hypertension and right-sided
HF.Mitral regurgitationMR may be functional, associated with LV and mitral
annular dilation of any cause, or structural, with congenital or acquired valve
deformity.
Acute, severe MR often presents as acute pulmonary edema, which may require
urgent intervention.
In chronic MR, unlike aortic valve disorders, symptoms of left-sided HF result
from direct LV ejection into the left atrium and therefore may occur in advance
of significant LV damage.
Mild symptoms may be manageable with diuretics, rate control, and vasodilators
to reduce both LV afterload and preload.
Factors affecting the decision for mitral repair or replacement include the
severity and progression of symptoms, the nature of the valve lesion, the
severity of regurgitant flow, and evidence for advancing LV dilation
(end-systolic diameter ≥40 mm) and dysfunction (LVEF ≤60%).53
Transcutaneous valve intervention for MR, in addition to reducing morbid and
fatal events, has been shown to significantly improve health status.59Tricuspid
valve diseaseTricuspid stenosis is rare and results in symptoms of right-sided
HF.
Structural TR results from valve pathology, whereas TR is most commonly
functional, associated with RV dilation attributable to myopathy, myocardial
infarction, pulmonic valve obstruction, pulmonary emboli, or any other cause of
pulmonary hypertension.
TR symptoms are those of right-sided HF, including functional incapacity, edema,
ascites, and hepatic congestion. In severe and chronic TR, hepatic failure may
occur with its attendant symptoms, including jaundice, and may obviate
procedures requiring general anesthesia.
TR may be better tolerated when not associated with excessive RV afterload.
Diuretics, pulmonary vasodilators, and nitrates often reduce symptoms of
right-sided heart failure, particularly in functional TR.
Structural intervention is considered in severe disease,53 particularly in the
case of valvular structural cause.
AR indicates aortic regurgitation; AS, aortic stenosis; HF, heart failure; LV,
left ventricular; LVEF, left ventricular ejection fraction; MR, mitral
regurgitation; MS, mitral stenosis; RV, right ventricular; and TR, tricuspid
regurgitation.
SEX DIFFERENCES
Symptoms differ between the sexes for aortic valve disease. Aortic stenosis is
typically asymptomatic for years. Women report dyspnea and exercise intolerance
more often than men as stenosis progresses. Women also are more likely to be
physically frail and to have a higher New York Heart Association class (III/IV)
than men. Men are more likely to have chest pain.60,61
CLINICAL APPLICATION OF MEASUREMENT
Symptom presence and severity are key in determining the stage of disease and
timing of surgical or transcatheter intervention. However, the implication of
symptoms differs across the various lesions. Quantitative symptom and functional
assessments have been important research tools in gauging the efficacy of
interventional treatment (Online Table). Given the importance of symptom
assessment, more work is needed to determine the incremental value of
quantitative symptom measurement as an aid to clinical management.
STROKE
ACUTE STROKE SYMPTOMS
Acute symptoms often predict disability and quality of life after stroke.62
Identifying and responding to stroke signs and symptoms quickly is essential for
proper treatment.63 Acronyms like FAST64 (face, arm, speech, time) and related
derivations were developed to facilitate lay public recognition and prehospital
response to the most common signs of stroke. Weakness and numbness, speech
problems, confusion, dizziness and loss of coordination/balance, and visual
changes have been associated with the likelihood of seeking emergency care,65,66
but timeliness of response differs by symptom.
For clinicians, classic stroke symptoms, in addition to nonclassic symptoms such
as partial sensory deficit, dysarthria, vertigo, and diplopia,67 require
consideration for activating a stroke response team.68 The Rapid Arterial
Occlusion Evaluation Scale69 and National Institutes of Health Stroke Scale show
the best diagnostic accuracy values,70 with the latter advocated for most
because of rapid performance, along with both accuracy and reliability (Online
Table).71
POSTSTROKE SYMPTOMS
After a stroke, acute symptoms may linger, becoming disabilities, or improve
with time or rehabilitation. Although there are others, the Stroke Specific
Quality of Life scale is the dominant means to assess physical function and is
shorter and easier to administer in daily practice compared with alternatives.72
Stroke severity, physical disability, and cognitive impairments after stroke are
associated with common poststroke symptoms of anxiety, depression, fatigue, and
pain.73–76 About one-fourth of stroke survivors experience anxiety,77 one-third
experience depression,75 at least half report fatigue,78 and up to half report
pain,79 all at various stages in stroke recovery.
SEX DIFFERENCES
A systematic review and meta-analysis revealed that women were more likely to
present with nonfocal symptoms (eg, headache, altered mentality, and
coma/stupor) than men.80 To enhance public education about stroke symptoms and
to facilitate the diagnosis and treatment of stroke, research is needed to
better understand the presentation of stroke symptoms by other select
demographic characteristics (eg, race and ethnicity, age, stroke subtype).
CLINICAL APPLICATION OF MEASUREMENT
The significance of time is evident for when to assess stroke symptoms in the
hyperacute and acute phases of stroke, but the optimal frequency of symptom
assessment is less clear for the subacute and chronic phases. All people who
experience a stroke should be screened for poststroke anxiety and depression and
other physical and psychological issues (Online Table).81 Stroke survivors at
high risk of depression (eg, high stroke severity, age ≤50 years, history of
depression, cognitive impairment) should be assessed at various stages
throughout the continuum of stroke care, especially at transition points.81
Although there are other means of assessing anxiety and depressive symptoms, in
a systematic review, only the Hospital Anxiety and Depression Scale was
recommended for its high sensitivity and specificity in stroke.82 The 2016
American Heart Association/American Stroke Association “Guidelines for Adult
Stroke Rehabilitation and Recovery” recommend the use of a structured depression
inventory (eg, Patient Health Questionnaire-2) to routinely screen for
poststroke depression.83
In a 2017 American Heart Association scientific statement on poststroke fatigue,
the frequently used Fatigue Severity Scale was recommended.73 Another tool, the
Neurological Fatigue Index for Stroke, has been shown to screen fatigue at all
levels of severity; it is easy to use and freely available from the authors.84
It is recommended to assess for poststroke fatigue at discharge from acute care;
at 3, 6, and 12 months; and then annually.73
Last, poststroke pain may involve neuropathic pain and nociceptive pain,
musculoskeletal pains, shoulder pain, spasticity-related pain76; there are no
stroke-specific measures of pain because of the heterogeneity of neurological
deficits in this population.79 Hence, general self-report questionnaires, pain
scales, and clinical assessment are used to assess poststroke pain. Poststroke
pain can take weeks to months to develop, with the highest prevalence rates at 4
to 6 months.79,85 Prevalence rates and individual responses should guide the
assessment of pain and anxiety after stroke.
RHYTHM DISORDERS
Cardiac arrhythmias, including atrial fibrillation (AF), atrial flutter,
supraventricular tachycardias, bradyarrhythmias, and ventricular tachycardia,
present with common symptoms. Palpitations (ie, perceiving the heartbeat as
irregular, rapid, fluttering, skipping, or pausing) is a characteristic symptom
of many cardiac arrhythmias. The most common cardiac arrhythmia, AF, may present
with palpitations or less specific symptoms (eg, fatigue, dyspnea, dizziness)
that occur in association with a broad range of disease conditions.86
Palpitations are considered the typical symptom presentation for AF, yet
patients with new-onset AF often present either asymptomatically or with
nonspecific symptoms.86 Palpitations (27%–70%), fatigue (26%–75%), and dyspnea
(28%–76%) are the most common symptoms reported by patients with AF, whereas
chest pain (12%–30%), dizziness (19%–44%), presyncope/syncope (3%–4%), and
anxiety (12%–50%) occur less frequently.87–90 Psychological distress also may be
associated with worse AF symptom severity.91 Last, AF symptoms do not correspond
to objectively measured AF episodes in all cases.92 Even within the same
individual, AF may fluctuate between symptomatic and asymptomatic.93
Tachycardia accounts for some symptom variability, although achieving heart rate
control does not always eliminate symptoms.94 AF ablation reduces symptoms,95
but the effect is not attributable solely to a reduction in AF burden. It is
interesting to note that in 1 study 52% of AF episodes were asymptomatic before
AF ablation and 79% were asymptomatic after ablation.96 AF also is a well-known
risk factor for developing stroke and dementia.97 Moreover, even among patients
without prior stroke, the diagnosis of AF is a risk factor for poor cognitive
function.98 Symptoms of AF are often erroneously attributed to deconditioning,
stress, or sleepiness, leading to delays in seeking medical attention for a week
or longer.99 Nonspecific (fatigue and dyspnea) and intermittent symptoms are
associated with a delay in seeking treatment for AF, whereas cardiac-specific
symptoms, including palpitations and chest pain, are not.100 In a longitudinal
cohort, patients with AF who initially presented with palpitations had lower
stroke and mortality rates, even after adjustment for thromboembolic risk and
anticoagulation.86 In ORBIT-AF (Outcomes Registry for Better Informed Treatment
of AF)101 and RACE II (Rate Control Efficacy in Permanent AF),102 worse AF
symptom severity was associated with higher hospitalization rates. Symptoms also
are the reason for presentation in 50% of patients presenting to the emergency
department for AF.103
SEX, AGE, AND RACIAL DIFFERENCES
Women and younger individuals with AF typically present with palpitations,14,86
whereas men are more commonly asymptomatic.86,104,105 Older age also increases
the likelihood of a nonclassic or asymptomatic presentation of AF.14,86,105 With
regards to race‚ 2 systematic reviews reported an AF paradox in terms of
symptoms associated with AF. Despite non-Hispanic Black individuals being at
lower risk for development of AF, Black patients are burdened more with
palpitations, dyspnea on exertion, exercise intolerance, dizziness, dyspnea at
rest, and chest discomfort compared with White or Hispanic patients.106,107
CLINICAL APPLICATION OF MEASUREMENT
Symptom monitoring and the association between symptoms and heart rate and
rhythm are essential components of medication titration for rate control and
selection of a rate versus rhythm control management strategy.108 Clinicians
underrepresent AF symptom severity102; hence, clinician-reported AF symptom
measures should be avoided unless absolutely necessary. Several measures are
available to quantify rhythm disorders; however, some are limited in terms of
validity testing or comprehensiveness of symptoms assessed (Online Table).
Correlating symptoms and rhythm also can present a challenge when symptoms occur
infrequently and unpredictably, but mobile health devices increase AF detection
compared with standard practice (eg, mobile devices, in-office ECGs, 24-hour
Holter) and therefore reduce diagnostic delay and improve symptom-rhythm
correlation.109
PERIPHERAL VASCULAR DISEASE
PERIPHERAL ARTERIAL DISEASE
Peripheral vascular disease and its associated symptoms can arise from either
arterial or venous pathology. Peripheral arterial disease (PAD) is a progressive
atherosclerotic disease resulting in insufficient blood flow to the lower
extremities. PAD symptoms vary, ranging from none (despite disease progression)
to leg pain at rest. Classic claudication occurs in approximately one-third of
patients and is defined as calf pain that occurs in 1 or both legs with exertion
(walking), does not begin at rest, and resolves within 10 minutes of standing
still or rest. Nonclassic symptoms (eg, noncalf exercise pain) are reported more
frequently than classic claudication symptoms. Assessing symptoms at rest,
during exercise, and during recovery can assist with classifying symptoms as
ischemic or not.110,111 Limb ischemia is the most severe form of PAD, with
individuals experiencing pain in their legs, feet, or toes. Symptomatic PAD is
associated with an increased risk of major adverse cardiovascular events, with
men at higher risk.112,113 Last, depression is common in PAD, with a prevalence
(3%–48%) similar to that of other types of CVD. Women, the elderly, individuals
of underrepresented races and ethnicities, and those with worse disease and
physical function are at increased risk of depression.114
PERIPHERAL VENOUS DISEASE
Similar to patients with PAD, individuals with peripheral venous disease (PVD)
can be symptomatic or asymptomatic. Clinical classification of PVD includes
symptoms such as leg pain, aching, fatigue, heaviness, cramping, tightness,
restless legs syndrome, and skin irritation. In a study of symptoms in chronic
venous disorders (n=38 750; 78% female), pain, heaviness, aching, and fatigue
were more common in people <65 years of age.115 Pain and heaviness are believed
to be caused by venous dilatation and hypoxia of the venous wall.115,116
Symptoms also may occur without visible signs of PVD.
SEX DIFFERENCES
Sex differences in peripheral vascular disease are specific to PAD. Women with
PAD are more likely to have nonclassic symptoms or an absence of symptoms.
Symptom attribution among women is complicated by comorbid musculoskeletal
diseases (eg, osteoarthritis) or the mistaken belief that PAD is more common in
men. Women with PAD also have a more rapid decline, worse quality of life, and
higher burden of depression.117
CLINICAL APPLICATION OF MEASUREMENT
Existing measures for PVD are quality-of-life measures that include symptoms,
limitations of activities of daily living, and psychological impact (Online
Table). Current PVD measures have limitations similar to other CVDs in terms of
data supporting responsiveness to change or minimally important differences.
Moreover, existing legacy measures of PVD are centered on clinician appraisal
versus patient-reported symptoms.
CONCLUSIONS
Amelioration of CVD symptoms is an integral part of CVD management. It is
important to recognize that CVD symptoms are simply not static and may vary in
occurrence or severity over time. Moreover, several symptoms such as dyspnea and
fatigue are common across disorders. Therefore, it is prudent to use established
measures or to develop reliable, valid, relevant, and responsive measures of CVD
symptoms for tracking over time. It is important to acknowledge that several
existing measures have limitations in terms of responsiveness to change or lack
of established minimally important differences. Most measures have not been
evaluated for measurement error based on sex, race, or ethnicity, which is
problematic given the lack of sex balance and racial representation in CVD
research. Many measures are used on the basis of legacy application versus
appropriateness for informing research or clinical care. Monitoring symptoms
with reliable and valid measures in research and clinical practice may enhance
clinical care by identifying those who may be at risk for poor outcomes more
quickly (eg, lower quality of life, hospitalization, death).
People living with CVD commonly have symptoms directly related to their CVD and
their other chronic conditions, as well as associated symptoms such as sleep
disturbance and depression (Table 3). Therefore, it is challenging for people
living with CVD to disambiguate and appropriately attribute their symptoms to
any one disorder. Furthermore, cognitive dysfunction and depression have a
bearing on patients’ ability to detect underlying changes in symptoms42,118–120;
therefore, both should be measured to establish a baseline and in response to
significant clinical changes. More information is needed on the relationship
between symptoms and clinical events, as well as underlying CVD pathogenesis,
especially among people living with multiple chronic conditions. Despite
limitations in measurement and complexities in how they are experienced,
symptoms have clear relevance to the diagnosis, monitoring, and treatment of
CVD.
Table 3. Common Symptoms Across CVD Diagnoses
AnxietyChest painDepressionDizzinessDyspneaFatigueACS
AF
HF
StrokeACS
Aortic stenosis
AFACS
HF
PAD
StrokeAF
StrokeACS
Aortic stenosis
AF
HFACS
AF
HF
PVD
Stroke
ACS indicates acute coronary syndrome; AF, atrial fibrillation; CVD,
cardiovascular disease; HF, heart failure; PAD, peripheral arterial disease; and
PVD, peripheral venous disease.
ARTICLE INFORMATION
DISCLOSURES
Writing Group Disclosures
Writing group memberEmploymentResearch grantOther research supportSpeakers’
bureau/honorariaExpert witnessOwnership interestConsultant/advisory
boardOtherCorrine Y. JurgensBoston College School of
NursingNoneNoneNoneNoneNoneNoneNoneChristopher S. LeeBoston CollegeNIH
(MPI/co-I)†; PCORI (DSMB chair)*NoneNoneNoneNoneNoneNoneDawn M. AycockGeorgia
State UniversityGordon and Betty Irene Moore Foundation (funded
grant)†NoneNoneNoneNoneNoneNoneQuin E. DenfeldOregon Health & Science University
School of NursingNIH/NINR (R01NR019054)†; NIH/ORWH
(K12HD043488)†NoneNoneNoneNoneNoneNoneHolli A. DeVonUniversity of California Los
Angeles School of NursingNoneNoneNoneNoneNoneNoneNoneLinda R. EversLinda Evers,
Stevens & LeeNoneNoneNoneNoneNoneNoneNoneMiyeon JungIndiana University School of
NursingAHA (PI)†; NIH/NINR (co-I)†; Indiana University School of Nursing (PI)*;
Midwest Nursing Research Society (a mentor on a dissertation
grant)*NoneNoneNoneNoneNoneNoneMarvin A. KonstamTufts Medical Center, The
CardioVascular CenterNoneLivaNova†; scPharma† (all clinical
trials)NoneNoneNoneBoehringer Ingelheim†; Cardurian†; Cytokinetics†; LivaNova†;
Luitpold*; Merck†; Pfizer†; scPharma†NoneRuth Masterson CreberWeill Cornell
MedicineNoneNoneNoneNoneNoneNoneNoneGianluca PucciarelliUniversity of Rome Tor
Vergata (Italy)NoneNoneNoneNoneNoneNoneNoneMegan M. StreurUniversity of
WashingtonNIH/NINR (K23NR017632 [PI])†NoneNoneNoneNoneNoneNone
This table represents the relationships of writing group members that may be
perceived as actual or reasonably perceived conflicts of interest as reported on
the Disclosure Questionnaire, which all members of the writing group are
required to complete and submit. A relationship is considered to be
“significant” if (a) the person receives $10 000 or more during any 12-month
period, or 5% or more of the person’s gross income; or (b) the person owns 5% or
more of the voting stock or share of the entity, or owns $10 000 or more of the
fair market value of the entity. A relationship is considered to be “modest” if
it is less than “significant” under the preceding definition.
* Modest.
† Significant.
Reviewer Disclosures
ReviewerEmploymentResearch grantOther research supportSpeakers’
bureau/honorariaExpert witnessOwnership interestConsultant/advisory
boardOtherJonathan AuldUniversity of WashingtonNational Institute of Nursing
Research (K23 award)†NoneNoneNoneNoneNoneNoneKenneth M. FaulknerStony Brook
UniversityNoneNoneNoneNoneNoneNoneNoneLisa KitkoPenn State
UniversityNoneNoneNoneNoneNoneNoneNoneLea Ann MaturaUniversity of
PennsylvaniaBayer (funding for an RCT to treat [nonpharmacologically] insomnia
and fatigue)†NoneNonePeter A. Allegra*NoneNoneNoneBunny J. PozehlUniversity of
Nebraska Medical CenterNoneNoneNoneNoneNoneNoneNoneJessica H. ThompsonUniversity
of KentuckyNIH (K award–BIRCWH recipient, fellow, University of
Kentucky)*NoneNoneNoneNoneNoneNone
This table represents the relationships of reviewers that may be perceived as
actual or reasonably perceived conflicts of interest as reported on the
Disclosure Questionnaire, which all reviewers are required to complete and
submit. A relationship is considered to be “significant” if (a) the person
receives $10 000 or more during any 12-month period, or 5% or more of the
person’s gross income; or (b) the person owns 5% or more of the voting stock or
share of the entity, or owns $10 000 or more of the fair market value of the
entity. A relationship is considered to be “modest” if it is less than
“significant” under the preceding definition.
* Modest.
† Significant.
FOOTNOTES
Circulation is available at www.ahajournals.org/journal/circ
Supplemental material is available at
https://www.ahajournals.org/doi/suppl/10.1161/CIR.0000000000001089.
The American Heart Association makes every effort to avoid any actual or
potential conflicts of interest that may arise as a result of an outside
relationship or a personal, professional, or business interest of a member of
the writing panel. Specifically, all members of the writing group are required
to complete and submit a Disclosure Questionnaire showing all such relationships
that might be perceived as real or potential conflicts of interest.
This statement was approved by the American Heart Association Science Advisory
and Coordinating Committee on April 27, 2022, and the American Heart Association
Executive Committee on May 16, 2022. A copy of the document is available at
https://professional.heart.org/statements by using either “Search for Guidelines
& Statements” or the “Browse by Topic” area. To purchase additional reprints,
call 215-356-2721 or email Meredith.Edelman@wolterskluwer.com.
The American Heart Association requests that this document be cited as follows:
Jurgens CY, Lee CS, Aycock DM, Masterson Creber R, Denfeld QE, DeVon HA, Evers
LR, Jung M, Pucciarelli G, Streur MM, Konstam MA; on behalf of the American
Heart Association Council on Cardiovascular and Stroke Nursing; Council on
Hypertension; and Stroke Council. State of the science: the relevance of
symptoms in cardiovascular disease and research: a scientific statement from the
American Heart Association. Circulation. 2022;146:e173–e184. doi:
10.1161/CIR.0000000000001089
The expert peer review of AHA-commissioned documents (eg, scientific statements,
clinical practice guidelines, systematic reviews) is conducted by the AHA Office
of Science Operations. For more on AHA statements and guidelines development,
visit https://professional.heart.org/statements. Select the “Guidelines &
Statements” drop-down menu, then click “Publication Development.”
Permissions: Multiple copies, modification, alteration, enhancement, and/or
distribution of this document are not permitted without the express permission
of the American Heart Association. Instructions for obtaining permission are
located at https://www.heart.org/permissions. A link to the “Copyright
Permissions Request Form” appears in the second paragraph
(https://www.heart.org/en/about-us/statements-and-policies/copyright-request-form).
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* Recommended
* LATE-BREAKING SCIENCE ABSTRACTS FROM THE AMERICAN HEART ASSOCIATION’S
SCIENTIFIC SESSIONS 2017 AND LATE-BREAKING ABSTRACTS IN RESUSCITATION
SCIENCE FROM THE RESUSCITATION SCIENCE SYMPOSIUM 2017
Vol. 136, No. 24 December 2017
* POSTSTROKE FATIGUE: EMERGING EVIDENCE AND APPROACHES TO MANAGEMENT: A
SCIENTIFIC STATEMENT FOR HEALTHCARE PROFESSIONALS FROM THE AMERICAN HEART
ASSOCIATION
* Janice L. Hinkle,
* Kyra J. Becker,
* Jong S. Kim,
* Smi Choi-Kwon,
* Karen L. Saban,
* Norma McNair and
* Gillian E. Mead
and on behalf of the American Heart Association Council on Cardiovascular
and Stroke Nursing and Stroke Council
Vol. 48, No. 7 May 2017
September 20, 2022
Vol 146, Issue 12
ARTICLE INFORMATION
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DISCLOSURES
Writing Group Disclosures
Writing group memberEmploymentResearch grantOther research supportSpeakers’
bureau/honorariaExpert witnessOwnership interestConsultant/advisory
boardOtherCorrine Y. JurgensBoston College School of
NursingNoneNoneNoneNoneNoneNoneNoneChristopher S. LeeBoston CollegeNIH
(MPI/co-I)†; PCORI (DSMB chair)*NoneNoneNoneNoneNoneNoneDawn M. AycockGeorgia
State UniversityGordon and Betty Irene Moore Foundation (funded
grant)†NoneNoneNoneNoneNoneNoneQuin E. DenfeldOregon Health & Science University
School of NursingNIH/NINR (R01NR019054)†; NIH/ORWH
(K12HD043488)†NoneNoneNoneNoneNoneNoneHolli A. DeVonUniversity of California Los
Angeles School of NursingNoneNoneNoneNoneNoneNoneNoneLinda R. EversLinda Evers,
Stevens & LeeNoneNoneNoneNoneNoneNoneNoneMiyeon JungIndiana University School of
NursingAHA (PI)†; NIH/NINR (co-I)†; Indiana University School of Nursing (PI)*;
Midwest Nursing Research Society (a mentor on a dissertation
grant)*NoneNoneNoneNoneNoneNoneMarvin A. KonstamTufts Medical Center, The
CardioVascular CenterNoneLivaNova†; scPharma† (all clinical
trials)NoneNoneNoneBoehringer Ingelheim†; Cardurian†; Cytokinetics†; LivaNova†;
Luitpold*; Merck†; Pfizer†; scPharma†NoneRuth Masterson CreberWeill Cornell
MedicineNoneNoneNoneNoneNoneNoneNoneGianluca PucciarelliUniversity of Rome Tor
Vergata (Italy)NoneNoneNoneNoneNoneNoneNoneMegan M. StreurUniversity of
WashingtonNIH/NINR (K23NR017632 [PI])†NoneNoneNoneNoneNoneNone
This table represents the relationships of writing group members that may be
perceived as actual or reasonably perceived conflicts of interest as reported on
the Disclosure Questionnaire, which all members of the writing group are
required to complete and submit. A relationship is considered to be
“significant” if (a) the person receives $10 000 or more during any 12-month
period, or 5% or more of the person’s gross income; or (b) the person owns 5% or
more of the voting stock or share of the entity, or owns $10 000 or more of the
fair market value of the entity. A relationship is considered to be “modest” if
it is less than “significant” under the preceding definition.
* Modest.
† Significant.
Reviewer Disclosures
ReviewerEmploymentResearch grantOther research supportSpeakers’
bureau/honorariaExpert witnessOwnership interestConsultant/advisory
boardOtherJonathan AuldUniversity of WashingtonNational Institute of Nursing
Research (K23 award)†NoneNoneNoneNoneNoneNoneKenneth M. FaulknerStony Brook
UniversityNoneNoneNoneNoneNoneNoneNoneLisa KitkoPenn State
UniversityNoneNoneNoneNoneNoneNoneNoneLea Ann MaturaUniversity of
PennsylvaniaBayer (funding for an RCT to treat [nonpharmacologically] insomnia
and fatigue)†NoneNonePeter A. Allegra*NoneNoneNoneBunny J. PozehlUniversity of
Nebraska Medical CenterNoneNoneNoneNoneNoneNoneNoneJessica H. ThompsonUniversity
of KentuckyNIH (K award–BIRCWH recipient, fellow, University of
Kentucky)*NoneNoneNoneNoneNoneNone
This table represents the relationships of reviewers that may be perceived as
actual or reasonably perceived conflicts of interest as reported on the
Disclosure Questionnaire, which all reviewers are required to complete and
submit. A relationship is considered to be “significant” if (a) the person
receives $10 000 or more during any 12-month period, or 5% or more of the
person’s gross income; or (b) the person owns 5% or more of the voting stock or
share of the entity, or owns $10 000 or more of the fair market value of the
entity. A relationship is considered to be “modest” if it is less than
“significant” under the preceding definition.
* Modest.
† Significant.
* © 2022 American Heart Association, Inc.
https://doi.org/10.1161/CIR.0000000000001089
PMID: 35979825
* Originally publishedAugust 18, 2022
Keywords
* stroke
* peripheral vascular disease
* patient-reported outcomes
* AHA Scientific Statements
* heart failure
* cardiovascular disease
* coronary artery disease
* arrhythmias
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